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Background There are limited conventional chemotherapy options for biliary tract cancers (BTCs), a heterogenous group of lethal, rare malignancies. The receptor tyrosine kinase (RTK) is closely associated with the progression of human malignancies through the regulation of cell cycle. Overexpression or amplification of RTKs has been investigated as a potential biomarker and therapeutic target in BTC; herein, we investigate the value of such interventions. Materials and Methods Overexpression of RTK proteins was examined by immunohistochemistry in 193 BTC samples, of which 137 were gallbladder carcinoma, 29 were perihilar cholangiocarcinoma, and 27 were intrahepatic cholangiocarcinoma. Silver in situ hybridization of MET and HER2 was performed to assess gene amplification. Results In the entire cancer group, gallbladder, perihilar, and intrahepatic, MET amplification rates were 15.7%, 19.0%, 3.4%, and 14.8%, respectively, and of HER2 amplification rates were 22.4%, 27.2%, 17.2%, and 3.7%, respectively. MET and HER2 protein expressions were significantly correlated with their gene amplification status. RTKs were significantly associated with adverse clinicopathologic features such as advanced pT category and lymph node metastasis. Overall survival was significantly shorter in MET- amplified (P  = .024) and EGFR-overexpressed cases (P  = .045). Recurrence-free survival was significantly correlated with HER2 -amplified (P  = .038) and EGFR-overexpressed cases (P  = .046) in all patient groups. Overall and recurrence-free survival were significantly shorter in patients who were double positive for HER2 and EGFR. Conclusion Our data suggested that MET, HER2, and EGFR might be potential therapeutic targets and that their co-expression is a strong prognostic factor for BTCs. [ABSTRACT FROM AUTHOR]

Background Treatment outcomes of incidental gallbladder cancer generally stem from tertiary referral centres, while many patients are initially diagnosed and managed in secondary care centres. Referral patterns of patients with incidental gallbladder cancer are poorly reported. This study aimed to evaluate incidental gallbladder cancer treatment in secondary centres, rates of referral to tertiary centres and its impact on survival. Methods Medical records of patients with incidental gallbladder cancer diagnosed between 2000 and 2019 in 27 Dutch secondary centres were retrospectively reviewed. Patient characteristics, surgical treatment, tumour characteristics, referral pattern and survival were assessed. Predictors for overall survival were determined using multivariable Cox regression. Results In total, 382 patients with incidental gallbladder cancer were included. Of 243 patients eligible for re-resection (pT1b–pT3, M0), 131 (53.9%) were referred to a tertiary centre. The reason not to refer, despite indication for re-resection, was not documented for 52 of 112 non-referred patients (46.4%). In total, 98 patients underwent additional surgery with curative intent (40.3%), 12 of these in the secondary centre. Median overall survival was 33 months (95% c.i. 24 to 42 months) in referred patients versus 17 months (95% c.i. 3 to 31 months) in the non-referred group (P = 0.019). Referral to a tertiary centre was independently associated with improved survival after correction for age, ASA classification, tumour stage and resection margin (HR 0.60, 95% c.i. 0.38 to 0.97; P = 0.037). Conclusion Poor incidental gallbladder cancer referral rates were associated with worse survival. Age, performance status, resection margin or tumour stage should not preclude referral of a patient with incidental gallbladder cancer to a tertiary centre. [ABSTRACT FROM AUTHOR]

This case shows the need for in-depth knowledge also on congenital biliary anomalies that can become subject to iatrogenic damage. The patient is 44-years old with echographically proven cholelithiasis with complaints of intermittent pain in the right upper quadrant. During laparoscopic cholecystectomy, after identification of cystic duct and cystic artery, after their clipping and resection and subsequent mobilization of the gallbladder from the liver parenchyma, a bile duct was opened. Subsequent identification revealed a cystohepatic duct, which is a rare anatomic anomaly. Plastic surgery was performed on the tangential lesion of the right hepatic duct and placement of a transcistic drain, as well as a drain from the right hepatic duct through the Fateri papilla. Postoperative transdrainage cholangiography established the integrity of the bile ducts and the free passage of contrast to the duodenum. Intraoperative identification of only two structures entering the gallbladder during cholecystectomy—cystic duct and cystic artery—is mandatory. [ABSTRACT FROM AUTHOR]

Neuroendocrine carcinomas (NECs) of the gallbladder are very rare and aggressive tumors with poor prognosis. Most of them are poorly differentiated and belong to the small cell type. We report a case of a 59-year-old woman who presented with abdominal pain and distension. Contrast-enhanced computed tomography revealed a large heterogeneous mass in the liver, adjacent to the gallbladder, and omental nodules. CA 19-9 level was elevated and ascitic fluid cytology was suspicious for malignancy. Percutaneous biopsy of the liver mass confirmed the diagnosis of small cell NEC of the gallbladder. The patient was considered inoperable and planned for chemotherapy, but she died 20 days after admission. This case illustrates the diagnostic challenges and the dismal outcome of small cell NEC of the gallbladder. Early detection and multimodal treatment are essential for improving the survival of these patients. [ABSTRACT FROM AUTHOR]

Since the early 1990's, laparoscopic cholecystectomy has become the gold standard for the treatment of symptomatic gallbladder disease. Although the incidence of postoperative complications is generally lower with this approach, gallbladder perforation represents a serious risk that is among the most common complications of laparoscopic cholecystectomy. The sequalae that can follow iatrogenic perforation have not been well documented and only a few case reports exist in the current literature. In this paper we discuss two case reports of delayed perihepatic abscesses following prior laparoscopic cholecystectomy, ultimately resulting in fistulous tracts. The course of the disease is discussed along with the diagnostic workup and eventual successful management of the aforementioned complications. Treating enteric fistulae requires a systematic approach and is carried out in phases. Enteric fistula formation following laparoscopic cholecystectomy is a rare complication of retained gallstones that can present months to years following the index operation. Significant care should be taken to avoid perforation and all efforts should be made to retrieve stones if spillage occurs. [ABSTRACT FROM AUTHOR]

A 53-year-old male patient with a previous diagnosis of dilatation of the common bile duct was admitted to the hospital due to recurrent episodes of vague epigastric pain over a 4-month period. After undergoing abdominal CT, MRI, MRCP, ERCP examinations, together with joint diagnosis by the radiology department and the gastroscopy unit, the diagnosis of a cystic dilatation of the common bile duct was excluded, and to preliminarily diagnose as cystic lesion at the hepatoduodenum ligament. A nasobiliary tube was preset before the surgery, and it was found that the gallbladder, the cyst, and the common bile duct were connected in sequence during the surgery, leading to the definitive diagnosis of biliary cyst of the cystic duct. During the surgery, the anatomical position of the common bile duct was accurately identified, avoiding iatrogenic biliary injury and preserving the integrity of the common bile duct structure. The patient recovered and was discharged from the hospital on the 14th postoperative day. Cystic duct cysts are a relatively new and rare condition. This case demonstrates that clinical decision-making by a multidisciplinary team is of great significance for such diseases, and preoperative assessment of the anatomical relationship between cystic dilation lesions in the hepatic portal region and the biliary system and gallbladder is also crucial. [ABSTRACT FROM AUTHOR]

