Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk.

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10-8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10-7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10-6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10-5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

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 validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the 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 a 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 nonsurgical 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 means 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-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Delta Radiomic Features Predict Resection Margin Status and Overall Survival in Neoadjuvant-Treated Pancreatic Cancer Patients.

BACKGROUND: Neoadjuvant therapy (NAT) emerged as the standard of care for patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgery; however, surgery is morbid, and tools to predict resection margin status (RMS) and prognosis in the preoperative setting are needed. Radiomic models, specifically delta radiomic features (DRFs), may provide insight into treatment dynamics to improve preoperative predictions. METHODS: We retrospectively collected clinical, pathological, and surgical data (patients with resectable, borderline, locally advanced, and metastatic disease), and pre/post-NAT contrast-enhanced computed tomography (CT) scans from PDAC patients at the University of Texas Southwestern Medical Center (UTSW; discovery) and Humanitas Hospital (validation cohort). Gross tumor volume was contoured from CT scans, and 257 radiomics features were extracted. DRFs were calculated by direct subtraction of pre/post-NAT radiomic features. Cox proportional models and binary prediction models, including/excluding clinical variables, were constructed to predict overall survival (OS), disease-free survival (DFS), and RMS. RESULTS: The discovery and validation cohorts comprised 58 and 31 patients, respectively. Both cohorts had similar clinical characteristics, apart from differences in NAT (FOLFIRINOX vs. gemcitabine/nab-paclitaxel; p < 0.05) and type of surgery resections (pancreatoduodenectomy, distal or total pancreatectomy; p < 0.05). The model that combined clinical variables (pre-NAT carbohydrate antigen (CA) 19-9, the change in CA19-9 after NAT (∆CA19-9), and resectability status) and DRFs outperformed the clinical feature-based models and other radiomics feature-based models in predicting OS (UTSW: 0.73; Humanitas: 0.66), DFS (UTSW: 0.75; Humanitas: 0.64), and RMS (UTSW 0.73; Humanitas: 0.69). CONCLUSIONS: Our externally validated, predictive/prognostic delta-radiomics models, which incorporate clinical variables, show promise in predicting the risk of predicting RMS in NAT-treated PDAC patients and their OS or DFS.

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.

Clinical usefulness of routinely performed drain fluid cultures after pancreaticoduodenectomy. A new ally to predict patients' outcomes?

BACKGROUND: Previous studies showed that bacterial contamination of surgical drains was associated with higher morbidity and mortality following pancreaticoduodenectomy (PD). However, there is still no agreement on the routine use of fluid drainage cultures in the management of patients underwent PD. Therefore, we aimed to clarify the role of surgical drain bacterial contamination in predicting patients' postoperative course. METHOD: Single-centre study including patients underwent PD at Humanitas Research Hospital (2010-2021). Preoperative, intraoperative and postoperative data were collected. Routinely performed fluid drain cultures on postoperative day (POD) 5 were analyzed and compared among patients throughout the cohort. RESULTS: A total of 825 patients were analyzed. Bacterial contamination of surgical drains was observed in 420 (50.9 %) patients and it was found to be associated with a higher rate of B/C grade pancreatic fistula (POPF) (P < 0.001), Clavien-Dindo≥3 (P < 0.001), 30-day mortality (P = 0.011), wound infection (P < 0.001), relaparotomies (P = 0.003) and greater length of hospital stay (LOS) (P < 0.001). Also, E. coli surgical drain contamination was demonstrated to double the risk of B/C grade POPF development (OR = 1.628, 95 % IC = 1.009-2.625, P = 0.046). Finally, preoperative biliary drainage (OR = 2.474, 95 % IC = 1.855-3.298, P < 0.001), age ≥75 years old (OR = 1.492, 95 % IC = 1.077-2.067, P = 0.016) and isolated Roux-en-Y pancreaticojejunostomy (OR = 1.639, 95 % IC = 1.229-2.188, P < 0.001) were identified as risk factors for surgical drains bacterial contamination. CONCLUSION: Bacterial contamination of surgical drains predicts the development of B/C grade POPF and other major complications after PD. Therefore, we suggest the routine use of fluid drain cultures following PD.

