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Abstract Background Value-based healthcare (VBHC) is an approach that focuses on delivering the highest possible value for patients while driving cost efficiency in health services. It emphasizes improving patient outcomes and experiences while optimizing the use of resources, shifting the healthcare system’s focus from the volume of services to the value delivered. Our study assessed the effectiveness of implementing a VBHC-principled, tailored preoperative evaluation in enhancing patient care and outcomes, as well as reducing healthcare costs. Methods We employed a quality improvement, before-and-after approach to assessing the effects of implementing VBHC strategies on the restructuring of the preoperative evaluation clinics at Humanitas Research Hospital. The intervention introduced a VBHC-tailored risk matrix during the postintervention phase (year 2021), and the results were compared with those of the preintervention phase (2019). The primary study outcome was the difference in the number of preoperative tests and visits at baseline and after the VBHC approach. Secondary outcomes were patient outcomes and costs. Results A total of 9722 patients were included: 5242 during 2019 (baseline) and 4,480 during 2021 (VBHC approach). The median age of the population was 63 (IQR 51–72), 23% of patients were classified as ASA 3 and 4, and 26.8% (2,955 cases) were day surgery cases. We found a considerable decrease in the number of preoperative tests ordered for each patient [6.2 (2.5) vs 5.3 (2.6) tests, p

IntroductionPancreatic ductal adenocarcinoma (PDAC) represents the complexity of interaction between cancer and cells of the tumor microenvironment (TME). Immune cells affect tumor cell behavior, thus driving cancer progression. Cancer-associated fibroblasts (CAFs) are responsible of the desmoplastic and fibrotic reaction by regulating deposition and remodeling of extracellular matrix (ECM). As tumor-promoting cells abundant in PDAC ECM, CAFs represent promising targets for novel anticancer interventions. However, relevant clinical trials are hampered by the lack of specific markers and elusive differences among CAF subtypes. Indeed, while single-cell transcriptomic analyses have provided important information on the cellular constituents of PDACs and related molecular pathways, studies based on the identification of protein markers in tissues aimed at identifying CAF subtypes and new molecular targets result incomplete.MethodsHerein, we applied multiplexed Imaging Mass Cytometry (IMC) at single-cell resolution on 8 human PDAC tissues to depict the PDAC composing cells, and profiling immune cells, endothelial cells (ECs), as well as endocrine cells and tumor cells.ResultsWe focused on CAFs by characterizing up to 19 clusters distinguished by phenotype, spatiality, and interaction with immune and tumor cells. We report evidence that specific subtypes of CAFs (CAFs 10 and 11) predominantly are enriched at the tumor-stroma interface and closely associated with tumor cells. CAFs expressing different combinations of FAP, podoplanin and cadherin-11, were associated with a higher level of CA19-9. Moreover, we identified specific subsets of FAP+ and podoplanin+/cadherin-11+ CAFs enriched in patients with negative prognosis.DiscussionThe present study provides new general insights into the complexity of the PDAC microenvironment by defining phenotypic heterogeneities and spatial distributions of CAFs, thus suggesting different functions of their subtypes in the PDAC microenvironment.

Abstract 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.

IntroductionMetabolic 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.MethodsWe 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.ResultsPancreatic 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.DiscussionPJ metabolic fingerprints reflect PDAC molecular subtypes and the immune microenvironment, confirming PJ as a promising source of biomarkers for personalized therapy.

Introduction: Infections caused by multidrug-resistant bacteria (MDR) occur more frequently after pancreaticoduodenectomy (PD) compared to other abdominal surgeries, and infective complications represent a major determinant of postoperative morbidity following PD. Preoperative biliary stent (PBS) placement often leads to biliary contamination, which plays a significant role in postoperative infections. The aim of this study is to evaluate the impact of MDR contamination on short-term postoperative outcomes in patients undergoing PD and to evaluate the relationship between MDR bacteria, PBS, and bile contamination. Methods: This is a retrospective study based on a prospectively maintained database including 825 consecutive patients who underwent pancreaticoduodenectomies (PDs). All procedures were performed by experienced pancreatic surgeons at a high-volume center and the patients were managed according to the same perioperative enhanced recovery protocol. Results: MDR bacteria were present in 17.5% of bile cultures, exclusively within the stented group. At the multivariate analysis, the development of major postoperative complications (MPC) was correlated with the presence of MDR bacteria in the bile (OR 1.66, 95% CI: 1.1–2.52; p = 0.02). MDR bacteria were detected early in the surgical drainage in 144 out of 825 patients (12.1%), with 72.2% having a previous biliary stent placement and 27.8% without stents (p < 0.001). Moreover, the development of an MPC was associated with the presence of MDR bacteria in the drainage (OR = 1.81, 95% CI: 1.21–2.73, p = 0.0042). Conclusions: We demonstrated that MDR contamination worsens the short-term outcomes of patients undergoing PDs. Specifically, when MDR bacteria are present in both the bile and drainage, there is a statistically significant increase in the incidence of major postoperative complications (MPC). Our data suggest that the majority of MDR surgical site infections stem from biliary contamination resulting from the placement of a preoperative biliary stent (PBS).

