Thirty-day prevalence and clinical impact of fluid collections at the resection margin after distal pancreatectomy: Follow-up of a multicentric randomized controlled trial.

BACKGROUND: Postoperative fluid collections at the resection margin of the pancreatic stump are frequent after distal pancreatectomy, yet their clinical impact is unclear. The aim of this study was to assess the 30-day prevalence of postoperative fluid collections after distal pancreatectomy and the factors associated with a clinically relevant condition. METHODS: Patients enrolled in a randomized controlled trial of parenchymal transection with either reinforced, triple-row staple, or ultrasonic dissector underwent routine magnetic resonance 30 days postoperatively. Postoperative fluid collection was defined as a cyst-like lesion of at least 1 cm at the pancreatic resection margin. Postoperative fluid collections requiring any therapy were defined as clinically relevant. RESULTS: A total of 133 patients were analyzed; 69 were in the triple-row staple transection arm, and 64 were in the ultrasonic dissector transection arm. The overall 30-day prevalence of postoperative fluid collections was 68% (n = 90), without any significant difference between the two trial arms. Postoperative serum hyperamylasemia was more frequent in patients with postoperative fluid collections than those without (31% vs 7%, P = .001). Among the postoperative fluid collection population, an early postoperative pancreatic fistula (odds ratio 14.9, P = .002), post pancreatectomy acute pancreatitis (odds ratio 12.7, P = .036), and postoperative fluid collection size larger than 50 mm (odds ratio 6.6, P = .046) were independently associated with a clinically relevant postoperative fluid collection. CONCLUSION: Postoperative fluid collections at the resection margin are common after distal pancreatectomy and can be predicted by early assessment of postoperative serum hyperamylasemia. A preceding pancreatectomy acute pancreatitis and/or postoperative pancreatic fistula and large collections (>50 mm) were associated with a clinically relevant postoperative fluid collection, representing targets for closer follow-up or earlier therapeutic interventions.

Toward a new paradigm of care: a surgical leaders' Delphi consensus on the organizational factors of the new pancreas units (E-AHPBA PUECOF study).

Pancreas units represent new organizational models of care that are now at the center of the European debate. The PUECOF study, endorsed by the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), aims to reach an expert consensus by enquiring surgical leaders about the Pancreas Units' most relevant organizational factors, with 30 surgical leaders from 14 countries participating in the Delphi survey. Results underline that surgeons believe in the need to organize multidisciplinary meetings, nurture team leadership, and create metrics. Clinical professionals and patients are considered the most relevant stakeholders, while the debate is open when considering different subjects like industry leaders and patient associations. Non-technical skills such as ethics, teamwork, professionalism, and leadership are highly considered, with mentoring, clinical cases, and training as the most appreciated facilitating factors. Surgeons show trust in functional leaders, key performance indicators, and the facilitating role played by nurse navigators and case managers. Pancreas units have a high potential to improve patients' outcomes. While the pancreas unit model of care will not change the technical content of pancreatic surgery, it may bring surgeons several benefits, including more cases, professional development, easier coordination, less stress, and opportunities to create fruitful connections with research institutions and industry leaders.

Outcomes of a 3-Year Prospective Surveillance in Individuals at High Risk of Pancreatic Cancer.

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.

The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS).

OBJECTIVE: To develop and update evidence-based and consensus-based guidelines on laparoscopic and robotic pancreatic surgery. SUMMARY BACKGROUND DATA: Minimally invasive pancreatic surgery (MIPS), including laparoscopic and robotic surgery, is complex and technically demanding. Minimizing the risk for patients requires stringent, evidence-based guidelines. Since the International Miami Guidelines on MIPS in 2019, new developments and key publications have been reported, necessitating an update. METHODS: Evidence-based guidelines on 22 topics in 8 domains were proposed: terminology, indications, patients, procedures, surgical techniques and instrumentation, assessment tools, implementation and training, and artificial intelligence. The Brescia Internationally Validated European Guidelines on Minimally Invasive Pancreatic Surgery (EGUMIPS, September 2022) used the Scottish Intercollegiate Guidelines Network (SIGN) methodology to assess the evidence and develop guideline recommendations, the Delphi method to establish consensus on the recommendations among the Expert Committee, and the AGREE II-GRS tool for guideline quality assessment and external validation by a Validation Committee. RESULTS: Overall, 27 European experts, 6 international experts, 22 international Validation Committee members, 11 Jury Committee members, 18 Research Committee members, and 121 registered attendees of the 2-day meeting were involved in the development and validation of the guidelines. In total, 98 recommendations were developed, including 33 on laparoscopic, 34 on robotic, and 31 on general MIPS, covering 22 topics in 8 domains. Out of 98 recommendations, 97 reached at least 80% consensus among the experts and congress attendees, and all recommendations were externally validated by the Validation Committee. CONCLUSIONS: The EGUMIPS evidence-based guidelines on laparoscopic and robotic MIPS can be applied in current clinical practice to provide guidance to patients, surgeons, policy-makers, and medical societies.