Management of Malignant Gastric Outlet Obstruction: A Comprehensive Review on the Old, the Classic and the Innovative Approaches.

Gastrojejunostomy is the principal method of palliation for unresectable malignant gastric outlet obstructions (GOO). Gastrojejunostomy was traditionally performed as a surgical procedure with an open approach butrecently, notable progress in the development of minimally invasive procedures such as laparoscopic gastrojejunostomies have emerged. Additionally, advancements in endoscopic techniques, including endoscopic stenting (ES) and endoscopic ultrasound-guided gastroenterostomy (EUS-GE), are becoming more prominent. ES involves the placement of self-expandable metal stents (SEMS) to restore luminal patency. ES is commonly the first choice for patients deemed unfit for surgery or at high surgical risk. However, although ES leads to rapid improvement of symptoms, it carries limitations like higher stent dysfunction rates and the need for frequent re-interventions. Recently, EUS-GE has emerged as a potential alternative, combining the minimally invasive nature of the endoscopic approach with the long-lasting effects of a gastrojejunostomy. Having reviewed the advantages and disadvantages of these different techniques, this article aims to provide a comprehensive review regarding the management of unresectable malignant GOO.

Total Pancreatectomy With Islet Autotransplantation as an Alternative to High-risk Pancreatojejunostomy After Pancreaticoduodenectomy: A Prospective Randomized Trial.

OBJECTIVE: To compare pancreaticoduodenectomy (PD) and total pancreatectomy (TP) with islet autotransplantation (IAT) in patients at high risk of postoperative pancreatic fistula (POPF). BACKGROUND: Criteria to predict the risk of POPF occurrence after PD are available. However, even when a high risk of POPF is predicted, TP is not currently accepted as an alternative to PD, because of its severe consequences on glycaemic control. Combining IAT with TP may mitigate such consequences. METHODS: Randomized, open-label, controlled, bicentric trial (NCT01346098). Candidates for PD at high-risk pancreatic anastomosis (ie, soft pancreas and duct diameter ≤3 mm) were randomly assigned (1:1) to undergo either PD or TP-IAT. The primary endpoint was the incidence of complications within 90 days after surgery. RESULTS: Between 2010 and 2019, 61 patients were assigned to PD (n=31) or TP-IAT (n=30). In the intention-to-treat analysis, morbidity rate was 90·3% after PD and 60% after TP-IAT ( P =0.008). According to complications' severity, PD was associated with an increased risk of grade ≥2 [odds ratio (OR)=7.64 (95% CI: 1.35-43.3), P =0.022], while the OR for grade ≥3 complications was 2.82 (95% CI: 0.86-9.24, P =0.086). After TP-IAT, the postoperative stay was shorter [median: 10.5 vs 16.0 days; P <0.001). No differences were observed in disease-free survival, site of recurrence, disease-specific survival, and overall survival. TP-IAT was associated with a higher risk of diabetes [hazard ratio=9.1 (95% CI: 3.76-21.9), P <0.0001], but most patients maintained good metabolic control and showed sustained C-peptide production over time. CONCLUSIONS: TP-IAT may become the standard treatment in candidates for PD, when a high risk of POPF is predicted.

Clinical Outcomes After Total Pancreatectomy: A Prospective Multicenter Pan-European Snapshot Study.