The aberrant migration of Ascaris lumbricoides may cause extra-intestinal ascariasis (EIA) involving hepato-biliary-pancreatic (HBP) or other extra-gastro-intestinal (EGI) organs. We performed a systematic review and meta-analysis to study the risk factors and clinical presentations of EIA, and differences in HBP and EGI ascariasis. Medline, Web of Science and Embase were searched for cases of EIA in the English language from India. From 1204 articles, 86 studies (105 cases) were included. The majority of the cases involved the HBP system (78%). Among HBP ascariasis, the most commonly involved site was the bile duct (53.6%). Females had 11.3 times higher odds (95% CI 2.852 to 44.856; p=0.001) of HBP ascariasis, while the pediatric population had lower odds (OR=0.323). Previous gallbladder disease was significantly associated with HBP ascariasis in adults (p=0.046), while a significantly higher number of cases of EGI ascariasis were observed among pediatric patients (p=0.003). Ocular symptoms occurred exclusively in the pediatric population (p=0.017). Overall, death was reported in 3.8% of patients (n=4). This review emphasizes the importance of the complications of EIA. It encourages future research into issues such as the reasons of higher gall bladder ascariasis in females and the implications of Ascaris -related complications following biliary tract interventions. It also suggests considering Ascaris as a differential diagnosis for airway obstuction in intubated critically ill patients. [ABSTRACT FROM AUTHOR]

A 101-year-old woman presented with a lesion on her abdomen, which was found to be a cholecystocutaneous fistula connecting the gallbladder to the skin. This rare condition is typically associated with untreated gallstone disease and can present as painless discharging lesions. While surgical management is common, this patient was treated conservatively with antibiotics. The article provides valuable insights into the cause and presentation of cholecystocutaneous fistulas, highlighting the importance of early diagnosis and appropriate management. [Extracted from the article]

Giant gallbladder (GGB) is a rare condition and its pathogenesis could not be explained clearly. It can result from cholelithiasis, chronic cholecystitis or neoplasm, but more rarely if created congenitally. Adequate vasculatization should support the development of this entity. A 47-year-old lady presented with a dull pain and right upper quadrant abdominal mass. A computed tomography scan showed 27 × 25 × 12 cms cystic mass expanding to the right illiac fossae, surrounded by a homogenous capsule. There were neither stones nor mass in the biliary tract and total cholecystectomy was done. Patient recovered well without signs of cholestasis 5 years postoperatively. A few cases of giant benign gall bladder have been reported in literature; however, no study has tried to investigate the mechanism of its etiology. To support the enlargement of the tissue or organ there must be some growth factors along with adequate vascularization. Vascular endothelial growth factor (VEGF) serum level and VEGF messenger ribonucleic acid (mRNA) gene expression were increased in this case. This GGB case suggests a congenital factor as its etiology. Cholecystectomy may relieve uncomfortable symptoms with good results. The incidence of GGB accompanied by increased serum VEGF levels and mRNA gene expression supports the hypothesis that VEGF plays a major role in supporting the vasculogenesis of GGBs. [ABSTRACT FROM AUTHOR]

We report a case of intracystic papillary neoplasms (ICPN) that was difficult to differentiate from adenocarcinoma of the gallbladder. A 64-year-old man visited our hospital for an examination of gallbladder tumors. At the preoperative examination, the tumor was revealed a papillary type of tumor in the body of the gallbladder without the findings that without the findings that suggested the tumor invasion into the deep subserosal layer. The patient underwent an extended cholecystectomy. Papillary lesions were observed mainly in the body of the gallbladder, with flattened elevated lesions at the gallbladder fundus. Within each of these tumors, cells corresponding to intraepithelial adenocarcinoma were irregularly interspersed, leading to a diagnosis of ICPN. The patient is currently undergoing follow-up with no recurrence postoperatively. The prognosis of ICPN is generally good; however, preoperative diagnosis remains challenging. Therefore, a treatment plan for gallbladder cancer should be applied. [ABSTRACT FROM AUTHOR]

Background: Studies of obesity with or without metabolic aberrations, commonly termed metabolically unhealthy or healthy obesity, in relation to cancer risk are scarce. Methods: We investigated body mass index (normal weight, overweight, obesity) jointly and in interaction with metabolic health status in relation to obesity-related cancer risk (n = 23 630) among 797 193 European individuals. A metabolic score comprising mid-blood pressure, plasma glucose, and triglycerides was used to define metabolically healthy and unhealthy status. Hazard ratios (HRs) and multiplicative interactions were assessed using Cox regression, and additive interactions were assessed using the relative excess risk for interaction. All statistical tests were 2-sided. Results: Metabolically unhealthy obesity, with a baseline prevalence of 7%, was, compared with metabolically healthy normal weight, associated with an increased relative risk of any obesity-related cancer and of colon, rectal, pancreas, endometrial, liver, gallbladder, and renal cell cancer (P < .05), with the highest risk estimates for endometrial, liver, and renal cell cancer (HR = 2.55-3.00). Metabolically healthy obesity showed a higher relative risk for any obesity-related cancer and colon (in men), endometrial, renal cell, liver, and gallbladder cancer, though the risk relationships were weaker. There were no multiplicative interactions, but there were additive, positive interactions between body mass index and metabolic health status on obesity-related and rectal cancer among men and on endometrial cancer (P < .05). Conclusions: This study highlights that the type of metabolic obesity phenotype is important when assessing obesity-related cancer risk. In general, metabolic aberrations further increased the obesity-induced cancer risk, suggesting that obesity and metabolic aberrations are useful targets for prevention. [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is the sixth most common cancer diagnosed at a late stage, causing significant loss of human lives. It is imperative to identify suitable biomarkers to diagnose it at an early stage as well as recognize important therapeutic targets to effectively treat the patients in the advanced stage of the disease. Multi-omics is a novel approach conceptualized to identify changes in every molecule produced in the cells/tissues at the genome, epigenome, transcriptome, proteome and metabolome level. The initiation and progression of tumors result from changes in the genes (mutation, epigenetic), evident at transcription, translation and metabolite levels. Identifying these changes can enhance the early diagnosis and therapeutic targeting of advanced tumors. The huge accrual of the multi-omics public data and its continuous enrichment are a valuable source to advance this research area by analyzing them diligently. The multi-omics approach has been applied to sub-categorize the tumors with the primary objective of clinical annotation, which includes tumor histology, response to therapies and the identification of predictive biomarkers to understand the response of targeted treatment. Herein, we have summarized the literature on the multi-omics data used to identify the suitable therapeutic targets for GBC patients. [ABSTRACT FROM AUTHOR]

One week after an elective laparoscopic cholecystectomy at an outside hospital, a 56-year-old male presented to the emergency department with right-sided abdominal pain. Computerized tomography (CT) revealed a complex fluid collection in the gallbladder fossa. The patient underwent drain placement and received broad-spectrum intravenous antibiotics. Drain output was suspicious for a chyle leak, which was confirmed by elevated fluid triglyceride levels. Magnetic resonance cholangiopancreatography (MRCP) and hepatobiliary iminodiacetic acid (HIDA) analysis showed evidence of a concurrent bile leak. After starting a low fat, high protein diet and octreotide, a common bile duct sphincterotomy with plastic stent placement was performed. The patient's symptoms and drain output proceeded to improve. The cause of the chyle leak is unclear. However, with consideration of the patient's concurrent bile leak, an injury to the right major lymphatic drainage pathway and adjacent bile duct is suspected. [ABSTRACT FROM AUTHOR]

Pancreaticobiliary maljunction (PBM) is a congenital malformation. The reflux of pancreatic juice into the biliary tract caused by PBM plays a significant role in the development of biliary tract cancers (BTCs), such as gallbladder cancer and cholangiocarcinoma. Previous studies have demonstrated a high incidence of BTC in patients with PBM. However, there are only a few reports of patients who developed BTC after a diagnosis of PBM. We report the cases of two patients who developed gallbladder cancer after being diagnosed with PBM. They had refused treatment and were being managed with follow-up observation alone after the diagnosis of PBM and developed gallbladder cancer after several years of observation. Thus, surgical treatment should be recommended for all patients with PBM in order to prevent the development of BTC. Moreover, long-term, close, regular follow-up is necessary to facilitate the early diagnosis of subsequent BTC in patients with untreated PBM. [ABSTRACT FROM AUTHOR]

Pancreatic heterotopia is characterized by ectopic pancreatic tissue found outside the pancreas without any anatomical or vascular connection to the pancreas. Pancreatic heterotopia of the gallbladder is a rare histological finding; there have been only a handful of cases described in the literature. Pancreatic heterotopia of the gallbladder is usually diagnosed incidentally at histological examination following cholecystectomy or autopsy. Clinical presentation of pancreatic heterotopia of the gallbladder can vary from biliary colic, biliary obstruction or it can be completely asymptomatic. It has been suggested that gallbladder pancreatic heterotopia may lead to pancreatitis of this ectopic tissue, which may present differently to typical biliary colic. Here, we present the case of a 43-year-old male that presented with 2 years of significant postprandial nausea and right upper quadrant pain. Histopathology following cholecystectomy revealed chronic cholecystitis with cholelithiasis, in addition to a focus of pancreatic heterotopia in the gallbladder wall. [ABSTRACT FROM AUTHOR]

Gallbladder agenesis (GA) is a rare congenital anomaly with conflicting epidemiology described in the literature. When present, it is misinterpreted as cholelitiasis, a highly prevalent condition. Nevertheless, surgeons and radiologists must be aware of it since it can lead to unnecessary invasive procedures. Diagnosis of GA is challenging due to the anatomical structures that sometimes resemble a shrunken gallbladder. We report the case of a 55-year-old man with preoperative diagnosis of cholelitiasis and further intraoperative find of GA. Since cholecystectomy is one of the most common surgeries worldwide, it demonstrates how relevant this case is to emphasize the need to recognize this diagnosis and be aware of its management to avoid unnecessary surgery. [ABSTRACT FROM AUTHOR]

Introduction Robotic cholecystectomy (RC) is a recent innovation in minimally invasive gallbladder surgery. The IDEAL (idea, development, exploration, assessment, long-term study) framework aims to provide a safe method for evaluating innovative procedures. This study aimed to understand how RC was introduced, in accordance with IDEAL guidelines. Methods Systematic searches were used to identify studies reporting RC. Eligible studies were classified according to IDEAL stage and data were collected on general study characteristics, patient selection, governance procedures, surgeon/centre expertise, and outcome reporting. Results Of 1425 abstracts screened, 90 studies were included (5 case reports, 38 case series, 44 non-randomized comparative studies, and 3 randomized clinical trials). Sixty-four were single-centre and 15 were prospective. No authors described their work in the context of IDEAL. One study was classified as IDEAL stage 1, 43 as IDEAL 2a, 43 as IDEAL 2b, and three as IDEAL 3. Sixty-four and 51 provided inclusion and exclusion criteria respectively. Ethical approval was reported in 51 and conflicts of interest in 34. Only 21 reported provision of training for surgeons in RC. A total of 864 outcomes were reported; 198 were used in only one study. Only 30 reported a follow-up interval which, in 13, was 1 month or less. Conclusion The IDEAL framework was not followed during the adoption of RC. Few studies were conducted within a research setting, many were retrospective, and outcomes were heterogeneous. There is a need to implement appropriate tools to facilitate the incremental evaluation and reporting of surgical innovation. [ABSTRACT FROM AUTHOR]

Background: There is a lack of consensus in selecting patients who do or do not benefit from surgery when patients present with abdominal pain and gallbladder stones are present. This review aimed to give an overview of results from recent trials and available literature to improve treatment decisions in patients with uncomplicated cholecystolithiasis. Methods: First, an overview of different symptom criteria for laparoscopic cholecystectomy in patients with uncomplicated cholecystolithiasis is given, based on national and international guidelines. Second, treatment outcomes (absence of biliary colic, pain-free state, biliary and surgical complications) are summarized, with data from three clinical trials. Finally, personal advice for treatment decisions in patients with uncomplicated cholecystolithiasis is provided, based on recent trials, the available literature, and expert opinion. Results: This review describes different guidelines and criteria sets for uncomplicated cholecystolithiasis, provides an overview of outcomes after cholecystectomy, and advises on treatment decisions in patients with abdominal pain and gallbladder stones. After cholecystectomy, biliary colic is resolved in 95 per cent of patients. However, non-specific abdominal pain persists in 40 per cent. Irritable bowel syndrome and functional dyspepsia significantly increase the risk of persistent pain. Age, previous abdominal surgery, baseline pain score on a visual analogue scale, pain characteristics, nausea, and heartburn are part of the SUCCESS criteria, and are associated with clinically relevant pain reduction after gallbladder removal. Conclusion: The surgical community can now give more personalized advice on surgery to improve care for patients with abdominal pain and uncomplicated cholecystolithiasis. [ABSTRACT FROM AUTHOR]

Background: Post-hepatectomy liver failure (PHLF) is one of the most serious postoperative complications after hepatectomy. The aim of this study was to assess the impact of the International Study Group of Liver Surgery (ISGLS) definition of PHLF on morbidity and short- and long-term survival after major hepatectomy. Methods: This was a retrospective review of all patients who underwent major hepatectomy (three or more liver segments) for various liver tumours between 2010 and 2018 at two Swedish tertiary centres for hepatopancreatobiliary surgery. Descriptive statistics, regression models, and survival analyses were used. Results: A total of 799 patients underwent major hepatectomy, of which 218 patients (27 per cent) developed ISGLS-defined PHLF, including 115 patients (14 per cent) with ISGLS grade A, 76 patients (10 per cent) with grade B, and 27 patients (3 per cent) with grade C. The presence of cirrhosis, perihilar cholangiocarcinoma, and gallbladder cancer, right-sided hemihepatectomy and trisectionectomy all significantly increased the risk of clinically relevant PHLF (grades B and C). Clinically relevant PHLF increased the risk of 90-day mortality and was associated with impaired long-term survival. ISGLS grade A had more major postoperative complications compared with no PHLF but failed to be an independent predictor of both 90-day mortality and long-term survival. The impact of PHLF grade B/C on long-term survival was no longer present in patients surviving the first 90 days after surgery. Conclusions: The presently used ISGLS definition for PHLF should be reconsidered regarding mortality as only PHLF grade B/C was associated with a negative impact on short-term survival; however, even ISGLS grade A had clinical implications. [ABSTRACT FROM AUTHOR]

