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Background Use of laparoscopic pancreaticoduodenectomy (LPD) in place of open pancreaticoduodenectomy (OPD) remains controversial. Our aim was to evaluate the results of LPD versus OPD in non-pancreatic periampullary adenocarcinoma (NPPC), a less aggressive tumor. Methods Here, 488 NPPC patients who underwent LPD or OPD were analyzed in this study. The propensity score matching was used to balance the patients in two groups. Statistical analysis was conducted to investigate the differences between LPD and OPD in patients with NPPC. Results The LPD group had shorter operative time, less intraoperative bleeding, and less postoperative hospital stay than OPD group. The 30- and 90-day mortality rates were significantly lower in LPD than in OPD group. There was no statistical difference in long-term survival between the two groups. Conclusions For NPPC, LPD may be the preferred surgical treatment due to its advantages over OPD in terms of intraoperative blood loss and short-term mortality.

Background A high-grade pancreatic injury is a life-threatening injury that is associated with high mortality and morbidity. It is currently unclear which treatment strategy results in good clinical outcomes. Case presentation A 23-year-old Japanese woman sustained severe injury in a motor vehicle accident. Abdominal computed tomography revealed severe pancreatic head injury with extravasation of contrast media. Since it was not possible to insert an endoscopic pancreatic stenting tube into the main pancreatic duct, damage control surgery was performed. On day 3, we could insert the endoscopic pancreatic stenting tube from the ampulla of Vater and an endoscopic nasopancreatic drainage tube in the distal pancreatic duct from the accessory ampulla before the second operation. Drainage tubes were placed around the pancreatic head in the second operation. The endoscopic nasopancreatic drainage tube tube was converted to endoscopic pancreatic stenting tube on day 9. On day 51, the patient was discharged on foot from our hospital without serious complications. Conclusion Early and effective hemostasis, staged pancreatic duct drainage with stenting, and surgical external drainage around the pancreas in combination with an endoscopic procedure and damage control surgery were considered appropriate therapeutic strategy for high-grade pancreatic injury.

BACKGROUND AND AIMS Biliary tract cancer (BTC) exhibits diverse molecular characteristics. However, reliable biomarkers that predict therapeutic responses are yet to be discovered. We aimed to identify the molecular features of treatment responses to chemotherapy and immunotherapy in BTCs. APPROACH AND RESULTS We enrolled 121 advanced BTC patients (68 cholangiocarcinomas [33 intrahepatic, 35 extrahepatic], 41 gallbladder cancers, and 12 Ampulla of Vater cancers) whose specimens were analyzed by clinical sequencing platforms. All patients received first-line palliative chemotherapy; 48 patients underwent programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy after failed chemotherapy. Molecular and histopathological characterization was performed using targeted sequencing and immunohistochemical staining to investigate treatment response-associated biomarkers. Genomic analysis revealed a broad spectrum of mutational profiles according to anatomical location. Favorable responses to chemotherapy were observed in the small-duct type compared with the large-duct type intrahepatic cholangiocarcinoma, with frequent mutations in BRCA1-associated protein-1/isocitrate dehydrogenase 1/2 and KRAS proto-oncogene, GTPase/SMAD family member 4 genes, respectively. The molecular features were further analyzed in BTCs, and transforming growth factor beta and DNA damage response pathway-altered tumors exhibited poor and favorable chemotherapy responses, respectively. In PD-1/PD-L1 blockade-treated patients, KRAS alteration and chromosomal instability tumors were associated with resistance to immunotherapy. The majority of patients (95.0%) with these resistance factors show no clinical benefit to PD-1/PD-L1 blockade and low tumor mutational burdens. Low tumor-infiltrating lymphocyte (TIL) density in tumors with these resistance factors indicated immune-suppressive tumor microenvironments, whereas high intratumoral TIL density was associated with a favorable immunotherapy response. CONCLUSIONS This study proposes predictive molecular features of chemotherapy and immunotherapy responses in advanced BTCs using clinical sequencing platforms. Our result provides an intuitive framework to guide the treatment of advanced BTCs benefiting from therapeutic agents based on the tumors' molecular features.

BACKGROUND AND AIMS Biliary tract cancer (BTC) is rare and has limited treatment options. We aimed to examine aspirin use on cancer-specific survival in various BTC subtypes, including gallbladder cancer, ampulla of Vater cancer, and cholangiocarcinoma. APPROACH AND RESULTS Nationwide prospective cohort of newly diagnosed BTC between 2007 and 2015 were included and followed until December 31, 2017. Three nationwide databases, namely the Cancer Registration, National Health Insurance, and Death Certification System, were used for computerized data linkage. Aspirin use was defined as one or more prescriptions, and the maximum defined daily dose was used to evaluate the dose-response relationship. Cox's proportional hazards models were applied for estimating HRs and 95% CIs. Analyses accounted for competing risk of cardiovascular deaths, and landmark analyses to avoid immortal time bias were performed. In total, 2,519 of patients with BTC were exposed to aspirin after their diagnosis (15.7%). After a mean follow-up of 1.59 years, the 5-year survival rate was 27.4%. The multivariate-adjusted HR for postdiagnosis aspirin users, as compared with nonusers, was 0.55 (95% CI: 0.51 to 0.58) for BTC-specific death. Adjusted HRs for BTC-specific death were 0.53 (95% CI: 0.48 to 0.59) and 0.42 (95% CI: 0.31 to 0.58) for ≤ 1 and > 1 maximum defined daily dose, respectively, and showed a dose-response trend (P

Multiple cancer patients who achieve long-term survival are sometimes encountered. Multiple carcinogenesis may occur due to genetic or environmental characteristics. We report the case of a 74-year-old woman who was diagnosed with synchronous double carcinoma of the duodenal papilla and gall bladder without clinical symptoms, who underwent postoperative follow-up for familiar adenomatous polyposis coli with multiple colonic adenocarcinomas, ileal adenocarcinoma, left urinary tract neoplasm, and left upper lobe lung adenocarcinoma. Computed tomography also showed an intraductal papillary mucinous neoplasm of the pancreas and a lesion that was suspected to be uterine body carcinoma; however, they did not show any clear malignant behavior. No metastatic lesions of either of these biliary cancers were observed. Based on preoperative diagnostic imaging, subtotal stomach preserving pancreaticoduodenectomy with gall bladder bed liver resection with D2 lymphadenectomy was planned and R0 resection was achieved. The postoperative histological diagnosis showed early carcinoma of the duodenal papilla and gall bladder pyloric gland adenoma without node metastasis. The postoperative course was uneventful and the patient had a good prognosis without tumor recurrence or new malignant lesions for two years after the last operation, without adjuvant therapy. Six metachronous carcinomas of eight different organ neoplasms were diagnosed, which is rare. This represents the first reported case of ampullary carcinoma in a patient with sextuple cancer.