Background and aim: Guidelines suggest endoscopic resection for rectal neuroendocrine tumors (rNETs) < 10 mm, but the most appropriate resection technique is unclear. In real-life clinical practice, the endoscopic removal of unrecognized rNETs can take place with “simple” techniques and without preliminary staging. The aim of the current study is to report our own experience at a referral center for both neuroendocrine neoplasms and endoscopy. Methods: Retrospective analyses of polypectomies were performed at the Humanitas Research Hospital for rNETs (already diagnosed or previously unrecognized). Results: A total of 19 patients were included, with a median lesion size of 5 mm (range 3–10 mm). Only five lesions were suspected as NETs before removal and underwent endoscopic ultrasound (EUS) before resection, being removed with advanced endoscopic techniques. Unsuspected rNETs were removed by cold polypectomy in eleven cases, EMR in two, and biopsy forceps in one. When described, the margins were negative in four cases, positive in four (R1), and indeterminate in one. The median follow-up was 40 months. A 10 mm polypoid lesion removed with cold snare polypectomy (G2 R1) needed subsequent surgery. Eighteen patients underwent EUS after a median time of 6.5 months from resection. The EUS identified local recurrence after 14 months in a 7 mm polypoid lesion removed with cold snare polypectomy (G1 R1); the lesion was treated with cap-assisted EMR. For all the other lesions, the follow-up was negative. Conclusions: When rNETs are improperly removed without prior staging, caution must be exercised. The data from our cohort suggest that even if inappropriate resection had happened, patients may be safely managed with early EUS evaluation.

Abstract Background The genomes of present-day non-Africans are composed of 1–3% of Neandertal-derived DNA as a consequence of admixture events between Neandertals and anatomically modern humans about 50–60 thousand years ago. Neandertal-introgressed single nucleotide polymorphisms (aSNPs) have been associated with modern human disease-related traits, which are risk factors for pancreatic ductal adenocarcinoma (PDAC), such as obesity, type 2 diabetes, and inflammation. In this study, we aimed at investigating the role of aSNPs in PDAC in three Eurasian populations. Results The high-coverage Vindija Neandertal genome was used to select aSNPs in non-African populations from 1000 Genomes project phase 3 data. Then, the association between aSNPs and PDAC risk was tested independently in Europeans and East Asians, using existing GWAS data on more than 200 000 individuals. We did not find any significant associations between aSNPs and PDAC in samples of European descent, whereas, in East Asians, we observed that the Chr10p12.1-rs117585753-T allele (MAF = 10%) increased the risk to develop PDAC (OR = 1.35, 95%CI 1.19–1.54, P = 3.59 × 10–6), with a P-value close to a threshold that takes into account multiple testing. Conclusions Our results show only a minimal contribution of Neandertal SNPs to PDAC risk.

Aim: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). Methods: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. Results: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. Conclusion: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.

There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological–molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.

Gastrointestinal tract breast cancer (BC) metastases represent a rare event and generally originate from the lobular subtype. Duodenal involvement was rarely described in previous case series. Abdominal symptoms are extremely unspecific and misleading. Diagnosis is challenging, and it consists of a few mandatory steps from radiological examinations to histological and immunohistochemical analyses. Here, we presented the clinical case of a 54-year-old postmenopausal woman who was hospitalized for vomiting and jaundice, presenting increased level of liver enzymes and minimal main bile duct and choledocus dilatation at abdominal ultrasonography. She underwent breast-conserving surgery and axillary lymph node dissection for stage IIIB lobular BC, 5 years before. Metastatic infiltration of the duodenal bulb originating from lobular BC was proven histologically, through fine-needle aspiration during endoscopic ultrasonography. Treatment was established after multidisciplinary team evaluation, based on the clinical status and prognosis of the patient. Pancreaticoduodenectomy was performed, and final histological examination confirmed the secondary localization of lobular BC, infiltrating the duodenal and gastric wall, pancreas parenchyma, and surrounding tissues. No metastatic lymph nodes were found. After surgery, the patient underwent first line of adjuvant systemic treatment with fulvestrant and ribociclib. After a follow-up of 21 months, the patient was in good clinical condition, without signs of locoregional or distant recurrence. This report stressed on the importance of a tailored therapeutic approach. Although systemic therapy generally represents the preferred option, surgery should not be excluded if an oncological radical resection can be performed achieving acceptable locoregional disease control.