OBJECTIVE: To assess outcomes among patients undergoing total pancreatectomy (TP) including predictors for complications and in-hospital mortality. BACKGROUND: Current studies on TP mostly originate from high-volume centers and span long time periods and therefore may not reflect daily practice. METHODS: This prospective pan-European snapshot study included patients who underwent elective (primary or completion) TP in 43 centers in 16 European countries (June 2018-June 2019). Subgroup analysis included cutoff values for annual volume of pancreatoduodenectomies (<60 vs ≥60).Predictors for major complications and in-hospital mortality were assessed in multivariable logistic regression. RESULTS: In total, 277 patients underwent TP, mostly for malignant disease (73%). Major postoperative complications occurred in 70 patients (25%). Median hospital stay was 12 days (IQR 9-18) and 40 patients were readmitted (15%). In-hospital mortality was 5% and 90-day mortality 8%. In the subgroup analysis, in-hospital mortality was lower in patients operated in centers with ≥60 pancreatoduodenectomies compared <60 (4% vs 10%, P = 0.046). In multivariable analysis, annual volume <60 pancreatoduodenectomies (OR 3.78, 95% CI 1.18-12.16, P = 0.026), age (OR 1.07, 95% CI 1.01-1.14, P = 0.046), and estimated blood loss ≥2L (OR 11.89, 95% CI 2.64-53.61, P = 0.001) were associated with in-hospital mortality. ASA ≥3 (OR 2.87, 95% CI 1.56-5.26, P = 0.001) and estimated blood loss ≥2L (OR 3.52, 95% CI 1.25-9.90, P = 0.017) were associated with major complications. CONCLUSION: This pan-European prospective snapshot study found a 5% inhospital mortality after TP. The identified predictors for mortality, including low-volume centers, age, and increased blood loss, may be used to improve outcomes.

Benchmarking of minimally invasive distal pancreatectomy with splenectomy: European multicentre study.

BACKGROUND: Benchmarking is the process to used assess the best achievable results and compare outcomes with that standard. This study aimed to assess best achievable outcomes in minimally invasive distal pancreatectomy with splenectomy (MIDPS). METHODS: This retrospective study included consecutive patients undergoing MIDPS for any indication, between 2003 and 2019, in 31 European centres. Benchmarks of the main clinical outcomes were calculated according to the Achievable Benchmark of Care (ABC™) method. After identifying independent risk factors for severe morbidity and conversion, risk-adjusted ABCs were calculated for each subgroup of patients at risk. RESULTS: A total of 1595 patients were included. The ABC was 2.5 per cent for conversion and 8.4 per cent for severe morbidity. ABC values were 160 min for duration of operation time, 8.3 per cent for POPF, 1.8 per cent for reoperation, and 0 per cent for mortality. Multivariable analysis showed that conversion was associated with male sex (OR 1.48), BMI exceeding 30 kg/m2 (OR 2.42), multivisceral resection (OR 3.04), and laparoscopy (OR 2.24). Increased risk of severe morbidity was associated with ASA fitness grade above II (OR 1.60), multivisceral resection (OR 1.88), and robotic approach (OR 1.87). CONCLUSION: The benchmark values obtained using the ABC method represent optimal outcomes from best achievable care, including low complication rates and zero mortality. These benchmarks should be used to set standards to improve patient outcomes.

Invasive IPMN relapse later and more often in lungs in comparison to pancreatic ductal adenocarcinoma.

BACKGROUND: The different oncological outcomes of invasive intraductal papillary mucinous neoplasm (I-IPMN) and pancreatic ductal adenocarcinoma (PDAC) are debated. This study aimed to compare disease recurrence patterns and histopathological characteristics in patients with resected I-IPMN and PDAC. METHODS: Consecutive patients undergoing surgical resection for stage I-III I-IPMN or PDAC between 2010 and 2016 were retrospectively analyzed. Patients treated with neoadjuvant therapy or resected for Tis neoplasia were excluded. All surgical specimens were re-staged according to AJCC-8th-edition. RESULTS: A total of 330 patients were included, of whom 43 had I-IPMN and 287 had PDAC. Median follow-up time was 26.7 (1.3-92.3) months and estimated median disease-free survival (DFS) was 60.3 months (47.2-73.4) for I-IPMN and 23.8 (19.3-28.2) months for PDAC (p < 0.001). During follow-up, 32.6% of I-IPMN and 67.9% of PDAC patients experienced recurrence (p < 0.001). The sites of first recurrence were the lungs (38.5% vs 13.1%, p = 0.027), liver (28.6% vs 45.0%, p = 0.180) and local (15.4% vs 36.6%, p = 0.101) for I-IPMN and PDAC, respectively. At multivariate analysis, I-IPMN histology remained an independent predictive factor for longer DFS (OR 0.528, CI 95% 0.278-1.000, p = 0.050), regardless of stage or adjuvant chemotherapy. I-IPMN and PDAC differed in rates of neuroinvasion (51.2% vs 97.2%) and positive lymph node status (N+) (46.5% vs 82.7%), especially in patients with lower T status. CONCLUSION: I-IPMN showed a different recurrence pattern compared to PDAC, with a higher lung tropism, and longer DFS. This different biological behavior is associated with lower rates of neuroinvasion and nodal involvement, especially in early-stage disease.

