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Background: Ampulla of Vater carcinoma (AVC) stage T3 was subdivided according to the degree of pancreatic invasion into T3a (≤ 0.5 cm) and T3b (> 0.5 cm) by the 8th edition of the Union for International Cancer Control (UICC)/American Joint Committee on Cancer (AJCC) cancer staging system. However, the differences in clinicopathological features and survival outcomes between the two categories have not been well discussed., Patients and Methods: We retrospectively analyzed 133 consecutive patients who underwent pancreatoduodenectomy for AVC at our institution between 2002 and 2020. Clinicopathological features and survival outcomes of patients with AVC were analyzed, with a focus on the depth of pancreatic invasion. In addition, the survival outcomes of patients with T3 AVC were compared with those of patients with resectable pancreatic head carcinoma (R-PhC) who underwent pancreatoduodenectomy during the same period., Results: The overall survival (OS) in patients with T3b AVC (n = 12) was significantly worse than that in patients with T3a AVC (n = 39) [median survival time (MST) 9.2 vs. 74.5 months, p < 0.001). A multivariate analysis identified T3b tumor (hazard ratio 5.64, p = 0.009) as an independent prognostic factor. The OS of patients with T3a AVC was significantly better than that of patients with R-PhC who received adjuvant chemotherapy (n = 276, MST 35.0 months, p = 0.007). In contrast, the OS of patients with T3b AVC tended to be worse than that of patients with R-PhC managed without adjuvant chemotherapy, although this difference was not statistically significant (n = 163; MST, 17.5; p = 0.140)., Conclusions: AVC with > 0.5 cm invasion into the pancreas was associated with poor survival and represented advanced tumor progression to systemic disease., (© 2024. Society of Surgical Oncology.)

Background: Ampullary cancer is a relatively rare malignant tumor in the digestive system. Its incidence has increased in recent years. As for now, its biological characteristics have not been fully clarified. Recent studies have primarily focused on the histological classification and genetic changes, but there are fewer investigations into the differences among site-specific subgroups. The clinicopathological characteristics of ampullary cancer occurring in different positions have not been elucidated. Furthermore, the role of adjuvant therapy in the treatment of patients with ampullary cancer remains controversial., Aim: To study the clinicopathological features of the two site-specific subgroups of ampullary cancer and explore the factors affecting prognosis., Methods: A total of 356 patients who met the inclusion and exclusion criteria were enrolled. Patients were divided into ampulla of Vater cancer (AVC) and duodenal papilla cancer (DPC) based on the gross and microscopic findings. Baseline data, admission examination results, and perioperative outcomes were collected and analyzed. The Kaplan-Meier curve was used for survival analysis. Univariate and multivariate analysis was performed to explore the independent risk factors affecting the overall survival (OS) of both groups., Results: The preoperative total bilirubin level in patients with AVC was significantly higher than those with DPC ( P = 0.04). The OS for patients with DPC was 58.90 ± 38.74 months, significantly longer than 44.31 ± 35.90 months for patients with AVC ( P < 0.01). The independent risk factors affecting the OS of AVC included: Preoperative albumin level ( P = 0.009), total bilirubin level ( P = 0.017), and number of positive lymph nodes ( P = 0.005). For DPC, risk factors included: Age ( P = 0.004), tumor size ( P = 0.023), number of positive lymph nodes ( P = 0.010) and adjuvant treatment ( P = 0.020). Adjuvant therapy significantly improved the OS rate of patients with DPC, but not for those with AVC., Conclusion: Patients with AVC had a shorter OS compared to those with DPC. The prognosis factors and the role of adjuvant therapy of two groups were different., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Sarcopenia and sarcopenic obesity, perceived as a reflection of cancer-induced cachexia, are often diagnosed in patients with periampullary malignancies. The pathophysiology of those conditions is multifactorial regarding the tumor microenvironment, immunological response, and the relationship to surrounding tissues., Methods: The PubMed and SCOPUS databases were systematically searched between November 2023 and December 2023. A total of 254 studies were primarily identified. Regarding the inclusion and exclusion criteria, 26 studies were finally included in the review., Results: Evaluated papers disclosed that sarcopenia was significantly associated with a higher incidence of postoperative complications, including pancreatic fistula (POPF) type B and C, with the odds ratio (OR) ranging from 2.65 (95%CI 1.43-4.93, p = 0.002) to 4.30 (95%CI 1.15-16.01, p < 0.03). Sarcopenic patients also suffered more often from delayed gastric emptying (DGE) with an OR of 6.04 (95%CI 1.13-32.32, p = 0.036). Infectious complications, postoperative hemorrhage, and intra-abdominal abscesses occurred more often in sarcopenic patients. Surgical complications were also noted more frequently when sarcopenic obesity was present. Preoperative nutritional prehabilitation seems to reduce the risk of postoperative complications. However, more prospective studies are needed., Conclusions: Sarcopenia and sarcopenic obesity were associated with a higher incidence of multiple postoperative complications, including POPF (type B and C), DGE, hemorrhage, and infectious complications.

