Real-world efficacy and safety of capecitabine with oxaliplatin in patients with advanced adenocarcinoma of the ampulla of Vater.

BACKGROUND: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. METHODS: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. RESULTS: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78-5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56-11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49-4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47-5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3-4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). CONCLUSIONS: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

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

BACKGROUND: Lymph 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. METHODS: We 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. RESULTS: Among 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. CONCLUSION: Our 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.

Prediction of tumor recurrence after surgical resection of ampullary adenocarcinoma using magnetic resonance imaging.

OBJECTIVES: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings. METHODS: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated. RESULTS: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746. CONCLUSIONS: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients. CLINICAL RELEVANCE STATEMENT: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma. KEY POINTS: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning.

Bile ductal mucosal dysplasia is a possible risk factor for adenocarcinoma in patients with adenomyomatous hyperplasia of the Vaterian system: a single-centre study from China.

BACKGROUND: The relationship between adenomyomatous hyperplasia of the Vaterian system(AV) and cancer is unclear, some reports suggest that AV is often combined with mucosal glandular dysplasia, but it is not clear whether mucosal glandular dysplasia is a risk factor for carcinogenesis of AV. The aim of this study was to retrospective analysis of role of ductal glandular dysplasia as a risk factor in the development of carcinoma in AV. METHODS: A total of 328 cases who underwent surgery with a final pathological diagnosis of adenomyomatous hyperplasia (AH) in the Chinese PLA General Hospital in BeiJing, China, between January 2005 and December 2021 were retrospectively collected. There were Seventeen cases(5%) in which the lesions were located in the common bile duct as well as the ampulla of Vater, and their clinical (age, sex, etc.), imaging (cholelithiasis, etc.) and pathological data (mucosal glandular dysplasia, etc.) were collected. Clinical data and pathological features of AV with or without mucosal glandular dysplasia were analyzed. RESULTS: There were 17 out of 328 cases of AH occurring in the Vaterian system (5%). Three of seventeen AV cases were associated with carcinoma (18%). Of three cases, two (12%) with the tumor lesions in the mucosal glands adjacent to the AH (biliary tract cancer and ampullary cancer), and one (6%) with carcinoma developed from AH itself in the ampulla of Vater. All carcinomas had adenomyomatous hyperplasia with nearby mucosal glandular dysplasia (MGD). The percentage of BTC or AC was higher in patients with concurrent AH and MGD compared to AH patients without MGD. The results show tendency toward statistical significance (P = 0.082). This difference was more obvious among AH with severe dysplasia compared to adenomyomatous hyperplasia with mild-moderate dysplasia (P = 0.018). CONCLUSION: This study is the first to find that AV is associated with biliary tract cancer and ampullary cancer. In AV, the mucosal glandular dysplasia may be a risk factor for the development of malignancy. The underlying mechanism for carcinogenesis of AV could be AH itself or its secretions stimulating mucosal glands hyperplasia, then mucosal glands dysplasia. AV may be a precancerous lesion.

New gel immersion endoscopic ultrasonography technique for accurate periampullary evaluation.

BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.

Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats.

Conjoining of the major pancreatic duct and common bile duct at the major duodenal papilla (MDP) is suspected to predispose cats to the clinical syndrome of "triaditis." However, microanatomy of the MDP or presence of lesions at the MDP has not been assessed in cats with or without triaditis. The aims of this study were to characterize feline MDP histomorphology and to identify associations between MDP anatomy/disease and the presence of biliary, pancreatic, or intestinal inflammation or neoplasia. Histologic assessment was prospectively performed on the MDP, duodenum, jejunum, ileum, liver, and pancreas from 124 client-owned cats undergoing postmortem examination. The majority of cats (104/124, 84%) had a complex ductular network at the MDP, with no distinction between pancreatic and common bile ducts. Lymphoid aggregates at the MDP were common (63/124, 51%). Inflammation of the MDP (MDPitis) was present in 35 of 124 cats (28%) and was often concurrent with cholangitis, pancreatitis, or enteritis (32/35, 91%), but was only associated with enteritis (19/35, 54%, P < .05). Triaditis was less common (19/124, 15%), but was associated with both conjoined MDP anatomy (19/19, 100%, P < .05) and MDPitis (12/19, 63%, P < .05). Neoplasia was present in 37 of 124 cats (29%), with lymphoma (28/37, 78%) predominating. Enteropathy-associated T-cell lymphoma type 2 (EATL2) was most common (n = 16/37, 43%) and was associated with triaditis and MDPitis (P < .05). These findings suggest that anatomy, immune activation, and/or inflammation of the MDP may play a role in the pathogenesis of triaditis. Further studies are needed to elucidate the relationships between triaditis, MDPitis, and EATL2.

