BACKGROUND: Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival.
METHODS: Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed.
RESULTS: In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00).
CONCLUSIONS: A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival.
METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching.
RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes.
CONCLUSIONS: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

UNASSIGNED: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN.
UNASSIGNED: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death.
UNASSIGNED: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths).
UNASSIGNED: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.

BACKGROUND: International guidelines on intraductal papillary mucinous neoplasm (IPMN) recommend a formal oncological resection including splenectomy when distal pancreatectomy is indicated. This study aimed to compare oncological and surgical outcomes after distal pancreatectomy with or without splenectomy in patients with presumed IPMN.
METHODS: An international, retrospective cohort study was undertaken in 14 high-volume centres from 7 countries including consecutive patients after distal pancreatectomy for IPMN (2005-2019). Patients were divided into spleen-preserving distal pancreatectomy (SPDP) and distal pancreatectomy with splenectomy (DPS). The primary outcome was lymph node metastasis (LNM). Secondary outcomes were overall survival, duration of operation, blood loss, and secondary splenectomy.
RESULTS: Overall, 700 patients were included after distal pancreatectomy for IPMN; 123 underwent SPDP (17.6%) and 577 DPS (82.4%). The rate of malignancy was 29.6% (137 patients) and the overall rate of LNM 6.7% (47 patients). Patients with preoperative suspicion of malignancy had a LNM rate of 17.2% (23 of 134) versus 4.3% (23 of 539) among patients without suspected malignancy (P < 0.001). Overall, SPDP was associated with a shorter operating time (median 180 versus 226 min; P = 0.001), less blood loss (100 versus 336 ml; P = 0.001), and shorter hospital stay (5 versus 8 days; P < 0.001). No significant difference in overall survival was observed between SPDP and DPS for IPMN after correction for prognostic factors (HR 0.50, 95% c.i. 0.22 to 1.18; P = 0.504).
CONCLUSIONS: This international cohort study found LNM in 6.7% of patients undergoing distal pancreatectomy for IPMN. In patients without preoperative suspicion of malignancy, SPDP seemed oncologically safe and was associated with improved short-term outcomes compared with DPS.

OBJECTIVE: Pancreatic intraductal papillary mucinous neoplasm (IPMN) is one of the most common precancerous lesions of pancreatic carcinoma. Studies have found that the tumoral microbiome has an important influence on pancreatic carcinoma. However, the tumoral microbiome of IPMNs has rarely been explored.
METHODS: Tumoral microbiome gene sequencing was carried out using 16 specimens of IPMN and 45 specimens of IPMN with associated invasive carcinoma (IPMN-IC) by 2bRAD sequencing for microbiome. The profile of the tumoral microbiome was summarized. Associations of the tumoral microbiome with disease grade, histological subtype, and prognosis were analyzed.
RESULTS: A total of 598 species of microbes were identified, comprising 228 genera, 109 families, 60 orders, 29 classes, 14 phyla, and 2 kingdoms. The genus Pseudomonas was detected more frequently and had higher relative abundance in IPMN-ICs; Alcaligenes faecalis was detected with higher relative abundance in IPMNs. Bifidobacterium pseudolongum had a higher relative abundance in the IPMN-IC group, regardless of histological subtype. Moreover, among patients with IPMN-ICs, those with a high relative abundance of B. pseudolongum had better overall survival than those with a low relative abundance. Patients who were positive for Staphylococcus aureus or Mycolicibacillus koreensis had shorter survival. The presence of S. aureus was an independent risk factor for poor prognosis.
CONCLUSIONS: There are enriching tumoral microbes in IPMN. The tumoral microbiome of IPMN is different from that of IPMN-IC.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN.
METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model.
RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN.
CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