Background: The clinical significance of the lymph node ratio (LNR), the number of metastatic lymph nodes per dissected lymph node, has not been sufficiently clarified in ampullary cancer., Methods: Among patients diagnosed histopathologically with ampullary cancer between 1980 and 2018, the study included 106 who underwent pathological radical resection by pancreaticoduodenectomy. The relationships between the LNR and metastatic lymph node sites and prognosis were examined., Results: Multivariate analysis revealed that sex and lymph node metastasis were independent prognostic factors. In the 46 patients (43%) with metastatic lymph nodes, the LNR in the recurrence group was significantly higher than that in the non-recurrence group (0.15 ± 0.11 vs. 0.089 ± 0.071, p = 0.025). The receiver operating characteristic curve demonstrated that the LNR cut-off value, 0.07 (area under the curve = 0.70, sensitivity 81%, specificity 56%), was a significant indicator for recurrence (22% vs. 61%, p = 0.016) and prognosis (5-year survival: 48% vs. 83%, p = 0.028). Among the metastatic lymph node sites in the 46 positive cases, lymph node metastases developed from the peripancreatic head region (80%, 37/46) to the superior mesenteric artery (33%, 15/46) and para-aortic (11%, 5/46) regions., Conclusion: Lymph node metastasis is an independent prognostic factor, and the LNR is a significant indicator for recurrence and prognosis in patients with ampullary cancer., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The purpose of this investigation was to assess the prognostic importance of the combination of preoperative hemoglobin (Hb) levels and Geriatric Nutritional Risk Index (GNRI) in forecasting postoperative survival outcomes for patients undergoing pancreaticoduodenectomy (PD) due to Vater ampulla carcinoma (VPC)., Methods: The GNRI nutritional screening was conducted for all patients, and patient outcomes, including overall survival (OS), were subsequently monitored. An H- GNRI scoring system was established using the optimal critical values of 125.5 g/L for Hb and 91.72 for GNRI, as determined by X-tile software. According to the H-GNRI score, the patients were categorized into three groups, namely low H-GNRI group (H-GNRI score = 0, n = 47) with Hb < 125.5 g/L and GNRI < 91.72; medium H-GNRI group (H-GNRI score = 1, n = 77) with Hb < 125.5 g/L and GNRI ≥ 91.72, or Hb ≥ 125.5 g/L and GNR < 91.72; and high H-GNRI group (H-GNRI score = 2, n = 51) with Hb ≥ 125.5 g/L and GNRI ≥ 91.72. The Kaplan-Meier analysis and log-rank tests were employed to evaluate the OS rate and compare survival disparities among various groups. Additionally, both univariate and multivariate analyses were conducted utilizing the Cox regression model, with p < 0.05 considered statistically significant. Finally, to evaluate the predictive effectiveness of Hb, GNRI, and H-GNRI, a receiver operating characteristic (ROC) curve was constructed to compare the area under curve (AUC) values., Results: The OS rate was higher in patients with high Hb levels (≥ 125.5 g/L) compared to those with low Hb levels (< 125.5 g/L). Likewise, patients in the high GNRI group (≥ 91.72) exhibited significantly superior OS compared to those in the low GNRI group (< 91.72). Compared with both the medium and low H-GNRI groups, the high H-GNRI group demonstrated a notably higher OS rate. The T stage (HR = 2.523, 95% CI: 1.694-3.757, p < 0.001), N stage (HR = 2.018, 95% CI: 1.255-3.246, p = 0.004), and the H-GNRI score (H-GNRI score of 2 used as the baseline; H-GNRI score of 0: HR = 2.569, 95% CI: 1.499-4.402, p < 0.001; H-GNRI score of 1: HR = 1.835, 95% CI: 1.118-3.014, p = 0.016), after adjusting for gender, were determined to be independent significant predictors affecting the OS of patients with VPC. The AUC of H-GNRI was 0.677, exceeding that of Hb levels (0.631) and GNRI (0.615)., Conclusions: The combination of preoperative Hb levels and GNRI demonstrates superior predictive efficacy for VPC patients undergoing PD, compared with either Hb levels or GNRI score alone. Therefore, the H-GNRI score can be utilized to promptly identify high-risk patients, establish comprehensive nutritional pre-rehabilitation plans through interdisciplinary collaboration, and inform decisions regarding additional adjunctive therapies., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Surgery remains debatable in para-aortic lymph node (PALN, station 16b1) metastasis in non-pancreatic periampullary cancer (NPPAC). This study examined the impact of PALN metastasis on outcomes following pancreaticoduodenectomy (PD) in NPPAC., Methods: A retrospective analysis of patients with NPPAC who were explored for PD with PALN dissection was performed. Based on the extent of nodal involvement on final histopathology, they were stratified as node-negative (N0), regional node involved (N+) and metastatic PALN (N16+) and their outcomes were compared., Results: Between 2011 and 2022, 153/887 PD patients underwent a PALN dissection, revealing N16+ in 42 patients (27.4%), of whom 32 patients underwent resection. The 3-years overall survival (OS) for patients with N16+ was 28% (95% confidence interval [CI] 13-60%), notably lower than the 67% (95% CI 53-83.5%; p = 0.007) for those without PALN metastasis. Stratified by nodal involvement, the median OS for N+ and N16+ patients was similar (28.4 months and 26.2 months, respectively). The N0 subgroup had a significantly longer 3-years OS of 87.5% (95% CI 79-96.7%; p = 0.0051). Interestingly, 10 patients not offered resection following N16+ identified on frozen section had a median survival of only 9 months. The perioperative morbidity and mortality in patients undergoing PD with PALN dissection were similar to standard resections., Conclusion: In a select group of patients with NPPAC, PD in isolated PALN metastasis was associated with improved OS. The survival in this group of patients was comparable with regional node-positive patients and significantly better than palliative treatment alone., (© 2024. The Author(s).)

Background: The role of adjuvant therapy in resected periampullary adenocarcinomas is equivocal due to contrasting data and limited prospective trials., Methods: The Multicentre Indian Pancreatic & Periampullary Adenocarcinoma Project (MIPPAP), included data from 8 institutions across India. Of the 1679 pancreatic resections, 736 patients with T3/T4 and/or Node positive adenocarcinomas (considered as high risk for recurrence) were included for analysis. Three (adjuvant): one (observation) matching, using T3/T4 T staging, nodal positivity and ampullary subtype was performed by using the nearest neighbour matching method., Results: Of 736 patients eligible for inclusion, 621 patients were matched of which 458 patients received adjuvant therapy (AT) (predominantly gemcitabine-based) and 163 patients were observed (O). With a median follow-up of 42 months, there was a statistical difference in overall survival in favour of patients receiving AT as compared to those on observation [68.7 months vs. 61.1 months, Hazard ratio: 0.73 (95% CI: 0.54-0.97); p = 0.03]. Besides AT, presence of nodal involvement (median OS: 65.4 months vs not reached; p = 0.04) predicted for inferior OS., Conclusions: The results of the match-pair analysis suggest that adjuvant therapy improves overall survival in periampullary adenocarcinomas at high risk of recurrence with a greater benefit in T3/T4, node-positive and ampullary subtypes., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: To predict tumor recurrence in patients who underwent surgical resection of ampullary adenocarcinoma using preoperative magnetic resonance (MR) imaging findings combined with clinical findings., Methods: In this multicenter study, a total of 113 patients (mean age, 62.9 ± 9.8 years; 58 men and 55 women) with ampullary adenocarcinoma who underwent preoperative MR imaging and surgery with margin-negative resection between 2006 and 2017 were retrospectively included. The MR imaging findings were evaluated by two radiologists. Preoperative clinical findings were obtained. Cox proportional regression analyses were used to identify the independent prognostic factors for recurrence-free survival (RFS). A nomogram was created based on the multivariable analysis and was internally validated., Results: Multivariable analysis revealed that presence of infiltrative tumor margin (hazard ratio [HR]: 2.18, p = 0.019), adjacent organ invasion (HR: 3.31, p = 0.006), adjacent vessel invasion (HR: 5.42, p = 0.041), peripancreatic lymph node enlargement (HR: 2.1, p = 0.019), and jaundice (HR: 1.93, p = 0.043) were significantly associated with worse RFS of ampullary adenocarcinoma after surgical resection. These MR imaging and clinical findings were used to construct a nomogram. On internal validation, the calibration plots showed excellent agreement between the predicted probabilities and the actual rates of tumor recurrence, with Harrell's c-index of 0.746., Conclusions: Combination of preoperative MR imaging and clinical findings can be useful for predicting tumor recurrence after surgical resection of ampullary adenocarcinoma. Identifying these features before surgery may aid in better treatment planning and management of these patients., Clinical Relevance Statement: A predictive nomogram using preoperative MR imaging and clinical findings can be useful in estimating the recurrence-free survival after surgical resection of ampullary adenocarcinoma., Key Points: • Presently, tumor size on imaging is the only non-invasive factor that correlates with recurrence-free survival from ampullary adenocarcinoma; other factors are obtained postoperatively. • Infiltrative tumor margin, adjacent organ invasion, adjacent vessel invasion, peripancreatic lymph node enlargement on MRI, and jaundice are significant predictors for recurrence. • A nomogram incorporating significant MR imaging and clinical findings showed good performance in predicting recurrence-free survival, which can help in treatment planning., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: Endoscopic papillectomy (EP) is recommended as the first-line therapy for ampullary tumors, despite a relatively high incidence of complications. Pancreatic and/or biliary stents are placed at the endoscopist's discretion to prevent post-EP complications. The present study aimed to evaluate the efficacy of different stents., Methods: A total of 117 patients who underwent EP and met the criteria between June 2006 and October 2022 were enrolled in the study. These patients were divided into a pancreatic stent group (PS group, n = 47), a biliary stent group (BS group, n = 38), and a two-stent group (PBS [PS and BS] group, n = 32). Relevant clinical data were collected and compared among the three groups. Multivariate logistic analyses were performed to explore risk factors for post-EP complications., Results: The incidence of all complications was 37.6% (44/117). Pancreatitis and hemorrhage were the two most common complications with incidence rates of 14.5% (17/117) and 17.9% (21/117). The incidence rates of post-EP pancreatitis were 10.6% (5/47), 23.7% (9/38), and 9.4% (3/32) in the PS group, BS group, and PBS group, respectively, with no significant differences. There were also no significant differences in other complications among the three groups. Age (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.91-0.99; P = 0.022) was independently associated with post-EP pancreatitis while tumor size (OR: 1.66; 95% CI: 1.06-2.60; P = 0.028) was independently associated with post-EP hemorrhage., Conclusions: While pancreatic stenting is the first choice to prevent post-EP pancreatitis, biliary stenting could also be considered as a substitute for patients with difficulties in pancreatic cannulation. Two-stent (biliary and pancreatic stent) placement is unnecessary unless it is required due to other concerns., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Periampullary cancers have a short overall survival (OS), and many prognostic factors have been studied for this purpose. They usually present with biliary obstruction, which negatively affects the liver, kidney, immune system, and cardiovascular system. This study aimed to investigate the effect of MELD-Na scores on OS in patients undergoing pancreaticoduodenectomy due to periampullary cancer. Patients who underwent pancreaticoduodenectomy due to periampullary cancer between January 2010 and January 2021 were included in the study. After applying the exclusion criteria, 80 of the 124 patients were included in the study. The demographic, laboratory, and pathologic data of the patients were analyzed retrospectively. Univariate analysis showed that MELD-Na score at admission, age-adjusted Charlson Comorbidity Index, adjuvant treatment, portal vein resection, lymphovascular invasion (LVI), T-stage, and tumor location were significantly associated with OS (p < 0.1). In multivariate analysis, MELD-Na score at admission (HR: 1.051, 95% CI [1.004-1.101]; p = 0.033), adjuvant treatment (HR: 4.717, 95% CI [2.371-9.383]; p < 0.001), LVI (HR: 2.473, 95% CI [1.355-4.515]; p = 0.003), and tumor location (HR: 2.380, 95% CI [1.274-4.445]; p = 0.007) were independent risk factors for OS. MELD-Na score, adjuvant treatment, LVI, and tumor location were independent risk factors for the OS of periampullary cancer. The MELD-Na score may be used to predict OS for patients undergoing pancreaticoduodenectomy due to periampullary cancer., (© 2024. The Author(s).)

