The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

The 2023 MANCTRA Acute Biliary Pancreatitis Care Bundle: A Joint Effort Between Human Knowledge and Artificial Intelligence (ChatGPT) to Optimize the Care of Patients With Acute Biliary Pancreatitis in Western Countries.

OBJECTIVE: To generate an up-to-date bundle to manage acute biliary pancreatitis using an evidence-based, artificial intelligence (AI)-assisted GRADE method. BACKGROUND: A care bundle is a set of core elements of care that are distilled from the most solid evidence-based practice guidelines and recommendations. METHODS: The research questions were addressed in this bundle following the PICO criteria. The working group summarized the effects of interventions with the strength of recommendation and quality of evidence applying the GRADE methodology. ChatGPT AI system was used to independently assess the quality of evidence of each element in the bundle, together with the strength of the recommendations. RESULTS: The 7 elements of the bundle discourage antibiotic prophylaxis in patients with acute biliary pancreatitis, support the use of a full-solid diet in patients with mild to moderately severe acute biliary pancreatitis, and recommend early enteral nutrition in patients unable to feed by mouth. The bundle states that endoscopic retrograde cholangiopancreatography should be performed within the first 48 to 72 hours of hospital admission in patients with cholangitis. Early laparoscopic cholecystectomy should be performed in patients with mild acute biliary pancreatitis. When operative intervention is needed for necrotizing pancreatitis, this should start with the endoscopic step-up approach. CONCLUSIONS: We have developed a new care bundle with 7 key elements for managing patients with acute biliary pancreatitis. This new bundle, whose scientific strength has been increased thanks to the alliance between human knowledge and AI from the new ChatGPT software, should be introduced to emergency departments, wards, and intensive care units.

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.

Robotic Approach for Perihilar Cholangiocarcinoma IIIA Type: Step-by-Step Procedure.

BACKGROUND: Perihilar cholangiocarcinoma is a challenging technique to be performed by minimally invasive approach being the type III among the most complex procedure. Nowadays, the robotic approach is gaining increasing interest among the surgical community, and more and more series describing robotic liver resection have been reported. However, few cases of minimally invasive Bismuth type IIIA cholangiocarcinoma have been reported. Robotic approach allows for a better dissection and suture thanks to the flexible and precise instruments movements, overcoming some of the limitations of the laparoscopic technique. Therefore, robotic technique can facilitate some of the critical steps of a technically demanding procedure, such as the extended right hepatectomy for perihilar cholangiocarcinoma Bismuth IIIA type. METHODS: In this multimedia video we describe, for the first time in the literature, a full robotic surgical step-by-step technique with some tips and tricks for treating a perihilar cholangiocarcinoma Bismuth IIIA type, performing a radical extended right hemihepatectomy, including segment I combined with regional lymphadenectomy anf left bile duct reconstruction. A 55-year-old woman with obstructive jaundice (10 mg/dl) was referred to our center. The endobiliary brushing confirmed adenocarcinoma, and MRI/CT showed a focal perihilar lesion of 2 cm, including the main biliary duct bifurcation and extending up to the right duct (Bismuth Type IIIA hilar cholangiocarcinoma). After endoscopic biliary stents placement and 6 weeks after right portal vein embolization, the future liver remnant, including segments II and III, reached an enough hypertrophy volume with a ratio of 30%. A right hemihepatectomy with caudate lobe, including standard standard lymphadenectomy and left biliary duct reconstruction was performed. RESULTS: The operation lasted 670 min with an estimated blood loss of 350 ml. Postoperative pathological examination revealed a moderately differentiated adenocarcinoma pT1N0 with 15 retrieved nodes and free margins. The patient experienced a type A biliary fistula and was discharged on the 21st postoperative day without abdominal drainage. CONCLUSIONS: Through the tips and tricks presented in this multimedia article, we show the advantages of the robotic approach for performing correctly one of the most complex surgeries.1-7.

