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World J Gastrointest Surg. 2024 Feb 27;16(2):622-627. doi: 10.4240/wjgs.v16.i2.622.
ABSTRACT
BACKGROUND: Gallbladder rupture is common in laparoscopic cholecystectomy because the gallbladder is usually in acute or chronic inflammation status. The gallstones may sometime be spilled into the peritoneal cavity, resulting in intra-abdominal abscess if the gallstones were not retrieved. The diagnosis of intra-abdominal abscess caused by unretrieved gallstone can usually be correctly identified in the routine imaging studies, such as abdominal ultrasonography or computed tomography (CT). Here we present a case of abscess formation from unretrieved gallstone following laparoscopic cholecystectomy, which mimics the imaging findings of metastatic gallbladder adenocarcinoma.
CASE SUMMARY: This case described a 78-year-old man who received laparoscopic cholecystectomy and gallbladder adenocarcinoma was diagnosed after surgery. After adjuvant chemotherapy, the following up abdominal CT showed several small nodules at right upper abdomen and peritoneal carcinomatosis is considered. Repeated laparoscopic surgery for the excision of seeding tumor was conducted and the pathological diagnosis of the nodules and mass was inflammatory tissues and gallbladder stone.
CONCLUSION: Spilled gallstones are a common complication during laparoscopic cholecystectomy and some gallstones fail to be retrieved due to the size or the restricted view of laparoscopic surgery. For spilled gall bladder stones, surgeons may consider regular computerized tomography follow-up, and if necessary, laparoscopic examination can be used as a means of confirming the diagnostic and treatment.
PMID:38463373 | PMC:PMC10921212 | DOI:10.4240/wjgs.v16.i2.622
Pathol Res Pract. 2024 Feb 23;256:155223. doi: 10.1016/j.prp.2024.155223. Online ahead of print.
ABSTRACT
Evidence suggests that long non-coding RNAs (lncRNAs) play a pivotal role in the carcinogenesis and progression of various human malignancies including gastrointestinal malignancies. This comprehensive review reports the functions and mechanisms of the lncRNA maternally expressed gene 3 (MEG3) involved in gastrointestinal malignancies. It summarizes its roles in mediating the regulation of cellular proliferation, apoptosis, migration, invasiveness, epithelial-to-mesenchymal transition, and drug resistance in several gastrointestinal cancers such as colorectal cancer, gall bladder cancer, pancreatic cancer, gastric cancer, esophageal cancer, cholangiocarcinoma, gastrointestinal stromal tumors and most importantly, hepatocellular carcinoma. In addition, the authors briefly highlight its implicated mechanistic role and interactions with different non-coding RNAs and oncogenic signaling cascades. This review presents the rationale for developing non coding RNA-based anticancer therapy via harnessing the power of MEG3 in gastrointestinal malignancies.
PMID:38452587 | DOI:10.1016/j.prp.2024.155223
BMC Gastroenterol. 2024 Mar 6;24(1):100. doi: 10.1186/s12876-024-03189-9.
ABSTRACT
BACKGROUND AND AIM: This study aims to examine the mortality rate and trend of gastrointestinal cancers, particularly gastric cancer, as the leading cause of death among cancers in northern Iran over a 9-year period. In light of the changing incidence and mortality rates of cancer in Iran and around the world, the importance of these diseases in people's lives, and the necessity of updating and monitoring the trend of cancer mortality, we have decided to report on the mortality trend of gastrointestinal cancers, based on crude and age-standardized rates.
METHOD: This study is a cross-sectional examination of deaths caused by gastrointestinal cancers in Babol city, Iran, between 2013 and 2021. Data was collected from the cause of death registration and classification system of Babol University of Medical Sciences. Population estimation was obtained from the latest census reports. The crude and age-standardized mortality rates and trends of the cancers were calculated.
RESULTS: Overall, there were 1345 deaths from gastrointestinal cancers with an average age of 69.11 ± 14.25 years. The crude and age-standardized rates of these cancers rose from 24.1 to 20.1 per hundred thousand people in 2012 to 29.5 and 25.5 per hundred thousand people, respectively. This trend became more prevalent significantly with the increase of each decade of age for both men (P-value Trend = 0.002) and women (P-value Trend = 0.012). An analysis of gastrointestinal cancers revealed a decreasing trend for cancers of the small intestine, an increasing trend for cancers of the colon, pancreas, and gallbladder, and a stable trend for the remaining cancers over the study period.
CONCLUSION: The age-standardized rate and the number of gastrointestinal cancers is rising, highlighting the importance of preventative measures such as screening, increasing public awareness, and appropriate diagnostic methods.
PMID:38448828 | PMC:PMC10916231 | DOI:10.1186/s12876-024-03189-9
J Robot Surg. 2024 Mar 5;18(1):111. doi: 10.1007/s11701-024-01851-8.
ABSTRACT
This meta-analysis aims to evaluate the safety and oncological outcomes of robotic surgery compared to open surgery in treating gallbladder cancer (GBC). In October 2023, we performed a literature search across major global databases such as PubMed, Embase, and the Cochrane Library. We employed a Review Manager for parameter comparisons. This study has been registered with PROSPERO under the identifier CRD42023476686. Our final meta-analysis incorporated 5 cohort studies, encompassing a total of 353 patients. Compared to the Open Group (OG), the Robotic Group (RG) had reduced intraoperative blood loss (WMD - 217.72 ml, 95% CI - 371.08 to - 64.35; p = 0.005), shorter hospital stay (WMD - 1.80 days, 95% CI - 2.66 to - 0.95; p < 0.0001), and fewer overall complications (OR 0.31, 95% CI 0.10-0.97; p = 0.04). However, there was no significant difference between the two groups in terms of operation duration, postoperative inpatient days, readmission rate, major complications, 1-year postoperative survival, 2-year postoperative survival, and mortality rates. In our study, we found that for patients with gallbladder cancer, robotic radical cholecystectomy offers certain potential advantages over open radical cholecystectomy. This suggests that robotic radical cholecystectomy might be the optimal choice for treating gallbladder cancer. However, further validation from high-quality randomized clinical trials is required.
PMID:38441753 | DOI:10.1007/s11701-024-01851-8
Cancer Rep (Hoboken). 2024 Mar;7(3):e1991. doi: 10.1002/cnr2.1991.
ABSTRACT
BACKGROUND: Surgical resection remains the primary treatment option for gallbladder carcinoma (GBC). However, there is a pressing demand for prognostic tools that can refine patients' treatment choices and tailor personalized therapies accordingly.
AIMS: The nomograms were constructed using the data of a training cohort (n = 378) of GBC patients at Eastern Hepatobiliary Surgery Hospital (EHBH) between 2008 and 2018. The model's performance was validated in GBC patients (n = 108) at Guangzhou Centre from 2007 to 2018.
METHODS AND RESULTS: The 5-year overall survival (OS) rate in the training cohort was 24.4%. Multivariate analyses were performed using preoperative and postoperative data to identify independent predictors of OS. These predictors were then incorporated into preoperative and postoperative nomograms, respectively. The C-index of the preoperative nomogram was 0.661 (95% CI, 0.627 to 0.694) for OS prediction and correctly delineated four subgroups (5-year OS rates: 48.1%, 19.0%, 15.6%, and 8.1%, p < 0.001). The C-index of the postoperative nomogram was 0.778 (95%CI, 0.756 -0.800). Furthermore, this nomogram was superior to the 8th TNM system in both C-index and the net benefit on decision curve analysis. The results were externally validated.
CONCLUSION: The two nomograms showed an optimally prognostic prediction in GBC patients after curative-intent resection.
PMID:38441306 | PMC:PMC10913079 | DOI:10.1002/cnr2.1991
Cancer Lett. 2024 Apr 1;586:216677. doi: 10.1016/j.canlet.2024.216677. Epub 2024 Feb 1.
ABSTRACT
Gallbladder cancer (GBC) is a common solid tumor of the biliary tract with a high mortality rate and limited curative benefits from surgical resection. Here, we aimed to elucidate the pathogenesis of GBC from the perspective of molecular mechanisms and determined that protein phosphatase 4 regulator subunit 1 (PP4R1) is overexpressed in GBC tissues and contributes to poor prognosis. Through a series of in vitro and in vivo experiments, we demonstrated that PP4R1 overexpression improved tumorigenesis in GBC cells. Further mechanistic exploration revealed that PP4R1 directly interacts with pyruvate kinase-M2 (PKM2), a key regulator of glycolysis. PP4R1 promotes the extracellular signal-related kinase 1 and 2 (ERK1/2)-mediated PKM2 nuclear translocation, thereby participating in the regulation of tumor glycolysis. Interestingly, we determined that PP4R1 strengthens the interaction between ERK1/2 and PKM2. Furthermore, PP4R1 enhanced the suppressive effects of the ERK inhibitor SCH772984 on GBC. In conclusion, our data showed that PP4R1 is a promising biomarker associated with GBC and confirmed that PP4R1 regulates PKM2-mediated tumor glycolysis, which provides a metabolic growth advantage to GBC cells, thereby promoting GBC tumor growth and metastasis1.
PMID:38301910 | DOI:10.1016/j.canlet.2024.216677
Cancer Lett. 2024 Apr 1;586:216675. doi: 10.1016/j.canlet.2024.216675. Epub 2024 Jan 25.
ABSTRACT
Gallbladder cancer (GBC) is among the most common malignancies of biliary tract system due to its limited treatments. The immunotherapeutic targets for T cells are appealing, however, heterogeneity of T cells hinds its further development. We systematically construct T cell atlas by single-cell RNA sequencing; and utilized the identified gene signatures of high_CNV_T cells to predict molecular subtyping towards personalized therapeutic treatments for GBC. We identified 12 T cell subtypes, where exhausted CD8+ T cells, activated/exhausted CD8+ T cells, and regulatory T cells were predominant in tumors. There appeared to be an inverse relationship between Th17 and Treg populations with Th17 levels significantly reduced, whereas Tregs were concomitantly increased. Furthermore, we first established subtyping criterion to identify three subtypes of GBC based on their pro-tumorigenic microenvironments, e.g., the type 1 group shows more M2 macrophages infiltration, while the type 2 group is infiltrated by highly exhausted CD8+ T cells, B cells and Tregs with suppressive activities. Our study provides valuable insights into T cell heterogeneity and suggests that molecular subtyping based on T cells might provide a potential immunotherapeutic strategy to improve GBC treatment.
PMID:38280478 | DOI:10.1016/j.canlet.2024.216675
Clin Nucl Med. 2024 Apr 1;49(4):344-345. doi: 10.1097/RLU.0000000000005121. Epub 2024 Feb 28.
ABSTRACT
An Al 18F-prostate-specific membrane antigen (PSMA) Q PET/CT scan was performed in a 67-year-old man to identify any potential recurrent prostate cancer lesions, which revealed no recurrent or metastatic lesions. However, a large gallbladder stone with increased PSMA uptake was incidentally detected, which could be a potential pitfall in the interpretation of PSMA PET imaging.
PMID:38427958 | DOI:10.1097/RLU.0000000000005121
Gastrointest Endosc. 2024 Feb 29:S0016-5107(24)00136-6. doi: 10.1016/j.gie.2024.02.015. Online ahead of print.
ABSTRACT
BACKGROUND AND AIMS: It is difficult to differentiate between neoplastic and non-neoplastic gallbladder (GB) polyps before surgery. Endoscopic ultrasound-elastography (EUS-EG) is a non-invasive complementary diagnostic method. The utility of EUS-EG in the differential diagnosis of GB polyps has not been investigated. We aimed to investigate the diagnostic performance of EUS-EG for the differential diagnosis of GB polyps.
METHODS: Patients with GB polyps were prospectively enrolled from June 2020 until November 2022. EUS-EG and semi-quantitative evaluation of the strain ratio (SR) were performed for differential diagnosis of GB polyps. Fifty-three eligible patients were divided into two groups based on the final diagnosis after surgery. Patient demographics, EUS characteristics, and SR values were compared. Receiver-operating characteristic (ROC) curve analysis was performed to determine the optimal cutoff SR value that discriminates between neoplastic and non-neoplastic GB polyps.
RESULTS: The median SR value for neoplastic polyps (32.93 [interquartile range: 22.37-69.02]) was significantly higher than for non-neoplastic polyps (5.40 [2.36-14.44]; p<0.001). There were significant differences in SR values between non-neoplastic, benign neoplastic (23.38 [13.62-39.04]), and malignant polyps (49.25 [27.90-82.00]). The optimal cut-off SR value to differentiate between neoplastic and non-neoplastic polyps was 18.4. In multivariable logistic regression, SR value >18.4 (odds ratio 33.604, 95% confidence interval 2.588-436.292) was an independent predictor of neoplastic polyps.
CONCLUSIONS: EUS-EG and SR values can be used as a supplementary method for evaluating GB polyps.
PMID:38431102 | DOI:10.1016/j.gie.2024.02.015
Indian J Gastroenterol. 2024 Mar 1. doi: 10.1007/s12664-024-01518-0. Online ahead of print.
ABSTRACT
Biliary tract cancers are malignant neoplasms arising from bile duct epithelial cells. They include cholangiocarcinomas and gallbladder cancer. Gallbladder cancer has a marked geographical preference and is one of the most common cancers in women in northern India. Biliary tract cancers are usually diagnosed at an advanced, unresectable stage. Hence, the prognosis is extremely dismal. The five-year survival rate in advanced gallbladder cancer is < 5%. Hence, early detection and radical surgery are critical to improving biliary tract cancer prognoses. Radiological imaging plays an essential role in diagnosing and managing biliary tract cancers. However, the diagnosis is challenging because the biliary tract is affected by many diseases that may have radiological appearances similar to cancer. Artificial intelligence (AI) can improve radiologists' performance in various tasks. Deep learning (DL)-based approaches are increasingly incorporated into medical imaging to improve diagnostic performance. This paper reviews the AI-based strategies in biliary tract cancers to improve the diagnosis and prognosis.
PMID:38427281 | DOI:10.1007/s12664-024-01518-0
Ecancermedicalscience. 2024 Jan 30;18:1660. doi: 10.3332/ecancer.2024.1660. eCollection 2024.
ABSTRACT
BACKGROUND: Gallbladder cancer is a rare malignancy characterised by poor survival with lack of durable response to treatment. Thus, novel biomarkers are needed to prognosticate patients. This systematic review and meta-analysis sought to examine the role of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet count (PC) and serum immune inflammation index in predicting the survival of patients with gallbladder cancer.
MATERIALS AND METHODS: A systematic search was done using PubMed, Cochrane, ClinicalTrials.gov and Google Scholar for articles published from inception until 8 February 2022. Hazard ratios (HR) with 95% confidence intervals (CI) were pooled and subgroup analyses were conducted according to treatment, region and cut-offs. The primary outcome of interest was overall survival (OS). Data were summarised using RevMan version 5.4.
RESULTS: Twenty studies comprising 5,183 patients were included in the analysis. High neutrophil-lymphocyte ratio (HR 1.72, 95% CI 1.47-2.02), platelet-lymphocyte ratio (HR 1.51, 95% CI 1.33-1.72), monocyte-lymphocyte ratio (HR 1.96, 95% CI 1.46-1.64), PC (HR 1.20, 95% CI 1.02-1.40) and serum inflammation index (HR 1.73, 95% CI 1.36-2.18) were all associated with worse survival. The association was consistent across most subgroups on race and cut-offs with a trend towards poor survival for PC above 252.5.
CONCLUSION: High neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, monocyte-lymphocyte ratio, PC and SII are associated with worse OS in gallbladder cancer and are potential biomarkers for prognostication. Prospective studies are recommended to further evaluate their use.
PMID:38425767 | PMC:PMC10901636 | DOI:10.3332/ecancer.2024.1660
Lipids Health Dis. 2024 Feb 28;23(1):61. doi: 10.1186/s12944-024-02053-9.
ABSTRACT
BACKGROUND: The roles of serum lipids on digestive system cancer (DSC) risk were still inconclusive. In this study, we systematically assessed indicative effects of signature lipidomic biomarkers (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG)) on DSC (oesophagus, stomach, colorectal, liver, gallbladder, and pancreas cancers) risk.
METHODS: HDL-C, LDL-C, and TG concentration measurements were respectively analyzed with enzyme immunoinhibition, enzymatic selective protection, and GPO-POD methods in AU5800 supplied from Beckman Coulter. The diagnoses of DSCs were coded using International Classification of Diseases, Tenth Revision (ICD-10) codes updated until October 2022 in the UK Biobank (UKB). In this study, we assessed phenotypic association patterns between signature lipidomic biomarkers and DSC risk using restricted cubic splines (RCSs) in multivariable-adjusted Cox proportional hazards regression models. Moreover, linear and nonlinear causal association patterns of signature lipidomic biomarkers with DSC risk were determined by linear and nonlinear Mendelian randomization (MR) analyses.
RESULTS: A median follow-up time of 11.8 years was recorded for 319,568 participants including 6916 DSC cases. A suggestive independent nonlinear phenotypic association was observed between LDL-C concentration and stomach cancer risk (Pnonlinearity < 0.05, Poverall < 0.05). Meanwhile, a remarkable independent linear negative phenotypic association was demonstrated between HDL-C concentration and stomach cancer risk (Pnonlinearity > 0.05, Poverall < 0.008 (0.05/6 outcomes, Bonferroni-adjusted P)), and suggestive independent linear positive associations were observed between HDL-C concentration and colorectal cancer risk, and between TG concentration and gallbladder cancer risk (Pnonlinearity > 0.05, Poverall < 0.05). Furthermore, based on nonlinear and linear MR-based evidences, we observed an suggestive independent negative causal association (hazard ratio (HR) per 1 mmol/L increase: 0.340 (0.137-0.843), P = 0.020) between LDL-C and stomach cancer risk without a nonlinear pattern (Quadratic P = 0.901, Cochran Q P = 0.434). Meanwhile, subgroup and stratified MR analyses both supported the category of LDL-C ≥ 4.1 mmol/L was suggestively protective against stomach cancer risk, especially among female participants (HR: 0.789 (0.637-0.977), P = 0.030) and participants aged 60 years or older (HR: 0.786 (0.638-0.969), P = 0.024), and the category of TG ≥ 2.2 mmol/L concluded to be a suggestive risk factor for gallbladder cancer risk in male participants (HR: 1.447 (1.020-2.052), P = 0.038) and participants aged 60 years or older (HR: 1.264 (1.003-1.593), P = 0.047).
CONCLUSIONS: Our findings confirmed indicative roles of signature lipidomic biomarkers on DSC risk, notably detecting suggestive evidences for a protective effect of high LDL-C concentration on stomach cancer risk, and a detrimental effect of high TG concentration on gallbladder cancer risk among given participants.
PMID:38419059 | PMC:PMC10900802 | DOI:10.1186/s12944-024-02053-9
Zhonghua Zhong Liu Za Zhi. 2024 Feb 23;46(2):155-160. doi: 10.3760/cma.j.cn112152-20231026-00269.