Background: The optima preoperative biliary drainage before pancreaticoduodenectomy in patients with biliary tract and pancreatic cancer remains controversial., Methods: A total of 898 patients who underwent preoperative biliary drainage via endoscopic retrograde biliary drainage, endoscopic transnasal biliary drainage, or percutaneous transhepatic biliary drainage before pancreaticoduodenectomy for biliary tract and pancreatic cancer were included. Perioperative and long-term outcomes were analyzed., Results: The Clavien-Dindo grade ≥3 morbidity rates after pancreaticoduodenectomy were higher in the endoscopic retrograde biliary drainage (21.9%; P = .001) or endoscopic transnasal biliary drainage (20.2%; P = .007) than in the percutaneous transhepatic biliary drainage (9.7%) groups. In biliary tract cancer, the frequency of dissemination after pancreaticoduodenectomy was higher in the percutaneous transhepatic biliary drainage (15.3%) than in the endoscopic retrograde biliary drainage (0.7%; P = .001) and endoscopic transnasal biliary drainage (4.1%; P = .037) groups; percutaneous transhepatic biliary drainage was an independent factor associated with worse disease-free survival (P = .04), whereas in pancreatic cancer the frequency of dissemination and survival was comparable among the 3 preoperative biliary drainage methods. Albumin <3.9 g/dL was independently associated with worse overall survival in patients with both pancreatic (P = .038) and biliary tract (P = .002) cancers, respectively. During biliary drainage, external drainage (P = .038) was independently associated with albumin <3.9 g/dL; albumin was higher in endoscopic retrograde biliary drainage group than in endoscopic transnasal biliary drainage or percutaneous transhepatic biliary drainage groups after 21 days from tube insertion., Conclusion: In biliary tract cancer, percutaneous transhepatic biliary drainage may carry the risk of increasing the incidence of disseminative recurrence. In pancreatic cancer, percutaneous transhepatic biliary drainage is preferable owing to fewer complications without influencing recurrence. However, if patients cannot undergo surgery immediately, endoscopic retrograde biliary drainage will be applicable to help the preservation of nutritional status, which can have an impact on survival., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Pancreatoduodenectomy is the only cure for cancers of the pancreas and the periampullary region but has considerable operative complications and uncertain prognosis. Our goal was to analyse temporal improvements and provide contemporary population-based benchmarks for outcomes following pancreatoduodenectomy., Methods: We empanelled a cohort comprising all patients in Sweden with pancreatic or periampullary cancer treated with pancreatoduodenectomy from 1964 to 2016 and achieved complete follow-up through 2016. We analysed postoperative deaths and disease-specific net survival., Results: We analysed 5923 patients with cancer of the pancreas (3876), duodenum (444), bile duct (504), or duodenal papilla (963) who underwent classic (3332) or modified (1652) Whipple's procedure or total pancreatectomy (803). Postoperative deaths declined from 17.2% in the 1960s to 1.6% in the contemporary time period (2010-2016). For all four cancer types, median, 1-year and 5-year survival improved substantially over time. Among patients operated between 2010 and 2016, 5-year survival was 29.0% (95% confidence interval (CI): 25.5, 33.0) for pancreatic cancer, 71.2% (95% CI: 62.9, 80.5) for duodenal cancer, 30.8% (95% CI: 23.0, 41.3) for bile duct cancer, and 62.7% (95% CI: 55.5, 70.8) for duodenal papilla cancer., Conclusion: There is a continuous and substantial improvement in the benefit-harm ratio after pancreatoduodenectomy for cancer., (© 2024. The Author(s).)

Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior., Methods: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC., Results: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P  =  0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size., Conclusions: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies., (© 2024. Society of Surgical Oncology.)

