Ampulla Of Vater Cancer Research Articles

Comparison of clinical characteristics and prognostic factors in two site-specific categories of ampullary cancer

BACKGROUND Ampullary cancer is a relatively rare malignant tumor in the digestive system. Its incidence has increased in recent years. As for now, its biological characteristics have not been fully clarified. Recent studies have primarily focused on the histological classification and genetic changes, but there are fewer investigations into the differences among site-specific subgroups. The clinicopathological characteristics of ampullary cancer occurring in different positions have not been elucidated. Furthermore, the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial. AIM To study the clinicopathological features of the two site-specific subgroups of ampullary cancer and explore the factors affecting prognosis. METHODS A total of 356 patients who met the inclusion and exclusion criteria were enrolled. Patients were divided into ampulla of Vater cancer (AVC) and duodenal papilla cancer (DPC) based on the gross and microscopic findings. Baseline data, admission examination results, and perioperative outcomes were collected and analyzed. The Kaplan-Meier curve was used for survival analysis. Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival (OS) of both groups. RESULTS The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC (P = 0.04). The OS for patients with DPC was 58.90 ± 38.74 months, significantly longer than 44.31 ± 35.90 months for patients with AVC (P < 0.01). The independent risk factors affecting the OS of AVC included: Preoperative albumin level (P = 0.009), total bilirubin level (P = 0.017), and number of positive lymph nodes (P = 0.005). For DPC, risk factors included: Age (P = 0.004), tumor size (P = 0.023), number of positive lymph nodes (P = 0.010) and adjuvant treatment (P = 0.020). Adjuvant therapy significantly improved the OS rate of patients with DPC, but not for those with AVC. CONCLUSION Patients with AVC had a shorter OS compared to those with DPC. The prognosis factors and the role of adjuvant therapy of two groups were different.

Predicting lymph node metastasis using preoperative parameters in patients with T1 ampulla of vater cancer

BackgroundLymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer.MethodsWe included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed.ResultsAmong 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 − 9 (CA 19 − 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728.ConclusionOur newly developed prediction model using age, CA 19 − 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer.

Pembrolizumab (Keytruda)

CADTH recommends that public drug plans reimburse Keytruda for the treatment of locally advanced unresectable or metastatic biliary tract carcinoma (BTC) if certain conditions are met. Keytruda in combination with gemcitabine-based chemotherapy should only be covered to treat patients with locally advanced unresectable or metastatic BTC who have not received prior treatment or who have completed treatment with nongemcitabine-based neoadjuvant or adjuvant therapy more than 6 months ago. Patients receiving Keytruda should be in relatively good health (i.e., have a good performance status, as determined by a specialist). Keytruda should only be reimbursed if it is used in combination with gemcitabine-based chemotherapy if prescribed by specialists with experience in managing BTC and if the cost of Keytruda does not exceed the cost of durvalumab. Keytruda should not be reimbursed if it is used to treat patients with Ampulla of Vater cancer.

Sarcopenia adversely impacts clinical outcomes in patients undergoing pancreaticoduodenectomy: A systematic review and meta-analysis.

Sarcopenia is a syndrome marked by a gradual and widespread reduction in skeletal muscle mass and strength, as well as a decline in functional ability, which is associated with malnutrition, hormonal changes, chronic inflammation, disturbance of intestinal flora, and exercise quality. Pancreatoduodenectomy is a commonly employed clinical intervention for conditions such as pancreatic head cancer, ampulla of Vater cancer, and cholangiocarcinoma, among others, with a notably high rate of postoperative complications. Sarcopenia is frequent in patients undergoing pancreatoduodenectomy. However, data regarding the effects of sarcopenia in patients undergoing pancreaticoduodenectomy (PD) are both limited and inconsistent. To assess the influence of sarcopenia on outcomes in patients undergoing PD. The PubMed, Cochrane Library, Web of Science, and Embase databases were screened for studies published from the time of database inception to June 2023 that described the effects of sarcopenia on the outcomes and complications of PD. Two researchers independently assessed the quality of the data extracted from the studies that met the inclusion criteria. Meta-analysis using RevMan 5.3.5 and Stata 14.0 software was conducted. Forest and funnel plots were used, respectively, to demonstrate the outcomes of the sarcopenia group vs the non-sarcopenia group after PD and to evaluate potential publication bias. Sixteen studies encompassing 2381 patients were included in the meta-analysis. The patients in the sarcopenia group (n = 833) had higher overall postoperative complication rates [odds ratio (OR) = 3.42, 95% confidence interval (CI): 1.95-5.99, P < 0.0001], higher Clavien-Dindo class ≥ III major complication rates (OR = 1.41, 95%CI: 1.04-1.90, P = 0.03), higher bacteremia rates (OR = 4.46, 95%CI: 1.42-13.98, P = 0.01), higher pneumonia rates (OR = 2.10, 95%CI: 1.34-3.27, P = 0.001), higher pancreatic fistula rates (OR = 1.42, 95%CI: 1.12-1.79, P = 0.003), longer hospital stays (OR = 2.86, 95%CI: 0.44-5.28, P = 0.02), higher mortality rates (OR = 3.17, 95%CI: 1.55-6.50, P = 0.002), and worse overall survival (hazard ratio = 2.81, 95%CI: 1.45-5.45, P = 0.002) than those in the non-sarcopenia group (n = 1548). However, no significant inter-group differences were observed regarding wound infections, urinary tract infections, biliary fistulas, or postoperative digestive bleeding. Sarcopenia is a common comorbidity in patients undergoing PD. Patients with preoperative sarcopenia have increased rates of complications and mortality, in addition to a poorer overall survival rate and longer hospital stays after PD.