Post-cholecystectomy syndrome (PCS) is a well-documented complication of incomplete cholecystectomy. The etiology is often post-surgical chronic inflammation from unresolved cholelithiasis, which is secondary to anatomical abnormalities, including a retained gallbladder or a large cystic duct remnant (CDR). An exceedingly rare consequence is retained gallstone fistulization into the gastrointestinal tract. We present a case of a 70-year-old female with multiple comorbidities 4 years status-post incomplete cholecystectomy, who developed PCS with cholecystoduodenal fistula secondary to retained gallstone in the remnant gallbladder, with CDR involvement, treated via robotic-assisted surgery. Reoperation in PCS has been traditionally performed via laparoscopic approach with recent advances made in robotic-assisted surgery. However, we report the first documented case of PCS complicated by bilioenteric fistula repaired with robotic-assisted surgery. This highlights the value of robotic-assisted surgery in complicated cases, where one must contend with post-surgical anatomic abnormalities and visualization difficulties. Subsequent investigation is necessary to objectively quantify the safety and reproducibility of our approach. [ABSTRACT FROM AUTHOR]

Mixed neuroendocrine-non-neuroendocrine neoplasms of the gallbladder are rare with a lack of established standardized therapeutic strategies. We report a case of gallbladder mixed neuroendocrine-non-neuroendocrine neoplasm with liver metastasis of neuroendocrine carcinoma. A patient who underwent radical cholecystectomy for gallbladder adenocarcinoma was detected with increasing liver mass, and hepatectomy was performed. Pathological report revealed neuroendocrine carcinoma. To find primary origin, pathological review of the old specimen from previous cholecystectomy with a slightly different perspective was conducted, where the neuroendocrine component was positively dyed. In conclusion, though it might be impossible to review every pathological result in cases with ambiguous findings, reviewing the previous specimen can be a useful option in diagnosis. [ABSTRACT FROM AUTHOR]

This is a corrigendum to: Mike van Dooren, Elise A J de Savornin Lohman, Rachel S van der Post, Joris I Erdmann, Frederik J H Hoogwater, Bas Groot Koerkamp, Peter B van den Boezem, Philip R de Reuver, Referral rate of patients with incidental gallbladder cancer and survival: outcomes of a multicentre retrospective study, BJS Open, Volume 8, Issue 2, April 2024, zrae013, https://doi.org/10.1093/bjsopen/zrae013In the originally published version of this article, Figure 1 was erroneous.The article has been updated with the correct version of the figure. [Extracted from the article]

Ductal biliary recurrence of cancers arising in other anatomical districts is a rare event, usually observed in the setting of disseminated disease; hence surgery is rarely a viable option. We present the case of a 56-year-old male who underwent subtotal gastric resection 7 years earlier for a poorly cohesive gastric cancer, presenting with obstructive jaundice. Magnetic resonance imaging and computed tomography scan suggested primary malignant obstruction of the main bile duct. Percutaneous transhepatic biliary drainage was performed to palliate jaundice and obtain biopsies; pathological examination suggested a ductal biliary recurrence of gastric carcinoma. Pancreaticoduodenectomy and bile duct resection were performed. Histology, immunohistochemistry and molecular profiling confirmed that the stenosis represented a gastric cancer metastasis. This is the first case of an isolated ductal biliary recurrence of gastric cancer amenable to surgical resection. This clinical case suggests that biliary obstructions in patients with previous oncological history require biliary biopsies to exclude a recurrent disease. [ABSTRACT FROM AUTHOR]

Background: There is ongoing debate concerning the necessity of routine histopathological examination following cholecystectomy. In order to reduce the pathology workload and save costs, a selective approach has been suggested, but evidence regarding its oncological safety is lacking. Methods: In this multicentre, prospective, cross-sectional study, all gallbladders removed for gallstone disease or cholecystitis were systematically examined by the surgeon for macroscopic abnormalities indicative of malignancy. Before sending all specimens to the pathologist, the surgeon judged whether histopathological examination was indicated. The main outcomes were the number of patients with hypothetically missed malignancy with clinical consequences (upper limit two-sided 95 per cent c.i. below 3:1000 considered oncologically safe) and potential cost savings of selective histopathological examination. Results: Twenty-two (2.19:1000) of 10 041 specimens exhibited malignancy with clinical consequences. In case of a selective policy, surgeons would have held back 7846 of 10041 (78.1 per cent) gallbladders from histopathological examination. Malignancy with clinical consequences would have been missed in seven of 7846 patients (0.89:1000, upper limit 95% c.i. 1.40:1000). No patient benefitted from the clinical consequences, while two were harmed (futile additional surgery). Of 15 patients in whom malignancy with clinical consequences would have been diagnosed, one benefitted (residual disease radically removed), two potentially benefitted (palliative systemic therapy), and four experienced harm (futile additional surgery). Estimated cost savings established by replacing routine for selective histopathological examination were €703 500 per 10 000 patients. Conclusion: Selective histopathological examination following cholecystectomy is oncologically safe and could reduce pathology workload, costs, and futile re-resections. [ABSTRACT FROM AUTHOR]

Laparoscopic cholecystectomy is a common surgical procedure, with potential for significant morbidity. The incidence of bile duct injuries has increased with the advent of laparoscopy, occurring in up to 1% of cases. Risk of injury increases with aberrant anatomy, acute inflammation and fibrosis. Preventative strategies include obtaining the critical view of safety, using a fundus-first approach and performing a subtotal cholecystectomy in the difficult gallbladder. Although controversy exists for routine cholangiography, its use is helpful in situations of obscure anatomy. We describe the case of a chronically inflamed and unusually small 1.5 cm gallbladder with an obliterated cystic duct. The critical view of safety was not able to be achieved and intraoperative cholangiography enabled identification of aberrant anatomy, with a dilated common duct mistaken as the gallbladder infundibulum. This case highlights the need to be vigilant to structural variation and the utility of selective cholangiography to clarify anatomy. [ABSTRACT FROM AUTHOR]