Survival benefit of adjuvant treatment for ampullary cancer with lymph nodal involvement: A systematic review and meta-analysis.

BACKGROUND: The efficacy of adjuvant treatment (AT) in ampullary cancer (AmC) remains controversial. This systematic review and meta-analysis aimed to evaluate the role of AT for AmC. DATA SOURCES: A comprehensive systematic search was performed in PubMed, EMBASE, Cochrane Library, and Web of Science databases. Studies comparing overall survival (OS) and recurrence-free survival (RFS) of patients who underwent AT or not following AmC resection were included. RESULTS: A total of 3971 patients in 21 studies were analyzed. Overall pooled data showed no significant difference in effect on the OS by AT [hazard ratio (HR) = 0.998, 95% confidence interval (CI): 0.768-1.297]. No significant difference in recurrence between the AT and non-AT (nAT) groups was noted (HR = 1.158, 95% CI: 0.764-1.755). In subgroup analysis, patients who received AT showed favorable outcomes in the OS compared with those who received nAT in nodal-positive AmC (HR = 0.627, 95% CI: 0.451-0.870). Neither AT consisted of adjuvant chemotherapy with radiotherapy (HR = 0.804, 95% CI: 0.563-1.149) nor AT with adjuvant chemotherapy (HR = 0.883, 95% CI: 0.642-1.214) showed any significant effect on the OS. CONCLUSIONS: The effect of AT in AmC on survival and recurrence did not show a significant benefit. Furthermore, effectiveness according to AT strategies did not show enhancement in survival. AT had an advantage in survival compared with nAT strategy in nodal-positive AmC. In cases of AmC with positive lymph nodal involvement, AT may be warranted regardless of detailed strategies.

Endoscopic and Surgical Management of Non-Metastatic Ampullary Neuroendocrine Neoplasia: A Multi-Institutional Pancreas2000/EPC Study.

INTRODUCTION: Ampullary neuroendocrine neoplasia (NEN) is rare and evidence regarding their management is scarce. This study aimed to describe clinicopathological features, management, and prognosis of ampullary NEN according to their endoscopic or surgical management. METHODS: From a multi-institutional international database, patients treated with either endoscopic papillectomy (EP), transduodenal surgical ampullectomy (TSA), or pancreaticoduodenectomy (PD) for ampullary NEN were included. Clinical features, post-procedure complications, and recurrences were assessed. RESULTS: 65 patients were included, 20 (30.8%) treated with EP, 19 (29.2%) with TSA, and 26 (40%) with PD. Patients were mostly asymptomatic (n = 46; 70.8%). Median tumor size was 17 mm (12-22), tumors were mostly grade 1 (70.8%) and pT2 (55.4%). Two (10%) EP resulted in severe American Society for Gastrointestinal Enterology (ASGE) adverse post-procedure complications and 10 (50%) were R0. Clavien 3-5 complications did not occur after TSA and in 4, including 1 postoperative death (15.4%) of patients after PD, with 17 (89.5%) and 26 R0 resection (100%), respectively. The pN1/2 rate was 51.9% (n = 14) after PD. Tumor size larger than 1 cm (i.e., pT stage >1) was a predictor for R1 resection (p < 0.001). Three-year overall survival and disease-free survival after EP, TSA, and PD were 92%, 68%, 92% and 92%, 85%, 73%, respectively. CONCLUSION: Management of ampullary NEN is challenging. EP should not be performed in lesions larger than 1 cm or with a endoscopic ultrasonography T stage beyond T1. Local resection by TSA seems safe and feasible for lesions without nodal involvement. PD should be preferred for larger ampullary NEN at risk of nodal metastasis.

