Magnetic resonance imaging short protocols for intraductal papillary mucinous neoplasm (IPMN) surveillance: The time has come.

BACKGROUND/OBJECTIVES: To analyze the diagnostic performance of three short magnetic resonance imaging (MRI) protocols for the follow-up of pancratic intraductal papillary mucinous neoplasms (IPMN). METHODS: Follow-up MRI examinations of 287 patients with IPMN performed in two centers were retrospectively retrieved. Four MRI protocols were identified as follows: T1-weighted (T1w), T2-weighted (T2w), and MRCP sequences (protocol 1); T1w, T2w, MRCP, and diffusion-weighted (DWI) sequences (protocol 2); T1w, T2w, MRCP, and post-contrast T1w-sequences (protocol 3); and a comprehensive protocol including all previous sequences (protocol 4). Three radiologists with different experience in abdominal imaging expressed their opinion upon the optimal patient's management upon the evaluation of each protocol. Intra-and inter-observer agreement and concordance with the clinical decision expressed by a pancreatic surgeon were calculated with Cohen's kappa test. RESULTS: 223 patients were included (66±10 years; 92 men, 131 women). 143 patients had branch-duct-IPMNs, 25 main-duct-IPMNs and 55 mixed-type-IPMNs. 79 patients underwent surgery, resulting in 52 high-grade dysplasia (HGD) and 27 low-grade dysplasia (LGD). Concordance for the expert reader between protocols 1, 2 and 3 and the actual clinical decision were 0.63, 0.72, and 0.74 respectively (95% CI, 0.53-0.73, 0.63-0.81, and 0.65-0.83). Inter-observer agreement between reader 1 and reader 2, reader 1 and reader 3, and reader 2 and reader 3 were: 0.71, 0.50, and 0.75 for protocol 1 (95% CI, 0.63-0.81, 0.40-0.60, and 0.66-0.84);0.68, 0.54, and 0.84 for protocol 2 (95% CI, 0.59-0.77, 0.44-0.64, and 0.76-0.91); and 0.77, 0.65, and 0.86 for protocol 3 (95% CI, 0.69-0.86, 0.55-0.74, and 0.80-0.93). CONCLUSIONS: Short MRI protocol is suitable for IPMN surveillance.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

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.

Predicting the Risk of Morbidity by GLIM-Based Nutritional Assessment and Body Composition Analysis in Oncologic Abdominal Surgery in the Context of Enhanced Recovery Programs : The PHase Angle Value in Abdominal Surgery (PHAVAS) Study.

BACKGROUND: Preoperative nutritional status and body structure affect short-term prognosis in patients undergoing major oncologic surgery. Bioimpedance vectorial analysis (BIVA) is a reliable tool to assess body composition. Low BIVA-derived phase angle (PA) indicates a decline of cell membrane integrity and function. The aim was to study the association between perioperative PA variations and postoperative morbidity following major oncologic upper-GI surgery. PATIENTS AND METHODS: Between 2019 and 2022 we prospectively performed BIVA in patients undergoing surgical resection for pancreatic, hepatic, and gastric malignancies on the day before surgery and on postoperative day (POD) 1. Malnutrition was defined as per the Global Leadership Initiative on Malnutrition criteria. The PA variation (ΔPA) between POD1 and preoperatively was considered as a marker for morbidity. Uni and multivariable logistic regression models were applied. RESULTS: Overall, 542 patients with a mean age of 64.6 years were analyzed, 279 (51.5%) underwent pancreatic, 201 (37.1%) underwent hepatobiliary, and 62 (11.4%) underwent gastric resections. The prevalence of preoperative malnutrition was 16.6%. The overall morbidity rate was 53.3%, 59% in those with ΔPA < -0.5 versus 46% when ΔPA ≥ -0.5. Age [odds ratio (OR) 1.11; 95% confidence interval (CI) (1.00; 1.22)], pancreatic resections [OR 2.27; 95% CI (1.24; 4.18)], estimated blood loss (OR 1.20; 95% CI (1.03; 1.39)], malnutrition [OR 1.77; 95% CI (1.27; 2.45)], and ΔPA [OR 1.59; 95% CI (1.54; 1.65)] were independently associated with postoperative complications in the multivariate analysis. CONCLUSIONS: Patients with preoperative malnutrition were significantly more likely to develop postoperative morbidity. Moreover, a decrease in PA on POD1 was independently associated with a 13% increase in the absolute risk of complications. Whether proactive interventions may reduce the downward shift of PA and the complication rate need further investigation.

The Difficulty of Detecting Occult Metastases in Patients with Potentially Resectable Pancreatic Cancer: Development and External Validation of a Preoperative Prediction Model.

Occult metastases are detected in 10-15% of patients during exploratory laparotomy for pancreatic cancer. This study developed and externally validated a model to predict occult metastases in patients with potentially resectable pancreatic cancer. Model development was performed within the Dutch Pancreatic Cancer Audit, including all patients operated for pancreatic cancer (January 2013-December 2017). Multivariable logistic regression analysis based on the Akaike Information Criteria was performed with intraoperative pathologically proven metastases as the outcome. The model was externally validated with a cohort from the University Hospital of Verona (January 2013-December 2017). For model development, 2262 patients were included of whom 235 (10%) had occult metastases, located in the liver (n = 143, 61%), peritoneum (n = 73, 31%), or both (n = 19, 8%). The model included age (OR 1.02, 95% CI 1.00-1.03), BMI (OR 0.96, 95% CI 0.93-0.99), preoperative nutritional support (OR 1.73, 95% CI 1.01-2.74), tumor diameter (OR 1.60, 95% CI 1.04-2.45), tumor composition (solid vs. cystic) (OR 2.33, 95% CI 1.20-4.35), and indeterminate lesions on preoperative imaging (OR 4.01, 95% CI 2.16-7.43). External validation showed poor discrimination with a C-statistic of 0.56. Although some predictor variables were significantly associated with occult metastases, the model performed insufficiently at external validation.

Prophylactic abdominal drainage after distal pancreatectomy (PANDORINA): an international, multicentre, open-label, randomised controlled, non-inferiority trial.

BACKGROUND: Prophylactic passive abdominal drainage is standard practice after distal pancreatectomy. This approach aims to mitigate the consequences of postoperative pancreatic fistula (POPF) but its added value, especially in patients at low risk of POPF, is currently being debated. We aimed to assess the non-inferiority of a no-drain policy in patients after distal pancreatectomy. METHODS: In this international, multicentre, open-label, randomised controlled, non-inferiority trial, we recruited patients aged 18 years or older undergoing open or minimally invasive elective distal pancreatectomy for all indications in 12 centres in the Netherlands and Italy. We excluded patients with an American Society of Anesthesiology (ASA) physical status of 4-5 or WHO performance status of 3-4, added by amendment following the death of a patient with ASA 4 due to a pre-existing cardiac condition. Patients were randomly assigned (1:1) intraoperatively by permuted blocks (size four to eight) to either no drain or prophylactic passive drain placement, stratified by annual centre volume (<40 or ≥40 distal pancreatectomies) and low risk or high risk of grade B or C POPF. High-risk was defined as a pancreatic duct of more than 3 mm in diameter, a pancreatic thickness at the neck of more than 19 mm, or both, based on the Distal Pancreatectomy Fistula Risk Score. Other patients were considered low-risk. The primary outcome was the rate of major morbidity (Clavien-Dindo score ≥III), and the most relevant secondary outcome was grade B or C POPF, grading per the International Study Group for Pancreatic Surgery. Outcomes were assessed up to 90 days postoperatively and analysed in the intention-to-treat population and per-protocol population, which only included patients who received the allocated treatment. A prespecified non-inferiority margin of 8% was compared with the upper limit of the two-sided 95% CI (Wald) of unadjusted risk difference to assess non-inferiority. This trial is closed and registered in the Netherlands Trial Registry, NL9116. FINDINGS: Between Oct 3, 2020, and April 28, 2023, 376 patients were screened for eligibility and 282 patients were randomly assigned to the no-drain group (n=138; 75 [54%] women and 63 [46%] men) or the drain group (n=144; 73 [51%] women and 71 [49%] men). Seven patients in the no-drain group received a drain intraoperatively; consequently, the per-protocol population included 131 patients in the no-drain group and 144 patients in the drain group. The rate of major morbidity was non-inferior in the no-drain group compared with the drain group in the intention-to-treat analysis (21 [15%] vs 29 [20%]; risk difference -4·9 percentage points [95% CI -13·8 to 4·0]; pnon-inferiority=0·0022) and the per-protocol analysis (21 [16%] vs 29 [20%]; risk difference -4·1 percentage points [-13·2 to 5·0]; pnon-inferiority=0·0045). Grade B or C POPF was observed in 16 (12%) patients in the no-drain group and in 39 (27%) patients in the drain group (risk difference -15·5 percentage points [95% CI -24·5 to -6·5]; pnon-inferiority<0·0001) in the intention-to-treat analysis. Three patients in the no-drain group died within 90 days; the cause of death in two was not considered related to the trial. The third death was a patient with an ASA score of 4 who died after sepsis and a watershed cerebral infarction at second admission, leading to multiple organ failure. No patients in the drain group died within 90 days. INTERPRETATION: A no-drain policy is safe in terms of major morbidity and reduced the detection of grade B or C POPF, and should be the new standard approach in eligible patients undergoing distal pancreatectomy. FUNDING: Ethicon UK (Johnson & Johnson Medical, Edinburgh, UK).

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). PATIENTS AND METHODS: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. RESULTS: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study.

OBJECTIVES: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. BACKGROUND: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. METHODS: All patients undergoing DP for any indication between 2015 and 2021 at three European referral Centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase (DFA), C-reactive protein (C-RP), and serum amylase were examined from postoperative-day (POD) 1 to 3. Biochemical leak (BL), POPF, POH, and post-pancreatectomy hemorrhage (PPH) were defined and graded according to ISGPS definitions. RESULTS: In total 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of DFA ≥2000 U/L on POD 1 (OR=2.11, 95% CI 1.68-2.86), C-RP ≥200 mg/L on POD 3 (OR=2.19, 95% CI 1.68-2.86), and POH (OR=1.58, 95% CI 1.14-2.19) were all independent early predictors of POPF (all P< 0.01). The presence of POH almost doubled the rate of POPF (43% vs. 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF= 12%; BL= 19%; B POPF= 24%; C POPF= 52%). Among patients developing POPF, patients with POH had higher rates of PPH (22% vs 9%, P= 0.001), sepsis (24% vs 13%; P=0.011), re-operation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P= 0.025). CONCLUSIONS: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention / mitigation strategies against pancreas specific complications.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validate guidelines on the perioperative care of patients with borderline resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to non-surgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive mean to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR- and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Adjuvant Therapy After Upfront Resection of Resectable Pancreatic Cancer: Patterns of Omission and Use-A Prospective Real-Life Study.

BACKGROUND: Little is known about adjuvant therapy (AT) omission and use outside of randomized trials. We aimed to assess the patterns of AT omission and use in a cohort of upfront resected pancreatic cancer patients in a real-life scenario. METHODS: From January 2019 to July 2022, 317 patients with resected pancreatic cancer and operated upfront were prospectively enrolled in this prospective observational trial according to the previously calculated sample size. The association between perioperative variables and the risk of AT omission and AT delay was analyzed using multivariable logistic regression. RESULTS: Eighty patients (25.2%) did not receive AT. The main reasons for AT omission were postoperative complications (38.8%), oncologist's choice (21.2%), baseline comorbidities (20%), patient's choice (10%), and early recurrence (10%). At the multivariable analysis, the odds of not receiving AT increased significantly for older patients (odds ratio [OR] 1.1, p < 0.001), those having an American Society of Anesthesiologists score ≥II (OR 2.03, p = 0.015), or developing postoperative pancreatic fistula (OR 2.5, p = 0.019). The likelihood of not receiving FOLFIRINOX as AT increased for older patients (OR 1.1, p < 0.001), in the presence of early-stage disease (stage I-IIa vs. IIb-III, OR 2.82, p =0.031; N0 vs. N+, OR 3, p = 0.03), and for patients who experienced postoperative major complications (OR 4.7, p = 0.009). A twofold increased likelihood of delay in AT was found in patients experiencing postoperative complications (OR 3.86, p = 0.011). CONCLUSIONS: AT is not delivered in about one-quarter of upfront resected pancreatic cancer patients. Age, comorbidities, and postoperative complications are the main drivers of AT omission and mFOLFIRINOX non-use. CLINICALTRIALS REGISTRATION: NCT03788382.

Outcomes after distal pancreatectomy with or without splenectomy for intraductal papillary mucinous neoplasm: international multicentre cohort study.

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). CONCLUSION: 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.

Resection to Exploration Ratios and Associated Outcomes in Patients with Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: To investigate resection/exploration ratios (RER), reasons for omission of pancreatectomy, and survival outcomes in patients undergoing surgical exploration with resection intent for pancreatic ductal adenocarcinoma (PDAC). SUMMARY BACKGROUND DATA: While surgical indications for PDAC are expanding, information about intraoperative attrition is lacking. METHODS: The RER was calculated in PDAC patients undergoing exploration from 2018 through 2020. Factors associated with uncompleted resection and survival were identified using multivariable models. RESULTS: In total, 681 patients were included. Upfront explorations were 296 (43.7%), and post-neoadjuvant explorations were 385 (56.3%). The overall RER was 89.7% (90.5% in the upfront setting and 89.1% post-neoadjuvant treatment). In this latter subgroup, the RER decreased from 96.1% in resectable disease to 86.6% in borderline resectable disease and 61.9% in locally advanced disease. The primary reasons for uncompleted resection were occult metastases in presumed resectable/borderline resectable disease (without difference between upfront and post-neoadjuvant operations) and local unresectability in locally advanced disease. No preoperative variable was associated with uncompleted resection in upfront explorations, while anatomical staging informed the likelihood of surgical attrition following neoadjuvant treatment. Uncompleted resection was invariably associated with a median survival of around one year. The median post-pancreatectomy survival was 36.9 months in the upfront setting and 29.5 months following neoadjuvant treatment. The median survival from diagnosis in patients receiving post-neoadjuvant resection was 34.5 months. CONCLUSIONS: This analysis provided contemporary information about resection rates, reasons for intraoperative attrition, and survival outcomes in the entire spectrum of PDAC patients selected for surgical exploration at an experienced institution.

International evidence-based Kyoto guidelines for the management of intraductal papillary mucinous neoplasm of the pancreas.

This study group aimed to revise the 2017 international consensus guidelines for the management of intraductal papillary mucinous neoplasm (IPMN) of the pancreas, and mainly focused on five topics; the revision of high-risk stigmata (HRS) and worrisome features (WF), surveillance of non-resected IPMN, surveillance after resection of IPMN, revision of pathological aspects, and investigation of molecular markers in cyst fluid. A new development from the prior guidelines is that systematic reviews were performed for each one of these topics, and published separately to provide evidence-based recommendations. One of the highlights of these new "evidence-based guidelines" is to propose a new management algorithm, and one major revision is to include into the assessment of HRS and WF the imaging findings from endoscopic ultrasound (EUS) and the results of cytological analysis from EUS-guided fine needle aspiration technique, when this is performed. Another key element of the current guidelines is to clarify whether lifetime surveillance for small IPMNs is required, and recommends two options, "stop surveillance" or "continue surveillance for possible development of concomitant pancreatic ductal adenocarcinoma", for small unchanged BD-IPMN after 5 years surveillance. Several other points are also discussed, including identifying high-risk features for recurrence in patients who underwent resection of non-invasive IPMN with negative surgical margin, summaries of the recent observations in the pathology of IPMN. In addition, the emerging role of cyst fluid markers that can aid in distinguishing IPMN from other pancreatic cysts and identify those IPMNs that harbor high-grade dysplasia or invasive carcinoma is discussed.

Optimal Surveillance Interval of Branch Duct Intraductal Papillary Mucinous Neoplasm of the Pancreas.

Importance: Despite the increasing prevalence of intraductal papillary mucinous neoplasm (IPMN), data on the growth and malignant conversion rates based on long-term surveillance cohorts are limited. Many international guidelines recommend surveillance for benign lesions, but the optimal interval and duration are unclear. Objective: To determine the optimal surveillance protocol for IPMN and propose which patients may be exempted from surveillance. Design, Setting, and Participants: This large-scale, international cohort study examined data of 3825 patients with IPMN treated at 5 tertiary pancreatic centers. Included were patients with branch duct (BD) IPMN who underwent surveillance or surgery between January 1, 1988, and December 31, 2020. After a thorough review, 3656 patients were included in the analytic sample. Changes in cyst size, worrisome features or high-risk stigmata, and malignant conversion rates were assessed. Patients who underwent surveillance over 5 years were compared to suggest discontinuation of surveillance protocol. Clinical data collection began in January 1, 2021, and the mean (SD) follow-up duration was 84 (47.7) months. The data analysis was performed from May 2, 2022, through September 14, 2022. Exposure: The patients with BD-IPMN were followed up based on International Association of Pancreatology guidelines. Patients with suspicious malignant neoplasms during surveillance underwent surgical resection. Main Outcome and Measures: The main outcome of this study was the optimal follow-up interval and duration of BD-IPMN surveillance. The association among cyst size, growth rate, and progression was examined using descriptive statistics. Results: Of the 3656 patients with BD-IPMN in the analytic sample (1973 [54.0%] female; mean [SD] age, 63.7 [10.2] years), 172 (4.7%) were confirmed to have malignant lesions through surgery. Considering cyst growth, the time to develop worrisome features, and malignant conversion, a 1.5-, 1-, and 0.5-year surveillance interval could be optimal for cysts smaller than 20 mm, 20 to 30 mm, and 30 mm, respectively, after initial short-term (6-month) follow-up. Patients with cysts smaller than 20 mm, no worrisome features, and no growth during 5-year surveillance did not show malignant conversion after 5 years of follow-up and had time to progression of greater than 10 years. Conclusions: These findings suggest that BD-IPMN surveillance may depend on the size of the cyst and morphologic changes at the initial 6-month follow-up. For patients with small cysts (ie, <20 mm) with no morphologic changes during the initial 5-year surveillance period, surveillance may be discontinued for those unfit for surgery or who have a limited life expectancy of 10 years or less.

