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Background: In recent decades, laparoscopic liver resection (LLR) has been gradually adopted at high-volume centers, particularly for hepatocellular carcinoma and liver metastasis. However, LLR in patients with gallbladder cancer (GBC) is a controversial issue, and there are few studies of LLR for GBC. Our aim was to compare the outcomes of patients who underwent laparoscopic or open liver resection for GBC. Materials and Methods: All patients admitted with stage II or III GBC requiring liver resection, together with cholecystectomy and lymphadenectomy, were analyzed retrospectively. Patients with thickness of the resected liver specimen >2 cm in pathology reports were included. Results: A total of 56 patients with stage II or III GBC were included in this study; 23 (41.1%) underwent laparoscopic surgery and 33 (58.9%) underwent open surgery. Propensity score matching was performed using a 1:1 matching scheme. After matching, 12 patients were included in each group. The preoperative characteristics of both groups were similar, as were the operative times (laparoscopic versus open group: 237.5 minutes versus 272.5 minutes, respectively; P = .319) and blood loss (300 mL versus 275 mL, respectively; P = .307). The laparoscopic group had a significantly shorter postoperative hospital stay than the open surgery group (4.5 days versus 8 days, respectively; P = .012). There were no major complications in either group. There was no difference between the groups in the number of lymph nodes harvested at surgery (P = .910). There were no differences between the two groups in disease-free (P = .503) or overall (P = .719) survival. Conclusion: LLR extended to GBC provides outcomes similar to those of open surgery. With increasing experience, LLR can be a viable alternative to open surgery for GBC.

The risk of neoplasia in gallbladder polyps seems to be low, but the evidence from populations at high-risk of gallbladder cancer is limited. We aimed to estimate the risk and to identify the factors associated with neoplastic polyps in a high-risk Hispanic population.A retrospective cohort was recruited between January 2010 and December 2019 at a Chilean university center. Multivariate survival analyses were conducted. Fine-Gray models were fitted to account for competing risks. Covariate adjustment was conducted using propensity scores. The main outcome was the development of gallbladder adenomas or adenocarcinoma.Overall, 748 patients were included, 59.6% underwent cholecystectomy. The median follow-up of patients not subjected to cholecystectomy was 54.7 months (12-128.6 months). Seventeen patients (2.27%) developed the outcome. After adjustment by age, sex, intralesional blood flow, lithiasis and gallbladder wall thickening, only polyp size (≥10 mm, adjusted-HR: 15.01, 95%CI: 5.4-48.2) and number of polyps (≥3 polyps, adjusted-HR: 0.11, 95%CI: 0.01-0.55) were associated with neoplasia.In a Hispanic population at high-risk for gallbladder cancer, gallbladder polyps seem to have a low risk of neoplasia. Polyp size was the main risk factor, while having multiple polyps was associated with an underlying benign condition.

Last few decades have seen changes in the approach toward the management of gallbladder cancer (GBCA). Availability of high-definition imaging modalities and accurate interpretations of their findings have helped in early and accurate diagnosis. A structured approach toward the disease with the aid of clinical, noninterventional/interventional radiology and laparoscopic findings has helped surgeons to choose between an aggressive approach of radical cholecystectomy for those with a resectable growth and suitable palliation for those who are unlikely to benefit from therapeutic laparotomy, thereby helping in proper and judicious utilization of health-care resources. Better understanding of the tumor biology is encouraging oncologists for trials with different targeted therapies in advanced disease. This review addresses some of the key issues related to the management of GBCA based on extensive search of available literatures and current international guidelines.

Gallbladder cancer has a poor prognosis, especially in peritoneal carcinomatosis related to perforation of the gallbladder followed by bile spillage. Previously, curative-intent treatment was not considered in carcinomatosis from cancer of the biliary tract. A 72-year-old male was referred to the hospital with a perforated gallbladder cancer. Intraoperatively, the tumor was confined to the gallbladder and liver. We presented a case of intention-to-curative resection of perforated gallbladder cancer followed by intraoperative hyperthermic intraperitoneal chemotherapy.

Background We have limited information about neuroendocrine carcinoma (NEC) of the gallbladder. The purpose of this paper is to compare clinical and pathological features between different age groups and prognostic factors for gallbladder NEC and how it differs from adenocarcinoma (ADC) of the gallbladder. Patients and methods This study included 28 gallbladder NEC patients and 137 ADC patients whose clinical characteristics and pathological findings were retrospectively collected. Propensity score matching and Cox regression analysis were used for the analysis of prognostic factors. Results We divided NEC patients into two groups based on the age more than or less than 60 years. Most of the NEC patients less than 60 years old complained of abdominal pain or discomfort (p = 0.038), and more younger patients accepted adjuvant therapy (p = 0.020) than older patients did. CD56 was positive in all patients more than 60 years old, which is significantly higher than that of younger patients (p = 0.039). The mean age was similar between NEC and ADC patients. After eliminating confounding factors between NEC and ADC patients, the overall survival rates were still lower in NEC patients. Univariate analysis extracted six possible risk factors. Multivariate analysis indicated that surgery type, tumor size, and existence of gallstones were independent prognostic factors. Conclusion The overall survival of gallbladder NEC is not associated with age. In this study, surgical method and tumor size were found to be independent risk factors for NECs. In addition, NEC patients have a worse prognosis than ADC patients with similar clinical and pathological features.

Background: Comprehensive genomic analysis of paired primary tumors and their metastatic lesions may provide new insights into the biology of metastatic processes and therefore guide the development of novel strategies for intervention. To date, our knowledge of the genetic divergence and phylogenetic relationships in gallbladder cancer (GBC) is limited.Methods:We performed whole exome sequencing (WES) for 5 patients with primary tumor, metastatic lymph node (LNM) and corresponding normal tissue. Mutations, mutation signatures and copy number variations were analyzed with state-of-art bioinformatics methods. Phylogenetic tree was also generated to infer metastatic pattern. Results:Five driver mutations were detected in these patients. Among which, TP53 was the only shared mutation between primary tumor and LNM. Although tumor mutational burden was comparable between primary tumor and LNM, higher mutation burden was observed in LNM of one patient. Copy number variations (CNVs) burden was higher in LNM than their primary tumor. Phylogenetic analysis indicated both linear and parallel progression of metastasis exist in these patients. TP53 mutation and CNVs were homogenously between primary tumor and LNM.Conclusions:High consistence of genetic landscape were shown between primary tumor and LNM in GBC. However, heterogenicity still exist between primary tumor and LNM in particular patients in term of driver mutation, TMB and CNV burden. Phylogenetic analysis indicated both Linear and parallel progression of metastasis were exist among these patients.

Background Analysis of long-term clinical outcomes of patients with familial adenomatous polyposis is critical in reducing or preventing the incidence of extracolonic malignancies after initial surgery. The aim of the present study was to clarify the long-term outcomes, and establish a surveillance strategy for surgically treated familial adenomatous polyposis patients. Methods Between January 1967 and March 2020, retrospective data were collected from 37 patients with familial adenomatous polyposis treated or monitored in our department. Occurrence of metachronous cancers, including rectal cancers and extracolonic malignancies, and other diseases was analyzed. Results The median follow-up duration after the first surgery was 13.8 years. Initially, 16 patients underwent total proctocolectomy with ileal pouch-anal anastomosis, 18 underwent total colectomy with ileorectal anastomosis, and three underwent other procedures. A secondary proctectomy was performed for 9 of the 18 patients who underwent ileorectal anastomosis. Rectal cancer was diagnosed in 6 patients who underwent ileorectal anastomosis. In addition, 5 gastric cancer, 2 duodenal cancer, 1 gallbladder cancer, and 1 thyroid cancer cases were diagnosed. The age at which the extracolonic malignancies were diagnosed was >50 years. 4 patients died due to metachronous rectal cancer, gastric cancer, or gallbladder cancer. Conclusion Careful consideration should be paid before choosing ileorectal anastomosis as the treatment procedure for familial adenomatous polyposis patients because completion proctectomy was eventually necessary for half of the patients. Long-term surveillance, with more frequent gastric surveillance for patients over 50 years, is important for the prevention and treatment of extracolonic malignancies in familial adenomatous polyposis patients.

