Evidence for molecular subtyping in pancreatic ductal adenocarcinoma: a systematic review.

BACKGROUND: Pancreatic Ductal Adenocarcinoma (PDAC) patients exhibit varied responses to multimodal therapy. RNA gene sequencing has unravelled distinct tumour biology subtypes, forming the focus of this review exploring its impact on survival outcomes. METHODS: A systematic search across PubMed, Medline, Embase, and CINAHL databases targeted studies assessing long-term overall and disease-free survival in PDAC patients with molecular subtyping. RESULTS: Fifteen studies including 2731 patients were identified. Molecular subtyping was performed by RNA sequencing and Immunohistochemistry in 14 studies and by Mass Spectrometry in 1 study. Two main tumour subtypes were identified (classical and basal-like or squamous) with basal like associated with poorer outcomes. Further subtypes were identified in individual studies. Superior survival was seen with classical subtype in all other analyses that compared the classical and basal subtypes. High risk stromal subtypes were identified on further analysis of the stroma and were associated with a worse survival independent of the tumour subtype. CONCLUSION: Molecular subtyping of PDAC specimens can identify patients with high-risk tumour biology and poor survival outcomes. Routine subtyping is limited by the cost of RNA sequencing and the volume of raw data generated which has made its translation into routine clinical practice difficult.

Intraductal papillary neoplasms of the bile ducts: a comparative study of a rare disease in Europe and Nagoya, Japan.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts (IPNB) is a rare disease in Western countries. The aim of this study was to compare tumor characteristics, management strategies, and outcomes between Western and Eastern patients who underwent surgical resection for IPNB. METHODS: A multi-institutional retrospective series of patients with IPNB undergoing surgery between January 2010 and December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA), and at Nagoya University Hospital, Japan. RESULTS: A total of 85 patients (51% male; median age 66 years) from 28 E-AHPBA centers were compared to 91 patients (64% male; median age 71 years) from Nagoya. Patients in Europe had more multiple lesions (23% vs 2%, P < .001), less invasive carcinoma (42% vs 85%, P < .001), and more intrahepatic tumors (52% vs 24%, P < .001) than in Nagoya. Patients in Europe experienced less 90-day grade >3 Clavien-Dindo complications (33% vs 68%, P < .001), but higher 90-day mortality rate (7.0% vs 0%, P = .03). R0 resections (81% vs 82%) were similar. Overall survival, excluding 90-day postoperative deaths, was similar in both regions. DISCUSSION: Despite performing more extensive resections, the low perioperative mortality rate observed in Nagoya was probably influenced by a combination of patient-, tumor-, and surgery-related factors.

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Liver transplantation for iatrogenic bile duct injury: a systematic review.

BACKGROUND: Bile duct injury (BDI) is an infrequent but serious complication of cholecystectomy, often with life-changing consequences. Liver transplantation (LT) may be required following severe BDI, however given the rarity, few large studies exist to guide management for complex BDI. METHODS: A systematic review was performed to assess post-operative complications, 30-day mortality, retransplant rate and 1-year and 5-year survival following LT for BDI in Medline, EMBASE, Web of Science or Cochrane Clinical Trials Database. RESULTS: Seven articles met inclusion criteria, describing 179 patients that underwent LT for BDI. Secondary biliary cirrhosis (SBC) was the main indication for LT (82.2% of patients). Median model for end-stage liver disease (MELD) scores at time of LT ranged from 16 to 20.5. Median 30-day mortality was 20.0%. The 1-year and 5-year survival ranges were 55.0-84.3% and 30.0-83.3% respectively, and the overall retransplant rate was 11.5%. CONCLUSION: BDI is rarely indicated for LT, predominantly for SBC following multiple prior interventions. MELD scores poorly reflect underlying morbidity, and exception criteria for waitlisting may avoid prolonged LT waiting times. 30-day mortality was higher than for non-BDI indications, with comparable long term survival, suggesting that LT remains a viable but high risk salvage option for severe BDI.

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases: an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE.

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. METHODS: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term "early metachronous metastases" applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with "late metachronous metastases" applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSIONS: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.

Outcomes After Liver Transplantation With Incidental Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is currently a contraindication to liver transplantation (LT) in the United Kingdom (UK). Incidental CCA occurs rarely in some patients undergoing LT. We report on retrospective outcomes of patients with incidental CCA from six UK LT centres. Cases were identified from pathology records. Data regarding tumour characteristics and post-transplant survival were collected. CCA was classified by TNM staging and anatomical location. 95 patients who underwent LT between 1988-2020 were identified. Median follow-up after LT was 2.1 years (14 days-18.6 years). Most patients were male (68.4%), median age at LT was 53 (IQR 46-62), and the majority had underlying PSC (61%). Overall median survival after LT was 4.4 years. Survival differed by tumour site: 1-, 3-, and 5-year estimated survival was 82.1%, 68.7%, and 57.1%, respectively, in intrahepatic CCA (n = 40) and 58.5%, 42.6%, and 30.2% in perihilar CCA (n = 42; p = 0.06). 1-, 3-, and 5-year estimated survival was 95.8%, 86.5%, and 80.6%, respectively, in pT1 tumours (28.2% of cohort), and 65.8%, 44.7%, and 31.1%, respectively, in pT2-4 (p = 0.018). Survival after LT for recipients with incidental CCA is inferior compared to usual outcomes for LT in the United Kingdom. LT for earlier stage CCA has similar survival to LT for hepatocellular cancer, and intrahepatic CCAs have better survival compared to perihilar CCAs. These observations may support LT for CCA in selected cases.

A fast-track surgery programme leads to timelier treatment and higher resection rates in pancreatic cancer.

BACKGROUND: The aim was to perform a propensity-matched comparison of patients with pancreatic cancer undergoing surgery, with and without biliary stenting and an intention to treat analysis of long-term survival between the two groups. METHODS: This was an observational study of a cohort of consecutive patients presenting with obstructive jaundice and undergoing pancreatoduodenectomy for pancreatic and periampullary malignancies between November 2015 and May 2019. RESULTS: In this study of 216 consecutive operable patients, 70 followed the fast-track pathway and 146 had pre-operative biliary drainage. All 70 patients in the FT group and 122 out of 146 in the PBD group proceeded to surgery (100% and 83.6% respectively, p = 0.001). Interval time from diagnostic CT scan to surgery and from MDT decision to treat to surgery was shorter in the FT group, (median 8 vs 43 days p < 0.001 and 3 vs 36 days p < 0.001 respectively) as was the overall time from diagnostic CT to adjuvant treatment (88 vs 121 days p < 0.001). Postoperative outcomes including complications, readmission and mortality rates were comparable in the two groups. There was no difference in survival. CONCLUSION: For a person with pancreatic cancer who is proceeding to surgery, the best approach is to avoid pre-operative biliary drainage.

Improving knowledge and confidence in foundation doctors during specialty changeover.

QUALITY PROBLEM: Foundation year junior doctors rotate every 4 months into different specialties. They are often expected to manage patients with complex underlying conditions despite inadequate clinical induction. INITIAL ASSESSMENT: No structured induction was offered to junior doctors rotating to hepato-pancreatico-biliary surgery, a complex and highly specialized discipline within general surgery. We hypothesized that junior doctors will be lacking in both knowledge and confidence when managing these patients. CHOICE OF SOLUTION: Create a structured induction programme and evaluate its effectiveness in improving knowledge and confidence amongst doctors. IMPLEMENTATION: Plan Do Study Act methodology was used along with driver diagrams to map change. A learning resource was developed in the form of a booklet, which included relevant clinical information, processes for escalation and referral as well as guidance for managing acutely unwell patients. A structured 1-hour teaching programme was delivered to junior doctors alongside this. Pre- and post-session questionnaires and statistical analysis were used to determine effect. EVALUATION: Marked improvements in both knowledge and confidence were seen. The intervention showed a statistically significant improvement. LESSONS LEARNED: Clinical induction resources can improve junior doctors' knowledge and confidence in managing their patients. Such induction is both valuable and necessary. Similar interventions can be used with allied health professionals and can involve the use of technology and virtual learning.

Vascular surgery: What increases the flow of students to the speciality?

OBJECTIVES: Vascular surgery is in increasing demand due to the higher prevalence of cardiovascular disease in the general population. Meanwhile, applications to join the speciality have been in decline in the last few years. St George's Surgical Society held a one-day conference to expose undergraduates to the speciality in the hope that this will inspire more undergraduates to pursue it as a career. METHODS: The conference consisted of introductory lectures delivered by a consultant vascular surgeon, followed by practical skills workshops simulating aortic anastomosis on porcine aortas. Pre-course and post-course questionnaires assessed positive and negative perceptions of vascular surgery, knowledge of and self-reported confidence in practical surgical skills and utility of the course in their decision to potentially pursue a career in vascular surgery. RESULTS: There was a significant increase of 27% ( p = 0.03) in the positive perception that vascular surgery includes a diverse range of procedures and subspecialties. Attendees reported a 27% significant increase ( p = 0.02) in the perception that vascular surgery had a wide array of opportunity for academic/research work. Finally, there was an 18% decrease ( p = 0.03) in the negative perception that vascular surgery is somehow female-unfriendly or discriminatory against females. There was also a significant rise in both interest (33%) and understanding (73%) of vascular surgery. CONCLUSIONS: A one-day conference can significantly impact students' perception especially when there is a lack of exposure within the undergraduate curriculum. This course helped to increase positive perception and dispute negative misconceptions about the speciality. The simulation workshops held at this conference increased students' confidence and awareness of relevant surgical skills. This conference provided a unique experience that positively impacted and inspired students and thus served as an important supplement to core medical curriculum.

Transoral Robotic Surgery and the Unknown Primary.

Carcinoma of unknown primary (CUP) comprises approximately 1%-5% of all head and neck malignancies. Primary site detection rates for metastatic cervical squamous cell carcinoma (SCC) remain variable, with current diagnostic imaging unable to identify all tumours. Prevailing evidence suggests that most head and neck CUP are located in the oropharynx. Diagnostic surgical efforts have been directed at sampling the entire oropharynx. Present techniques that make this possible include transoral robotic surgery (TORS). TORS Lingual tonsillectomy or tongue base mucosectomy performed in the setting of head and neck CUP increases the detection rate of occult tumour. The indication, surgical technique, evidence base, and controversies of performing TORS in the context of the unknown primary are presented.

A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

Extracellular Vesicles as Drug Delivery Systems in Organ Transplantation: The Next Frontier.

Extracellular vesicles are lipid bilayer-delimited nanoparticles excreted into the extracellular space by all cells. They carry a cargo rich in proteins, lipids and DNA, as well as a full complement of RNA species, which they deliver to recipient cells to induce downstream signalling, and they play a key role in many physiological and pathological processes. There is evidence that native and hybrid EVs may be used as effective drug delivery systems, with their intrinsic ability to protect and deliver a functional cargo by utilising endogenous cellular mechanisms making them attractive as therapeutics. Organ transplantation is the gold standard for treatment for suitable patients with end-stage organ failure. However, significant challenges still remain in organ transplantation; prevention of graft rejection requires heavy immunosuppression and the lack of donor organs results in a failure to meet demand, as manifested by growing waiting lists. Pre-clinical studies have demonstrated the ability of EVs to prevent rejection in transplantation and mitigate ischemia reperfusion injury in several disease models. The findings of this work have made clinical translation of EVs possible, with several clinical trials actively recruiting patients. However, there is much to be uncovered, and it is essential to understand the mechanisms behind the therapeutic benefits of EVs. Machine perfusion of isolated organs provides an unparalleled platform for the investigation of EV biology and the testing of the pharmacokinetic and pharmacodynamic properties of EVs. This review classifies EVs and their biogenesis routes, and discusses the isolation and characterisation methods adopted by the international EV research community, before delving into what is known about EVs as drug delivery systems and why organ transplantation represents an ideal platform for their development as drug delivery systems.

Intraoperative pancreas stump perfusion assessment during pancreaticoduodenectomy: A systematic scoping review.

BACKGROUND: Post-operative pancreatic fistula (POPF) is the primary cause of morbidity following pancreaticoduodenectomy. Rates of POPF have remained high despite well known risk factors. The theory that hypoperfusion of the pancreatic stump leads to anastomotic failure has recently gained interest. AIM: To define the published literature with regards to intraoperative pancreas perfusion assessment and its correlation with POPF. METHODS: A systematic search of available literature was performed in November 2022. Data extracted included study characteristics, method of assessment of pancreas stump perfusion, POPF and other post-pancreatic surgery specific complications. RESULTS: Five eligible studies comprised two prospective non-randomised studies and three case reports, total 156 patients. Four studies used indocyanine green fluorescence angiography to assess the pancreatic stump, with the remaining study assessing pancreas perfusion by visual inspection of arterial bleeding of the pancreatic stump. There was significant heterogeneity in the definition of POPF. Studies had a combined POPF rate of 12%; intraoperative perfusion assessment revealed hypoperfusion was present in 39% of patients who developed POPF. The rate of POPF was 11% in patients with no evidence of hypoperfusion and 13% in those with evidence of hypoperfusion, suggesting that not all hypoperfusion gives rise to POPF and further analysis is required to analyse if there is a clinically relevant cut off. Significant variance in practice was seen in the pancreatic stump management once hypoperfusion was identified. CONCLUSION: The current published evidence around pancreas perfusion during pancreaticoduodenectomy is of poor quality. It does not support a causative link between hypoperfusion and POPF. Further well-designed prospective studies are required to investigate this.

Irreversible Electroporation for Liver Metastases from Colorectal Cancer: A Systematic Review.

BACKGROUND: Irreversible electroporation (IRE) is a non-thermal form of ablation based on the delivery of pulsed electrical fields. It has been used to treat liver lesions, particularly those in proximity to major hepatic vasculature. The role of this technique in the portfolio of treatments for colorectal hepatic metastases has not been clearly defined. This study undertakes a systematic review of IRE for treatment of colorectal hepatic metastases. METHODS: The study protocol was registered with the PROSPERO register of systematic reviews (CRD42022332866) and reports in compliance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Ovid MEDLINE®, EMBASE, Web of Science and Cochrane databases were queried in April 2022. The search terms 'irreversible electroporation', 'colon cancer', 'rectum cancer' and 'liver metastases' were used in combinations. Studies were included if they provided information on the use of IRE for patients with colorectal hepatic metastases and reported procedure and disease-specific outcomes. The searches returned 647 unique articles and the exclusions left a total of eight articles. These were assessed for bias using the methodological index for nonrandomized studies (MINORS criteria) and reported using the synthesis without meta-analysis guideline (SWiM). RESULTS: One hundred eighty patients underwent treatment for liver metastases from colorectal cancer. The median transverse diameter of tumours treated by IRE was <3 cm. Ninety-four (52%) tumours were adjacent to major hepatic inflow/outflow structures or the vena cava. IRE was undertaken under general anaesthesia with cardiac cycle synchronisation and with the use of either CT or ultrasound for lesion localisation. Probe spacing was less than 3.2 cm for all ablations. There were two (1.1%) procedure-related deaths in 180 patients. There was one (0.5%) post-operative haemorrhage requiring laparotomy, one (0.5%) bile leak, five (2.8%) post-procedure biliary strictures and a zero incidence of post-IRE liver failure. CONCLUSIONS: This systematic review shows that IRE for colorectal liver metastases can be accomplished with low procedure-related morbidity and mortality. Further prospective study is required to assess the role of IRE in the portfolio of treatments for patients with liver metastases from colorectal cancer.