Total pancreatectomy as alternative to pancreatico-jejunal anastomosis in patients with high fistula risk score: the choice of the fearful or of the wise?

PURPOSE: Patients with fistula risk score (FRS) ≥7 are at the highest risk of developing clinically relevant post-operative pancreatic fistula (CR-POPF). There is no agreement on the management of this subpopulation. The primary outcome of the study was the definition of the role of intraoperative completion pancreatectomy (ICP) in patients at high risk for CR-POPF, as an alternative to high-risk pancreaticoduodenectomy (PD). METHODS: This is an observational study set in a single tertiary referral center. Patients scheduled for PD in our center between 2010 and 2019 with FRS ≥7 were included in the study. Data were prospectively collected. RESULTS: A total of 738 patients were scheduled for between 2010 and 2019, and 62 had FRS ≥7. Thirty-five patients were managed with PD and pancreatico-jejunal anastomosis (group A), and 27 with ICP (group B). Overall complication rate was significantly higher in group A than group B (95 versus 59%; p=0.005) and there was a not significantly higher rate of major complications (Clavien-Dindo ≥3) (43 versus 26%; p=0.192). In group A, 49% of patients had a CR-POPF. Median post-operative length of stay was 15 days in group A and 12 in group B (p=0.043). Readmission was observed only in group A (26%). In multivariate analysis, PD was an independent predictive factor of major post-operative morbidity (RR 9.27; CI 1.74-49.31). No patients in either group suffered major adverse events related to endocrine and exocrine insufficiency. CONCLUSION: In high-FRS patients, ICP has good short-term outcomes relative to PD without major long-term events related to endocrine and exocrine insufficiency. ICP could be considered as a feasible alternative in selected cases.

Preoperative adiposity at bioimpedance vector analysis improves the ability of Fistula Risk Score (FRS) in predicting pancreatic fistula after pancreatoduodenectomy.

BACKGROUND: Anthropometric parameters have been associated with increased risk of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Nonetheless, conventional metrics to predict POPF do not include the assessment of body composition. We aimed to validate the most used Fistula Risk Score (FRS), and to assess whether the appraisal of adipose compartment at bioimpedance vector analysis (BIVA) improves the accuracy of FRS in CR-POPF prediction. METHOD: PD patients from 3 Italian academic institutions were prospectively included over a 2-year period. Patients with ASA score ≥3, heart failure, chronic kidney disease, or compartmentalized fluid collections were excluded. BIVA was performed on the day prior to surgery. CR-POPF occurrence and severity were classified per the ISGPS classification. RESULTS: Out of 148 PDs, 84 patients (56.8%) had pancreatic cancer, and 29 (19.6%) experienced CR-POPF. FRS elements, namely soft pancreatic texture (p = 0.009), small pancreatic duct diameter (p = 0.029), but not blood loss (p = 0.450), as well as high BMI (p = 0.004) were associated with CR-POPF. Also, the preoperative fat mass (FM) amount measured at BIVA was significantly higher in patients who developed CR-POPF, compared to those who did not (median FM = 19.4 kg/m2 vs. 14.4 kg/m2, respectively; p = 0.005). The predictive ability of a multivariate model adding FM to the FRS, assessed at the receiver operating characteristics curve showed a higher accuracy than the FRS alone (AUC = 0.774 and AUC = 0.738, respectively). CONCLUSIONS: Assessment of preoperative FM at BIVA can improve the accuracy of FRS in predicting CR-POPF following pancreatoduodenectomy.