BACKGROUND: Identifying malignant transformation in pancreatic branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) remains challenging, but the standardized uptake value (SUV) obtained from 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET)/CT has the potential to become a valuable parameter for differentiation. This study aimed to assess the effectiveness of SUV of FDG-PET/CT in distinguishing low-grade dysplasia (LGD), high-grade dysplasia (HGD), and intraductal papillary mucinous carcinoma (IPMC) within BD-IPMNs.
METHODS: We assessed 58 patients with confirmed BD-IPMN undergoing surgery between 2008 and 2022. Receiver operating characteristic curves were plotted using the tumor-to-blood pool ratio (TBR) of FDG-PET/CT in two scenarios: one considering HGD + IPMC as positive and the other considering only IPMC as positive.
RESULTS: In the cohort of 58 cases, there were 39 females, and the median age was 71 years. The median TBR value was 1.45 (range, 0.35-25.44). The TBRs exhibited a significant correlation with each histopathology (p < 0.001). Furthermore, in the multivariate analysis, TBR was independently significant in both scenarios, with HGD + IPMC defined as malignant (p = 0.001) and with only IPMC defined as malignant (p = 0.024).
CONCLUSIONS: TBR might have the potential to serve as a valuable parameter for indicating malignant transformation in pancreatic BD-IPMNs.

OBJECTIVE: This international multicenter cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasm (IPMN).
BACKGROUND: Recurrence patterns and treatment of recurrence postresection of adenocarcinoma arising from IPMN are poorly explored.
METHODS: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 and December 2020 at 18 pancreatic centers were identified. Survival analysis was performed using the Kaplan-Meier log-rank test and multivariable logistic regression by Cox-Proportional Hazards modeling. End points were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided).
RESULTS: Four hundred fifty-nine patients were included (median, 70 years; interquartile range, 64-76; male, 54%) with a median follow-up of 78.1 months. Recurrence occurred in 209 patients [45.5%; median time to recurrence, 12.8 months; early recurrence (within 1 years), 23.2%]. Eighty-three (18.1%) patients experienced a local regional recurrence, and 164 (35.7%) patients experienced a distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (hazard ratio 1.09; P =0.669) One hundred twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months ( P <0.001), with no significant difference between treatment modalities. There was no significant difference in survival between locations of recurrence ( P =0.401).
CONCLUSIONS: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

CA19-9 is a tumor marker for pancreatic cancer (PC), and the nondiabetic cut-off level is 37 U/mL. CA19-9 levels are said to rise in patients with tumors like PC and intraductal papillary mucinous neoplasm (IPMN). CA19-9 levels have also been shown to be related to HbA1c levels. We hypothesized that the CA19-9 cut-off levels would differ between patients with poorly controlled diabetes. This real-world trial was designed to test our hypotheses. This was a retrospective cohort study. All inpatients with poorly controlled diabetes had mean HbA1c levels of 10.0% and were divided into three groups: those with pancreatic cancer (PC group, N = 20), those with IPMN (IPMN group, N = 55), and those with neither (NC group, N = 985). Serum CA19-9 levels in the PC group were significantly higher than in the IPMN and NC groups (p < 0.001). CA19-9 levels did not differ statistically between the IPMN and NC groups. According to the receiver operating characteristic (ROC) analysis, serum CA19-9 levels of 98.4 U/mL had the highest sensitivity and specificity to detect PC, when comparing PC to IPMN + NC groups. Using this cut-off, the sensitivity and specificity of CA19-9 for PC were 70.0% and 96.5%, respectively, with a 0.81 area under the ROC curve. CA19-9 levels in two inpatients were >98.4 U/mL, most likely due to hepatocellular carcinoma and esophageal cancer. CA19-9 cut-off levels were thought to be 98.4 U/mL. However, we should keep in mind that the sensitivity and specificity were not 100%.

BACKGROUND: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN.
METHODS: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted.
RESULTS: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group ( P =0.003), but overall survival (OS) was not ( P =0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P =0.402; stage II, P =0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P =0.481; N+, P =0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P <0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P =0.005) were identified as adverse prognostic factors in resected invasive IPMN.
CONCLUSIONS: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended.