Surgery as a Principle and Technical Consideration for Primary Tumor Resection of Small Bowel Neuroendocrine Tumors.

Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.

Assessment of Outcomes by Intention-to-Treat Comparison for Locally Advanced Pancreatic Cancer: A Population-Derived Cohort Study.

BACKGROUND: The overall treatment response among patients with locally advanced pancreatic cancer (LAPC) is poorly understood as most studies report solely on resected patients. We aimed to investigate the outcomes in patients with LAPC as an intention-to-treat-analysis from the time of diagnosis from a complete source population. PATIENTS AND METHODS: An observational cohort study in a population-defined region within a universal healthcare system. All consecutive patients discussed at multi-disciplinary tumour board (MDT), aged ≥ 18 years and diagnosed with LAPC were included. Exposure was set as recommended treatment by MDT (i.e. upfront surgery, neoadjuvant therapy, palliative treatment or best supportive care). Outcome measures were overall survival analysed by Kaplan-Meier survival estimates and multivariable analyses using logistic regression for odds ratios (OR) and Cox proportional hazard analysis for hazard ratios (HR). RESULTS: In total, 8803 MDT events (6055 unique patients) with pancreatic disease were held during the study period. Some 1436 (24%) had pancreatic cancer, of which 162 (11%) had LAPC and 134 met the population-defined criteria. In overall survival analyses, the patients who were recommended neoadjuvant therapy (± surgery) demonstrated no significant difference to palliative chemotherapy (median 11.0 months vs. 11.8 months; p = 0.226). In multivariable analysis, adjusted OR for overall survival comparing the treatment groups was 0.27 (95% CI 0.02-3.29, p = 0.306) and Cox proportional HR 0.96 (95% CI 0.58-1.59, p = 0.865). CONCLUSIONS: In patients with LAPC, survival was not statistically different between those recommended for attempt at neoadjuvant (± surgery) compared with those recommended palliative chemotherapy. The findings suggest that conversion/downstaging chemotherapy is successful in only a select few.

Surveillance after surgery for pancreatic cancer: a global scoping review of guidelines and a nordic Survey of contemporary practice.

OBJECTIVES: Most patients with pancreatic cancer who have undergone surgical resection eventually develop disease recurrence. |This study aimed to investigate whether there is evidence to support routine surveillance after pancreatic cancer surgery, with a secondary aim of analyzing the implementation of surveillance strategies in the Nordic countries. MATERIALS AND METHODS: A scoping review was conducted to identify clinical practice guidelines globally and research studies relating to surveillance after pancreatic cancer resection. This was followed by a survey among 20 pancreatic units from four Nordic countries to assess their current practice of follow-up for operated patients. RESULTS: Altogether 16 clinical practice guidelines and 17 research studies were included. The guidelines provided inconsistent recommendations regarding postoperative surveillance of pancreatic cancer. The clinical research data were mainly based on retrospective cohort studies with low level of evidence and lead-time bias was not addressed. Active surveillance was recommended in Sweden and Denmark, but not in Norway beyond the post-operative/adjuvant period. Finland had no national recommendations for surveillance. The Nordic survey revealed a wide variation in reported practice among the different units. About 75% (15 of 20 units) performed routine postoperative surveillance. Routine CA 19-9 testing was used by 80% and routine CT by 67% as part of surveillance. About 73% of centers continued follow-up until 5 years postoperatively. CONCLUSION: Evidence for routine long-term (i.e. 5 years) surveillance after pancreatic cancer surgery remains limited. Most pancreatic units in the Nordic countries conduct regular follow-up, but protocols vary.

Internal and external factors affecting the performance score of surgical trainees doing laparoscopic appendectomy: a prospective, observational cohort study in a structured training programme.

BACKGROUND: Laparoscopic appendectomy is a common procedure and introduced early in general surgical training. How internal (i.e. surgeon's experience) or external (i.e. disease severity) may affect procedure performance is not well-studied. The aim of this study was to evaluate factors that may have an influence on the performance scores for surgical trainees. METHODS: A prospective, observational cohort study of laparoscopic appendectomies performed by surgical trainees (experience < 4 years) operating under supervision. Trainers evaluated trainees' overall performance on a 6-point scale for proficiency. Perioperative data were recorded, including appendicitis severity, operating time and the overall difficulty of the procedure as assessed by the trainer. A "Challenging" procedure was defined as a combination of either/or "perforation" and "difficult". Trainees who had performed > 30 appendectomies were defined as "experienced". The trainees were asked if they had used simulation or web-based tools the week prior to surgery. RESULTS: 142 procedure evaluation forms were included of which 19 (13%) were "perforated", 14 (10%) "difficult" and 24 (17%) "Challenging". Perforated appendicitis was strongly associated with procedure difficulty (OR 21.2, 95% CI 6.0-75.6). Experienced trainees performed "proficient" more often than non-experienced (OR 34.5, 95% CI 6.8-176.5). "Difficult" procedures were inversely associated with proficiency (OR 0.1, 95% CI 0.0-0.9). In "Challenging" procedures, identifying the appendix had lowest proficiency (OR 0.4, 95% CI 0.1-0.9). The procedures assessed as "difficult" had significantly longer operating time with a median (IQR) of 90 (75-100) min compared to 59 (25-120) min for the non-difficult (p < 0.001). CONCLUSION: Both internal and external factors contribute to the performance score. Perforated appendicitis, technical difficult procedures and trainee experience all play a role, but a "difficult" procedure had most overall impact on proficiency evaluation.

Benefits and barriers to accreditation of HPB center and fellowship programs in Europe: a strength-weakness-opportunity-and-threats (SWOT) analysis by an E-AHPBA-ESSO-UEMS ad hoc working committee.

BACKGROUND: Training in HPB surgery lacks uniformity across regions covered by the E-AHPBA. Accreditation has been in place for centers and fellowship programs, but with low uptake. The decision whether to continue, change or cease such accreditation is being discussed. Thus, a strengths, weaknesses, opportunities, and threats (SWOT) analysis was conducted. METHODS: A mixed-methods, cross-sectional study among stakeholders in E-AHPBA, ESSO and UEMS under the E-AHPBA executive council was founded, ensuring representation by gender and geographic distribution. RESULTS: Responses were collected from across E-AHPBA regions, with response from 15 of 24 subchapters. The most frequent and recurring themes are presented in a SWOT matrix which allows for paired evaluations of factors deemed to be helpful (Strengths and Opportunities), those that are harmful (Weaknesses and Threats). CONCLUSION: This study identified both helpful and harmful effects to an accreditation process of HPB centers or HPB fellowship training across the E-AHPBA membership region. Formal accreditation of centers is not within the scope, nor jurisdiction nor financial capacity for E-AHPBA in the current situation. A strong interest in formal HPB training should be capitalized into E-AHPBA strategic planning towards a structured accreditation system for HPB fellowship programs or HPB training tracks.

Clinical trials of neoadjuvant immune checkpoint inhibitors for early-stage operable colon and rectal cancer.