Prognostic Impact of Mucin Expression in Curatively Resected Ampulla of Vater Cancer.

Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods: Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results: Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions: Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer.

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining

BackgroundThe histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance.MethodsSeventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors.ResultsClassifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI.ConclusionsClassification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence. We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers. Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Real-world treatment patterns and survival outcomes for treated biliary tract cancer patients using administrative databases in Ontario.

There are limited data available on treatment patterns and outcomes of biliary tract cancers (BTCs) in Canada. The aim of this study was to understand treatment patterns, survival outcomes and healthcare resource use of BTC patients in Ontario, Canada. We conducted a retrospective population-level study using administrative data of patients diagnosed with advanced or metastatic BTC between January 1, 2010 and December 31, 2019. A total of 2,142 BTC patients were identified; 702 (32.8%) with intrahepatic cholangiocarcinoma, 688 (32.1%) with extrahepatic cholangiocarcinoma, 363 (16.9%) with gallbladder cancer, 174 (8.1%) with ampulla of Vater cancer, and 215 (10.0%) with other types of BTC. In total, 1,314 patients (61.3%) were recurrent cases, and 828 (38.7%) were diagnosed with de novo advanced disease. A total of 1,727 patients (80.6%) received first-line systemic treatment of cisplatin plus gemcitabine (75.2%), FOLFOX [5-fluorouracil (5-FU), folinic acid (FA), and oxaliplatin] or FOLFIRI (5-FU, FA, and irinotecan) (11.5%), carboplatin plus gemcitabine (7.6%), or gemcitabine plus taxane (5.7%). Five hundred and twelve patients (29.6%) went on to receive a second-line treatment. Mean and median overall survival from diagnosis was 20.6 and 11.0 months, respectively. Mean and median overall survival from diagnosis was much higher among patients who received a systemic treatment at 23.8 and 14.1 months, respectively compared to 7.0 and 3.3 months, respectively for untreated patients (P<0.0001). Platinum and gemcitabine combinations are the most common first-line treatments. However, only a small proportion of patients go on to receive subsequent treatments. Survival in treated patients is higher than that in untreated patients. Our findings highlight the unmet need for effective systemic therapies for BTC.

Comparison of clinical features by primary sites in patients with biliary tract cancer who received gemcitabine-based chemotherapy: An exploratory analysis of JCOG1113.

548 Background: Biliary tract cancers (BTCs) include gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC), and ampulla of Vater cancer (AV). Although it was previously reported that there were differences in clinical features individually, the reported data were limited to data from some subgroup analyses of recent randomized controlled trials. JCOG1113 (UMIN000010667) showed the non-inferiority of gemcitabine plus S-1 to gemcitabine plus cisplatin in terms of overall survival (OS) in patients (pts) with advanced BTCs. We aimed to compare clinical features among the primary sites of BTCs using JCOG1113 data. Methods: Among the 354 pts enrolled in JCOG1113, 352 pts were included in this analysis except for 2 pts without BTCs. We compared the patient characteristics and treatment outcomes, such as OS, progression-free survival (PFS), and objective response rate (ORR), among the four primary sites. Results: Of the 352 pts, 137 pts (38.9%), 94 pts (26.7%), 108 pts (30.7%) and 13 pts (3.7%) had GBC, IHCC, EHCC, and AV, respectively. GBC was more common in females (58.4%) than males, in contrast to the other primary sites. The percentage of pts with metastatic disease for GBC was the highest (78.1%) and involved multiple metastatic organs (41.6%), in contrast with the other primary sites. The median OS for GBC, IHCC, EHCC and AV were 12.6 months (reference), 15.7 months (hazard ratio [HR]; 0.749, 95% confidence interval [CI], 0.559-1.005), 16.3 months (0.704, 0.532-0.934) and 11.5 months (1.148, 0.633-2.080), respectively. The median PFS for GBC, IHCC, EHCC and AV were 5.7 months (reference), 6.2 months (0.843, 0.644-1.104), 8.7 months (0.636, 0.489-0.826) and 4.1 months (1.506, 0.851-2.665), respectively. The ORRs for GBC, IHCC, EHCC and AV were 34.4%, 28.9%, 34.4%, and 0.0%, respectively. Conclusions: Except for AV which included a few patients in this trial, GBC showed a poorer prognosis compared with the other primary sites. Furthermore, it was more likely to include metastatic disease and multiple metastases, and this is likely one of the causes of the poorer prognosis. [Table: see text]

The epidemiological trends of biliary tract cancers in the United States of America

BackgroundBiliary tract cancers (BTCs) are a series of heterogeneous malignancies that are broadly grouped based on the anatomical site where they arise into subtypes including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC).Methods and ResultsThe present study provides an overview of the epidemiology of the various BTCs based on data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2018. Distinct differences in both incidence and mortality rates were observed for these BTCs as a function of age, sex, ethnicity, and calendar year. In 2018, BTCs emerged as the fifth most prevalent form of alimentary tract cancer in the USA. While the incidence and mortality of ICC appear to be increasing, the incidence rates of GBC, ECC, and AVC have remained stable, as have the corresponding mortality rates. The most common and deadliest BTCs in 2018 were ICC and GBC among males and females, respectively. The ethnic groups exhibiting the highest incidence rates of these different BTCs were American Indians and Alaska Natives for GBC, and Asian and Pacific Islanders for ICC, ECC, and AVC. The incidence of all of these forms of BTC rose with age. There were some variations in BTCs in terms of staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes from 2000 to 2018.ConclusionsThe epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.

Epidemiologic patterns of biliary tract cancer in the United States: 2001–2015

BackgroundBiliary tract cancer (BTC) includes intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer (AVC). Although BTC is rare in the US, incidence is increasing and elevated in certain populations. This study examined BTC epidemiology in the US by age, sex, race/ethnicity, geographic region, and anatomic site.MethodsBTC incidence, prevalence, mortality, and survival from 2001 to 2015 were evaluated using the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program and the Centers for Disease Control and Prevention’s National Program of Cancer Registries databases. Incidence and mortality rates were calculated and reported as age-standardized rates. Data were assessed by age, anatomic sites, geographic region, and race/ethnicity, and a joinpoint regression model was used to predict trends for age-adjusted BTC incidence and mortality rates.ResultsBTC incidence increased during the study period (annual percent change = 1.76, 95% confidence interval [1.59–1.92]), with the highest increase in ICC (6.65 [6.11–7.19]). Incidence of unspecified BTC initially increased but has recently begun to drop. Hispanic, Asian/Pacific Islander, Black, or American Indian/Alaska Native race/ethnicity was associated with higher BTC mortality rates than White race/ethnicity. Patients with ICC had the highest mortality rate (age-standardized rate = 1.87/100,000 person-years [1.85–1.88]). Five-year survival was 15.2% for all BTC, ranging from 8.5% (ICC) to 34.5% (AVC), and patients with distant disease at diagnosis had lower survival (3%) compared with those with regional (19.1%) or locally advanced disease (31.5%).ConclusionsBTC incidence increased, survival was low across all subtypes, and mortality was greatest in patients with ICC. This underscores the serious, increasing unmet need among patients with BTC. Treatment options are limited, although clinical studies investigating immunotherapy, targeted therapies, and alternative chemotherapy combinations are ongoing. Epidemiological insights may improve patient care and inform the integration of novel therapies for BTC.

Preliminary results of laparoscopic versus open pancreaticoduodenectomy in Vietnam: A retrospective analysis from a multi-center research

IntroductionThe goal of this study was to compare the results of LPD with those of open pancreaticoduodenectomy (OPD). MethodData were retrospectively collected from a database of patients who underwent PD from January 2010 to May 2020. Intraoperative, postoperative, and follow-up assessment studies were conducted. ResultsA total of 149 patients were selected. Compared with OPD, LPD was fewer intraoperative blood transfusions (p = 0.015), a longer median operative time (p < 0.001), hospital stay (p = 0.034), a higher rate of bile leakage (p = 0.02), overall morbidity (p = 0.045), and re-operation (p = 0.044). There was no difference between the two groups in severe pancreatic fistula, postoperative bleeding, delayed gastric emptying, Clavien-Dindo classification ≥ III, or 30-day mortality. LPD had a similar number of excised lymph nodes, R0 resection rate, and long-term survival cases involving malignant tumors, ampulla of Vater cancer, and pancreatic ductal adenocarcinoma. ConclusionIn the early period, the benefit of LPD has not been found as there was a high rate of conversion to laparotomy, morbidity, and re-operation. Despite that, LPD is a feasible oncological approach with long-term survival comparable to OPD.

Trastuzumab plus FOLFOX for gemcitabine/cisplatin refractory HER2-positive biliary tract cancer: A multi-institutional phase II trial of the Korean Cancer Study Group (KCSG-HB19-14).

4096 Background: HER2 over-expression/amplification, which accounts for roughly 15% of total biliary tract cancer (BTC) patients, has been identified as a druggable molecular target by recent genomic profilings, Trastuzumab is a humanized monoclonal antibody against HER2 that has been shown to be effective in patients with HER2-positive breast and gastric cancer, but it has not been studied prospectively in HER2-positive BTC. In the phase III ABC-06 trial, the FOLFOX regimen showed survival benefit as a second-line therapy of BTC. We report the result of a multi-institutional phase II trial of Trastuzumab plus modified-FOLFOX as a second- or third-line treatment for HER2-positive BTC (KCSG-HB19-14; NCT04722133). Methods: HER2-positive (defined as IHC3+ or IHC2+/ISH+ or ERBB2 gene copy number ≥6.0 by NGS) BTC (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer and ampulla of vater cancer) patients who progressed on gemcitabine/cisplatin containing chemotherapy (1 or 2 previous chemotherapy lines permitted) were enrolled. Pts received trastuzumab 4mg/kg (after 6mg/kg load) D1, oxaliplatin 85mg/m2 D1, Leucovorin 200mg/m2 D1, 5-FU 400mg/m2 bolus D1, and 5-FU 2400mg/m2 infusion D1-2 every 2 weeks until unacceptable toxicities or disease progression. The primary endpoint was ORR per RECIST v1.1. Secondary endpoints included PFS, DCR, OS, safety, QOL and correlative biomarker exploration. Results: Total of 34 pts were treated with median follow up of 9.9 months, and 6 pts remained on treatment (treatment duration range: 1.0 to 14.7 months). The primary endpoint was met, with 29.4% (95%CI 15.1-47.5) ORR (PR n = 10), and 79.4% DCR. Median PFS was 5.1 months (95%CI 3.6-6.7) and median OS was not reached (95%CI 7.1-NR; 12-months OS rate 50.6%, 95%CI 29.3-63.6). Pts with HER2 IHC3+ (n = 23, 67.6%) showed tendency for better PFS compared to pts with HER2 IHC 2+/ISH+ (median 5.5 vs 4.9 months, HR 0.52, 95%CI 0.23-1.16). Pts with HER2 3+ tumor cell proportion ≥30% (n = 10) by an artificial intelligence-powered automated HER2 IHC analyzer (Lunit SCOPE HER2) showed significantly better PFS compared to pts without (median 6.67 vs 4.87 months, HR 0.33 95%CI 0.13-0.88). Targeted-panel sequencings were done with tumor tissues from 32 pts and tissue HER2-amplification by NGS did not confer better survival. Treatment-related AE (≥G3) occurred in 29 pts (85.3%) including 19 pts (55.9%) with neutropenia G3-4 and 4 pts (11.8%) with peripheral neuropathy G3-4. No pt showed cardiac AE nor treatment-related study discontinuation. Conclusions: For HER2-positive BTC, 2nd- or 3rd-line trastuzumab plus FOLFOX exhibited a promising efficacy with acceptable toxicity, warranting further investigations. Targeted NGS analyses with ctDNAs from pre-treatment and post-progression liquid biopsies are ongoing. Clinical trial information: NCT04722133.

