Italian survey about intraperitoneal drain use in distal pancreatectomy.

Intraperitoneal prophylactic drain (IPD) use in distal pancreatectomy (DP) is still controversial. A survey was carried out through the Italian community of pancreatic surgeons using institutional emails, Twitter, and Facebook accounts of the Italian Association for the Study of the Pancreas (AISP) and the Italian Association of Hepato-biliary-pancreatic Surgery (AICEP). The survey was structured to learn surgeons' practice in using IPD through questions and one clinical vignette. Respondents were asked to report their regrets for omission and commission regarding the IPD use for the clinical scenario, eliciting a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were built to identify respondents' attitudes. One hundred six surgeons completed the survey. Sixty-three (59.4%) respondents confirmed using at least 1 drain, while 43 (40.6%) placed 2 IPDs. Only 13 respondents (12.3%) declared a change in IPD strategy in patients at high risk of clinically relevant postoperative pancreatic fistula (CR-POPF), while 9 (9.4%) respondents changed their strategy in low-risk POPF situations. Thirty-five (35.5%) respondents declared they would remove the IPD within the third postoperative day (POD) in the absence of CR-POPF suspicion. The median omission regret, which proved to be the wrong decision, was 80 (50-100, IQR). The median regret due to the commission of IPD, which turned out to be useless, was 2.5 (1-20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 7% (1-35, IQR). The threshold to perceive drain omission as the least regrettable choice was higher in female surgeons (P < 0.001), in surgeons who modulated the strategies based on the risk of CR-POPF, and in high volume centers (p = 0.039). The threshold was lower in surgeons who performed minimally invasive distal pancreatectomy (P < 0.001), adopted a closed system (P < 0.001), placed two IPDs (P < 0.001), or perceived the IPD as important to prevent reintervention (p = 0.047). Drain management after DP remains very heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients (7% of CR-POPF), leading to low regret in the case of the wrong decision, making it an acceptable clinical decision.

Integrating metabolic profiling of pancreatic juice with transcriptomic analysis of pancreatic cancer tissue identifies distinct clinical subgroups.

Introduction: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities. Methods: We performed a transcriptomic analysis of 26 PDAC samples grouped into 3 metabolic clusters (M_CL) according to their PJ metabolic profile. We analyzed molecular subtypes and transcriptional differences. Validation was performed by multidimensional imaging on tumor slides. Results: Pancreatic juice metabolic profiling was associated with PDAC transcriptomic molecular subtypes (p=0.004). Tumors identified as M_CL1 exhibited a non-squamous molecular phenotype and demonstrated longer survival. Enrichment analysis revealed the upregulation of immune genes and pathways in M_CL1 samples compared to M_CL2, the group with worse prognosis, a difference confirmed by immunofluorescence on tissue slides. Enrichment analysis of 39 immune signatures by xCell confirmed decreased immune signatures in M_CL2 compared to M_CL1 and allowed a stratification of patients associated with longer survival. Discussion: PJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy.

Impact of Preoperative Malnutrition on Patients with Pancreatic Neoplasms Post-Duodenopancreatectomy: A Retrospective Cohort Study.

BACKGROUND: Preoperative malnutrition is a significant factor in patients with pancreatic tumors undergoing pancreaticoduodenectomy. The aim of this study was to assess the association between preoperative malnutrition and delayed discharge within a ten-day timeframe and potential correlations between preoperative malnutrition and postoperative surgical complications. METHODS: A retrospective cohort study was conducted, recruiting a final sample of 79 patients with benign or malignant cephalic pancreatic tumors from 2015 to 2022. The risk of malnutrition was assessed using the Malnutrition Universal Screening Tool, while length of hospital stay and relevant clinical data were extracted from clinical documentation. RESULTS: The preoperative malnutrition risk was high in 21.52% of the sample, moderate in 36.71%, and low in 41.77%. Body mass index (BMI) (p = 0.007) and postoperative surgical complications (p < 0.001) were significantly correlated with delayed discharge. No statistically significant differences were found between levels of malnutrition risk and delayed discharge (p = 0.122), or postoperative surgical complications (p = 0.874). CONCLUSIONS: Postoperative complications and BMI emerge as significant risk factors. The limited sample size may have compromised the collection of homogeneous and significant data. Future studies should evaluate the implementation of personalized nutritional screening tools, nutritional assessment plans, and the involvement of specialized health professionals.

The use of Arista AH as a local haemostatic agent in distal splenopancreatectomy: report of two cases.

Bleeding is still one of the most feared intraoperative and postoperative complications that can lead to an increase in morbidity, mortality, length of hospital stay and costs. Nowadays, in addition to accurate surgical techniques, several local haemostatic agents are available and can be used in case of oozing bleeding. Herein, we report our experience with a ready-to-use polysaccharide powder in two patients undergoing distal splenopancreatectomy. Bleeding control was achieved in both cases. No patient showed postoperative bleeding, and no other complications were reported.

Autologous Pancreatic Islet Cell Transplantation Following Pancreatectomy for Pancreas Diseases Other Than Chronic Pancreatitis: A 15-y Study of the Milan Protocol.

