Tissue CD14+CD8+ T cells reprogrammed by myeloid cells and modulated by LPS.

The liver is bathed in bacterial products, including lipopolysaccharide transported from the intestinal portal vasculature, but maintains a state of tolerance that is exploited by persistent pathogens and tumours1-4. The cellular basis mediating this tolerance, yet allowing a switch to immunity or immunopathology, needs to be better understood for successful immunotherapy of liver diseases. Here we show that a variable proportion of CD8+ T cells compartmentalized in the human liver co-stain for CD14 and other prototypic myeloid membrane proteins and are enriched in close proximity to CD14high myeloid cells in hepatic zone 2. CD14+CD8+ T cells preferentially accumulate within the donor pool in liver allografts, among hepatic virus-specific and tumour-infiltrating responses, and in cirrhotic ascites. CD14+CD8+ T cells exhibit increased turnover, activation and constitutive immunomodulatory features with high homeostatic IL-10 and IL-2 production ex vivo, and enhanced antiviral/anti-tumour effector function after TCR engagement. This CD14+CD8+ T cell profile can be recapitulated by the acquisition of membrane proteins-including the lipopolysaccharide receptor complex-from mononuclear phagocytes, resulting in augmented tumour killing by TCR-redirected T cells in vitro. CD14+CD8+ T cells express integrins and chemokine receptors that favour interactions with the local stroma, which can promote their induction through CXCL12. Lipopolysaccharide can also increase the frequency of CD14+CD8+ T cells in vitro and in vivo, and skew their function towards the production of chemotactic and regenerative cytokines. Thus, bacterial products in the gut-liver axis and tissue stromal factors can tune liver immunity by driving myeloid instruction of CD8+ T cells with immunomodulatory ability.

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 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.

REDISCOVER International Guidelines on the Perioperative Care of Surgical Patients With Borderline-resectable and Locally Advanced Pancreatic Cancer.

OBJECTIVE: The REDISCOVER consensus conference aimed at developing and validating guidelines on the perioperative care of patients with borderline-resectable (BR-) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Coupled with improvements in chemotherapy and radiation, the contemporary approach to pancreatic surgery supports the resection of BR-PDAC and, to a lesser extent, LA-PDAC. Guidelines outlining the selection and perioperative care for these patients are lacking. METHODS: The Scottish Intercollegiate Guidelines Network (SIGN) methodology was used to develop the REDISCOVER guidelines and create recommendations. The Delphi approach was used to reach a consensus (agreement ≥80%) among experts. Recommendations were approved after a debate and vote among international experts in pancreatic surgery and pancreatic cancer management. A Validation Committee used the AGREE II-GRS tool to assess the methodological quality of the guidelines. Moreover, an independent multidisciplinary advisory group revised the statements to ensure adherence to nonsurgical guidelines. RESULTS: Overall, 34 recommendations were created targeting centralization, training, staging, patient selection for surgery, possibility of surgery in uncommon scenarios, timing of surgery, avoidance of vascular reconstruction, details of vascular resection/reconstruction, arterial divestment, frozen section histology of perivascular tissue, extent of lymphadenectomy, anticoagulation prophylaxis, and role of minimally invasive surgery. The level of evidence was however low for 29 of 34 clinical questions. Participants agreed that the most conducive means to promptly advance our understanding in this field is to establish an international registry addressing this patient population ( https://rediscover.unipi.it/ ). CONCLUSIONS: The REDISCOVER guidelines provide clinical recommendations pertaining to pancreatectomy with vascular resection for patients with BR-PDAC and LA-PDAC, and serve as the basis of a new international registry for this patient population.

Harmonizing Definitions and Perspectives in Extreme Liver Surgery: A Delphi Experts Consensus.