ABSTRACT
Objective: To explore the application value and operation skills of ultrasound-guided percutaneous thermal ablation assisted by artificial ascites or/and soft tissue edema in the treatment of special hepatic tumors located nearby the diaphragm, heart, stomach, gastrointestinal tract, gall bladder, kidney, and other organs. Methods: The clinical data of 132 patients with special-region hepatic tumors treated with ultrasound-guided percutaneous thermal ablation aided by artificial ascites and/or artificial soft tissue edema were retrospectively analyzed. Intraoperative contrast-enhanced ultrasound was used to guide ablation when necessary. During the operation, the ablation needle was lifted or pressed down, or the direction of the needle handle was changed to protect vital organs. The technical success rate of artificial ascites and/or soft tissue edema formation, the complete in activation rate of the tumor, and the complications were observed. Results: There were 74 patients (108 lesions) treated with radiofrequency ablation and 58 patients (82 lesions) treated with microwave ablation. Among them, 81 cases was successfully injected artificial abdominal ascites, with a water volume of (1 301±685) ml; artificial soft tissue edema was successfully formed for 19 patients, with a water volume of (534±258) ml. Both artificial ascites and artificial soft tissue edema were built for 30 patients. The success rate of this hydro-isolation technique was 98.5% (130/132). 129 patients successfully completed the treatment, and the complete inactivation rate of the tumor was 92.5% (172/186). The average postoperative hospital stay was three days. No patient had serious complications, such as surface tumor rupture, gastrointestinal injury, or diaphragm perforation. Conclusions: For hepatic tumors located adjacent to other organs such as the diaphragm, heart, gastrointestinal tract, gallbladder, and kidney, the application of artificial ascites and/or artificial soft tissue edema can reduce the damage to these organs, as well as reduce the possibility of tumor rupture and diaphragm perforation. These methods are safe and effective in ultrasound-guided percutaneous thermal ablation.
PMID:38418190 | DOI:10.3760/cma.j.cn112152-20231026-00269
JNMA J Nepal Med Assoc. 2024 Feb 24;62(270):152-154. doi: 10.31729/jnma.8444.
ABSTRACT
Large cell neuroendocrine carcinoma of the gallbladder is an extremely rare tumour with aggressive behaviour and a bad prognosis. Here, we report a case of a 65-year-old lady suspected of carcinoma of the gallbladder and underwent extended cholecystectomy. The histopathology report revealed neuroendocrine carcinoma of a large cell type of gall bladder infiltrating the liver and three periportal and pericholedochal lymph nodes. She had an uneventful perioperative period and was doing good till 6 months of follow-up. The only potentially curative treatment for large cell neuroendocrine carcinoma of the gallbladder is aggressive surgical resection, owing to its aggressive behaviour and bad prognosis.
KEYWORDS: carcinoma; case reports; cholecystectomy; gallbladder.
PMID:38409975 | PMC:PMC10924531 | DOI:10.31729/jnma.8444
Langenbecks Arch Surg. 2024 Feb 27;409(1):75. doi: 10.1007/s00423-024-03267-2.
ABSTRACT
PURPOSE: Cholelithiasis occurs often after gastrectomy. However, no consensus has been established regarding the difference in the incidence of postgastrectomy cholelithiasis with different reconstruction methods. In this study, we examined the frequency of cholelithiasis after two major reconstruction methods, namely Billroth-I (B-I) and Roux-en-Y (R-Y) following laparoscopic distal gastrectomy (LDG) for gastric cancer.
METHODS: Among 696 gastric cancer patients who underwent LDG between April 2000 and March 2017, after applying the exclusion criteria, 284 patients who underwent B-I and 310 who underwent R-Y were examined retrospectively. The estimated incidence of cholelithiasis was compared between the methods, and factors associated with the development of cholelithiasis in the gallbladder and/or common bile duct were investigated.
RESULTS: During the median follow-up of 61.2 months, 52 patients (8.8%) developed cholelithiasis postgastrectomy; 12 patients (4.2%) after B-I and 40 (12.9%) after R-Y (p = 0.0002). Among them, choledocholithiasis was more frequent in patients who underwent R-Y (n = 11, 27.5%) vs. B-I (n = 1, 8.3%) (p = 0.0056). Univariate and multivariate analyses revealed that male sex, body mass index > 22.5 kg/m2, and R-Y reconstruction were significant predictors of the development of postLDG cholelithiasis.
CONCLUSION: Regarding cholelithiasis development, B-I reconstruction should be preferred whenever possible during distal gastrectomy.
PMID:38409456 | DOI:10.1007/s00423-024-03267-2
BMC Cancer. 2024 Feb 26;24(1):273. doi: 10.1186/s12885-024-12006-1.
ABSTRACT
BACKGROUND: Traditional nanodrug delivery systems have some limitations, such as eliciting immune responses and inaccuracy in targeting tumor microenvironments.
MATERIALS AND METHODS: Targeted drugs (Sorafenib, Sora) nanometers (hollow mesoporous silicon, HMSN) were designed, and then coated with platelet membranes to form aPD-1-PLTM-HMSNs@Sora to enhance the precision of drug delivery systems to the tumor microenvironment, so that more effective immunotherapy was achieved.
RESULTS: These biomimetic nanoparticles were validated to have the same abilities as platelet membranes (PLTM), including evading the immune system. The successful coating of HMSNs@Sora with PLTM was corroborated by transmission electron microscopy (TEM), western blot and confocal laser microscopy. The affinity of aPD-1-PLTM-HMSNs@Sora to tumor cells was stronger than that of HMSNs@Sora. After drug-loaded particles were intravenously injected into hepatocellular carcinoma model mice, they were demonstrated to not only directly activate toxic T cells, but also increase the triggering release of Sora. The combination of targeted therapy and immunotherapy was found to be of gratifying antineoplastic function on inhibiting primary tumor growth.
CONCLUSIONS: The aPD-1-PLTM-HMSNs@Sora nanocarriers that co-delivery of aPD-1 and Sorafenib integrates unique biomimetic properties and excellent targeting performance, and provides a neoteric idea for drug delivery of personalized therapy for primary hepatocellular carcinoma (HCC).
PMID:38409035 | PMC:PMC10898182 | DOI:10.1186/s12885-024-12006-1
2024 Feb 22. In: Feingold KR, Anawalt B, Blackman MR, Boyce A, Chrousos G, Corpas E, de Herder WW, Dhatariya K, Dungan K, Hofland J, Kalra S, Kaltsas G, Kapoor N, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, New M, Purnell J, Sahay R, Shah AS, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–.
ABSTRACT
Gastrointestinal manifestations of type 1 and 2 diabetes are common and represent a substantial cause of morbidity and health care costs, as well as a diagnostic and therapeutic challenge. Predominant among them, and most extensively studied, is abnormally delayed gastric emptying or diabetic gastroparesis. Abnormally increased retention of gastric contents may be associated with symptoms, including nausea, vomiting, postprandial fullness, bloating, and early satiety, which may be debilitating. However, the relationship of upper gastrointestinal symptoms with the rate of gastric emptying is relatively weak. Moreover, gastrointestinal symptoms also occur frequently in people without diabetes, which may compromise the capacity to discriminate gastrointestinal dysfunction resulting from diabetes from common gastrointestinal disorders such as functional dyspepsia. A definitive diagnosis of gastroparesis thus necessitates measurement of gastric emptying by a sensitive technique, such as scintigraphy or a stable-isotope breath test. There is an inter-dependent relationship of gastric emptying with postprandial glycemia. Elevated blood glucose (hyperglycemia) slows gastric emptying while, conversely, the rate of emptying is a major determinant of the glycemic response to a meal. The latter recognition has stimulated the development of dietary and pharmacological (e.g. short-acting GLP-1 receptor agonists) approaches to improve postprandial glycemic control in type 2 diabetes by slowing gastric emptying. The outcome of current management of symptomatic diabetic gastroparesis is often sub-optimal - optimizing glycemic control, the correction of nutritional deficiencies, and use of pharmacotherapy, are important. A number of promising and novel pharmacotherapeutic agents are in development. This chapter focusses on gastric motor function, but also provides an overview of the manifestations of esophageal, gall bladder, small and large intestinal function, in diabetes. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.
Medicine (Baltimore). 2024 Feb 23;103(8):e37302. doi: 10.1097/MD.0000000000037302.
ABSTRACT
RATIONALE: Melanoma is one of a common cutaneous malignancy. Currently, metastatic malignant melanoma is difficult to be diagnosed through imaging examinations. Furthermore, the incidence of metastatic melanoma affecting the gallbladder and ureter is exceptionally rare.
PATIENT CONCERNS: A 54-year-old female was admitted to the hospital with a half-month history of left lower back pain. Correlative examination revealed an occupying lesion in the mid-left ureter and the neck of the gallbladder.
DIAGNOSES: The patient was initially diagnosed with gallbladder cancer and left ureteral carcinoma based on imaging. Following 2 operations, immunohistochemical staining confirmed the presence of metastatic melanoma involving both the gallbladder and ureter.
INTERVENTION: After multidisciplinary consultation and obtaining consent from the patient and her family, the patient underwent left radical nephroureterectomy, radical cholecystectomy, laparoscopic partial hepatectomy (Hep IV, Hep V), and lymph node dissection of hepatoduodenal ligament.
OUTCOMES: One month after treatment, the patient imaging showed no disease progression, and at 6 months of follow-up, the patient was still alive.
LESSONS: It is difficult to distinguish metastatic melanoma from carcinoma in situ by imaging. In addition, metastatic malignant melanoma lacks specific clinical manifestations and is prone to misdiagnosis, which emphasizes the highly aggressive nature of malignant melanoma.
PMID:38394528 | PMC:PMC10883631 | DOI:10.1097/MD.0000000000037302
Medicine (Baltimore). 2024 Feb 23;103(8):e37187. doi: 10.1097/MD.0000000000037187.
ABSTRACT
The improvement of digestive cancer survival results in increased morbidity of noncancerous comorbidities. This study aimed at clarifying causes of death (COD) and predicting overall survival (OS) in patients diagnosed with liver cancer, gallbladder cancer, cholangiocarcinoma, and pancreatic cancer. We used the Surveillance, Epidemic, and End Results database to extract information. Nomograms of multivariate Cox regression was used to predict OS of cancer patients. The models were evaluated using the concordance indexes (C-indexes), the receiver operating characteristic curves and calibration curves. Respectively 58,895, 15,324, 30,708, and 109,995 cases with cancer of liver, gallbladder, bile duct or pancreas were retrieved between 2000 and 2020. Approximately 80% deaths occurred within 1 years after cancer diagnosis. Sequence in noncancerous COD proportion was diverse, while diseases of heart always accounted for a great part. Risks of death from most noncancerous COD were significantly higher than that of the cancer-free population. Nomograms were developed by predictors of interest such as age, therapy and TNM stage. The concordance indexes of nomograms were 0.756, 0.729, 0.763, and 0.760 respectively, well-calibrating to the reality. The 0.5-, 1-, and 2-year areas under the receiver operating characteristic curve were about 0.800, indicating good reliability and accuracy. Noncancerous COD accounted for larger part in gallbladder cancer and cholangiocarcinoma. Noncancerous COD showed an upward trend as follow-up time extended and the majorities were diseases of heart, cerebrovascular disease, chronic liver disease and cirrhosis. The novel OS-nomograms can provide personalized prognosis information with satisfactory accuracy.
PMID:38394524 | DOI:10.1097/MD.0000000000037187
Medicine (Baltimore). 2024 Feb 23;103(8):e37093. doi: 10.1097/MD.0000000000037093.
ABSTRACT
BACKGROUND: Situs inversus is a rare congenital anatomical variant that involves a group of anomalies regarding the arrangement of intrathoracic and intraabdominal organs. Being able to find in the abdominal region the liver, gallbladder, inferior vena cava, and head of the pancreas and ascending colon on the left side of the abdomen, while on the right side there is the spleen, the stomach, the body of the pancreas, the ligament of Treitz, descending colon among others. In this same way, the thoracic organs, lungs and heart, are changed in their position in a mirror translocation.
METHODS: We systematically searched MEDLINE, Web of Science, Google Scholar, CINAHL, Scopus, and LILACS; the search strategy included a combination of the following terms: "Situs inversus," "Situs inversus totalis," "Cancer," "Neoplasm," "Abdominopelvic regions," and "clinical anatomy."
RESULTS: Within the 41 included studies, 46 patients with situs inversus who had cancer, in addition to being found in this organ and in these regions, we also found as a result that the majority of the studies in the research were in stage II; finally, no one study could assert the direct relationship between the situs inversus totalis and the cancer.
CONCLUSION: If our hallmarks could make us think that more exhaustive follow-up of the stomach and other organs should be carried out in these patients, there could also be other predisposing factors for cancer, which is why more studies are suggested to give future diagnostic and treatment guidelines treatment.
PMID:38394506 | DOI:10.1097/MD.0000000000037093
Langenbecks Arch Surg. 2024 Feb 23;409(1):73. doi: 10.1007/s00423-024-03261-8.
ABSTRACT
The main purpose of this study is to explore the outcomes of patients found to have gallbladder cancer during investigation and diagnosis of acute cholecystitis. The incidence of primary gallbladder cancer co-existing in acute cholecystitis is not well defined in the literature, with anecdotal reports suggesting that they experience worse outcomes than patients with gallbladder cancer found incidentally.
METHODS: A retrospective review of all patients with gallbladder cancer managed at the Canberra Health Service between 1998 and May 2022 were identified and reviewed.
RESULTS: A total of 65 patients were diagnosed with primary gallbladder cancer during the study period with a mean age of 70.4 years (SD 11.4, range 59-81.8 years) and a female preponderance (74% versus 26%) with a ratio of 2.8. Twenty (31%) patients presented with acute calculus cholecystitis and were found to have a primary gallbladder cancer. This group of patients were older and predominantly female, but the difference was not statistically significant. The overall 5-year survival in the cohort was 20% (stage 1 63%, stage 2 23%, stage 3 16%, and stage 4 0%). There was no statistically significant difference in survival between those who presented with acute cholecystitis vs other presentations.
CONCLUSIONS: A third of the patients with gallbladder cancer presented with acute cholecystitis. There was no statistically significant difference in survival in those with bile spillage during cholecystectomy as well those presenting with acute cholecystitis.
PMID:38393412 | PMC:PMC10891216 | DOI:10.1007/s00423-024-03261-8
Cancer Biol Ther. 2024 Dec 31;25(1):2315651. doi: 10.1080/15384047.2024.2315651. Epub 2024 Feb 23.
ABSTRACT
Metabolic reprogramming plays a critical role in hepatocarcinogenesis. However, the mechanisms regulating metabolic reprogramming in primary liver cancer (PLC) are unknown. Differentially expressed miRNAs between PLC and normal tissues were identified using bioinformatic analysis. RT-qPCR was used to determine miR-10b-5p and SCL38A2 expression levels. IHC, WB, and TUNEL assays were used to assess the proliferation and apoptosis of the tissues. The proliferation, migration, invasion, and apoptosis of PLC cells were determined using the CCK-8 assay, Transwell assay, and flow cytometry. The interaction between miR-10b-5p and SLC38A2 was determined using dual-luciferase reporter assay. A PLC xenograft model in BALB/c nude mice was established, and tumorigenicity and SLC38A2 expression were estimated. Finally, liquid chromatography - mass spectrometry (LC-MS) untargeted metabolomics was used to analyze the metabolic profiles of xenograft PLC tissues in nude mice. miR-10b-5p was a key molecule in the regulation of PLC. Compared with para-carcinoma tissues, miR-10b-5p expression was increased in tumor tissues. miR-10b-5p facilitated proliferation, migration, and invasion of PLC cells. Mechanistically, miR-10b-5p targeted SLC38A2 to promote PLC tumor growth. Additionally, miR-10b-5p altered the metabolic features of PLC in vivo. Overexpression of miR-10b-5p resulted in remarkably higher amounts of lumichrome, folic acid, octanoylcarnitine, and Beta-Nicotinamide adenine dinucleotide, but lower levels of 2-methylpropanal, glycyl-leucine, and 2-hydroxycaproic acid. miR-10b-5p facilitates the metabolic reprogramming of PLC by targeting SLC38A2, which ultimately boosts the proliferation, migration, and invasion of PLC cells. Therefore, miR-10b-5p and SLC38A2 are potential targets for PLC diagnosis and treatment.
PMID:38390840 | PMC:PMC10896153 | DOI:10.1080/15384047.2024.2315651
World J Surg Oncol. 2024 Feb 22;22(1):63. doi: 10.1186/s12957-024-03347-z.
ABSTRACT
BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer.
CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor.
CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.
PMID:38389074 | PMC:PMC10882841 | DOI:10.1186/s12957-024-03347-z
Diabetes Care. 2024 Mar 1;47(3):353-361. doi: 10.2337/dc23-0386.
ABSTRACT
OBJECTIVE: Diabetes presenting at a younger age has a more aggressive nature. We aimed to explore the association of age at type 2 diabetes mellitus (T2DM) diagnosis with subsequent cancer incidence in a large Chinese population.
RESEARCH DESIGN AND METHODS: The prospective population-based longitudinal cohort included 428,568 newly diagnosed T2DM patients from 2011 to 2018. Participants were divided into six groups according to their age at diagnosis: 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years. The incidence of overall and 14 site-specific cancers was compared with the Shanghai general population including 100,649,346 person-years.
RESULTS: A total of 18,853 and 582,643 overall cancer cases were recorded in the T2DM cohort and the general population. The age-standardized rate of overall cancer in T2DM patients was 501 (95% CI: 491, 511) per 100,000 person-years, and the standardized incidence ratio (SIR) was 1.10 (1.09, 1.12). Younger age at T2DM diagnosis was associated with higher incidence of overall and site-specific cancers. SIRs for overall cancer with T2DM diagnosis at ages 20-54, 55-59, 60-64, 65-69, 70-74, and ≥75 years were 1.48 (1.41, 1.54), 1.30 (1.25, 1.35), 1.19 (1.15, 1.23), 1.16 (1.12, 1.20), 1.06 (1.02, 1.10), and 0.86 (0.84, 0.89), respectively. Similar trends were observed for site-specific cancers, including respiratory, colorectum, stomach, liver, pancreatic, bladder, central nervous system, kidney, and gallbladder cancer and lymphoma among both males and females.
CONCLUSIONS: Our findings highlight the necessity of stratifying management for T2DM according to age of diagnosis. As with a range of vascular outcomes, age-standardized cancer risks are greater in earlier compared with later onset T2DM.
PMID:38237119 | PMC:PMC10909688 | DOI:10.2337/dc23-0386
Front Endocrinol (Lausanne). 2024 Feb 8;15:1326112. doi: 10.3389/fendo.2024.1326112. eCollection 2024.
ABSTRACT
BACKGROUND: Gallbladder neuroendocrine neoplasms (GB-NENs) are a rare malignant disease, with most cases diagnosed at advanced stages, often resulting in poor prognosis. However, studies regarding the prognosis of this condition and its comparison with gallbladder adenocarcinomas (GB-ADCs) have yet to yield convincing conclusions.
