Ampulla Of Vater Cancer Research Articles

Targeting BRAF-Mutant Biliary Tract Cancer: Recent Advances and Future Challenges.

Background:Biliary tract cancers (BTCs) represent a heterogeneous group of aggressive solid tumors with limited therapeutic options, and include gallbladder cancer (GBC), ampulla of Vater cancer (AVC), intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA).Methods & Results:In the current review, we will discuss recent results of clinical trials testing targeted therapies in BRAF-mutant BTCs, with a particular focus on the recently published Phase II ROAR trial and ongoing active and recruiting clinical trials.Conclusions:Although the extended use of molecular profiling has paved the way toward a new era in BTC management, targeted therapies are limited to iCCA so far, and the prognosis of patients with metastatic disease has substantially not changed in the last decade. In this discouraging scenario, BRAF inhibition is currently emerging as a novel treatment option in patients harboring BRAF mutations.

Role of cholangitis in predicting survival in patients with carcinoma of the ampulla of vater

BackgroundThere have been strong suggestions that acute inflammation promotes tumour growth, and has a tendency for increased invasiveness, leading to poor survival after surgery. When cholangitis coexists with ampulla of vater cancer, the patient's prognosis may be influenced by the acute inflammatory status of the bile duct. We evaluated the relationship between the severity of acute cholangitis, preoperative CRP levels and survival. MethodsWe retrospectively analysed 154 patients who underwent surgical resection for AOV cancer between January 2003 and November 2018. Cholangitis was graded according to Tokyo Guidelines 2018. Patients were categorised into two groups based on their CRP levels: CRP > 1 mg/L and CRP ≤ 1 mg/L. Relationship of cholangitis grade and CRP >1 mg/L with survival was assessed. ResultsThe mean age of the patients was 65.8 years. Preoperative cholangitis was present in 40 (25.9%) patients, of which 28 (18.2%) had mild cholangitis, 11 (7.1%) had moderate cholangitis, and one (0.6%) had severe cholangitis. CRP was elevated preoperatively in 56 (36.4%) patients. The median follow-up period was 33.5 months. Severity of cholangitis significantly affected the overall survival (P < 0.001) and disease-free survival (P < 0.001). Patients with mild cholangitis had a median overall survival of 43 months compared to 14 months in those with moderate cholangitis. A preoperative CRP level of >1 mg/L was significantly associated with poor overall survival (P = 0.023) but not with disease-free survival (P = 0.128), although it was associated with a trend towards poorer survival. The survival rate of patients with CRP ≤1 mg/L was 77.4%, whereas that of patients with CRP >1 mg/L was 56.7%. In multivariable analysis, age >65 years (P = 0.015), cholangitis grade (P = 0.050), CRP > 1 mg/L (P = 0.045), venous invasion (P = 0.005), and perineural invasion (P = 0.034) were independent prognostic factors for overall survival while cholangitis grade (P = 0.049) and perineural invasion (P = 0.004) were independent prognostic factors for disease-free survival. ConclusionAcute inflammation when associated with cancer can have a negative effect on patient's survival. Patients with higher grades of cholangitis should be adequately treated to improve the inflammatory status.

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine.

Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3–5% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated. A late diagnosis highly compromises surgery, the only potentially curative option. Current treatment regimens include a combination of chemotherapeutic drugs gemcitabine with cisplatin that have a limited efficiency since more than 50% of patients relapse in the first year. More recently, an inhibitor of fibroblast growth factor receptor 2 (FGFR2) was approved as a second-line treatment, based on the promising results from the NCT02924376 clinical trial. However, novel secondary treatment options are urgently needed. Recent molecular characterization of CCA and GBC highlighted the molecular heterogeneity, etiology, and epidemiology in BTC development and lead to the classification of the extrahepatic CCA into four types: metabolic, proliferating, mesenchymal, and immune type. Differences in the immune infiltration and tumor microenvironment (TME) have been described as well, showing that only a small subset of BTCs could be classified as an immune “hot” and targeted with the immunotherapeutic drugs. This recent evidence has opened a way to new clinical trials for BTCs, and new drug approvals are highly expected by the medical community.

A Comparative Study of Laparoscopic versus Open Pancreaticoduodenectomy for Ampulla of Vater Carcinoma.

