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.

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.

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.

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.

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.

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.

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.

Discrimination Toward Women in Surgery: A Systematic Scoping Review.

BACKGROUND: Over the past twenty years explicit gender bias toward women in surgery has been replaced by more subtle barriers, which represent indirect forms of discrimination and prevents equality. OBJECTIVE: The aim of our scoping review is to summarize the different forms of discrimination toward women in surgery. METHODS: The database search consisted of original studies regarding discrimination toward female surgeons. RESULTS: Of 3615 studies meeting research criteria, 63 were included. Of these articles, 11 (18%) were focused on gender-based discrimination, 14 (22%) on discrimination in authorship, research productivity, and research funding, 21 (33%) on discrimination in academic surgery, 7 (11%) on discrimination in surgical leadership positions and 10 (16%) on discrimination during conferences and in surgical societies. The majority (n = 53, 84%) of the included studies were conducted in the U.S.A. According to our analysis, female surgeons experience discrimination from male colleagues, healthcare workers, but also from patients and trainees. Possible solutions may include acknowledgment of the problem, increased education of diversity and integration for the younger generations, mentorship, coaching, and more active engagement by male and female partners to support women in the surgical field. CONCLUSIONS: Gender-based discrimination toward women in the field of surgery has evolved over the past twenty years, from an explicit to a more subtle attitude. A work-environment where diversity and flexibility are valued would allow female surgeons to better realize their full potential.

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

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

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.

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.

401 consecutive minimally invasive distal pancreatectomies: lessons learned from 20 years of experience.

BACKGROUND: This study aimed to discuss and report the trend, outcomes, and learning curve effect after minimally invasive distal pancreatectomy (MIDP) at two high-volume centres. METHODS: Patients undergoing MIDP between January 1999 and December 2018 were retrospectively identified from prospectively maintained electronic databases. The entire cohort was divided into two groups constituting the "early" and "recent" phases. The learning curve effect was analyzed for laparoscopic (LDP) and robotic distal pancreatectomy (RDP). The follow-up was at least 2 years. RESULTS: The study population included 401 consecutive patients (LDP n = 300, RDP n = 101). Twelve surgeons performed MIDP during the study period. Although patients were more carefully selected in the early phase, in terms of median age (49 vs. 55 years, p = 0.026), ASA class higher than 2 (3% vs. 9%, p = 0.018), previous abdominal surgery (10% vs. 34%, p < 0.001), and pancreatic adenocarcinoma (PDAC) (7% vs. 15%, p = 0.017), the recent phase had similar perioperative outcomes. The increase of experience in LDP was inversely associated with the operative time (240 vs 210 min, p < 0.001), morbidity rate (56.5% vs. 40.1%, p = 0.005), intra-abdominal collection (28.3% vs. 17.3%, p = 0.023), and length of stay (8 vs. 7 days, p = 0.009). Median survival in the PDAC subgroup was 53 months. CONCLUSION: In the setting of high-volume centres, the surgical training of MIDP is associated with acceptable rates of morbidity. The learning curve can be largely achieved by several team members, improving outcomes over time. Whenever possible resection of PDAC guarantees adequate oncological results and survival.

A randomized controlled trial of stapled versus ultrasonic transection in distal pancreatectomy.

BACKGROUND: The pancreatic transection method during distal pancreatectomy is thought to influence postoperative fistula rates. Yet, the optimal technique for minimizing fistula occurrence is still unclear. The present randomized controlled trial compared stapled versus ultrasonic transection in elective distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy from July 2018 to July 2020 at two high-volume institutions were considered for inclusion. Exclusion criteria were contiguous organ resection and a parenchymal thickness > 17 mm on intraoperative ultrasound. Eligible patients were randomized in a 1:1 ratio to stapled transection (Endo GIA Reinforced Reload with Tri-Staple Technology®) or ultrasonic transection (Harmonic Focus® + or Harmonic Ace® + shears). The primary endpoint was postoperative pancreatic fistula. Secondary endpoints included overall complications, abdominal collections, and length of hospital stay. RESULTS: Overall, 72 patients were randomized in the stapled transection arm and 73 patients in the ultrasonic transection arm. Postoperative pancreatic fistula occurred in 23 patients (16%), with a comparable incidence between groups (12% in stapled transection versus 19% in ultrasonic dissection arm, p = 0.191). Overall complications did not differ substantially (35% in stapled transection versus 44% in ultrasonic transection arm, p = 0.170). There was an increased incidence of abdominal collections in the ultrasonic dissection group (32% versus 14%, p = 0.009), yet the need for percutaneous drain did not differ between randomization arms (p = 0.169). The median length of stay was 8 days in both groups (p = 0.880). Intraoperative blood transfusion was the only factor independently associated with postoperative pancreatic fistula on logistic regression analysis (OR 4.8, 95% CI 1.2-20.0, p = 0.032). CONCLUSION: The present randomized controlled trial of stapled versus ultrasonic transection in elective distal pancreatectomy demonstrated no significant difference in postoperative pancreatic fistula rates and no substantial clinical impact on other secondary endpoints.