Study Question: Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?Summary Answer: Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.What Is Known Already: Long and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.Study Design, Size, Duration: Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015.Participants/materials, Setting, Methods: We followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14-17, 18-22 and 29-46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.Main Results and the Role Of Chance: We documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29-46 years had an 11% (95% CI: 2-21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9-39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09-1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14-17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02-1.81).Limitations, Reasons For Caution: Our study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.Wider Implications Of the Findings: Women with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.Study Funding/competing Interest: This work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Background  Perioesophageal vagal nerve (VN) injury after atrial fibrillation (AF) ablation remains an important complication. The VN provides parasympathetic innervation to the majority of the abdominal organs—including the stomach and the sphincter of Oddi (SO)—and regulates smooth muscle contraction. We present an unusual case of SO spasm induced by VN injury after cryoballoon ablation (CBA). Case summary  A 71-year-old woman presented to our institution with paroxysmal AF. The patient had a history of cholecystectomy and SO dysfunction. She had undergone CBA for AF. Immediately after the procedure, the patient developed epigastric pain. Computed tomography showed dilation of the intra- and extrahepatic bile ducts, with the diameter of the common bile duct measuring ∼15.6 mm. Blood tests on postoperative Day 1 revealed severely elevated aminotransferase levels (aspartate aminotransferase, 3156 U/L; alanine aminotransferase, 2084 U/L; lactate dehydrogenase, 2279 U/L; total bilirubin 1.7 mg/dL). Discussion  It is known that VN denervation induces SO spasms. The right and left vagal trunks descend alongside the oesophagus, forming a perioesophageal plexus and innervating most of the gastrointestinal organs. In our case, SO spasm was induced as a result of the perioesophageal plexus injury caused by CBA. Underlying SO dysfunction and post-cholecystectomy also played an important role. Coupled with the absence of the gallbladder, which is the reservoir of bile juice and coordinator of SO, SO spasm caused severe elevation of the bile duct pressure. Care should be taken when performing AF ablation with regards to the stomach and the SO. [ABSTRACT FROM AUTHOR]

Synchronous malignancies of the bile duct and the gallbladder are rare. These cases are often associated with pancreaticobiliary maljunction which is characterized by a long common shared pancreatobiliary channel leading to the Sphincter of Oddi. This predisposes the biliary epithelium to pancreatic enzyme reflux and makes the development of neoplasia more likely. We describe the case of a 64-year-old Caucasian female who presented with new jaundice and severe cholecystitis secondary to an impacted gallstone which was seen on ultrasound. Magnetic resonance cholangiopancreatography was organized with suspicion of a possible Mirizzi syndrome. This revealed a mid-distal bile duct cancer in addition to cholecystitis from an impacted gallstone. She was treated with intravenous antibiotics for her cholecystitis and underwent an urgent endoscopic retrograde cholangiopancreatography procedure for biliary decompression and stenting for her obstructive jaundice. The patient proceeded to pancreaticoduodenectomy with final histopathology revealing a synchronous primary gallbladder malignancy in addition to the known bile duct cancer. [ABSTRACT FROM AUTHOR]

True left-sided gallbladder (LSGB) is a rare congenital anomaly with an incidence of 0.1–1.2%. It is more common in women than in men at a ratio of 5:1. Its etiology is unknown, although several theories have been proposed. The symptoms are similar to those of a normal gallbladder, which makes the preoperative diagnosis difficult despite imaging studies. In most cases, the diagnosis is achieved intraoperatively. LSGB is associated with biliary anomalies, and the incidence of biliary tract lesions is high. Four-port laparoscopic cholecystectomy is a safe procedure for LSGB. Surgical technique varies according to each case. Preoperative imaging studies have low sensitivity for diagnosis, and the surgeon should be familiar with ductal and vascular anatomical variants in addition to possessing the ability to change the conventional surgical technique to optimize the exposure and minimize the risk of bile duct injury. [ABSTRACT FROM AUTHOR]

Portal venous gas (PVG) generally suggests critically ill conditions such as severe bowel ischemia. We herein report a rare case of gallbladder torsion with PVG. An 88-year-old woman complained of right hypogastric pain. Ultrasonography (US) showed diffuse wall thickening of her gallbladder and mobile echogenic foci moving inside the portal venous branches. Computed tomography showed a thickened wall of the gallbladder with poor enhancement and tiny pockets of air in the portal venous branches (segments 4 and 5). There was no evidence of other visceral ischemia. She was diagnosed with necrotic cholecystitis and immediately underwent an emergency operation. We found a gangrenous gallbladder with 180° clockwise rotation along the longitudinal axis and performed cholecystectomy. We confirmed the disappearance of PVG with US after the operation. Her postoperative course was uneventful. Gallbladder diseases can produce PVG, and US might be a useful diagnostic modality to evaluate changes in PVG. [ABSTRACT FROM AUTHOR]

Endobiliary stents placed for benign and malignant indications can spontaneously dislocate from the biliary system and migrate to the distal gastrointestinal tract. Stent migration can result in gastrointestinal perforation, with the most common locations in the sigmoid and distal colon, and may require surgical intervention. We describe the case of a 60-year-old female presenting with an ascending colonic perforation secondary to a dislodged plastic biliary stent placed for palliation of her gallbladder carcinoma. The patient was managed with a combined laparoendoscopic approach by a multidisciplinary team—gastroenterology performed an endoscopic stent retrieval and colorectal surgery identified the location of the perforation laparoscopically and performed colonic serosal repairs. The patient had an uneventful postoperative course and was discharged on postoperative day 4. This case demonstrates a novel minimally invasive laparoendoscopic approach at a high-volume academic center for the treatment of ascending colonic perforation secondary to biliary stent migration. [ABSTRACT FROM AUTHOR]

Representing 90–95% of all malignant gallbladder neoplasms, adenocarcinoma is by far the most common subtype. Adenosquamous carcinoma is a rare subtype, accounting for only 1–5% of all gallbladder carcinomas. These tumors have been shown to have aggressive biologic behavior, commonly extending to adjacent structures. Some studies have shown that the squamous component often displayed a greater proliferative capacity than the adenocarcinomatous component (possibly even up to twice as fast). Complete surgical resection is currently the mainstay of treatment but the prognosis is often poor. In this paper, we present a case of a 69-year-old male with an AJCC Stage IV moderately differentiated adenosquamous carcinoma of the gallbladder treated with radical cholecystectomy including liver segments IVb, V, VI. [ABSTRACT FROM AUTHOR]

Predictive prognostic markers for immunotherapy are crucial and desperately required for clinical precise medicine. This retrospective study aimed to assess the efficacy of anti‐PD‐1 (programmed cell death protein 1) treatment and find the therapeutic prognostic biomarkers in advanced biliary tract cancer (BTC). A total of 60 patients of advanced BTC who received at least one dose of anti‐PD‐1 therapy between June 2016 and October 2019 were recruited and followed up till April 2020. Systemic immune‐inflammation index (SII) and neutrophils‐to‐lymphocytes ration (NLR) were obtained from the routine circulating hematologic analysis before treatment. Serum 45‐Plex Panel cytokines were detected using multiplexed bead immunoassays. Logistic regression nomogram was used to construct the algorithm model for prognosis prediction. Of the 60 patients, the overall benefit rate (OBR) was 38.3%, the median progression free survival (PFS), and overall survival (OS) were 4.0 mo (95% confidence interval [CI]: 2.28–5.72) and 13.0 mo (95% CI: 8.05–17.95), respectively. High levels of SII (≥720), NLR (≥4.3) and cytokine IFN‐inducible protein‐10 (IP‐10; ≥45 pg/ml) indicated worse OS. Those with high SII (≥720) and high IP‐10 (≥45 pg/ml) also had shorter PFS. The nomogram algorithm combining above three independent factors (SII, IP‐10, and macrophage inflammatory protein‐1β) had better efficacy in predicting OBR. Our study offers a simple, affordable, and noninvasive method to help physicians predict therapeutic response in BTC patients receiving anti‐PD‐1 antibody treatment. [ABSTRACT FROM AUTHOR]

