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Objective: To assess the probability of being cured of pancreatic ductal adenocarcinoma (PDAC) by pancreatic surgery., Background: Statistical cure implies that a patient treated for a specific disease will have the same life expectancy as if he/she never had that disease., Methods: Patients who underwent pancreatic resection for PDAC between 2010 and 2021 were retrospectively identified using a multi-institutional database. A nonmixture statistical cure model was applied to compare disease-free survival to the survival expected for a matched general population., Results: Among 2554 patients, either in the setting of upfront (n=1691) or neoadjuvant strategy (n=863), the cure model showed that the probability that surgery would offer the same life expectancy (and tumor-free) as the matched general population was 20.4% (95% CI: 18.3, 22.5). Cure likelihood reached the 95% of certainty (time to cure) after 5.3 years (95% CI: 4.7, 6.0). A preoperative model was developed based on tumor stage at diagnosis ( P =0.001), radiologic size ( P =0.001), response to chemotherapy ( P =0.007), American Society of Anesthesiology class ( P =0.001), and preoperative Ca19-9 ( P =0.001). A postoperative model with the addition of surgery type ( P =0.015), pathologic size ( P =0.001), tumor grading ( P =0.001), resection margin ( P =0.001), positive lymph node ratio ( P =0.001), and the receipt of adjuvant therapy ( P =0.001) was also developed., Conclusions: Patients operated for PDAC can achieve a life expectancy similar to that of the general population, and the likelihood of cure increases with the passage of recurrence-free time. An online calculator was developed and available at https://aicep.website/?cff-form=15 ., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Long-term survivors (LTSs) after pancreatic resection of pancreatic ductal adenocarcinoma (PDAC) represent a particular subgroup of patients that remains poorly understood. The primary endpoint was to identify clinicopathological factors associated with LTSs after pancreatic resection for PDAC., Methods: This was a retrospective study of patients who had undergone pancreatic resection for PDAC. Long survival was defined as a patient who survived at least 60 months. Patients were divided in two groups: LTS and short-term survivor (STS). The two groups were compared regarding epidemiological, clinical, and pathological data. Propensity score matching (PSM) was used to reduce selection bias with a 1:2 ratio. Multivariable analysis of significative predictive factors before and after PSM was done., Results: Three hundred and thirty-three patients were enrolled: 46 (13.8%) in the LTS group and 287 (86.2%) in the STS group. Using PSM, 138 patients were analyzed: 46 in the LTS group and 92 in the STS group. At the multivariate analysis of significative predictive factor after PSM, adjuvant chemotherapy, well-differentiated tumors (G1), and R0 status were related to long-term survival (p = 0.052, 0.010 and p = 0.019, respectively). Kaplan-Meier survival curves confirmed these data. Additionally, Kaplan-Meier survival curves showed that pathological stage I was a favorable factor with respect to stage II, III, and IV., Conclusions: Long-term survival is possible after pancreatic cancer resection, even if in a small percentage. Significant predictors of long-term survival are administration of adjuvant chemotherapy, American Join Committee on Cancer stage I, well-differentiated tumor (G1), and R0 resection., (© 2024 The Author(s). World Journal of Surgery published by John Wiley & Sons Ltd on behalf of International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Importance: There are currently no clinically relevant criteria to predict a futile up-front pancreatectomy in patients with anatomically resectable pancreatic ductal adenocarcinoma., Objectives: To develop a futility risk model using a multi-institutional database and provide unified criteria associated with a futility likelihood below a safety threshold of 20%., Design, Setting, and Participants: This retrospective study took place from January 2010 through December 2021 at 5 high- or very high-volume centers in Italy. Data were analyzed during April 2024. Participants included consecutive patients undergoing up-front pancreatectomy at the participating institutions., Exposure: Standard management, per existing guidelines., Main Outcomes and Measures: The main outcome measure was the rate of futile pancreatectomy, defined as an operation resulting in patient death or disease recurrence within 6 months. Dichotomous criteria were constructed to maintain the futility likelihood below 20%, corresponding to the chance of not receiving postneoadjuvant resection from existing pooled data., Results: This study included 1426 patients. The median age was 69 (interquartile range, 62-75) years, 759 patients were male (53.2%), and 1076 had head cancer (75.4%). The rate of adjuvant treatment receipt was 73.7%. For the model construction, the study sample was split into a derivation (n = 885) and a validation cohort (n = 541). The rate of futile pancreatectomy was 18.9% (19.2% in the development and 18.6% in the validation cohort). Preoperative variables associated with futile resection were American Society of Anesthesiologists class (95% CI for coefficients, 0.68-0.87), cancer antigen (CA) 19.9 serum levels (95% CI, for coefficients 0.05-0.75), and tumor size (95% CI for coefficients, 0.28-0.46). Three risk groups associated with an escalating likelihood of futile resection, worse pathological features, and worse outcomes were identified. Four discrete conditions (defined as CA 19.9 levels-adjusted-to-size criteria: tumor size less than 2 cm with CA 19.9 levels less than 1000 U/mL; tumor size less than 3 cm with CA 19.9 levels less than 500 U/mL; tumor size less than 4 cm with CA 19.9 levels less than 150 U/mL; and tumor size less than 5 cm with CA 19.9 levels less than 50 U/mL) were associated with a futility likelihood below 20%. Both disease-free survival and overall survival were significantly longer in patients fulfilling the criteria., Conclusions and Relevance: In this study, a preoperative model (MetroPancreas) and dichotomous criteria to determine the risk of futile pancreatectomy were developed. This might help in selecting patients for up-front resection or neoadjuvant therapy.