Background Outcomes in ampullary cancer (AC) may differ by pathologic subtype. No guidelines exist for the administration of adjuvant therapy (AT). We sought to evaluate the effect of subtype and AT on survival. Methods An institutional review of patients undergoing resection for AC from 2008-17 was performed. Recurrence-free (RFS) and overall survival (OS) were assessed by Kaplan-Meier and Cox proportional hazards modeling. Results Of 53 patients, two-thirds (62%) were stage III. Histologic subtype was evenly split between intestinal and pancreatobiliary (43% and 40%). Half of patients received AT. RFS and OS were 25 (95% CI 16–32) and 41 (CI 22–60) months, respectively, without significant difference by subtype. Stage II/III disease was associated with worse OS (HR 3.7, P = 0.03), which was improved with receipt of AT (HR 0.44, P Conclusion Stage is the primary determinant of survival in AC, which may be improved with AT.

Determination of the primary tumor in periampullary region carcinomas can be difficult, and the pathological assessment and clinicopathological characteristics remain elusive. In this study, we investigated the current recognition and practices for periampullary region adenocarcinoma with an indeterminable origin among expert pathologists through a cognitive survey. Simultaneously, we analyzed a prospective collection of cases with an indeterminable primary tumor diagnosed from 2008 to 2018 to elucidate their clinicopathological features. All cases with pathological indeterminable primary tumors were reported and discussed in a clinicopathological conference to elucidate if it was possible to distinguish the primary tumor clinically and pathologically. From the cognitive survey, over 85% of the pathologists had experienced cases with indeterminable primary tumors; however, 70% of the cases was reported as pancreatic cancer without definitive grounds. Interpretation of the main tumor mass varied, and no standardized method was developed to determine the primary tumor. During a prospective study, 42 of the 392 periampullary carcinoma cases (10.7%) were considered as tumors with a pathological indeterminable origin. After the clinicopathological conferences, 21 (5.4%) remained indeterminable and were considered final indeterminable cases. Histological studies showed that the tumors spread along both the bile duct and main pancreatic duct; this was the most representative finding of the final indeterminable cases. This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin. Adequate assessment of primary tumors in periampullary region carcinomas will help to optimize epidemiological data of pancreatic and bile duct cancer., This study is the first to elucidate and recognize the current clinicopathological features of periampullary region adenocarcinomas with an indeterminable origin.

BACKGROUND Tumor invasion is the most significant prognostic factor in ampullary cancer and is thus a crucial factor in decision making for treatment. Endoscopic ultrasound can be performed to evaluate tumor invasion, but its diagnostic accuracy varies depending on the endoscopist. This study aimed to assess the usefulness of fluorodeoxyglucose positron emission tomography (FDG-PET) for preoperatively predicting tumor invasion in ampullary cancer. METHODS We retrospectively evaluated 44 patients with ampullary cancer (adenoma, n = 6; adenocarcinoma, n = 38) who underwent surgical resection. The SUVmax of the ampullary tumor site was assessed using FDG-PET, and the correlation among tumor invasion, lymph node metastasis, and other clinicopathological factors was evaluated. RESULTS The SUVmax of the ampullary tumor site gradually increased depending on the extent of tumor invasion (p = 0.0075). Moreover, the SUVmax was significantly different between ≤T1a and ≥T1b, which is an indication for endoscopic papillectomy or surgical resection (p = 0.0015). The SUVmax of the ampullary section was significantly correlated with lymph node metastasis (p = 0.035). CONCLUSION The SUVmax of the ampullary tumor site is correlated with tumor invasion and lymph node metastasis in ampullary cancer. Thus, FDG-PET can be a useful modality for preoperative staging and treatment strategy.

Background Adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is exceedingly rare with more aggressive behavior and worse prognosis than adenocarcinoma. The finding of ASC at the AmV in combination to the gastric adenocarcinoma has never been reported in the literature before. Case presentation An old lady was diagnosed as gastric adenocarcinoma at stage IV with enlargement of supraclavicular lymph nodes by gastroscopy and histopathological evaluation 3 years ago. Afterwards, the patient achieved complete remission after regular chemotherapy. However, the patient manifested yellow sclera and skin, choluria and clay colored stool 3 months ago. Preoperative contrast-enhanced CT, ERCP, MRCP, and PET/CT revealed the presence of an ampullary tumor. The patient then underwent laparoscopic radical gastrectomy and pancreaticoduodenectomy with regional lymph node dissection. Postoperative cytological analyses confirmed the diagnosis of gastric ulcer with complete response to neoadjuvant therapy and ASC at the AmV. The patient’s postoperative outcome was uneventful. Conclusion Drawing firm conclusions about the diagnosis of ampullary ASC is difficult because of the difficulty in acquiring both adenocarcinoma and SCC components by fine needle biopsy. The rarity of ASC of the AmV coexistent with gastric carcinoma makes it difficult to elucidate their clinicopathological characteristics, therapeutic strategies and overall prognosis. Surgical resection still remains the main treatment method.

Background: Although duodenal diverticula are associated with less frequent pathology than the colonic diverticula in the large intestine, their periampullary position may have significant clinical implications. The aim of the study was to identify any possible correlation between the type of localisation of the major duodenal papilla, duodenal diverticula, and some particular clinical issues. Materials and methods: In total, 628 patients (408 females and 220 males; aged 21–91 years), who underwent endoscopic retrograde cholangiopancreatography were included in this study. The patients were divided into two groups: a study group comprising 66 (10.5%) patients with periampullary position of diverticula (group A), and a control group comprising 562 (89.5%) patients without diverticula (group B). Results: A duodenal diverticulum was diagnosed in the periampullary position in 66/628 (10.5%) patients: 41 women (aged 52–91 years) and 25 men (aged 54–83 years). Conclusions: Three types of localisation were observed for the major duodenal papilla with regard to the diverticula, with the most common type being next to each other (type III). In patients with diverticula, similar frequencies of gallstone occurrence are observed in men and women. Patients with papilla in the diverticulum who underwent cholecystectomy are more prone to develop lithiasis.

The role of neoadjuvant therapy (NT) for ampullary carcinoma (AC) has not been clearly established.Patients who underwent pancreatoduodenectomy for AC between 2004 and 2016 were identified in the National Cancer Database. Overall survival (OS) was compared between those who received NT before resection and those who underwent surgery first (SF). Propensity score matching (PSM) was performed using age, pathologic T and N stage, and tumor differentiation.Among 8688 patients with AC, 175 (2.0%) received NT before surgery. While patients who received NT were younger (p = .022) and more likely to have nodal metastasis (43.3% vs. 35.1%, p .001), there was no difference in OS on univariate (43 vs. 33 months; hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.88-1.37, p = .401) or multivariate (HR: 1.09, 95% CI: 0.88-1.36, p = .416) analysis between groups. After PSM, there remained no difference in OS between NT or SF groups on univariate (37 vs. 32 months; HR: 1.20, 95% CI: 0.87-1.64, p = .350) or multivariate (HR: 0.99, 95% CI: 0.71-1.38, p = .943) analysis.NT followed by surgery was not associated with improved survival outcomes compared with SF among patients with localized AC. While NT is an acceptable alternative for patients with advanced disease, SF should remain the standard of care.