Trans-duodenal ampullectomy for ampullary neoplasms: early and long-term outcomes in 36 consecutive patients.

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

Enhanced Recovery After Pancreatic Surgery Does One Size Really Fit All? A Clinical Score to Predict the Failure of an Enhanced Recovery Protocol After Pancreaticoduodenectomy.

BACKGROUND: The inability to comply with enhanced recovery protocols (ERp) after pancreaticoduodenectomy (PD) is a real but understated issue. Our goal is to report our experience and a potential tool to predict ERp failure in order to better characterize this problem. METHODS: From January 1, 2014, to January 31, 2016, 205 consecutive patients underwent PD in our center and were managed according to an ERp. Failure to comply with postoperative protocol items was defined as any of: no active ambulation on postoperative day 1 (POD1); less than 4 h out of bed on POD2; removal of nasogastric tube and bladder catheter after POD1 and POD3, respectively; reintroduction of oral feeding after POD4; and continuation of intravenous infusions after POD4. Data were collected in a prospective database. RESULTS: Taking in consideration the number of failed items and the length of stay, we defined failure of the ERp as no compliance to two or more items. A total of 116 patients (56.6%) met this definition of failure. We created a predictive model consisting of age, BMI, operative time, and pancreatic stump consistency. These variables were independent predictors of failure (OR 1.03 [1.001-1.06] p = 0.01; OR 1.11 [1.01-1.22] p = 0.03; OR 1.004 [1.001-1.009] p = 0.02 and OR 2.89 [1.48-5.67] p = 0.002, respectively). Patient final score predicted the failure of the ERp with an area under the ROC curve of 0.747. CONCLUSIONS: It seems to be possible to predict ERp failure after PD. Patients at high risk of failure may benefit more from a specific ERp.

Pancreatic serous cystoadenoma (CSA) showing increased tracer uptake at 68-GaDOTA-peptide Positron Emission Tomography (68Ga-DOTA-peptide PET-CT): a case report.

BACKGROUND: Serous cysto-adenoma (SCA) is a rare benign neoplasm of the pancreas. SCA can mimic other pancreatic lesions, such as neuroendocrine tumours. 68Gallium-DOTA-peptide Positron Emission Tomography (PET) is able to image in vivo the over-expression of the somatostatin receptors, playing an important role for the identification of neuroendocrine neoplasms. CASE PRESENTATION: We reported a case of 63-year-old man, with a solid lesion of 7 cm of diameter of the body-tail of the pancreas. Two fine-needle-aspirations (FNA) were inconclusive. A 68Ga-DOTA-peptide PET-CT revealed a pathological uptake of the pancreatic lesion. The diagnosis of a pancreatic neuroendocrine neoplasm was established and a laparoscopic distal splenopancreatectomy and cholecystectomy was performed. Final histopathological report revealed the presence of a micro-cystic SCA. CONCLUSIONS: The current case firstly reports a pancreatic SCA showing increased radiopharmaceutical uptake at 68Ga-DOTA-peptide PET-CT images. This unexpected finding should be taken into account during the diagnostic algorithm of a pancreatic lesion, in order to minimize the risk of misdiagnosis and overtreatment of SCA.

Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis.