Levels of Robotic Mesopancreas Dissection According to Malignancy and Vascular Anatomy: What Surgeons Need to Know.

INTRODUCTION: The robotic approach is attracting increasing interest among the surgical community, and more and more series describing robotic pancreatoduodenectomy have been reported. Thus, surgeons performing robotic pancreatoduodenectomy should be confident with this critical step's potential scenarios. MATERIALS AND METHODS: According to Yosuke et al., there are three different levels of mesopancreas dissection. We describe the main steps for a safe mesopancreas dissection by robotic approach. RESULTS: This multimedia article provides, for the first time in literature, a comprehensive step-by-step overview of the mesopancreas dissection during robotic pancreatoduodenectomy (PD) and its three different levels according to tumor type. CONCLUSIONS: Through the tips and indications presented in this multimedia article, we aim to familiarize surgeons with the mesopancreas dissections levels according to type of malignancy and vascular anatomy.

Differences in Lymph Node Metastases Patterns Among Non-pancreatic Periampullary Cancers and Histologic Subtypes: An International Multicenter Retrospective Cohort Study and Systematic Review.

BACKGROUND: Standard lymphadenectomy for pancreatoduodenectomy is defined for pancreatic ductal adenocarcinoma and adopted for patients with non-pancreatic periampullary cancer (NPPC), ampullary adenocarcinoma (AAC), distal cholangiocarcinoma (dCCA), or duodenal adenocarcinoma (DAC). This study aimed to compare the patterns of lymph node metastases among the different NPPCs in a large series and in a systematic review to guide the discussion on surgical lymphadenectomy and pathology assessment. METHODS: This retrospective cohort study included patients after pancreatoduodenectomy for NPPC with at least one lymph node metastasis (2010-2021) from 24 centers in nine countries. The primary outcome was identification of lymph node stations affected in case of a lymph node metastasis per NPPC. A separate systematic review included studies on lymph node metastases patterns of AAC, dCCA, and DAC. RESULTS: The study included 2367 patients, of whom 1535 had AAC, 616 had dCCA, and 216 had DAC. More patients with pancreatobiliary type AAC had one or more lymph node metastasis (67.2% vs 44.8%; P < 0.001) compared with intestinal-type, but no differences in metastasis pattern were observed. Stations 13 and 17 were most frequently involved (95%, 94%, and 90%). Whereas dCCA metastasized more frequently to station 12 (13.0% vs 6.4% and 7.0%, P = 0.005), DAC metastasized more frequently to stations 6 (5.0% vs 0% and 2.7%; P < 0.001) and 14 (17.0% vs 8.4% and 11.7%, P = 0.015). CONCLUSION: This study is the first to comprehensively demonstrate the differences and similarities in lymph node metastases spread among NPPCs, to identify the existing research gaps, and to underscore the importance of standardized lymphadenectomy and pathologic assessment for AAC, dCCA, and DAC.

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Towards a tailored approach for patients with acute diverticulitis and abscess formation. The DivAbsc2023 multicentre case-control study.