PURPOSE For unresectable gallbladder cancer (GBC), gemcitabine and platinum is standard combination; however, outcome is poor. We conducted this study to find feasibility of modified flourouracil, oxaliplatin, and irinotecan in this group. MATERIALS AND METHODS We conducted a prospective, phase II single-arm pilot study. Inclusion criteria were histologically proven GBC and Eastern Cooperative Oncology Group 0-1. Primary end points were overall response rates and overall survival. The following treatment was given: oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, and irinotecan 150 mg/m2, all once on day 1, fluorouracil 2,400 mg/m2 continuous intra-venous infusion over 46 hours repeated every 2 weeks, and maximum 12 doses, with primary granulocyte colony-stimulating factor prophylaxis. RESULTS Between February 2019 and July 2020, 29 patients with unresectable GBC were enrolled. The median age was 52 years, and 18 were females. The Eastern Cooperative Oncology Group was 0 in 4. Five had bilirubin > normal, and 15 each had high serum alkaline phosphatase and carbohydrate antigen 19-9. Twenty-five patients had stage IV disease, and remaining unresectable locally advanced disease. A median of 8.5 cycles was given, and 11 completed treatment. Nine stopped chemotherapy because of progression, and one because of toxicity, and treatment is ongoing in three. Twenty-two required dose reduction. A treatment delay of 1-2 weeks was seen in 25 patients. Best response was complete response 1, partial response 13 (overall response rate 48.2%), and stable disease 9. Four patients with metastatic disease underwent R0 resection. As on cutoff date, nine are surviving (three without disease). Eighteen died of PD, and in two, cause was unknown. There was no toxic death. The median overall survival and progression-free survival were 309 and 252 days, respectively. Twenty-three patients experienced grade III or IV toxicity, and common were diarrhea (13), vomiting (12), and anemia (7). CONCLUSION First-line modified flourouracil, oxaliplatin, and irinotecan is feasible in unresectable GBC with encouraging responses. Toxicities are higher but manageable. Higher response rates make this an option to explore in borderline resectable cases.

Summary: Previous studies have explored the role of laparoscopic surgery (LS) in the surgical management of gallbladder carcinoma (GBC) and obtained satisfactory outcomes versus conventional open surgery. However, most of them either included a small number of patients or mainly focused on the early-staged lesions. Therefore, their results were less statistical powerful and a more comprehensive evaluation on the role of LS in GBC is warranted. A thorough database searching was performed in PubMed, EMBASE and Cochrane Library for comparative studies between the laparoscopic and open approach in the surgical management of GBC and 18 comparative studies were finally identified. RevMan 5.3 and Stata 13.0 software were used for statistical analyses. Pooled results revealed that patients in the laparoscopic group recovered faster with less intraoperative hemorrhage and less postoperative morbidity. Comparable operative time, overall recurrence rate, R0 resection rate, lymph node yield, intraoperative gallbladder violation rate and postoperative survival outcomes were also acquired. Regarding the debating issue of port-site recurrence, a significantly higher incidence of port-site recurrence was observed in laparoscopic group. However, having excluded studies on incidental gallbladder carcinoma, the subsequent pooled result showed no significant difference. Considering the inherent inconsistency of the surgical indication between laparoscopic and open surgeries and the deficiency of advanced lesions, we drew a conclusion that laparoscopic surgery seems to be only safe and feasible for early- or middle-staged lesions. Upcoming random controlled trials or comparative studies with equivalent surgical indication focused on advanced lesions are warranted for further evaluation.

The Gallbladder Reporting and Data System (GB-RADS) ultrasound (US) risk stratification is proposed to improve consistency in US interpretations, reporting, and assessment of risk of malignancy in gallbladder wall thickening in non-acute setting. It was developed based on a systematic review of the literature and the consensus of an international multidisciplinary committee comprising expert radiologists, gastroenterologists, gastrointestinal surgeons, surgical oncologists, medical oncologists, and pathologists using modified Delphi method. For risk stratification, the GB-RADS system recommends six categories (GB-RADS 0–5) of gallbladder wall thickening with gradually increasing risk of malignancy. GB-RADS is based on gallbladder wall features on US including symmetry and extent (focal vs. circumferential) of involvement, layered appearance, intramural features (including intramural cysts and echogenic foci), and interface with the liver. GB-RADS represents the first collaborative effort at risk stratifying the gallbladder wall thickening. This concept is in line with the other US-based risk stratification systems which have been shown to increase the accuracy of detection of malignant lesions and improve management. Graphical abstract: [Figure not available: see fulltext.].

To determine the association of malignancy potential of gallbladder polyps with tumor markers and cholesterol levels, and at which value the presence of malignancy should be suspected.Observational study.University of Health Sciences, Adana City training and research Hospital from December 2017 to November 2020.Ninety patients diagnosed with gallbladder polyp by abdominal ultrasonography, were included in the study. Patients were divided into subgroups of true pseudopolyp, cholesterol-non-cholesterolpolyp, malignant-non-malignant polyp. The groups were compared in terms of age, gender, polyp size, number of polyps, preoperative total cholesterol, HDL (high-density lipoprotein), LDL (low-density lipoprotein), triglyceride, Ca 19-9 (carbohydrate antigen 19-9), Ca 72-4 (carbohydrate antigen 72-4), Cea (carcinoembryonic antigen) levels.In the true polyp group, polyp size, Ca 19-9, Ca 72-4 and Cea median values were significantly higher (p=0.001, p=0.029, p=0.003, and p=0.007, respectively); whereas, triglyceride levels were significantly lower compared to the pseudopolyp group (p=0.002). Polyp size was significantly lower in cholesterol polyp group compared to non-cholesterol polyp group (p= 0.032), and LDL and triglyceride medians were significantly higher (p=0.031, and p0.001) in cholesterol group. Among the true polyps, polyp size, Ca 19-9, Ca 72-4 and Cea levels were significantly higher in adenocarcinoma group than non-malignant polyp groups (p0.05). Cut-off values were determined as11 mm AUC: 0.906 for size,24.1 U/mL. AUC: 1.00 for Ca 19-9,9.6 U/mL AUC: 1.00 for Ca 72-4, and40 ng/mL AUC: 0.984 for CEA, respectively.Polyps larger than 11mm with high levels of CEA, Ca 72-4, Ca 19-9, evaluated together, may act as a guide for the clinician in predicting malignancy. The availability of economical and accessible parameters may allow a new algorithm to be developed in the treatment and follow-up approach of gallbladder polyps. Key Words: Gallbladder polpys, Ca 19-9 antigen, Ca 72-4 antigen, Tumor marker, Gallbladder cancer.