US-Guided Percutaneous Radiofrequency Ablation of Locally Advanced Pancreatic Adenocarcinoma: A 5-Year High-Volume Center Experience.

PURPOSE: The aim of this study was to investigate the safety and effectiveness of percutaneous radiofrequency ablation (RFA) in locally advanced pancreatic cancer (LAPC) of the pancreatic body by assessing the overall survival of patients and evaluating the effects of the procedure in the clinical and radiological follow-up. MATERIALS AND METHODS: Patients with unresectable LAPC after failed chemoradiotherapy for at least six months were retrospectively included. Percutaneous RFA was performed after a preliminary ultrasound (US) feasibility evaluation. Contrast-enhanced computed tomography (CT) and CA 19.9 sampling were performed before and 24 hours and 30 days after the procedure to evaluate the effects of the ablation. Patients were followed-up after discharge considering the two main endpoints: procedure-related complications and death. RESULTS: 35 patients were included, 5 were excluded. All patients underwent RFA with no procedure-related complications reported. The mean size of tumors was 49 mm before treatment. The mean dimension of the ablated necrotic zone was 32 mm, with a mean extension of 65 % compared to the whole tumor size. Tumor density was statistically reduced one day after the procedure (p < 0.001). The mean CA 19.9 levels before and 24 hours and 30 days after the procedure were 285.8 U/mL, 635.2 U/mL, and 336.0 U/mL, respectively, with a decrease or stability at the 30-day evaluation in 80 % of cases. The mean survival was 310 (65-718) days. CONCLUSION: Percutaneous RFA of LAPC is a feasible technique in patients who cannot undergo surgery, with great debulking effects and a very low complication rate.

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.

Open radiofrequency ablation as upfront treatment for locally advanced pancreatic cancer: Requiem from a randomized controlled trial.

BACKGROUND: Local ablation of pancreatic cancer has been suggested as an option to manage locally advanced pancreatic cancer (LAPC) although no robust evidence has been published to date to support its application. The aim of this study is to compare overall survival (OS) and progression-free survival (PFS) in patients receiving both radiofrequency ablation (RFA) and conventional chemoradiotherapy (CHRT) with patients receiving CHRT only. METHODS: This is a multicentre prospective randomized controlled trial (RCT). Patients with LAPC diagnosed by the Pancreas-Ablation-Team-Verona were randomly assigned to open RFA (Group A) or CHRT (Group B). Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. Statistical significance was set at p < 0.05. RESULTS: One hundred LAPC patients were enrolled from January 2014 to August 2016. 33% of patients in Group A did not receive the designated procedure because of intraoperative findings of liver (18.7%) or peritoneal metastases (43.8%), or technical contraindications (37.5%). We did not observe any statistically significant survival benefit from RFA compared to CHRT, neither in terms of OS (medians of 14.2 months and 18.1 months, respectively, p = 0.639) nor PFS (medians of 8 months and 6 months respectively, p = 0.570). Mortality was nil and RFA-related morbidity was 15.6%. In 13% of subjects, conversion to surgery occurred (2 after RFA and 11 after CHRT). CONCLUSIONS: This is the first RCT evaluating the impact of upfront RFA in the multimodal treatment of LAPC. Compared to CHRT, RFA alone did not provide any advantage in terms of OS or PFS. It could be considered as a therapeutic option for LAPC within a multimodal context and after neoadjuvant therapies.

Role of next-generation genomic sequencing in targeted agents repositioning for pancreaticoduodenal cancer patients.