BACKGROUND: This multicentre case-control study aimed to identify risk factors associated with non-operative treatment failure for patients with CT scan Hinchey Ib-IIb and WSES Ib-IIa diverticular abscesses. METHODS: This study included a cohort of adult patients experiencing their first episode of CT-diagnosed diverticular abscess, all of whom underwent initial non-operative treatment comprising either antibiotics alone or in combination with percutaneous drainage. The cohort was stratified based on the outcome of non-operative treatment, specifically identifying those who required emergency surgical intervention as cases of treatment failure. Multivariable logistic regression analysis to identify independent risk factors associated with the failure of non-operative treatment was employed. RESULTS: Failure of conservative treatment occurred for 116 patients (27.04%). CT scan Hinchey classification IIb (aOR 2.54, 95%CI 1.61;4.01, P < 0.01), tobacco smoking (aOR 2.01, 95%CI 1.24;3.25, P < 0.01), and presence of air bubbles inside the abscess (aOR 1.59, 95%CI 1.00;2.52, P = 0.04) were independent predictors of failure. In the subgroup of patients with abscesses > 5 cm, percutaneous drainage was not associated with the risk of failure or success of the non-operative treatment (aOR 2.78, 95%CI - 0.66;3.70, P = 0.23). CONCLUSIONS: Non-operative treatment is generally effective for diverticular abscesses. Tobacco smoking's role as an independent risk factor for treatment failure underscores the need for targeted behavioural interventions in diverticular disease management. IIb Hinchey diverticulitis patients, particularly young smokers, require vigilant monitoring due to increased risks of treatment failure and septic progression. Further research into the efficacy of image-guided percutaneous drainage should involve randomized, multicentre studies focussing on homogeneous patient groups.

The impact of vascular margin invasion on local recurrence after pancreatoduodenectomy in pancreatic adenocarcinoma.

PURPOSE: Pancreatic ductal adenocarcinoma (PADC) still has nowadays a very impaired long-term survival. Most studies are focused on overall survival; however, local recurrence occurs about up to 50% of cases and seems to be highly related with margin resection status. We aim to analyze the impact of vascular resection margins on local recurrence (LR) and to assess its impact on overall and disease-free survival. METHODS: Eighty out of 191 patients who underwent pancreatoduodenectomy in a university hospital between 2006 and 2021 with PDAC diagnosis were analyzed and vascular margin status specifically addressed. Univariate and multivariate were performed. Time to LR was compared by using the Kaplan-Meier method and prognostic factors assessed using Cox regression hazards model. RESULTS: LR appeared in 10 (50%) of the overall R1 resections in the venous margin and 9 (60%) in the arterial one. Time to LR was significantly shorter when any margin was overall affected (23.2 vs 44.7 months, p = 0.01) and specifically in the arterial margin involvement (13.7 vs 32.1 months, p = 0.009). Overall R1 resections (HR 2.61, p = 0.013) and a positive arterial margin (HR 2.84, p = 0.012) were associated with local recurrence on univariate analysis, whereas arterial positive margin remained significant on multivariate analysis (HR 2.70, p = 0.031). CONCLUSIONS: Arterial margin invasion is correlated in our cohort with local recurrence. Given the limited ability to modify this margin intraoperatively, preoperative therapies should be considered to improve local margin clearance.

The influence of socioeconomic inequity and guidelines compliance on clinical outcomes of patients with acute biliary pancreatitis. An international multicentric cohort study.

BACKGROUND: There is lack of data on the association between socioeconomic factors, guidelines compliance and clinical outcomes among patients with acute biliary pancreatitis (ABP). METHODS: Post-hoc analysis of the international MANCTRA-1 registry evaluating the impact of regional disparities as indicated by the Human Development Index (HDI), and guideline compliance on ABP clinical outcomes. Multivariable logistic regression models were employed to identify prognostic factors associated with mortality and readmission. RESULTS: Among 5313 individuals from 151 centres across 42 countries marked disparities in comorbid conditions, ABP severity, and medical procedure usage were observed. Patients from lower HDI countries had higher guideline non-compliance (p < 0.001) and mortality (5.0% vs. 3.2%, p = 0.019) in comparison with very high HDI countries. On adjusted analysis, ASA score (OR 1.810, p = 0.037), severe ABP (OR 2.735, p < 0.001), infected necrosis (OR 2.225, p = 0.006), organ failure (OR 4.511, p = 0.001) and guideline non-compliance (OR 2.554, p = 0.002 and OR 2.178, p = 0.015) were associated with increased mortality. HDI was a critical socio-economic factor affecting both mortality (OR 2.452, p = 0.007) and readmission (OR 1.542, p = 0.046). CONCLUSION: These data highlight the importance of collaborative research to characterise challenges and disparities in global ABP management. Less developed regions with lower HDI scores showed lower adherence to clinical guidelines and higher rates of mortality and recurrence.

