Neoadjuvant Therapy for Duodenal and Ampullary Adenocarcinoma: A Systematic Review.

BACKGROUND: The role of systemic therapy in the management of ampullary (AA) and duodenal adenocarcinoma (DA) remains poorly understood. This study sought to synthesize current evidence supporting the use of neoadjuvant therapy (NAT) in AA and DA. METHODS: The study searched PubMed, Cochrane Library (Wiley), Embase (Elsevier), CINAHL (EBSCO), and ClinicalTrials.gov databases for observational or randomized studies published between 2002 and 2022 evaluating survival outcomes for patients with non-metastatic AA or DA who received systemic therapy and surgical resection. The data extracted included overall survival, progression-free survival, and pathologic response (PR) rate. RESULTS: From the 347 abstracts identified in this study, 29 reports were reviewed in full, and 15 were included in the final review. The selected studies published from 2007 to 2022 were retrospective. Eight were single-center studies; five used the National Cancer Database (NCDB); and two were European multicenter/national studies. Overall, no studies identified survival differences between NAT and upfront surgery (with or without adjuvant therapy). Two NCDB studies reported longer survival with NAT/AT than with surgery. Five single-center studies reported a significant portion of NAT patients who achieved PR, and one study identified major PR as an independent predictor of survival. Other outcomes associated with NAT included conversion from unresectable to resectable disease, reduced lymph node positivity, and decreased local recurrence rate. CONCLUSION: Evidence supporting the use of NAT in AA and DA is weak. No randomized studies exist, and observational data show mixed results. For patients with DA and AA, NAT appears safe, but better evidence is needed to understand the preferred multidisciplinary management of DA and AA periampullary malignancies.

Ampullary Adenocarcinoma, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Ampullary cancers refer to tumors originating from the ampulla of Vater (the ampulla, the intraduodenal portion of the bile duct, and the intraduodenal portion of the pancreatic duct), while periampullary cancers may arise from locations encompassing the head of the pancreas, distal bile duct, duodenum, or ampulla of Vater. Ampullary cancers are rare gastrointestinal malignancies, and prognosis varies greatly based on factors such as patient age, TNM classification, differentiation grade, and treatment modality received. Systemic therapy is used in all stages of ampullary cancer, including neoadjuvant therapy, adjuvant therapy, and first-line or subsequent-line therapy for locally advanced, metastatic, and recurrent disease. Radiation therapy may be used in localized ampullary cancer, sometimes in combination with chemotherapy, but there is no high-level evidence to support its utility. Select tumors may be treated surgically. This article describes NCCN recommendations regarding management of ampullary adenocarcinoma.

Ampullary Carcinoma: An Overview of a Rare Entity and Discussion of Current and Future Therapeutic Challenges.

Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors.

Treatment Approach to Adenocarcinoma of the Ampulla of Vater.

OPINION STATEMENT: ACs are rare tumors, and thus, there is a lack of prospective trials supporting treatment decisions. Moreover, although anatomically uniform, ACs comprise of biologically distinct entities, depending on what cell type they arise from. This makes the interpretation of limited data even more challenging. Overall, the clinical outcomes of patients with AC are better than those with pancreatic cancer. However, recurrence rates remain high after curative resection. Despite the absence of definitive evidence, we believe that these high recurrence rates are a rational justification for consideration of adjuvant therapy in resected disease, and therapy selection should take tumor biology, stage, resection margins, as well as patient comorbidities and performance status into account. Largely extrapolating from pancreas cancer, we recommend consideration of adjuvant chemotherapy with 6 months of dose-modified FOLFIRINOX in fit patients with pancreatobiliary subtype tumors. Alternative regimens include gemcitabine in combination with capecitabine. If chemoradiotherapy is being added, 6 weeks of radiotherapy in conjunction with 5-FU or capecitabine can be considered. For intestinal subtypes, we recommend 3-6 months of adjuvant FOLFOX. Future studies are needed to evaluate the role of contemporary, multi-agent chemotherapy and chemoradiotherapy in patients with resected and advanced ampullary adenocarcinoma. However, the logistics of performing large randomized trials in patients with a rare cancer is challenging, and the data collection, even in a carefully designed study, would likely take many years. As such, relying on data from basket trials and retrospective analysis will likely serve as guidance for treatment decisions in the near future. Treatment of metastatic disease should employ regimens that are typically used to treat pancreas cancer for tumors of pancreatobiliary subtype and 5-FU-based regimens for intestinal subtypes. Studies specific for patients with advanced AC are much needed. Molecular testing using next-generation sequencing and testing for microsatellite instability (MSI) should be performed on all tumors. We now have disease agnostic options based on these results. Pembrolizumab is approved for MSI-H tumors and tumors with high tumor mutational burden regardless of the primary site. Larotrectinib is approved for tumors with NTRK fusions. At a time when numerous therapeutic agents are in development, for example, those targeting specific K-RAS alterations or NRG fusions, identifying molecular aberrations can significantly impact patient outcomes as well as provide further insights into the biology of disease. In addition, based on recent data suggesting a significant prevalence of germline alterations in patients with ampullary tumors, referral to genetics counselors and germline testing is warranted in a significant proportion of patients with AC.