Proposal of nomograms to predict clinical outcomes in patients with ampulla of vater cancer based on the Korea-Japan collaborative study: A retrospective study

Proposal of nomograms to predict clinical outcomes in patients with ampulla of vater cancer based on the Korea-Japan collaborative study: A retrospective study

Long-term survival after liver metastatectomy followed by palliative chemotherapy for ampulla of vater cancer with single liver metastasis

Long-term survival after liver metastatectomy followed by palliative chemotherapy for ampulla of vater cancer with single liver metastasis

Descriptive epidemiology of biliary tract cancer incidence and geographic variation in Japan.

The epidemiologic features of each biliary tract cancer (BTC) subtype have not been studied and disclosed in detail. The objective of this study was to provide an up-to-date description of the epidemiologic features of BTC by subtypes, especially in terms of the geographic variation of its incidence. We calculated the age-standardized incidence rate (ASR) of each BTC subtype at national and prefectural levels using the data from the national cancer registry in 2016 and 2017. The geographic distribution of each BTC subtype incidence was assessed by calculating the ASR ratio (ASRR) against median ASR at the prefectural level and reflecting them on the Japanese map. A total of 58 438 people diagnosed with malignant BTC were registered in the national cancer registry in 2016 and 2017 [12 497 for intrahepatic bile duct cancer (IHBDC), 16 568 for gallbladder cancer (GBC), 24 602 for extrahepatic bile duct cancer (EHBDC), 4613 for ampulla of Vater cancer (AVC) and 158 for others]. ASR was higher in men than in women for IHBDC, EHBDC and AVC, and similar between men and women for GBC. The ASR of EHBDC was approximately 2 times higher than those of the other subtypes for men and similar to that of GBC for women. The geographic distribution of ASRR was different among BTC subtypes, with larger variability in EHBDC, which was remarkably higher in the north-eastern region in both men and women. The pattern of the geographic distribution of incidence in each BTC subtype was different, which suggests different etiology among subtypes.

Predictors and Recurrence Patterns After Radical Surgery in Ampulla of Vater Cancer: Comparative Analysis Between Early and Late Recurrence

ObjectiveTumor recurrence remains the main dilemma after surgical treatment of ampulla of Vater carcinoma. This study was designed to identify the prognostic factors and evaluate the recurrence patterns of ampulla of Vater cancer.MethodsA total of 286 patients who underwent surgical resection of ampulla of Vater cancer in two medical centers from January 2000 to October 2016 were collected. Data on clinicopathologic factors, survival rate, and recurrence patterns were retrospectively analyzed.ResultsA total of 158 patients (55.2%) survived without evidence of recurrence (non-recurrence), whereas 65 (22.7%) and 63 patients (22.1%) suffered from recurrence of the disease within 12 months (early recurrence) and after 12 months (late recurrence), respectively. Early-recurrence patients exhibited a more advanced disease (advanced tumor stage, lymph node involvement, pancreas invasion, and late TNM stage) than late-recurrence patients. The first or primary location of cancer recurrence in 33 patients (25.8%) was locoregional. Metastasis developed in the liver in 30 patients (23.4%), peritoneum in 13 patients (10.2%), lungs in 10 patients (7.8%), and para-aortic or superior mesenteric artery lymph node in 10 patients (7.8%). Multiple metastases were observed in 26 patients (20.3%).ConclusionThe most common patterns of postoperative recurrence are locoregional and recurrent liver metastasis. The recurrence patterns with the worst prognosis are peritoneal and multiple metastases.

Phase II study of sitravatinib in combination with tislelizumab in patients with advanced biliary tract cancer who have failed to at least 1 prior systemic treatment: Trial in progress.