Long-term Outcomes After Laparoscopic, Robotic, and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: An International Propensity Score-matched Cohort Study.

OBJECTIVE: This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND: A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS: This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS: Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION: Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.

Robotic Distal Pancreatectomy: A Novel Standard of Care? Benchmark Values for Surgical Outcomes From 16 International Expert Centers.

BACKGROUND AND OBJECTIVE: Robotic distal pancreatectomy (DP) is an emerging attractive approach, but its role compared with laparoscopic or open surgery remains unclear. Benchmark values are novel and objective tools for such comparisons. The aim of this study was to identify benchmark cutoffs for many outcome parameters for DP with or without splenectomy beyond the learning curve. METHODS: This study analyzed outcomes from international expert centers from patients undergoing robotic DP for malignant or benign lesions. After excluding the first 10 cases in each center to reduce the effect of the learning curve, consecutive patients were included from the start of robotic DP up to June 2020. Benchmark patients had no significant comorbidities. Benchmark cutoff values were derived from the 75th or the 25th percentile of the median values of all benchmark centers. Benchmark values were compared with a laparoscopic control group from 4 high-volume centers and published open DP landmark series. RESULTS: Sixteen centers contributed 755 cases, whereof 345 benchmark patients (46%) were included the analysis. Benchmark cutoffs included: operation time ≤300 minutes, conversion rate ≤3%, clinically relevant postoperative pancreatic fistula ≤32%, 3 months major complication rate ≤26.7%, and lymph node retrieval ≥9. The comprehensive complication index at 3 months was ≤8.7 without deterioration thereafter. Compared with robotic DP, laparoscopy had significantly higher conversion rates (5×) and overall complications, while open DP was associated with more blood loss and longer hospital stay. CONCLUSION: This first benchmark study demonstrates that robotic DP provides superior postoperative outcomes compared with laparoscopic and open DP. Robotic DP may be expected to become the approach of choice in minimally invasive DP.

Superior Mesenteric Artery First Approach for Minimally Invasive Pancreaticoduodenectomy: A Step-By-Step Surgical Technique Video.

INTRODUCTION: In the past decade, minimally invasive pancreaticoduodenectomy has been gaining interest. However, minimally invasive pancreaticoduodenectomy remains technically challenging and is associated with a steep learning curve. Additionally, the operating surgeon should be cognizant of replicating the same oncological steps as observed in the typical open approach. In view of this, there exist various maneuvers that are designed to achieve negative margins and a safer mesopancreatic dissection. One of these techniques is the superior mesenteric artery first approach, which is garnering interest among pancreatic surgeons. MATERIAL AND METHODS: According to existing literature, there are several superior mesenteric artery dissections approaches. We describes 5 different minimally invasive approaches. RESULTS: This multimedia manuscript provide, for the first time in literature, a comprehensive step-by-step overview of the superior mesenteric artery first approach for minimally invasive pancreaticoduodenectomy by a team of expert surgeons from various international institutions. CONCLUSIONS: Through the tips and indications presented in this article, we aim to guide the choice of this approach according to tumor location, type of minimally invasive approach and the operating surgeon's experience and increase familiarity with such a complex procedure.

Is occlusion of the main pancreatic duct by thermal ablation really safe? A surgical innovation assessed according to IDEAL recommendations.