[Multimodal treatment of periampullary carcinoma]. / Multimodale Therapie ampullärer Karzinome.

Ampullary carcinoma is a rare malignant neoplasm and arises in the region of Vater's ampulla. The differentiation from pancreatic and distal cholangiocarcinoma can be difficult. The prognosis is more favorable than for pancreatic ductal adenocarcinoma but recurrences are frequent. An exact diagnostic clarification and differentiation from pancreatic carcinoma is therefore essential. Although the resection of periampullary carcinoma is established, prospectively controlled studies on the role of multimodal treatment are rare. Adjuvant chemotherapy is oriented to the protocols for pancreatic carcinoma and could be of benefit in lymph node metastases, advanced T stage and low differentiation of tumors. Intestinal and pancreatobiliary subtypes can be differentiated histologically, which is relevant for systemic treatment strategies. Patients with pancreatobiliary differentiated tumors in particular could benefit from gemcitabine-based treatment but insufficient evidence exists for chemoradiotherapy. The role of neoadjuvant and perioperative treatment strategies is currently unclear. Molecular characterization can help to identify familial risk constellations and targeted treatment strategies for this rare tumor entity.

Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer.

Ampullary cancer is a rare periampullary cancer currently with no targeted therapeutic agent. It is important to develop a deeper understanding of the carcinogenesis of ampullary cancer. We attempted to explore the characteristics of ampullary cancer in our dataset and a public database, followed by a search for potential drugs. We used a bioinformatics pipeline to analyze complementary (c)DNA microarray data of ampullary cancer and surrounding normal duodenal tissues from five patients. A public database from the National Center for Biotechnology Information Gene Expression Omnibus (NCBI GEO) was applied for external validation. Bioinformatics tools used included the Gene Set Enrichment Analysis (GSEA), Database for Annotation, Visualization and Integrated Discovery (DAVID), MetaCore, Kyoto Encyclopedia of Genes and Genomes (KEGG), Hallmark, BioCarta, Reactome, and Connectivity Map (CMap). In total, 9097 genes were upregulated in the five ampullary cancer samples compared to normal duodenal tissues. From the MetaCore analysis, genes of peroxisome proliferator-activated receptor alpha (PPARA) and retinoid X receptor (RXR)-regulated lipid metabolism were overexpressed in ampullary cancer tissues. Further a GSEA of the KEGG, Hallmark, Reactome, and Gene Ontology databases revealed that PPARA and lipid metabolism-related genes were enriched in our specimens of ampullary cancer and in the NCBI GSE39409 database. Expressions of PPARA messenger (m)RNA and the PPAR-α protein were higher in clinical samples and cell lines of ampullary cancer. US Food and Drug Administration (FDA)-approved drugs, including alvespimycin, trichostatin A (a histone deacetylase inhibitor), and cytochalasin B, may have novel therapeutic effects in ampullary cancer patients as predicted by the CMap analysis. Trichostatin A was the most potent agent for ampullary cancer with a half maximal inhibitory concentration of < 0.3 µM. According to our results, upregulation of PPARA and lipid metabolism-related genes are potential pathways in the carcinogenesis and development of ampullary cancer. Results from the CMap analysis suggested potential drugs for patients with ampullary cancer.

Cachexia, dietetic consultation, and survival in patients with pancreatic and periampullary cancer: A multicenter cohort study.