Ampullary Neuroendocrine Neoplasm: Clinicopathological Characteristics and Novel Endoscopic Entity.

BACKGROUND: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN. METHODS: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN). RESULTS: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of 4 cases of neuroendocrine tumor Grade 1 (NET G1), 1 NET G2 (Grade 2), and 5 neuroendocrine carcinomas (NECs). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 (<10 mm) with endoscopic papillectomy and large NET G1 with pancreaticoduodenectomy. There were no cases of recurrence after resection. All ampullary NECs presented with the characteristic endoscopic finding of a "crater sign" similar to deep-mining ulcers seen in gastric malignant lymphoma. Four cases underwent surgical resection, and 1 case was unresectable. Two patients who underwent multidisciplinary treatment were maintained without recurrence for over 2 years. CONCLUSIONS: Endoscopic findings showed identifiable distinctions between ampullary NETs and NECs.

Long-term outcomes of endoscopic papillectomy for ampullary adenoma with high-grade dysplasia or adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: Evidence of endoscopic papillectomy (EP) for ampullar adenoma with high-grade dysplasia (HGD) or adenocarcinoma is insufficient. Here we investigated the long-term outcomes of the advanced ampullary tumors treated by EP with careful surveillance comparing to subsequent surgery after EP. METHODS: Patients treated with EP for ampullary adenoma with HGD or adenocarcinoma from the multi-center retrospective Korean cohort of ampulla of Vater tumor were categorized into EP alone versus EP with subsequent surgery groups. The overall survival (OS) and recurrence-free survival (RFS) were analyzed for unmatched and matched cohorts using propensity score with nearest neighbor method. RESULTS: During a median 43.3 months of follow-up, 5-year OS was not significantly different between the EP alone and EP surgery groups (91.9% vs. 82.3%, P = 0.443 for unmatched cohort; 89.2% vs. 82.3%, P = 0.861 for matched cohort, respectively). Furthermore, 5-year RFS was not significantly different between the two groups (82.1% vs. 86.7%, P = 0.520 for unmatched cohort; 66.1% vs. 86.7%, P = 0.052 for matched cohort, respectively). However, the patients with positive both (lateral and deep) margins showed significantly poorer survival outcomes than those with negative margins within the EP alone group (P = 0.007). CONCLUSION: EP alone with careful surveillance showed comparable survival outcomes to those of EP with subsequent surgery for ampullar HGD or adenocarcinoma. Resection margin status could be a parameter to determine whether to perform subsequent radical surgery after EP.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

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

BACKGROUND: Biliary 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. METHODS: BTC 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. RESULTS: BTC 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%). CONCLUSIONS: BTC 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.

Differentiating between benign and malignant ampullary strictures: a prediction model using a nomogram based on CT imaging and clinical findings.