OBJECTIVE: To propose to our community a common language about extreme liver surgery. BACKGROUND: The lack of a clear definition of extreme liver surgery prevents convincing comparisons of results among centers. METHODS: We used a two-round Delphi methodology to quantify consensus among liver surgery experts. For inclusion in the final recommendations, we established a consensus when the positive responses (agree and totally agree) exceeded 70%. The study steering group summarized and reported the recommendations. In general, a five-point Likert scale with a neutral central value was used, and in a few cases multiple choices. Results are displayed as numbers and percentages. RESULTS: A two-round Delphi study was completed by 38 expert surgeons in complex hepatobiliary surgery. The surgeon´s median age was 58 years old (52-63) and the median years of experience was 25 years (20-31). For the proposed definitions of total vascular occlusion, hepatic flow occlusion and inferior vein occlusion, the degree of agreement was 97%, 81% and 84%, respectively. In situ approach (64%) was the preferred, followed by ante situ (22%) and ex situ (14%). Autologous or cadaveric graft for hepatic artery or hepatic vein repair were the most recommended (89%). The use of veno-venous bypass or portocaval shunt revealed the divergence depending on the case. Overall, 75% of the experts agreed with the proposed definition for extreme liver surgery. CONCLUSION: Obtaining a consensus on the definition of extreme liver surgery is essential to guarantee the correct management of patients with highly complex hepatobiliary oncological disease. The management of candidates for extreme liver surgery involves comprehensive care ranging from adequate patient selection to the appropriate surgical strategy.

The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). PATIENTS AND METHODS: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. RESULTS: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

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.

Assessment of Internet Available Patient Information on Chronic Pancreatitis Using the Ensuring Quality Information for Patients Tool: A Systematic Search and Evaluation.

INTRODUCTION: Chronic pancreatitis (CP) is a relevant chronic medical problem whereby delayed presentation and poor patient understanding can cause adverse effects. Quality of patient information available on the internet about CP is not known. METHODS: A systematic review of the information about CP available online using the search term "chronic pancreatitis" in using the search engine Google has been conducted. The quality of the top 100 websites returned from this search term was analysed using the validated Ensuring Quality Information for Patients (EQIP) tool (maximum score 36). Additional items were included in the website analysis specific to CP. RESULTS: In total, 45 websites were eligible for analysis. The median EQIP score of the websites was 16 (interquartile range 12-19.5). The majority of websites originated from the USA and the United Kingdom with 31 and 11 websites, respectively. Provision of additional information was inconsistent, with most websites covering information regarding aetiology and advocating alcohol and tobacco cessation, but only few reporting on more complex issues. CONCLUSION: Internet available information about CP is of limited quality. There is an immediate need for high quality, patient targeted, and informative literature accessible on the internet about this topic.

Short-term Outcomes After Spleen-preserving Minimally Invasive Distal Pancreatectomy With or Without Preservation of Splenic Vessels: A Pan-European Retrospective Study in High-volume Centers.

OBJECTIVE: To compare short-term clinical outcomes after Kimura and Warshaw MIDP. BACKGROUND: Spleen preservation during distal pancreatectomy can be achieved by either preservation (Kimura) or resection (Warshaw) of the splenic vessels. Multicenter studies reporting outcomes of Kimura and Warshaw spleen-preserving MIDP are scarce. METHODS: Multicenter retrospective study including consecutive MIDP procedures intended to be spleen-preserving from 29 high-volume centers (≥15 distal pancreatectomies annually) in 8 European countries. Primary outcomes were secondary splenectomy for ischemia and major (Clavien-Dindo grade ≥III) complications. Sensitivity analysis assessed the impact of excluding ("rescue") Warshaw procedures which were performed in centers that typically (>75%) performed Kimura MIDP. RESULTS: Overall, 1095 patients after MIDP were included with successful splenic preservation in 878 patients (80%), including 634 Kimura and 244 Warshaw procedures. Rates of clinically relevant splenic ischemia (0.6% vs 1.6%, P = 0.127) and major complications (11.5% vs 14.4%, P = 0.308) did not differ significantly between Kimura and Warshaw MIDP, respectively. Mortality rates were higher after Warshaw MIDP (0.0% vs 1.2%, P = 0.023), and decreased in the sensitivity analysis (0.0% vs 0.6%, P = 0.052). Kimura MIDP was associated with longer operative time (202 vs 184 minutes, P = 0.033) and less blood loss (100 vs 150 mL, P < 0.001) as compared to Warshaw MIDP. Unplanned splenectomy was associated with a higher conversion rate (20.7% vs 5.0%, P < 0.001). CONCLUSIONS: Kimura and Warshaw spleen-preserving MIDP provide equivalent short-term outcomes with low rates of secondary splenectomy and postoperative morbidity. Further analyses of long-term outcomes are needed.

Robot-Assisted Versus Laparoscopic Distal Pancreatectomy in Patients with Resectable Pancreatic Cancer: An International, Retrospective, Cohort Study.