Perioperative NALIRIFOX in patients with resectable pancreatic ductal adenocarcinoma: The open-label, multicenter, phase II nITRO trial.

BACKGROUND: Upfront surgery followed by postoperative treatment is a commonly adopted treatment for resectable pancreatic ductal adenocarcinoma (rPDAC). However, the risk of positive surgical margins, the poor recovery that often impairs postoperative treatments, and the risk of recurrence might limit the outcome of this strategy. This study evaluated the safety and the activity of liposomal irinotecan 50 mg/m2 + 5-fluorouracil 2400 mg/m2 + leucovorin 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX) in the perioperative treatment of patients with rPDAC. METHODS: Eligible patients had a rPDAC with < 180° interface with major veins' wall. Patients received 3 cycles before and 3 cycles after resection with NALIRIFOX, days 1 and 15 of a 28-day cycle. The primary endpoint was the proportion of patients undergoing an R0 resection. RESULTS: 107 patients began preoperative treatment. Nine patients discontinued the treatment because of related or unrelated adverse events. Disease-control rate was 92.9%. 87 patients underwent surgical exploration, 11 had intraoperative evidence of metastatic disease, and 1 died for surgical complications. R0 resection rate was 65.3%. 49 patients completed the three postoperative cycles. The most common grade ≥ 3 adverse events were diarrhea and neutropenia. Median overall survival (OS) of ITT patients was 32.3 months (95% CI 27.8-44.3). Median disease-free and OS from surgery of resected patients were 19.3 (95% CI 12.6-34.1) and 40.3 months (95% CI 29-NA), respectively. CONCLUSION: Perioperative NALIRIFOX was manageable and active, and deserves further investigation in randomized trials comparing it with standard upfront surgery followed by adjuvant therapy.

Surveillance of Individuals at High Risk of Developing Pancreatic Cancer: A Prevalence Meta-analysis to Estimate the Rate of Low-yield Surgery.

OBJECTIVE: To quantify the rate of low-yield surgery, defined as no high-grade dysplastic precursor lesions or T1N0M0 pancreatic cancer at pathology, during pancreatic cancer surveillance. BACKGROUND: Global efforts have been made in pancreatic cancer surveillance to anticipate the diagnosis of pancreatic cancer at an early stage and improve survival in high-risk individuals (HRIs) with a hereditary predisposition. The negative impact of pancreatic cancer surveillance when surgery is performed for low-grade dysplasia or a non-neoplastic condition is not well quantified. MATERIALS AND METHODS: A systematic search and prevalence meta-analysis was performed for studies reporting surgery with final diagnoses other than those defined by the Cancer of the Pancreas Screening (CAPS) goals from January 2000 to July 2023. The secondary outcome was the pooled proportion of final diagnoses matching the CAPS goals (PROSPERO: #CRD42022300408). RESULTS: Twenty-three articles with 5027 patients (median 109 patients/study, interquartile range 251) were included. The pooled prevalence of low-yield surgery was 2.1% (95% CI: 0.9-3.7, I2 : 83%). In the subgroup analysis, this prevalence was nonsignificantly higher in studies that only included familial pancreatic cancer subjects without known pathogenic variants, compared with those enrolling pathogenic variant carriers. No effect modifiers were found. Overall, the pooled prevalence of subjects under surveillance who had a pancreatic resection that contained target lesions was 0.8% (95% CI, 0.3-1.5, I2 : 24%]. The temporal analysis showed that the rate of low-yield surgeries decreased in the last decades and stabilized at around 1% (test for subgroup differences P <0.01). CONCLUSIONS: The risk of "low-yield" surgery during pancreatic cancer surveillance is relatively low but should be thoroughly discussed with individuals under surveillance.