The guidelines recently recognized the intra-ampullary papillary tubular neoplasm (IAPN) as a distinct tumor entity. However, the data on IAPN and its distinction from other ampullary tumors remain limited. A detailed clinicopathologic analysis of 72 previously unpublished IAPNs was performed. The patients were: male/female=1.8; mean age=67 years (range: 42 to 86 y); mean size=2.3 cm. Gross-microscopic correlation was crucial. From the duodenal perspective, the ampulla was typically raised symmetrically, with a patulous orifice, and was otherwise covered by stretched normal duodenal mucosa. However, in 6 cases, the protrusion of the intra-ampullary tumor to the duodenal surface gave the impression of an "ampullary-duodenal tumor," with the accurate diagnosis of IAPN established only by microscopic correlation illustrating the abrupt ending of the lesion at the edge of the ampulla. Microscopically, the preinvasive component often revealed mixed phenotypes (44.4% predominantly nonintestinal). The invasion was common (94%), typically small (mean=1.2 cm), primarily pancreatobiliary-type (75%), and showed aggressive features (lymphovascular invasion in 66%, perineural invasion in 41%, high budding in 30%). In 6 cases, the preinvasive component was pure intestinal, but the invasive component was pancreatobiliary. LN metastasis was identified in 42% (32% in those with ≤1 cm invasion). The prognosis was significantly better than ampullary-ductal carcinomas (median: 69 vs. 41 months; 3-year: 68% vs. 55%; and 5-year: 51% vs. 35%, P =0.047). In conclusion, unlike ampullary-duodenal carcinomas, IAPNs are often (44.4%) predominantly nonintestinal and commonly (94%) invasive, displaying aggressive features and LN metastasis even when minimally invasive, all of which render them less amenable to ampullectomy. However, their prognosis is still better than that of the "ampullary-ductal" carcinomas, with which IAPNs are currently grouped in CAP protocols (while IAPNs are kindreds of intraductal tumors of the pancreatobiliary tract, the latter represents the ampullary counterpart of pancreatic adenocarcinoma/cholangiocarcinoma)., Competing Interests: Conflicts of Interest and Source of Funding: O.B. has been supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. For the remaining authors none were declared., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To define the role of adjuvant therapy in duodenal adenocarcinoma (DAC) and intestinal subtype ampullary carcinoma (iAC)., Background: DAC and iAC share a similar histologic differentiation but the benefit of adjuvant therapy remains unclear., Methods: Patients undergoing curative intent surgical resection for DAC and iAC between 2010 and 2021 at 5 high-volume centers were included. Patient baseline, perioperative, and long-term oncological outcomes were evaluated. Statistical testing was performed with SPSS 25 (IBM)., Results: A total of 136 patients with DAC and 171 with iAC were identified. Patients with DAC had more advanced tumors than those with iAC. Median overall survival (OS) in patients with DAC was 101 months versus 155 months for patients with iAC ( P = 0.098). DAC had a higher rate of local (14.1% vs 1.2%, P < 0.001) and systemic recurrence (30.4% vs 3.5%, P < 0.001). Adjuvant therapy failed to improve OS in all patients with DAC and iAC. For DAC, patients with perineural invasion, but not other negative prognostic factors, had improved OS rates with adjuvant therapy (72 vs 44 m, P = 0.044). Patients with iAC with N+ (190 vs 57 m, P = 0.003), T3-T4 (177 vs 59 m, P = 0.050), and perineural invasion (150 vs 59 m, P = 0.019) had improved OS rates with adjuvant therapy., Conclusions: While adjuvant therapy fails to improve OS in all patients with DAC and iAC in the current study, it improved OS in patients with DAC with perineural invasion and in patients with iAC with T3-T4 tumors, positive lymph nodes, and perineural invasion., Competing Interests: L.B. received a grant from the German Research Foundation (DFG): BO 5659. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Background: Lymph node (LN) metastasis is an established prognostic factor for patients with surgically resected ampulla of Vater (AoV) cancer. The standard procedure for radical resection, including removal of regional LNs, is pancreaticoduodenectomy (PD); however, local excision has been considered as an alternative option for patients in the early stage cancer with significant comorbidities. In the present study, we elucidated the preoperative factors associated with LN metastasis to determine the appropriate surgical extent for T1 AoV cancer., Methods: We included patients who underwent surgery for T1 AoV cancer at Samsung Medical Center and Severance Hospital between 2000 and 2019. Risk factors were analyzed to identify the preoperative parameters associated with LN metastasis or regional LN recurrence during follow-up. Finally, using the identified risk factors, a prediction model was constructed., Results: Among 342 patients, 311 patients underwent PD, whereas 31 patients underwent transduodenal ampullectomy. Fourty-eight patients had LN metastasis according to pathology report, and two patients presented with regional LN recurrence. Age, carbohydrate antigen 19 - 9 (CA 19 - 9), and tumor differentiation were identified as factors associated with the increased risk of LN metastasis or regional LN recurrence. The area under the curve of the prediction model with these three factors was 0.728., Conclusion: Our newly developed prediction model using age, CA 19 - 9, and tumor differentiation can help select patients who require PD over local excision. Nevertheless, additional in-depth analysis is warranted to select appropriate surgical extent for patients with presumed T1 AoV cancer., (© 2024. The Author(s).)

Background: Recently, endoscopic ultrasound-guided (EUS) gastrojejunostomy (GJ) has emerged as an alternative option to surgical palliation and endoscopic duodenal stenting for malignant gastric outlet obstruction (GOO). Although early success rates are commonly reported with the technique, there is a paucity of data regarding the long-term efficacy of this approach. In this study, we investigated long-term outcomes in patients that underwent EUS-guided GJ for palliation of periampullary malignancies., Methods: From a total of 192 studies that were reviewed, 6 studies with a follow-up time frame of a minimum of 5 months were analyzed, totaling 238 patients. Outcome variables included technical success rate, clinical success rate, adverse events, symptom recurrence, and re-intervention rates., Results: The cohort of 238 patients had a technical success rate of 93.7% and a clinical success rate of 92.9%. A total of 25 patients (10.5%) experienced adverse events associated with EUS-GJ. A total of 14 patients (5.9%) experienced recurrence of GOO symptoms within 5 months. A total of 14 patients (5.9%) underwent re-intervention with the first 5 months., Conclusions: This systematic review shows that data are scarce regarding long-term effectiveness of EUS-guided GJ. Even though early success rates have been reported, further studies are needed to focus on long-term efficacy of this approach. Until such studies become available, surgical palliation should continue to be the treatment of choice for patients with malignant GOO with a prolonged life expectancy., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Disclosure All authors disclosed no financial relationships. Commentary In this case, authors describe a successful endoscopic papillectomy for the management of ampullary neuroendocrine tumor (NET). Duodenal NETs are uncommon. with a prevalence of 2.6% of all NETs. Ampullary NETs are exceedingly rare, with a <0.3% incidence of all GI NETs. Ampullary NET has an aggressive nature by default, with a higher tendency for metastasis regardless of tumor size. As such, it is essential to thoroughly assess patients with ampullary NETs for local and distant metastasis before endoscopic resection. Patients with ampullary NETs that are well differentiated and low grade, without involvement of the pancreatic or bile duct, and without peritoneal lymphadenopathy or distant metastasis, are ideal candidates for endoscopic resection. Although endoscopic papillectomy is an excellent alternative for pancreaticoduodenectomy, it is associated with a higher risk of pancreatitis. The risk of postprocedure pancreatitis is substantial, ranging between 6% and 58% in published reports. This risk can be potentially decreased with prophylactic placement of biliary and pancreatic stents. In consideration of the aggressive naure of these tumors, close surveillance after resection with serial endoscopy and radiologic imaging is recommended. Tara Keihanian, MD, MPH, Assistant Professor, Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA. Amy Tyberg, MD, FASGE, FACG, Associate Editor for Focal Points

Transduodenal Ampullectomy (TA) is a procedure for resecting low-malignancy ampullary tumors, with postoperative fistula as a notable complication. This study aims to clarify the indications for TA, outline the surgical robotic technique, and emphasize the importance of comprehensive complication management alongside the surgical approach. This multimedia article provides a detailed exposition of the robotic TA surgical technique, including the most important steps involved in exposing and reimplanting biliary and pancreatic ducts. The procedure encompasses the mobilization of the hepatic flexure of the colon, an extensive Kocher maneuver for duodenal mobilization, and ampulla exposure through a duodenal incision. Employing retraction loop sutures enhances surgical field visibility. Reconstruction involves securing pancreatic and biliary ducts to the duodenal mucosa, each tutored with a silicon catheter, and suturing for ampullectomy completion. The total operative time was 380 min. Final histopathology disclosed high-grade dysplasia with an isolated focus of adenocarcinoma (pT1), accompanied by clear resection margins. A postoperative duodenal fistula occurred, managed successfully through conservative treatment, utilizing subcutaneous drainage. Despite accurate robotic TA execution, complications may arise. This study underscores the importance of a comprehensive approach, incorporating meticulous surgical technique and effective complication management, to optimize patient outcomes., (© 2024. Italian Society of Surgery (SIC).)

Purpose: Transduodenal surgical ampullectomy (tAMP) with papillary reimplantation is a valid alternative to pancreaticoduodenectomy for lesions of the periampullary region not amenable to endoscopic resection. As tAMP is burdened by high rates of biliopancreatic-enteric anastomotic leak, we tested preventive endoluminal vacuum therapy (eVAC) combined with post-operative continuous perianastomotic irrigation (CPI) to reduce such anastomotic leak., Methods: Between 10/2013 and 09/2023, 37 patients undergoing laparotomic tAMP (with or without jejunal transposition) and papillary reimplantation at Hirslanden Klinik Zurich were retrospectively analysed; of these, 16 received prophylactic eVAC combined with CPI, while the remaining represented the historical cohort., Results: The eVAC-CPI-group and the historical-cohort were homogeneous in demographic characteristics. Surgery in the prophylactic eVAC-CPI-group lasted about 30 min longer due to eVAC application (p = 0.008). The biliopancreatico-enteric anastomotic leak rates were 6.2% in the eVAC-CIP-group vs. 19.0% in the historical-cohort (p = 0.266). Along, a strong trend of less severe post-operative complications in general (p = 0.073), and borderline-significantly less cases of acute pancreatitis (p = 0.057) and tAMP-related re-operations or re-interventions (p = 0.057) in particular, were observed in the eVAC-CPI-group. The only anastomotic leak in the eVAC-CPI-group was successfully managed through repeated cycles of eVAC. The device was well tolerated by all patients; no vacuum/irrigation-related complications or malfunctioning occurred., Conclusion: Our study is the first to provide some technical insights demonstrating the safety and feasibility of a prophylactic approach with eVAC and perianastomotic irrigation to reduce anastomotic leak after tAMP. Increasing the number of subjects will confirm the benefit of our promising results., (© 2024. The Author(s).)

Background/aims: : Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the long-term outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes., Methods: : This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean follow-up duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis., Results: : Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021)., Conclusions: : Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Introduction: Ampulla of Vater carcinoma (AVC) with para-aortic node (PAN) metastasis is considered unresectable and is equivalent to distant metastasis, contributing to poor outcomes., Case Presentation: A 60-year-old man was referred to our hospital and was diagnosed with an unresectable ampulla of Vater carcinoma that had metastasized to the para-aortic nodes. The patient received a systemic chemotherapy regimen comprising a combination of gemcitabine and cisplatin. Following five cycles of treatment, imaging studies revealed a significant reduction in the primary tumor and para-aortic node metastasis, rendering detection difficult. Pancreatoduodenectomy with para-aortic node dissection was performed as a radical surgery. Upon pathological examination, no residual tumors were identified in the resected specimen, indicating that the systemic chemotherapy achieved a complete pathological response. The postoperative course of the patient was uneventful, and he was discharged on the 25th postoperative day. The patient was followed up as an outpatient and remained stable without any recurrence for two months after surgery., Conclusion: Neoadjuvant chemotherapy with gemcitabine and cisplatin was useful for downstaging the ampulla in patients with Vater carcinoma. This finding may help physicians manage patients with similar presentations.

Introduction: Studies comparing laparoscopic pancreaticoduodenectomy (LPD) with open pancreaticoduodenectomy (OPD) for ampullary carcinoma (AC) are limited. This study aimed to compare short- and long-term outcomes between LPD and OPD for AC., Methods: This study included patients with AC who underwent pancreaticoduodenectomy (PD) with curative intention at Ogaki Municipal Hospital from April 2008 to March 2023., Results: Fifty-five patients underwent LPD (n = 26) or OPD (n = 29). There were no significant differences in the demographics between the two groups. The LPD group had a significantly longer operative time (268 vs. 225 min), less blood loss (125 vs. 450 mL), and shorter postoperative hospital stay (18 vs. 23 days) than the OPD group. There was no significant difference in the morbidity ratio. Fewer lymph nodes were harvested in the LPD group than OPD group (9.5 vs. 16.0), but there were no significant differences in lymph node metastasis or pathological stages. There were no significant differences in overall survival (OS) or recurrence-free survival (RFS). The 3- and 5-year OS rates in the LPD group and the OPD group were 63.0% and 54%, 64.8%, and 61.2%, respectively. The 3- and 5-year RFS rates were 57.4% and 57.4%, 58.1%, and 54.4%, respectively., Conclusions: LPD for AC had short- and long-term outcomes comparable with those of OPD. LPD could be considered the standard treatments for AC because of less blood loss and a shorter hospital stay., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Endoscopic papillectomy (EP) is less invasive than surgery but procedure-related adverse events (AEs) still frequently occur. This study compared the benefits of EP using a new optimal endoCUT setting on the VIO (Erbe) electrosurgical unit (VIO-EP) with those using the conventional electrosurgical unit setting (ICC-EP, Erbe)., Methods: This multicenter, retrospective, comparative cohort study included 57 patients who underwent VIO-EP and 91 who underwent ICC-EP. The primary outcome was occurrence of EP-related AEs. Secondary outcomes were pathological findings (the resection margins, the R0 resection, and residual lesions)., Results: Pancreatitis tended to be less common in the VIO-EP group (5.3% vs. 9.9%, p = .248). Evaluation of computed tomography images showed that pancreatitis was confined to the pancreatic head in 77.8% of cases in the ICC-EP group and in 33.3% of those in the VIO-EP group. After exclusion of cases of delayed bleeding, pancreatitis tended to be less common in the VIO-EP group; this finding was not statistically significant (2.3% vs. 8.2%, p = .184). In pathological findings, residual lesions were significantly less common in the VIO-EP group., Conclusions: The risks of pancreatitis and residual lesions after EP may be lower when the VIO electrosurgical unit is used with the optimal setting., (© 2024 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

Background: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB., Patients and Methods: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS)., Results: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively)., Discussion: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Competing Interests: Declaration of competing interest There are no conflicts of interest among the authors.

Background: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment., Methods: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC., Results: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015)., Conclusion: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC., (© 2024. The Author(s).)

Objectives: Endoscopic papillectomy (EP) is a minimally invasive therapy for the management of ampullary adenomas (AA). We conducted this multicenter study to assess the incidence of and factors related to the recurrence of AA after EP in patients with familial adenomatous polyposis (FAP) compared to sporadic AA., Methods: We included patients who underwent EP for AA at 10 tertiary hospitals. Adenomatous tissue at the resection site at the time of surveillance endoscopies was considered recurrent disease., Results: In all, 257 patients, 100 (38.9%) with FAP and 157 (61%) patients with sporadic AA, were included. Over a median of 31 (range, 11-61) months, recurrence occurred in 48/100 (48%) of patients with FAP and 58/157 (36.9%) with sporadic AA (P = 0.07). Two (2%) FAP patients and 10 (6.3%) patients with sporadic AA underwent surgery for recurrence. On multivariable regression analysis, the recurrence in FAP was higher than in sporadic patients after the first year of follow-up. AA size (hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.001, 1.056), periampullary extension (HR 2.5, 95% CI 1.5, 4.01), and biliary duct dilation (HR 2.04, 95% CI 1.2, 3.4) increased the risk, while en bloc resection (HR 0.6, 95% CI 0.41, 0.9) decreased the risk of recurrence., Conclusion: Recurrence rates are high after EP. Most recurrences in sporadic patients occur within the first year of follow-up, but after the first year of follow-up in patients with FAP. Recurrences are higher with larger adenomas, biliary duct dilation, and periampullary extensions, and may be mitigated by en bloc resection. These factors should be considered in decision-making with the patients., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Competing Interests: Conflict of interest None.

Background: Communication between caregivers and clinical team members is critical for transitional care, but its quality and potential impact on outcomes are not well understood. This study reports on caregiver-reported quality of communication with clinical team members in the postpancreatectomy period and examines associations of these reports with patient and caregiver outcomes., Methods: Caregivers of patients with pancreatic and periampullary malignancies who had undergone pancreatectomy were surveyed. Instrument measures assessed care experiences using the Caregiver Perceptions About Communication with Clinical Team Members (CAPACITY) instrument. The instrument has two main subscales: communication, assessing the extent to which providers helped caregivers comprehend details of clinical visits, and capacity, defined as the extent to which providers assessed whether caregivers were able to care for patients., Results: Of 265 caregivers who were approached, 240 (90.6%) enrolled in the study. The mean communication and capacity subscale scores were 2.7 ± 0.6 and 1.5 ± 0.6, respectively (range, 0-4 [higher = better]). Communication subscale scores were lower among caregivers of patients who experienced (vs. those who did not experience) a 30-day readmission (2.6 ± 0.5 vs. 2.8 ± 0.6, respectively; p = .047). Capacity subscale scores were inversely associated with restriction in patient daily activities (a 0.04 decrement in the capacity score for every 1 point in daily activity restriction; p = .008)., Conclusions: After pancreatectomy, patients with pancreatic and periampullary cancer whose caregivers reported worse communication with care providers were more likely to experience readmission. Caregivers of patients with greater daily activity restrictions were less likely to report being asked about the caregiver's skill and capacity by clinicians., Plain Language Summary: This prospective study used a validated survey instrument and reports on the quality of communication between health care providers and caregivers as reported by caregivers of patients with pancreatic and periampullary cancer after pancreatectomy. In an analysis of 240 caregivers enrolled in the study, lower communication scores (the extent to which providers helped caregivers understand clinical details) were associated with higher odds of 30-day patient readmission to the hospital. In addition, lower capacity scores (the extent to which providers assessed caregivers' ability to care for patients) were associated with greater impairment in caregivers. The strikingly low communication quality and capacity assessment scores suggest substantial room for improvement, with the potential to improve both caregiver and patient outcomes., (© 2023 American Cancer Society.)

Background and Objectives: In ampullary cancer, 5-year survival rates are 30-50%, even with optimal resection and perioperative systemic therapies. We sought to determine the important clinicopathological features and adjuvant treatments in terms of the prognosis of patients with operable-stage ampullary carcinomas. Materials and Methods: We included 197 patients who underwent pancreaticoduodenectomy to treat ampullary carcinomas between December 2003 and May 2019. Demographics, clinical features, treatments, and outcomes/survival were analyzed. Results: The median disease-free survival (mDFS) and median overall survival (mOS) were 40.9 vs. 63.4 months, respectively. The mDFS was significantly lower in patients with lymphovascular invasion ( p < 0.001) and lymph node involvement ( p = 0.027). Potential predictors of decreased OS on univariate analysis included age ≥ 50 years ( p = 0.045), poor performance status ( p = 0.048), weight loss ( p = 0.045), T3-T4 tumors ( p = 0.018), surgical margin positivity ( p = 0.01), lymph node involvement ( p = 0.001), lymphovascular invasion ( p < 0.001), perineural invasion ( p = 0.007), and poor histological grade ( p = 0.042). For the multivariate analysis, only nodal status (hazard ratio [HR]1.98; 95% confidence interval [CI], 1.08-3.65; p = 0.027) and surgical margin status (HR 2.61; 95% CI, 1.09-6.24; p = 0.03) were associated with OS. Conclusions: Nodal status and a positive surgical margin were independent predictors of a poor mOS for patients with ampullary carcinomas. Additional studies are required to explore the role of adjuvant therapy in patients with ampullary carcinomas.

Periampullary cancers, including pancreatic ductal adenocarcinoma, ampullary-, cholangio-, and duodenal carcinoma, are frequently diagnosed in an advanced stage and are associated with poor overall survival. They are difficult to differentiate from each other and challenging to distinguish from benign periampullary disease preoperatively. To improve the preoperative diagnostics of periampullary neoplasms, clinical or biological markers are warranted.In this study, 28 blood plasma amino acids and derivatives from preoperative patients with benign (N = 45) and malignant (N = 72) periampullary disease were analyzed by LC-MS/MS.Principal component analysis and consensus clustering both separated the patients with cancer and the patients with benign disease. Glutamic acid had significantly higher plasma expression and 15 other metabolites significantly lower plasma expression in patients with malignant disease compared with patients having benign disease. Phenylalanine was the only metabolite associated with improved overall survival (HR = 0.50, CI 0.30-0.83, P < 0.01).Taken together, plasma metabolite profiles from patients with malignant and benign periampullary disease were significantly different and have the potential to distinguish malignant from benign disease preoperatively., (© 2024. The Author(s).)

Background: The value of the textbook outcome in pancreatic surgery (TOPS) score, a composite measure of surgical performance for quality assurance, was evaluated in a South African tertiary hospital cohort of pancreaticoduodenectomies (PD) performed for adenocarcinoma of the ampulla of Vater (AAV)., Methods: A review of all patients undergoing a PD for AAV at a single centre between January 1999 and December 2023 was performed. Demographic, operative, pathological and postoperative variables were recorded. Ten clinical and histological variables were used to construct a TOPS score. These included an R0 resection, no postoperative pancreatic fistula (POPF), no bile leak, no post-pancreatectomy haemorrhage, no delayed gastric emptying, no major postoperative complications (< Gr 3 Clavien-Dindo), no readmission to ICU, length of stay ≤ 10 days, no 30-day readmission or intervention and no 30-day mortality. A textbook outcome (TO) was defined as the fulfilment of all 10 variables. In patients in whom TO was not achieved, the reasons for failure were identified. In addition, the number of patients who had major complications and died were categorised as failure to rescue (FTR)., Results: A positive TOPS score was achieved in 27 of 79 (34.2%) patients undergoing a PD. Overall five-year survival after PD was 33.9%. TOPS conferred a significant 1-year survival benefit, 88.9% vs 66.7% (OR 4.12, 95% CI 1.08-15.67, p = 0.038). There was no significant difference in 5-year survival between TOPS and non-TOPS patients, 40.0% vs 32.4% (OR 1.39, 95% CI 0.48-3.99, p = 0.54). A POPF occurred in 31.6% patients, resulting in a significantly longer hospital admission, 17 vs 10 days (95% CI 2.66-11.34, p = 0.0019). Twenty-one (26.6%) patients developed a major complication, five of whom died (FTR = 6.3%)., Conclusion: This study confirmed the value of TOPS as a useful measurement to assess hospital quality metrics and short-term survival after PD for AAV. One quarter of patients developed a major complication with a 6.3% FTR., (Copyright© Authors.)

Objectives: Unresectable ampullary cancer (AC) is a rare disease entity. The risk factors for recurrent biliary obstruction (RBO) following endoscopic biliary stenting (EBS) for unresectable AC remain unknown. In this study we aimed to evaluate the cumulative RBO rate and to identify risk factors for RBO following palliative EBS in patients with unresectable AC., Methods: This multicenter retrospective observational study enrolled consecutive patients with unresectable AC who had undergone palliative EBS between April 2011 and December 2021. The cumulative rate of and risk factors for RBO following palliative EBS were evaluated via multivariate analysis., Results: The study analysis comprised 107 patients with a median age of 84 years (interquartile range 79-88 years). Plastic stents (PSs) and self-expandable metal stents (SEMSs) were placed in 53 and 54 patients, respectively. Functional success was accomplished in 104 (97.2%) patients. Of these, RBO occurred in 62 (59.6%) patients, with obstruction and complete/partial migration occurring in 47 and 15 patients, respectively. The median time to RBO was 190 days. Multivariate analysis showed that PS was associated with a higher rate of RBO compared to SEMS (hazard ratio [HR] 2.48; P < 0.01) and that the presence of common bile duct stones/sludge immediately after EBS was an independent risk factor for RBO (HR 1.99; P = 0.04)., Conclusions: The use of SEMS compared to PS during EBS reduced the time to RBO in patients with unresectable AC. Common bile duct stones/sludge immediately after EBS was a risk factor for RBO., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Neuroendocrine tumors (NETs) of the ampulla of Vater are rare. Therefore, there is a lack of comprehensive information regarding their pathogenesis. We herein present the case of a patient with a 5-mm ampullary NET who demonstrated the presence of lymphatic invasion after undergoing endoscopic papillectomy. A 44-year-old woman was referred to our hospital for treatment of a grade 1 NET in the ampulla of Vater. Endoscopic ultrasonography revealed a hypoechoic mass within the submucosal layer without obvious infiltration into the common bile duct or the main pancreatic duct. We performed underwater endoscopic papillectomy (UEP) to remove the tumor with a negative margin. Pathological evaluation of the resected specimen showed a grade 1 NET with a negative margin. However, pancreaticoduodenectomy was subsequently performed because of the risk of lymph node metastasis, which was expected due to the significant number of NET cells infiltrating the endothelium of the lymphatic vessels. No lymph node metastasis or recurrence was observed during the 26-month follow-up period. UEP is a useful method to achieve complete resection for diagnostic and therapeutic purposes. UEP may be a novel option for endoscopic treatment of ampullary NET., (© 2024. Japanese Society of Gastroenterology.)