OBJECTIVE: To evaluate whether perioperative bioimpedance vector analysis (BIVA) predicts the occurrence of surgery-related morbidity. SUMMARY BACKGROUND DATA: BIVA is a reliable tool to assess hydration status and compartimentalized fluid distribution. METHODS: The BIVA of patients undergoing resection for pancreatic malignancies was prospectively measured on the day prior to surgery and on postoperative day (POD)1. Postoperative morbidity was scored per the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI). RESULTS: Out of 249 patients, the overall and major complication rates were 61% and 16.5% respectively. The median CCI was 24 (IQR 0.0-24.2), and 24 patients (9.6%) had a complication burden with CCI≥40. At baseline the impedance vectors of severe complicated patients were shorter compared to the vectors of uncomplicated patients only for the female subgroup (P=0.016). The preoperative extracellular water (ECW) was significantly higher in patients who experienced severe morbidity according to the CDC or not [19.4L (17.5-22.0) vs. 18.2L (15.6-20.6), P=0.009, respectively] and CCI≥40, or not [20.3L (18.5-22.7) vs. 18.3L (15.6-20.6), P=0.002, respectively]. The hydration index on POD1 was significantly higher in patients who experienced major complications than in uncomplicated patients (P=0.020 and P=0.025 for CDC and CCI, respectively).At a linear regression model, age (ß=0.14, P=0.035), sex female (ß=0.40, P<0.001), BMI (ß=0.30, P<0.001), and malnutrition (ß=0.14, P=0.037) were independent predictors of postoperative ECW. CONCLUSION: The amount of extracellular fluid accumulation predicts major morbidity after pancreatic surgery. Female, obese and malnourished patients were at high risk of extracellular fluid accumulation.

The evolution of post-operative pancreatic fistula (POPF) classification: A single-center experience.

BACKGROUND: The ISGPS classification of post-operative pancreatic fistula (POPF) was recently revised, introducing the concept of biochemical leak (BL) which replaced grade A POPF. More recently, an additional distinction on three different subclasses for grade B (B1-B3) POPF was proposed. The aim of this study was to evaluate the impact of these modifications in clinical practice. METHODS: All pancreatico-duodenectomies (PD) and distal pancreatectomies (DP) performed between 2010 and 2016 were retrospectively evaluated. Incidence and grade of POPF using the old and new ISGPS classification were evaluated. Three grade B subclasses (B1: maintenance of abdominal drain >3 weeks; B2: adoption of specific medical treatments for POPF; B3: use of radiological procedures) were evaluated for clinical severity. RESULTS: A total of 716 patients (502 PD, 214 DP) were evaluated. The new ISGPS classification reduced the reported rate of POPF (30.7% vs 35.2% for PD, p > 0.05; 28% vs 44.9% for DP, p < 0.05), due to the abolition of grade A POPF. Grade B1, B2 and B3 rates were 3.1%, 73.8% and 23.1% in PD and 12.3%, 47.4% and 40.3% in DP, respectively. Passing from B1 to B3, significant increases in wound infection (0-40%), mean length of stay in PD (14.7-22.5 days; p < 0.05) and readmission rate in DP (0-39.1%) were observed. CONCLUSIONS: The new ISGPS classification significantly reduces the reported rate of POPF, particularly after DP. The three different grade B subclasses (B1-B3) better discriminate the severity of post-operative course, especially after PD.

Pancreatic Neuroendocrine Tumours: The Role of Endoscopic Ultrasound Biopsy in Diagnosis and Grading Based on the WHO 2017 Classification.

BACKGROUND: One of the controversial issues in the diagnosis of pancreatic neuroendocrine tumours (pNETs) is the accurate prediction of their clinical behaviour. OBJECTIVES: The aim of the study was to evaluate the role of endoscopic ultrasound (EUS) biopsy in the diagnosis and grading of pNETs in a certified ENETS Center. METHODS: A prospectively maintained database of EUS biopsy procedures was retrospectively reviewed to identify all consecutive patients referred to a certified ENETS Center with a suspicion of pNET between June 2014 and April 2017. The cytological and/or histological specimens were stained and the Ki-67 labeling index was evaluated. In patients undergoing surgery, the grade obtained with EUS-guided biopsy was compared with the final histological grade. The grade was evaluated according to the 2017 WHO classifications and grading. RESULTS: The study population included 59 patients. EUS biopsy material reached an adequacy of 98.3% and was adequate for Ki-67 evaluation in 84.7% of cases. Twenty-nine patients (49.2%) underwent surgery. Of these, 25 patients had Ki-67 evaluated on EUS biopsy: the agreement between EUS biopsy grading and surgical specimen grading was 84%. CONCLUSION: EUS biopsy is an accurate method for the diagnosis and grading of pNETs based on the WHO 2017 Ki-67 labelling scheme.