Several studies have compared laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with periampullary carcinoma; however, only a few studies have made such a comparison on patients with ampulla of Vater cancer (AVC). We compared the perioperative and oncologic outcomes between LPD and OPD in patients with AVC using propensity-score-matched analysis. A total of 359 patients underwent PD due to AVC during the study period (76 LPD, 283 OPD). After propensity score matching, the LPD group showed significantly longer operation time than did the OPD group (400.2 vs. 344.6 min, p < 0.001). Nevertheless, the LPD group had fewer painkiller administrations (8.3 vs. 11.1, p < 0.049), fewer Grade II or more severe postoperative complications (15.9% vs. 34.8%, p = 0.012), and shorter postoperative hospital stays (13.7 vs. 17.3 days, p = 0.048), compared with the OPD group. There was no significant difference in recurrence-free outcomes and overall survival between the two groups (p = 0.754 and 0.768, respectively). Compared with OPD, LPD for AVC had comparative oncologic outcomes with less pain, less postoperative morbidity, and shorter hospital stays. LPD may serve as a promising alternative to OPD in patients with AVC.

Adverse oncologic effects of preoperative biliary drainage on early stage ampulla of Vater cancer

BackgroundThe preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer. Methods313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed. Results167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p < 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p < 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202–3.826], p = 0.010). ConclusionFor T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project

Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear. We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study. During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only. We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography. Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.

Preoperative prognostic nutritional index as an independent prognostic factor for resected ampulla of Vater cancer.

IntroductionPrognostic nutritional index (PNI) reflects the nutritional and immunologic status of the patients. The clinical application of PNI is already well-known in various kinds of solid tumors. However, there is no study investigating the relationship between PNI and oncological outcome of the resected ampulla of Vater (AoV) cancer.Materials and methodsFrom January 2005 to December 2012, the medical records of patients who underwent pancreaticoduodenectomy for pathologically confirmed AoV cancer were retrospectively reviewed. Long-term oncological outcomes were compared according to the preoperative PNI value.ResultA total of 118 patients were enrolled in this study. The preoperative PNI was 46.13±6.63, while the mean disease-free survival was 43.88 months and the mean disease-specific survival was 55.3 months. In the multivariate Cox analysis, initial CA19-9 (p = 0.0399), lymphovascular invasion (p = 0.0031), AJCC 8th N-stage (p = 0.0018), and preoperative PNI (p = 0.0081) were identified as significant prognostic factors for resected AoV cancer. The disease-specific survival was better in the high preoperative PNI group (≤48.85: 40.77 months vs. >48.85: 68.05 months, p = 0.0015). A highly accurate nomogram was developed based on four clinical components to predict the 1, 3, and 5-year disease-specific survival probability (C-index 0.8169, 0.8426, and 0.8233, respectively).ConclusionIn resected AoV cancer, preoperative PNI can play a significant role as an independent prognostic factor for predicting disease-specific survival.

The world-wide incidence of biliary tract cancer (BTC).

585 Background: Existing epidemiologic research for BTC is limited to certain subtypes, eg gallbladder cancer (GBC), or combines BTC with liver cancer, and only reports regional statistics. Main sources for global BTC epidemiology (particularly anatomic sites) are literature reviews, which can be subject to limitations like inconsistent classification of subtypes, and varying standard population adjustment and comparison timeframes. Given the increasing incidence of BTC, it is critical to monitor global epidemiology to provide insight to public health management and clinical program development. Methods: We evaluated BTC incidence in 15 countries using the Cancer Incidence in Five Continents database Volume XI (CI5 XI) from the International Agency for Research on Cancer. Most CI5 XI registries cover data from 2008-12 with some variations. Incidence was examined by country, region, and anatomic site (extrahepatic cholangiocarcinoma, ECC; intrahepatic cholangiocarcinoma, ICC; GBC; ampulla of Vater cancer, AVC; and unspecified BTCs). Incidence was adjusted to standard world population and reported as age-standardized rate (ASR; per 100,000 person-years) with standard error (SE). Results: The highest incidence of total BTC was in South Korea (SK; ASR = 3.00, SE = 0.02) and lowest in the UK (ASR = 0.66, SE = 0.01). Overall, BTC incidence was higher in Asian countries than Western, and in Asian-Americans than the general US population (ASR = 1.00, SE = 0.02 and 0.77, SE &gt; 0.01, respectively). In Thailand, BTC incidence was higher in the North than South (ASR = 1.93, SE = 0.05 and 1.05, SE = 0.03, respectively). GBC and ECC are the top common subtypes in most countries reported. SK had the highest incidence of all subtypes, with ASR &gt; 2 in GBC, ECC, and ICC. Outside of SK, GBC and ECC were most common in Japan (ASR = 1.93, SE = 0.02 and 2.66, SE = 0.03, respectively); ICC was most common in Thailand (ASR = 1.73, SE = 0.05) and high in France (ASR = 1.01, SE = 0.03). Conclusions: These registry data support past reports of higher BTC incidence in Asian vs Western countries as well as regional variation within countries. Data also suggests that high BTC rates in Asian populations may not be entirely geographical as Asian-Americans suffer a higher BTC incidence than the overall US population.