BACKGROUND: Robot-assisted distal pancreatectomy (RDP) is increasingly used as an alternative to laparoscopic distal pancreatectomy (LDP) in patients with resectable pancreatic cancer but comparative multicenter studies confirming the safety and efficacy of RDP are lacking. METHODS: An international, multicenter, retrospective, cohort study, including consecutive patients undergoing RDP and LDP for resectable pancreatic cancer in 33 experienced centers from 11 countries (2010-2019). The primary outcome was R0-resection. Secondary outcomes included lymph node yield, major complications, conversion rate, and overall survival. RESULTS: In total, 542 patients after minimally invasive distal pancreatectomy were included: 103 RDP (19%) and 439 LDP (81%). The R0-resection rate was comparable (75.7% RDP vs. 69.3% LDP, p = 0.404). RDP was associated with longer operative time (290 vs. 240 min, p < 0.001), more vascular resections (7.6% vs. 2.7%, p = 0.030), lower conversion rate (4.9% vs. 17.3%, p = 0.001), more major complications (26.2% vs. 16.3%, p = 0.019), improved lymph node yield (18 vs. 16, p = 0.021), and longer hospital stay (10 vs. 8 days, p = 0.001). The 90-day mortality (1.9% vs. 0.7%, p = 0.268) and overall survival (median 28 vs. 31 months, p = 0.599) did not differ significantly between RDP and LDP, respectively. CONCLUSIONS: In selected patients with resectable pancreatic cancer, RDP and LDP provide a comparable R0-resection rate and overall survival in experienced centers. Although the lymph node yield and conversion rate appeared favorable after RDP, LDP was associated with shorter operating time, less major complications, and shorter hospital stay. The specific benefits associated with each approach should be confirmed by multicenter, randomized trials.

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.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Results from the european survey on preoperative management and optimization protocols for PeriHilar cholangiocarcinoma.

BACKGROUND: Major surgery, along with preoperative cholestasis-related complications, are responsible for the increased risk of morbidity and mortality in perihilar cholangiocarcinoma (pCCA). The aim of the present survey is to provide a snapshot of current preoperative management and optimization strategies in Europe. METHODS: 61 European centers, experienced in hepato-biliary surgery completed a 59-questions survey regarding pCCA preoperative management. Centers were stratified according to surgical caseload (<5 and ≥ 5 cases/year) and preoperative management protocols' application. RESULTS: The overall case volume consisted of 6333 patients. Multidisciplinary discussion was routinely performed in 91.8% of centers. Most respondents (96.7%) recognized the importance of a well-structured preoperative protocol. The preferred method for biliary drainage was percutaneous transhepatic biliary drainage (60.7%) while portal vein embolization was the preferred technique for liver hypertrophy (90.2%). Differences in preoperative pathologic confirmation of malignancy (35.8% vs 28.7%; p < 0.001), number of mismanaged referred patients (88.2% vs 50.8%; p < 0.001), biliary drainage (65.1% vs 55.6%; p = 0.015) and liver function evaluation (37.2% vs 5.6%; p = 0.001) were found between centers according to groups' stratification. CONCLUSION: The importance of a correct preoperative management is recognized. Nevertheless, the current lack of guidelines leads to wide heterogeneity of behaviors among centers. This survey can provide recommendations to improve pCCA perioperative outcomes.

Postpancreatectomy Acute Pancreatitis (PPAP): Definition and Grading From the International Study Group for Pancreatic Surgery (ISGPS).

OBJECTIVE: The ISGPS aimed to develop a universally accepted definition for PPAP for standardized reporting and outcome comparison. BACKGROUND: PPAP is an increasingly recognized complication after partial pancreatic resections, but its incidence and clinical impact, and even its existence are variable because an internationally accepted consensus definition and grading system are lacking. METHODS: The ISGPS developed a consensus definition and grading of PPAP with its members after an evidence review and after a series of discussions and multiple revisions from April 2020 to May 2021. RESULTS: We defined PPAP as an acute inflammatory condition of the pancreatic remnant beginning within the first 3 postoperative days after a partial pancreatic resection. The diagnosis requires (1) a sustained postoperative serum hyperamylasemia (POH) greater than the institutional upper limit of normal for at least the first 48 hours postoperatively, (2) associated with clinically relevant features, and (3) radiologic alterations consistent with PPAP. Three different PPAP grades were defined based on the clinical impact: (1) grade postoperative hyperamylasemia, biochemical changes only; (2) grade B, mild or moderate complications; and (3) grade C, severe life-threatening complications. DISCUSSIONS: The present definition and grading scale of PPAP, based on biochemical, radiologic, and clinical criteria, are instrumental for a better understanding of PPAP and the spectrum of postoperative complications related to this emerging entity. The current terminology will serve as a reference point for standard assessment and lend itself to developing specific treatments and prevention strategies.