BACKGROUND: Pancreatogenic diabetes, a consequence of pancreatic tissue loss following pancreatectomy, poses a significant challenge for patients undergoing pancreatic surgery. Islet autotransplantation (IAT) offers a promising approach to prevent or alleviate pancreatogenic diabetes, but its application has been limited to individuals with painful chronic pancreatitis. METHODS: This study presents a 15-y clinical experience with the Milan Protocol, which expands IAT after pancreatectomy to a broader spectrum of patients with malignant and nonmalignant pancreatic diseases. The analysis evaluates feasibility, efficacy, and safety of IAT. Modified Igls criteria validated through the arginine test and mixed meal tolerance tests were used to assess long-term metabolic outcomes. RESULTS: Between November 2008 and June 2023, IAT procedures were performed on 114 of 147 candidates. IAT-related complications occurred in 19 of 114 patients (16.7%), with 5 being potentially serious. Patients exhibited sustained C-peptide secretion over the 10-y follow-up period, demonstrating a prevalence of optimal and good beta-cell function. Individuals who underwent partial pancreatectomy demonstrated superior metabolic outcomes, including sustained C-peptide secretion and a reduced risk of developing diabetes or insulin dependence compared with those who underwent total pancreatectomy. For patients who had total pancreatectomy, the quantity of infused islets and tissue volume were identified as critical factors influencing metabolic outcomes. An increased risk of recurrence or progression of baseline diseases was not observed in subjects with neoplasms. CONCLUSIONS: These findings provide valuable insights into the benefits and applications of IAT as a therapeutic option for pancreatogenic diabetes after pancreatic surgery, expanding its potential beyond painful chronic pancreatitis.

Intraperitoneal prophylactic drain after pancreaticoduodenectomy: an Italian survey.

Intraperitoneal prophylactic drain (IPD) use in pancreaticoduodenectomy (PD) is still controversial. A survey was designed to investigate surgeons' use of IPD in PD patients through 23 questions and one clinical vignette. For the clinical scenario, respondents were asked to report their regret of omission and commission regarding the use of IPD elicited on a scale between 0 (no regret) and 100 (maximum regret). The threshold model and a multilevel mixed regression were applied. One hundred three (97.2%) respondents confirmed using at least two IPDs. The median regret due to the omission of IPD was 84 (67-100, IQR). The median regret due to the commission of IPD was 10 (3.5-20, IQR). The CR-POPF probability threshold at which drainage omission was the less regrettable choice was 3% (1-50, IQR). The threshold was lower for those surgeons who performed minimally invasive PD (P = 0.048), adopted late removal (P = 0.002), perceived FRS able to predict the risk (P = 0.006), and IPD able to avoid relaparotomy P = 0.036). Drain management policies after PD remain heterogeneous among surgeons. The regret model suggested that IPD omission could be performed in low-risk patients.

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.

REDISCOVER guidelines for borderline-resectable and locally advanced pancreatic cancer: management algorithm, unanswered questions, and future perspectives.

The REDISCOVER guidelines present 34 recommendations for the selection and perioperative care of borderline-resectable (BR-PDAC) and locally advanced ductal adenocarcinoma of the pancreas (LA-PDAC). These guidelines represent a significant shift from previous approaches, prioritizing tumor biology over anatomical features as the primary indication for resection. Condensed herein, they provide a practical management algorithm for clinical practice. However, the guidelines also highlight the need to redefine LA-PDAC to align with modern treatment strategies and to solve some contradictions within the current definition, such as grouping "difficult" and "impossible" to resect tumors together. Furthermore, the REDISCOVER guidelines highlight several areas requiring urgent research. These include the resection of the superior mesenteric artery, the management strategies for patients with LA-PDAC who are fit for surgery but unable to receive multi-agent neoadjuvant chemotherapy, the approach to patients with LA-PDAC who are fit for surgery but demonstrate high serum Ca 19.9 levels even after neoadjuvant treatment, and the optimal timing and number of chemotherapy cycles prior to surgery. Additionally, the role of primary chemoradiotherapy versus chemotherapy alone in LA-PDAC, the timing of surgical resection post-neoadjuvant/primary chemoradiotherapy, the efficacy of ablation therapies, and the management of oligometastasis in patients with LA-PDAC warrant investigation. Given the limited evidence for many issues, refining existing management strategies is imperative. The establishment of the REDISCOVER registry ( https://rediscover.unipi.it/ ) offers promise of a unified research platform to advance understanding and improve the management of BR-PDAC and LA-PDAC.

Updates in the management of postoperative pancreatic fistula.

Postoperative pancreatic fistula (POPF) remains a common and dreaded complication after pancreatic resections and is associated with increased morbidity and mortality. Over the years, several different strategies have been investigated to prevent and mitigate POPF. However, when a POPF occurs, a consensus on the optimal management strategy of grade B and grade C POPF is still lacking, and the current management strategy is often based on local expertise and driven by patient's condition. Nevertheless, whereas the incidence of POPF after pancreatic surgery has remained stable, the overall mortality related to this complication has decreased over the years. This reflects an improvement in the management of this complication, which has become increasingly conservative. The aim of this review is to provide an updated evidence- based overview on the management strategies of POPF for surgeons and physicians in the clinical practice.