Objective Endoscopic papillectomy(EP) is a minimally invasive treatment for early ampullary tumors. However, the optimal method is unclear. The aim of this study is to explore the efficacy and safety of traction-assisted EP treatments for ampullary early tumors. Methods We retrospective analyzed the patients with ampullary adenoma or early adenocarcinoma underwent endoscopic papillectomy between January 2010 and August 2023, including patient characteristics, lesion size, papilla type, pathological diagnosis and lesion surrounding conditions, en-bloc resection rate, complete resection rate, procedure time, complications, recurrences. Results During the study period, a total of 106 patients with ampullary adenoma or early adenocarcinoma underwent EP. The number of patients in traction group (clip combined with dental floss traction, CDT-EP) and non-traction group (hot snare papillectomy, HSP or endoscopic mucosal resection, EMR) were 45 and 61 respectively. The traction group has a higher en-bloc resection rate and complete resection rate than the non-traction group (92.86% vs. 68.85%, p  = 0.003; 90.48% vs. 60.66%, p  = 0.001), and the procedure time is slightly shorter[(1.57 ± 1.93)min vs. (1.98 ± 1.76)min, p  = 0.039]. The complications and recurrence in the traction group were lower than those in the non-traction group (7.14% vs. 19.72%, p  = 0.076; 7.14% vs. 11.78%, p  = 0.466), and all complications were successfully treated by endoscopy or conservative medical treatment. There was no statistical difference between the two groups in terms of patient characteristics, papilla type, pathological diagnosis and lesion surrounding conditions ( p  > 0.050), but there were differences in lesion size[(13 ± 1.09)mm vs. (11 ± 1.65)mm, p  = 0.002]. The recurrence rate of the traction group is lower than that of the non-traction group, but the difference is not significant(7.14% vs. 13.11%, p  = 0.335), and the non-traction group mainly has early recurrence. Further analysis shows that the size of the lesion, whether en-bloc resection or not, and the method of resection as independent risk factors for incomplete resection (OR = 1.732, p  = 0.031; OR = 3.716, p  = 0.049; OR = 2.120, p  = 0.027). Conclusions CDT- EP, HSP and EMR are all suitable methods for the treatment of ampullary adenoma or early adenocarcinoma. Assisted traction technology can reduce the operation difficulty of large and difficult to expose lesions, thereby improving the efficacy and safety of EP.

Background and Aims: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied., Methods: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test., Results: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months)., Conclusions: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla., Competing Interests: Disclosure The following authors disclosed financial relationships: M. Bruno: honoraria from Boston Scientific for lectures and research support. E. Wedi and A. Schmidt: honoraria from Ovesco for lectures and research support. M. Hollenbach: honoraria from Fujifilm for lectures and expert panel. All of the other authors disclosed no financial relationships., (Copyright © 2024. Published by Elsevier Inc.)

Background/purpose: There is currently no consensus on the use of endoscopic papillectomy (EP) for early stage duodenal ampullary adenocarcinoma. This study aimed to evaluate the feasibility of EP for patients with early stage duodenal ampullary adenocarcinoma., Methods: Patients who underwent EP for ampullary adenocarcinomas were investigated. Complete and clinical complete resection rates were evaluated. Clinical complete resection was defined as either complete resection or resection with positive or unknown margins but no cancer in the surgically resected specimen, or no recurrence on endoscopy after at least a 1-year follow-up., Results: Adenocarcinoma developed in 30 patients (carcinoma in situ [Tis]: 21, mucosal tumors [T1a(M)]: 4, tumors in the sphincter of Oddi [T1a(OD)]: 5). The complete resection rate was 60.0% (18/30) (Tis: 66.7% [14/21], T1a[M]: 50.0% [2/4], and T1a[OD]: 40.0% [2/5]). The mean follow-up period was 46.8 months. The recurrence rate for all patients was 6.7% (2/30). The clinical complete resection rates of adenocarcinoma were 89.2% (25/28); rates for Tis, T1a(M), and T1a(OD) were 89.4% (17/19), 100% (4/4), and 80% (4/5), respectively., Conclusions: EP may potentially achieve clinical complete resection of early stage (Tis and T1a) duodenal ampullary adenocarcinomas., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: In this Danish nationwide population-based study, we evaluated the prognostically relevant minimum tumour-free margin width following pancreaticoduodenectomy (PD) for ampullary adenocarcinoma (AAC) and evaluated whether certain margins hold independent prognostic information., Methods: We included 128 patients who underwent PD for AAC from 2015 to 2019. Clinical and pathological data including well-known prognostic factors were retrieved from the Danish Pancreatic Cancer Database. Missing data were obtained by review of pathology reports and re-microscopy of resection specimens. All PD specimens were examined using a standardised pathological protocol including multicolour inking, axial slicing and exact reporting of margin widths. The cohort was dichotomised into involved and uninvolved groups, using different margin clearance definitions (0.5-≥3.0 mm)., Results: Following PD for AAC, margin clearance of ≥1 mm was independently associated with improved chance of survival compared with <1 mm (HR: 0.30, 95 % CI: 0.14-0.64 (p = 0.002)). Posterior and anterior margin widths were narrower compared with superior mesenteric artery and vein margins. Posterior margin and anterior surface had isolated prognostic significance in multivariable analysis., Conclusion: Following PD for AAC, margin clearance of at least 1 mm is independently associated with improved survival. Our data further indicate that anterior surface and posterior margin hold particular prognostic value., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background/purpose: Data on the prognosis of endoscopic papillectomy (EP) for ampullary carcinoma (AC) is limited; therefore, we aimed to identify the factors associated with endoscopically controlled AC., Methods: Between January 2003 and October 2022, 75 patients underwent EP for ampullary tumors and were diagnosed with AC based on the pathological features of the resected tissue. The factors associated with additional surgery after EP were also evaluated., Results: A total of 67 patients had ACs ranging from carcinoma in situ to tumors limited to the mucosa (M group), and eight patients had ACs ranging from those limited to the sphincter of Oddi to those invading the duodenal muscularis propria (OD group). The 3-year endoscopic tumor control (condition not requiring additional surgery) rates in the M and OD groups were 90.8% and 84.6% (p = .033), respectively. In the M group, the presence of tumor components in the resection margins was the only significant factor associated with additional surgeries (p = .010) in the univariate analysis. The 3-year endoscopic tumor control rates were 100% for negative and uncertain resection margins and 76.6% for positive margins (p = .009)., Conclusions: If the AC is confined to the mucosa and the resection margins are negative or uncertain, the tumor can be well-controlled endoscopically., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Endoscopic papillectomy (EP) offers a safe and effective method for resection of ampullary adenomas. Data regarding the long-term resolution of adenoma following EP are limited. The aim of this study therefore was to examine the timing of recurrence after EP of ampullary adenomas., Methods: This was a single-center retrospective study including patients who received EP for ampullary adenomas from 8/2000 to 1/2018. Patients with confirmed complete eradication of adenoma were included in the recurrence analysis with recurrence defined as finding adenomatous histology after 1 negative surveillance endoscopy. Kaplan-Meier estimates were calculated to determine recurrence rates., Results: Of the 165 patients who underwent EP, 136 patients (mean age 61.9, 51.5% female) had adenomatous histology with a mean lesion size of 21.2 mm. A total of 124 (91.2%) achieved complete eradication with a follow-up of 345.8 person-years. Recurrence occurred in 20 (16.1%) patients at a mean of 3.2 (± 3) years (range 0.5-9.75 years) for a recurrence rate of 5.8 (95% CI 3.6-8.8) per 100 person-years. Nine (45%) recurrences occurred after the 1st 2 years of surveillance. Recurrence rate did not differ by baseline pathology [low-grade dysplasia: 5.2 (95% CI 3.0-9.0), high-grade dysplasia: 6.9 (95% CI 2.3-15.5), adenocarcinoma: 7.7 (95% CI 0.9-25.1)]., Conclusion: Recurrence remains a significant concern after EP. Given the timing of recurrence, long surveillance periods may be necessary. Larger multicenter studies are needed, however, to determine appropriate surveillance intervals., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/objective: Robotic pancreaticoduodenectomy in ampullary cancer has never been studied. This study aimed to clarify the feasibility and justification of robotic pancreaticoduodenectomy in ampullary cancer in terms of surgical risks, and oncologic and survival outcomes., Methods: A propensity score-matching comparison of robotic and open pancreaticoduodenectomy based on seven factors commonly used to predict the survival outcomes in ampullary cancer patients., Results: A total of 147 patients were enrolled, of which 101 and 46 underwent robotic and open pancreaticoduodenectomies, respectively. After propensity score-matching with a 2:1 ratio, 88 and 44 patients in the robotic and open pancreaticoduodenectomy groups were included. The operation time was of no significant difference after matching. The median intraoperative blood loss was much less in those who underwent robotic pancreaticoduodenectomy, both before (median, 120 vs. 320 c.c. P < 0.001) and after (100 vs. 335 mL P < 0.001) score-matching. There were no significant differences in terms of surgical risks, including surgical mortality, surgical morbidity, Clavien-Dindo severity classification, postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, chyle leak, bile leak, and wound infection, both before or after score-matching. The survival outcomes were also similar between the two groups, regardless of matching., Conclusions: Robotic pancreaticoduodenectomy for ampullary cancer is not only technically feasible and safe without increasing surgical risks, but also oncologically justifiable without compromising surgical radicality and survival outcomes., Competing Interests: Declaration of competing interest Bor-Shiuan Shyr, Shin-E Wang, Shih-Chin Chen, Yi-Ming Shyr, Bor-Uei Shyr have no conflicts of interest or financial ties to disclose., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: The relationship between adenomyomatous hyperplasia of the Vaterian system(AV) and cancer is unclear, some reports suggest that AV is often combined with mucosal glandular dysplasia, but it is not clear whether mucosal glandular dysplasia is a risk factor for carcinogenesis of AV. The aim of this study was to retrospective analysis of role of ductal glandular dysplasia as a risk factor in the development of carcinoma in AV., Methods: A total of 328 cases who underwent surgery with a final pathological diagnosis of adenomyomatous hyperplasia (AH) in the Chinese PLA General Hospital in BeiJing, China, between January 2005 and December 2021 were retrospectively collected. There were Seventeen cases(5%) in which the lesions were located in the common bile duct as well as the ampulla of Vater, and their clinical (age, sex, etc.), imaging (cholelithiasis, etc.) and pathological data (mucosal glandular dysplasia, etc.) were collected. Clinical data and pathological features of AV with or without mucosal glandular dysplasia were analyzed., Results: There were 17 out of 328 cases of AH occurring in the Vaterian system (5%). Three of seventeen AV cases were associated with carcinoma (18%). Of three cases, two (12%) with the tumor lesions in the mucosal glands adjacent to the AH (biliary tract cancer and ampullary cancer), and one (6%) with carcinoma developed from AH itself in the ampulla of Vater. All carcinomas had adenomyomatous hyperplasia with nearby mucosal glandular dysplasia (MGD). The percentage of BTC or AC was higher in patients with concurrent AH and MGD compared to AH patients without MGD. The results show tendency toward statistical significance (P = 0.082). This difference was more obvious among AH with severe dysplasia compared to adenomyomatous hyperplasia with mild-moderate dysplasia (P = 0.018)., Conclusion: This study is the first to find that AV is associated with biliary tract cancer and ampullary cancer. In AV, the mucosal glandular dysplasia may be a risk factor for the development of malignancy. The underlying mechanism for carcinogenesis of AV could be AH itself or its secretions stimulating mucosal glands hyperplasia, then mucosal glands dysplasia. AV may be a precancerous lesion., (© 2023. The Author(s).)