Background: Endoscopic retrograde cholangiopancreatography is carried out under moderate sedation mostly by use of propofol, opioids and benzodizepines. The aim of study is to assess difficulty in cannulation of ampulla of vater with the use of fentanyl.Methods: A prospective randomized double blind comparative study was conducted at Bharatpur Hospital from August 2019 to August 2020 among patients undergoing Endoscopic retrograde cholangiopancreatography. Total 100 patients were enrolled in study and were divided in two groups – Group P (propofol and midazolam) and Group FP (propofol, midazolam and fentanyl). Ease of cannulation was determined using Freeman scale. Independent sample t-test was used to compare mean between two groups and Chi Square test was used to compare categorical variables.Results: Mean age (51.36±17.750 years versus 56.74±16.995 years), weight (58.88±8.151 kg versus 57.32±8.431 kg) and gender distribution (14 versus 12 male patients and 36 versus 38 female patients) were comparable in both groups-Group P and Group FP. There were 34 patients in Group P and 37 patients in Group FP with easy cannulation and 16 patients in Group P and 13 patients in Group FP with difficult cannulation, which was comparable (p value=0.509) Conclusions: Cannulation of ampulla of vater is not affected by the use of fentanyl in combination with propofol when compared to propofol alone and can be routinely used during endoscopic retrograde cholangiopancreatography.Keywords: Ampulla of vater; endoscopic retrograde cholangiopancreatography; fentanyl; propofol

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.

Background Pancreaticoduodenectomy is the only curative treatment option for patients with resectable ampullary adenocarcinoma (AA). Excellent disease free survival (DFS) can be achieved in patients with clear resection margins but it is poorly understood which patients are at increased risk of recurrence and hence would benefit from adjuvant chemotherapy. There is evolving evidence that the anatomical location of incomplete resection margins influences DFS in pancreatic adenocarcinoma. It is unknown if this also pertains to AA and therefore this study aimed to assess individual resection margin status and other predictors of DFS in AA. Material & methods Consecutive patients undergoing pancreaticoduodenectomy for AA at our institution from 1996 to 2017 were analysed. Pancreas neck, posterior and superior mesenteric vein margins were assessed individually. Cox proportional hazards modelling was used to identify predictors of 5-year DFS. Factors with p Results Analysis of 104 patients revealed median OS and DFS of 56 and 34 months, respectively. Predictors associated with worse DFS on multivariate analysis were T3-stage (HR 3.6, p = 0.048), N1 (HR 2.9, p = 0.01) and N2 -stage (HR 3.6, p = 0.006), R1 status at the posterior margin (HR 3.0, p = 0.009) and a visible mass on CT (HR 2.0, p = 0.039). Conclusion Routine histopathological assessment of individual resection margins may aid in predicting recurrence of AA. Future studies to assess if routine mesopancreas excision during pancreaticoduodenectomy can reduce the incidence of R1 status at the posterior margin are warranted.

There have been strong suggestions that acute inflammation promotes tumour growth, and has a tendency for increased invasiveness, leading to poor survival after surgery. When cholangitis coexists with ampulla of vater cancer, the patient's prognosis may be influenced by the acute inflammatory status of the bile duct. We evaluated the relationship between the severity of acute cholangitis, preoperative CRP levels and survival.We retrospectively analysed 154 patients who underwent surgical resection for AOV cancer between January 2003 and November 2018. Cholangitis was graded according to Tokyo Guidelines 2018. Patients were categorised into two groups based on their CRP levels: CRP1 mg/L and CRP ≤ 1 mg/L. Relationship of cholangitis grade and CRP1 mg/L with survival was assessed.The mean age of the patients was 65.8 years. Preoperative cholangitis was present in 40 (25.9%) patients, of which 28 (18.2%) had mild cholangitis, 11 (7.1%) had moderate cholangitis, and one (0.6%) had severe cholangitis. CRP was elevated preoperatively in 56 (36.4%) patients. The median follow-up period was 33.5 months. Severity of cholangitis significantly affected the overall survival (P 0.001) and disease-free survival (P 0.001). Patients with mild cholangitis had a median overall survival of 43 months compared to 14 months in those with moderate cholangitis. A preoperative CRP level of1 mg/L was significantly associated with poor overall survival (P = 0.023) but not with disease-free survival (P = 0.128), although it was associated with a trend towards poorer survival. The survival rate of patients with CRP ≤1 mg/L was 77.4%, whereas that of patients with CRP1 mg/L was 56.7%. In multivariable analysis, age65 years (P = 0.015), cholangitis grade (P = 0.050), CRP 1 mg/L (P = 0.045), venous invasion (P = 0.005), and perineural invasion (P = 0.034) were independent prognostic factors for overall survival while cholangitis grade (P = 0.049) and perineural invasion (P = 0.004) were independent prognostic factors for disease-free survival.Acute inflammation when associated with cancer can have a negative effect on patient's survival. Patients with higher grades of cholangitis should be adequately treated to improve the inflammatory status.

Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32–82%) and 51% (28–73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.

BackgroundBiliary tract cancer (BTC) has a poor prognosis and lacks a standardized second-line therapy. Vascular endothelial growth factor (VEGF), fibroblast growth factor receptor (FGFR) 4, and platelet-derived growth factor receptor (PDGFR) are highly expressed in BTC. Therefore, lenvatinib (a known inhibitor of VEGF receptors 1–3, FGFRs 1–4, and PDGFR-α) was evaluated for second-line treatment of BTC.MethodsIn this single-arm, multicenter, open-label, phase 2 study, patients with BTC received lenvatinib 24 mg orally once daily in 28-day cycles. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), PFS rate at 12 weeks, disease control rate, clinical benefit rate, safety and pharmacokinetic profiles.ResultsTwenty-six Japanese patients were enrolled and treated; 3 had a confirmed partial response per investigator assessment and per independent imaging review (IIR); ORR was 11.5% (90% confidence interval [CI]: 3.2–27.2). Median PFS was 3.19 months (95% CI: 2.79–7.23) per investigator assessment and 1.64 months (95% CI: 1.41–3.19) per IIR. Median OS was 7.35 months (95% CI: 4.50–11.27). Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 21 patients (80.8%) and included hypertension (n = 10 [38.5%]), proteinuria (n = 3 [11.5%]), palmar-plantar erythrodysesthesia (n = 3 [11.5%]), decreased appetite (n = 3 [11.5%]), and anemia (n = 3 [11.5%]). Two deaths occurred due to TEAEs between treatment initiation and 30 days after last dose, but neither were considered treatment related.ConclusionsLenvatinib demonstrated antitumor activity in BTC, with a tolerable safety profile, and should be further evaluated as potential second-line therapy for this difficult to treat population.Trial registrationClinicalTrials.govNCT02579616. Date of registration: October 19, 2015.