Background. Survival after surgery for pancreatic ductal adenocarcinoma (PDAC) remains poor, due to early recurrence (ER) of the disease. A global definition of ER is lacking and different cut-off values (6, 8, and 12 months) have been adopted. The aims of this study were to define the optimal cut-off for the definition of ER and predictive factors for ER. Methods. Recurrence was recorded for all consecutive patients undergoing upfront surgery for PDAC at our institute between 2010 and 2017. Receiver operating characteristic (ROC) curves were utilized, to estimate the optimal cut-off for the definition of ER as a predictive factor for poor post-progression survival (PPS). To identify predictive factors of ER, univariable and multivariable logistic regression models were used. Results. Three hundred and fifty one cases were retrospectively evaluated. The recurrence rate was 76.9%. ER rates were 29.0%, 37.6%, and 47.6%, when adopting 6, 8, and 12 months as cut-offs, respectively. A significant difference in median PPS was only shown between ER and late recurrence using 12 months as cut-off (p = 0.005). In the multivariate analysis, a pre-operative value of CA 19-9 > 70.5 UI/L (OR 3.10 (1.41–6.81); p = 0.005) and the omission of adjuvant treatment (OR 0.18 (0.08–0.41); p < 0.001) were significant predictive factors of ER. Conclusions. A twelve-months cut-off should be adopted for the definition of ER. Almost 50% of upfront-resected patients presented ER, and it significantly affected the prognosis. A high preoperative value of CA 19-9 and the omission of adjuvant treatment were the only predictive factors for ER.

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.

Summary: 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.

IntroductionMalnutrition and alteration of body composition are early features in pancreatic cancer and appear to be predictors of advanced stages and dismal overall survival. Whether specific patient characteristics measured at the preoperative bioimpedance analysis (BIA) could be associated with long-term outcomes following curative resection has not been yet described.MethodsIn a prospective multicenter study, all histologically proven resected pancreatic cancer patients were included in the analysis. BIA was measured for all patients on the day before surgery. Demographics, perioperative data, and postoperative outcomes were prospectively collected. Patients who experienced 90-day mortality were excluded from the analysis. Survival data were obtained through follow-up visits and phone interviews. Bioimpedance variables were analyzed according to the overall survival using the Kaplan–Meier curves and the univariate and multivariate Cox regression model.ResultsOverall, 161 pancreatic cancer patients were included. The median age was 66 (60–74) years, and 27.3% received systemic neoadjuvant treatment. There were 23 (14.3%) patients malnourished in the preoperative evaluation. Median OS was 34.0 (25.7–42.3) months. Several bioimpedance variables were associated with OS at the univariate analysis, namely the phase angle [HR 0.85, 95% CI 0.74–0.98)], standardized phase angle [HR 0.91, 95% CI 0.82–0.99)], and an increased ratio between the fat and lean mass (FM/FFM) [HR 4.27, 95% CI 1.10–16.64)]. At the multivariate analysis, the FM/FFM ratio was a confirmed independent predictor of OS following radical resection, together with a positive lymph nodal status.ConclusionAlteration of body composition at the preoperative bioimpedance vector analysis (BIVA) can predict dismal oncologic outcomes following pancreatic resection for cancer.

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.