Objective: The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial., Materials and Method: We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid's databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included., Results: The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001)., Conclusions: PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD., (Copyright: © 2024 Permanyer.)

Objectives: This study aimed to compare the intestinal and pancreatobiliary subtypes of ampullary adenocarcinoma in a large patient group due to limited data on survival and risk factors., Methods: A retrospective analysis of the clinical and pathological findings and the survival of 184 patients with ampullary adenocarcinoma who underwent curative operation between 2007 and 2018 was performed., Results: Pancreatobiliary subtype had a higher prevalence of jaundice before operation than the intestinal subtype (p < 0.05). Pancreatobiliary subtype had a larger tumor size (> 2 mm) (p < 0.01) and poorer differentiation (p < 0.05) than the intestinal subtype. Perineural invasion more frequently occurred in pancreatobiliary subtype than the intestinal subtype (p < 0.01) and pancreatobiliary subtype had a higher prevalence of positive dissected lymph nodes (p < 0.05) with an advanced disease stage (p < 0.01) than the intestinal subtype. Patients of the pancreatobiliary subtype had poorer disease-free and overall survival than patients of the intestinal subtype. No survival benefit of adjuvant chemotherapy was found in either patients of the intestinal subtype or pancreatobiliary subtype. No significant difference was found in any subtypes regarding the recurrent regions., Conclusions: Pancreatobiliary subtype exhibited a higher recurrence rate and a poorer overall survival rate with more unfavorable pathological characteristics than the intestinal subtype., (Copyright: © 2024 Permanyer.)

Background: Metastatic disease in the regional lymph nodes (LNs) is a strong indicator of worse outcomes among patients after curative-intent resection of ampullary cancer (AC). This study aimed to ascertain the threshold number of examined LNs (ELNs) for AC to compare the prognosis accuracy of various nodal classification schemes relative to long-term prognosis., Methods: Patients who underwent pancreatoduodenectomy (PD) for AC (2004-2019) were identified using the National Cancer Database. Locally weighted regression scatter plot smoothing (LOWESS) curves were used to ascertain the optimal cut point for ELNs. The accuracy of the American Joint Committee on Cancer N classification, LN ratio, and log odds transformation (LODDS) ratio to stratify patients relative to survival was examined., Results: Among 8127 patients with AC, 67% were male with a median age of 67 years (IQR, 59-74). Tumors were most frequently classified as T3 (34.9%), followed by T2 (30.6%); T1 (12.9%) and T4 (17.6%) were less common. LN metastasis was identified in 4606 patients (56.7%). Among patients with nodal disease, 37.0% and 19.7% had N1 and N2 disease, respectively. The LOWESS curves identified an inflection cutoff point in the hazard of survival at 20 ELNs. The survival benefit of 20 ELNs was more pronounced among patients without LN metastasis vs patients with N1 disease (median overall survival [OS]: 54.1 months [IQR, 45.9-62.1] in ≥20 ELNs vs 39.0 months [IQR, 35.8-42.2] in <20 ELNs; P < .001) or N2 disease (median OS: 22.5 months [IQR, 18.9-26.2] in ≥20 ELNs vs 25.4 months [IQR, 23.3-27.6] in <20 ELNs; P < .001). When comparing the 4 different N classification schemes, the LODDS classification scheme yielded the highest predictive ability., Conclusions: Evaluation of a minimum of 20 LNs was needed to stratify patients with AC relative to the prognosis and to minimize stage migration. The LODDS nodal classification scheme had the highest prognostic accuracy to differentiate survival among patients after PD for AC., (Copyright © 2023 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.