METHODS: We extracted cases of GB-NENs and GB-ADCs from the Surveillance, Epidemiology, and End Results (SEER) database in the United States. Firstly, we corrected differences in clinical characteristics between the two groups using propensity score matching (PSM). Subsequently, we visualized and compared the survival outcomes of the two groups using the Kaplan-Meier method. Next, we employed the least absolute shrinkage and selection operator (LASSO) regression and Cox regression to identify prognostic factors for GB-NENs and constructed two nomograms for predicting prognosis. These nomograms were validated with an internal validation dataset from the SEER database and an external validation dataset from a hospital. Finally, we categorized patients into high-risk and low-risk groups based on their overall survival (OS) scores.
RESULTS: A total of 7,105 patients were enrolled in the study, comprising 287 GB-NENs patients and, 6,818 GB-ADCs patients. There were substantial differences in clinical characteristics between patients, and GB-NENs exhibited a significantly better prognosis. Even after balancing these differences using PSM, the superior prognosis of GB-NENs remained evident. Independent prognostic factors selected through LASSO and Cox regression were age, histology type, first primary malignancy, tumor size, and surgery. Two nomograms for prognosis were developed based on these factors, and their performance was verified from three perspectives: discrimination, calibration, and clinical applicability using training, internal validation, and external validation datasets, all of which exhibited excellent validation results. Using a cutoff value of 166.5 for the OS nomogram score, patient mortality risk can be identified effectively.
CONCLUSION: Patients with GB-NENs have a better overall prognosis compared to those with GB-ADCs. Nomograms for GB-NENs prognosis have been effectively established and validated, making them a valuable tool for assessing the risk of mortality in clinical practice.
PMID:38390209 | PMC:PMC10882707 | DOI:10.3389/fendo.2024.1326112
J Cancer Res Ther. 2023 Oct 1;19(7):1908-1914. doi: 10.4103/jcrt.jcrt_1117_21. Epub 2023 Apr 26.
ABSTRACT
AIM: In the present case-controlled study, we explored the role of genetic polymorphism in three xenobiotic metabolizing genes, GSTM1, GSTT1 and GSTP1, and their association to gallbladder cancer (GBC) risk in a North Indian population. Its etiology is influenced by genetic, food habits, lifestyle, and environmental factors. GBC incidence is significantly higher in the Gangetic belt, India. Therefore, we explored the prognostic factors in the susceptibility of GBC through gene-gene and gene-environment interaction in this region.
MATERIAL AND METHODS: Genetic polymorphism was analyzed in 108 GBC patients from Kamala Nehru Memorial Cancer Hospital, Prayagraj and 142 matched controls. GSTM1 and GSTT1 genotypes were analyzed by multiplex PCR method, while restriction fragment length polymorphism (RFLP) was performed to analyze GSTP1 genotypes. Logistic regression analysis calculating the odds ratio (OR) and 95% confidence interval (CI) was performed to analyze the GBC risk.
RESULTS: GSTT1 (null) genotype was at a significantly higher risk and susceptible to GBC (OR = 2.044, CI = 1.225-3.411, P = 0.006), while GSTM1 and GSTP1 genotypes did not show any association to GBC risk. After sex stratification, females diagnosed with GBC had higher GSTT1 (null) genotype (OR = 2.754, CI = 1.428-5.310, P = 0.003) compared to males. GBC patients dwelling in rural areas show higher GSTT1 (null) genotype with two-fold GBC risk (OR = 2.031, CI = 1.200-3.439, P = 0.008). Further, GBC patients with histopathology of adenocarcinoma also showed higher GSTT1 (null) genotype (OR = 2.113, CI = 1.248-3.578, P = 0.005). Gene-gene interaction between GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val), enhance the GBC risk (OR = 1.840, CI = 1.135-2.982, P = 0.013).
CONCLUSIONS: The present study suggests that GSTT1 (null) genotype has higher susceptibility and risk towards GBC in North Indian population. Female patients, patients with histopathology of adenocarcinoma and rural dwelling GBC patients have higher GSTT1 (null) genotypes and may be at risk of developing GBC. The genotype combination GSTT1 (non-null)/GSTP1 (Ile/Val + Val/Val) has increased GBC susceptibility and may be considered as 'at risk' genotypes for GBC in North Indians.
PMID:38376296 | DOI:10.4103/jcrt.jcrt_1117_21
Front Immunol. 2024 Feb 2;15:1353430. doi: 10.3389/fimmu.2024.1353430. eCollection 2024.
ABSTRACT
INTRODUCTION: Biliary tract cancers (BTC) are often diagnosed at an advanced stage where prognosis is poor and curative-intent surgery is infeasible. First-line cisplatin-gemcitabine chemotherapy for advanced gallbladder cancer has remained unchanged over more than a decade, but recent developments in immunotherapy such as durvalumab have highlighted promise as a combination treatment regime with current standard chemotherapy.
METHODS: In this case description, we present a case of locally-advanced gallbladder adenocarcinoma involving the biliary confluence that was initially planned for an extended right hepatectomy after portal vein embolization. Interval imaging revealed peritoneal metastasis, which was confirmed on diagnostic laparoscopy and biopsy. The patient underwent 8 cycles of cisplatin 25 mg/m2 and gemcitabine 1,000 mg/m2 chemotherapy on days 1 and 8 of each 21-day cycle, with durvalumab (Imfinzi®) 1,500 mg immunotherapy on day 1 of every cycle, in accordance with the treatment protocol of the TOPAZ-1 trial. Repeat imaging demonstrated a stable primary lesion with no further evidence of peritoneal disease. The patient subsequently underwent curative-intent conversion surgery with an extended right hepatectomy and Roux-en-Y hepaticojejunostomy, which were completed through a fully minimally-invasive laparoscopic approach.
RESULTS: Final pathological TNM classification was ypT1aN0, with near-complete pathological response to pre-surgical therapy, uninvolved margins (R0 resection) and tumour shrinkage from 2.5 centimetres on pre-operative cross-sectional imaging to 0.5 centimetres on final histology. The patient had an uneventful post-operative course, and was fit for discharge by the fourth post-operative day. He remained well after three months of routine post-operative follow-up, with no significant post-operative complications and biochemical or radiological evidence of disease recurrence.
CONCLUSION: Our case description highlights the immense potential of combination durvalumab immunotherapy with cisplatin-gemcitabine chemotherapy in the treatment of advanced gallbladder adenocarcinoma. The patient's locally advanced disease was initially planned for complex open surgery, prior to discovery of peritoneal metastasis rendering it inoperable. This was successfully down-staged with combination therapy to eventual R0 resection via minimally-invasive surgery. In addition, this case description demonstrates the feasibility of a fully laparoscopic approach with postulated benefits of diagnostic re-evaluation of peritoneal disease, reduced wound pain and shorter length of hospital stay.
PMID:38370411 | PMC:PMC10869450 | DOI:10.3389/fimmu.2024.1353430
EJNMMI Radiopharm Chem. 2024 Feb 19;9(1):14. doi: 10.1186/s41181-024-00243-5.
ABSTRACT
BACKGROUND: Programmed cell death ligand 1 (PD-L1) plays a critical role in the tumor microenvironment and overexpression in several solid cancers has been reported. This was associated with a downregulation of the local immune response, specifically of T-cells. Immune checkpoint inhibitors showed a potential to break this localized immune paralysis, but only 30% of patients are considered responders. New diagnostic approaches are therefore needed to determine patient eligibility. Small molecule radiotracers targeting PD-L1, may serve as such diagnostic tools, addressing the heterogeneous PD-L1 expression between and within tumor lesions, thus aiding in therapy decisions.
RESULTS: Four biphenyl-based small-molecule PD-L1 ligands were synthesized using a convergent synthetic route with a linear sequence of up to eleven steps. As a chelator NODA-GA, CB-TE2A or DiAmSar was used to allow radiolabeling with copper-64 ([64Cu]Cu-14-[64Cu]Cu-16). In addition, a dimeric structure based on DiAmSar was synthesized ([64Cu]Cu-17). All four radioligands exhibited high proteolytic stability (> 95%) up to 48 h post-radiolabeling. Saturation binding yielded moderate affinities toward PD-L1, ranging from 100 to 265 nM. Real-time radioligand binding provided more promising KD values around 20 nM for [64Cu]Cu-14 and [64Cu]Cu-15. In vivo PET imaging in mice bearing both PC3 PD-L1 overexpressing and PD-L1-mock tumors was performed at 0-2, 4-5 and 24-25 h post injection (p.i.). This revealed considerably different pharmacokinetic profiles, depending on the substituted chelator. [64Cu]Cu-14, substituted with NODA-GA, showed renal clearance with low liver uptake, whereas substitution with the cross-bridged cyclam chelator CB-TE2A resulted in a primarily hepatobiliary clearance. Notably, the monomeric DiAmSar radioligand [64Cu]Cu-16 demonstrated a higher liver uptake than [64Cu]Cu-15, but was still renally cleared as evidenced by the lack of uptake in gall bladder and intestines. The dimeric structure [64Cu]Cu-17 showed extensive accumulation and trapping in the liver but was also cleared via the renal pathway. Of all tracer candidates and across all timepoints, [64Cu]Cu-17 showed the highest accumulation at 24 h p.i. in the PD-L1-overexpressing tumor of all timepoints and all radiotracers, indicating drastically increased circulation time upon dimerization of two PD-L1 binding motifs.
CONCLUSIONS: This study shows that chelator choice significantly influences the pharmacokinetic profile of biphenyl-based small molecule PD-L1 radioligands. The NODA-GA-conjugated radioligand [64Cu]Cu-14 exhibited favorable renal clearance; however, the limited uptake in tumors suggests the need for structural modifications to the binding motif for future PD-L1 radiotracers.
PMID:38372838 | PMC:PMC10876507 | DOI:10.1186/s41181-024-00243-5
Radiographics. 2024 Mar;44(3):e230109. doi: 10.1148/rg.230109.
ABSTRACT
Biliary abnormalities in children are uncommon, and the spectrum of biliary disorders is broader than in adult patients. Unlike in adults, biliary disorders in children are rarely neoplastic and are more commonly rhabdomyosarcoma rather than cholangiocarcinoma. Pediatric biliary disorders may be embryologic or congenital, such as anatomic gallbladder anomalies, anomalous pancreaticobiliary tracts, various cholestatic processes, congenital cystic lesions, or genetic conditions. They may also be benign, such as biliary filling anomalies, biliary motility disorders, and biliary inflammatory and infectious disorders. Distinguishing these entities with a single imaging modality is challenging. US is the primary imaging modality for initial evaluation of biliary abnormalities in children, due to its wide availability, lack of ionizing radiation, and low cost and because it requires no sedation. Other examinations such as MRI, CT, and nuclear medicine examinations may provide anatomic and functional information to narrow the diagnosis further. Hepatobiliary-specific contrast material with MRI can provide better assessment of biliary anatomy on delayed images than can traditional MRI contrast material. MR cholangiopancreatography (MRCP) allows visualization of the intra- and extrahepatic biliary ducts, which may not be possible with endoscopic retrograde cholangiopancreatography (ERCP). Suspected biliary atresia requires multiple modalities for diagnosis and timely treatment. Determining the type of choledochal cyst calls for a combination of initial US and MRCP. Many benign and malignant biliary masses require biopsy for definitive diagnosis. Knowledge of the imaging appearances of different pediatric biliary abnormalities is necessary for appropriate imaging workup, providing a diagnosis or differential diagnosis, and guiding appropriate management. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.
PMID:38358937 | DOI:10.1148/rg.230109
EBioMedicine. 2024 Feb;100:104977. doi: 10.1016/j.ebiom.2024.104977. Epub 2024 Jan 29.
ABSTRACT
BACKGROUND: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development.
METHODS: Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analysis using the Olink Oncology-II platform (48% of participants were female; 52% male). To identify proteins which may be altered by the weight-loss intervention, the difference in protein levels between groups at baseline and 1 year was examined using linear regression. Mendelian randomization (MR) was performed to extend these results to evaluate cancer risk and elucidate possible biological mechanisms linking type 2 diabetes and cancer development. MR analyses were conducted using independent datasets, including large cancer meta-analyses, UK Biobank, and FinnGen, to estimate potential causal relationships between proteins modified during intentional weight loss and the risk of colorectal, breast, endometrial, gallbladder, liver, and pancreatic cancers.
FINDINGS: Nine proteins were modified by the intervention: glycoprotein Nmb; furin; Wnt inhibitory factor 1; toll-like receptor 3; pancreatic prohormone; erb-b2 receptor tyrosine kinase 2; hepatocyte growth factor; endothelial cell specific molecule 1 and Ret proto-oncogene (Holm corrected P-value <0.05). Mendelian randomization analyses indicated a causal relationship between predicted circulating furin and glycoprotein Nmb on breast cancer risk (odds ratio (OR) = 0.81, 95% confidence interval (CI) = 0.67-0.99, P-value = 0.03; and OR = 0.88, 95% CI = 0.78-0.99, P-value = 0.04 respectively), though these results were not supported in sensitivity analyses examining violations of MR assumptions.
INTERPRETATION: Intentional weight loss among individuals with recently diagnosed diabetes may modify levels of cancer-related proteins in serum. Further evaluation of the proteins identified in this analysis could reveal molecular pathways that mediate the effect of adiposity and type 2 diabetes on cancer risk.
FUNDING: The main sources of funding for this work were Diabetes UK, Cancer Research UK, World Cancer Research Fund, and Wellcome.
PMID:38290287 | PMC:PMC10844806 | DOI:10.1016/j.ebiom.2024.104977
Dig Dis Sci. 2024 Feb;69(2):502-509. doi: 10.1007/s10620-023-08216-5. Epub 2023 Dec 22.
ABSTRACT
BACKGROUND: Promoter hypermethylation of tumor suppressor genes has been demonstrated to be one of the major mechanisms of their epigenetic regulation in various reports. We have studied the promoter methylation status of PEBP1 and evaluated its correlation with gallbladder carcinogenesis.
AIMS: PEBP1, an endogenous inhibitor of Raf/MEK/ERK signaling pathway, is a tumor suppressor gene. We aimed to study the expression profile of PEBP1 and understand the mechanism and significance of its deregulation in gallbladder cancer.
METHODS: PEBP1 expression analysis and its promoter methylation status were investigated in 77 gallbladder carcinoma (GBC) and tissue biopsies from 28 patients of gallstone disease by RT-PCR and MS-PCR, respectively.
RESULTS: Our results of the mRNA expression profiling demonstrate that PEBP1 is down-regulated in 62.3% (48/77), while 31.2% (24/77) of the gallbladder cancer biopsies show no significant change and 6.5% (5/77) show up-regulated expression compared to tissue samples of gallstone diseases. In GBC, 48.1% (N = 37) GBC biopsy samples exhibited significantly heterozygous promoter hypermethylation compared to tissue samples from gallstone diseases which show promoter hypermethylation in 3 (10.7%) samples only. In gallbladder cancer, the PEBP1 methylation is significantly associated with lymph node metastasis and shorter period of survival.
CONCLUSION: PEBP1 is frequently down-regulated and hypermethylated in gallbladder cancer and its promoter hypermethylation is a frequent and early inactivating mechanism in GBC.
PMID:38135812 | DOI:10.1007/s10620-023-08216-5
Lab Chip. 2024 Jan 17;24(2):375-382. doi: 10.1039/d3lc00862b.
ABSTRACT
Cholangiocarcinoma (CCA) is an aggressive cancer that originates from the epithelial cells lining the bile ducts. Due to its location deep within the body and nonspecific symptoms in the early stages, it is often diagnosed at the advanced stage, thus leading to worse prognosis. Circulating tumor cells within liquid biopsies (i.e. blood) have been considered as promising biomarkers for CCA diagnosis, though current methods for profiling them are not satisfactory in terms of sensitivity and specificity. Herein we developed a new cancer cell probing and immuno-tracking assay known as "CAPTURE", which was performed on an integrated microfluidic system (IMS) to automate CCA diagnosis from bile with a sample amount of only 1 mL. The assay utilized magnetic beads surface-coated with two affinity reagents, a nucleic acid aptamer (HN16) and a glycosaminoglycan (SCH 45-mix), for capturing cancer cells in bile; the "gold standard" anti-epithelial cell adhesion molecule was used as a comparison. In a single-blind test of 54 CCA-positive (+) and 102 CCA-negative (-) clinical samples, sensitivities and specificities of 96 and 80%, respectively, were documented with the CAPTURE assay on-bench. An IMS composed of a centrifugal module for sample pretreatment and a CAPTURE module for cell capture and staining was integrated with a new "vertical integration module" for detecting cancer cells from bile without human intervention. Furthermore, a novel micro-tier structure within the centrifugal module was designed to block passage of gallbladder stones with diameters >1 mm, thereby preventing their interference during the subsequent CAPTURE assay. Improved sensitivity and specificity (100 & 83%, respectively) by using three affinity reagents were achieved on the IMS when using 26 clinical bile samples, confirming its clinical bio-applicability for CCA diagnosis. This approach could be therefore used for early-stage CCA diagnostics, ideally enabling effective treatment, as well as reducing potential for relapse.
PMID:38126571 | DOI:10.1039/d3lc00862b
J Surg Oncol. 2024 Feb 13. doi: 10.1002/jso.27600. Online ahead of print.
ABSTRACT
INTRODUCTION: Neuroendocrine neoplasms (NENs) are classified as neuroendocrine tumors (NETs), neuroendocrine carcinomas (NECs), and mixed neuroendocrine and nonneuroendocrine neoplasms (MiNENs) according to World Health Organization classification. We present our experience of NENs of the gallbladder (GB) from a high-volume cancer hospital.
MATERIALS AND METHODS: The present study is a retrospective analysis of all patients with GB NENs who presented between January 2015 and June 2023. The patient details and treatment received with follow-up were noted. The primary endpoint was overall survival (OS).
RESULTS: A total of 147 patients were included in the study. The median age was 52 (27-81) years. There was a female predominance (70.7%). NEC was the most common subtype (84.4%) followed by MiNEN (12.9%) and NET (2.7%). The most common stage at presentation was metastatic (70.7%) followed by locally advanced (21.8%), and early disease (7.5%). The median follow-up was 9.92 (1.77-76.06) months. Median OS was 6.14 (3.93-8.35) months. Median OS in patients who received multimodality treatment was 20.20 (17.99-22.41) months versus 4.00 (2.91-5.10) months in those who did not receive it.
CONCLUSION: GB NENs are rare, but aggressive tumors with NEC being the most common type. Multimodality treatment yields favorable outcomes. However, the development of better systemic therapy is needed to help improve survival further.
PMID:38348696 | DOI:10.1002/jso.27600
Rev Esp Enferm Dig. 2024 Feb 12;116. doi: 10.17235/reed.2024.10206/2023. Online ahead of print.
ABSTRACT
Obesity is considered a chronic disease and a serious public-health issue in Spain, as well as in many other countries, primarily because of it being a significant risk factor for multiple chronic conditions, including diabetes mellitus type 2, cardiovascular disease, respiratory disease, metabolic dysfunction-associated fatty liver disease, gastrointestinal conditions (gastroesophageal reflux, diverticulosis), musculoskeletal difficulties, infertility, and even development of some malignancies such as postmenopausal breast cancer, and colorectal, endometrial, renal, esophageal, pancreatic, hepatic, and gallbladder neoplasms. Furthermore, weight loss, whether as therapy goal or voluntary, has been shown to be beneficial for virtually all these health conditions, the more so the greater weight loss.