Purpose This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.Materials and Methods Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.Results The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).Conclusion AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Background Periampullary neuroendocrine tumors (NETs) arise from the duodenum, ampulla, and periampullary pancreas. Duodenal and ampullary NETs are rare and may have distinct biologic behavior from pancreatic NETs (P-NETs). We examined the outcomes of these entities. Methods An institutional database was queried for patients undergoing resection for pancreatic head, duodenal, or ampullary NETs from 2000 to 2018. Patients with MEN1 syndrome or follow up less than 12 months were excluded. Results Three hundred and ten patients were identified. Tumor locations were ampulla (n = 15), duodenum (n = 35) and pancreas (n = 260). Median follow-up and recurrence-free survival (RFS) were 60.9 (interquartile range [IQR]: 34.8-99.3) and 171.7 (IQR: 84.0-NR) months. Clinicopathologic data and survival outcomes were similar for duodenal and ampullary NETs (RFS: p = .347 and overall survival [OS]: p = .246) and were combined into an intestinal subtype (IS) group. There were no differences in OS or RFS when comparing IS-NET and P-NET. On multivariate analysis, tissue of origin was not associated with risk of recurrence. The current American Joint Committee on Cancer staging guidelines, which account for origin tissue, were predictive of outcomes for all subtypes. Conclusion Tissue of origin does not appear to impact long-term outcomes when comparing IS-NETs and P-NETs. The AJCC staging system offers good discriminatory capacity in the context of the tissue type.

Background: Conventionally, it is well accepted that the intestinal obstructions in children, especially gastric outlet obstruction are associated with significant metabolic derangement which has impact on its outcome. The study aimed to compare the metabolic profile and treatment outcome of pre- and post-ampullary gastrointestinal obstruction in children at a tertiary care setting. Materials and Methods: A prospective observational study was conducted on 30 children with intestinal obstruction and categorised into Group 1 (pre-ampullary, n = 11) and Group 2 (post-ampullary, n = 19) as per their anatomical site of pathology. Patients were evaluated at both pre- and post-operative period (Day 1 and 10) with haematological, biochemical and blood gas. The pre- and post-operative metabolic profile, resuscitative time and outcome were compared in two groups. Results: Except mild leucocytosis (Group II > I), rest of the pre-operative and post-operative haematological parameters were within normal range and statistically comparable among groups. Although the pre-operative sodium values were within the normal limit in both groups, it was relatively higher in Group I (Group I = 137.82 ± 4.238 vs. Group II = 134.26 ± 4.653), (P = 0.04). The mean bicarbonate values were within the normal limit in both groups (22.49 and 19.34), but the difference was statistically significant (P = 0.031). Mean partial pressure of carbon dioxide level was higher than normal range in Group I (38.464 ± 20.6493) but was comparable with Group II (P = 0.15). The time required for pre-operative resuscitation was 16.6 versus 24.87 h in Group I versus Group II (P = 0.02). In Group I, all children were improved, whereas four children expired in Group II. Conclusion: Metabolic profile in both pre- and post-ampullary intestinal obstruction was found to be normal in majority of the scenario. Children with post-ampullary obstruction need extensive pre-operative resuscitation and have relatively poor outcome.

Background Metallic stents placed in the descending duodenum can cause compression of the major duodenal papilla, resulting in biliary obstruction and pancreatitis. These are notable early adverse events of duodenal stent placement; however, they have been rarely examined. This study aimed to assess the incidence of and risk factors for biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum. Methods We retrospectively reviewed data of consecutive patients who underwent metallic stent placement in the descending duodenum for malignant gastric outlet obstruction at a tertiary referral cancer center between April 2014 and December 2019. Risk factors for biliary obstruction and/or pancreatitis were analyzed using a logistic regression model. Results Sixty-five patients were included. Biliary obstruction and/or pancreatitis occurred in 12 patients (18%): 8 with biliary obstruction, 2 with pancreatitis, and 2 with both biliary obstruction and pancreatitis. Multivariate analysis indicated that female sex (odds ratio: 9.2, 95% confidence interval: 1.4–58.6, P = 0.02), absence of biliary stents (odds ratio: 12.9, 95% confidence interval: 1.8–90.2, P = 0.01), and tumor invasion to the major duodenal papilla (odds ratio: 25.8, 95% confidence interval: 2.0–340.0, P = 0.01) were significant independent risk factors for biliary obstruction and/or pancreatitis. Conclusions The incidence of biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum was non-negligible. Female sex, absence of biliary stents, and tumor invasion to the major duodenal papilla were the primary risk factors. Risk stratification can allow endoscopists to better identify patients at significant risk and permit detailed informed consent.

Background Gallbladder cancer (GBC) has a female predominance, while the other biliary tract cancers (BTC) have a male predominance, suggesting sex hormones may be involved in carcinogenesis. We sought to evaluate the association between menopausal hormone therapy (MHT) and the risk of BTC in women. Methods This nested case-control study was conducted in the UK Clinical Practice Research Datalink. Cases diagnosed between 1990-2017 with incident primary cancers of the gallbladder (GBC), cholangiocarcinoma, ampulla of Vater (AVC), and mixed type were matched to five controls on birth year, diagnosis year, and years in the general practice using incidence density sampling. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MHT use and BTC type. Results The sample consisted of 1,682 BTC cases (483 GBC, 870 cholangiocarcinoma, 105 AVC, and 224 mixed) and 8,419 matched controls with a mean age of 73 (standard deviation: 11) years. Combined formulations (estrogen-progesterone) were associated with an increased GBC risk (OR: 1.97; 95% CI: 1.08, 3.59). Orally administered MHT was associated with an increased GBC risk (OR: 2.28, 95% CI: 1.24, 4.17). Estrogen-only formulations (OR: 0.59; 95% CI: 0.34, 0.93) and cream or suppository administrations (OR: 0.57; 95% CI: 0.34, 0.95) were associated with decreased cholangiocarcinoma risk. The number of prescriptions, dose, duration of use, and time since last use were not associated with GBC or cholangiocarcinoma risk. MHT use was not associated with risk of AVC or mixed cancer. Conclusion Combination MHT formulations and oral administrations are associated with increased GBC risk, while estrogen-only formulations were associated with a lower cholangiocarcinoma risk. MHT formulation and administration should be carefully considered when prescribing.

Non-ampullary duodenal tumors are relatively rare; however, in recent years, they have been encountered more frequently. We analyzed the surgical outcomes and clinicopathological findings in 20 patients who underwent surgery based on preoperative diagnoses of non-ampullary duodenal tumors at our hospital between January 2011 and April 2021. We performed surgery for 3 cases of GIST, 4 cases of adenoma, and 13 cases of adenocarcinoma. The average age of the patients was 64.3 years and the male-to-female ratio was 17:3. The location of the tumor was the blub in 5 cases, the superior duodenal angle in 2 cases, the descending portion in 9 cases, the horizontal portion in 3 cases, and the ascending portion in 1 case. The histological type of adenocarcinoma was tub1 in all cases of early cancer, whereas in advanced cancer, there were many cases with histological types other than tub1. Various surgical procedures from duodenal local resection to pancreatoduodenectomy can be performed for treating non-ampullary duodenal tumors depending on the tumor location and the necessity of lymph node dissection. It is important to establish a treatment policy that considers both curability and invasiveness.

Difficult cannulation in cases of endoscopic retrograde cholangiopancreatography (ERCP) could be associated with several factors, including: type of major papilla, however, there are limited data regarding this possible association.To determine the association between the type of papilla and difficult biliary cannulation.A retrospective cross-sectional analytical study was conducted in patients over 18 years old who underwent ERCP on papilla naive, from July 2019 to April 2021, in a private institution. Unsuccessful cannulations were excluded. The papilla was classified based on Haraldsson classification. The crude association and adjusted for possible confounders between the type of papilla and difficult cannulation was evaluated. Relative risks (RR) and 95% confidence intervals were calculated.188 patients were included. The mean age was 55 years, 66% female. The most frequent indication was choledocholithiasis with 88.5%. The most frequent type of major duodenal papilla was type 1 (32%), followed by type 3 (27%), type 2 (25%) and type 4 (16%). Type 2, 3, 4 papillae showed a significant relationship with difficult cannulation compared to type 1 (p0.001, p0.001 and p=0.008 respectively). The indication other than choledocholithiasis also showed a significant relationship with difficult cannulation (p0.001). In the adjusted analysis, the RR for difficult cannulation compared to type 1 papilla was: 2.51 (95% CI 1.23-5.94) for type 2 papilla, 3.72 (95% CI 1.79-7.71) for papilla type 3 and 3.41 (95% CI 1.54-7.71) for type 4. Theindication other than choledocholithiasis was also associated with a higher risk of difficult cannulation with a RR of 2.36 (95% CI 1.57-3.56). The fistulotomy type precut was used more frequently in the type 3 papilla (46%), while the use of cannula was more frequent in the type 4 papilla (29.6%).Papilla types 2, 3 and 4 are associated with a higher risk of difficult cannulation. This should be considered when performing ERCP in order to reduce the risk of complications.

Intracystic papillary neoplasm (ICPN) of the gallbladder is a rare clinicopathological entity with a wide range of malignant potentials. Here, we report a case of mucin-producing gallbladder carcinoma possibly derived from ICPN. A 78-year-old female patient was referred to our hospital for examination of jaundice. Abdominal CT showed dilated biliary trees and a contrast-enhanced large polypoid mass in the gallbladder. Duodenoscopy showed a large amount of mucin extravasating from the ampulla of Vater. Bile cytology showed no evidence of malignancy. Under the diagnosis of mucin-producing gallbladder tumor, we performed laparoscopic cholecystectomy. Macroscopically, there was a large papillary tumor throughout the entire gallbladder mucosa. Pathological examinations showed a gallbladder adenocarcinoma localized to the mucosa in association with ICPN. Immunohistochemical analysis of the tumor revealed positive staining for MUC2 and MUC5AC but negative for MUC1 and MUC6, suggestive of the intestinal type.

Background The significance of DNA mismatch repair (MMR) deficiency in ampullary cancers (ACs) has not been established. Methods In total, 127 ACs with invasive carcinomas measuring ≥3 mmthat had adequate tissue were analyzed immunohistochemically. Results MMR loss was detected in 18% of ACs (higher than in colorectal cancers). Twelve tumors with MLH1-PMS2 loss were negative for BRAF V600E mutation, suggesting a Lynch syndrome association. MMR-deficient tumors (n = 23), comparedwith MMR-intact tumors (n = 104), showed a striking male predominance (male:female ratio, 4.7). Although the deficient tumors had slightly larger invasion size (2.7 vs 2.1 cm), they also had more expansile growth and less invasiveness, including less perineural invasion, and they ultimately had lower tumor (T) classification and less lymph node metastasis (30% vs 53%; P = .04). More important, patients who had MMR-deficient tumors had better clinical outcomes, with a 5-year overall survival rate of 68% versus 45% (P = .03), which was even more pronounced in those who had higher Tclassification (5-year overall survival, 69% vs 34%; P = .04). MMR deficiencyhad a statistically significant association with medullary phenotype, pushing-border invasion, and tumor-infiltrating immune cells, and it occurred more frequently in ampullary-duodenal type tumors. Programed cell death-ligand 1 (PD-L1) levels analyzed in the 22 MMR-deficient ACs revealed that all medullary carcinomas were positive. Nonmedullary MMR-deficient carcinomas expressed PD-L1 in 33% of tumors cells according to the criteria for a combined positive score ≥1, but all were negative according to the tumor proportion score≥1 method. Conclusions In ACs, MMR deficiency is even more frequent (18%) than in colon cancer and often has a Lynch-suggestive profile, thus routine testing is warranted. Male gender, pushing-border infiltration, ampullary-duodenal origin, medullary histology, and tumor-related inflammation have a significantly higher association with MMR deficiency. MMR-deficient tumors have less aggressive behavior. PD-L1 expression is common in medullary-phenotype ACs, thus immunotherapy should be considered at least for this group.

The incidence of adenocarcinoma of the ampulla of Vater has been increasing over the past years. Nevertheless, it is still a rare disease and the prognostic factors predicting long-term survival are not sufficiently clarified. This study aims to evaluate the association between histopathological characteristics and long-term survival of patients with ampullary cancer after curative resection, as well as the efficiency of immunohistochemical expression of CK7, CK20, and CDX2 to distinguish the histopathological (intestinal or pancreaticobiliary) patterns. Demographic, histopathological data, pTNM stage, and immunohistochemical expression patterns were collected from 65 patients with adenocarcinoma of the ampulla of Vater. Five and 10-year overall and disease-free survival rates after curative resection were determined. Of the 65 patients with ampullary carcinoma, 47 (72%) underwent radical resection. The 5- and 10-year overall survival rate was 46% and 37%, respectively. Our results demonstrate that the main prognostic factors were the presence and number of lymph node metastases, lymph node ratio (LNR), differentiation grade, and lymphovascular invasion. After multivariate analysis, only lymph node ratio ≥ 20% remained an independent prognostic factor of survival (HR: 2.63 95% CI: 1.05–6.61; p = 0.039). Here, we demonstrated more evidence that the lymph node metastases are associated with poor prognosis in ampullary carcinoma. Particularly, the relation between the number of metastatic lymph nodes and the number of harvested lymph node (LNR) should be considered a major prognostic factor.