Survival by line of therapy of older patients with advanced biliary tract cancer (BTC).

497 Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.

Prediction model for survival in patients with biliary tract cancer: a development and validation study

Objective: The aim of the present study was to investigate the survival rate and its prognostic factors for patients with biliary tract cancer, and then a prognostic risk prediction model was constructed to predict the survival probability of patients. Methods: A total of 14 005 patients with biliary tract cancer (including gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer), who were diagnosed between 2010 and 2015 in the US National Cancer Institute Surveillance, Epidemiology, and End Results Program (SEER) were included in the development cohort. The prognostic risk factors of biliary tract cancer were investigated using multivariate Cox regression models. The predictive nomograms were then constructed to predict the overall survival probability of 1, 3, and 5 years, and the predictive discrimination and calibration ability of the nomograms were further evaluated. Meanwhile, 11 953 patients who were diagnosed during 2004 to 2009 from SEER Program were then selected to validate the external predictive accuracy of the prediction models. Results: The 1, 3 and 5-year cumulative survival rates of patients with biliary tract cancer were 41.9%, 20.4% and 15.3%, respectively, in the development cohort. Age greater than 50 years, African Americans and Native Americans and Alaska Natives, higher T, N and M stage and poor histological differentiation grade were risk factors for death, while married status, Asia-Pacific Islanders, insured status and surgery on primary site were protective factors. Gender was not significantly associated with the overall survival. The C statistic of the prediction model was 0.73 (95%CI: 0.72-0.74), and the calibration curve showed that the interaction curves of predictive and actual survival rates of 1, 3 and 5 years were close to the 45 degree diagonal. Results in the validation cohort were similar with those in the construction cohort, with a C statistic of 0.70 (95%CI: 0.69-0.72), indicating high external applicability of the prediction model. Findings from gallbladder cancer, extrahepatic bile duct cancer, and ampulla of Vater cancer are in consistent with the overall biliary tract cancer. Conclusions: The survival rate of patients with biliary tract cancer is relatively poor, and the survival prediction model based on prognostic factors has high prediction accuracy. In the future, this prognostic prediction model could be applied to clinical practice to guide individualized treatment for patients with biliary tract cancer.