PMID:38345504 | DOI:10.17235/reed.2024.10206/2023
Cell Biochem Funct. 2024 Mar;42(2):e3952. doi: 10.1002/cbf.3952.
ABSTRACT
This study uncovered the potential clinical value and molecular driving mechanisms of circular RNAs (circRNAs) in gallbladder cancer (GBC). Differentially expressed circRNAs in GBC cells were screened by high-throughput sequencing. CircRNA_CDKN1A (circBase ID: hsa_circ_0076194) was knocked out in BGC-SD cells through transfection with sh-circRNA_CDKN1A. Then, proliferation was investigated via CCK8 and EdU assays, apoptosis via flow cytometry, migration via wound healing assays, and invasion via Transwell assays. Bioinformatics analysis of circRNA_CDKN1A-related signaling pathways was performed using MetScape and g:Profiler. Results showed that the knockdown of circRNA_CDKN1A enhanced the proliferation, migration, and invasion of GBC cells and inhibited apoptosis. In addition, knocking out circRNA_CDKN1A promoted GBC cell proliferation and enhanced the dry indices of the OCT4 protein and CD34 expression levels. The knockdown of circRNA_CDKN1A activated the epithelial-mesenchymal transition pathway. Bioinformatics analysis revealed that the biological role of circRNA_CDKN1A in GBC cells involved the NF-κB pathway. LY2409881, which is an NF-κB inhibitor, reversed the effects induced by the knockdown of circRNA_CDKN1A in GBC-SD cells. In summary, the knockdown of circRNA_CDKN1A promoted the progression of GBC by activating the NF-κB signaling pathway. For the first time, this study revealed the mechanism of circRNA_CDKN1A-mediated regulatory action in GBC and identified the newly discovered circRNA_CDKN1A-NF-κB signaling axis as a potentially important candidate for clinical therapy and prognostic diagnosis of GBC.
PMID:38343018 | DOI:10.1002/cbf.3952
Int J Surg Case Rep. 2024 Mar;116:109344. doi: 10.1016/j.ijscr.2024.109344. Epub 2024 Feb 8.
ABSTRACT
INTRODUCTION AND IMPORTANCE: Synchronous primary cancers in the stomach and gallbladder were not previously reported in the medical literature. Pseudotumor pancreatitis was also described many years ago. It was misdiagnosed and required surgery for pancreatic head neoplasms.
PRESENTATION OF CASE: A 57-year-old male patient went to our hospital for abdominal pain. He was indicated for gastroduodenal endoscopy, and the result was adenocarcinoma. Abdominal ultrasound and Ctscan detected the gallbladder fundus's localized thickening structure and the pancreatic head's hyperechoic structure. The endoscopic ultrasound and MRI showed a gallbladder + pancreatic head tumor with chronic pancreatitis with pancreatic stones. The patient underwent distal gastrectomy, cholecystectomy, and pancreaticoduodenectomy.
CLINICAL DISCUSSION: The detection of gastric cancer is often based on upper gastrointestinal endoscopy and biopsy results. Gallbladder cancer is often diagnosed at an advanced stage, and only very few patients are diagnosed early. Pancreatic cancer often occurs in the head of the pancreas. Symptoms may include obstruction of the common bile and Wirsung duct, often in advanced stages. Surgery for the gallbladder, distal stomach, and head of pancreatic tumors are related to each other located in a neighboring location in the anatomy, so surgery to remove all three tumors is relatively similar to a pancreaticoduodenectomy procedure.
CONCLUSION: Synchronous tumors of gastric carcinoma combined with gallbladder cancer and pseudotumor chronic pancreatitis are rare. The attitude of treating these three diseases at the same time requires a tumor board. Simultaneous surgery for gallbladder, stomach, and pancreatic head tumors can be performed if the tumors are still in the resectable stage.
PMID:38340624 | PMC:PMC10943665 | DOI:10.1016/j.ijscr.2024.109344
Endoscopy. 2024 Dec;56(S 01):E129. doi: 10.1055/a-2241-1656. Epub 2024 Feb 7.
NO ABSTRACT
PMID:38325418 | PMC:PMC10849835 | DOI:10.1055/a-2241-1656
Ann Hepatobiliary Pancreat Surg. 2024 Feb 29;28(1):114. doi: 10.14701/ahbps.28-1_C. Epub 2024 Feb 7.
NO ABSTRACT
PMID:38321654 | PMC:PMC10896688 | DOI:10.14701/ahbps.28-1_C
Curr Opin Gastroenterol. 2024 Mar 1;40(2):92-98. doi: 10.1097/MOG.0000000000001005. Epub 2024 Feb 8.
ABSTRACT
PURPOSE OF REVIEW: This review discusses evidence regarding progenitor populations of the biliary tree in the tissue regeneration and homeostasis, and the pathobiology of cholangiopathies and malignancies.
RECENT FINDINGS: In embryogenesis biliary multipotent progenitor subpopulation contributes cells not only to the pancreas and gall bladder but also to the liver. Cells equipped with a constellation of markers suggestive of the primitive endodermal phenotype exist in the peribiliary glands, the bile duct glands, of the intra- and extrahepatic bile ducts. These cells are able to be isolated and cultured easily, which demonstrates the persistence of a stable phenotype during in vitro expansion, the ability to self-renew in vitro, and the ability to differentiate between hepatocyte and biliary and pancreatic islet fates.
SUMMARY: In normal human livers, stem/progenitors cells are mostly restricted in two distinct niches, which are the bile ductules/canals of Hering and the peribiliary glands (PBGs) present inside the wall of large intrahepatic bile ducts. The existence of a network of stem/progenitor cell niches within the liver and along the entire biliary tree inform a patho-biological-based translational approach to biliary diseases and cholangiocarcinoma since it poses the basis to understand biliary regeneration after extensive or chronic injuries and progression to fibrosis and cancer.
PMID:38320197 | DOI:10.1097/MOG.0000000000001005
Arch Iran Med. 2023 Sep 1;26(9):504-509. doi: 10.34172/aim.2023.76.
ABSTRACT
BACKGROUND: Epidemiological research on the high-risk population might be helpful in early detection and prevention of biliary tract malignancies. This study assesses the prevalence of biliary tract cancer (BTC) in the Golestan province, northeastern Iran, between 2004 and 2016.
METHODS: The current study used information from the Golestan Population-based Cancer Registry (GPCR) to access the epidemiology of BTC across a 13-year period while taking into account temporal and geographic differences. The number of cases, crude rates, age-standardized incidence rates (ASRs) per 100,000 person-years, average annual percent change (AAPC), age-specific incidence rates, and 95% confidence intervals (CI) were reported for each year with respect to gender and place of residence.
RESULTS: Totally, 224 instances of BTC overall (54% of whom were females) were reported throughout the research period. The ASR of BTC was 1.7 (95% CI: 1.4‒2) for females and 1.4 (95% CI: 1.1‒1.6) for men, respectively. Males exhibited a growing time trend in incidence (AAPC: 7.18; CI: 0.06‒14.81; P-value:0.048), whereas females had a decreasing trend (AAPC: 0.82; CI: -5.94‒4.57; P-value: 0.740). Both sexes saw an increase in age-specific incidence rates starting at the age of 45; however, males experienced a significant increase in incidence in the age group of 75 to 79 while the female rates grew steadily.
CONCLUSION: The focus for cancer control in this region may be given to demographic groups with a combination of risk factors, including male gender, older age, and urban residence.
PMID:38310406 | PMC:PMC10862055 | DOI:10.34172/aim.2023.76
Langenbecks Arch Surg. 2024 Feb 2;409(1):51. doi: 10.1007/s00423-024-03247-6.
ABSTRACT
BACKGROUND: The neutrophil-lymphocyte ratio (NLR) and platelet distribution width (PDW) are associated with poor prognosis in various cancers. We aimed to analyze the prognostic value of the combination of preoperative NLR and PDW in patients with gallbladder carcinoma (GBC).
METHODS: A total of 287 GBC patients who underwent curative-intent surgery in our institution was included. The relationship between NLR and PDW and clinicopathological features were analyzed. The receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for NLR and PDW. Overall survival (OS) was estimated using the Kaplan-Meier method. Meanwhile, the univariate and multivariate Cox regression models were used to assess the risk factors for OS.
RESULTS: The optimal cutoff value of NLR and PDW was 3.00 and 14.76, respectively. In addition, survival analysis demonstrated that patients with NLR > 3.00 and PDW > 14.76 had a worse prognosis than patients with NLR ≤ 3.00 and PDW ≤ 14.76, respectively. The multivariate analysis showed that NLR and PDW were independent prognostic factors in the patients with GBC. When we combined NLR and PDW, the area under the ROC curve increased from 0.665 (NLR) and 0.632 (PDW) to 0.676. Moreover, the 1-, 3-, and 5-year OS of group A (patients with NLR ≤ 3.00 and PDW ≤ 14.76), group B (patients with either of NLR > 3.00 or PDW > 14.76) and group C (patients with NLR > 3.00 and PDW > 14.76) were 88.7%, 62.6%, 28.1%, 65.1%, 26.9%, 13.1%, and 34.8%, 8.3%, 0%, respectively.
CONCLUSION: The combination of NLR and PDW may serve as a significant prognostic biomarker for GBC patients superior to either NLR or PDW alone.
PMID:38305889 | DOI:10.1007/s00423-024-03247-6
Gan To Kagaku Ryoho. 2023 Dec;50(13):1609-1611.
ABSTRACT
An 88-year-old woman had been diagnosed with hilar cholangiocarcinoma for 3 years since she received metallic stents for malignant biliary obstruction, and observed without any aggressive medical treatment. She was admitted to our hospital for further investigation of her abdominal pain. Abdominal CT showed an enlarged gallbladder, fluid collection in the right paracolic gutter, and swollen appendix. Laboratory tests showed high-grade inflammation. She was diagnosed with acute perforated appendicitis with acute cholecystitis. Laparoscopic cholecystectomy and appendectomy were performed. Perforation was confirmed intraoperatively in the appendix wall and accumulation of pus was found in the right paracolic gutter. There were no macroscopic findings of metastasis and peritoneal dissemination. Microscopic examination of the resected appendix showed adenocarcinoma cells positive for CK7 and negative for CK20 and CDX2, and were predominantly infiltrated from the muscular layer to the serosa of the appendix wall, with a diagnosis of appendiceal metastasis from hilar cholangiocarcinoma. Metastatic appendiceal carcinoma is rare, and appendiceal metastasis from hilar cholangiocarcinoma is extremely rare. Herein, we report a rare case of metastatic appendiceal carcinoma from hilar bile duct cancer with acute perforated appendicitis and cholecystitis along with findings of previous literature.
PMID:38303357
Gan To Kagaku Ryoho. 2023 Dec;50(13):1962-1964.
ABSTRACT
A 73-year-old female was diagnosed with gallbladder cancer, but the future liver remnant volume was deemed insufficient for curative resection. Consequently, transileocolic portal vein embolization was performed. During laparotomy, multiple nodules were palpable on the peritoneal surface of the pelvic floor. Subsequently, staging laparoscopy confirmed the pathological diagnosis of adenocarcinoma in the resected nodules, indicating peritoneal dissemination of gall bladder cancer. Due to this peritoneal dissemination, surgical resection was deemed inappropriate, and the patient was initiated on systemic chemotherapy consisting of gemcitabine and cisplatin. Following 22 courses of chemotherapy, contrast-enhanced computed tomography demonstrated no significant changes in the size of the primary tumor or its location relative to the main vessels, although a small metastatic lesion was identified in the gallbladder bed. At the second staging laparoscopy, any nodules suggesting peritoneal dissemination were observed. Based on these findings, we decided to perform curative resection. The surgical procedure involved right hepatectomy plus segment 4a resection, extrahepatic bile duct resection, and hepaticojejunostomy. Pathological examination revealed ypT3bN0M1(HEP), ypStage ⅣB, with the achievement of R0 resection. The patient survived with no recurrences for 40 months after surgery. These results suggest that aggressive therapeutic strategies, including conversion surgery following systemic chemotherapy, may be beneficial for patients initially deemed unresectable due to gallbladder cancer.
PMID:38303265
Gan To Kagaku Ryoho. 2023 Dec;50(13):1792-1794.
ABSTRACT
All three patients were female, one in her 50s, and the other two in their 60s. The one in her 50s had liver metastasis and the other two had unresectable advanced cholecystic carcinomas with peritoneal dissemination. All three received 8-12 courses of gemcitabine plus CDDP(GC). After GC, all three were deemed to be candidates for R0 resection and underwent resection of two central liver segments. In addition, the second patient required an extrahepatic cholangiectomy; an extended cholecystectomy, plus an extrahepatic cholangiectomy, plus a complete omental resection; and the third needed an extended cholecystectomy, plus an extrahepatic cholangiectomy with a partial transverse colon resection, plus a partial duodenectomy. The pathologic response to chemotherapy was moderate in the patient with liver metastases, mild in the one who underwent the omental resection, and moderate in the patient who had the partial resection of the digestive tract. All three patients continued with postoperative chemotherapy. The patient with liver metastases and the one with the partial gastrointestinal tract resection have survived without recurrence for 52 months and 43 months, respectively, after the initial treatment. The patient with the omental resection has survived 44 months after the initial treatment with recurrent peritoneal dissemination and is continuing chemotherapy as an outpatient. Although further study is needed to accumulate more cases, the results suggest the usefulness of multidisciplinary treatment including conversion surgery in cases such as these.
PMID:38303209
Hum Pathol. 2024 Feb;144:46-52. doi: 10.1016/j.humpath.2024.01.011. Epub 2024 Jan 30.
ABSTRACT
Enteroblastic carcinoma is clinically characterized by an elevated serum level of alpha-fetoprotein (AFP) and is histologically characterized by cancer cells with a clear cytoplasm and 'blastic' coarse chromatin. It sometimes has an element of hepatoid carcinoma; therefore, these two neoplasms are often regarded as sister entities. Although hepatoid carcinoma in the biliary tree has been reported, enteroblastic cholangiocarcinoma is extremely uncommon. In the present study, four cases of enteroblastic cholangiocarcinoma were examined. Tumors were located inside the liver (n = 2) or common bile duct (n = 2). The two intrahepatic cases had a history of primary sclerosing cholangitis, and serum AFP levels were elevated in both. One unresectable case was diagnosed by needle liver biopsy, while the remaining three underwent surgical resection. Histologically, all cases showed similar microscopic features. Cuboidal or polygonal cancer cells with the characteristic clear cytoplasm and subnuclear vacuoles were arranged in a papillary, micropapillary, tubular, or solid architecture. One case had an element of pancreatobiliary-type adenocarcinoma, while a hepatoid carcinoma element was not observed in any cases. All cases were positive for AFP, glypican 3, and SALL4, with SALL4 being the most widely expressed. Heppar-1 and arginase-1 were negative, except for one case, which was positive for Heppar-1. In conclusion, enteroblastic cholangiocarcinoma is an uncommon subtype of biliary tract malignancy. These cases may have been categorized as 'clear cell' cholangiocarcinoma. Although enteroblastic cholangiocarcinoma seems to occur more commonly in extrahepatic regions, including the gallbladder, it may also develop in the liver, particularly in patients with primary sclerosing cholangitis.
PMID:38301963 | DOI:10.1016/j.humpath.2024.01.011
Arch Iran Med. 2023 Jul 1;26(7):411-412. doi: 10.34172/aim.2023.62.
ABSTRACT
Gallbladder neuroendocrine tumors remain relatively rare in the clinical setting. They are generally asymptomatic and reported as incidental findings. The diagnosis is exclusively made by histopathological and immunohistological examination according to the recent WHO guidelines. Here, we present the case of a 58-year-old woman with small-cell gallbladder neuroendocrine carcinoma.
PMID:38301101 | PMC:PMC10685815 | DOI:10.34172/aim.2023.62
World J Gastrointest Oncol. 2024 Jan 15;16(1):13-29. doi: 10.4251/wjgo.v16.i1.13.
ABSTRACT
Gallbladder (GB) carcinoma, although relatively rare, is the most common biliary tree cholangiocarcinoma with aggressiveness and poor prognosis. It is closely associated with cholelithiasis and long-standing large (> 3 cm) gallstones in up to 90% of cases. The other main predisposing factors for GB carcinoma include molecular factors such as mutated genes, GB wall calcification (porcelain) or mainly mucosal microcalcifications, and GB polyps ≥ 1 cm in size. Diagnosis is made by ultrasound, computed tomography (CT), and, more precisely, magnetic resonance imaging (MRI). Preoperative staging is of great importance in decision-making regarding therapeutic management. Preoperative staging is based on MRI findings, the leading technique for liver metastasis imaging, enhanced three-phase CT angiography, or magnetic resonance angiography for major vessel assessment. It is also necessary to use positron emission tomography (PET)-CT or 18F-FDG PET-MRI to more accurately detect metastases and any other occult deposits with active metabolic uptake. Staging laparoscopy may detect dissemination not otherwise found in 20%-28.6% of cases. Multimodality treatment is needed, including surgical resection, targeted therapy by biological agents according to molecular testing gene mapping, chemotherapy, radiation therapy, and immunotherapy. It is of great importance to understand the updated guidelines and current treatment options. The extent of surgical intervention depends on the disease stage, ranging from simple cholecystectomy (T1a) to extended resections and including extended cholecystectomy (T1b), with wide lymph node resection in every case or IV-V segmentectomy (T2), hepatic trisegmentectomy or major hepatectomy accompanied by hepaticojejunostomy Roux-Y, and adjacent organ resection if necessary (T3). Laparoscopic or robotic surgery shows fewer postoperative complications and equivalent oncological outcomes when compared to open surgery, but much attention must be paid to avoiding injuries. In addition to surgery, novel targeted treatment along with immunotherapy and recent improvements in radiotherapy and chemotherapy (neoadjuvant-adjuvant capecitabine, cisplatin, gemcitabine) have yielded promising results even in inoperable cases calling for palliation (T4). Thus, individualized treatment must be applied.
PMID:38292841 | PMC:PMC10824116 | DOI:10.4251/wjgo.v16.i1.13
J Med Case Rep. 2024 Jan 31;18(1):62. doi: 10.1186/s13256-023-04323-z.
ABSTRACT
BACKGROUND: Angiosarcoma of the gallbladder is a rare diagnostic entity rarely encountered by pathologists and has rarely been reported in literature. This review aimed to examine the clinicopathological features, immunohistochemistry, treatment, and outcomes of gallbladder angiosarcoma.
METHODS: A search of the PubMed, Science Direct and Google Scholar was done with the search terms ("angiosarcoma" OR "angiosarcomas") AND ("gallbladder" OR "gallbladders"). Based on inclusion and exclusion criteria, only case reports could be used for this review.