Background: Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs., Methods: NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life., Results: From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery., Conclusion: Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

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., Competing Interests: S.G.B.: support from Flinders Foundation grant: 49358025, NHMRC Ideas Grant: 2021009, Pankind 21.R7.INV.CB.UOSA.6.2. F.M.: Tsumura, Inc., Scientific Advisory Board. M.D.C. is a co-PI of a Boston Scientific–sponsored study and he has been awarded an industry grant by Haemonetics, Inc. M.H.: Intuitive Surgical—teaches courses and proctors. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Immunotherapy has emerged as promising treatment in sarcomas, but the high variability in terms of histology, clinical behavior and response to treatments determines a particular challenge for its role in these neoplasms. Tumor immune microenvironment (TiME) of sarcomas reflects the heterogeneity of these tumors originating from mesenchymal cells and encompassing more than 100 histologies. Advances in the understanding of the complexity of TiME have led to an improvement of the immunotherapeutic responsiveness in sarcomas, that at first showed disappointing results. The proposed immune-classification of sarcomas based on the interaction between immune cell populations and tumor cells showed to have a prognostic and potential predictive role for immunotherapies. Several studies have explored the clinical impact of immune therapies in the management of these histotypes leading to controversial results. The presence of Tumor Infiltrating Lymphocytes (TIL) seems to correlate with an improvement in the survival of patients and with a higher responsiveness to immunotherapy. In this context, it is important to consider that also immune-related genes (IRGs) have been demonstrated to have a key role in tumorigenesis and in the building of tumor immune microenvironment. The IRGs landscape in soft tissue and bone sarcomas is characterized by the connection between several tumor-related genes that can assume a potential prognostic and predictive therapeutic role. In this paper, we reviewed the state of art of the principal immune strategies in the management of sarcomas including their clinical and translational relevance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Recine, Vanni, Bongiovanni, Fausti, Mercatali, Miserocchi, Liverani, Pieri, Casadei, Cavaliere, Falbo, Diano, Ibrahim and De Vita.)

Background: Magnetic resonance imaging (MRI) is regarded as gold-standard for intraductal papillary mucinous neoplasms (IPMNs) follow-up. Given the low risk of transformation and the increasing population under surveillance, there is growing interest in identifying optimal follow-up strategies., Aim: To evaluate reliability of abdominal ultrasound (US) for characterization of low-risk IPMN, compared to MRI., Methods: Prospective monocentric study among 79 consecutive patients with a suspected BD-IPMN on US. Each patient underwent confirmatory MRI. We evaluated Cohen's kappa statistic and concordance rate (CR) between MRI and US., Results: Of 79 suspected IPMNs on US, MRI confirmed 71 BD-IPMNs. There was high agreement for cyst location and number (CR and kappa of 77.5 % and 81.7 % and 0.66±0.08 and 0.62±0.11 respectively). We found high agreement for cyst size (CR=96.5 %, kappa=0.93±0.05) and main pancreatic duct (MPD) dilatation (CR=100 %, kappa=1). There was a good agreement for thickened septa (CR=80.3 %, kappa=0.38±0.12). US seems inferior to MRI for the identification of mural nodules < 5 mm (CR=97.2 %, kappa=0)., Conclusions: In a cohort of low-risk BD-IPMN, US presented high agreement rate with MRI regarding location, number, and size. There was a good agreement for MPD dilatation and thickened septa, while US underperform for detection of mural nodules < 5 mm., Competing Interests: Conflict of interest Nothing to report., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The superiority of early drain removal (EDR) versus late (LDR) after pancreaticoduodenectomy (PD) has been demonstrated only in RCTs., Methods: A meta-analysis was conducted using a random-effects model and trial sequential analysis. The critical endpoints were morbidity, redrainage, relaparotomy, and postoperative pancreatic fistula (CR-POPF). Hemorrhage (PPH), delayed gastric emptying (DGE), length of stay (LOS), and readmission rates were also evaluated. Risk ratios (RRs) and mean differences (MDs) with a 95% confidence interval (CI) were calculated. Type I and type II errors were excluded, comparing the accrued sample size (ASS) with the required sample size (RIS). When RIS is superior to ASS, type I or II errors can be hypothesized., Results: ASS was 632 for all endpoints except DGE and PPH (557 patients). The major morbidity (RR 0.55; 95% CI 0.32-0.97) was lower in the EDR group. The CR-POPF rate was lower in the EDR than in the LDR group (RR 0.50), but this difference is not statistically significant (95% CI 0.24-1.03). The RIS to confirm or exclude these results can be reached by randomizing 5959 patients. The need for percutaneous drainage, relaparotomy, PPH, DGE, and readmission rates was similar. The related RISs were higher than ASS, and type II errors cannot be excluded. LOS was shorter in the EDR than the LDR group (MD - 2.25; 95% CI - 3.23 to - 1.28). The RIS was 567, and type I errors can be excluded., Conclusions: EDR, compared with LDR, is associated with lower major morbidity and shorter LOS., (© 2024. The Author(s).)

Introduction: Pancreatic cancer (PC) surveillance of high-risk individuals (HRI) is becoming more common worldwide, aiming at anticipating PC diagnosis at a preclinical stage. In 2015, the Italian Registry of Families at Risk of Pancreatic Cancer was created. We aimed to assess the prevalence and incidence of pancreatic findings, oncological outcomes, and harms 7 years after the Italian Registry of Families at Risk of Pancreatic Cancer inception, focusing on individuals with at least a 3-year follow-up or developing events before., Methods: HRI (subjects with a family history or mutation carriers with/without a family history were enrolled in 18 centers). They underwent annual magnetic resonance with cholangiopancreatography or endoscopic ultrasound (NCT04095195)., Results: During the study period (June 2015-September 2022), 679 individuals were enrolled. Of these, 524 (77.2%) underwent at least baseline imaging, and 156 (29.8%) with at least a 3-year follow-up or pancreatic malignancy/premalignancy-related events, and represented the study population. The median age was 51 (interquartile range 16) years. Familial PC cases accounted for 81.4% of HRI and individuals with pathogenic variant for 18.6%. Malignant (n = 8) and premalignant (1 PanIN3) lesions were found in 9 individuals. Five of these 8 cases occurred in pathogenic variant carriers, 4 in familial PC cases (2 tested negative at germline testing and 2 others were not tested). Three of the 8 PC were stage I. Five of the 8 PC were resectable, 3 Stage I, all advanced cases being prevalent. The 1-, 2-, and 3-year cumulative hazard of PC was 1.7%, 2.5%, and 3%, respectively. Median overall and disease-free survival of patients with resected PC were 18 and 12 months (95% CI not computable). Considering HRI who underwent baseline imaging, 6 pancreatic neuroendocrine neoplasms (1 resected) and 1 low-yield surgery (low-grade mixed-intraductal papillary mucinous neoplasm) were also reported., Discussion: PC surveillance in a fully public health care system is feasible and safe, and leads to early PC or premalignant lesions diagnoses, mostly at baseline but also over time., (Copyright © 2023 by The American College of Gastroenterology.)

Background: Physical prehabilitation is recommended before major abdominal surgery to ameliorate short-term outcomes., Methods: A frequentist, random-effects network meta-analysis (NMA) was performed to clarify which type of preoperative physical activity among aerobic exercise (AE), inspiratory muscle training (IMT), and resistance training produces benefits in patients who underwent major abdominal surgery. The surface under the P-score, odds ratio (OR), or mean difference (MD) with a 95% confidence interval (CI) were reported. The results were adjusted by using the component network approach. The critical endpoints were overall and major morbidity rate and mortality rate. The important but not critical endpoints were the length of stay (LOS) and pneumonia., Results: The meta-analysis included 25 studies. The best approaches for overall morbidity rate were AE and AE + IMT (OR = 0.61, p-score = 0.76, and OR = 0.66, p-score = 0.68). The best approaches for pneumonia were AE + IMT and AE (OR = 0.21, p-score = 0.91, and OR = 0.52, p-score = 0.68). The component analysis confirmed that the best incremental OR (0.30; 95% CI 0.12-0.74) could be obtained using AE + IMT. The best approach for LOS was AE alone (MD - 1.63 days; 95% CI - 3.43 to 0.18). The best combination of components was AE + IMT (MD - 1.70; 95% CI - 2.06 to - 1.27)., Conclusions: Physical prehabilitation reduces the overall morbidity rate, pneumonia, and length of stay. The most relevant effect of prehabilitation requires the simultaneous use of AE and IMT., (© 2023. The Author(s).)