BACKGROUND: Immune checkpoint inhibitors (ICI) have become first-line treatment for metastatic colorectal cancer (CRC) with deficient mismatch repair (dMMR). Despite the remarkable response reported in preliminary trials, the role of ICI in patients with early-stage, operable CRC remains unclear. The aim of this study was to investigate trials on neoadjuvant ICI in operable CRC. MATERIALS AND METHODS: Scoping review of clinical trial registries (Clinicaltrials.gov and EU clinical trial registers) and PubMed/Medline database of trials on neoadjuvant ICI for operable CRC was done up to December 2022. RESULTS: Some 40 trials investigating neoadjuvant ICI for early-stage, operable CRC were identified, including five published trials and three conference abstracts. Preclinical phase I/II trial predominated with only three clinical phase III trials. Few trials investigated neoadjuvant ICI as the only intervention (monotherapy). Trials in rectal cancer were designed for combined ICI with chemo(radio)therapy, only 8 trials stating an MSI/dMMR status for inclusion, one designed for MSS/pMMR only and, the rest agnostic for MMR status. Thirty-eight (95%) trials investigated programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitors. PD-1/PD-L1 inhibitors were combined with vascular endothelial growth factor (VEGF) inhibitor or with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitor, in two trials each, respectively. Pathological complete response as primary outcome after surgery was the most frequently used study endpoint. In rectal cancer, six trials included a "watch and wait" strategy for patients with complete clinical response. No "watch and wait" study design for colon cancer after neoadjuvant ICI were identified. CONCLUSION: High response rates from neoadjuvant ICI in early-stage colon and rectal cancer are reported in phase I/II studies. Contemporary trial designs are heterogeneous, with few comparable inclusion criteria, use of several drug combinations and durations and, wide variation of endpoints reported. Harmonizing clinical and translational aspects including survival data is needed for improved future trial designs with clinical impact.

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.

E-AHPBA-ESSO-ESSR Innsbruck consensus guidelines for preoperative liver function assessment before hepatectomy.

BACKGROUND: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment. METHODS: A modified Delphi approach was used to achieve consensus. The expert panel consisted of hepatobiliary surgeons, radiologists, nuclear medicine specialists, and hepatologists. The guideline process was supervised by a methodologist and reviewed by a patient representative. A systematic literature search was performed in PubMed/MEDLINE, the Cochrane library, and the WHO International Clinical Trials Registry. Evidence assessment and statement development followed Scottish Intercollegiate Guidelines Network methodology. RESULTS: Based on 271 publications covering 4 key areas, 21 statements (at least 85 per cent agreement) were produced (median level of evidence 2- to 2+). Only a few systematic reviews (2++) and one RCT (1+) were identified. Preoperative liver function assessment should be considered before complex resections, and in patients with suspected or known underlying liver disease, or chemotherapy-associated or drug-induced liver injury. Clinical assessment and blood-based scores reflecting liver function or portal hypertension (for example albumin/bilirubin, platelet count) aid in identifying risk of PHLF. Volumetry of the future liver remnant represents the foundation for assessment, and can be combined with indocyanine green clearance or LiMAx® according to local expertise and availability. Functional MRI and liver scintigraphy are alternatives, combining FLR volume and function in one examination. CONCLUSION: These guidelines reflect established methods to assess preoperative liver function and PHLF risk, and have uncovered evidence gaps of interest for future research.

Liver surgery is an effective treatment for liver tumours. Liver failure is a major problem in patients with a poor liver quality or having large operations. The treatment options for liver failure are limited, with high death rates. To estimate patient risk, assessing liver function before surgery is important. Many methods exist for this purpose, including functional, blood, and imaging tests. This guideline summarizes the available literature and expert opinions, and aids clinicians in planning safe liver surgery.

Early Diagnosis of Pancreatic Cancer: Clinical Premonitions, Timely Precursor Detection and Increased Curative-Intent Surgery.

BACKGROUND: The overall poor prognosis in pancreatic cancer is related to late clinical detection. Early diagnosis remains a considerable challenge in pancreatic cancer. Unfortunately, the onset of clinical symptoms in patients usually indicate advanced disease or presence of metastasis. ANALYSIS AND RESULTS: Currently, there are no designated diagnostic or screening tests for pancreatic cancer in clinical use. Thus, identifying risk groups, preclinical risk factors or surveillance strategies to facilitate early detection is a target for ongoing research. Hereditary genetic syndromes are a obvious, but small group at risk, and warrants close surveillance as suggested by society guidelines. Screening for pancreatic cancer in asymptomatic individuals is currently associated with the risk of false positive tests and, thus, risk of harms that outweigh benefits. The promise of cancer biomarkers and use of 'omics' technology (genomic, transcriptomics, metabolomics etc.) has yet to see a clinical breakthrough. Several proposed biomarker studies for early cancer detection lack external validation or, when externally validated, have shown considerably lower accuracy than in the original data. Biopsies or tissues are often taken at the time of diagnosis in research studies, hence invalidating the value of a time-dependent lag of the biomarker to detect a pre-clinical, asymptomatic yet operable cancer. New technologies will be essential for early diagnosis, with emerging data from image-based radiomics approaches, artificial intelligence and machine learning suggesting avenues for improved detection. CONCLUSIONS: Early detection may come from analytics of various body fluids (eg 'liquid biopsies' from blood or urine). In this review we present some the technological platforms that are explored for their ability to detect pancreatic cancer, some of which may eventually change the prospects and outcomes of patients with pancreatic cancer.