RESULT: 8 case reports were chosen in the end for analysis. The mean age of the patients at presentation was 65 years. It was most frequently observed in males. Abdominal pain and palpable mass were the most commonly reported symptoms. Cholelithiasis and anemia were also reported. On histopathology morphologically epithelioid appearance of angiosarcoma was evident. Cytokeratin (CK) AE1/AE3, Von willebrand factor, Factor VIII antigen, Vimentin, CD31 were positive. Meanwhile, UEA, CD34, CD117, S-100, Keratin, EMA, and CEA showed negative outcome. Surgery was the preferred method of treatment and a mean 10-months follow-up was done.
CONCLUSION: Despite the unavailability of convincing data, histological and immunohistochemical analyses play a major role in the diagnosis of gallbladder angiosarcoma. Nevertheless, more comprehensive clinical studies are required to provide universal guidelines for the treatment and diagnosis of angiosarcoma of the gallbladder.
PMID:38291481 | PMC:PMC10829334 | DOI:10.1186/s13256-023-04323-z
Gastroenterol Clin North Am. 2024 Mar;53(1):85-108. doi: 10.1016/j.gtc.2023.10.001. Epub 2023 Nov 17.
ABSTRACT
Most precursor lesions and early cancerous changes in the gallbladder and bile ducts present as clinically/grossly inapparent lesions. Low-grade dysplasia is difficult to define and clinically inconsequential by itself; however, extra sampling is required to exclude accompanying significant lesions. For high-grade dysplasia ('carcinoma in situ'), a complete sampling is necessary to rule out invasion. Tumoral intramucosal neoplasms (ie, intracholecystic and intraductal neoplasia) form radiologically/grossly visible masses, and they account for (present in the background of) about 5% to 10% of invasive cancers of the region. These reveal a spectrum of papilla/tubule formation, cell lineages, and dysplastic transformation. Some subtypes such as intracholecystic tubular non-mucinous neoplasm of the gallbladder (almost never invasive) and intraductal oncocytic or intraductal tubulopapillary neoplasms of the bile ducts (may have a protracted clinical course even when invasive) are to be noted separately. Other types of intracholecystic/intraductal neoplasia have a high frequency of invasive carcinoma and progressive behavior, which often culminates in mortality.
PMID:38280752 | DOI:10.1016/j.gtc.2023.10.001
Discov Med. 2024 Jan;36(180):48-60. doi: 10.24976/Discov.Med.202436180.4.
ABSTRACT
Biliary tract malignant tumors account for about 3% of gastrointestinal malignancies. Based on anatomical location, biliary tract malignant tumors can be divided into gallbladder carcinoma, intrahepatic cholangiocarcinoma (ICC), hilar cholangiocarcinoma, and distal cholangiocarcinoma. Surgical treatment is the main treatment for early-stage biliary malignant tumors, the insidious nature of the disease often leads to late diagnoses, causing many patients missing the window for surgical intervention. Gemcitabine combined with cisplatin serves as a first-line treatment for patients with advanced or unresectable lesions, however, a definitive standard for second-line treatment has not yet been established. In recent years, many advances have occurred in the study of the molecular mechanisms contributing to the occurrence and development of biliary malignancies, providing a foundation for targeted treatments of the disease. This review summarizes the existing literature and explores potential second-line treatment options for advanced biliary malignancies based on our understanding of the molecular pathogenesis and tumor pathology.
PMID:38273745 | DOI:10.24976/Discov.Med.202436180.4
Korean J Gastroenterol. 2024 Jan 25;83(1):1-5. doi: 10.4166/kjg.2023.135.
ABSTRACT
Biliary tract cancers encompass a group of malignancies that affect the bile ducts and gallbladder and are associated with a poor prognosis, often due to late diagnosis and limited treatment options. The incidence of biliary tract cancer has been increasing gradually, underscoring the need for a better understanding of its pathogenesis and potential risk factors. Research suggests that biliary tract cancer may develop through a combination of genetic and epigenetic alterations, as well as environmental factors. The role of microbial exposure and the human microbiome in the pathogenesis of biliary tract cancer is an emerging area of interest. Traditionally, the biliary tree was considered sterile under normal conditions, but recent studies have identified associations between specific microbiological patterns and inflammatory biliary diseases and cancer. The human microbiome plays a crucial role in maintaining host homeostasis and interacting with the host's immune system. Dysbiosis, or an imbalance in the microbiome composition, has been implicated in the development of various diseases, including cancer. Hence, dysbiosis in the biliary tract might trigger the pathogenesis of biliary tract cancer. Advances in next-generation sequencing technology have provided researchers with a more comprehensive view of the microbiota and their potential roles in health and disease, providing more evidence of the relationship between the microbiota and biliary tract cancer. This review summarizes the latest evidence of the microbiome that would be associated with biliary tract cancer.
PMID:38268162 | DOI:10.4166/kjg.2023.135
Eur J Cancer. 2024 Mar;199:113564. doi: 10.1016/j.ejca.2024.113564. Epub 2024 Jan 20.
ABSTRACT
Biliary tract cancers (BTCs) encompass a heterogeneous group of rare tumors, including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC) and ampullary cancer (AC). The present first-line palliative treatment regimen comprises gemcitabine and cisplatin in combination with immunotherapy based on two randomized controlled studies. Despite the thorough investigation of these palliative treatments, long-term survival remains low. Moving beyond conventional chemotherapies and immunotherapies, the realm of precision medicine has demonstrated remarkable efficacy in malignancies such as breast and gastric cancers, characterized by notable HER2 overexpression rates. In the context of biliary tract cancer, significant HER2 alterations are observed, particularly within eCCA and GBC, heightening the interest in precision medicine. Various anti-HER2 therapies, including trastuzumab, pertuzumab, trastuzumab-deruxtecan, zanidatamab and neratinib, have undergone investigation. The objective of this review is to summarize the current evidence and outline future directions of targeted HER2 treatment therapy in patients with biliary tract tumors, specially extrahepatic cholangiocarcinoma and gallbladder cancer.
PMID:38266541 | DOI:10.1016/j.ejca.2024.113564
J Cancer Res Ther. 2024 Jan 22. doi: 10.4103/jcrt.jcrt_172_23. Online ahead of print.
ABSTRACT
INTRODUCTION: Ultrasound- and CT-guided fine needle aspiration cytology (FNAC) increases the accessibility of intra-abdominal masses to the liver and gall bladder with the advantages of low cost and high diagnostic yield. Cell block technique has been known for further increasing the diagnostic accuracy.
AIMS AND OBJECTIVES: We aimed to study the effectiveness of FNAC and the cell block method in cytological diagnosis of liver and gall bladder masses. We also followed a step-wise approach to increase the success rate.
MATERIALS AND METHODS: A 2-year observational study was done from July 2020 to June 2022. Total 80 guided (CT and ultrasound) aspirations were done from space occupying/mass lesions in the liver [74 (92.5%)] and gall bladder [6 (7.5%)], out of which cell blocks by the plasma thrombin method were prepared in 12 cases (15%). The on-site radiological details were noted, and rapid on-site evaluation was done in 65 cases (81.25%). The prepared cytology slides were stained with Papanicolaou, H and E and May-Grunwald Giemsa (MGG) stain. The cytological diagnosis was noted, and the uses and limitations (if any) were observed in each case. A step-wise structured questionnaire format was developed to assist the reporting pathologist so as not to miss out on important diagnostic observations, if present.
RESULTS: FNAC in 71 cases (88.7%) gave a conclusive diagnosis. The maximum number of cases were of adenocarcinoma [38 (51.3%)] from the liver followed by hepatocellular carcinoma in 10 cases (13.5%). In gall bladder masses, all 6 cases (100%) were positive for malignancy, out of which 4 cases (66.7%) could be characterized as adenocarcinoma. The cell block preparation was helpful in reaching the diagnosis as well as typing the malignancy in 10 cases (83.3%). The chief limitation observed on conventional cytology smears was inadequate cellularity, which caused inconclusive diagnosis in 9 cases (11.25%). The reporting questionnaire was helpful chiefly in terms of time-efficient reporting in 34 cases (42.5%), increasing the ease and confidence in 69 cases (86.25%) and the advantage of reproducibility of data in all cases (100%) according to the case-by-case evaluation by the reporting pathologists.
CONCLUSION: Guided FNAC in conjunction with the cell block technique is extremely helpful in the evaluation of mass lesions of the liver and gall bladder for cytological diagnosis. A proper step-wise approach may be useful to reach a quick and effective diagnosis.
PMID:38261468 | DOI:10.4103/jcrt.jcrt_172_23
Indian J Cancer. 2023 Oct 1;60(4):447-448. doi: 10.4103/ijc.ijc_2_24. Epub 2024 Jan 23.
NO ABSTRACT
PMID:38258868 | DOI:10.4103/ijc.ijc_2_24
Langenbecks Arch Surg. 2024 Jan 22;409(1):45. doi: 10.1007/s00423-024-03233-y.
ABSTRACT
PURPOSE: To elucidate the clinical significance of peritoneal washing cytology (PWC) in patients with resectable biliary tract cancer (BTC).
METHODS: Clinical data of patients with BTC, who received PWC at curative intent surgery from March 2009 to December 2021, were retrospectively analyzed. Eligible patients were stratified into two groups according to positive or negative PWC. Recurrence-free survival and overall survival were compared between the two groups. Independent factors associated with positive PWC were investigated using multivariate analysis.
RESULTS: Among the 284 patients analyzed, all 53 patients with ampullary carcinoma showed negative PWC and these patients were excluded. Among the remaining eligible 231 patients, 41 patients had intrahepatic cholangiocarcinoma, 55 had gall bladder carcinoma, 72 had hilar cholangiocarcinoma, and 63 had distal cholangiocarcinoma. Eleven (4.8%) patients had positive PWC, and 220 (95.2%) had negative PWC. The median recurrence-free survival in the positive and negative PWC groups were 12.0 vs. 60.7 months (p = 0.005); the median overall survival times were 17.0 vs. 60.6 months (p = 0.008), respectively. Multivariate analysis revealed that serum carbohydrate antigen 19-9 level over 80 U/mL and multiple lymph node metastasis were independently associated with positive PWC (odds ratio [OR]: 5.84, p = 0.031; OR: 5.28, p = 0.021, respectively).
CONCLUSION: Patients with positive PWC exhibited earlier recurrence and shorter survival times compared with those with negative PWC.
PMID:38252293 | PMC:PMC10803468 | DOI:10.1007/s00423-024-03233-y
ANZ J Surg. 2024 Jan 22. doi: 10.1111/ans.18869. Online ahead of print.
ABSTRACT
BACKGROUND: Management of early-stage gallbladder cancer is becoming more important as the rate of early detection is increasing. Although there have been many studies about the clinical implication of the invasion depth or peritoneal/hepatic location of gallbladder cancers, there is no study on the clinical implication of the geometric location of cancer along the longitudinal length of the gallbladder.
METHODS: The location of gallbladder cancer was defined as the geometric center of the primary site of a tumour, which lies on the longitudinal diameter of the surgical specimens. We compared the oncologic outcomes following surgery between gallbladder cancers located on the fundal end and those located on the cystic ductal end. We also analysed patients with stage 1 gallbladder cancer who recurred after surgery.
RESULTS: A total of 575 patients with gallbladder cancer were included in this study. Patients with gallbladder cancer on the cystic ductal end had significantly lower rates of recurrence-free survival (P = 0.016) and overall survival (P = 0.023) compared to those with gallbladder cancer on the fundal end. Among 90 patients with stage 1 gallbladder cancer, three patients had a recurrence, all of whom had cystic ductal end gallbladder cancer and showed cystic duct invasion or concomitant xanthogranulomatous cholecystitis in permanent pathology.
CONCLUSIONS: Gallbladder cancers on the cystic ductal end had worse postoperative oncologic outcomes compared with those on the fundal end.
PMID:38251805 | DOI:10.1111/ans.18869
Curr Probl Cardiol. 2024 Mar;49(3):102403. doi: 10.1016/j.cpcardiol.2024.102403. Epub 2024 Jan 17.
ABSTRACT
BACKGROUND: Randomized controlled trials (RCTs) have shown variable cardiovascular (CV) outcomes in overweight or obese patients without diabetes mellitus (DM) who are treated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) vs. placebo. We conducted a meta-analysis of the available studies.
METHODS: Online databases were searched for RCTs comparing GLP-1 RA to placebo in overweight or obese non-diabetic patients. The clinical endpoints of interest were major adverse CV events (MACE), CV death, all cause death, myocardial infarction (MI), stroke, revascularization, total adverse events and their subtypes. Pooled odds ratios (OR) and 95 % confidence intervals (CI) were calculated using a random-effects model.
RESULTS: A total of 10 RCTs with 29,325 patients (n = 16,900 GLP-1 RA, n = 12,425 placebo) were included. The mean age was 48 years and 34 % of patients were men. As compared with placebo, the GLP-1 RA group was associated with significant reduction of MACE (OR 0.79, 95 % CI 0.71-0.89, p < 0.0001), all cause death (OR 0.80, 95 % CI 0.70-0.92, p = 0.002), MI (OR 0.72, 95 % CI 0.61-0.85, p = 0.0001) and revascularization (OR 0.76, 95 % CI 0.67-0.86, p < 0.0001), without any differences in CV death or stroke. Total adverse events, gastrointestinal and gallbladder-related disorders were higher in the GLP-1 RA group, with a similar rate of renal adverse events, malignant neoplasms and acute pancreatitis to placebo.
CONCLUSION: In overweight or obese patients without DM, patients treated with GLP-1 RAs had significantly reduced MACE, all cause death, MI and revascularization when compared with placebo.
PMID:38237815 | DOI:10.1016/j.cpcardiol.2024.102403
Acad Radiol. 2024 Jan 16:S1076-6332(23)00677-3. doi: 10.1016/j.acra.2023.12.002. Online ahead of print.
ABSTRACT
RATIONALE AND OBJECTIVES: Fibroblast Activation Protein (FAP) expressing cancer-associated fibroblasts has been a major breakthrough causing a paradigm shift in targeted theranostics focusing on the tumor microenvironment. In this study, a squaric acid derivative DOTA.SA.FAPi (SA.FAPi) has been evaluated as a potential diagnostic probe in diverse epithelial cancers and compared to the standard-of-care 18F-FDG.
METHODS: 25 patients enrolled in this prospective study underwent 18F-FDG and 68Ga-SA.FAPi PET scans on two different days. For biodistribution, standardized uptake values (SUV) were computed by delineating region-of-interest on various body organs. For comparative analysis in disease identification, lesion tracer uptake was quantified using SUVs corrected for lean body mass (SUL), SUVmax, tumor-to-background ratio (TBR) with liver and blood pool as the reference, total lesion glycolysis (TLG for 18F-FDG) and total lesion FAP expression (TLF for 68Ga-SA.FAPi).
RESULTS: 25 patients (mean age: 58 ± 8 years) with four types of cancers including hepatocellular carcinoma (HCC, 56% of cohort), gall bladder carcinoma (GB Ca, 12%), adrenocortical carcinoma (ACC, 16%), and breast carcinoma (breast Ca, 16%) were prospectively evaluated. Physiological tracer uptake of 68Ga-SA.FAPi was noted in the salivary glands, thyroid, liver, pancreas, muscles and kidneys with variable uptake in the lacrimal glands, extra-ocular muscles, oral mucosa and uterus. Lesion-based comparative analysis between both the radiotracers demonstrated complete concordant findings in detection of all primary lesions and distant metastases in liver, bones, adrenals and peritoneum whereas discordant findings were noted in lung nodules (20%) and lymph nodes (13%). In overall analysis, 68Ga-SA.FAPi exhibited significantly higher SUVmax (10.3 vs 8.8, p-0.019), SULpeak (6.8 vs 4.9, p-0.000) and SULavg (5.4 vs 4.1, p-0.019) in comparison to 18F-FDG whereas TBR was comparable for both the tracers [TBRLiver: median 1.9 (IQR: 2.6-1.4) vs 1.8 (2.6-1.1), p-0.275; TBRBloodpool: 2.1 (3.7-1.4) vs 2.0 (2.7-1.4), p-0.207]. In subcategorical analysis, 68Ga-SA.FAPi demonstrated higher SUVmax, SULpeak and SULavg values for primary disease (SUVmax: 14.8 (18.7-9.7) vs (12.9-6.6), p-0.087; SULpeak: 8.2 (11.2-6.8) vs 6.3 (8.5-4.4), p-0.037; SULavg: 6.9 ± 2.5 vs 5.1 ± 2.2, p-0.023] and distant metastases (8.8 vs 7.2, p-0.038); 6.3 (8.8-4.4) vs 3.6 (4.4-2.0), p-0.000; 5.4 vs 3.5, p-0.000] whereas comparable values were noted for both the tracers in nodal metastases [9 (13.5-4.1) vs 8 (12.7-4.7), p-0.726; 4.5 (6.2-1.8) vs 4.3 (5.7-2.2), p-0.727; 4.1 ± 2.3 vs 3.7 ± 1.8, p-0.129]. In primary disease, highest 68Ga-SA.FAPi avidity was noted in ACC followed by GB Ca and HCC. In distant metastases, gall bladder, lung and skeletal lesions demonstrated higher 68Ga-SA.FAPi avidity. Moreover, 68Ga-SA.FAPi identified five additional lung lesions which were missed by 18F-FDG in one case of ACC.
CONCLUSION: 68Ga-SA.FAPi emerged as an effective, versatile diagnostic probe for imaging various epithelial malignancies similar to 18F-FDG.
PMID:38233261 | DOI:10.1016/j.acra.2023.12.002
Korean J Clin Oncol. 2023 Dec;19(2):88-92. doi: 10.14216/kjco.23016. Epub 2024 Dec 31.
ABSTRACT
A 78-year-old female patient was initially treated with laparoscopic radical cholecystectomy for gallbladder cancer (pT2aN1M0, stage IIIB). The patient then received adjuvant chemotherapy with gemcitabine. After completion of adjuvant chemotherapy, multiple lymph node metastases were observed in follow-up computed tomography (CT) scan, but the patient refused to go through further chemotherapy. One year after the recurrence, carbohydrate antigen 19-9 (CA19-9) level was 1,925 U/mL with follow-up high-resolution CT/abdomen-pelvic CT showing the increased size of multiple lymph node metastases, and the patient began to undergo Viscum album therapy (0.2 mg, subcutaneously, three times a week). After the V. album therapy was initiated, a decrease in the size of metastatic lymph nodes and CA19-9 level, which was decreased to 252 U/mL, was observed. Seventeen months after continuous V. album therapy, the patient agreed to have palliative chemotherapy. The patient underwent gemcitabine plus cisplatin chemotherapy and showed stable disease during follow-up. This case report suggests that V. album therapy showed anticancer effects and may act as a bridge to palliative chemotherapy for patients with inappropriate general conditions to undergo chemotherapy for recurrent gallbladder cancer.
PMID:38229495 | PMC:PMC10792366 | DOI:10.14216/kjco.23016
PET Clin. 2024 Apr;19(2):163-175. doi: 10.1016/j.cpet.2023.12.003. Epub 2024 Jan 11.