TPS490 Background: In biliary tract cancer (BTC), there was a positive association of overall survival (OS) with high levels of tumor-infiltrating CD4+, CD8+, and Foxp3+ T lymphocytes, whereas increases in PD-1+/CD8+ tumor-infiltrating lymphocytes had a negative association with OS (Tariq NU et al. 2018). Therefore, immune-modulating treatment can be promising option to overcome a dismal prognosis in BTC patients. However, immune checkpoint inhibitor (ICI) monotherapy, including tislelizumab (anti-PD-1 monoclonal antibody), has a modest effect in advanced BTC (Desai J et al. 2020). Thus, several combination strategies to improve the anti-tumor effect of ICI are being conducted. Anti-angiogenic agent in combination with ICI is one of the promising strategies in which anti-angiogenic agent induced improved anti-tumor immune responses by increasing tumor antigen presentation and promoting lymphocyte infiltration and migration (Song Y et al. 2020). However, this combination have not been widely tested in BTC patients. Sitravatinib is a potent inhibitor of multiple receptor tyrosine kinases including Axl, MER, MET, KIT, FLT3, RET, VEGFR1-3, PDGFRα, which targets are expressed in a number of immune cell types and promote an immunosuppressive tumor microenvironment. This study aim to evaluate the efficacy of the combination strategy of sitravatinib with tislelizumab in advanced BTC and to reveal the immune-modulation through the combination of ICI and antiangiogenic agents. Methods: This study is an open-label, phase 2 study to evaluate the efficacy of sitravatinib and tislelizumab combination treatment in advanced BTC patients who have failed to first-line chemotherapy. Eligible patients have histologically proven BTC (including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer, and ampulla of Vater cancer) and have failed one prior systemic chemotherapy. Patients who have previously received ICI can be enrolled. However, patients who have experienced unacceptable toxicity during prior ICI treatment are excluded. All patients will receive sitravatinib 120mg orally once daily in combination with tislelizumab 200mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. The primary endpoint is disease control rate, with key secondary endpoints including overall response rate, progression-free survival, overall survival, and safety. For evaluating metabolic response, 18F-FDG PET-CT scan will be performed before treatment and at the first response evaluation. Tissue biopsies will be conducted three times in total: screening, the first response evaluation, and disease progression. Blood samples are being collected every cycles for translational biomarker studies. Clinical trial information: NCT04727996.

Factors influencing patterns of recurrence following pancreaticoduodenectomy for patients with distal bile duct cancer and ampulla of Vater cancer.

Backgrounds/AimsPancreaticoduodenectomy (PD) is a standard surgical procedure for patients with periampullary cancer. During the follow-up period after PD, recurrence can be observed in various places with different prognosis. The aim of this study was to clarify the pattern of recurrence and factors affecting the survival of patients with periampullary cancer.MethodsOverall, 88 patients who received PD for distal common bile duct cancer or ampulla of Vater cancer were finally included and their clinical characteristics were analyzed. Patients were divided into three groups: recurrence-free (RF) group, an isolated locoregional recurrence (LR) group, and a distant metastasis (DM) group. Prognostic factors affecting recurrence in each group were analyzed and a survival analysis was performed.ResultsPerineural invasion (PNI), T stage, and lymphovascular invasion (LVI) were significant risk factors for LR and PNI, lymph node metastasis, LVI, and T stage were associated with DM group compared to RF group in univariate analysis, respectively. N stage and PNI were significant risk factors (p = 0.046, p = 0.041) in overall survival of the LR and the DM groups. There was no significant difference in 5-year overall survival between the LR and DM groups.ConclusionsT stage was a significant risk factor of LR, while PNI was a significant risk factor of DM. There was no significant difference in overall survival depending on the site of recurrence.

Cholecystectomy reduces the risk of cholangiocarcinoma in patients with complicated gallstones, but has negligible effect on hepatocellular carcinoma.

Gallstones have been reported to be positively associated with hepatobiliary cancers. However, risks of these cancers by cholecystectomy or in patients with complicated gallstones are controversial. We studied the effect of cholecystectomy on the risk of cholangiocarcinoma (CCA) or hepatocellular carcinoma (HCC) in patients with gallstones and subgroup of complicated gallstones. Patients with gallstone disease (n=958677) and age-matched and sex-matched controls (n=9586770) were identified using the Korean National Health Insurance database. Complicated gallstones were defined as gallstones associated with acute cholecystitis or acute cholangitis. Adjusted hazard ratios (adjusted hazard ratios, 95% confidence interval) of CCA and HCC incidences were evaluated in patients with gallstones who received cholecystectomy compared to the controls. We also analyzed these effects in patients with complicated gallstones. Patients with gallstones showed increased risks of CCA (1.80, 1.67-1.93) and HCC (1.03, 1.00-1.07) compared with controls. Cholecystectomy had minimal effects on the risks of CCA (1.94, 1.76-2.14) and HCC (0.93, 0.87-0.99) compared with those without cholecystectomy. However, patients with complicated gallstones showed highly increased CCA risk (5.62, 4.89-6.46) and a 30% risk reduction after cholecystectomy (3.91, 3.43-4.46). Risk reduction by cholecystectomy was greater for extrahepatic CCA than for intrahepatic CCA or ampulla of Vater cancer. However, the risk of HCC was not different in patients with complicated gallstones and those who underwent cholecystectomy compared to controls. The risk of CCA was markedly increased in patients with complicated gallstones and was partially reduced by cholecystectomy. The risk change of HCC was minimal with gallstones or cholecystectomy.