Hepatic Artery Anomalies in Pancreaticoduodenectomy: Outcomes from a High-Volume Center.

INTRODUCTION: Hepatic artery anomalies (HAA) may have an impact on surgical and oncological outcomes of patients undergoing pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at our institution between July 2015 and January 2020 were retrospectively reviewed and classified into two groups: group 1, with presence of HAA, and group 2, with no HAA. A weighted logistic regression model was employed to assess the association between HAA and postoperative complications, and to assess the association between HAA and R status in patients with pancreatic cancer. RESULTS: 502 patients were considered for analysis, with 75 (15%) of them in group 1. They had either an accessory (n = 28, 40.8%) or replaced (n = 26, 36.6%) right hepatic artery. Most patients underwent surgery for a malignancy (n = 451; 90%); among them, vascular resection was performed in 69 cases (15%). The presence of a HAA was reported at preoperative imaging only in 4 cases (5%) and the aberrant vessel was preserved in 72% of patients. At weighted multivariable logistic regression analysis, HAA were not associated to higher odds of morbidity (odds ratio [OR]: 0.753, 95% confidence interval [CI]: 0.543-1.043) nor to R1 status in case of pancreatic cancer (OR: 1.583, 95% CI: 0.979-2.561). CONCLUSION: At our institution, the presence of HAA does not have an impact on postoperative outcomes or affects oncological clearance after PD. Hospitals', surgeons', volume and systematic review of preoperative imaging are all factors that help reduce possible adverse events.

ERAS with or without supplemental artificial nutrition in open pancreatoduodenectomy for cancer. A multicenter, randomized, open labeled trial (RASTA study protocol).

Purpose: The role of supplemental artificial nutrition in patients perioperatively treated according to enhanced recovery programs (ERAS) on surgery-related morbidity is not known. Therefore, there is a need of a clinical trials specifically designed to explore whether given a full nutritional requirement by parenteral feeding after surgery coupled with oral food "at will" compared to oral food "at will" alone, within an established ERAS program, could achieve a reduction of the morbidity burden. Materials and analysis: RASTA will be a multicenter, randomized, parallel-arm, open labeled, superiority trial. The trial will be conducted in five Italian Institutions with proven experience in pancreatic surgery and already applying an established ERAS program. Adult patients (age ≥ 18 and < 90 years of age) candidate to elective open pancreatoduodenectomy (PD) for any periampullary or pancreatic cancer will be randomized to receive a full ERAS protocol that establishes oral food "at will" plus parenteral nutrition (PN) from postoperative day 1 to day 5 (treatment arm), or to ERAS protocol without PN (control arm). The primary endpoint of the trial is the complication burden within 90 days after the day of surgery. The complication burden will be assessed by the Comprehensive Complication Index, that incorporates all complications and their severity as defined by the Clavien-Dindo classification, and summarizes postoperative morbidity with a numerical scale ranging from 0 to 100. The H0 hypothesis tested is that he administration of a parenteral nutrition added to the ERAS protocol will not affect the CCI as compared to standard of care (ERAS). The H1 hypothesis is that the administration of a parenteral nutrition added to the ERAS protocol will positively affect the CCI as compared to standard of care (ERAS). The trial has been registered at ClinicalTrials.gov (number: NCT04438447; date: 18/05/2020). Conclusion: This upcoming trial will permit to establish if early postoperative artificial nutritional support after PD may improve postoperative outcomes compared to oral nutrition alone within an established ERAS program.

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Surgeons' perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey.

BACKGROUND: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons' knowledge and perception of using AI-based tools in clinical decision-making processes. METHODS: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society's website and Twitter profile. RESULTS: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons' preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. DISCUSSION: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI.

Surgical and Oncological Outcomes After Preoperative FOLFIRINOX Chemotherapy in Resected Pancreatic Cancer: An International Multicenter Cohort Study.