ABSTRACT
[18F] Fluorodeoxyglucose (18F-FDG) PET/CT can improve the staging accuracy and clinical management of patients with hepatobiliary and pancreatic cancers, by detection of unsuspected metastases. 18F-FDG PET/CT metabolic parameters are valuable in predicting treatment response and survival. Metabolic response on 18F-FDG PET/CT can predict preoperative pathologic response to neoadjuvant therapy in patients with pancreatic cancer and determine prognosis. Several novel non-FDG tracers, such as 68Ga prostate-specific membrane antigen (PSMA) and 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT, show promise for imaging hepatobiliary and pancreatic cancers with potential for radioligand therapy.
PMID:38212214 | DOI:10.1016/j.cpet.2023.12.003
JAMA Netw Open. 2024 Jan 2;7(1):e2351502. doi: 10.1001/jamanetworkopen.2023.51502.
ABSTRACT
IMPORTANCE: The association of adjuvant chemotherapy (AC) with survival in the general population of patients with resected biliary tract cancer (BTC) remains controversial. As such, the role of this treatment in the treatment of older adult patients (aged ≥70 years) needs to be evaluated.
OBJECTIVE: To describe the patterns of use of AC and compare survival outcomes of AC and observation in older adult patients following resection of BTC.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 8091 older adult patients with resected BTC with data available in the National Cancer Database from January 1, 2004, to December 31, 2019. Patients were divided into 2 cohorts: AC and observation. The AC cohort was subdivided into single-agent and multiagent AC treatment.
EXPOSURES: Adjuvant chemotherapy vs observation following BTC resection.
MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS) of patients who received AC compared with observation following resection of BTC as evaluated using Kaplan-Meier estimates and multivariable Cox proportional hazards regression models. Inverse probability of treatment weighting and propensity score matching were performed to address indication bias.
RESULTS: Between 2004 and 2019, of 8091 older adult patients with resected BTC identified (median [range] age, 77 [70-90] years; 5136 women [63.5%]; 2955 men [36.5%]), only one-third (2632 [32.5%]) received AC. There was an increase in the use of AC across the study period from 20.7% (n = 495) in 2004 to 2009 to 41.2% (n = 856) in 2016 to 2019. Age 80 years or older (odds ratio, 0.29; 95% CI, 0.25-0.33; P < .001) and gallbladder primary site (odds ratio, 0.71; 95% CI, 0.61-0.83; P < .001) were associated with a lower odds of AC. Following inverse probability of treatment weighting, as a composite, AC was not associated with improved survival (median OS, 20.5 months; 95% CI, 19.2-21.7 months) compared with observation (median OS, 19.0 months; 95% CI, 18.1-20.3 months). A longer median OS was associated with single-agent AC (21.5 months; 95% CI, 19.9-24.0 months) but not multiagent AC (19.1 months; 95% CI, 17.5-21.1 months) compared with observation (median OS, 17.3 months; 95% CI, 16.1-18.4 months). This improvement in OS with single-agent AC was not apparent on multivariable analysis (hazard ratio [HR], 0.97; 95% CI, 0.89-1.05; P = .44). However, age at diagnosis of 80 years or older (HR, 1.35; 95% CI, 1.28-1.42; P < .001) and treatment at nonacademic centers (HR, 1.14; 95% CI, 1.07-1.20, P < .001) were associated with worse OS.
CONCLUSIONS AND RELEVANCE: In this cohort study of older adult patients, AC was not associated with an improvement in survival compared with observation following BTC resection. These findings suggest the need for further study of AC for older adult patients who may benefit after curative intent surgery for BTC.
PMID:38206623 | PMC:PMC10784855 | DOI:10.1001/jamanetworkopen.2023.51502
Int J Mol Sci. 2023 Dec 30;25(1):543. doi: 10.3390/ijms25010543.
ABSTRACT
Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunotherapeutic approaches, as well as antibody-drug conjugates. This review provides an overview of the current landscape of treatment options, as well as promising future therapeutic targets.
PMID:38203714 | PMC:PMC10779232 | DOI:10.3390/ijms25010543
J Immunother Cancer. 2024 Jan 9;12(1):e008355. doi: 10.1136/jitc-2023-008355.
ABSTRACT
BACKGROUND: As an unconventional subpopulation of T lymphocytes, γδ T cells can recognize antigens independently of major histocompatibility complex restrictions. Recent studies have indicated that γδ T cells play contrasting roles in tumor microenvironments-promoting tumor progression in some cancers (eg, gallbladder and leukemia) while suppressing it in others (eg, lung and gastric). γδ T cells are mainly enriched in peripheral mucosal tissues. As the cervix is a mucosa-rich tissue, the role of γδ T cells in cervical cancer warrants further investigation.
METHODS: We employed a multiomics strategy that integrated abundant data from single-cell and bulk transcriptome sequencing, whole exome sequencing, genotyping array, immunohistochemistry, and MRI.
RESULTS: Heterogeneity was observed in the level of γδ T-cell infiltration in cervical cancer tissues, mainly associated with the tumor somatic mutational landscape. Definitely, γδ T cells play a beneficial role in the prognosis of patients with cervical cancer. First, γδ T cells exert direct cytotoxic effects in the tumor microenvironment of cervical cancer through the dynamic evolution of cellular states at both poles. Second, higher levels of γδ T-cell infiltration also shape the microenvironment of immune activation with cancer-suppressive properties. We found that these intricate features can be observed by MRI-based radiomics models to non-invasively assess γδ T-cell proportions in tumor tissues in patients. Importantly, patients with high infiltration levels of γδ T cells may be more amenable to immunotherapies including immune checkpoint inhibitors and autologous tumor-infiltrating lymphocyte therapies, than to chemoradiotherapy.
CONCLUSIONS: γδ T cells play a beneficial role in antitumor immunity in cervical cancer. The abundance of γδ T cells in cervical cancerous tissue is associated with higher response rates to immunotherapy.
PMID:38199610 | PMC:PMC10806547 | DOI:10.1136/jitc-2023-008355
Z Gastroenterol. 2024 Jan;62(1):37-42. doi: 10.1055/a-2207-5519. Epub 2024 Jan 9.
ABSTRACT
BACKGROUND: Patients with primary sclerosing cholangitis (PSC) carry increased risks for malignancy, among which cholangiocarcinoma (CCA) is the most frequent. We aimed to characterise a cohort of patients with PSC and intrahepatic CCA (iCCA) and to compare this cohort with CCA in different localisations.
METHODS: We performed a retrospective analysis of our medical database from 01.01.2007 to 30.06.2023 and differentiated CCA according to its localisation within the biliary tract into iCCA, perihilar CCA (pCCA), distal CCA (dCCA), and gallbladder carcinoma (GBC).
RESULTS: We identified 8 (28%) patients with iCCA, 14 (48%) patients with pCCA, 6 (21%) patients with GBC, and 1 (3%) patient with dCCA without significant differences in gender distribution and mean age. Mean time between diagnosis of PSC and CCA was 158±84 months for iCCA, 93±94 months for pCCA, and 77±69 months for GBC (p=0.230). At the time of CCA diagnosis, advanced-stage disease was present in 6 (75%) patients with iCCA, 13 (93%) patients with pCCA, and 2 (40%) patients with GBC (p=0.050). Only 5 (63%) patients with iCCA received curatively intended surgery, of whom 4 (80%) patients developed recurrence after a mean time of 38±31 months. Mean survival time in patients with iCCA (35±33 months) lay between patients with pCCA (14±8 months) and patients with GBC (57±58 months), but the difference was not statistically significant (p=0.131).
CONCLUSION: Patients with PSC and iCCA showed an advanced tumour stage at diagnosis and limited long-time survival, which was classified between pCCA with worse prognosis and GBC with better prognosis.
PMID:38195106 | DOI:10.1055/a-2207-5519
Cancer Imaging. 2024 Jan 8;24(1):7. doi: 10.1186/s40644-023-00651-x.
ABSTRACT
BACKGROUND: Ultrasound (US) has been widely used in screening and differential diagnosis of gallbladder wall thickening (GWT). However, the sensitivity and specificity for diagnosing wall-thickening type gallbladder cancer are limited, leading to delayed treatment or overtreatment. We aim to explore the value of high frame rate contrast enhanced ultrasound (H-CEUS) in distinguishing wall-thickening type gallbladder cancer (malignant) from GWT mimicking malignancy (benign).
METHODS: This retrospective study enrolled consecutive patients with non-acute GWT who underwent US and H-CEUS examination before cholecystectomy. Clinical information, US image and H-CEUS image characteristics between malignant and benign GWT were compared. The independent risk factors for malignant GWT on H-CEUS images were selected by multivariate logistic regression analysis. The diagnostic performance of H-CEUS in determining malignant GWT was compared with that of the gallbladder reporting and data system (GB-RADS) score.
RESULTS: Forty-six patients included 30 benign GWTs and 16 malignant GWTs. Only mural layering and interface with liver on US images were significantly different between malignant and benign GWT (P < 0.05). Differences in enhancement direction, vascular morphology, serous layer continuity, wash-out time and mural layering in the venous phase of GWT on H-CEUS images were significant between malignant and benign GWT (P < 0.05). The sensitivity, specificity and accuracy of H-CEUS based on enhancement direction, vascular morphology and wash-out time in the diagnosis of malignant GWT were 93.75%, 90.00%, and 91.30%, respectively. However, the sensitivity, specificity and accuracy of the GB-RADS score were only 68.75%, 73.33% and 71.74%, respectively. The area under ROC curve (AUC) of H-CEUS was significantly higher than that of the GB-RADS score (AUC = 0.965 vs. 0.756).
CONCLUSIONS: H-CEUS can accurately detect enhancement direction, vascular morphology and wash-out time of GWT, with a higher diagnostic performance than the GB-RADS score in determining wall-thickening type gallbladder cancer. This study provides a novel imaging means with high accuracy for the diagnosis of wall-thickening type gallbladder cancer, thus may be better avoiding delayed treatment or overtreatment.
PMID:38191513 | PMC:PMC10775603 | DOI:10.1186/s40644-023-00651-x
Lancet Gastroenterol Hepatol. 2024 Mar;9(3):229-237. doi: 10.1016/S2468-1253(23)00366-7. Epub 2024 Jan 4.
ABSTRACT
BACKGROUND: Gastrointestinal cancers account for a quarter of the global cancer incidence and a third of cancer-related deaths. We sought to estimate the lifetime risks of developing and dying from gastrointestinal cancers at the country, world region, and global levels in 2020.
METHODS: For this population-based systematic analysis, we obtained estimates of gastrointestinal cancer incidence and mortality rates from GLOBOCAN for 185 countries, alongside all-cause mortality and population data from the UN. Countries were categorised into quartiles of the Human Development Index (HDI). The lifetime risk of gastrointestinal cancers was estimated with a standard method that adjusts for multiple primaries, taking into account competing risks of death from causes other than cancer and life expectancy.
FINDINGS: The global lifetime risks of developing and dying from gastrointestinal cancers from birth to death was 8·20% (95% CI 8·18-8·21) and 6·17% (6·16-6·18) in 2020. For men, the risk of developing gastrointestinal cancers was 9·53% (95% CI 9·51-9·55) and of dying from them 7·23% (7·22-7·25); for women, the risk of developing gastrointestinal cancers was 6·84% (6·82-6·85) and of dying from them 5·09% (5·08-5·10). Colorectal cancer presented the highest risk, accounting for 38·5% of the total lifetime risk of developing, and 28·2% of dying from, gastrointestinal cancers, followed by cancers of the stomach, liver, oesophagus, pancreas, and gallbladder. Eastern Asia has the highest lifetime risks for cancers of the stomach, liver, oesophagus, and gallbladder, Australia and New Zealand for colorectal cancer, and Western Europe for pancreatic cancer. The lifetime risk of gastrointestinal cancers increased consistently with increasing level of HDI; however, high HDI countries (the third HDI quartile) had the highest death risk.
INTERPRETATION: The global lifetime risk of gastrointestinal cancers translates to one in 12 people developing, and one in 16 people dying from, gastrointestinal cancers. The identified high risk and observed disparities across countries warrants context-specific targeted gastrointestinal cancer control and health systems planning.
FUNDING: Beijing Nova Program, CAMS Innovation Fund for Medical Sciences, and Talent Incentive Program of Cancer Hospital, CAMS (Hope Star).
PMID:38185129 | PMC:PMC10849975 | DOI:10.1016/S2468-1253(23)00366-7
Cancer Epidemiol. 2024 Feb;88:102519. doi: 10.1016/j.canep.2023.102519. Epub 2024 Jan 5.
ABSTRACT
INTRODUCTION: Comparing cancer mortality and associated risk factors among immigrant populations in a host country to those in their country of origin reveals disparities in cancer risk, access to care, diagnosis, and disease management. This study compares cancer mortality between the German resident population and Germany-born individuals who migrated to the US.
METHODS: Cancer mortality data from 2008-2018 were derived for Germans from the World Health Organization database and for Germany-born Americans resident in four states (California, Florida, Massachusetts, and New York) from respective Departments of Vital Statistics. We calculated age-standardized mortality rates (ASMRs) using the European standard population and standardized mortality ratios (SMR) compared to the German resident population along with 95% confidence intervals (CIs).
RESULTS: Germany-born American males had lower ASMRs (253.8 per 100,000) than German resident population (325.6 per 100,000). The difference in females was modest, with ASMRs of 200.7 and 203.7 per 100,000, respectively. For all cancers, Germany-born American males had an SMR of 0.72 (95% CI: 0.70-0.74) and females 0.98 (95% CI: 0.95-1.00). Male SMRs among Germany-born Americans were significantly below one for oral cavity, stomach, colorectal, liver, lung, prostate, and kidney cancer. Among females, SMRs were below one for oral cavity, stomach, colorectal, gallbladder, breast, cervix uteri, and kidney cancer. For both sexes, SMRs were over one for bladder cancer (1.14 for males, 1.21 for females). Mortality was higher for lung cancer (SMR: 1.68), non-Hodgkin's lymphoma (1.18) and uterine cancer (1.22) among Germany-born American females compared to the German resident population.
CONCLUSION: Germany-born American males but not females showed lower cancer mortality than German resident population. Disparities may stem from variations in risk factors (e.g., smoking and alcohol use) as well as differences in screening practices and participation, cancer treatment, besides some residual potential "healthy immigrant effect".
PMID:38183748 | DOI:10.1016/j.canep.2023.102519
Clin Nucl Med. 2024 Mar 1;49(3):253-254. doi: 10.1097/RLU.0000000000005035. Epub 2024 Jan 5.
ABSTRACT
We present the imaging findings of a 77-year-old man with a history of malignant cutis melanoma that metastasized to the gallbladder. A restaging 18 F-FDG PET/CT scan showed uneven thickening and elevated 18 F-FDG uptake in the gallbladder wall. Subsequently, the patient underwent laparoscopic cholecystectomy, and histopathologic findings confirmed the diagnosis of metastatic melanoma of the gallbladder.
PMID:38181300 | DOI:10.1097/RLU.0000000000005035
Curr Treat Options Oncol. 2024 Jan;25(1):127-160. doi: 10.1007/s11864-023-01153-5. Epub 2024 Jan 5.
ABSTRACT
Biliary tract cancers are molecularly and anatomically diverse cancers which include intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, and gallbladder cancer. While recognized as distinct entities, the rarer incidence of these cancers combined with diagnostic challenges in classifying anatomic origin has resulted in clinical trials and guideline recommended strategies being generalized patients with all types of biliary tract cancer. In this review, we delve into the unique aspects, subtype-specific clinical trial outcomes, and multidisciplinary management of patients with extrahepatic cholangiocarcinoma. When resectable, definitive surgery followed by adjuvant chemotherapy (sometimes with selective radiation/chemoradiation) is current standard of care. Due to high recurrence rates, there is growing interest in the use of upfront/neoadjuvant therapy to improve surgical outcomes and to downstage patients who may not initially be resectable. Select patients with perihilar cholangiocarcinoma are being successfully treated with novel approaches such as liver transplant. In the advanced disease setting, combination gemcitabine and cisplatin remains the standard base for systemic therapy and was recently improved upon with the addition of immune checkpoint blockade to the chemotherapy doublet in the recently reported TOPAZ-1 and KEYNOTE-966 trials. Second-line all-comer treatments for these patients remain limited in both options and efficacy, so clinical trial participation should be strongly considered. With increased use of molecular testing, detection of actionable mutations and opportunities to receive indicated targeted therapies are on the rise and are the most significant driver of improved survival for patients with advanced stage disease. Though these targeted therapies are currently reserved for the second or later line, future trials are looking at moving these to earlier treatment settings and use in combination with chemotherapy and immunotherapy. In addition to cross-disciplinary management with surgical, medical, and radiation oncology, patient-centered care should also include collaboration with advanced endoscopists, palliative care specialists, and nutritionists to improve global patient outcomes.
PMID:38177560 | PMC:PMC10824875 | DOI:10.1007/s11864-023-01153-5
World J Clin Cases. 2023 Dec 26;11(36):8519-8526. doi: 10.12998/wjcc.v11.i36.8519.
ABSTRACT
BACKGROUND: Cholecystoenteric fistula (CEF) involves the formation of a spontaneous anomalous tract between the gallbladder and the adjacent gastrointestinal tract. Chronic gallbladder inflammation can lead to tissue necrosis, perforation, and fistulogenesis. The most prevalent cause of CEF is chronic cholelithiasis, which rarely results from malignancy. Because the symptoms and laboratory findings associated with CEF are nonspecific, the condition is often misdiagnosed, presenting a challenge to the surgeon when detected intraoperatively. Therefore, a preoperative diagnosis of CEF is crucial.
CASE SUMMARY: We present the case of a 57-year-old male with advanced gallbladder cancer (GBC) who arrived at the emergency room with persistent vomiting, abdominal pain, and diarrhea. An abdominopelvic computed tomography scan revealed a contracted gallbladder with bubbles in the fundus connected to the second portion of the duodenum and transverse colon. We suspected that GBC had invaded the adjacent gastrointestinal tract through a cholecystoduodenal fistula (CDF) or a cholecystocolonic fistula (CCF). He underwent multiple examinations, including esophagogastroduodenoscopy, an upper gastrointestinal series, colonoscopy, and magnetic resonance cholangiopancreatography; the results of these tests confirmed a diagnosis of synchronous CDF and CCF. The patient underwent a Roux-en-Y gastrojejunostomy and loop ileostomy to address the severe adhesions that were previously observed to cover the second portion of the duodenum and hepatic flexure of the colon. His symptoms improved with supportive treatment while hospitalized. He initiated oral targeted therapy with lenvatinib for further anticancer treatment.
CONCLUSION: The combination of imaging and surgery can enhance preoperative diagnosis and alleviate symptoms in patients with GBC complicated by CEF.
PMID:38188217 | PMC:PMC10768506 | DOI:10.12998/wjcc.v11.i36.8519
Indian J Surg Oncol. 2023 Dec;14(4):796-799. doi: 10.1007/s13193-023-01778-w. Epub 2023 Jun 17.