INTRODUCTION: Pre-clinical studies suggest that thermal ablation of the main pancreatic duct (TAMPD) is more recommendable than glue for reducing postoperative pancreatic fistula (POPF). Our aims were (1) to analyze the changes in the pancreas of patients after TAMPD and (2) to correlate the clinical findings with those obtained from a study on an animal model. MATERIALS AND METHODS: A retrospective early feasibility study of a marketed device for a novel clinical application was carried out on a small number of subjects (n = 8) in whom TAMPD was conducted to manage the pancreatic stump after a pancreatectoduodenectomy (PD). Morphological changes in the remaining pancreas were assessed by computed tomography for 365 days after TAMPD. RESULTS: All the patients showed either Grade A or B POPF, which generally resolved within the first 30 days. The duct's maximum diameter significantly increased after TAMPD from 1.5 ± 0.8 mm to 8.6 ± 2.9 mm after 7 days (p = .025) and was then reduced to 2.6 ± 0.8 mm after 365 days PO (p < .0001). The animal model suggests that TAMPD induces dilation of the duct lumen by enzymatic digestion of ablated tissue after a few days and complete exocrine atrophy after a few weeks. CONCLUSIONS: TAMPD leads to long-term exocrine pancreatic atrophy by completely occluding the duct. However, the ductal dilatation that occurred soon after TAMPD could even favor POPF, which suggests that TAMPD should be conducted several weeks before PD, ideally by digestive endoscopy.

The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.

BACKGROUND: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). METHODS: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). RESULTS: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. CONCLUSIONS: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. PROTOCOL REGISTRATION: PROSPERO (CRD42021277495) on the 25th of October 2021.

Liver prometastatic reaction: Stimulating factors and responsive cancer phenotypes.

Cancer is first a localized tissue disorder, whose soluble and exosomal molecules and invasive cells induce a host response providing the stromal components of the primary tumor microenvironment (TME). Once the TME is developed, cancer-derived molecules and cells can more efficiently spread out and a whole-body response takes place, whose pathophysiological changes may result in a paraneoplastic syndrome. Remote organ-specific prometastatic reactions may also occur at this time, facilitating metastatic activities of circulating tumor cells (CTCs) through premetastatic niche development at targeted organs. However, additional signaling factors from the inter-organ communication network involved in the pathophysiology and comorbidities of cancer patients may also regulate prometastatic reaction-stimulating effects of cancer and non-cancer tissue factors. This article provides a conceptual overview of our ongoing clinical research on the liver prometastatic reaction (LPR) of patients with colorectal cancer (CRC), their portal vein- and hepatic artery-driven LPR-Stimulating Factors (LPR-SF), and their resulting LPR-derived Metastasis-Stimulating Factors (LPR-MSF) acting on liver-invading CRC cells. In addition, we also provide new insights on the molecular subtyping of LPR-responsive cancer phenotypes in patients with CRC and melanoma; and on how to investigate and interpret the prometastatic infrastructure in the real pathophysiological context of patients with cancer undergoing surgical procedures and receiving pharmacological treatments with multiple side effects, including those affecting the LPR, its stimulating factors and responsive cancer phenotypes.

coMpliAnce with evideNce-based cliniCal guidelines in the managemenT of acute biliaRy pancreAtitis): The MANCTRA-1 international audit.

BACKGROUND/OBJECTIVES: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines. METHODS: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study. Categorical data were reported as percentages representing the proportion of all study patients or different and well-defined cohorts for each variable. Continuous data were expressed as mean and standard deviation. Differences between the compliance obtained in the four different subgroups were compared using the Mann-Whitney U, Student's t, ANOVA or Kruskal-Wallis tests for continuous data, and the Chi-square test or the Fisher's exact test for categorical data. RESULTS: Complete data were available for 5275 patients. The most commonly discordant gaps between daily clinical practice and recommendations included the optimal timing for the index CT scan (6.1%, χ2 6.71, P = 0.081), use of prophylactic antibiotics (44.2%, χ2 221.05, P < 0.00001), early enteral feeding (33.2%, χ2 11.51, P = 0.009), and the implementation of early cholecystectomy strategies (29%, χ2 354.64, P < 0.00001), with wide variability based on the admitting speciality. CONCLUSIONS: The results of this study showed an overall poor compliance with evidence-based guidelines in the management of ABP, with wide variability based on the admitting speciality. Study protocol registered in ClinicalTrials.Gov (ID Number NCT04747990).