Background and aimsBody composition parameters and immunonutritional indexes provide useful information on the nutritional and inflammatory status of patients. We sought to investigate whether they predict the postoperative outcome in patients with pancreatic cancer (PC) who received neoadjuvant therapy (NAT) and then pancreaticoduodenectomy.MethodsData from locally advanced PC patients who underwent NAT followed by pancreaticoduodenectomy between January 2012 and December 2019 in four high-volume institutions were collected retrospectively. Only patients with two available CT scans (before and after NAT) and immunonutritional indexes (before surgery) available were included. Body composition was assessed and immunonutritional indexes collected were: VAT, SAT, SMI, SMA, PLR, NLR, LMR, and PNI. The postoperative outcomes evaluated were overall morbidity (any complication occurring), major complications (Clavien-Dindo ≥ 3), and length of stay.ResultsOne hundred twenty-one patients met the inclusion criteria and constituted the study population. The median age at the diagnosis was 64 years (IQR16), and the median BMI was 24 kg/m2 (IQR 4.1). The median time between the two CT-scan examined was 188 days (IQR 48). Skeletal muscle index (SMI) decreased after NAT, with a median delta of −7.8 cm2/m2 (p < 0.05). Major complications occurred more frequently in patients with a lower pre-NAT SMI (p = 0.035) and in those who gained in subcutaneous adipose tissue (SAT) compartment during NAT (p = 0.043). Patients with a gain in SMI experienced fewer major postoperative complications (p = 0.002). The presence of Low muscle mass after NAT was associated with a longer hospital stay [Beta 5.1, 95%CI (1.5, 8.7), p = 0.006]. An increase in SMI from 35 to 40 cm2/m2 was a protective factor with respect to overall postoperative complications [OR 0.43, 95% (CI 0.21, 0.86), p < 0.001]. None of the immunonutritional indexes investigated predicted the postoperative outcome.ConclusionBody composition changes during NAT are associated with surgical outcome in PC patients who receive pancreaticoduodenectomy after NAT. An increase in SMI during NAT should be favored to ameliorate the postoperative outcome. Immunonutritional indexes did not show to be capable of predicting the surgical outcome.

Abstract Background Recently, the first randomized trials comparing minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for non-malignant and malignant disease showed a 2-day reduction in time to functional recovery after MIDP. However, for pancreatic ductal adenocarcinoma (PDAC), concerns have been raised regarding the oncologic safety (i.e., radical resection, lymph node retrieval, and survival) of MIDP, as compared to ODP. Therefore, a randomized controlled trial comparing MIDP and ODP in PDAC regarding oncological safety is warranted. We hypothesize that the microscopically radical resection (R0) rate is non-inferior for MIDP, as compared to ODP. Methods/design DIPLOMA is an international randomized controlled, patient- and pathologist-blinded, non-inferiority trial performed in 38 pancreatic centers in Europe and the USA. A total of 258 patients with an indication for elective distal pancreatectomy with splenectomy because of proven or highly suspected PDAC of the pancreatic body or tail will be randomly allocated to MIDP (laparoscopic or robot-assisted) or ODP in a 1:1 ratio. The primary outcome is the microscopically radical resection margin (R0, distance tumor to pancreatic transection and posterior margin ≥ 1 mm), which is assessed using a standardized histopathology assessment protocol. The sample size is calculated with the following assumptions: 5% one-sided significance level (α), 80% power (1-β), expected R0 rate in the open group of 58%, expected R0 resection rate in the minimally invasive group of 67%, and a non-inferiority margin of 7%. Secondary outcomes include time to functional recovery, operative outcomes (e.g., blood loss, operative time, and conversion to open surgery), other histopathology findings (e.g., lymph node retrieval, perineural- and lymphovascular invasion), postoperative outcomes (e.g., clinically relevant complications, hospital stay, and administration of adjuvant treatment), time and site of disease recurrence, survival, quality of life, and costs. Follow-up will be performed at the outpatient clinic after 6, 12, 18, 24, and 36 months postoperatively. Discussion The DIPLOMA trial is designed to investigate the non-inferiority of MIDP versus ODP regarding the microscopically radical resection rate of PDAC in an international setting. Trial registration ISRCTN registry ISRCTN44897265 . Prospectively registered on 16 April 2018.

The choice of the most appropriate suture threads for pancreatic anastomoses may play an important role in reducing the incidence of post-operative pancreatic fistula (POPF). The literature on this topic is still not conclusive. The aim of this study was to analyze the mechanical characteristics of suture materials to find the best suture threads for pancreatic anastomoses. A single-axial electromagnetic actuation machine was used to obtain the stress–deformation relationship curves and to measure both the ultimate tensile strength (UTS) and the Young’s modulus at the 0–3% deformation range (E0–3) of four different suture materials (Poliglecaprone 25, Polydioxanone, Polyglactin 910, and Polypropylene) at baseline and after incubation in saline solution, bile, and pancreatic juice for 1, 3, and 7 days. Polydioxanone and Polypropylene showed stable values of UTS and E0–3 in all conditions. Polyglactin 910 presented significant UTS and E0–3 variations between different time intervals in all types of liquids analyzed. Poliglecaprone 25 lost half of its strength in all biological liquids analyzed but maintained low E0–3 values, which could reduce the risk of lacerations of soft tissues. These results suggest that Polydioxanone and Poliglecaprone 25 could be the best suture materials to use for pancreatic anastomoses. In vivo experiments will be organized to obtain further confirmations of this in vitro evidence.

Abstract 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.