PCN322 TREATMENT OF ADVANCED BILIARY TRACT CANCER (BTC) AFTER PROGRESSION ON FIRST-LINE (1L) SYSTEMIC THERAPY

In the absence of clear recommendations for the treatment of BTC after progression on 1L therapy, information on second-line (2L) treatment in the real-world setting is sparse. This study describes 2L treatment patterns for advanced BTC in an older US population. We identified patients with BTC aged ≥66 years using the Surveillance, Epidemiology, and End. Results cancer registry data linked with Medicare claims. We included patients with advanced, microscopically confirmed BTC who had gallbladder, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or ampulla of Vater cancer between 2010 and 2013. Chemotherapy use over time was described using Medicare claims; lines were inferred from changes and gaps in therapy. Patients receiving ≥1 line of treatment were followed from initial diagnosis to end of follow-up, second primary cancer, or switch to managed care. 1461 patients with advanced BTC were identified, of whom 38% had gallbladder, 26% had intrahepatic, 22% had extrahepatic, and 8% had ampulla of Vater cancer. Median age at diagnosis was 77 years, with a median follow-up of 8.5 months (88% died). 558 patients (38%) received 1L therapy. Of these, 39% (n=220) received 2L treatment. Median time from diagnosis to start of 2L was 34 weeks (95% CI, 23–49). Median time from end of 1L to start of 2L was 49 days (95% CI, 21–90). There was wide variability in 2L treatments, including 25 unique treatment combinations. Some combination of fluorouracil (including capecitabine), gemcitabine, or platinum therapy was used. Most patients received monotherapy (n=107 [49%]), with 31% (n=68) receiving a doublet. Variations in 2L regimens in this older population reflects the lack of consensus on how to treat older patients with advanced BTC whose 1L treatment failed. These findings highlight the unmet medical need in 2L BTC, an indication in need of effective new agents.

Laparoscopic pancreaticoduodenectomy for periampullary tumors: lessons learned from 500 consecutive patients in a single center.

Laparoscopic pancreaticoduodenectomy (LPD) is a feasible option in selected patients. However, its use has not yet been generalized since it is time-consuming, physically demanding, and technically challenging. It might be essential to share the experience of high-volume centers to understand its use. We retrospectively reviewed the data of 500 consecutive patients who underwent LPD at a single institution between January 2007 and December 2017. The patients included 272 women and 228 men (mean age, 57.1years). The most common indication for LPD was intraductal papillary neoplasm (n = 104, 20.8%). Overall and major (Clavien-Dindo grades III-V) complication rates were 37.2% and 4.8%, respectively. Fifty-four patients (10.8%) had clinically relevant (grade B/C) pancreatic fistulas. There were 3 (0.6%) 90-day mortalities. The most common late complication was bilioenteric stricture (25, 5%). Two hundred thirty patients were diagnosed with periampullary cancer. The 5-year overall survival rates of pancreatic cancer, common bile duct cancer, ampulla of Vater cancer, and duodenal cancer were 37.4, 63.2, 78, and 88.9%, respectively. We analyzed learning curves of first-generation and second-generation surgeons. A risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 cases for LPD with the first-generation surgeon and earlier competency with the second-generation surgeon. LPD has the potential to become an alternative surgery to open pancreaticoduodenectomy for periampullary tumors with acceptable outcomes. We could reduce the steep learning curve with structured training, close supervision, and well-trained operation teams. Perioperative and oncologic outcomes of LPD will be optimized after overcoming the learning curve.

Is there any differences in post-operative course among the three main types of periampullary tumour?

Background and objectives: There have been many reports of pancreaticoduodenectomy performed for the surgical treatment of periampullary cancer. However, any differences in the perioperative courses of different types of periampullary tumour are unclear. In this study, we evaluated the differences in morbidity among the three main types of periampullary tumour. Methods: Prospectively collected data from patients who underwent pancreaticoduodenectomy for periampullary tumour between 2004 to 2018 were reviewed. The patients were divided into three groups: those with pancreatic head cancer, ampulla of Vater (AOV) cancer, or distal common bile duct (CBD) cancer. Results: Among the 645 patients who underwent pancreaticoduodenectomy, 298 (46.2%) were diagnosed with pancreatic head cancer, 172 (26.7%) with AOV cancer, and 175 (27.1%) with distal CBD cancer. The group with distal CBD cancer had the highest mean age (68.45 ± 9.2 years; p = 0.002) and the highest total bilirubin level (8.72 ± 0.6) mg/dl among the three groups. The group with pancreatic head cancer had the highest rate of firm pancreatic texture (71.7%) and the greatest duct diameter (4.64 ± 0.2 mm) among the three groups. Pancreatic fistula and pulmonary complications were more frequent in the groups with AOV cancer and distal CBD cancer. Post-operative haemorrhage occurred at a higher rate in the group with distal CBD cancer (12%). The hospital stay was longer in the group with distal CBD cancer (27.30 ± 1.3 days). Conclusion: Among the three main types of periampullary tumour, the group with distal CBD cancer had the highest complication rate and the longest hospital stay.

Incidence and Mortality Rates of Second Pancreatic Cancer Among Survivors of Digestive Cancers: A Nationwide Population-Based Study.