It is unclear to what extent patients with pancreatic cancer have cachexia and had a dietetic consult for nutritional support. The aim was to assess the prevalence of cachexia, dietitian consultation, and overall survival in these patients. This prospective multicenter cohort study included patients with pancreatic cancer, who participated in the Dutch Pancreatic Cancer Project and completed patient reported outcome measures (2015-2018). Additional data were obtained from the Netherlands Cancer Registry. Cachexia was defined as self-reported >5% body weight loss, or >2% in patients with a BMI <20 kg/m2 over the past half year. The Kaplan-Meier method was used to analyze overall survival. In total, 202 patients were included from 18 centers. Cachexia was present in 144 patients (71%) and 81 of those patients (56%) had dietetic consultation. Cachexia was present in 63% of 94 patients who underwent surgery, 77% of 70 patients who received palliative chemotherapy and 82% of 38 patients who had best supportive care. Dietitian consultation was reported in 53%, 52%, and 71%, respectively. Median overall survival did not differ between patients with and without cachexia, but decreased in those with severe weight loss (12 months (IQR 7-20) vs. 16 months (IQR 8-31), p = 0.02), as compared to those with <10% weight loss during the past half year. Two-thirds of patients with pancreatic cancer present with cachexia of which nearly half had no dietetic consultation. Survival was comparable in patients with and without cachexia, but decreased in patients with more severe weight loss.

Adjuvant therapy for true ampullary cancer: a systematic review.

BACKGROUND: Given the lack of evidence on the best adjuvant approach, this review closely examines optimal adjuvant management for resected true ampullary cancer and its histological subtypes. MATERIALS AND METHODS: A comprehensive literature search of PubMed was performed to identify studies on resected true ampullary cancers, published between January 2010 and December 2018. Data including the use of radiation, chemotherapy or chemoradiation and the outcomes were extracted. RESULTS: A total of 116 records were identified, of which 65 screened were selected. Finally, nine studies were included. Only two of the studies reported separately the outcomes of pancreatobiliary and intestinal subtypes. Patients in the selected studies were treated with a pancreaticoduodenectomy with negative margins. Patients treated with adjuvant therapy were more likely to be pT3-4 and have positive nodes; median survival ranged from 30 to 47 months. A significant benefit for adjuvant treatment was observed in four of the studies, restricted to patients at stage IIB or higher. Likewise, patients with positive nodes may have a longer median survival with adjuvant chemoradiation compared to observation. CONCLUSIONS: The present review suggests a benefit for adjuvant treatment for patients with locally advanced tumors. Randomized trials are needed to ascertain the topic, as well as studies reporting toxicity and quality of life of resected true ampullary cancer patients.

Initial Experience of ERCP-Guided Radiofrequency Ablation as the Primary Therapy for Inoperable Ampullary Carcinomas.

BACKGROUND: Endoscopic ablation of duodenal ampullary malignancy has not been fully assessed. AIMS: The study aimed to evaluate the efficacy and safety of Endoscopic retrograde cholangiopancreatograpy (ERCP)-guided radiofrequency ablation (RFA) for inoperable ampullary cancer. METHODS: Patients with inoperable ampullary cancer underwent ERCP-guided RFA from January 2012 to August 2017. RF energy (7-10 W) was delivered using bipolar RFA electrodes under endoscopic guidance. RFAs were repeated every 1-3 months until visible tumor was eliminated. All patients were followed up till June 2018, during which any biliary event was noted and managed endoscopically. RESULTS: Twenty-three patients underwent a median of two RFA sessions (range 1-6) at a median interval of 56 (range 35-90) days. Among 18 (78.3%) patients who received endoscopic re-evaluations, nine patients showed no remaining lesion and nine showed more than 50% tumor size reduction. During a median follow-up duration of 517 days (range 60-1836 days), eight (34.8%) patients required endoscopic re-interventions. The re-intervention rate at 6 months after RFA was 36.8%. Twelve patients were alive, among whom six required no biliary stenting. The accumulative mean survival was 1081 (95% CI 757.8-1404.0) days. RFA-related adverse events occurred in four cases (7.7%) including mild pancreatitis (1), bleeding (1), and late distal biliary stenosis (2). CONCLUSION: This pilot study shows that ERCP-guided RFA is safe to use and able to reduce tumor volume and re-interventions in patients with inoperable ampullary cancer.