Development of human-compatible tissues is an active field of research that is leading to the production of optimized biological scaffolds to support regenerative medicine. Xenogenic acellular matrices are known to have strongly influenced the field of breast surgery, playing an integral role in wound healing and in preventing the foreign body reaction to silicone implants. Here, we present our experience in using a biological matrix for aesthetic revision surgery with malposition and severe capsular contracture. Revisions were performed using the new MASQUE equine acellular-pericardium-matrix (APM) as an anterior cover for the synthetic prosthesis. Acting as an internal support, the thin APM layer provides a biological and biocompatible interface between the synthetic implant and living tissues, exerting a protective function against fibrotic responses and capsular contracture. The role of an APM in matrix-assisted mammoplasty has yet to be fully established. Our early experience of APM-assisted aesthetic revision surgery shows promising results, laying the foundations for equine biological matrices as a valid tool for the management of capsular contracture-susceptible patients., Competing Interests: The authors have no financial interest to declare in relation to the content of this article., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.

Microglia represent the primary immune defense system within the central nervous system and play a role in the inflammatory processes occurring in numerous disorders, such as Parkinson's disease (PD). PD onset and progression are associated with factors considered possible causes of neuroinflammation, i.e. genetic mutations. In vitro models of microglial cells were established to identify specific molecular targets in PD through the analysis of gene expression data. Recently, the Human Microglial Clone 3 cell line (HMC3) has been characterized and a new human microglia model has emerged. Here we perform RT-qPCR analyses to evaluate the expression of ten reference genes in HMC3, untreated or stimulated to a pro-inflammatory status. The comparative ∆C T method, BestKeeper, Normfinder, geNorm and RefFinder algorithms were used to assess the stability of the candidate genes. The results showed that the most suitable internal controls are HPRT1, RPS18 and B2M genes. In addition, the most stable and unstable reference genes were used to normalize the expression of a gene of interest in HMC3, resulting in a difference in the statistical significance in cells treated with Rotenone. This is the first reference gene validation study in HMC3 cell line in pro-inflammatory status and can contribute to more reliable gene expression analysis in the field of neurodegenerative and neuroinflammatory research., (© 2024. The Author(s).)

Background: The safety and efficacy of minimally invasive radical antegrade modular pancreatosplenectomy (MI-RAMPS) remain to be established in pancreatic cancer (PDAC) METHODS: Eighty-five open (O)-RAMPS were compared to 93 MI-RAMPS. The entropy balance matching approach was used to compare the two cohorts, eliminating the selection bias. Three models were created. Model 1 made O-RAMPS equal to the MI-RAMPS cohort (i.e., compared the two procedures for resectable PDAC); model 2 made MI-RAMPS equal to O-RAMPS (i.e., compared the two procedures for borderline-resectable PDAC); model 3, compared robotic and laparoscopic RAMPS., Results: O-RAMPS and MI-RAMPS showed "non-small" differences for BMI, comorbidity, back pain, tumor size, vascular resection, anterior or posterior RAMPS, multi-visceral resection, stump management, grading, and neoadjuvant therapy. Before reweighting, O-RAMPS had fewer clinically relevant postoperative pancreatic fistulae (CR-POPF) (20.0% vs. 40.9%; p = 0.003), while MI-RAMPS had a higher mean of lymph nodes (25.7 vs. 31.7; p = 0.011). In model 1, MI-RAMPS and O-RAMPS achieved similar results. In model 2, O-RAMPS was associated with lower comprehensive complication index scores (MD = 11.2; p = 0.038), and CR-POPF rates (OR = 0.2; p = 0.001). In model 3, robotic-RAMPS had a higher probability of negative resection margins., Conclusion: In patients with anatomically resectable PDAC, MI-RAMPS is feasible and as safe as O-RAMPS., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)