BACKGROUND: Pancreaticoduodenal cancer (PDC) is a group of malignant tumors arising in the ampullary region, which lack approved targeted therapies for their treatment. METHODS: This retrospective, observational study is based on Secondary Data Use (SDU) previously collected during a multicenter collaboration, which were subsequently entered into a predefined database and analyzed. FoundationOne CDx or Liquid, a next-generation DNA sequencing (NGS) service, was used to identify genomic alterations of patients who failed standard treatments. Detected alterations were described according to ESMO Scale of Clinical Actionability for molecular Targets (ESCAT). RESULTS: NGS analysis was performed in 68 patients affected by PDC. At least one alteration ranking tier I, II, III, or IV according to ESCAT classification was detected in 8, 1, 9, and 12 patients respectively (44.1%). Ten of them (33.3%) received a matched therapy. Patients with ESCAT tier I to IV were generally younger than the overall population (median = 54, range = 26-71 years), had an EGOG performance status score = 0 (83.3%), and an uncommon histological or clinical presentation. The most common mutations with clinical evidence of actionability (ESCAT tier I-III) involved genes of the RAF (10.3%), BRCA (5.9%) or FGFR pathways (5.9%). We present the activity of the RAF kinases inhibitor sorafenib in patients with RAF-mutated advanced PDC. CONCLUSIONS: In advanced PDC, NGS is a feasible and valuable method for enabling precision oncology. This genomic profiling method might be considered after standard treatments failure, especially in young patients maintaining a good performance status, in order to detect potentially actionable mutations and offer molecularly targeted therapeutic approaches.

Artificial Intelligence Surgery: How Do We Get to Autonomous Actions in Surgery?

Most surgeons are skeptical as to the feasibility of autonomous actions in surgery. Interestingly, many examples of autonomous actions already exist and have been around for years. Since the beginning of this millennium, the field of artificial intelligence (AI) has grown exponentially with the development of machine learning (ML), deep learning (DL), computer vision (CV) and natural language processing (NLP). All of these facets of AI will be fundamental to the development of more autonomous actions in surgery, unfortunately, only a limited number of surgeons have or seek expertise in this rapidly evolving field. As opposed to AI in medicine, AI surgery (AIS) involves autonomous movements. Fortuitously, as the field of robotics in surgery has improved, more surgeons are becoming interested in technology and the potential of autonomous actions in procedures such as interventional radiology, endoscopy and surgery. The lack of haptics, or the sensation of touch, has hindered the wider adoption of robotics by many surgeons; however, now that the true potential of robotics can be comprehended, the embracing of AI by the surgical community is more important than ever before. Although current complete surgical systems are mainly only examples of tele-manipulation, for surgeons to get to more autonomously functioning robots, haptics is perhaps not the most important aspect. If the goal is for robots to ultimately become more and more independent, perhaps research should not focus on the concept of haptics as it is perceived by humans, and the focus should be on haptics as it is perceived by robots/computers. This article will discuss aspects of ML, DL, CV and NLP as they pertain to the modern practice of surgery, with a focus on current AI issues and advances that will enable us to get to more autonomous actions in surgery. Ultimately, there may be a paradigm shift that needs to occur in the surgical community as more surgeons with expertise in AI may be needed to fully unlock the potential of AIS in a safe, efficacious and timely manner.

Management of Pancreatic Cystic Lesions.

BACKGROUND: The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance. METHODS: We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery. RESULTS: The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies. CONCLUSIONS: Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need.

Delivery of hepato-pancreato-biliary surgery during the COVID-19 pandemic: an European-African Hepato-Pancreato-Biliary Association (E-AHPBA) cross-sectional survey.

BACKGROUND: The extent of the COVID-19 pandemic and the resulting response has varied globally. The European and African Hepato-Pancreato-Biliary Association (E-AHPBA), the premier representative body for practicing HPB surgeons in Europe and Africa, conducted this survey to assess the impact of COVID-19 on HPB surgery. METHODS: An online survey was disseminated to all E-AHPBA members to assess the effects of the pandemic on unit capacity, management of HPB cancers, use of COVID-19 screening and other aspects of service delivery. RESULTS: Overall, 145 (25%) members responded. Most units, particularly in COVID-high countries (>100,000 cases) reported insufficient critical care capacity and reduced HPB operating sessions compared to COVID-low countries. Delayed access to cancer surgery necessitated alternatives including increased neoadjuvant chemotherapy for pancreatic cancer and colorectal liver metastases, and locoregional treatments for hepatocellular carcinoma. Other aspects of service delivery including COVID-19 screening and personal protective equipment varied between units and countries. CONCLUSION: This study demonstrates that the COVID-19 pandemic has had a profound adverse impact on the delivery of HPB cancer care across the continents of Europe and Africa. The findings illustrate the need for safe resumption of cancer surgery in a "new" normal world with screening of patients and staff for COVID-19.