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma.

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined. Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype. Design, Setting, and Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates. Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy. Main Outcomes and Measures: Overall survival. Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41). Conclusions and Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.

Downstaging Locally Advanced Cholangiocarcinoma Pre-Liver Transplantation: A Prospective Pilot Study.

BACKGROUND: Orthotopic liver transplantation (OLT) after neoadjuvant therapy (NT) in well-selected patients with unresectable hilar cholangiocarcinoma (CCA) achieves excellent recurrence-free survival. Current criteria for NT-OLT exclude patients with locally advanced hilar and intrahepatic CCA from potential cure. We sought to evaluate the efficacy of NT in downstaging locally advanced CCA, and examine outcomes after OLT. METHODS: Among 24 patients referred for unresectable hilar and intrahepatic CCA from January 2013 through August 2017, 18 met center-specific inclusion criteria for the NT-OLT treatment protocol: hilar tumor size ≤3.5 cm or intrahepatic ≤8 cm, and regional lymphadenopathy but without distant metastasis. Median follow-up was 22.1 mo from diagnosis. RESULTS: Of 18 patients who initiated NT, 11 were removed from the protocol due to tumor progression (n = 6) or uncontrolled infection and failure-to-thrive (n = 5). Median NT duration tended to be shorter for patients progressing to dropout than for those surviving to OLT (5.5 versus 13.5 mo, P = 0.109). Among five patients who received OLT, 1-y post-OLT patient survival was 80%: three survive recurrence-free (14.5-29.2 mo post-OLT); one developed an isolated tumor recurrence in a single portacaval lymph node at 12 mo post-OLT; and one experienced non-tumor-related death. All dropout patients died at a median of 14.4 mo after diagnosis. CONCLUSIONS: This is the first prospective study to show successful NT downstaging of unresectable locally advanced hilar and intrahepatic CCA before OLT. NT-OLT for select patients with locally advanced hilar and intrahepatic CCA achieved acceptable short-term recurrence-free survival.

[A Case of Long-Term Survival after Repeated Multidisciplinary Treatment for Liver Metastasis of Ampullary Cancer].

The patient was a 79-year-old man. He underwent endoscopic papillectomy for ampullary cancer when he was 70 years old. At the ages of 71 and 73 years, liver metastasis in segment 6 was detected, and radiofrequency ablation(RFA)was performed and adjuvant chemotherapy(gemcitabine, S-1)was administered. At the age of 79 years, recurrence of liver metastasis appeared. Because there were no other metastatic lesions, we performed S6 subsegmentectomy. Five months after the surgery, no recurrence was observed. In general, the prognosis of patients with ampullary cancer with distant metastasis is very poor. This case suggested the efficacy of multidisciplinary treatment, including surgery, RFA, and chemotherapy, in a patient with ampullary cancer with distant metastasis.

Prognostic Factors and the Role of Adjuvant Treatment in Periampullary Carcinoma: a Single-Centre Experience of 95 Patients.

PURPOSE: The effect of adjuvant treatment on those undergoing pancreaticoduodenectomy (PD) for periampullary carcinomas (PAC) is not well studied. Most studies employed chemoradiation as the adjuvant modality. We aimed to analyse clinicopathological differences between types of PACs, the prognostic factors and the role of adjuvant therapy (chemotherapy in the majority). METHODS: Patients with PAC who underwent PD from Jan 2011 to Dec 2015 were retrospectively analysed. RESULTS: Ninety-five patients with PAC underwent PD in the study period. Ampullary carcinoma (AC) was the most common. Pancreatic carcinomas (PC) were larger. AC had lower T stage, perineural invasion (PNI) and R1 resections. Median overall survival (OS) was 32.7 months. On multivariate analysis, lymph node ratio (LNR) ≥ 0.2 and advanced T stage adversely affected the OS. Fifty-seven (66.3%) patients received adjuvant treatment, of which 50 had chemotherapy alone. Adjuvant treatment resulted in better OS in patients with T stage ≥ 3, lymph node involvement, LNR ≥ 0.2, lymphovascular invasion, PNI, tumour size > 2 cm, higher grade and distal cholangiocarcinoma. CONCLUSION: In patients of PAC undergoing PD, AC had favourable clinicopathological profile. LNR ≥ 0.2 and advanced T stage adversely affected OS. Adjuvant treatment resulted in significantly better OS in patients with high-risk features.