A 53-year-old man with prior history of resection of liposarcoma in his leg presented with gallbladder mass. Computed tomography showed 4-cm tumor at gallbladder fundus with weak enhancement with IV contrast. Differential diagnoses included hemangioma and liposarcoma, and laparoscopic cholecystectomy was recommended. In the operating room, the tumor appeared without serosal and liver invasions and uncomplicated laparoscopic cholecystectomy was completed. Histopathological examination revealed the tumor as myxoid liposarcoma with round cells. Adjuvant chemotherapy was not given, and he was placed on imaging surveillance. At 16 months after the operation, he developed recurrence of liposarcoma in the left popliteal fossa. [ABSTRACT FROM AUTHOR]

Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) has been reported to play an essential role in the development and progression of various human cancers. However, its expression pattern and possible mechanism in human hepatocellular carcinoma (HCC) remain to be elucidated. In this study, we used western blot and immunohistochemical staining to detect protein expression. The effects of ANP32A on the proliferation, migration and invasion of HCC cells were examined using 5-ethynyl-20-deoxyuridine (EdU), colony formation, CCK-8, and transwell assays. RT-qPCR was performed to detect mRNA expression. The interaction between ANP32A and the high mobility group A1 (HMGA1) mRNA was assessed using RNA immunoprecipitation (RIP). The tumorigenicity of ANP32A was assessed by establishing a xenograft tumor model in Balb/c nude mice. We found that the ANP32A protein was expressed at high levels in patients with HCC, which was associated with a poor prognosis. Functional experiments revealed that the silencing of ANP32A inhibited the proliferation, migration, and invasion of HCC cells, whereas overexpression of ANP32A promoted these processes. Further investigations indicated that ANP32A bound the HMGA1 mRNA and maintained its stability to promote the expression of HMGA1, thereby increasing the expression and activation of STAT3. Finally, a xenograft tumor model of Balb/c nude mice confirmed the tumorigenicity of ANP32A. This study found that ANP32A is up-regulated in patients with HCC and may accelerate the proliferation, migration and invasion of HCC cells by modulating the HMGA1/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Gallbladder adenocarcinoma is a rare gastrointestinal malignancy and is associated with a poor prognosis. These malignancies are most often discovered incidentally in |$\sim$| 1% of all cholecystectomy procedures. We report an 80-year-old male patient with iron deficiency anemia, who underwent an unremarkable endoscopy and colonoscopy, and was subsequently found to have hemobilia discovered on capsule endoscopy. Magnetic resonance cholangiopancreatography revealed a space-occupying process involving the posterior wall of the gallbladder. The patient underwent an unremarkable laparoscopic cholecystectomy with final pathology revealing a well-differentiated, 8 cm intracystic papillary neoplasm with high-grade dysplasia involving the majority of the gallbladder, with focally invasive adenocarcinoma invading the muscular layer of the gallbladder wall. Postoperative staging work-up revealed no evidence of metastatic disease. Patient then underwent a radical resection of segments 4B/5 of the gallbladder fossa and lymph node resection of the porta hepatis. Final pathology revealed Stage I adenocarcinoma of the gallbladder (T1bNxM0). [ABSTRACT FROM AUTHOR]

Gallbladder cancer (GBC) is a highly fatal cancer that can be cured through cholecystectomy if identified early. The presence of gallstones is the primary risk factor for GBC, but few people with gallstones develop GBC. A key question is what drives the development of GBC among persons with gallstones. We initiated the Chile Biliary Longitudinal Study (Chile BiLS) to address this question. From 2016 to 2019, Chile BiLS enrolled 4,726 women aged 50–74 years with ultrasound-detected gallstones from southern-central Chile, accounting for an estimated 36% of eligible women with gallstones in the study area. The median age was 59 years; 25% of the women were Amerindian (Mapuche), 60% were obese, 25% had diabetes, and 6% had cardiovascular disease. Participants will be followed for gallbladder dysplasia or cancer for 6 years. As of April 30, 2020, over 91% of those eligible completed the year 2 follow-up visit. Data being collected include epidemiologic and sociodemographic information, anthropometric measurements, blood pressure, and tooth counts. Biosamples being taken include baseline plasma, buffy coat, red blood cells, serum, blood clot from serum, and PAXgene whole blood (PreAnalytiX GmbH, Hombrechtikon, Switzerland). Complete gallbladder sampling is conducted for most participants undergoing cholecystectomy. The Chile BiLS cohort study will increase our understanding of GBC etiology and could identify potential risk stratification and early detection strategies in high-risk areas. [ABSTRACT FROM AUTHOR]

We herein report a case in which a cystic artery arising from the middle hepatic artery (MHA) was encountered during cholecystectomy. A 42-year-old man visited the outpatient department complaining of chronic epigastric pain and a laparoscopic cholecystectomy was decided upon. During the preoperative evaluation, an interesting finding was observed on computed tomography. The patient had a cystic artery arising from the MHA. An MHA derived from the hilum of the proper hepatic artery runs along the medial border of the gallbladder and enters segment IV. In the operative field, the MHA that entered segment IV was observed. Dissecting downward along the MHA, a cystic artery was observed around the cystic duct. The cystic artery and duct were isolated and each was separately ligated and cut. Rare anatomical variations of the cystic artery, as in this case, can be a pitfall inducing complications during cholecystectomy. [ABSTRACT FROM AUTHOR]

Bilobed gallbladder (BG) is a rare congenital anomaly with just 24 cases documented in medical literature in the past 127 years. There are only three documented cases of BG's managed with laparoscopic cholecystectomy, and in all three cases the bilobed anomaly was discovered preoperatively. We present a case of symptomatic cholelithiasis in a BG that was discovered intraoperatively. Both the surgical techniques used to ensure complete and safe removal of all gallbladder components and the elements associated with the preoperative diagnosis of these rare anomalies are discussed. [ABSTRACT FROM AUTHOR]