A core set of quality performance indicators for HPB procedures: a global consensus for hepatectomy, pancreatectomy, and complex biliary surgery.

BACKGROUND: Surgery for hepatopancreaticobiliary (HPB) conditions is performed worldwide. This investigation aimed to develop a set of globally accepted procedural quality performance indicators (QPI) for HPB surgical procedures. METHODS: A systematic literature review generated a dataset of published QPI for hepatectomy, pancreatectomy, complex biliary surgery and cholecystectomy. Using a modified Delphi process, three rounds were conducted with working groups composed of self-nominating members of the International Hepatopancreaticobiliary Association (IHPBA). The final set of QPI was circulated to the full membership of the IHPBA for review. RESULTS: Seven "core" indicators were agreed for hepatectomy, pancreatectomy, and complex biliary surgery (availability of specific services on site, a specialised surgical team with at least two certified HPB surgeons, a satisfactory institutional case volume, synoptic pathology reporting, undertaking of unplanned reintervention procedures within 90 days, the incidence of post-procedure bile leak and Clavien-Dindo grade ≥III complications and 90-day post-procedural mortality). Three further procedure specific QPI were proposed for pancreatectomy, six for hepatectomy and complex biliary surgery. Nine procedure-specific QPIs were proposed for cholecystectomy. The final set of proposed indicators were reviewed and approved by 102 IHPBA members from 34 countries. CONCLUSIONS: This work presents a core set of internationally agreed QPI for HPB surgery.

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.

A young man with acute abdomen and anaemia. / En ung mann med akutte magesmerter og anemi.

A young man was hospitalised with acute abdomen and signs of pancreatitis. He became seriously ill and required surgery to address the underlying cause.

Incidence, Mechanisms of Injury and Mortality of Severe Traumatic Brain Injury: An Observational Population-Based Cohort Study from New Zealand and Norway.

BACKGROUND: Comparing trauma registry data from different countries can help to identify possible differences in epidemiology, which may help to improve the care of trauma patients. METHODS: This study directly compares the incidence, mechanisms of injuries and mortality of severe TBI based on population-based data from the two national trauma registries from New Zealand and Norway. All patients prospectively registered with severe TBI in either of the national registries for the 4-year study period were included. Patient and injury variables were described and age-adjusted incidence and mortality rates were calculated. RESULTS: A total of 1378 trauma patients were identified of whom 751 (54.5%) from New Zealand and 627 (45.5%) from Norway. The patient cohort from New Zealand was significantly younger (median 32 versus 53 years; p < 0.001) and more patients from New Zealand were injured in road traffic crashes (37% versus 13%; p < 0.001). The age-adjusted incidence rate of severe TBI was 3.8 per 100,000 in New Zealand and 2.9 per 100,000 in Norway. The age-adjusted mortality rates were 1.5 per 100,000 in New Zealand and 1.2 per 100,000 in Norway. The fatality rates were 38.5% in New Zealand and 34.2% in Norway (p = 0.112). CONCLUSIONS: Road traffic crashes in younger patients were more common in New Zealand whereas falls in elderly patients were the main cause for severe TBI in Norway. The age-adjusted incidence and mortality rates of severe TBI among trauma patients are similar in New Zealand and Norway. The fatality rates of severe TBI are still considerable with more than one third of patients dying.

Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report.

BACKGROUND: Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. METHODS AND FINDINGS: The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. CONCLUSIONS: To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.

A Risk Model of Admitting Patients With Silent SARS-CoV-2 Infection to Surgery and Development of Severe Postoperative Outcomes and Death: Projections Over 24 Months for 5 Geographical Regions.

OBJECTIVE: To model the risk of admitting silent COVID-19-infected patients to surgery with subsequent risk of severe pulmonary complications and mortality. SUMMARY BACKGROUND DATA: With millions of operations cancelled during the COVID-19 pandemic, pressure is mounting to reopen and increase surgical activity. The risk of admitting patients who have silent SARS-Cov-2 infection to surgery is not well investigated, but surgery on patients with COVID-19 is associated with poor outcomes. We aimed to model the risk of operating on nonsymptomatic infected individuals and associated risk of perioperative adverse outcomes and death. METHODS: We developed 2 sets of models to evaluate the risk of admitting silent COVID-19-infected patients to surgery. A static model let the underlying infection rate (R rate) and the gross population-rate of surgery vary. In a stochastic model, the dynamics of the COVID-19 prevalence and a fixed population-rate of surgery was considered. We generated uncertainty intervals (UIs) for our estimates by running low and high scenarios using the lower and upper 90% uncertainty limits. The modelling was applied for high-income regions (eg, United Kingdom (UK), USA (US) and European Union without UK (EU27), and for the World (WORLD) based on the WHO standard population. RESULTS: Both models provided concerning rates of perioperative risk over a 24-months period. For the US, the modelled rates were 92,000 (UI 68,000-124,000) pulmonary complications and almost 30,000 deaths (UI 22,000-40·000), respectively; for Europe, some 131,000 patients (UI 97,000-178,000) with pulmonary complications and close to 47,000 deaths (UI 34,000-63,000) were modelled. For the UK, the model suggested a median daily number of operations on silently infected ranging between 25 and 90, accumulating about 18,700 (UI 13,700-25,300) perioperative pulmonary complications and 6400 (UI 4600-8600) deaths. In high-income regions combined, we estimated around 259,000 (UI 191,000-351,000) pulmonary complications and 89,000 deaths (UI 65,000-120,000). For the WORLD, even low surgery rates estimated a global number of 1.2 million pulmonary complications and 350,000 deaths. CONCLUSIONS: The model highlights a considerable risk of admitting patients with silent COVID-19 to surgery with an associated risk for adverse perioperative outcomes and deaths. Strategies to avoid excessive complications and deaths after surgery during the pandemic are needed.

Meta-analysis and Meta-regression of Survival After Liver Transplantation for Unresectable Perihilar Cholangiocarcinoma.

OBJECTIVE: To systematically review studies reporting survival data following neoadjuvant chemoradiation and orthotopic liver transplantation (NCR-OLT) for unresectable perihilar cholangiocarcinoma (pCC). BACKGROUND: Despite survival improvements for other cancers, the prognosis of pCC remains dismal. Since publication of the Mayo protocol in 2000, increasing numbers of series globally are reporting outcomes after NCR-OLT. METHODS: MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from January 2000 to February 2019. A meta-analysis of proportions was conducted, pooling 1, 3-, and 5-year overall survival and recurrence rates following NCR-OLT across centers. Per protocol and intention to treat data were interrogated. Meta-regression was used to evaluate PSC as a confounder affecting survival. RESULTS: Twenty studies comprising 428 patients were eligible for analysis. No RCTs were retrieved; the majority of studies were noncomparative cohort studies. The pooled 1, 3-, and 5-year overall survival rates following OLT without neoadjuvant therapy were 71.2% (95% CI 62.2%-79.4%), 48.0% (95% CI 35.0%-60.9%), and 31.6% (95% CI 23.1%-40.7%). These improved to 82.8% (95% CI 73.0%-90.8%), 65.5% (95% CI 48.7%-80.5%), and 65.1% (95% CI 55.1%-74.5%) if neoadjuvant chemoradiation was completed. Pooled recurrence after 3 years was 24.1% (95% CI 17.9%-30.9%) with neoadjuvant chemoradiation, 51.7% (95% CI 33.8%-69.4%) without. CONCLUSIONS: In unresectable pCC, NCR-OLT confers long-term survival in highly selected patients able to complete neoadjuvant chemoradiation followed by transplantation. PSC patients appear to have the most favorable outcomes. A high recurrence rate is of concern when considering extending national graft selection policy to pCC.