Microbial composition associated with biliary stents in patients undergoing pancreatic resection for cancer.

Malignant bile duct obstruction is typically treated by biliary stenting, which however increases the risk of bacterial infections. Here, we analyzed the microbial content of the biliary stents from 56 patients finding widespread microbial colonization. Seventeen of 36 prevalent stent species are common oral microbiome members, associate with disease conditions when present in the gut, and include dozens of biofilm- and antimicrobial resistance-related genes. This work provides an overview of the microbial communities populating the stents.

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.

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.

Analysis of the Mechanical Characteristics of Human Pancreas through Indentation: Preliminary In Vitro Results on Surgical Samples.

Pancreatic surgery is extremely challenging and demands an extended learning curve to be executed with a low incidence of post-operative complications. The soft consistency of the human pancreas poses a primary challenge for pancreatic surgeons. This study aimed to analyze the preliminary mechanical characteristics of the human pancreas to develop a realistic synthetic phantom for surgical simulations in the near future. Pancreatic specimens, comprehensive of the pancreatic parenchyma and main pancreatic duct, were collected during pancreatic resections and analyzed through nano-bio-indentation (BioindenterTM UNHT3 Bio, Anton Paar GmbH, Graz, Austria) to measure the elastic modulus. Comparisons were made between slow and fast loading rates, immediate and post-freezing analyses, and multipoint indentations. The results demonstrated that a slow loading rate (30 µN/min), immediate analysis, and multipoint measurements are crucial for obtaining accurate values of the elastic modulus of the human pancreas (1.40 ± 0.47 kPa). In particular, the study revealed that analysis after freezing could impact the outcomes of the indentation. Moreover, the study suggested that both the pancreatic parenchyma and the main pancreatic duct should be analyzed to achieve a more precise and comprehensive definition of the. mechanical features of the pancreas. These preliminary findings represent the initial steps toward defining the consistency and mechanical characteristics of human pancreatic tissue with the goal of creating a realistic synthetic phantom.

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.

Alteration of the immunophenotype and cytokine profiles in patients affected by neuroendocrine neoplasms.

PURPOSE: Neuroendocrine neoplasms (NENs) are tumors that arise from cells of the endocrine system and are most common in the gastrointestinal tract, the pancreas, and the lungs. Their incidence is rapidly increasing and the therapeutic options available are limited. METHODS: Since the immune system can interfere with tumor growth and response to therapy, using flow cytometry we investigated the immunophenotype in samples of peripheral blood leukocytes from patients with pancreatic (Pan-NENs) and pulmonary NENs (Lung-NENs). Moreover, we performed a multiplex analysis of 13 key cytokines and growth factors essential for the immune response in the plasma of NEN patients and controls. RESULTS: Patients presented with a higher percentage of granulocytes, a lower percentage of lymphocytes, and an increase in the granulocytes to lymphocytes ratio compared to healthy donors. These alterations were more marked in patients with metastasis. Somatostatin analogs (SSAs) restored the immunophenotype of patients to that seen in healthy donors. Finally, Pan-NEN patients showed a higher plasma concentration of IP-10, MCP-1, and IL-8 compared to healthy donors, suggesting a potential role for these cytokines as diagnostic biomarkers. CONCLUSION: This study highlighted differences in the immunophenotype of patients with Pan- and Lung-NENs compared to healthy individuals; these alterations were partially restored by therapy.

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.

Exploring a novel composite method using non-contrast EUS enhanced microvascular imaging and cyst fluid analysis to differentiate pancreatic cystic lesions.

BACKGROUND AND AIMS: Differentiating pancreatic cystic lesions (PCLs) remains a diagnostic challenge. The use of high-definition imaging modalities which detect tumor microvasculature have been described in solid lesions. We aim to evaluate the usefulness of cystic microvasculature when used in combination with cyst fluid biochemistry to differentiate PCLs. METHODS: We retrospectively analyzed 110 consecutive patients with PCLs from 2 Italian Hospitals who underwent EUS with H-Flow and EUS fine needle aspiration to obtain cystic fluid. The accuracy of fluid biomarkers was evaluated against morphological features on radiology and EUS. Gold standard for diagnosis was surgical resection. A clinical and radiological follow up was applied in those patients who were not resected because not surgical indication and no signs of malignancy were shown. RESULTS: Of 110 patients, 65 were diagnosed with a mucinous cyst, 41 with a non-mucinous cyst, and 4 with an undetermined cyst. Fluid analysis alone yielded 76.7% sensitivity, 56.7% specificity, 77.8 positive predictive value (PPV), 55.3 negative predictive value (NPV) and 56% accuracy in diagnosing pancreatic cysts alone. Our composite method yielded 97.3% sensitivity, 77.1% specificity, 90.1% PPV, 93.1% NPV, 73.2% accuracy. CONCLUSIONS: This new composite could be applied to the holistic approach of combining cyst morphology, vascularity, and fluid analysis alongside endoscopist expertise.

Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial.

Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.