Intraductal papillary mucinous neoplasm of the bile duct (IPNB) is an epithelial tumor that can cause obstructive jaundice and cholangitis due to mucin production. Although the effectiveness of argon plasma coagulation in IPNB treatment has been demonstrated, the long-term effect of the therapy is largely unknown. Here, we have presented a patient with IPNB who underwent argon plasma coagulation with a follow-up period of more than 2 years. A 74-year-old woman was referred to our department for treatment of obstructive jaundice. Endoscopic retrograde cholangiopancreatography revealed marked dilation of intrahepatic and extrahepatic bile ducts and thick mucin drainage from the ampulla of Vater. IPNB was diagnosed pathologically from biopsy specimens. Surgery was not recommended because of the extensive intrahepatic spread of the lesion. Endoscopic sphincterotomy, endoscopic papillary large balloon dilation, and insertion of a metallic stent could not resolve the obstructive jaundice. Finally, argon plasma coagulation with percutaneous cholangioscopy was performed 3 times over 1 month. After treatment, obstructive jaundice was resolved and the patient's clinical condition has been stable for more than 2 years, except for a single episode of transient cholangitis. In conclusion, argon plasma coagulation may be an alternative to surgery for the palliation of jaundice with IPNB.

Background and aims In recent years, with the development of endoscopic techniques, endoscopic resection is widely used for duodenal papillary adenomas, but conventional endoscopic resection has a high rate of incomplete resection and recurrence. On this basis, we have employed a novel modified endoscopic papillectomy (ESP). In this study, we evaluated the feasibility and advantages of this ESP for the treatment of duodenal major papilla adenoma. Methods A total of 56 patients with duodenal major papilla adenoma confirmed by endoscopic ultrasonography, intraluminal ultrasound and gastroscopic biopsy from October 2007 to June 2017 were collected in the Department of Gastroenterology, Nanjing Drum Tower Hospital. The diameter of the adenoma ranged from 1.41 to 2.02 cm. 16 cases were given the conventional method and 40 cases underwent the modified ESP procedure in which a small incision was made by cutting current when anchoring the snare tip on the distal side of the adenoma. Results En bloc resection rate was significantly higher in the modified group (100%, 40/40) than that in the conventional group (81.3%, 13/16; P = 0.02). However, no significance was seen between the modified group and the conventional group in complete resection rate (92.5%, 37/40 vs 93.8%, 15/16; P = 1.00). There was no significant difference in the number and difficulty of postoperative pancreatic and biliary stents placement between the two groups (P = 0.20). Total bleeding occurrence was much lower in the modified group (37.5%, 15/40 vs 87.5%, 14/16; P = 0.001), and no significant differences were found in other short-term complications and the 3, 6, 12 and 24 months recurrences rate between the conventional and modified ESP groups. Conclusions The modified ESP improves the treatment outcome of duodenal major papilla adenoma with higher en bloc resection rate and lowering bleeding rate.

Background and aim Papilla with hooknose or long protruding shape may increase the difficulty of cannulation during endoscopic retrograde cholangiopancreatography (ERCP). However, the relationship between papilla anatomy and complications of ERCP has not been fully understood. We aimed to investigate the effect of major duodenal papilla morphology on post-ERCP pancreatitis (PEP) and the procedure of cannulation. Methods Patients with native papilla who underwent ERCP were recruited to this multicenter study. Papilla-related variables were collected, including the length of long axis (L), short axis (S) and opening width (OW), transverse fold, periampullary diverticulum (PAD), papilla location, orientation, swelling, and presence of duodenal stenosis. Demographic data and the procedure of cannulation were also prospectively evaluated. The primary outcome was PEP incidence. Multivariate analysis was used to identify high risk factors for PEP. Results Six hundred and fifty-eight patients were enrolled. Overall PEP incidence was 4.7% (31/658). The papilla of patients complicated with PEP had higher long to short axis (L/S) ratio (odds ratio [OR] 3.84, 95% confidence interval [CI]: 1.37-10.74, P = 0.010), higher long axis to opening width (L/OW) ratio (OR 1.35, 95%CI: 1.06-1.71, P = 0.014), more transverse folds (OR 2.53, 95%CI: 1.02-6.26, P = 0.044), and less periampullary diverticulum (OR 0.21, 95%CI: 0.06-0.70, P = 0.011). Multivariate analysis revealed that the indication of common bile duct stones, normal bilirubin, inadvertent pancreatic duct cannulation > 1, L/S ratio ≥ 1.5, and absence of PAD were independent risk factors for PEP. Conclusion Besides patient-related and procedure-related factors, papilla-related variables, such as L/S ratio and PAD, can be considered as a third type of factors associated with PEP (Clinicaltrials.gov number: NCT03550768).

BACKGROUND Different types of periampullary diverticulum (PAD) may differentially affect the success of endoscopic retrograde cholangiopancreatography (ERCP) cannulation, but the clinical significance of the two current PAD classifications for cannulation is limited. AIM To verify the clinical value of our newly proposed PAD classification. METHODS A new PAD classification (Li-Tanaka classification) was proposed at our center. All PAD patients with native papillae who underwent ERCP from January 2012 to December 2017 were classified according to three classification systems, and the effects of various types of PAD on ERCP cannulation were compared. RESULTS A total of 3564 patients with native papillae were enrolled, including 967 (27.13%) PAD patients and 2597 (72.87%) non-PAD patients. In the Li-Tanaka classification, type I PAD patients exhibited the highest difficult cannulation rate (23.1%, P = 0.01), and type II and IV patients had the highest cannulation success rates (99.4% in type II and 99.3% in type IV, P < 0.001). In a multivariable-adjusted logistic model, the overall successful cannulation rate in PAD patients was higher than that in non-PAD patients [odds ratio (OR) = 1.87, 95% confidence interval (CI): 1.04-3037, P = 0.037]. In addition, compared to the non-PAD group, the difficulty of cannulation in the type I PAD group according to the Li-Tanaka classification was greater (OR = 2.04, 95%CI: 1.13-3.68, P = 0.004), and the successful cannulation rate was lower (OR = 0.27, 95%CI: 0.11-0.66, P < 0.001), while it was higher in the type II PAD group (OR = 4.44, 95%CI: 1.61-12.29, P < 0.01). CONCLUSION Among the three PAD classifications, the Li-Tanaka classification has an obvious clinical advantage for ERCP cannulation, and it is helpful for evaluating potentially difficult and successful cannulation cases among different types of PAD patients.

Background Pancreatic cancer is a devastating disease with a dismal prognosis. Despite profound medical advances in systemic therapies for other types of aggressive tumours during recent years, a diagnosis of pancreatic cancer is still often synonymous with a fatal outcome. The term periampullary cancer includes pancreatic cancer and applies to the group of tumours found in proximity to the ampulla of Vater. Molecular events and immune response in the host during chemotherapy remain largely unexplored in this group of tumours. Therefore, the “Chemotherapy, Host Response and Molecular Dynamics in Periampullary Cancer (CHAMP)” study aims to monitor these processes to gain new insight into this perplexing disease. Methods The CHAMP study is a prospective, single-arm observational study. All patients diagnosed with pancreatic or other periampullary adenocarcinoma undergoing adjuvant or palliative chemotherapy treatment in the Department of Oncology, Skåne University Hospital, are invited to participate. Clinical and pathological data will be compiled at study entry. A single tissue microarray (TMA) block is constructed for each patient with a resected tumour and blood samples are drawn before, during and after chemotherapy in order to sample peripheral blood mononuclear cells (PBMC), cytokines and circulating tumour DNA (ctDNA). Next generation sequencing will be performed on tumour tissue and ctDNA to detect changes in the clonal landscape over space and time. Discussion Despite the recent emergence of some promising biomarkers for periampullary cancer, there has been a lack of success in clinical implementation. Cancer cells continuously adapt and become resistant to treatment during chemotherapy. To be able to keep pace with and hopefully overtake this rapid evolution we must, with the help of new diagnostic tools, be ready to adapt and alter treatment accordingly. It seems to us that the only way forward is to gain a better understanding of the dynamics of the disease during treatment. With insights gained from the CHAMP study we hope to find answers to key questions in this largely unexplored territory. Trial registration This study has been registered 30th October 2018 at clinicaltrials.gov as NCT03724994.