We analyzed the incidence and mortality rates of second pancreatic ductal adenocarcinoma (PDAC) among survivors of digestive cancers in South Korea. We evaluated data from the Korea National Health Insurance to identify individuals with digestive cancers in 2005 to 2015. The standardized incidence ratios (SIRs) of second PDACs and survival rates were evaluated. Among 772,534 patients with first digestive cancers, 1696 (0.22%) developed second PDACs. The incidence of second PDACs increased until 10 years since the first cancer diagnosis. Patients with biliary tract cancers (BTCs) showed a higher incidence of second PDACs than did those with gastrointestinal cancers or hepatocellular carcinoma. In ages 20 to 49 years, SIRs (95% confidence interval) were higher in survivors of hepatocellular carcinoma (3.08; 1.04-3.08), gastric cancer (3.40; 1.90-3.40), colorectal cancer (5.00; 2.75-5.00), gallbladder cancer (58.52; 11.81-58.52), intrahepatic cholangiocarcinoma (86.99; 1.73-86.99), extrahepatic cholangiocarcinoma (89.41; 27.42-89.41), and ampulla of Vater cancer (156.78; 48.08-156.78). In ages 50 to 64 years, colorectal cancer (1.42; 1.04-1.42), gastric cancer (1.66; 1.29-1.66), and BTCs revealed higher SIRs. In ages more than 65 years, SIR was increased only in BTCs. Second PDACs revealed a more favorable prognosis than first PDACs. Careful surveillance for second PDACs after curative treatment of BTCs and colorectal cancers should be considered.

Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis.

Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65). Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA.

Biliary tract cancer incidence and trends in the United States by demographic group, 1999-2013.

Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites. This study characterized demographic differences in BTC incidence rates and time trends by anatomic site. Population-based North American Association of Central Cancer Registries data were used to calculate age-adjusted incidence rates, incidence rate ratios (IRRs), and estimated annual percent changes (eAPCs) for 1999-2013 by site and demographic group. For sites with significant differences in eAPC by age group, IRRs were compared by age group. GBC incidence rates declined among women (eAPC, -0.5%/y; P=.01) and all racial/ethnic groups except for non-Hispanic blacks, among whom rates increased (1.8%/y; P<.0001). Although GBC rates increased among 18- to 44-year-olds (eAPC, 1.8%/y; P=.01), they decreased among people 45 years old or older (-0.4%/y; P=.009). Sex (P<.0001) and racial/ethnic differences (P=.003 to .02) in GBC incidence were larger for younger people than older people. During this period, ICC (eAPC, 3.2%/y; P<.0001) and ECC rates (1.8%/y; P=.001) steadily increased across sex and racial/ethnic groups. Although AVC incidence rates increased among younger adults (eAPC, 1.8%/y; P=.03) but not older adults (-0.20%/y; P=.30), sex and racial/ethnic IRRs did not differ by age. Differential patterns of BTC rates and temporal trends have been identified by anatomic site and demographic groups. These findings highlight the need for large pooling projects to evaluate BTC risk factors by anatomic site.

Factors Associated with Malignant Biliary Strictures in Patients with Atypical or Suspicious Cells on Brush Cytology.

Background/AimsPathological diagnosis of biliary strictures with atypical or suspicious cells on endoscopic retrograde brush cytology and indeterminate strictures on imaging is challenging. The aim of this study was to identify markers for malignant strictures in such cases. MethodsWe retrospectively analyzed data collected from 146 consecutive patients with indeterminate biliary strictures on imaging who underwent endoscopic retrograde brush cytology from 2007 to 2013. Factors associated with malignant strictures in patients with atypical or suspicious cells on brush cytology were identified. ResultsAmong the 67 patients with a malignant disease (48 cholangiocarcinoma, 6 gallbladder cancer, 5 pancreatic cancer, 5 ampulla of Vater cancer, and 3 other types), 36 (53.7%) had atypical or suspicious cells on brush cytology. Among these, the factors that independently correlated with malignant strictures were stricture length (odds ratio [OR], 5.259; 95% confidence interval [CI], 1.802– 15.294) and elevated carbohydrate antigen 19-9 (CA19-9) (OR, 3.492; 95% CI, 1.242–9.815), carcinoembryonic antigen (CEA) (OR, 4.909; 95% CI, 1.694–14.224), alkaline phosphatase (ALP) (OR, 3.362; 95% CI, 1.207–9.361), and gamma-glutamyl transpeptidase (rGT) (OR, 4.318; 95% CI, 1.512–12.262). ConclusionsElevated levels of CA19-9, CEA, ALP, and rGT and stricture length are associated with malignant strictures in patients with indeterminate biliary strictures on imaging and atypical or suspicious cells on brush cytology.