Backgrounds/aims Extended cholecystectomy (EC) is the mainstay of treatment in most patients with potentially curable gallbladder cancer (GBC). The optimum extent of hepatic resection in EC is debatable. Methods This retrospective study was conducted on patients with GBC who received EC from May 2009 to February 2019. Based on the extent of hepatic resection, patients were divided into ECB (EC involving bi-segmentectomy s4b&5) and ECW (EC involving wedge hepatic resection) groups. Patients with T1 GBC, T4 GBC, and benign diseases were excluded. Post-exclusion, both groups were matched for T and N stage. Matched groups were then compared. Results Out of a total of 161 patients who received EC, 86 patients had ECB and 75 patients had ECW. After exclusion and matching, both ECB and ECW groups had 35 patients. Their demographic and clinical profiles were comparable. Surgical blood loss (p = 0.005) and postoperative complication rate (p = 0.035) were significantly less in the ECB group. For ECB vs. ECW, mean recurrence-free survival (RFS) was 58.2 months vs. 42.3 months (p = 0.264) and overall survival (OS) was 61.5 months vs. 43.4 months (p = 0.161). On univariate analysis, higher T and N stages were associated with poor prognosis. On multivariate analysis, higher T stage, N stage, and American Society of Anaesthesiologists grade were associated with poor RFS and OS. Conclusions The survival after ECB for T2 and T3 GBC was not significantly superior to that after ECW. However, surgical blood loss and postoperative complications were lower following ECB.

Gallbladder cancer (GBC) is an uncommon but very aggressive malignancy with poor prognosis. Concerns for oncological inferiority related to the technical difficulties in performing laparoscopic portal lymphadenectomy discourage many surgeons to undertake this operation minimally invasively. With wide application of robotic technology to solve limitations of conventional laparoscopy, we describe our initial outcomes of robotic central hepatectomy and portal lymphadenectomy for gallbladder carcinoma in 15 consecutive patients. Data were presented as median (mean ± SD). Patients were 70 (73 ± 10.9) years old with BMI of 26 (26 ± 3.6) kg/m2. Tumor size was 3(4 ± 1.9) cm. Operative duration was 222 (237 ± 85.7) minutes and estimated blood loss was 200 (222 ± 135.4) mL. There were no intraoperative complications and complete resection (R0) was obtained in nearly all patients. Postoperative complications were seen in two patients (bile leak (n = 1) and respiratory failure (n = 1)). Length of stay was 3 (4 ± 4.0) days without 30-day mortality. Robotic approach is safe and effective for the treatment of GBC.

Introduction: Gallbladder carcinoma is often difficult to distinguish from benign gallbladder diseases. While the diagnostic accuracy of endoscopic transpapillary gallbladder drainage (ETGD) has been reported, these results were obtained retrospectively. This prospective study aimed to evaluate the cytological diagnostic accuracy of ETGD in patients with gallbladder disease. Methods: This single-arm prospective clinical trial included a total of 35 patients scheduled to undergo ETGD between March 2017 and September 2019. A 5F pigtail nasobiliary drainage tube was inserted into the gallbladder, and bile was collected over 5 times; if ETGD failed, a drainage tube was placed into the bile duct. The endpoints were, first, the cytological diagnostic accuracy of ETGD and, second, technical success rates and adverse events. Results: Of the 35 patients, 19 were finally diagnosed with gallbladder cancer. The success rate of ETGD tube insertion was 85.7%, and the morphological pattern of the cystic duct with the angle down and located on the right side had a significantly lower success rate for ETGD than that of other cystic duct patterns (odds ratio, 13.5; 95% confidence interval, 1.7–143.7; p = 0.02). Cytological samples were collected 5 times on median. The sensitivity, specificity, and accuracy in all patients were 78.9%, 100%, and 88.6%, respectively, while those in 30 patients with successful ETGD were 87.5%, 100%, and 93.3%, respectively. Adverse events occurred in 3 patients: mild pancreatitis in 1 patient and obstructive jaundice in 2 patients; all complications were resolved with conservative therapy. Discussion/Conclusions: Cytology using an ETGD tube is useful in differentiating benign and malignant gallbladder diseases (Clinical Trial Registry No. UMIN000026929).

Background The genetic changes underlying carcinogenesis in patients with risk factors of gallbladder carcinoma (GBC) remains controversial, especially in patients with pancreaticobiliary maljunction (PBM). This study aimed to clarify the association between risk factors of GBC and genetic changes using next-generation sequencing (NGS). Methods We retrospectively analyzed resected tissues of 64 patients who were diagnosed with GBC (n = 26), PBM [with GBC (n = 8), without GBC (n = 20)], and chronic cholecystitis, used as a control group (n = 10). DNA was extracted from tumors and their surrounding tissues, which were precisely separated by laser-capture microdissection. Gene alterations of 50 cancer-related genes were detected by NGS and compared with clinical information, including PBM status. Results The most frequent gene alterations in GBC tissues occurred in TP53 (50%), followed by EGFR (20.6%), RB1 (17.6%), and ERBB2 (17.6%). Gene alterations that were targetable by molecular targeted drugs were detected in 20 cases (58.8%). Statistical analysis of gene alterations and risk factors revealed that TP53 alteration rate was higher in GBC patients with PBM than those without PBM (p = 0.038), and the TP53 mutation rates in the epithelium of control patients, epithelium of PBM patients without GBC, peritumoral mucosa of GBC patients with PBM, and tumor tissue of GBC patients with PBM were 10, 10, 38, and 75%, respectively (p Conclusions TP53 alteration more than KRAS mutation was revealed to underlie carcinogenesis in patients with PBM.

Preoperative diagnosis for suspected gallbladder cancers is challenging, with a risk of overtreating benign disease, for example, xanthogranulomatous cholecystitis, with radical cholecystectomies. We retrospectively evaluated the surgeon's intraoperative assessment alone, and with the addition of intraoperative frozen sections, for suspected gallbladder cancers from a tertiary hepatobiliary multidisciplinary team (MDT).MDT patients with complex gallbladder disease were included. Collated data included demographics, MDT discussion, operative details, and patient outcomes.A total of 454 patients with complex gallbladder disease were reviewed, 48 (10.6%) were offered radical surgery for suspected cancer. Twenty-five underwent frozen section that led to radical surgery in 6 (25%). All frozen sections were congruent with final histopathology but doubled the operating time (p 0.0001). Both the surgeon's subjective and additional frozen section's objective assessment, allowed for de-escalation of unnecessary radical surgery, comparing favourably to a 13.0% cancer diagnosis among radical surgery historically.The MDT process was highly sensitive in identifying gallbladder cancers but lacked specificity. The surgeon's intraoperative assessment is paramount in suspected cancers, and deescalated unnecessary radical surgery. Intraoperative frozen section was a safe and viable adjunct at a cost of resources and operative time.

Background Achieving microscopically negative (R0) surgical margins in gallbladder cancer often requires a partial hepatectomy with associated risk of morbidity and potential to delay adjuvant therapy. Prior studies on the importance of margin status in resectable gall bladder cancer include small numbers of patients with positive (R1) resection margins and are underpowered. Methods We queried the National Cancer Database to identify patients undergoing resection of gallbladder adenocarcinoma between 2004 and 2015. Patients presenting with metastatic disease, those who received neoadjuvant therapy, and those with fewer than 3 lymph nodes assessed were excluded. 1:1 propensity score matching was used to develop cohorts undergoing either R0 or R1 resection, matched for demographic, pathologic, and facility characteristics. Kaplan–Meier analysis was used to assess the association between margin status and overall survival. Results A total of 1,439 patients met inclusion criteria; 1,285 underwent R0 and 154 underwent R1 resection. On Kaplan–Meier analysis of propensity-matched cohorts, patients undergoing R0 resection had a median overall survival that was 18 months longer than those undergoing R1 resection (34.6 ± 2.0 months vs 16.3 ± 1.7 months, P, Highlights • R0 resection is associated with an 18-month survival benefit. • Age, histologic grade, and tumor size were associated with receipt of R0 resection. • Chemotherapy was associated with improved survival, independent of grade and stage.