Pancreatic neuroendocrine tumor (PNET) behavior assessment is a daily challenge for physicians. Modern PNET management varies from a watch-and-wait strategy to surgery depending on tumor aggressiveness. Therefore, the aggressiveness definition plays a pivotal role in the PNET work-up. The aggressiveness of PNETs is mainly based on the dimensions and histological grading, with sometimes a lack of specificity and sensibility. In the last twenty years, EUS has become a cornerstone in the diagnostic phase of PNET management for its high diagnostic yield and the possibility of obtaining a histological specimen. The number of EUS applications in the PNET work-up has been rapidly increasing with new and powerful possibilities. The application of contrast has led to an important step in PNET detection; in recent years, it has been gaining interesting applications in aggressiveness assessment. In this review, we underline the latest experiences and opportunities in the behavior assessment of PNETs using contact-enhanced EUS and contested enhanced harmonic EUS with a particular focus on the future application and possibility that these techniques could provide.

Objectives:. To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. Background:. The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Methods:. Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss’ k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or 180° (k range: 0.619–0.756). Neither reviewers’ specialty nor hospital volume influenced the agreement. Conclusions:. There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.

Introduction:. Postoperative pancreatic fistula (POPF) is the most dreaded complication after distal pancreatectomy (DP). This multicenter randomized trial evaluated the efficacy, safety, and tolerance of Hemopatch in preventing clinically relevant (grades B/C according to the ISGPS classification) POPF after DP. Material and methods:. After stump closure, patients were randomized to affix Hemopatch to the stump or not. Statistical significance was set at 0.025. Clinical significance was defined as the number of patients needed to treat (NNT) to avoid 1 B/C POPF. Results:. Of 631 eligible patients, 360 were randomized and 315 analyzed per protocol (155 in the standard closure group; 160 in the Hemopatch group). The rates of B/C POPF (the primary endpoint) were 23.2% and 16.3% (P = 0.120), while the number of patients with 1 or more complications (including patients with B/C POPF) was 34.8% and 24.4% (P = 0.049) in the standard and Hemopatch groups, respectively. In patients with hand-sewn stump and main duct closure, the rates were 26.2% versus 10.0% (P = 0.014) and 23.3% versus 7.7% (P = 0.015) in the standard and Hemopatch groups, respectively. The NNT in these 2 subgroups was 6 and 6.4, respectively. Conclusion:. The results of the first randomized trial evaluating Hemopatch-reinforced pancreatic stump after DP to prevent type B/C POPF do not allow us to conclude that the risk of B/C POPF was lower. Based on the NNT, however, routine use of Hemopatch after DP may result in fewer complications (including POPF) overall, especially in cases with hand-sewn closure of the pancreatic stump or main pancreatic duct.

Introduction: The optimal treatment for small, asymptomatic, nonfunctioning pancreatic neuroendocrine neoplasms (NF-PanNEN) is still controversial. European Neuroendocrine Tumor Society (ENETS) guidelines recommend a watchful strategy for asymptomatic NF-PanNEN 18 years, the presence of asymptomatic sporadic NF-PanNEN ≤2 cm proven by a positive fine-needle aspiration (FNA) or by the presence of a measurable nodule on high-quality imaging techniques that is positive at 68Gallium DOTATOC-PET scan.Conclusion: The ASPEN study is designed to investigate if an active surveillance of asymptomatic NF-PanNEN ≤2 cm is safe as compared to surgical approach.

PurposeTo appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma.MethodsA cohort of 100 patients was included in this retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index.ResultsA clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively.ConclusionA CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.

Background and aimsPancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.MethodsMS-status was screened by a panel of 5 mononucleotide repeats (Bat26, Bat25, NR-21, NR-24 and NR-27) in 338 consecutive pancreatic ductal adenocarcinoma (PDAC), resected at two Italian and one German referral centres. The personal history of pancreatic cancer was assessed in an independent set of 58 probands with LS and in 138 first degree relatives who had cancers.ResultsOnly one PDAC (0.3%) showed MSI. This was a medullary type cancer, with hMLH1-deficiency, and no identified germ-line mutation but methylation of hMLH1. Pancreatic cancer occurred in 5 (2.5%) LS patients. Histological sampling was available for 2 cases, revealing PDAC in one case and an ampullary cancer in the other one.ConclusionsMSI prevalence is negligible in sporadic, resected PDAC. Differently, the prevalence of pancreatic cancer is 2.5% in LS patients, and cancers other than PDAC may be encountered in this setting. Surveillance for pancreatic cancer should be advised in LS mutation carriers at referral centers.