The oncologic outcomes of the preoperative biliary drainage in the ampulla of Vater cancer

Introduction: Since the hyperbilirubinemia with resectable periampullary malignancies has been found to be relevant to increase the risk of complications, the biliary drainage (BD) has been routinely performed preoperatively. However, recently published studies have been concerned about the routine preoperative BD. But, because those data were not corrected according to the pathologic stage, they cannot be free from the selection bias. Therefore, the purpose of this study is to evaluate the oncologic effect of preoperative BD on the long-term survival outcome. Method: The medical data of 313 patients who received the pancreaticoduodenectomy (PD) and pathologically diagnosed the ampulla of Vater (AoV) cancer in Seoul National University Hospital (SNUH) from Jan 2000 to Dec 2014 were reviewed retrospectively. Result: 146 patients (46.6%) had not received BD, the other 167 patients (53.4%) underwent the preoperative BD. Compared according to BD or not, the overall survival (OS) (BD 62 months vs. No drainage 129 months, p<0.001) and the 5-year disease-free survival rate (5Y-DFSR) (BD 53.8% vs. No drainage 74.3%, p<0.001) were significantly better in the BD group. In analyses of subgroups based on T stage, 5Y-DFSRs showed significant differences in T1 (BD 71.5% vs. No drainage 92.3%, p=0.011) and T2 (BD 51.0% vs. No drainage 75.2%, p=0.020). In N0 stage, 5Y-DFSR showed significant difference (BD 63.4% vs. No drainage 83.9%). In multivariate analysis, age 63 years or over (HR 1.549 [1.054-2.276], p=0.026), advanced histologic grade (HR 3.130 [1.787-5.481], p<0.001), N1 stage (HR 2.230 [1.504-3.307], p<0.001) significantly influenced on the DFS. But, BD did not have a significant effect on DFS (HR 1.375 [0.914-2.069], p=0.127). Conclusion: Preoperative BD did not affect DFS in AoV cancer as compared with age, histologic grade, and N stage. However, in early stage AoV cancer, BD can cause the early recurrence, so it is necessary to consider BD with more strict criteria.

Sarcopenia is associated with postoperative complication after pancreaticoduodenectomy

Introduction: The sarcopenia which is skeletal muscle depletion has been reported to be associated with postoperative recurrence as well as postoperative complications. The aim of this study was to examine whether sarcopenia affects postoperative complications and cancer recurrence. Method: From January 2010 to December 2016, the data of 128 patients who underwent pancreaticoduodenectomy for pancreatic ductal adenocarcinoma, distal bile duct cancer, or ampulla of Vater cancer were consecutively collected. Sarcopenia was validated by lumbar skeletal muscle index, and mean muscle attenuation (Hounsfield units) by computed tomography (CT). The index was measured before surgery, within 1 month after surgery, and between 2 months and 8 months after surgery. The risk factors of postoperative complication and tumor recurrence were investigated. Result: The median age was 69 years (range, 23 to 95). The value obtained by dividing the measured muscle mass by BMI was associated with both postoperative general complications and severe complications in multivariate analysis (p = 0.008 and p = 0.033, respectively). However, the muscle mass index was not associated with clinically relevant pancreatic fistula (p = 0.253). The index measured between 2 months and 8 months after surgery was lower than that measured before surgery. However, the index was not associated with cancer recurrence or death in the survival analysis. Conclusion: The skeletal muscle index measured by CT image was associated with general complication but not pancreatic fistula or survival after pancreaticoduodenectomy.

Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults.

Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to conduct a population-based, case-control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63-41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73-10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03-7.75]), gallbladder cancer (2.06 [1.27-3.33]) and ampulla of Vater cancer (6.29 [4.29-9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30-6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94-8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.