Gallbladder cancer is a rare, aggressive malignancy that has a poor overall prognosis. Effective treatment consists of early detection and surgical treatment. With the wide spread treatment of gallbladder disease with minimally invasive techniques, the rate of incidental gallbladder cancer has seen an equitable rise along with stage migration towards earlier disease. Although the treatment remains mostly surgical, newer modalities such as regional therapy as well as directed therapy based on molecular medicine has led to improved outcomes in patients with advanced disease. We aim to summarize the management of gallbladder cancer along with the newer developments in this formidable disease process.

Background Diagnostic laparoscopy is often a necessary, albeit invasive, procedure to help resolve undiagnosed peritoneal diseases. Previous retrospective studies reported that EUS-FNA is feasible on peritoneal and omental lesions, however, EUS-FNA provided a limited amount of tissue for immunohistochemistry stain (IHC). Aim This pilot study aims to prospectively determine the effectiveness of EUS-FNB regarding adequacy of tissue for IHC staining, diagnostic rate and the avoidance rate of diagnostic laparoscopy or percutaneous biopsy in patients with these lesions. Methods From March 2017 to June 2018, patients with peritoneal or omental lesions identified by CT or MRI at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand were prospectively enrolled in the study. All Patients underwent EUS-FNB. For those with negative pathological results of EUS-FNB, percutaneous biopsy or diagnostic laparoscopy was planned. Analysis uses percentages only due to small sample sizes. Results A total of 30 EUS-FNB passes were completed, with a median of 3 passes (range 2–3 passes) per case. For EUS-FNB, the sensitivity, specificity, PPV, NPV and accuracy of EUS-FNB from peritoneal lesions were 63.6%, 100%, 100%, 20% and 66.7% respectively. Adequate tissue for IHC stain was found in 25/30 passes (80%). The tissues from EUS results were found malignant in 7/12 patients (58.3%). IHC could be done in 10/12 patients (83.3%). Among the five patients with negative EUS results, two underwent either liver biopsy of mass or abdominal paracentesis, showing gallbladder cancer and adenocarcinoma. Two patients refused laparoscopy due to advanced pancreatic cancer and worsening ovarian cancer. The fifth patient had post-surgical inflammation only with spontaneous resolution. The avoidance rate of laparoscopic diagnosis was 58.3%. No major adverse event was observed. Conclusions EUS-FNB from peritoneal lesions provided sufficient core tissue for diagnosis and IHC. Diagnostic laparoscopy can often be avoided in patients with peritoneal lesions.

This study aimed to investigate the impact of surgery on outcomes in patients with recurrent biliary tract cancer (BTC) and elucidate factors affecting survival after surgery for this disease.A single-center study was undertaken in 178 patients with recurrent BTC, of whom 24 underwent surgery for recurrence, 85 received chemotherapy, and 69 received best supportive care. Then, we carried out a multicenter study in 52 patients undergoing surgery for recurrent BTC (gallbladder cancer, 39%; distal cholangiocarcinoma, 27%; perihilar cholangiocarcinoma, 21%; intrahepatic cholangiocarcinoma, 13%).In the single-center study, 3-year survival after recurrence was 53% in patients who underwent surgery, 4% in those who received chemotherapy, and 0% in those who received best supportive care (p 0.001). Surgery was an independently prognostic factor (p 0.001). In the multicenter series, the respective 3-year and 5-year survival after surgery for recurrence was 50% and 29% in the 52 patients. Initial site of recurrence was the only independent prognostic factor (p = 0.019). Five-year survival after surgery for recurrence in patients with single distant, multifocal distant, and locoregional recurrence was 51%, 0%, and 0%, respectively (p = 0.002). Sites of single distant recurrence included the liver (n = 13, 54%), distant lymph nodes (all from gallbladder cancer, n = 7, 29%), lung (n = 2, 9%), peritoneum (n = 1, 4%), and abdominal wall (n = 1, 4%).Surgery may be an effective option for patients with less aggressive tumor biology characterized by single distant recurrence in recurrent BTC.

Metastatic melanoma of the gallbladder is extremely rare. It has a poor prognosis. Its optimal treatment remains unclear. Surgical resection is generally considered the mainstay of treatment. However, there are no standards to guide the choice between open surgery and laparoscopic surgery. Criteria for the extent of surgical dissection have not been established yet either. We report a patient diagnosed with gallbladder cancer who underwent extended cholecystectomy but had metastatic melanoma at the final biopsy. We reviewed the literature on the treatment of metastatic melanoma in the gallbladder and compared it with our case to determine a treatment strategy.

Aim of doing this review was to give a uniform consensus on prognostic impact of tumor location (hepatic vs peritoneal), liver resection and adjuvant chemotherapy in gall bladder cancer and, to compare them with previous well-studied factors of survival. We systematically review PubMed, Scopus and Cochrane for relevant articles with no date restrictions, language was restricted to English. Those articles were included that had provided Hazard ratio (HR) of survival for T2 gall bladder cancer. We identified nine retrospective studies published between 2014 and 2020 with 2345 patients. Meta-analysis showed that T2b (hepatic) cancers had higher odds of mortality (HR 3.16 [2.11, 4.74], I2 = 0%). Liver resection was associated with significantly higher odds of 5-year overall survival only in T2b (2.20 [1.33, 3.63], I2 = 67%), adjuvant chemotherapy was not associated with any significant decrease in mortality risk (0.98 [0.83–1.16]. I2 = 20%). Hepatic sided gall bladder tumors carry higher odds for mortality and recurrence. T2a tumors can be managed without hepatic resection. To risk stratify patients we also formulated a scoring system for mortality risk.

Objectives Evaluation of the association of PARP1 rs1136410 (A/G) polymorphism with gallbladder cancer susceptibility and its prognosis in the Indian population of eastern Uttar Pradesh and western Bihar. Methods PARP1 rs1136410 was genotyped by PCR-RFLP and its association with the prognosis of gallbladder cancer patients were analyzed using Kaplan-Meier plot and log-rank tests. Results Our results demonstrate that minor allele G is more frequent in gallbladder cancer patients than controls. The frequencies of minor allele G and GG genotype are significantly associated with increased risk of gallbladder cancer. Our data suggest that the minor allele G and homozygous genotype GG are significant predisposing factors for the early age of onset of gallbladder cancer. Similarly, women patients having AG and GG genotypes demonstrate an increased risk of gallbladder cancer. The risk group genotypes (AG + GG) are significantly more frequent in patients with thick gallbladder wall, with jaundice and with the presence of lymph node than in patients with normal gallbladder wall thickness, without jaundice and absence of lymph node involvement. Survival analysis data suggest that patients with risk group genotype (AG + GG) presenting jaundice have shorter overall survival. Conclusion Our study suggests that the minor allele G of PARP1 rs1136410 (A/G) is a predisposing factor for gallbladder carcinogenesis and is significantly associated with early onset of the disease. Interestingly, the minor allele G is significantly more frequent in the patients with jaundice, lymph node metastasis and gallbladder wall thickness.