OBJECTIVES: To construct a predictive nomogram for differentiating malignant from benign ampullary strictures using contrast-enhanced computed tomography (CT) findings combined with clinical findings. METHODS: In this retrospective study, 152 patients with ampullary stricture (98 benign and 54 malignant) who underwent contrast-enhanced CT were included. Various imaging findings of the ampulla, bile duct, main pancreatic duct, and periampullary area were evaluated and clinical findings including the presence of jaundice, carbohydrate antigen 19-9 level, and history of cholecystectomy were collected. Among them, statistically significant findings were identified using univariable and multivariable logistic regression analyses. A nomogram was constructed to differentiate benign and malignant ampullary strictures and was internally validated. RESULTS: Multivariable analysis revealed that jaundice (odds ratio [OR]: 17.33, p < 0.001), presence of an ampullary mass (OR: 24.40, p < 0.001), non-similar enhancement of the ampulla to the duodenum (OR: 31.96, p = 0.003), and proportional dilatation of the bile duct (OR: 7.98, p = 0.001) were independent significant factors for predicting the malignant ampullary stricture, and were used to construct a nomogram. Among them, non-similar enhancement of the ampulla to the duodenum showed the highest OR and predictor point on the nomogram. The calibration plots showed excellent agreement between the predicted probabilities and the actual rates of malignant ampullary strictures, on internal validation. CONCLUSIONS: Combination of clinical and imaging findings could aid in predicting malignant ampullary strictures using significant findings of jaundice, presence of ampullary mass, non-similar enhancement of the ampulla to the duodenum, and proportional dilatation of the bile duct. KEY POINTS: • The presence of jaundice, ampullary mass, non-similar enhancement of the ampulla, and proportional bile duct dilatation were significant findings for predicting malignant ampullary strictures. • Non-similar enhancement of the ampulla to the duodenum was a significant feature with the highest odds ratio for differentiating benign and malignant ampullary strictures. • The nomogram constructed using contrast-enhanced computed tomography imaging and clinical findings could aid in predicting malignant ampullary strictures.

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

BACKGROUND: Biliary 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 RESULTS: The 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. CONCLUSIONS: The epidemiological characteristics, staging, locoregional surgical treatments, adjuvant therapies, and prognostic outcomes were distinct for each of these BTCs.

Peri-ampullary diverticulum was associated with a higher rate of acute cholangitis among patients with choledocholithiasis.

BACKGROUND: Choledocholithiasis is a commonly encountered disease that is associated with various clinical presentations ranging from mild form of biliary colic to severe life-threatening acute cholangitis. Recently, peri-ampullary diverticulum (PAD) has been linked to the development of biliary diseases; however, data regarding its association with the development of acute cholangitis in the setting of choledocholithiasis are scarce. AIMS: We aimed to identify predictors, specifically PAD, for the development of acute cholangitis in patients with choledocholithiasis. METHODS: We performed a retrospective cross-sectional study of all patients admitted to Galilee Medical Center from 1 January 2010 to 31 December 2019 with different clinical presentations of documented choledocholithiasis including cholangitis, biliary pancreatitis, and biliary colic with abnormal liver enzymes. RESULTS: Overall, 651 patients were included in the final analysis. Among them, 88 patients (13.5%) had choledocholithiasis associated with acute cholangitis (group A), as compared to 563 patients (86.5%) without acute cholangitis (group B). The average ages in groups A and B were 77.8 ± 13.6 and 62.4 ± 20.4 years, respectively (P < 0.0001). The rate of PAD was significantly higher in group A as compared to group B (35.2% vs. 19%, P = 0.0002). However, the rate of smoking, chronic liver diseases, hemolytic anemia, and post-cholecystectomy status were not different between the groups (P = 0.3, P = 0.3, P = 0.2, and P = 0.3), respectively. On univariate analysis, age (OR 1.05, P < 0.0001) and PAD (OR 2.32, P = 0.0006) were significantly associated with acute cholangitis. On multivariate logistic regression analysis, the effects of age and PAD were preserved (OR 1.05, 95% CI 1.03-1.07, P < 0.0001 and OR 1.64, 95% CI 1.02-2.72, P = 0.049), respectively. CONCLUSION: PAD showed a significant association with the development of acute cholangitis among patients with choledocholithiasis. Identification of gallbladder and biliary stones in patients with PAD is of paramount importance since early diagnosis and treatment might prevent further life-threatening complications.

Prediction of tumor recurrence and poor survival of ampullary adenocarcinoma using preoperative clinical and CT findings.