Impact of Sarcopenic Obesity on Failure to Rescue from Major Complications Following Pancreaticoduodenectomy for Cancer: Results from a Multicenter Study.

BACKGROUND: Failure to rescue (FTR) is a quality-of-care indicator in pancreatic surgery, but may also identify patients who may not tolerate major postoperative complications despite being treated with best available care. Previous studies found that high visceral adipose tissue-to-skeletal muscle ratio is associated with poor outcomes following pancreaticoduodenectomy (PD). The aim of the study is to assess the impact of sarcopenic obesity on occurrence of FTR from major complications in cancer patients undergoing PD. METHODS: Prospectively collected data from three high-volume hospitals were reviewed. Total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed at preoperative staging computed tomography scan. Sarcopenic obesity was defined as high VFA/TAMA ratio. FTR was defined as postoperative mortality following major complication. RESULTS: 120 patients with major complications were included. FTR occurred in 23 (19.2%) patients. The "seminal" complications leading to FTR were pancreatic or biliary fistula-related sepsis (n = 14), postoperative pancreatic fistula (POPF)-related hemorrhage (n = 5), and duodenojejunal anastomosis leak-related sepsis (n = 1). On univariate analysis, older age [odds ratio (OR) 3.5, p = 0.034], American Society of Anesthesiologists (ASA) score 3+ (OR 4.2, p = 0.005), cardiovascular disease (OR 3.3, p = 0.013), low serum albumin (OR 2.6, p = 0.042), sarcopenic obesity (OR 4.2, p = 0.009), POPF (OR 3.1, p = 0.027), and cardiorespiratory complications (OR 3.7, p = 0.011) were significantly associated with FTR. On multivariate analysis, sarcopenic obesity [OR 5.7, 95% confidence interval (CI) 1.6-20.7, p = 0.008], ASA score 3+ (OR 4.1, 95% CI 1.2-14.3, p = 0.025), and pancreatic fistula (OR 3.2, 95% CI 1.0-10.2, p = 0.045) were independently associated with FTR. CONCLUSION: Sarcopenic obesity, low preoperative physical status, and occurrence of pancreatic fistula are associated with significantly higher risk of FTR from major complications after PD.

Management and Outcomes of Pancreatic Resections Performed in High-Volume Referral and Low-Volume Community Hospitals Lead by Surgeons Who Shared the Same Mentor: The Importance of Training.

BACKGROUND: High hospital volume improves outcomes after pancreatic resection. The aim of this study was to assess if practice and outcomes differed between high- and low-volume centers across which chief surgeons shared a similar training and mentoring. METHODS: Data on patients undergoing standard pancreatic resections (2010-2013) at 7 Italian hospitals were collected. Chiefs of pancreatic surgery at each hospital had received the same training, with the same mentor. Two centers were high-volume referral hospitals for pancreatic disease, while 5 were low-volume hospitals. RESULTS: A total of 856 patients were included, with median annual volume of resections 82 at high-volume referral hospitals and 11 at low-volume hospitals. Patients at low-volume hospitals were older, had more comorbidities, and were more often referred from the emergency room. Intraoperative techniques and reconstruction methods were similar. Comparable rates of major postoperative complications (18 vs. 22%; p = 0.236) and pancreatic fistula (29 vs. 32%; p = 0.287) were achieved in both groups, with no significant increases in failure to rescue from grade B-C fistula (6.2 vs. 15.0%; p = 0.108) and mortality (2.4 vs. 4.1%; p = 0.233) in low-volume hospitals. Postoperative length of stay was shorter in high-volume referral hospitals (10 vs. 15 days; p < 0.001). CONCLUSION: Similar postoperative outcomes can be achieved across high- and low-volume centers where chief surgeons shared a similar training and mentoring. However, multidisciplinary postoperative provision more often associated with high-volume centers may also affect outcomes.