Advanced glycation endproducts (AGEs) may contribute to liver carcinogenesis because of their proinflammatory and prooxidative properties. Diet is a major source of AGEs, but there is sparse human evidence on the role of AGEs intake in liver cancer etiology. We examined the association between dietary AGEs and the risk of hepatobiliary cancers in the European Prospective Investigation into Cancer and Nutrition prospective cohort (n = 450 111). Dietary intake of three AGEs, Nε‐[carboxymethyl]lysine (CML), Nε‐[1‐carboxyethyl]lysine (CEL) and Nδ‐[5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl]‐ornithine (MG‐H1), was estimated using country‐specific dietary questionnaires linked to an AGEs database. Cause‐specific hazard ratios (HR) and their 95% confidence intervals (CI) for associations between dietary AGEs and risk of hepatocellular carcinoma (HCC), gallbladder and biliary tract cancers were estimated using multivariable Cox proportional hazard regression. After a median follow‐up time of 14.9 years, 255 cases of HCC, 100 cases of gallbladder cancer and 173 biliary tract cancers were ascertained. Higher intakes of dietary AGEs were inversely associated with the risk of HCC (per 1 SD increment, HR‐CML = 0.87, 95% CI: 0.76‐0.99, HR‐CEL = 0.84, 95% CI: 0.74‐0.96 and HR‐MH‐G1 = 0.84, 95% CI: 0.74‐0.97). In contrast, positive associations were observed with risk of gallbladder cancer (per 1 SD, HR‐CML = 1.28, 95% CI: 1.05‐1.56, HR‐CEL = 1.17; 95% CI: 0.96‐1.40, HR‐MH‐G1 = 1.27, 95% CI: 1.06‐1.54). No associations were observed for cancers of the intra and extrahepatic bile ducts. Our findings suggest that higher intakes of dietary AGEs are inversely associated with the risk of HCC and positively associated with the risk of gallbladder cancer., What's new? Advanced glycation endproducts (AGEs) are proteins or lipids with sugars added to them, and they can form in foods during cooking. They have pro‐inflammatory and pro‐oxidative properties in the body. These authors investigated whether dietary consumption of AGEs affect risk of liver cancer, using the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants filled out food questionnaires to determine AGE consumption. Higher intakes of AGEs were associated with reduced risk of hepatocellular carcinoma (HCC) and increased risk of gallbladder cancer. However, it's still not entirely clear how much AGEs in the diet contribute to circulating AGE levels.

Item does not contain fulltext OBJECTIVE: The aim of this study was to develop and validate a clinical prediction model to predict overall survival in patients with nonmetastatic, resected gallbladder cancer (GBC). BACKGROUND: Although several tools are available, no optimal method has been identified to assess survival in patients with resected GBC. METHODS: Data from a Dutch, nation-wide cohort of patients with resected GBC was used to develop a prediction model for overall survival. The model was internally validated and a cohort of Australian GBC patients who underwent resection was used for external validation. The performance of the American Joint Committee on Cancer (AJCC) staging system and the present model were compared. RESULTS: In total, 446 patients were included; 380 patients in the development cohort and 66 patients in the validation cohort. In the development cohort median survival was 22 months (median follow-up 75 months). Age, T/N classification, resection margin, differentiation grade, and vascular invasion were independent predictors of survival. The externally validated C-index was 0.75 (95%CI: 0.69-0.80), implying good discriminatory capacity. The discriminative ability of the present model after internal validation was superior to the ability of the AJCC staging system (Harrell C-index 0.71, [95%CI: 0.69-0.72) vs. 0.59 (95% CI: 0.57-0.60)]. CONCLUSION: The proposed model for the prediction of overall survival in patients with resected GBC demonstrates good discriminatory capacity, reasonable calibration and outperforms the authoritative AJCC staging system. This model can be a useful tool for physicians and patients to obtain information about survival after resection and is available from https:// gallbladderresearch.shinyapps.io/Predict_GBC_survival/.

Invasive gallbladder carcinoma (GBC) is preceded by two main types of precursor lesions: intracholecystic papillary-tubular neoplasms (ICPNs) and biliary intraepithelial neoplasias (BilINs). Invasive GBCs with an ICPN component have more favorable prognoses than those without an ICPN component. Some BilINs show a relatively exophytic papillary pattern but do not meet the ICPN criteria; at our institution, we call these papillary neoplasias. To clarify the clinical significance of papillary neoplasia, we herein examined 80 invasive GBCs and classified them into three groups based on the type of preinvasive lesions: those with ICPN (ICPN group, n = 35), those with papillary neoplasia (pap-neoplasia group, n = 13), and those without ICPN/papillary neoplasia (group without ICPN/pap-neoplasia, n = 32). We then compared the prognostic differences and characterized the tumors of each group by determining the immunohistochemical expressions of various biomarkers. The overall survival periods of the ICPN and pap-neoplasia groups were significantly longer than that of the group without ICPN/pap-neoplasia (P 0.0001, P = 0.0036, respectively). Multivariate analysis revealed that lacking ICPN/papillary neoplasia was independently associated with poor prognosis (P = 0.0007), as were poor differentiation (P = 0.0395), presence of preoperative symptoms (P = 0.0488), and advanced stage (P = 0.0234). Invasive components of the ICPN and pap-neoplasia groups were characterized by higher expressions of p16 and p53 compared with those of the group without ICPN/pap-neoplasia. The prognoses of the invasive GBCs with either papillary neoplasia or ICPN were thus more favorable than those of the invasive GBCs without ICPN/pap-neoplasia. Invasive GBCs with exophytic papillary preinvasive lesions (ICPN and papillary neoplasia) may be biologically different from those without such lesions.

BACKGROUND: Coagulation and fibrinolysis activation are frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis and worse long-term outcome. The specific aim of this study was to develop an effective prognostic nomogram to help make individualized estimates for patients with resected gallbladder cancer (GBC). METHODS: Patients with resected GBC who were diagnosed between 2006 and 2014 at Xinhua Hospital were selected. Model performance was measured by c-index and calibration curve. The results were further validated using bootstrap and a cohort of 38 patients from a branch hospital who underwent surgery from 2006 to 2014. RESULTS: Backward stepwise selection and Lasso were applied respectively to select predictors. T stage, N stage, and preoperative serum fibrinogen were included in the final model. Predictions correlated well with observed 1- and 3-year survival. The c-index for predicting survival was 0.74 (95% confidence interval, 0.70–0.78), which was statistically higher than that of the AJCC 7th system and Nevin system (P=0.04, 0.04, respectively). In the validation cohort, the nomogram performed better than the other two staging systems (c-index: 0.71 vs. 0.67 and 0.67). CONCLUSIONS: The validated nomogram is a practical tool for predicting the overall survival (OS) of postoperative GBC patients. Preoperative serum fibrinogen levels were associated with tumor progression and may be an independent predictor for GBC patients.

Background Krukenberg tumors are uncommon and are indicative of an ovarian metastatic carcinoma that originates from another site of primary malignancy. The majority of metastases to ovaries are derived from the stomach and colon. We present a rare case of a metastatic ovarian malignant tumor that originated from gallbladder adenocarcinoma. Case presentation A 45-year-old premenopausal Korean woman presented with abdominal distension. Bilateral multiseptated ovarian tumors and a wall-thickened gallbladder were found on abdominal computed tomography. The patient was diagnosed with metastatic ovarian carcinoma arising from gallbladder adenocarcinoma and was treated with adjuvant chemotherapy. Conclusions Metastases to the ovaries from other sites, including the gallbladder, are rare and usually resemble primary ovarian tumors. Therefore, potential metastatic ovarian tumors of newly diagnosed pelvic masses should be considered in differential diagnoses.

Background Although gallbladder cancer (GBCA) is characterized by a dismal prognosis, there is a proportion of patients who are cured. The aim of this study was to analyze the profile of these patients. Methods A database was queried for patients who underwent curative resection with a follow-up of at least 5 years. Patients were prospectively treated and registered by the same surgical team. A multivariate regression analysis was used to identify factors associated with long-term survival. Results From 1988 to 2013, 461 patients were evaluated and 112 who underwent resection were analyzed. Among the patients, five year survival was 57% while lymph node and liver compromise were the only independent factors associated with survival. On the other hand, the elapsed time between the cholecystectomy and the resection, the differentiation grade and the level of wall invasion did not have an independent effect on the prognosis. Conclusion Despite its poor prognosis, a subset of patients can be cured of GBCA. R0 resection of patients without lymph and liver infiltration are key to GBCA survival.

Background The first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC. Methods The data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events. Results A total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3-4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group. Conclusions mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.

BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

Neuroendocrine neoplasms (NENs) of the gallbladder are very rare. As a result, the classification of pathologic specimens from gallbladder NENs, currently classified as gallbladder neuroendocrine tumors (GB-NETs) and carcinomas (GB-NECs), is inconsistent and makes nomenclature, classification, and management difficult. Our study aims to evaluate the epidemiological trend, tumor biology, and outcomes of GB-NET and GB-NEC over the last 5 decades. This is a retrospective analysis of the SEER database from 1973 to 2016. The epidemiological trend was analyzed using the age-adjusted Joinpoint regression analysis. Survival was assessed with Kaplan–Meier analysis and Cox regression was used to assess predictors of poor survival. A total of 482 patients with GB-NEN were identified. Mean age at diagnosis was 65.2 ± 14.3 years. Females outnumbered males (65.6% vs. 34.4%). The Joinpoint nationwide trend analysis showed a 7% increase per year from 1973 to 2016. The mean survival time after diagnosis of GB-NEN was 37.11 ± 55.3 months. The most common pattern of nodal distribution was N0 (50.2%) followed by N1 (30.9%) and N2 (19.2%). Advanced tumor spread (into the liver, regional, and distant metastasis) was seen in 60.3% of patients. Patients who underwent surgery had a significant survival advantage (111.0 ± 8.3 vs. 8.3 ± 1.2 months, p

Gallbladder cancer (GBC) is a relatively uncommon malignancy of the gastrointestinal tract, but it has a poor prognosis. Most cases of GBC are initially diagnosed in advanced stage and the efficacy of currently available treatments have been disappointing. Sex and gender medicine investigates the clinical impact of sex and gender difference on diseases and it may provide a good starting point for the personalized medicine. In this article, sex and gender differences in GBC are explained based on an overview of epidemiology and risk factors focusing on recent researches.

This study was designed to evaluate the correlation of expression profiles of MUC2, MUC4, and MUC5AC to the clinico-pathological parameters in gallbladder cancer. We recruited biopsies of a total of 60 subjects including 50 primary tumor biopsies from histopathologically proven gallbladder cancer and 10 cases of chronic cholecystitis as control. We have investigated the expression levels of MUC2, MUC4, and MUC5AC by semi-quantitative RT-PCR and immune-histochemistry in gallbladder cancer biopsies, and chronic cholecystitis as a control. Clinical correlation of the differential expression of MUC2, MUC4, and MUC5AC was determined using appropriate statistical methods. Our results demonstrated that MUC2 was significantly (p = 0.004) upregulated in 16%, MUC4 was significantly (p = 0.0004) upregulated in 24%, and MUC5AC was significantly (p = 0.003) upregulated in 32% samples at transcript levels in primary gallbladder cancer biopsies in comparison to the control. Similar to RT-PCR data, MUC2 was significantly (p = 0.001) upregulated in 30%, MUC4 was significantly (p = 0.047) upregulated in 48%, and MUC5AC was significantly (p = 0.002) upregulated in 52% samples at proteome levels in primary gallbladder cancer biopsies in comparison to the control. In conclusion, the MUC2, MUC4, and MUC5AC expression were found to be significantly upregulated in gallbladder cancer group than control. The overexpression of MUC2, MUC4, and MUC5AC suggested their association with gallbladder cancer.

Background Presence of jaundice in gallbladder carcinoma (GBC) is considered a sign of inoperability with no defined treatment pathways. Methods Retrospective analysis of all surgically treated GBC patients from January 2010 to December 2019 was performed for evaluating etiology of obstructive jaundice, resectability, postoperative morbidity, mortality, disease-free survival (DFS) and overall survival (OS). Results Out of 954 patients, 521 patients (54.61%) were locally advanced gallbladder carcinoma (LAGBC: Stage III and IV) and 113 patients (11.84%) had jaundice at presentation. Thirty-four (30%) patients had benign cause of obstructive jaundice. Median OS of the whole cohort (n=113) was 22 months (16.5-27.49 months) with resectability rate of 62% (70/113). Median OS of curative resection group (n=70) was 32 months and DFS was 25 months. Treatment completion was achieved in 30% (n= 21/70) patients with median OS of 46 months and median DFS of 27 months. Isolated bile duct infiltration subgroup fared the best with median OS of 74 months with a 5-year survival of 66.7%. Conclusion Surgical resection as a part of multimodality treatment improves survival in carefully selected locally advanced gallbladder cancer patients with jaundice. Early introduction of systemic therapy is the key in the management of this disease with aggressive tumor biology.

Elevated systemic levels of soluble cluster of differentiation 14 (sCD14) have been associated with gallbladder cancer (GBC), but the association with sCD14 levels within the gallbladder has not been investigated. Here, we evaluated sCD14 in the bile of 41 GBC cases and 117 gallstone controls with data on 65 bile inflammation markers. We examined the relationship between bile sCD14 levels and GBC using logistic regression and stratified the analysis by stage. We included GBC-associated inflammatory biomarkers in the model to evaluate the influence of local inflammation. Bile sCD14 levels (third versus first tertile) were associated with GBC (adjusted odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.2–8.0). The association was equally strong for stage I/II (OR: 3.3, 95% CI: 0.9–15.6) and stage III/IV (OR: 3.2, 95% CI: 1.0–12.4) cancers. Including the GBC-associated inflammatory markers in the model removed the association between bile sCD14 and GBC (OR: 1.0, 95% CI: 0.3–3.5). The findings suggest that immune activation within the gallbladder may be related to GBC development, and the effect of sCD14 is influenced by inflammation. Similar associations across tumor stages suggest that elevated bile sCD14 levels may reflect changes early in GBC pathogenesis. Associations between GBC and sCD14 levels in both bile and plasma suggest sCD14 could be a potential biomarker for GBC.

Background: Gallbladder (GB) cancer is a rare malignancy with a variable incidence worldwide. Imaging detection at an early stage is elusive. Preoperative imaging for tumour recognition and non-invasive staging is essential to triage patients to appropriate care. Objectives: To describe the CT imaging findings of GB cancer among Nigerians. Methods: A retrospective review of the CT images of 15 patients who had gall bladder carcinoma between January 2015 and June 2017 at a private diagnostic facility in Lagos was done. Results: The age of the patients ranged from 39 to 73 years with a mean age of 60.9 years. The male to female ratio was 1:4.3. Clinical presentations included abdominal pain (61.5%) and jaundice (38.5%). Irregular GB wall thickening (61.5%) and focal mass lesions in the GB (38.5%) were the main features on imaging while 38.5% had associated gall stones. Infiltration of the adjacent liver was found in 76.9% and 60 % of those who had local infiltration of the liver also had intrahepatic metastasis. Conclusion: A majority of gall bladder cancer cases are still diagnosed in their late stages. CT scan readily delineates regional spread into adjacent organs which may be obscured in other imaging modalities due to adjacent bowel gas.

Associations of obesity have been established for at least 11 cancer sites in observational studies, though some questions remain as to causality, strength of associations, and timing of associations throughout the life course. In recent years, Mendelian randomization (MR) has provided complementary information to traditional approaches, but the validity requires that the genetic instrumental variables be causally related to cancers only mediated by the exposure. We summarize and evaluate existing evidence from MR studies in comparison with conventional observational studies to provide insights into the complex relationship between obesity and multiple cancers. MR studies further establish the causality of adult obesity with esophageal adenocarcinoma and cancers of the colorectum, endometrium, ovary, kidney, and pancreas, as well as the inverse association of early life obesity with breast cancer. MR studies, which might account for lifelong adiposity, suggest that the associations in observational studies typically based on single measurement may underestimate the magnitude of the association. For lung cancer, MR studies find a positive association with obesity, supporting that the inverse association observed in some conventional observational studies likely reflects reverse causality (loss of lean body mass before diagnosis) and confounding by smoking. However, MR studies have not had sufficient power for gallbladder cancer, gastric cardia cancer, and multiple myeloma. In addition, more MR studies are needed to explore the effect of obesity at different timepoints on postmenopausal breast cancer and aggressive prostate cancer.

Among the malignant neoplasms of the hepatobiliary zone, gallbladder cancer (GBC) is rare. The incidence of GBC is highest in patients over 65 years of age. In the early stages GBC rarely has clinical manifestations, and often occurs under the guise of other gastroenterological diseases, and is often an accidental finding. Since GBC tends to show high dissemination, at the time of diagnosis, almost every second patient has an advanced form of the disease that is not the subject to surgical treatment. Most authors tend to believe that the use of combined treatment of GBC (extended resection and adjuvant chemotherapy) significantly increases the survival rate of patients. Currently, about 1/3 of patients receive adjuvant chemotherapy in the treatment of GBC. This is due to a small number of prospective randomized trials. Today, most experts recognize that surgery is the only treatment that can be performed in patients with early stages of prostate cancer. At the same time, a reduction in the risk of complications and a large percentage of five- and ten-year survival are achieved. Traditional cholecystectomy can be used to treat stage 1a PCa, this is possible if PC is accidentally found during surgical treatment of GSD. Unfortunately, prostate cancer and bile ducts belongs to the group of malignant neoplasms, in which most patients are unable to perform radical surgical treatment due to for the rapid dissemination of the process. When determining the tactics of patient supervision, it is necessary to take into account the prognostic factors of overall survival in prostate cancer: the type of surgery, the patient's age and sex, the size of the tumor, the presence of metastases in the regional lymph nodes, the presence of adjuvant chemotherapy. There is still a dispute between specialists about the appointment of adjuvanted chemotherapy to patients after surgical treatment of prostate cancer. Many authors acknowledge that adjuvant chemotherapy plays a positive role in improving patient survival after surgery. RAD is recognized as a chemosensitive cancer. Several drugs are active in relation to RS, used for adjuvant chemotherapy: fluorouracil, gemcitabine, mitomycin, cisplatin, capecitabine, epirubicin, and oxaliplatin. This article provides an overview of current research that is aimed at studying the effectiveness of adjuvant chemotherapy in patients with verified GBC of various stages.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Background The study aimed at establishing a nodal staging score (NSS) to quantify the likelihood that pathologic node-negative gallbladder cancer (GBC) patients are indeed free of lymph node (LN) metastasis. Methods Clinicopathological data of 1374 GBC patients with T1b-T2 stages were collected from the Surveillance, Epidemiology and End Result database (design cohort [DC], n = 1289) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 85). NSS was derived from the count of examined LNs (ELNs) and T stage by using a beta-binomial model, and represented the probability that a node-negative patient is correctly staged. The prognostic value of NSS in node-negative GBC was evaluated by survival analysis. Results The probability of missing a nodal disease in node-negative GBC patients with T1b-T2 stages (pT1bN0 and pT2N0) decreased as the number of ELNs increased. NSS increased as the number of ELNs increased. For pT1bN0 and pT2N0 patients, examination of 5 and 27 lymph nodes could ensure an NSS of 90.0%, respectively. Multivariate analysis revealed that NSS was an independent predictor for overall survival in pT1bN0 and pT2N0 GBC patients (DC, HR:0.53, 95%CI: 0.42–0.66, p Conclusion NSS could evaluate the adequacy of nodal staging and predict the prognosis in pT1bN0 and pT2N0 GBC patients, and hence was helpful to guide their treatment strategies.

Objective: We aimed to find the frequency of gallbladder carcinoma and the relationship between dysplasia and metaplasia, which are among predisposing factors for carcinoma.Material and Methods: In this study, the histopathological results of 815 patients who underwent cholecystectomy between 2016-2019 in Ahi Evran Training and Research Hospital, Department of General Surgery were retrospectively analyzed.Results: Of the patients who underwent cholecystectomy, 591 (72.5%) were female and 224 (27.5%) were male. The average age was 50.5 years for women and 54.1 years for men. The general average age was 51.5 years. Cholecystectomy was performed laparoscopically in 698 (85.6%) patients while in 117 (14.4%) patients the operation was either started as open cholecystectomy or the decision to convert to open cholecystectomy was made later during the operation for different reasons. Gallbladder carcinoma was detected in two (0.24%) patients, one 62-year-old male and one 67-year-old female. The rate of gallbladder carcinoma was 0.4%for male patients and 0.1%for female patients. Metaplasia in the gallbladder was detected in 16 (1.96%) patients, 15 of which were female and one was male. The average age of these patients was 43.6 years. Dysplasia was detected in only a 48-year-old male patient (0.12%).Conclusion: Chronic irritation caused by the presence of gallstones leads to metaplasia which is a precancerous lesion. Therefore, we think that patients with gallstones should be evaluated for surgery or close follow-up, even if they do not have symptoms., Amaç: Çalışmamızda kliniğimizde yapılan kolesistektomileri retrospektif olarak tarayarak safra kesesi karsinomu sıklığını ve karsinom predispozan faktörleri arasında yer alan displazi ve metaplazi arasındaki ilişkiyi bulmayı amaçladık.Gereç ve Yöntemler: Bu çalışmada Ahi Evran Eğitim ve Araştırma Hastanesi Genel Cerrahi Anabilim Dalında 2016-2019 yılları arasında kolesistektomi ameliyatı yapılan 815 hastanın histopatolojik sonuçları retrospektif olarak incelenmiştir.Bulgular: Kolesistektomi yapılan hastaların 591’i (%72.5) kadın 224’ü (%27.5) erkekti. Yaş ortalaması kadınlarda 50.5 yıl, erkeklerde 54.1 yıl olarak bulundu. Genel yaş ortalaması 51.5 yıl idi. Kolesistektomi ameliyatı 698 (%85.6) hastaya laparoskopik olarak yapılmış, 117 (%14.4) hastada ise ya açık olarak başlanmış ya da sonradan farklı sebeplerle açık kolesistektomiye geçilmişti. Biri 62 yaşında erkek, diğeri 67 yaşında kadın olmak üzere iki (%0.24) hastada safra kesesi karsinomu saptandı. Erkek ve kadın cinsiyete göre safra kesesi karsinomu oranı sırasıyla %0.4 ve %.0.1 idi. Safra kesesinde metaplazi 16 (%1.96) hastada saptandı. Hastaların 15 tanesi kadın, bir tanesi erkekti. Bu hastaların yaş ortalaması 43.6 yıl idi. Sadece 48 yaşında bir erkek hastada displazi saptandı (%0.12).Sonuç: Safra taşı varlığının neden olduğu kronik irritasyon, prekanseröz bir lezyon olan metaplaziye yol açmaktadır. Bu nedenle safra taşı olan hastaların semptomları olmasa dahi ameliyat için değerlendirilmesinin ya da yakın takibinin uygun olacağını düşünmekteyiz.