Background: Routine histopathological examination after cholecystectomy is costly, but the prevalence of unsuspected gallbladder cancer (incidental GBC) is low. This study determined whether selective histopathological examination is safe. Methods: A comprehensive search of PubMed, Embase, Web of Science and the Cochrane Library was performed. Pooled incidences of incidental and truly incidental GBC (GBC detected during histopathological examination without preoperative or intraoperative suspicion) were estimated using a random‐effects model. The clinical consequences of truly incidental GBC were assessed. Results: Seventy‐three studies (232 155 patients) were included. In low‐incidence countries, the pooled incidence was 0·32 (95 per cent c.i. 0·25 to 0·42) per cent for incidental GBC and 0·18 (0·10 to 0·35) per cent for truly incidental GBC. Subgroup analysis of studies in which surgeons systematically examined the gallbladder revealed a pooled incidence of 0·04 (0·01 to 0·14) per cent. In high‐incidence countries, corresponding pooled incidences were 0·83 (0·58 to 1·18), 0·44 (0·21 to 0·91) and 0·08 (0·02 to 0·39) per cent respectively. Clinical consequences were reported for 176 (39·3 per cent) of 448 patients with truly incidental GBC. Thirty‐three patients (18·8 per cent) underwent secondary surgery. Subgroup analysis showed that at least half of GBC not detected during the surgeon's systematic examination of the gallbladder was early stage (T1a status or below) and of no clinical consequence. Conclusion: Selective histopathological examination of the gallbladder after initial macroscopic assessment by the surgeon seems safe and could reduce costs. [ABSTRACT FROM AUTHOR]

Background: HER2 overexpression has been investigated as a potential biomarker and therapeutic target in biliary tract cancer (BTC), but a prognostic role of such alteration has not been demonstrated yet. Materials and Methods: We retrospectively evaluated HER2 protein expression by immunohistochemistry (IHC) in 100 patients with radically resected BTC. HER2 gene amplification was assessed by fluorescence in situ hybridization (FISH) in 2+ and 3+ cases at IHC. High HER2 protein expression was defined as either IHC 3+ or 2+ associated with FISH positivity. The primary objective of the study was to evaluate the prognostic role of HER2 overexpression in terms of disease‐free survival (DFS) and overall survival (OS). Secondary endpoints were the prevalence of HER2 overexpression and the possible correlation with other clinicopathological features. Results: HER2 overexpression was identified in 11 patients and was not related to other clinicopathological factors. DFS was significantly shorter in HER2‐positive compared with HER2‐negative patients (10.6 vs. 20.9 months, log‐rank p =.017). HER2 confirmed its prognostic value for DFS at multivariate analysis (hazard ratio 2.512; 95% confidence interval, 1.232–5.125; p =.011) together with nodal stage (p <.001), resection margin (p =.027), and tumor site (p =.030). There was no difference in OS between HER2‐positive and ‐negative patients (p =.068). Conclusion: HER2 overexpression represents an independent prognostic factor for disease recurrence in patients with BTC treated with potentially curative surgery. Implications for Practice: HER2 overexpression may play an independent role in promoting an aggressive behavior in resectable biliary tract cancer. This evidence could be helpful in improving prognostic stratification after resection and, primarily, should endorse the rationale to investigate HER2 as a therapeutic target in biliary tract cancer. Studies suggest that the HER2 pathway could play a role in the development and growth of biliary tract cancer. This study investigated the incidence and effect of HER2 expression on the risk of recurrence in a large series of resected biliary tract cancer cases at a single Institution. [ABSTRACT FROM AUTHOR]

Background: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. Methods: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. Results: Data from 937 patients were available for evaluation. The overall 5‐year disease‐free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5‐year disease‐free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5‐year disease‐free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five‐year disease‐free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. Conclusion: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection. [ABSTRACT FROM AUTHOR]

Background: Biliary tract cancers (BTCs) are highly fatal malignancies that make up less than 1% of all cancers. BTC is often diagnosed at an unresectable stage; surgical resection remains the only definitive treatment. Brain metastases (BMs) from BTC are extremely rare, and few studies on patients with BMs from BTC exist. The aim of this study was to identify clinical characteristics associated with poor prognosis for patients with BMs from BTC. Materials and Methods: We performed a retrospective review of electronic medical records for patients with BMs from BTC managed at Mount Sinai Hospital from 2000 to 2017. Data on patient characteristics, magnetic resonance imaging findings, treatment regimens, and clinical outcomes were analyzed. Results: We identified 1,910 patients with BTC. Nine patients developed BMs, with an incidence of 0.47%. Of these nine patients, six had intrahepatic cholangiocarcinoma, two had extrahepatic cholangiocarcinoma, and one had gallbladder cancer. Six (66.7%) patients had one BM, one (11.1%) patient had two BMs, and two (22.2%) patients had three or more BMs. Four (44.4%) patients underwent BM resection, and seven (77.8%) received BM radiation. Median overall survival from time of BM diagnosis was 3.8 months (95% confidence interval 0.1–16.9). Conclusion: Development of BMs from BTC is rare; however, prognosis is less than 4 months. BM diagnosis can occur within 2 years of primary diagnosis. As targeted therapeutics emerge, future studies ought to focus on identifying genomic BM markers associated with BTC subtypes. Implications for Practice: In the largest retrospective study of biliary tract cancer brain metastases, the clinical presentation and outcomes are reported of nine patients with an extremely rare clinical entity. The genomic literature and potential therapeutic targets for these patients with limited treatment options is comprehensively and exhaustively discussed. A better understanding of clinical outcomes of patients with biliary tract cancer who develop brain metastases. This article expands on the existing literature by describing outcomes for patients who developed brain metastases from biliary tract cancer within the context of the genomic era. [ABSTRACT FROM AUTHOR]

Background: The safety and oncological efficacy of laparoscopic re‐resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re‐resection of incidentally discovered gallbladder cancer while minimizing selection bias. Methods: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re‐resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence‐free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. Results: A total of 255 patients underwent re‐resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re‐resection (median 4 versus 6 days; P < 0·001). Three‐year OS rates for laparoscopic and open re‐resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re‐resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing‐risks analysis, the RFS incidence was higher for laparoscopic re‐resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). Conclusion: Laparoscopic re‐resection for selected patients with incidental gallbladder cancer is oncologically non‐inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation. [ABSTRACT FROM AUTHOR]

Objective: The SELECT trial showed progression-free survival (PFS) benefit for lenvatinib for advanced radioiodinerefractory differentiated thyroid cancer (RAI-refractory or RR-DTC) patients, on which current clinical practice is based. We assessed whether the effectiveness and toxicity of lenvatinib in real-life clinical practice in the Netherlands were comparable to the pivotal SELECT trial. Methods: From three Dutch centres Electronic Health Records (EHRs) of p atients treated in the lenvatinib compassionate use program or as standard of care were reviewed and checked for SELECT eligibility criteria. Baseline characteristics, safety, and efficacy measures were compared and PFS and overall survival (OS) were calculated. Furthermore, PFS was compared to estimates of PFS reported in o ther studies. Results: A total of 39 DTC patients with a median age of 62 years were analysed. Of these, 27 patients (69%) did not fulfil the SELECT eligibility criteria. The most common grade =3 toxicities were hypertension (n = 11, 28%), diarrhoea (n = 7, 18%), vomiting (n = 4, 10%), and gallbladder disease (n = 3, 8%). Median PFS and median OS were 9.7 (95% confidence interval (CI): 4.0-15.5) and 18.3 (95% CI: 4.9-31.7) months, respectively, response rate was 38% (95% CI: 23-54%). PFS in the Dutch real-life situation was comparable to previous real-life studies, but inferior to PFS as shown in the SELECT trial (P = 0.04). Conclusions: PFS in our non-trial population was significantly shorter than in the SELECT trial population. In the interpretation of results, differences in the real-life populati on and the SELECT study population regarding patient characteristics should be taken into account. [ABSTRACT FROM AUTHOR]