ABSTRACT
Xanthogranulomatous cholecystitis (XGC) is one of the rare variants of chronic cholecystitis which is characterized by inflammation of gall bladder along with infiltration by acute and chronic inflammatory cells. Intramural accumulation of lipid laden macrophages in GB wall is the hallmark of the disease. XGC results in dense adhesion of gall bladder (GB) to surrounding structures, like duodenum, colon, and stomach. The intense GB inflammation results in gall bladder perforation and development of fistulous communication between gall bladder and surrounding structures. This may also lead to formation of inflammatory mass which closely mimic gall bladder malignancy. Often differentiation from carcinoma of GB (Ca GB) on the basis of clinical presentation and even on intra-operative and radiological findings is difficult, and the issue could only be resolved on final Histopathology (HPE). We review presentation and investigation of a patient, discuss our approach in managing dilemma in treating such cases of XGC, and review the literature.
PMID:38187839 | PMC:PMC10767170 | DOI:10.1007/s13193-023-01778-w
Exp Oncol. 2023 Dec 28;45(3):379-385. doi: 10.15407/exp-oncology.2023.03.379.
ABSTRACT
The right trisectionectomy is the main treatment modality for locally advanced gallbladder cancer with invasion of the intraparenchymal portal vein branches because it allows the achievement of negative resection margins (R0). However, only 10%-25% of such patients are eligible for surgery. The cryosurgical method has been successfully used in the complex treatment of hepatopancreatobiliary malignant neoplasms for many years. The possibility of its application close to major blood vessels is one of its advantages. In the presented case, the cryodestruction of the residual tumor with invasion into the anterior wall of the left branch of the portal vein was used as a debulking option during liver resection (R2) due to locally advanced gallbladder cancer. The cryodestruction was performed with application method with a double cryocycle and spontaneous thawing using a Cryo-Pulse device and liquid nitrogen as a cryoagent. No postoperative complications related to cryodestruction were noted. The cryogenic technologies application in the debulking surgery of gallbladder cancer can be a safe treatment modality for residual tumors with invasion into the intraparenchymal branches of the portal vein.
PMID:38186017 | DOI:10.15407/exp-oncology.2023.03.379
Ann Surg Oncol. 2024 Feb;31(2):1282-1283. doi: 10.1245/s10434-023-14645-3. Epub 2023 Nov 30.
NO ABSTRACT
PMID:38032466 | DOI:10.1245/s10434-023-14645-3
BMC Gastroenterol. 2024 Jan 2;24(1):7. doi: 10.1186/s12876-023-03094-7.
ABSTRACT
Gallbladder polyps are a common biliary tract disease whose treatment options have yet to be fully established. The indication of "polyps ≥ 10 mm in diameter" for cholecystectomy increases the possibility of gallbladder excision due to benign polyps. Compared to enumeration of risk factors in clinical guidelines, predictive models based on statistical methods and artificial intelligence provide a more intuitive representation of the malignancy degree of gallbladder polyps. Minimally invasive gallbladder-preserving polypectomy procedures, as a combination of checking and therapeutic approaches that allow for eradication of lesions and preservation of a functional gallbladder at the same time, have been shown to maximize the benefits to patients with benign polyps. Despite the reported good outcomes of predictive models and gallbladder-preserving polypectomy procedures, the studies were associated with various limitations, including small sample sizes, insufficient data types, and unknown long-term efficacy, thereby enhancing the need for multicenter and large-scale clinical studies. In conclusion, the emergence of predictive models and minimally invasive gallbladder-preserving polypectomy procedures has signaled an ever increasing attention to the role of the gallbladder and clinical management of gallbladder polyps.
PMID:38166603 | PMC:PMC10759486 | DOI:10.1186/s12876-023-03094-7
BMJ Case Rep. 2024 Jan 4;17(1):e257753. doi: 10.1136/bcr-2023-257753.
ABSTRACT
Gallbladder cancer (GBC) is the 23rd most common cancer worldwide and one of the three leading cancers in North and Northeast India. GBC has inferior outcomes due to its advanced presentation and poor response to chemotherapy. The approximate 5-year survival rate for metastatic GBC is less than 5%, with a median survival of around 6 months. Distant metastases from GBC to the bones happen in the later part of the natural history of the disease. Presentation with bony metastasis is infrequent, and less than 25 cases have been reported. Our case was an elderly man in his 70s who presented with back pain and, on workup, was detected to have adenocarcinoma of the gall bladder with disseminated lytic bony metastasis without any visceral metastasis. This case describes the natural history of such cases and discusses the role of bone scan or fluorodeoxyglucose positron emission tomography in the workup for GBC.
PMID:38176748 | PMC:PMC10773285 | DOI:10.1136/bcr-2023-257753
World J Gastrointest Oncol. 2023 Dec 15;15(12):2053-2063. doi: 10.4251/wjgo.v15.i12.2053.
ABSTRACT
Gall bladder cancer (GBC) is becoming a very devastating form of hepatobiliary cancer in India. Every year new cases of GBC are quite high in India. Despite recent advanced multimodality treatment options, the survival of GBC patients is very low. If the disease is diagnosed at the advanced stage (with local nodal metastasis or distant metastasis) or surgical resection is inoperable, the prognosis of those patients is very poor. So, perspectives of targeted therapy are being taken. Targeted therapy includes hormone therapy, proteasome inhibitors, signal transduction and apoptosis inhibitors, angiogenesis inhibitors, and immunotherapeutic agents. One such signal transduction inhibitor is the specific short interfering RNA (siRNA) or short hairpin RNA (shRNA). For developing siRNA-mediated therapy shRNA, although several preclinical studies to evaluate the efficacy of these key molecules have been performed using gall bladder cells, many more clinical trials are required. To date, many such genes have been identified. This review will discuss the recently identified genes associated with GBC and those that have implications in its treatment by siRNA or shRNA.
PMID:38173427 | PMC:PMC10758643 | DOI:10.4251/wjgo.v15.i12.2053
JGH Open. 2023 Nov 10;7(12):1006-1008. doi: 10.1002/jgh3.12994. eCollection 2023 Dec.
ABSTRACT
The mechanisms underlying the progression of intracholecystic papillary neoplasms (ICPNs) to gallbladder cancer and invasive cancer remain relatively unclear. In the present case, metastatic liver tumors were suspected in an 83-year-old man at presentation; however, the primary tumor was unknown. The patient died shortly thereafter as a result of rapid tumor progression. An autopsy revealed multiple liver, lung, and lymph node metastases. Additionally, a fragile papillary tumor with a high-grade dysplastic epithelium with tubulopapillary morphology and admixed foci of a low-grade dysplastic epithelium were detected at the fundus of the gallbladder. The well-differentiated tubular adenocarcinoma had extensively invaded the wall's granular mucosal surface along with the solitary papillary tumor. Based on pathological findings, a diagnosis of an ICPN with an associated invasive carcinoma was established. This case is novel because it showed that an ICPN can progress aggressively.
PMID:38162850 | PMC:PMC10757481 | DOI:10.1002/jgh3.12994
Clin Radiol. 2024 Feb;79(2):e247-e255. doi: 10.1016/j.crad.2023.10.033. Epub 2023 Nov 16.
ABSTRACT
AIM: To evaluate apparent diffusion coefficient (ADC) and its standard deviation (SDADC) in preoperative predicting liver invasion by T3-staged gallbladder carcinoma (GBC).
MATERIALS AND METHODS: Forty-one consecutive patients with T3-staged resectable GBC were included and divided into two sets with (n=27) and without (n=14) liver invasion. All patients underwent DWI at b-values of 0, 20, 50, 80, 100, 200, 400, 600, 800, and 1,000 s/mm2 with a 3 T magnetic resonance imaging scanner before surgery. ADC and SDADC of tumour-adjacent and tumour-distant liver tissues were measured on DWI, and were compared by Mann-Whitney U-tests. If there was a significant difference in any derived parameter, the area under the receiver operating characteristic curve (AUC) was used to assess performance of this parameter to predict liver invasion.
RESULTS: DWI could differentiate between patients with and without liver invasion when b = 0, 1,000 s/mm2 (AUCs of ADC and SDADC were 0.697 and 0.714, respectively). In patients with liver invasion, mean ADC and SDADC of tumour-adjacent liver tissue were lower than of tumour-distant liver tissue when b = 0, 800 s/mm2, and = 0, 1,000 s/mm2 (all p-values <0.05). To differentiate tumour-adjacent from tumour-distant liver tissues in patients with liver invasion, AUCs of ADC were 0.687 (b = 0, 800 s/mm2) and 0.680 (b = 0, 1,000 s/mm2), and AUCs of SDADC were 0.673 (b = 0, 800 s/mm2) and 0.731 (b = 0, 1,000 s/mm2).
CONCLUSIONS: DWI could have potential value in preoperative predicting liver invasion by T3-staged GBC.
PMID:38007337 | DOI:10.1016/j.crad.2023.10.033
J Cachexia Sarcopenia Muscle. 2023 Dec;14(6):2509-2519. doi: 10.1002/jcsm.13371. Epub 2023 Nov 22.
ABSTRACT
Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.
PMID:37990969 | PMC:PMC10751448 | DOI:10.1002/jcsm.13371
J Gastroenterol Hepatol. 2023 Dec;38(12):2247-2253. doi: 10.1111/jgh.16399. Epub 2023 Nov 5.
ABSTRACT
BACKGROUND AND AIM: We aimed to determine the risk and predictors of gallbladder cancer in all individuals with gallbladder polyps (GP) including those who did not have cholecystectomy.
METHODS: The STROCSS guideline was followed to conduct a retrospective cohort study. All individuals with GP between 2010 and 2019 were followed up to determine the risk and predictors of gallbladder cancer. The primary outcomes were gallbladder cancer and gallbladder dysplasia, and the secondary outcomes included polyp growth rate and polyp disappearance rate. Binary logistic regression analysis and receiver operating characteristic curve analysis were conducted to evaluate the outcomes.
RESULTS: Analysis of 438 patients showed risk of gallbladder cancer was 0.7% in all polyps (0% in polyps < 10 mm; 5.9% in polyps ≥ 10 mm). The risk of gallbladder dysplasia or cancer was 1.1% in all polyps (0% in polyps < 10 mm; 10% in polyps ≥ 10 mm). The polyp size (P = 0.0001) was predictor of cancer; however, patient's age (P = 0.1085), number of polyps (P = 0.9983), symptomatic polyps (P = 0.3267), and change in size (P = 0.9012) were not. Size of 21 mm was cut-off for risk of cancer (area under the curve [AUC]: 0.995, P < 0.001) and 11.8 mm for risk of dysplasia or cancer (AUC: 0.986, P < 0.001). The mean polyp growth rate was 0.3 mm/year and polyp disappearance rate was 16%.
CONCLUSIONS: The GP size remains the only predictor of malignant changes regardless of patient's age, patient's symptoms and number of polyps. The polyp growth rate is unremarkable, and a significant proportion disappears during follow-up. We changed our follow-up protocol with reduced number of scans and early discharge policy.
PMID:37926936 | DOI:10.1111/jgh.16399
Medicine (Baltimore). 2023 Dec 22;102(51):e36622. doi: 10.1097/MD.0000000000036622.
ABSTRACT
RATIONALE: Gallbladder polyps are a general term for localized lesions in which the gallbladder wall protrudes into the gallbladder cavity, and benign lesions are common. Although current guidelines recommend cholecystectomy for gallbladder polyps ≥ 10 mm in size, the probability of finding cancer in postoperative pathological specimens is low. We should avoid unnecessary cholecystectomy and treat polyps with gallbladder preservation. Microwave ablation is safe and effective for the treatment of solid lesions, and can inactivates polyps while preserving gallbladder. Hence, we report a case of ultrasound-guided percutaneous microwave ablation of gallbladder polyps.
PATIENT CONCERNS: A 72-year-old female patient had previously diagnosed a gallbladder polyp, but it was not taken seriously. Recently, the patient had occasional right upper abdominal discomfort and a desire to preserve gallbladder.
DIAGNOSES: Ultrasound showed a medium hyperechoic papillary protrusion in the gallbladder without echo behind, and the changed position did not move. Contrast-enhanced ultrasound (CEUS) showed no malignant signs. The diagnosis was a gallbladder polyp.
INTERVENTIONS: The bile is drained and the drainage tube is fixed under real-time ultrasound guidance, then the gallbladder cavity is flushed and filled. Saline was injected between the serous and mucosal layers of the gallbladder to form an "edema band" to protect the gallbladder wall. Then, ultrasound-guided biopsy of gallbladder polyps was performed and sent for histological examination. Finally, the microwave needle was inserted into the target area under real-time ultrasonic guidance, and ablation was performed for 3 minutes (20 W). Postoperative CEUS: No significant enhancement was observed in the lesion.
OUTCOMES: Within 6 months of follow-up, the patient's gallbladder systolic function was normal, and there was no discomfort and no recurrence. The lesion reduction rate reached 100% at 1 week after surgery.
LESSONS: Ultrasound guided percutaneous microwave ablation of gallbladder polyps not only preserves the gallbladder but also inactivates the polyps without affecting the systolic function of the gallbladder, which provides a new idea for the treatment of gallbladder polyps.
PMID:38134113 | PMC:PMC10735141 | DOI:10.1097/MD.0000000000036622
J Gynecol Oncol. 2023 Dec 11. doi: 10.3802/jgo.2024.35.e25. Online ahead of print.
ABSTRACT
OBJECTIVE: Metastases in the supragastric lesser sac (SGLS) are not only occult but are also barriers to complete resection of ovarian cancer. We describe a cohort of patients with SGLS disease undergoing debulking surgery.
METHODS: We identified all patients who underwent evaluation and eventual resection of SGLS disease as part of cytoreductive surgery for stage IIIC-IVB high-grade epithelial ovarian cancer at our institution from January 2018 to August 2022.
RESULTS: Thirty-three of 286 patients (11.5%) underwent resection of SGLS disease. Metastases in the SGLS were identified by preoperative imaging in 4 of 33 patients (12.1%). The median peritoneal cancer index score was 22 (range, 9-33). Through surgical exploration, metastases were frequently seen in the right diaphragm (100%), hepatorenal recess (97%), lesser omentum (81.8%), left diaphragm (78.8%), supracolic omentum (75.8%), anterior transverse mesocolon (72.7%), splenic hilum (63.6%), ligamentum teres hepatis (60.6%), and gallbladder fossa (51.5%). The lesser omentum was normal in 6 of 33 (18.2%) patients, despite metastases within the SGLS. A total of 54.5% of patients underwent complex surgery (surgical complexity scores; median, 8; range, 3-14). Complete resections were achieved in 19 (57.6%) patients. No complications were related to the resection of SGLS disease. The median length of progression-free survival was 24.8 months (95% confidence interval=16.6-32.9).
CONCLUSION: Metastases to the SGLS are not uncommon in advanced ovarian cancer, particularly those with widely disseminated disease. Disease in this recess is rarely identified by preoperative imaging and deserves systematic surgical exploration to attain complete cytoreduction.
PMID:38130134 | DOI:10.3802/jgo.2024.35.e25
Hum Vaccin Immunother. 2023 Dec 15;19(3):2294575. doi: 10.1080/21645515.2023.2294575. Epub 2023 Dec 21.
ABSTRACT
Biliary tract cancer (BTC) is an aggressive malignancy with few options for advanced-stage treatment. The combination of PD-1/PD-L1 inhibitors with famitinib, a receptor tyrosine kinase (RTK) inhibitor, has demonstrated improved clinical outcomes in several clinical trials. We herein reported a case of a gallbladder cancer (GBC) patient with liver metastases, previously resistant to traditional chemotherapy. Remarkably, the patient achieved a complete response (CR) with a long-lasting survival benefit exceeding 3 years. This was achieved using a novel regimen combining SHR-1701, an anti-PD-L1/TGF-βR fusion protein, and famitinib, even though the patient had proficient mismatch repair (pMMR) and tested negative for PD-L1. Adverse events were limited and manageable. This is the first report of such a treatment regimen being applied in a clinical setting, suggesting that the SHR-1701 and famitinib combination may be a promising immunotherapeutic approach for patients with refractory advanced GBC.
PMID:38126815 | PMC:PMC10760368 | DOI:10.1080/21645515.2023.2294575
BMJ Case Rep. 2023 Dec 20;16(12):e255403. doi: 10.1136/bcr-2023-255403.
ABSTRACT
Advanced gallbladder cancer (GBC) is not amenable to surgical resection. There are limited treatment options and the prognosis is dismal. The role of immune checkpoint inhibitors in conversion therapy remains unclear for initially unresectable advanced GBC. We present a case of a woman in her late 60s diagnosed with stage IV GBC with liver and para-aortic and retroperitoneal lymph node metastases, who achieved a pathological complete response after three cycles of programmed cell death-ligand 1 inhibitor durvalumab combined with gemcitabine and cisplatin regimen and underwent conversion surgery without complication. The patient went on to develop disease progression without adjuvant therapy 6 months after surgery.
PMID:38123314 | PMC:PMC10749147 | DOI:10.1136/bcr-2023-255403
Medicina (B Aires). 2023;83(6):998-1002.
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is an uncommon malignant neoplasm that accounts for 3% of all malignant tumors in adults. This tumor exhibits a high tendency to develop synchronous or metachronous metastases in different anatomical sites. Although gallbladder metastasis from ccRCC is extremely rare, sporadic cases have been reported in the medical literature. We present the case of a 78-year-old woman with a history of undifferentiated nasopharyngeal carcinoma, basal cell carcinoma, and ccRCC in the right kidney. She underwent radical nephrectomy. Histopathological analysis confirmed the diagnosis of ccRCC without vascular or ureteral invasion. Two years later, during follow-up, a nodular lesion was detected in the gallbladder through computed tomography. Despite the absence of symptoms, surgical resection was decided. Laparoscopic cholecystectomy was performed without complications. Histopathological examination confirmed the presence of ccRCC metastasis in the gallbladder. The patient had a favorable outcome and is currently under follow-up without recurrence. Gallbladder metastasis from ccRCC is extremely rare, but surgeons should consider this possibility in patients with a history of ccRCC. Preoperative differential diagnosis between primary gallbladder carcinoma and ccRCC metastasis can be challenging and is often confirmed through histopathological examination. Complete surgical resection is the best treatment option to achieve disease-free survival.
PMID:38117722
Minerva Endocrinol (Torino). 2023 Dec 21. doi: 10.23736/S2724-6507.23.04101-5. Online ahead of print.
ABSTRACT
Glucagon-like peptide-1 (GLP-1) receptor agonists are used in diabetes management and can have a potential application in cancer therapy. While their involvement in cancer treatment is still being studied, recent research suggests they may have benefits in cancer therapy. A comprehensive literature search was conducted using search engines like Google Scholar, Scopus, and PubMed to explore the effects of GLP-1 receptor agonists in tumor suppression and regression. Mostly in-vitro studies on GLP-1 receptor agonists have shown promising effects in inhibiting cancer cell growth, inducing apoptosis, and modulating angiogenesis and have been reported to be beneficial in colon, prostate, gall bladder, ovarian, and endometrial carcinomas. However, concerns have been raised about potential tumorigeneses, as liraglutide has been reported to be associated with increased incidence of breast, thyroid, and pancreatic carcinomas. Whereas combination therapy of exendin-4 with gemcitabine may be beneficial in pancreatic cancer. GLP-1 receptor agonists may have significant potential in oncology, due to their various mechanisms of action and favorable safety profiles. Limited clinical application, lack of awareness, and the need for further research are current barriers. Future studies should focus on optimal dosage, patient selection, and interdisciplinary collaboration to integrate GLP-1 receptor agonists into routine oncological practice for improved outcomes, warranting large randomized clinical trials in this field.