Evolving Trends in the Management of Acute Appendicitis During COVID-19 Waves: The ACIE Appy II Study.

BACKGROUND: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. METHODS: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. RESULTS: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. CONCLUSION: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide.

Surgery for liver metastases from primary melanoma: a systematic review and meta-analysis.

BACKGROUND: Historically , liver metastases due to melanoma have been associated with dismal prognosis. Moreover, the actual survival benefit from the treatment of melanoma liver metastases is still controversial. Hence, this study aims to evaluate the difference in surgical versus non-surgical options for melanoma liver metastases. METHODS: Four databases (PubMed, EMBASE, Scopus, and Cochrane Library) were searched from inception to July 17, 2022. Studies were included if they compared outcomes between surgical and non-surgical treatment for patients with liver metastases from resectable melanoma. Meta-analyses were performed for the outcomes of 1-year, 2-year, 3-year and 5-year OS. Sensitivity analyses were performed for outcomes with substantial statistical heterogeneity. To account for possible moderators that might contribute to statistical heterogeneity, univariate meta-regression with mixed-effects models and subgroup analyses were conducted for the outcome of 2-year OS. RESULTS: The search yielded 6610 articles; 13 studies were included in our analysis. Meta-analyses showed that survival outcomes were in favour of patients undergoing surgery as compared to non-surgery: 1-year OS (HR = 0.29, 95%CI 0.19-0.44, p < 0.00001), 2-year OS (HR = 0.19, 95%CI 0.09-0.38, p < 0.00001), 3-year OS (HR = 0.07, 95%CI 0.03-0.19, p < 0.00001) and 5-year OS (HR = 0.07, 95%CI 0.02-0.22, p < 0.00001). All included studies were of high quality. There was moderate-to-high statistical heterogeneity. Findings were robust to sensitivity analyses. Subgroup analyses and univariate meta-regression revealed neoadjuvant therapy and age as statistically significant subgroup and moderator respectively. CONCLUSIONS: This study suggests that surgical treatment of melanoma liver metastases could offer better OS outcomes compared with non-surgical treatment.

Right-side colectomy with complete mesocolic excision vs conventional right-side colectomy in the treatment of colon cancer: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to investigate the role of complete mesocolic excision (CME) in the treatment of right-side colon cancer when compared with standard right-side hemicolectomy, focusing on oncological outcomes, mortality and morbidity rates. MATERIALS AND METHODS: A systematic literature search was performed on MEDLINE and EMBASE archives, including studies on CME in right-side colon cancer. Primary outcomes were five-year disease-free survival and five-year overall survival. Secondary outcomes investigated were mortality and morbidity rates, intraoperative blood loss, anastomotic leakage, postoperative ileus, day of postoperative flatus, pulmonary infection, duration of hospital stay and number of lymph nodes harvested. RESULTS: Seventeen studies have been included in this meta-analysis for a total of 3918 patients. The five-year disease-free survival (DFS) and overall survival (OS) results improved in the CME group with respect to conventional right-side colectomy with an OR 1.88 (95% CI 1.02-3.45) and OR 2.77 (95% CI 1.33-5.74), respectively. The incidence of mortality and morbidity was comparable between the two groups. Moreover, conventional surgery time was faster than CME (MD 33.69 min, 95% CI 12.79-54.59), while no significant differences were reported in mean blood loss and hospital stay. Furthermore, the CME group showed a higher mean number of harvested lymph nodes (MD 7.08 lymph nodes 95% CI 4.90-9.27). CONCLUSION: Complete mesocolic excision of the right-side colectomy improves oncological outcomes without increasing mortality and morbidity rates compared to standard right-side hemicolectomy. CME should therefore be routinely performed in the treatment of right-side colon cancer.