The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC.Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated.214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA0.5 ng/ml 128 vs. CEA0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 40 IU/ml 147 vs. CA19-940IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p 0.001), N stage (N0 159 vs. N+ 110 months, p 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients.Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.

Background Endoscopic ampullectomy (EA) offers an insignificantly intrusive strategy for viably treating mucosal and occasionally submucosal lesions of the ampulla of Vater and encompassing periampullary area with high achievement and is more secure. The aim of this study was to present safety, efficacy, and outcomes of EA in the treatment of benign lesions of ampulla Vater performed by single experienced endoscopists in a high volume center. Methods This retrospective study was conducted in patients referred to our hospital (Turkey High Speciality Training and Research Hospital, Turkey) for endoscopic evaluation of ampullary benign lesions over an 8-year period (between October 2011 and September 2019). Success rate was defined as complete resection of lesions. Results Twenty-nine patients with a median age of 64 years were included. Twenty-five patients had lesions confined to the ampulla vateri (86.2%). Accordingly, 2 lesions had intraductal extension adenoma (IDA) (6.9%) and 2 were lateral spreading adenoma (6.9%). The median size of the lesion was 17.5 mm (10 to 36 mm). Nineteen lesions (65.5%) were resected en bloc and 10 lesions (34.5%) were resected in piecemeal manner. Complete resection was achieved in 21 of 23 patients with benign ampullary lesions. The procedure success rate was 91.3%. Complications occurred in 6 patients (20.6%) of these 3 had (10.3%) bleeding, 2 (6.8%) had pancreatitis, and 1 had (3.4%) perforation. Four patients (13.7%) had a recurrence. Conclusions Deep resection of the benign ampullary lesions increases the complete resection rate, cannulation rate of the pancreatic duct, and stenting rate of the pancreatic duct. EA is a safe and successful procedure in patients with benign lesions of ampulla vater.

Background Periampullary cancers (PAC) including pancreatic, ampulla of Vater (AOV), and common bile duct (CBD) cancers are highly aggressive with a lack of useful prognostic markers beyond T stage. However, T staging can be biased due to the anatomic complexity of this region. Recently, several markers related to cancer stem cells and epithelial-mesenchymal transition (EMT) such as octamer transcription factor-4 (Oct4) and fibroblast growth factor receptor 1 (FGFR1) respectively, have been proposed as new promising markers in other solid cancers. The aim of this study was to assess the expression and prognostic significance of stem cell/EMT markers in PACs. Methods Formalin-fixed, paraffin-embedded tissues of surgically excised PACs from the laboratory archives from 1998 to 2014 were evaluated by immunohistochemical staining for stem cell/EMT markers using tissue microarray. The clinicopathologic parameters were documented and statistically analyzed with the immunohistochemical findings. Survival and recurrence data were collected and analyzed. Results A total of 126 PAC cases were evaluated. The average age was 63 years, with 76 male and 50 female patient samples. Age less than 74 years, AOV cancers, lower T & N stage, lower tumor size, no lymphatic, vascular, perineural invasion and histologic well differentiation, intestinal type, no fibrosis, severe inflammation were significantly associated with the better overall survival High expression levels of FGFR1 as well as CK20, CDX2, and VEGF were significantly related to better overall survival, while other stem cell markers were not related. Similar findings were observed for tumor recurrence using disease-free survival. Conclusions In addition to other clinicopathologic parameters, severe fibrosis was related to frequent tumor recurrence, and high FGFR1 expression was associated with better overall survival. Histologic changes such as extensive fibrosis need to be investigated further in relation to EMT of PACs.

Background: Endoscopic biliary stenting (EBS) using a plastic stent is currently widely performed for preoperative biliary drainage for periampullary cancer. The aim of this study was to investigat...

Background The distant metastasis (DM) mode and treatment efficacies in the advanced biliary tract cancer (BTC) were obscure, and a credible evaluation is urgently needed. Method A total of 6348 advanced BTC patients (ICC, intrahepatic cholangiocarcinoma, n = 1762; PHCC, perihilar cholangiocarcinoma, n = 1103; GBC, gallbladder cancer, n = 2580; DCC, distal cholangiocarcinoma, n = 538; AVC, carcinoma of Vater ampulla, n = 365) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) process was carried out for less bias. Result The proportion of M1 patients in each subtype at first diagnosis was 26.4% (ICC), 37.2% (PHCC), 41. 0% (GBC), 24.5% (DCC), and 12.7% (AVC), and the constitution of DM sites in different subtypes varied apparently. Moreover, the survival of metastasis sites was different (P, Using a large population, we provided a detailed landscape about the DM mode of the advanced biliary tract cancer (BTC), found the survival differences among DM sites, and revealed the different chemotherapy efficacies in the BTC subtypes. The constitution and the survival of the DM sites varied significantly in different subtypes, and the chemotherapy efficacies manifested different among the subtypes.

Background and aim Many post-ERCP pancreatitis (PEP) risk factors, including pancreatic duct cannulation, have been identified; however, whether the number of repeated and unintentional wire placements (WPs) in the pancreatic duct during wire-guided cannulation affects PEP risk is unknown. We aimed to identify the effects of repeated WP in the pancreatic duct and other potential risk factors on PEP incidence. Methods We retrospectively analyzed 877 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP). We examined potential patient-related and procedure-related risk factors, and PEP incidence by univariable and multivariable logistic regression analyses. Results Thirty-four patients (3.9%) had PEP. Univariable analysis revealed younger age, malignant common bile duct or ampulla of Vater stricture, two or more episodes of WPs in the pancreatic duct, and metal biliary stent as risk factors for PEP. Following multivariable analysis, two or more episodes of WPs in the pancreatic duct and metal biliary stent remained in the final model. PEP did not increase significantly in case of a one episode of WP (4.0%) compared with no episode of WP in the pancreatic duct (2.7%). However, patients with two episodes of WPs had 8.0% incidence and three or more episodes of WPs had 14.3%. Conclusions A WP in the pancreatic duct and a metal biliary stent were associated with increased PEP incidence in patients undergoing ERCP. As for the pancreatic duct wire cannulation, two or more WPs considerably increased PEP incidence. This suggests that preventive measures or alternative procedures might be considered in patients with such cases during and after ERCP.