This paper is to conduct a strategic analysis of the information system to improve the immunity system of gallbladder cancer patients. The subjects of the study were 146 people who visited internal medicine clinics located in Chungcheong Province from March 11 to May 13, 2019. The group of people who mediated the information system was classified as 53 people and those who did not mediated the information system were classified as 53 people. The change in patient condition was analyzed as t-test following the application of the information system. The application of the body’s immune system to the information system was measured at 4, 8, 12, 16, 20 and 24 weeks. The results of this study are as follows. First, LDL, a bad cholesterol decreased significantly after the information system was applied(t=3.72, p

SummaryBackground Combination therapy of gemcitabine with cisplatin (GC) is a standard first-line therapy for unresectable or recurrent biliary tract cancer (BTC). S-1 is often used as a second-line therapy in clinical practice, based on the results of some clinical studies investigating its efficacy and safety following gemcitabine monotherapy. However, few studies have reported on the clinical outcomes of S-1 following GC. The purpose of this study was to elucidate the efficacy and safety of S-1 following GC for unresectable and recurrent BTC. Methods We retrospectively collected the data of 116 patients (pts) who were treated with S-1 as a second-line therapy following GC for unresectable or recurrent BTC at Shizuoka Cancer Center (November 2009 to July 2019). Results Of these 116 pts., 84 were assessable. Patient characteristics were as follows: intrahepatic bile duct/extrahepatic bile duct/gallbladder cancer, 30/23/31 pts.; metastatic/recurrent/locally advanced, 57/17/10 pts. The median time to treatment failure and overall survival were 2.5 and 6.0 months, respectively. Among 65 pts. with measurable lesions, the overall response rate was 3.1% (2/65 pts) and the disease control rate was 24.6% (19/65 pts). The common grade 3/4 toxicities included anemia (12%), neutropenia (4%), infections (16%), fatigue (6%), and diarrhea (4%). Dose reduction or treatment schedule modification of S-1 was required in 29 pts. (34.5%), and 17 pts. (20%) terminated S-1 due to adverse events. Conclusions The efficacy and safety of S-1 following GC were almost the same as those of S-1 following GEM monotherapy for unresectable or recurrent BTC.

Background Biliary tract cancers (BTCs) are heterogeneous cancers that include cancers of the bile duct and gallbladder. Although they are relatively uncommon, most patients with BTC are diagnosed at advanced-stage disease with high mortality rates. Recently, systemic therapy options for patients with BTC have evolved. This paper reviews recent advancements in systemic therapy and the results of key clinical trials in BTC. Methods A literature search in PubMed and Google Scholar was performed using keywords related to BTC and systemic therapy. Studies that were presented in major international cancer research conferences were also included. Results The evidence shows that adjuvant capecitabine has been associated with a lower relapse rate in early-stage BTC. In unselected patients with advanced BTC, combination chemotherapy is a standard treatment option. However, with a better understanding of the molecular profile of BTC, there has been a shift toward targeted agents in BTC that have shown promising responses. The evolving data also support the evolving role of immunotherapy in patients with deficient DNA mismatch repair or PD-L1-positive BTC. Discussion Systemic treatment options for BTC have improved. The future identification of new targets, novel compounds, and predictive markers is a key step toward the use of personalized medicine in BTC.

Background Metachronous pancreatic and gallbladder cancer is a rare condition and has a dismal prognosis. Herein, we present a patient with triple metachronous primary pancreatic and gallbladder cancer associated with pancreaticobiliary maljunction who achieved long-term survival after undergoing repeat curative surgery. Case presentation A 65-year-old female patient with advanced gallbladder cancer associated with pancreaticobiliary maljunction underwent extended cholecystectomy with extrahepatic bile duct resection. The pathological diagnosis was T3N0M0 stage III A papillary adenocarcinoma with hepatic invasion. During a monthly follow-up, a diffuse hypovascular 2.0 × 1.5-cm mass was detected in the pancreatic head 6.2 years after the initial surgery. Hence, the patient underwent pancreaticoduodenectomy. Histological examination revealed T3N0M0 stage IIA well-differentiated adenocarcinoma without lymph node metastases. Marked inflammatory reaction was observed in the non-cancerous lesions of the proximal pancreatic head parenchyma containing bile pigment within ductular lumens. After 12.5 years from the initial surgery, total pancreatectomy for a 4.0 × 3.0-cm mass in the remnant pancreas was performed. Histological examination revealed T3N1M0 stage IIB moderately differentiated adenocarcinoma with lymph node metastases. Hence, surgical curative resection was achieved. Based on the pathological findings, a definitive diagnosis of triple metachronous pancreatic and gallbladder cancer was made. The pathology suggests no precursor lesions such as pancreatic intraepithelial neoplasia (PanIN) and atypical flat lesions, but marked inflammations in the non-cancerous lesions, strengthening our hypothesis that chronic inflammation induced by the pancreaticobiliary maljunction is related to carcinogenesis of the pancreas. Despite further adjuvant chemotherapy, the patient’s general condition worsened; however, she remained alive 15.2 years after the initial surgery while receiving the best supportive care. Conclusions Repeat curative surgery for triple metachronous cancer was associated with a favorable prognosis. Both the biliary tract and the pancreas should be closely monitored during follow-up among patients with pancreaticobiliary maljunction, which can be managed with curative surgery.

We report a 48-year-old fit and healthy woman who was incidentally diagnosed to have adenocarcinoma of gallbladder after laparoscopic cholecystectomy. Subsequent imaging showed no evidence of regional or distant spread. She was scheduled for elective laparotomy and resection of gallbladder bed, but during laparotomy frozen section analysis of an incidentally discovered peritoneal deposit confirmed metastasis, so the procedure was abandoned. Thereafter, she received cisplatin and gemcitabine chemotherapy. However, surveillance computed tomography incidentally noted a urinary bladder mass which had not been present before. Transurethral resection of the bladder lesion revealed moderately differentiated adenocarcinoma of urinary bladder. The appearance and immunoprofile of the lesion confirmed metastasis from the primary gallbladder cancer, which has not been documented in the literature to the best of our knowledge. Her disease progressed and she is being challenged with gemcitabine and carboplatin as second-line palliative chemotherapy. She is still alive two years after the initial diagnosis.

Gallbladder cancer is a highly aggressive malignancy with an extremely poor prognosis. Germline BRCA1 mutation in gallbladder cancer is very rare. Herein, we present a case of a 73-year-old Asian patient diagnosed with lymph nodes and peritoneal metastases just two months after surgery for primary gallbladder cancer. The patient had a past history of early-stage breast cancer and received a left radical mastectomy 27 years ago. Next-generation sequencing (NGS) was performed as the patient refused to receive systemic chemotherapy. According to NGS result of germline BRCA1 mutation, the patient was administered first-line Olaparib and obtained a progression-free survival of about 6 months. Furthermore, we briefly summarized the current targeted treatment of gallbladder cancer. To the best of our knowledge, this is the first report of germline BRCA1 p. S451Lfs*20 mutation and first-line Olaparib treatment in a metastatic gallbladder cancer patient. As a highly heterogeneous and aggressive malignancy, we suggest making clinical decisions according to a precision medicine concept based on gene sequencing in advanced gallbladder cancer.