BACKGROUND: Preoperative FOLFIRINOX chemotherapy is increasingly administered to patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC) to improve overall survival (OS). Multicenter studies reporting on the impact from the number of preoperative cycles and the use of adjuvant chemotherapy in relation to outcomes in this setting are lacking. This study aimed to assess the outcome of pancreatectomy after preoperative FOLFIRINOX, including predictors of OS. METHODS: This international multicenter retrospective cohort study included patients from 31 centers in 19 European countries and the United States undergoing pancreatectomy after preoperative FOLFIRINOX chemotherapy (2012-2016). The primary end point was OS from diagnosis. Survival was assessed using Kaplan-Meier analysis and Cox regression. RESULTS: The study included 423 patients who underwent pancreatectomy after a median of six (IQR 5-8) preoperative cycles of FOLFIRINOX. Postoperative major morbidity occurred for 88 (20.8%) patients and 90-day mortality for 12 (2.8%) patients. An R0 resection was achieved for 243 (57.4%) patients, and 259 (61.2%) patients received adjuvant chemotherapy. The median OS was 38 months (95% confidence interval [CI] 34-42 months) for BRPC and 33 months (95% CI 27-45 months) for LAPC. Overall survival was significantly associated with R0 resection (hazard ratio [HR] 1.63; 95% CI 1.20-2.20) and tumor differentiation (HR 1.43; 95% CI 1.08-1.91). Neither the number of preoperative chemotherapy cycles nor the use adjuvant chemotherapy was associated with OS. CONCLUSIONS: This international multicenter study found that pancreatectomy after FOLFIRINOX chemotherapy is associated with favorable outcomes for patients with BRPC and those with LAPC. Future studies should confirm that the number of neoadjuvant cycles and the use adjuvant chemotherapy have no relation to OS after resection.

Telemedicine and Pancreatic Cancer: A Systematic Review.

Introduction: Pancreatic cancer requires a multidisciplinary approach in a high-volume center for all the steps of the diagnostic-therapeutic course. However, the most experienced centers are not evenly distributed throughout the country causing a real "health migration" that involves patients and families with relevant economic, time, and energy costs to bear. The COVID-19 pandemic had a deep impact on surgical and oncological care and the travel limits due to COVID-related restrictions, have delayed the care of cancer patient living far from the referral centers. In this scenario, several telemedicine approaches have been proposed to reduce the distance between clinicians and patients and to allow a fast and effective access to care even for patients distant from referral centers. The aim of the study is to analyze the evidence and describe the current utility of telemedicine tool for patients with pancreatic cancer. Methods: We systematically searched the literature in the following databases: Web of Science, PubMed, Scopus, and MEDLINE. The inclusion criteria were article describing a telemedicine intervention (virtual visits, telephone follow-up/counseling, mobile or online apps, telemonitoring) and focusing on adult patients with pancreatic cancer at any stage of the disease. Results: In total, 846 titles/abstracts were identified. Following quality assessment, the review included 40 studies. Telemedicine has been proposed in multiple clinical settings, demonstrating high levels of patient and health professional satisfaction. Conclusion: Successful telemedicine applications in patients with pancreatic cancer are telerehabilitation and nutritional assessment, remote symptom control, teledischarge after pancreatic surgery, tele-education and medical mentoring regarding pancreatic disease as well as telepathology.

CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in Pancreatic Cancer: CXCL12 Predicts Survival of Radically Resected Patients.

Pancreatic ductal adenocarcinoma (PDAC) is currently the most deadly cancer. Although characterized by 5-20% of neoplastic cells in the highly fibrotic stroma, immunotherapy is not a valid option in PDAC treatment. As CXCR4-CXCL12 regulates tumor invasion and T-cell access and PD-1/PD-L1 controls immune tolerance, 76 PDACs were evaluated for CXCR4-CXCL12-CXCR7 and PD-1/PD-L1 in the epithelial and stromal component. Neoplastic CXCR4 and CXCL12 discriminated PDACs for recurrence-free survival (RFS), while CXCL12 and CXCR7 discriminated patients for cancer-specific survival (CSS). Interestingly, among patients with radical resection (R0), high tumor CXCR4 clustered patients with worse RFS, high CXCL12 identified poor prognostic patients for both RFS and CSS, while stromal lymphocytic-monocytic PD-L1 associated with improved RFS and CSS. PD-1 was only sporadically expressed (<1%) in focal lymphocyte infiltrate and does not impact prognosis. In multivariate analysis, tumoral CXCL12, perineural invasion, and AJCC lymph node status were independent prognostic factors for RFS; tumoral CXCL12, AJCC Stage, and vascular invasion were independent prognostic factors for CSS. CXCL12's poor prognostic meaning was confirmed in an additional perspective-independent 13 fine-needle aspiration cytology advanced stage-PDACs. Thus, CXCR4-CXCL12 evaluation in PDAC identifies prognostic categories and could orient therapeutic approaches.