Background: The incidence of intrahepatic cholangiocarcinoma (iCCA) is increasing. The aim of the study was to provide reference survival data for patients with advanced iCCA treated with first-line cisplatin-gemcitabine chemotherapy (current standard of care).Methods: Individual data from patients with iCCA recruited into the prospective, random assignment Advanced Biliary Tract Cancer (ABC)-01, -02, and -03 studies were retrieved. The prevalence and survival of liver-only iCCA was also assessed. Survival analysis was performed using univariate and multivariable Cox regression. All statistical tests were two-sided.Results: Of 534 patients recruited into the ABC-01, -02, and -03 studies, 109 (20.4%) had iCCA. Most patients (n = 86, 78.9%) had metastatic disease at the time of recruitment; 52 patients (47.7%) had liver-only disease. Following random assignment, 66 (60.6%) iCCA patients received cisplatin and gemcitabine. The median progression-free and overall survival (OS) were 8.4 months (95% confidence interval [CI] = 5.9 to 8.9 months) and 15.4 months (95% CI = 11.1 to 17.9 months), respectively. Of these 66 patients, 34 patients (51.5%) had liver-only disease. Following chemotherapy, 30 (45.5%) and 21 (31.8%) were progression-free at 3 and 6 months from chemotherapy commencement, respectively. The median OS for patients with liver-only iCCA at diagnosis and after 3 and 6 months of chemotherapy was 16.7 months (95% CI = 8.7 to 20.2 months), 17.9 months (95% CI = 11.7 to 20.9 months), and 18.9 months (95% CI = 16.7 to 25.9 months), respectively. Multivariable analysis confirmed that iCCA had a longer OS compared with other non-iCCA biliary tract cancers (hazard ratio = 0.58, 95% CI = 0.35 to 0.95, P value = .03); liver-only iCCA patients also showed longer OS even though findings did not reach statistical significance (hazard ratio = 0.65, 95% CI = 0.36 to 1.19, P value = .16).Conclusions: Patients diagnosed with advanced iCCA have a better OS compared with other biliary tract cancers; a similar trend was identified for patients diagnosed with liver-only iCCA. These findings are to be considered for future clinical trial design. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is a highly lethal malignancy of the gastrointestinal tract. Despite extensive research, the underlying molecular mechanism of GBC remains largely unclear. Deleted in malignant brain tumors 1 (DMBT1) is low-expression during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. Here, we found that DMBT1 was significantly low-expression and deletion of copy number in GBC tissues by qRT-PCR and Western blot. Overexpression of DMBT1 impaired survival, promoted apoptosis in GBC cells in vitro, and inhibited tumor progression in vivo. Further study of underlying mechanisms demonstrated that DMBT1 combined with PTEN which could stabilize PTEN protein, resulting in inhibiting the activation of PI3K/AKT signaling pathway. Our study revealed a new sight of DMBT1 as a tumor-suppressor gene on the PI3K/AKT pathway in GBC, which may be a potential therapeutic target for improving treatment. Down-regulation of DMBT1 suppresses progression of gallbladder carcinoma through PI3K/AKT signaling pathway activation by targeting PTEN. [ABSTRACT FROM AUTHOR]

Background: Tobacco and alcohol are well-established risk factors for numerous cancers, yet their relationship to biliary tract cancers remains unclear.Methods: We pooled data from 26 prospective studies to evaluate associations of cigarette smoking and alcohol consumption with biliary tract cancer risk. Study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for associations with smoking and alcohol consumption were calculated. Random-effects meta-analysis produced summary estimates. All statistical tests were two-sided.Results: Over a period of 38 369 156 person-years of follow-up, 1391 gallbladder, 758 intrahepatic bile duct, 1208 extrahepatic bile duct, and 623 ampulla of Vater cancer cases were identified. Ever, former, and current smoking were associated with increased extrahepatic bile duct and ampulla of Vater cancers risk (eg, current vs never smokers HR = 1.69, 95% CI = 1.34 to 2.13 and 2.22, 95% CI = 1.69 to 2.92, respectively), with dose-response effects for smoking pack-years, duration, and intensity (all Ptrend < .01). Current smoking and smoking intensity were also associated with intrahepatic bile duct cancer (eg, >40 cigarettes per day vs never smokers HR = 2.15, 95 % CI = 1.15 to 4.00; Ptrend = .001). No convincing association was observed between smoking and gallbladder cancer. Alcohol consumption was only associated with intrahepatic bile duct cancer, with increased risk for individuals consuming five or more vs zero drinks per day (HR = 2.35, 95%CI = 1.46 to 3.78; Ptrend = .04). There was evidence of statistical heterogeneity among several cancer sites, particularly between gallbladder cancer and the other biliary tract cancers.Conclusions: Smoking appears to increase the risk of developing all biliary tract cancers except gallbladder cancer. Alcohol may increase the risk of intrahepatic bile duct cancer. Findings highlight etiologic heterogeneity across the biliary tract. [ABSTRACT FROM AUTHOR]

Background Whether the extra-hepatic bile duct (EHBD) should be routinely resected for gallbladder carcinoma (GBC) remains controversial. The current study aimed to determine the clinical impact of combined EHBD resection during curative surgery for advanced GBC. Methods In total, 213 patients who underwent curative surgery for T2, T3 or T4 GBC were enrolled. The clinicopathological features were compared between the patients treated with EHBD resection and those without EHBD resection. Meanwhile, univariable and multivariable Cox-proportional hazards regression models were used to identify risk factors for overall survival (OS). Results Among the 213 patients identified, 87 (40.8%) underwent combined EHBD resection. Compared with patients without EHBD resection, patients with EHBD resection suffered more post-operative complications (33.3% vs. 21.4%, P  = 0.046). However, the median OS of the EHBD resection group was longer than that of the non-EHBD resection group (25 vs. 11 months, P  = 0.008). Subgroup analyses were also performed according to tumor (T) category and lymph-node metastasis. The median OS was significantly longer in the EHBD resection group than in the non-EHBD resection group for patients with T3 lesion (15 vs. 7 months, P  = 0.002), T4 lesion (11 vs. 6 months, P  = 0.021) or lymph-node metastasis (12 vs. 7 months, P  < 0.001). No survival benefit of EHBD resection was observed in GBC patients with T2 lesion or without lymph-node metastasis. T category, lymph-node metastasis, margin status, pre-operative CA19-9 level and EHBD resection were identified as independent prognostic factors for OS of patients with advanced GBC (all P values <0.05). Conclusions EHBD resection can independently affect the OS in advanced GBC. For GBC patients with T3 lesion, T4 lesion and lymph-node metastasis, combined EHBD resection is justified and may improve OS. [ABSTRACT FROM AUTHOR]