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods.

BACKGROUND: Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. METHODS: Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006-2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. RESULTS: Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. CONCLUSION: Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently.

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.

Assessing the Impact of Primary Tumour Location on Survival After Resection of Colorectal Liver Metastases: A Propensity Weighted Retrospective Cohort Study.

BACKGROUND: Right-sided colonic tumours appear to have poorer survival after resection of colorectal liver metastases, although this may be confounded by various factors including advanced stage and emergency presentation. METHODS: Medical records of consecutive patients undergoing resection of colorectal liver metastases at a single centre from 2008 to 2015 were retrospectively reviewed. Cases were categorised by primary tumour location (right colon, left colon, rectum). Each primary location was weighted using propensity scores to balance covariates, including staging and mode of presentation. Cox regression was then applied to derive multivariable hazard ratios (HR) of survival after liver resection. Primary outcomes were 10-year overall survival (OS) and 5-year disease-free survival (DFS) after liver resection based on PTL. RESULTS: 414 patients were included in the analysis. Left colonic tumours were significantly associated with higher rates of bilobar liver metastasis (36.2% vs. 20.1% and 30.1%) and larger maximum size of liver metastases compared with rectal and right-sided tumours, respectively. There was no difference in rates of extra-hepatic metastases, recurrence in the liver after resection or RAS, BRAF or p53 mutational status. After propensity weighting and Cox-regression, right-sided tumours were independently associated with significantly reduced 10 year OS (HR 1.56, 95% CI 1.03-2.36, p = 0.04) but not 5 year DFS (HR 1.36, 95% CI 0.89-2.08, p = 0.15). CONCLUSIONS: Compared with left colonic and rectal tumours, right-sided colonic tumours are independently associated with inferior OS after resection of CRLM. This is despite higher rates of bilobar liver metastases and larger metastases with left-sided tumours.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Perihilar Cholangiocarcinoma - Novel Benchmark Values for Surgical and Oncological Outcomes From 24 Expert Centers.

OBJECTIVE: The aim of this study was to define robust benchmark values for the surgical treatment of perihilar cholangiocarcinomas (PHC) to enable unbiased comparisons. BACKGROUND: Despite ongoing efforts, postoperative mortality and morbidity remains high after complex liver surgery for PHC. Benchmark data of best achievable results in surgical PHC treatment are however still lacking. METHODS: This study analyzed consecutive patients undergoing major liver surgery for PHC in 24 high-volume centers in 3 continents over the recent 5-year period (2014-2018) with a minimum follow-up of 1 year in each patient. Benchmark patients were those operated at high-volume centers (≥50 cases during the study period) without the need for vascular reconstruction due to tumor invasion, or the presence of significant co-morbidities such as severe obesity (body mass index ≥35), diabetes, or cardiovascular diseases. Benchmark cutoff values were derived from the 75th or 25th percentile of the median values of all benchmark centers. RESULTS: Seven hundred eight (39%) of a total of 1829 consecutive patients qualified as benchmark cases. Benchmark cut-offs included: R0 resection ≥57%, postoperative liver failure (International Study Group of Liver Surgery): ≤35%; in-hospital and 3-month mortality rates ≤8% and ≤13%, respectively; 3-month grade 3 complications and the CCI: ≤70% and ≤30.5, respectively; bile leak-rate: ≤47% and 5-year overall survival of ≥39.7%. Centers operating mostly on complex cases disclosed better outcome including lower post-operative liver failure rates (4% vs 13%; P = 0.002). Centers from Asia disclosed better outcomes. CONCLUSION: Surgery for PHC remains associated with high morbidity and mortality with now the availability of benchmark values covering 21 outcome parameters, which may serve as key references for comparison in any future analyses of individuals, group of patients or centers.