Massive hemobilia following plastic stent removal in common bile duct cancer associated with primary sclerosing cholangitis (with video).

Hemobilia is defined as bleeding into the biliary tract. Herein, we report a very rare case of massive hemobilia following plastic stent (PS) removal in common bile duct (CBD) cancer. A 72-year-old man with primary sclerosing cholangitis had undergone repeated insertion of a PS into the CBD. Biliary tract biopsy was performed based on suspicion of combined CBD cancer. Biopsy revealed poorly differentiated adenocarcinoma of the CBD. One month after the biliary tract biopsy, he was admitted for acute cholangitis, and endoscopic retrograde cholangiography was performed for the exchange of the PS. When one of the two biliary PSs was removed, spurting bleeding from the major papilla began abruptly. The massive bleeding caused the patient to be in a pre-shock state. A retrieval balloon catheter was compressed against the papilla for hemostasis. Although he was treated conservatively, the patient developed a bloody discharge. Upper gastrointestinal endoscopy revealed that the pulsatile bleeding beside the PSs started immediately after the removal of the coagula. Emergent contrast-enhanced computed tomography showed right hepatic artery aneurysm across the CBD. Therefore, transarterial embolization was performed. The patient's post-therapeutic course was uneventful. He received chemotherapy, but died about a half year after hemobilia occurred.

Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a Surveillance, Epidemiology, and End Results (SEER) cohort study.

BACKGROUND: Ampullary cancer accounts for only 0.2% of gastrointestinal cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS: Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS: A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs. 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (hazard ratio 4.5, 95% CI: 3.93-5.09, P=0.000). CONCLUSIONS: The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier.

Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012.

BACKGROUND AND OBJECTIVES: Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. METHODS: PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. RESULTS: The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). CONCLUSION: Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT.

Percutaneous transhepatic cholangial drainage combined with percutaneous endoscopic jejunostomy for maintaining nutrition state in patients with advanced ampullary neoplasms.

PURPOSE: To investigate the role of percutaneous transhepatic cholangial drainage (PTCD) combined with percutaneous endoscopic jejunostomy (PEJ) in maintaining the nutrition state in patients with advanced ampullary neoplasms. MATERIALS AND METHODS: Sixty patients who suffered from advanced ampullary neoplasms and could not tolerate internal drainage operation or biliary stent placement were enrolled. After PTCD, PEJ was implemented, and then the enteral nutrient solution + bile were instilled through PEJ tube for enteral nutrition support. Before and 1, 2, 3, and 4 weeks after surgery, the body weight, bilirubin, liver function, nutritional status, and immunologic function indexes were detected and compared. RESULTS: All patients had successfully completed PTCD combined with PEJ, and no serious complication occurred. The body mass index of the patients from 4 weeks after surgery was significantly higher than before (P < 0.05). From 2 weeks, both serum total bilirubin and direct bilirubin levels were significantly lower than before (P < 0.05). From 1 week, both alanine aminotransferase and aspartate aminotransferase levels were significantly lower than before (P < 0.05); from 2 weeks, the level of gamma-glutamyl transferase was significantly lower than before (P < 0.05). From 1 week, the levels of albumin, transferrin, and prealbumin were significantly increased compared with before (P < 0.05), and serum CD3+ cell content, CD4+ cell content, and CD4+/CD8+ ratio were significantly improved compared with before (P < 0.05). CONCLUSION: PTCD combined with PEJ is a safe and effective method for maintaining nutrition state in patients with advanced ampullary neoplasms.

Long-term complete remission of a patient with high grade neuroendocrine carcinoma of ampulla of Vater.

We describe a case report of a 53-year-old man with a 5-months history of progressive jaundice and upper abdominal pain. The patient was further evaluated and finally diagnosed with a high-grade ampullary neuroendocrine tumour (based on endoscopic-guided biopsy). Thereafter, he underwent pancreatoduodenectomy and adjuvant platinum-based chemotherapy. This extremely rare case presents his long-lasting disease-free survival compared with similar cases; this case report exemplifies a new, potentially efficient method for treating high-grade papillary neuroendocrine tumour and may pave the way for further clinical trials utilising this blueprint in the treatment of related conditions.

Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience.

INTRODUCTION: Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS: A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS: Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS: Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.