Using Laser Speckle Contrast Imaging to Quantify Perfusion Quality in Kidney and Pancreas Grafts on Vascular Reperfusion: A Proof-of-Principle Study.

The accuracy of intraoperative graft perfusion assessment still remains subjective, with doppler examination being the only objective adjunct. Laser speckle contrast imaging (LSCI) has been used to assess intraoperative blood flow in neurosurgery and in various surgical specialties. Despite its ability to accurately quantify perfusion at the microvascular level, it has not been clinically evaluated in kidney/kidney-pancreas transplantation for perfusion characterization. We aimed to evaluate the utility of LSCI and identify objective parameters that can be quantified at reperfusion. Methods: This study was registered in ClinicalTrials.gov (NCT04202237). The Moor FLPI-2 blood flow imager was used in 4 patients (1 Simultaneous Pancreas and Kidney, 2 deceased, and 1 living donor kidney transplants) during reperfusion to capture reperfusion data. The following parameters were measured: flux (average speed × concentration of moving red blood cells in the sample volume), doppler centroid, total and valid pixels, valid rate, and total and valid area. Flux data were analyzed with Moor FLPI analysis software. Results: The perfusion characteristics and flux images correlated with initial graft function. Conclusions: LSCI is a safe, noncontact imaging modality that provides real-time, accurate, high-resolution, full field blood flow images and a wide range of flux data to objectively quantify organ reperfusion intraoperatively in kidney/kidney-pancreas transplantation. This modality could be used to develop a robust numerical quantification system for the evaluation and reporting of intraoperative organ perfusion, and aid intraoperative decision-making. Perfusion data could be combined with biomarkers and immunological parameters to more accurately predict graft outcomes.

Pancreas transplantation today: quo vadis?

Successful pancreas or islet transplantation is currently the only cure for type 1 diabetes mellitus. Since the first pancreas transplant in 1966, there have been various refinements of surgical technique along with improved immunosuppressive regimens, resulting in significantly improved outcomes, with contemporary research into graft monitoring and newer biomarkers, potentially lengthening graft survival rates further. Patients with insulin-dependent diabetes mellitus who are eligible for pancreas or islet transplantation represent a select group, the tip of the iceberg for a significant global diabetes disease burden. In the last 50 years, there have been quantum advances in alternative technologies in diabetes therapy, both experimental and translational. Further development and improved access are required to treat the larger proportion of people suffering from diabetes. Emerging stem cell therapy is still experimental whereas alternatives including automated insulin delivery systems and islet cell transplantation are already used in some countries. Whilst automated insulin delivery systems have increased in efficacy, they still do not achieve the near physiological control of blood sugar, which can be achieved by successful pancreas or islet transplantation. This state-of-the-art review provides a summary of pancreas and islet transplantation to its current place in diabetes therapy, along with alternative and future therapies, including the obstacles associated with the dissemination of these new therapies. With the advent of these modern cellular and technological advances, this review addresses the question: are we entering an era where whole organ pancreas transplantation could be replaced entirely by modern technological advances in diabetes therapy?

Surgical outcomes of gallbladder cancer: the OMEGA retrospective, multicentre, international cohort study.