OBJECTIVES: To predict poor survival and tumor recurrence in patients with ampullary adenocarcinoma using preoperative clinical and CT findings. MATERIALS AND METHODS: A total of 216 patients with ampullary adenocarcinoma who underwent preoperative CT and surgery were retrospectively included. CT was assessed by two radiologists. Clinical and histopathological characteristics including histologic subtypes were investigated. A Cox proportional hazard model and the Kaplan-Meier method were used to identify disease-free survival (DFS) and overall survival (OS). A nomogram was created based on the multivariate analysis. The optimal cutoff size of the tumor was evaluated and validated by internal cross validation. RESULTS: The median OS was 62.8 ± 37.9, and the median DFS was 54.3 ± 41.2 months. For OS, tumor size (hazard ratio [HR] 2.79, p < 0.001), papillary bulging (HR 0.63, p = 0.049), organ invasion on CT (HR 1.92, p = 0.04), male sex (HR 1.59, p = 0.046), elevated CA 19-9 (HR 1.92, p = 0.01), pT stage (HR 2.45, p = 0.001), and pN stage (HR 3.04, p < 0.001) were important predictors of survival. In terms of recurrence, tumor size (HR 2.37, p = 0.04), pT stage (HR 1.76, p = 0.03), pN stage (HR 2.23, p = 0.001), and histologic differentiation (HR 4.31, p = 0.008) were important predictors of recurrence. In terms of tumor size on CT, 2.65 cm and 3.15 cm were significant cutoff values for poor OS and RFS (p < 0.001). CONCLUSION: Preoperative clinical and CT findings were useful to predict the outcomes of ampullary adenocarcinoma. In particular, tumor size, papillary bulging, organ invasion on CT, male sex, and elevated CA 19-9 were important predictors of poor survival after surgery. KEY POINTS: • Clinical staging based on preoperative clinical information and CT findings can be useful to predict the prognosis of ampullary adenocarcinoma patients. • In terms of survival, tumor size (HR 2.79), papillary bulging (HR 0.63), organ invasion on CT (HR 1.92), male sex (HR 1.59), and elevated CA 19-9 (HR 1.92) were important clinical predictors of poor survival. • Tumor size on CT was of special importance for both poor overall survival and disease-free survival, with optimal cutoff values of 2.65 cm and 3.15 cm, respectively (p < 0.001).

Preoperative 2-[18F]FDG PET-CT aids in the prognostic stratification for patients with primary ampullary carcinoma.

OBJECTIVES: We sought to investigate whether preoperative dual-phase 2-[18F]FDG PET-CT identify predictors for poor survival in patients with ampullary carcinoma receiving pancreaticoduodenectomy. METHODS: The preoperative PET-CT images of patients with resected ampullary carcinoma from June 2007 to July 2017 were analyzed. Survival curves were analyzed using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard model was used to identify potential prognostic factors associated with disease-free survival (DFS) and overall survival (OS). RESULTS: Fifty-four subjects (26 men, 28 women) were enrolled with a median tumor size of 20 mm. All patients were followed for a median period of 36.9 months with 3- and 5-year DFS of 50.3% and 44.2%, and OS of 77.0% and 68.2%, respectively. Parameters associated with DFS in multivariate analysis were lymphovascular invasion (hazard ratio [HR]: 9.45, p < 0.001), involved margin in pathology (HR: 7.67, p < 0.001), and tumor retention index (RI) from the dual-phase PET (HR: 2.41, p = 0.03), whereas involved margin (HR: 13.14, p < 0.001), post-recurrence chemotherapy (HR: 0.10, p < 0.001), and metabolic tumor volume (MTV) (HR: 4.62, p = 0.009) emerged as independent prognostic factors for OS. CONCLUSIONS: Preoperative 2-[18F]FDG PET-CT offered independent prognostic biomarkers in patients with ampullary carcinoma receiving standard surgical resection. KEY POINTS: • 2-[18F]FDG PET-CT offers good survival prediction before operation in primary malignant neoplasms at ampulla of Vater. • Dual-phase PET scan with bowel distention can better delineate Ampulla of Vater and characterize tumor physiology. • Preoperative risk stratification might aid in better treatment planning.