Background HHLA2 is a recently discovered member of the B7-family of immune checkpoint molecules with limited expression in normal tissues but overexpression in several types of cancer. The aim was to determine the expression, prevalence and biological relevance of HHLA2 protein expression in two closely related human cancer types, namely pancreatic cancer and ampullary cancer. Methods HHLA2 expression levels were retrospectively determined by immunohistochemistry in tissue micro-arrays of surgically resected tumours of 122 pancreatic cancer patients and 72 patients with ampullary cancer of the pancreato-biliary subtype. Results HHLA2 was expressed at variable levels by tumour cells in 67% of pancreatic tumours and 93% of ampullary tumours. In the combined cohort high tumoural HHLA2 expression levels were significantly associated with delayed cancer recurrence and improved post-operative cancer-specific survival. The association of HHLA2 expression with cancer-specific survival and recurrence was statistically significant for the pancreatic cancer subgroup while a similar trend was found for the ampullary cancer subgroup. In multivariable analysis together with clinicopathologic characteristics, higher HHLA2 expression was an independent predictor of cancer-specific survival. Conclusion The wide expression of HHLA2 in tumour cells and its association with cancer recurrence and patient survival suggest that HHLA2 represents a relevant immune checkpoint molecule in pancreatic and ampullary cancers.

BACKGROUND The accuracy of the current staging system for predicting the overall survival (OS) of patients with ampullary carcinoma (AC) is still unsatisfactory, especially in node-negative (N0) patients. We aimed at establishing a nomogram to accurately predict OS in N0 AC. METHODS This study enrolled 697 N0 AC patients from the Surveillance, Epidemiology, and End Results database (design cohort [DC], n = 697) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 112), who underwent surgical resection. The nomogram was established by using prognostic factors determined by univariate and multivariate regression analyses. RESULTS The nomogram for OS was developed by using four independent prognostic factors, including age, grade, T stage, and a number of examined lymph nodes. The C-index of a nomogram for OS in DC and VC was 0.665 and 0.731, respectively. Calibration curves showed good consistency of the nomogram. The nomogram had a better accuracy in predicting OS compared with conventional staging system (P

Background/aim The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. Patients and methods Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. Results Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. Conclusion PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.

Aims: To demonstrate the prevalence, accompanying pathologies, imaging and follow up findings of Duodenal Diverticula (DD) with Multidetector Computed Tomography (MDCT). Materials and Methods: Consecutive 2910 abdominal MDCTs were retrospectively reviewed on axial, coronal and sagittal planes. DD were evaluated for prevalence, location, number, size, contents, diverticular neck, accompanying pancreaticobiliary pathologies, jejunal and colonic diverticula, respectively. Results: DD were diagnosed in 157 cases (5.4%) and found mostly in the second part of the duodenum. Juxta-ampullary DD was the most common type (78.3%) and mostly located ventral (n:86, 69.9%) to the ampulla of Vater. DD was solitary in 123 patients (78.3%) and more than one in 34 patients (21.7%). The median diameter of DD was 2.5 cm (range 1.5-3.6 cm) in the long-axis. The lumen of DD contains air and contrast agent (n:96, 61.1%); air, contrast agent and debris (n:42, 26.7%) in most cases. Colonic diverticula (n:36, 22.9%), cholelithiasis (n:32, 20.4%), choledocholithiasis (n:7, 4.4%), and biliary dilatation (n:8, 5.1%) were the most common additional findings. Median follow-up time was 23 months (range 11 to 41 months). In three cases, new findings (cholelithiasis, n:3, choledocholithiasis, n:1) were detected. Conclusion: Accompanying pathologies with DD diagnosis are valuable for physicians in order to manage the patients. Following clinical and radiological features of well-diagnosed DD might reduce the possible complications.

The role of adjuvant radiotherapy for resected ampullary carcinoma (AC) remains controversial. The aim of this study was to assess the effect of adjuvant radiotherapy on survival in patients who underwent resection for AC.The Surveillance, Epidemiology and End Results (SEER) database was used to identify patients diagnosed with AC from 2004 to 2012. Kaplan-Meier survival curve and multivariable Cox proportional hazards analyses were conducted to determine the effect of adjuvant radiotherapy on overall survival (OS) and disease-specific survival (DSS). Propensity score matching (PSM) method was used to balance the differences of clinicopathological characteristics between groups.A total of 1227 patients were included. Patients who received adjuvant radiotherapy were younger, had more advanced T stage and N stage tumors and were more likely to receive chemotherapy (p 0.001). Adjuvant radiotherapy failed to improve either OS (p = 0.119) or DSS (p = 0.188) in PSM cohorts. In subgroup analysis, no subgroup benefited from adjuvant radiotherapy and in patients older than 70 years, radiotherapy was associated with a worse OS and DSS.Patients with resected AC do not benefit from adjuvant radiotherapy.

BACKGROUND For periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes. AIM To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC. METHODS Between January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter. RESULTS In total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s). CONCLUSION Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

Trans-duodenal ampullectomy (TDA) is a surgical option for the treatment of selected ampullary neoplasms. The aim of this study was to evaluate our experience with TDA for the treatment of ampullary neoplasms, focusing on indications, technical aspects, and short- and long-term outcomes. All TDAs for ampullary neoplasms performed between January 2010 and December 2018 at our institution were retrospectively evaluated. Patients had ampullary neoplasms with low-grade dysplasia or in situ carcinoma (Tis) not suitable for an endoscopic approach, ampullary carcinoma unfit for pancreaticoduodenectomy (PD), or ampullary neuroendocrine G1-tumours. Thirty-six patients were included in the study: 9 (25.0%) with neoplasms with low-grade dysplasia, 4 (11.1%) with G1 neuroendocrine tumours and 23 (63.9%) with Tis or invasive carcinoma. Mean operative time was 252.5 min. Overall and severe (Clavien–Dindo > IIIa) morbidity rate was 44.4% and 13.9%, respectively. No 90-day mortality was observed. At follow-up, no deaths were observed and local recurrence rate was 11.1% for patients with ampullary adenomas with low-grade dysplasia. Among four patients with neuroendocrine neoplasms, only one developed recurrence (pulmonary). Tis, T1 and T2 lesions were found in 16 (69.6%), 2 (8.7%) and 5 (21.7%) patients, respectively: recurrence occurred in 3 patients with Tis lesions (one malignant), no patients with T1 neoplasms and 2 patients with T2 lesions (3 patients had a survival of > 3 years). TDA is a feasible and effective surgical procedure for the treatment of ampullary adenomas with low-grade dysplasia when endoscopic approach is contraindicated or has failed. For lesions with evidence of malignancy, TDA seems to be an oncological safe procedure for Tis ampullary cancer and a good palliative procedure for patients unfit for PD. Moreover, TDA may be appropriate for the treatment of G1 ampullary neuroendocrine neoplasms. A large multicentre study of TDA for early ampullary cancers is needed.