Background: Gallbladder cancer (GBC) is rare but aggressive. The extent of surgical intervention for different GBC stages is non-uniform, ranging from cholecystectomy alone to extended resections including major hepatectomy, resection of adjacent organs and routine extrahepatic bile duct resection (EBDR). Robust evidence here is lacking, however, and survival benefit poorly defined. This study assesses factors associated with recurrence-free survival (RFS), overall survival (OS) and morbidity and mortality following GBC surgery in high income countries (HIC) and low and middle income countries (LMIC). Methods: The multicentre, retrospective Operative Management of Gallbladder Cancer (OMEGA) cohort study included all patients who underwent GBC resection across 133 centres between 1st January 2010 and 31st December 2020. Regression analyses assessed factors associated with OS, RFS and morbidity. Findings: On multivariable analysis of all 3676 patients, wedge resection and segment IVb/V resection failed to improve RFS (HR 1.04 [0.84-1.29], p = 0.711 and HR 1.18 [0.95-1.46], p = 0.13 respectively) or OS (HR 0.96 [0.79-1.17], p = 0.67 and HR 1.48 [1.16-1.88], p = 0.49 respectively), while major hepatectomy was associated with worse RFS (HR 1.33 [1.02-1.74], p = 0.037) and OS (HR 1.26 [1.03-1.53], p = 0.022). Furthermore, EBDR (OR 2.86 [2.3-3.52], p < 0.0010), resection of additional organs (OR 2.22 [1.62-3.02], p < 0.0010) and major hepatectomy (OR 3.81 [2.55-5.73], p < 0.0010) were all associated with increased morbidity and mortality. Compared to LMIC, patients in HIC were associated with poorer RFS (HR 1.18 [1.02-1.37], p = 0.031) but not OS (HR 1.05 [0.91-1.22], p = 0.48). Adjuvant and neoadjuvant treatments were infrequently used. Interpretation: In this large, multicentre analysis of GBC surgical outcomes, liver resection was not conclusively associated with improved survival, and extended resections were associated with greater morbidity and mortality without oncological benefit. Aggressive upfront resections do not benefit higher stage GBC, and international collaborations are needed to develop evidence-based neoadjuvant and adjuvant treatment strategies to minimise surgical morbidity and prioritise prognostic benefit. Funding: Cambridge Hepatopancreatobiliary Department Research Fund.

Intraductal papillary neoplasms of the bile duct: a European retrospective multicenter observational study (EUR-IPNB study).

BACKGROUND/PURPOSE: Intraductal papillary neoplasm of the bile duct (IPNB) is a rare disease in Western countries. The main aim of this study was to characterize current surgical strategies and outcomes in the mainly European participating centers. METHODS: A multi-institutional retrospective series of patients with a diagnosis of IPNB undergoing surgery between 1 January 2010 and 31 December 2020 was gathered under the auspices of the European-African Hepato-Pancreato-Biliary Association. The textbook outcome (TO) was defined as a non-prolonged length of hospital stay plus the absence of any Clavien-Dindo grade at least III complications, readmission, or mortality within 90 postoperative days. RESULTS: A total of 28 centers contributed 85 patients who underwent surgery for IPNB. The median age was 66 years (55-72), 49.4% were women, and 87.1% were Caucasian. Open surgery was performed in 72 patients (84.7%) and laparoscopic in 13 (15.3%). TO was achieved in 54.1% of patients, reaching 63.8% after liver resection and 32.0% after pancreas resection. Median overall survival was 5.72 years, with 5-year overall survival of 63% (95% CI: 50-82). Overall survival was better in patients with Charlson comorbidity score 4 or less versus more than 4 ( P =0.016), intrahepatic versus extrahepatic tumor ( P =0.027), single versus multiple tumors ( P =0.007), those who underwent hepatic versus pancreatic resection ( P =0.017), or achieved versus failed TO ( P =0.029). Multivariable Cox regression analysis showed that not achieving TO (HR: 4.20; 95% CI: 1.11-15.94; P =0.03) was an independent prognostic factor of poor overall survival. CONCLUSIONS: Patients undergoing liver resection for IPNB were more likely to achieve a TO outcome than those requiring a pancreatic resection. Comorbidity, tumor location, and tumor multiplicity influenced overall survival. TO was an independent prognostic factor of overall survival.