Immunohistochemical staining for IMP3 in patients with duodenal papilla tumors: assessment of the potential for diagnosing endoscopic resectability and predicting prognosis.

BACKGROUND: Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.' Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. METHODS: Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. RESULTS: The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). CONCLUSION: IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

Can prophylactic argon plasma coagulation reduce delayed post-papillectomy bleeding? A prospective multicenter trial.

BACKGROUND AND AIM: Endoscopic post-papillectomy bleeding occurs in 3% to 20% of the cases, and delayed bleeding is also problematic. However, there is no consensus on how to reduce delayed post-papillectomy bleeding. The aim of this study was to evaluate the efficacy of prophylactic argon plasma coagulation (APC) to minimize delayed bleeding and reduce the persistence of residual tumors after endoscopic papillectomy. METHODS: In a prospective pilot study of patients with benign ampullary tumors, the prophylactic APC group underwent APC at the resection margin following a conventional snaring papillectomy. Then, 24 h later after the papillectomy, all patients underwent a follow-up duodenoscopy to identify post-papillectomy bleeding and were followed up until 12 months. The main outcomes were the delayed (≥24 h) post-papillectomy bleeding rate and the tumor persistence rate. RESULTS: The delayed post-papillectomy bleeding rate was 30.8% (8/26) in the prophylactic APC group and 21.4% (6/28) in the non-APC group (P = 0.434). The post-procedure pancreatitis rates were 23.1% (6/26) and 35.7% (10/28), respectively (P = 0.310). The rate of tumor persistence did not differ between the two groups at 1 month (12.5% vs 7.4%, P = 0.656), 3 months (4.2% vs 3.7%, P = 1.00), 6 months (8.3% vs 3.7%, P = 0.595), and 12 months (0% vs 3.7%, P = 1.00). There were no procedure-related mortalities or serious complications. CONCLUSION: Prophylactic APC may not be effective in reducing delayed post-papillectomy bleeding or remnant tumor ablation immediately after conventional papillectomy (Clinical trial registration-cris.nih.go.kr; KCT0001955).

Endoscopic ampullectomy for non-invasive ampullary lesions: a single-center 10-year retrospective cohort study.

BACKGROUND: Lesions involving the ampulla of Vater have traditionally been managed by surgical resection, albeit with high rates of morbidity and mortality. Endoscopic ampullectomy is increasingly recognized as an efficacious and safer treatment option. This study aims to evaluate the safety and efficacy of endoscopic ampullectomy for non-invasive ampullary lesions in a single tertiary referral center. METHODS: Patients with non-invasive ampullary lesions, with or without familial adenomatous polyposis (FAP), were identified using pathology and endoscopy databases. The study included all patients who underwent the index ampullectomy between January 2007 and January 2017. Outcome parameters included accuracy of forceps biopsies, adverse events, success of endoscopic resection, and rate of recurrence. RESULTS: A total of 53 patients underwent endoscopic ampullectomy over the 10-year period. Histological upstaging was seen in 37.8% of cases at ampullectomy compared to biopsy, including 5 cases (9.4%) of invasive adenocarcinoma. Adverse events occurred in 10 patients (18.9%) consisting of bleeding (11.3%), benign papillary stenosis (3.8%), acute pancreatitis (1.9%), and duodenal perforation (1.9%). Recurrence occurred in 32.7% over a median follow-up of 30 months (range 6-104 months), with the majority (18.4%) occurring at the first surveillance endoscopy. Nonetheless, 75% of recurrences were able to be cleared endoscopically. Endoscopic resection was successful in 91.1% of patients. CONCLUSIONS: Endoscopic ampullectomy is an effective and safer therapeutic modality for non-invasive ampullary lesions, in addition to being a valuable diagnostic and staging tool. Nevertheless, careful patient selection and a commitment to endoscopic follow-up are of primary importance to achieve an optimal therapeutic outcome.