PMID:38127407 | DOI:10.23736/S2724-6507.23.04101-5
Medicine (Baltimore). 2023 Dec 15;102(50):e36608. doi: 10.1097/MD.0000000000036608.
ABSTRACT
BACKGROUND: This study aimed to explore the value of tumor-infiltrating Forkhead box P3(FoxP3+) regulatory T cells (Tregs) in evaluating the prognosis of biliary tract cancer.
METHODS: Four electronic databases were searched using 2 computers: PubMed, Embase, Web of Science, and Cochrane Library. The vocabulary and syntax were adapted according to the database. Two researchers independently selected the studies, collected information, and assessed the risk of bias. The Meta-analysis was performed using STATA 17.0, and HR and its corresponding 95% CI were used to evaluate the correlation between FoxP3+ Tregs and the overall survival of patients with biliary tract cancer. In addition, the quality of the included studies was evaluated.
RESULTS: Ten articles were included in this study. The results of the meta-analysis showed that patients with high FoxP3+ Tregs infiltration had worse overall survival (OS) (HR = 1.34,95% CI 1.16 to 1.71; P < .001). Subgroup analysis of gallbladder carcinoma and cholangiocarcinoma showed that the high infiltration of FoxP3+ Tregs was significantly correlated with the OS of the former (HR = 1.55,95% CI 1.11 to 2.00; P < .001), but not with the OS of the latter (HR = 1.00,95% CI 0.62 to 1.38; P > .05).
CONCLUSIONS: Our meta-analysis reveals that high infiltration of FoxP3 + Tregs is significantly associated with reduced overall survival in gallbladder carcinoma, endorsing their use as a prognostic biomarker for this subtype. In contrast, no significant prognostic correlation was identified for FoxP3+ Tregs in cholangiocarcinoma, indicating the need for subtype-specific evaluation of their prognostic relevance in biliary tract cancers.
PMID:38115302 | PMC:PMC10727656 | DOI:10.1097/MD.0000000000036608
Am J Surg Pathol. 2024 Jan 1;48(1):88-96. doi: 10.1097/PAS.0000000000002135. Epub 2023 Sep 28.
ABSTRACT
Perivascular epithelioid cell neoplasms (PEComas) are tumors of uncertain cell lineage that show a strong female predominance. Their hallmark is the presence of combined smooth muscle and melanocytic differentiation. In most cases, melanocytic differentiation is detectable only by immunohistochemistry, but there are rare reports of PEComa with extensive melanin accumulation (so-called "melanotic PEComa"). Here we report a clinicopathologic series of 7 melanotic PEComas that occurred across a wide patient age range of 21 to 82 years (median: 41 y) and with a wide anatomic distribution, including 2 cases in the pelvis and 1 case each in the gallbladder, cervix, eyelid, epidural space, and femur. All tumors were heavily pigmented and, like conventional PEComas, were composed of variably sized neoplastic cells with voluminous granular, or less commonly clear, cytoplasm with prominent nucleoli. All tumors expressed HMB45 by immunohistochemistry, and 6 of 7 showed nuclear TFE3 expression. Where tested, tumors were uniformly negative for Mart-1/Melan-A, S100, desmin, and smooth muscle actin. Molecular analysis identified TFE3 gene rearrangement in 5 of 7 cases, 4 of which were demonstrated by fluorescence in situ hybridization and one by whole-exome RNA sequencing which revealed a SFPQ::TFE3 fusion. The one tumor negative for TFE3 by immunohistochemistry was found instead to harbor a SFPQ::TFEB fusion, the first reported example to our knowledge of TFEB fusion in a PEComa. Clinical follow-up was available for 6 of 7 patients (median: 2.5 y: range: 0.75 to 7 y). The patient whose tumor harbored SFPQ::TFEB died of metastatic disease 9 months after diagnosis. The other tumors behaved in an indolent fashion: 4 patients were alive without evidence of disease at the most recent follow-up and 1 patient died of an unrelated cancer 4 years after diagnosis of the melanotic PEComa. Our results expand the morphologic and molecular spectrum of melanotic PEComa, and awareness of this rare but distinctive subtype is important to ensure accurate diagnosis within the broader family of heavily pigmented neoplasms.
PMID:38117287 | DOI:10.1097/PAS.0000000000002135
World J Gastrointest Surg. 2023 Nov 27;15(11):2413-2422. doi: 10.4240/wjgs.v15.i11.2413.
ABSTRACT
BACKGROUND: Gallbladder cancer (GC) is a common malignant tumor and one of the leading causes of cancer-related death worldwide. It is typically highly invasive, difficult to detect in the early stages, and has poor treatment outcomes, resulting in high mortality rates. The available treatment options for GC are relatively limited. One emerging treatment modality is hyperthermic intraperitoneal chemotherapy (HIPEC). HIPEC involves delivering heated chemotherapy directly into the abdominal cavity. It combines the strategies of surgical tumor resection and localized chemotherapy administration under hyperthermic conditions, aiming to enhance the concentration and effectiveness of drugs within the local tumor site while minimizing systemic toxicity.
AIM: To determine the effects of cytoreductive surgery (CRS) combined with HIPEC on the short-term prognosis of patients with advanced GC.
METHODS: Data from 80 patients treated at the Punan Branch of Renji Hospital, Shanghai Jiao Tong University School of Medicine between January 2018 and January 2020 were retrospectively analyzed. The control group comprised 44 patients treated with CRS, and the research group comprised 36 patients treated with CRS combined with HIPEC. Then, the survival time and prognostic factors of the two groups were compared, as well as liver and kidney function indices before and six days after surgery. Adverse reactions and complications were recorded in both groups.
RESULTS: The baseline data of the research and control groups were similar (P > 0.05). Six days after surgery, the alanine aminotransferase, aspartate aminotransferase, total bilirubin, and direct bilirubin levels significantly decreased compared to the preoperative levels in both groups (P < 0.05). However, the values did not differ between the two groups six days postoperatively (P > 0.05). Similarly, the postoperative creatinine and blood urea nitrogen levels were significantly lower than the preoperative levels in both groups (P < 0.05), but they did not differ between the groups six days postoperatively (P > 0.05). Furthermore, the research group had fewer postoperative adverse reactions than the control group (P = 0.027). Finally, a multivariate Cox analysis identified the tumor stage, distant metastasis, and the treatment plan as independent factors affecting prognosis (P < 0.05). The three-year survival rate in the study group was higher than that in the control group (P = 0.002).
CONCLUSION: CRS combined with HIPEC lowers the incidence of adverse reactions and improves survival in patients with advanced GC.
PMID:38111760 | PMC:PMC10725543 | DOI:10.4240/wjgs.v15.i11.2413
Fam Med Community Health. 2023 Dec 17;11(Suppl 1):e002397. doi: 10.1136/fmch-2023-002397.
ABSTRACT
OBJECTIVE: Despite the established cancer screening programme for oral, breast and cervical cancer by the Government of India, the screening coverage remains inadequate. This study aimed to describe the determinants for oral, breast and cervical cancer prevention in a rural community at the primary care level of Northern India and its policy implications.
DESIGN: This was a camp-based project conducted for 1 year, using oral visual examination, clinical breast examination and visual inspection of cervix by application of 5% acetic acid according to primary healthcare operational guidelines. During the project, screen-positive participants were followed through reverse navigation. Information about socio-demographic profile, clinical and behavioural history and screening were collected. Predictors for screen-positivity and follow-up compliance were identified through multivariable analysis.
SETTINGS: Based on the aim of project, one of the remotely located and low socioeconomic rural blocks, having 148 villages (estimated population of 254 285) in Varanasi district, India was selected as the service site. There is an established healthcare delivery and referral system as per the National Health Mission of Government of India. Oral, breast, gallbladder and cervical cancers are the leading cancers in the district.
PARTICIPANTS: We invited all men and women aged 30-65 years residing in the selected block for the last 6 months for the screening camps. Unmarried women, women with active vaginal bleeding, those currently pregnant and those who have undergone hysterectomy were excluded from cervical cancer screening.
RESULTS: A total of 14 338 participants were screened through 190 camps and the majority (61.9%) were women. Hindu religion, tobacco use, intention to quit tobacco and presence of symptoms were significantly associated with screen-positivity. Nearly one-third (220; 30.1%) of the screened-positives complied with follow-up. Young age and illiteracy were significantly associated with lower compliance.
CONCLUSION: Poor follow-up compliance, despite the availability of tertiary cancer care, patient navigation, free transportation and diagnostic services, calls for research to explore the role of contextual factors and develop pragmatic interventions to justify 'close the care gap'. Community cancer screening needs strengthening through cancer awareness, establishing referral system and integration with the National Tobacco Control and Cancer Registry Programmes.
PMID:38105243 | PMC:PMC10729271 | DOI:10.1136/fmch-2023-002397
Semin Liver Dis. 2023 Nov;43(4):472-484. doi: 10.1055/a-2207-9834. Epub 2023 Nov 9.
ABSTRACT
Biliary tract cancer is a devastating malignancy of the bile ducts and gallbladder with a dismal prognosis. The study of precancerous lesions has received considerable attention and led to a histopathological classification which, in some respects, remains an evolving field. Consequently, increasing efforts have been devoted to characterizing the molecular pathogenesis of the precursor lesions, with the aim of better understanding the mechanisms of tumor progression, and with the ultimate goal of meeting the challenges of early diagnosis and treatment. This review delves into the molecular mechanisms that initiate and promote the development of precursor lesions of intra- and extrahepatic cholangiocarcinoma and of gallbladder carcinoma. It addresses the genomic, epigenomic, and transcriptomic landscape of these precursors and provides an overview of animal and organoid models used to study them. In conclusion, this review summarizes the known molecular features of precancerous lesions in biliary tract cancer and highlights our fragmentary knowledge of the molecular pathogenesis of tumor initiation.
PMID:37944999 | DOI:10.1055/a-2207-9834
Cureus. 2023 Nov 16;15(11):e48894. doi: 10.7759/cureus.48894. eCollection 2023 Nov.
ABSTRACT
Carcinosarcomas of the biliary tract are an extremely rare type of malignancy and may be low on a differential when presenting as multiple metastatic masses. In this case report, we report a case of a female who presented with an aggressive late-stage disease whose initial workup did not indicate a malignant process. Further complicating her care, biopsy samples taken from extra-hepatic masses were culture-positive for Lactobacillus rhamnosu. Given the late stage of the patient's disease, hospice care was initiated. The patient passed away four months after the initial presentation.
PMID:38106784 | PMC:PMC10725195 | DOI:10.7759/cureus.48894
Int J Oncol. 2024 Feb;64(2):16. doi: 10.3892/ijo.2023.5604. Epub 2023 Dec 15.
ABSTRACT
Due to the lack of specific symptoms, characteristic diagnostic markers and effective comprehensive treatment, gallbladder cancer (GBC) is currently considered one of the most malignant abdominal tumors. With the rapid development of biological technologies, long non‑coding RNAs (lncRNAs), once regarded as transcriptional junk, have been demonstrated to participate in almost the whole process of the central dogma of molecular biology. The central dogma deals with the transfer of sequential information at the level of individual residues. LncRNAs have an effect on multiple cancer types. However, evidence of dysregulated lncRNA functions in GBC is limited. In the present review, the regulatory mechanisms of lncRNA function on gene expression were examined, including epigenetic modification, transcriptional regulation and post‑translational modulation. These mechanisms are strongly associated with tumor development and metastasis. Next, it was summarized how lncRNAs affect GBC diverse malignant phenotypes through various mechanisms. Moreover, predictions of lncRNA interactions with other functional molecules in malignancies were made using several valuable databases, including crosstalk between lncRNA and DNA, mRNA, microRNA, and protein. Additionally, several potential therapeutic methods targeting pathological lncRNAs in tumors were identified. Finally, perspectives about lncRNA research and applications in GBC were presented in the current study, including viewpoints of coding potential of lncRNAs and feasible usage of micropeptides encoded by lncRNAs; roles of lncRNAs in tumor cell metabolic reprogramming and tumor microenvironment; and function of lncRNAs as possible biomarkers and therapeutic targets for improving GBC diagnosis, treatment and prognosis.
PMID:38099359 | DOI:10.3892/ijo.2023.5604
Langenbecks Arch Surg. 2023 Dec 13;409(1):2. doi: 10.1007/s00423-023-03199-3.
ABSTRACT
PURPOSES: The current study was performed to comparatively evaluate the similarities and differences between cases with radically re-resected incidental gallbladder carcinoma (RRIGBC) and those with primary radically resected gallbladder carcinoma (PRGBC).
METHODS: Comparative analysis between patients with RRIGBC and those with PRGBC were performed in terms of clinic-pathological features and long-terms survival.
RESULTS: A total of 330 surgically treated GBC patients with 110 patients with IGBC were identified. PRGBCs were generally in a more advanced tumor stage, sharing more aggressive tumor biological features and worse prognosis than those with RRIGBC. Subgroup analyses indicated a comparable prognosis among T1-2 patients between RRIGBC and PRGBC groups. However, among T3-4 patients, patients in the PRGBC group shared a much worse prognosis. Moreover, IGBC itself can be regarded as a prognostic factor but cannot be regarded as an independent prognostic factor. It is the tumor stage which really determined the overall prognosis.
CONCLUSION: Patients with RRIGBC were generally in a much earlier tumor stage and shared a much better prognosis than those with PRGBC. IGBC itself can be regarded as a prognostic factor but cannot be regarded as the independent prognostic factors. It is the tumor stage which really determine the overall prognosis.
PMID:38087066 | DOI:10.1007/s00423-023-03199-3
Clin Imaging. 2024 Jan;105:109997. doi: 10.1016/j.clinimag.2023.109997. Epub 2023 Oct 13.
ABSTRACT
Radiologists across many imaging modalities commonly encounter gallbladder adenomyomatosis. The classic imaging appearances of gallbladder adenomyomatosis are well described and confirm benignity. However, in clinical practice, adenomyomatosis can be challenging to differentiate from other gallbladder pathologies that require cholecystectomy. In this article, we describe the common and uncommon appearances of gallbladder adenomyomatosis on multimodality imaging, helping differentiate adenomyomatosis from non-benign gallbladder abnormalities. Accurately differentiating adenomyomatosis from its mimics provides the surgical team with important clinical and surgical management information, improving patient outcomes.
PMID:37989017 | DOI:10.1016/j.clinimag.2023.109997
Cancer Discov. 2023 Dec 12;13(12):2492. doi: 10.1158/2159-8290.CD-NB2023-0079.
ABSTRACT
In a phase I trial of the MTA-cooperative PRMT5 inhibitor AMG 193, five of 39 patients with advanced MTAP-deleted solid tumors who had scans following initial treatment experienced partial responses. The responses occurred in five tumor types-esophageal, pancreatic, renal cell, gallbladder, and ovarian Sertoli-Leydig cell cancer.
PMID:37847607 | DOI:10.1158/2159-8290.CD-NB2023-0079
Int J Surg Case Rep. 2023 Dec 8;114:109110. doi: 10.1016/j.ijscr.2023.109110. Online ahead of print.
ABSTRACT
INTRODUCTION AND IMPORTANCE: Primary cystic duct carcinoma, an uncommon and aggressive biliary cancer variant, poses a significant challenge in clinical practice. This study examines recent clinical cases, focusing on diagnostics, interventions, and implications in managing this disease, with a prevalence ranging from 0.03 % to 0.05 %, contributing to 2.6-12.6 % of extrahepatic biliary neoplasms.
CASE PRESENTATION: A 57-year-old male, a smoker with hypertension and hyperuricemia, presented symptoms of severe upper right abdominal pain, jaundice, and altered stool color. Diagnosis revealed ulcerated papillary adenocarcinoma invading all gallbladder layers (2.5 cm). Surgical resection and Roux-en-Y anastomosis were performed. Histopathological examination showed invasive tumor proliferation, preserved lymph node architecture, and severe hepatic microsteatosis. Lymph nodes were tumor-free, and a benign hepatic biopsy (0.5 cm) displayed chronic portitis. The final diagnosis confirmed cystic duct carcinoma, emphasizing the complex diagnostic and therapeutic aspects in biliary cases.
CLINICAL DISCUSSION: The clinical discussion unveils the complexities associated with primary cystic duct carcinomas. Emphasizing the necessity of a multidisciplinary approach, this case highlights the importance of efficient management strategies-from initial diagnosis to surgical intervention-in dealing with this challenging malignancy.
CONCLUSION: In conclusion, this case underscores the intricate nature of primary cystic duct carcinomas. It accentuates the essential role of a multidisciplinary approach, urging the need for continuous research endeavors to further comprehend and enhance the treatment methodologies for this rare and complex malignancy.
PMID:38086134 | PMC:PMC10726233 | DOI:10.1016/j.ijscr.2023.109110
Minerva Surg. 2023 Dec;78(6):657-670. doi: 10.23736/S2724-5691.23.10104-3.
ABSTRACT
Metabolic and bariatric surgery (MBS) is the most effective intervention for weight loss leading to significant resolution of obesity-related medical conditions. Recent literature has demonstrated risk reduction of certain cancer types after MBS. Studies have shown an overall reduction in the risk of hormonal cancer, such as breast and endometrial cancer. However, the association between bariatric surgery and the incidence of various types of non-hormonal cancer such as esophageal, gastric, liver, gallbladder, colorectal, pancreatic and kidney cancer remains contested. The aim of this study was to highlight obesity and its relationship to cancer development as well as bariatric surgery and its role in cancer reduction with focus on non-hormonal cancers.
PMID:38059440 | DOI:10.23736/S2724-5691.23.10104-3
Iran J Otorhinolaryngol. 2023 Nov;35(131):325-328. doi: 10.22038/IJORL.2023.73099.3471.
ABSTRACT
INTRODUCTION: Ectopic thyroid is an uncommon condition resulting from the aberrant development of the normal thyroid gland and is usually found along the thyroglossal tract: lingual, submandibular, thyroglossal cysts, intra-tracheal and mediastinal, or, on rare occasions, in the adrenal gland, gallbladder, gastrointestinal tract, pancreas, and struma ovarii.
CASE REPORTS: We describe a novel case where primary papillary thyroid carcinoma (PTC) was found after a trans-oral excision of a tumor containing ectopic thyroid tissue at the posterior pharynx, an area not known to be a location for ectopic thyroid. Delays due to the COVID-19 pandemic resulted in regional cervical metastases and multifocal PTC. The female patient successfully underwent total thyroidectomy, selective cervical and central lymph node dissection, followed by adjuvant radioactive iodine ablation, with no evidence of distant metastases.
CONCLUSIONS: Ectopic thyroid tissue is uncommon and may be in the posterior pharynx. The principles of management remain those of differentiated thyroid malignancy: complete surgical resection of any tumor focus, total thyroidectomy, and node dissection of involved lymph nodes, followed by adjuvant radioactive iodine in iodine-sensitive tumors.
PMID:38074483 | PMC:PMC10701244 | DOI:10.22038/IJORL.2023.73099.3471