Prognostic Factors After Pancreatectomy for Pancreatic Cancer Initially Metastatic to the Liver.

BACKGROUND: Resection of initially oligometastatic pancreatic ductal adenocarcinoma (PDAC) following response to first-line chemotherapy is controversial. We herein updated a previous case series to investigate the oncologic outcomes and preoperative factors that could drive the decision-making process. METHODS: This retrospective analysis was limited to patients with liver-only synchronous metastases who experienced complete regression of the metastatic component and underwent pancreatectomy between October 2008 and July 2020 at two high-volume institutions. Clinical-pathologic variables were captured, and inflammation-based prognostic scores were calculated. Recurrence and survival analyses were performed using standard statistical methods. RESULTS: Overall, 52 patients were included. FOLFIRINOX was the most employed chemotherapy regimen (63.5%). Post-treatment tumor size, serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) were significantly decreased relative to baseline evaluation. The median time from diagnosis to pancreatectomy was 10.2 months, while the median time from chemotherapy completion to pancreatectomy was 2 months. Major postoperative complications occurred in 26.9% of patients, while postoperative mortality was nil. The median disease-free survival (DFS) and overall survival (OS) from pancreatectomy were 16.5 and 23.0 months, respectively, and the median OS from diagnosis was 37.2 months. At multivariable analysis, vascular resection, operative time, prognostic nutrition index (PNI) and neutrophil-to-lymphocyte ratio (NLR) were associated with OS. Operative time, platelet × neutrophil/lymphocyte count (SII), and PNI were associated with DFS. CONCLUSIONS: We confirm promising outcomes of selected patients who underwent pancreatectomy following downstaging of liver metastases. The absence of vascular involvement of the primary tumor, good nutritional status, and low inflammatory index scores could be useful to select candidates for resection.

The Advances in Computer Vision That Are Enabling More Autonomous Actions in Surgery: A Systematic Review of the Literature.

This is a review focused on advances and current limitations of computer vision (CV) and how CV can help us obtain to more autonomous actions in surgery. It is a follow-up article to one that we previously published in Sensors entitled, "Artificial Intelligence Surgery: How Do We Get to Autonomous Actions in Surgery?" As opposed to that article that also discussed issues of machine learning, deep learning and natural language processing, this review will delve deeper into the field of CV. Additionally, non-visual forms of data that can aid computerized robots in the performance of more autonomous actions, such as instrument priors and audio haptics, will also be highlighted. Furthermore, the current existential crisis for surgeons, endoscopists and interventional radiologists regarding more autonomy during procedures will be discussed. In summary, this paper will discuss how to harness the power of CV to keep doctors who do interventions in the loop.

Early Barriers to Career Progression of Women in Surgery and Solutions to Improve Them: A Systematic Scoping Review.

OBJECTIVE: This study aims to summarize the evidence concerning the barriers that exist to the career progression of women in surgery and to provide potential solutions to overcome these obstacles. BACKGROUND: Visible and invisible impediments can hinder female doctors' pursuit of a surgical career, from choosing a surgical specialty to training opportunities and all the way through career progression. METHODS: Database search of original studies about barriers for female surgeons during choice of surgical career, residency, and career progression. A query including possible solutions such as mentorship and network was included. RESULTS: Of 4618 total articles; 4497 were excluded as duplicates, having incorrect study focus, or not being original studies; leaving 120 studies meeting the inclusion criteria. Of the articles included, 22 (18%) focused on factors affecting the pursuit of a surgical career, such as surgical work hours and limited time for outside interests, 55 (46%) analyzed the main barriers that exist during surgical residency and fellowship training, such as discrimination and sexual harassment, 27 (23%) focused on barriers to career advancement, heavy workloads, ineffective mentorship, unclear expectations for advancement, inequality in pay or work-home conflicts. Among studies reporting on possible solutions, 8 (6.5%) articles reported on the role of effective mentorship to support career advancement and to provide moral support and 8 (6.5%) on the emerging role of social media for networking. Our analysis showed how different impediments hinder surgical career progression for women, with notable consequences on burnout and attrition. CONCLUSIONS: Identification and recognition of obstacles to career progression is the first step to addressing the gender gap in surgery. Active strategies should be improved to promote a culture of diversity and to create equal opportunity for women in surgery, while implementing structured mentoring programs and investing on an adequate communication on social media to engage the future generations.

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

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