A template to quantify the location and density of CD3 + and CD8 + tumor-infiltrating lymphocytes in colon cancer by digital pathology on whole slides for an objective, standardized immune score assessment.

BACKGROUND: In colon cancer, the location and density of tumor-infiltrating lymphocytes (TILs) can classify patients into low and high-risk groups for prognostication. While a commercially available 'Immunoscore®' exists, the incurred expenses and copyrights may prevent universal use. The aim of this study was to develop a robust and objective quantification method of TILs in colon cancer. METHODS: A consecutive, unselected series of specimens from patients with colon cancer were available for immunohistochemistry and assessment of TILs by automated digital pathology. CD3 + and CD8 + cells at the invasive margin and in tumor center were assessed on consecutive sections using automated digital pathology and image analysis software (Visiopharm®). An algorithm template for whole slide assessment, generated cell counts per square millimeters (cells/mm2), from which the immune score was calculated using distribution volumes. Furthermore, immune score was compared with clinical and histopathological characteristics to confirm its relevance. RESULTS: Based on the quantified TILs numbers by digital image analyses, patients were classified into low (n = 83, 69.7%), intermediate (n = 14, 11.8%) and high (n = 22, 18.5%) immune score groups. High immune score was associated with stage I-II tumors (p = 0.017) and a higher prevalence of microsatellite instable (MSI) tumors (p = 0.030). MSI tumors had a significantly higher numbers of CD3 + TILs in the invasive margin and CD8 + TILs in both tumor center and invasive margin, compared to microsatellite stable (MSS) tumors. CONCLUSION: A digital template to quantify an easy-to-use immune score corresponds with clinicopathological features and MSI in colon cancer.

Impact of Randomized Controlled Trials in the Social Media: Does Science Trend As Much As Everyday Events?

BACKGROUND: The approach to the scientific literature is evolving. Currently, dissemination of articles happens in real time through social media (SoMe) channels, and little is known about its impact in medicine. The aim of this study was to investigate if SoMe dissemination followed trends independent from articles type and content. METHODS: First, the SoMe engagement of a popular theme (#BlackFriday) and a relevant theme (#ClimateChange) was compared using a SoMe analytic tool to test if the popular theme would reach more engagement. In a second analysis, themes in colorectal surgery in the SoMe community were explored. Altmetric Explorer was searched for the term "colorectal surgery" and the outputs were categorized into 'randomized controlled trials' (RCTs) and 'other studies'. Subgroups were compared for the Altmetric scores using statistical analyses. RESULTS: The analytic tool documented that #BlackFriday outnumbered #ClimateChange in mentions and engagement (1.6 million vs 127.000 mentions). Following, Altmetric Explorer identified 1381 articles, including 92 RCTs (7.1%). Overall, 25,554 mentions were documented from 1205 outputs (97.0% by Twitter). A greater percentage of "other studies" ranked in the lower Altmetric score categories (p = 0.0007). Similarly, the median Altmetric score was higher in the RCT subgroup comparing with "other studies" (6.5 vs. 2.0, Mann-Whitney p = 0.0001). CONCLUSIONS: In this study, RCTs represented just the 7.1% of the studies and produced 11% of Twitter outputs. The median Altmetric scores obtained by RCTs were higher than those of other studies.

Comparison of Performance Score for Female and Male Residents in General Surgery Doing Supervised Real-Life Laparoscopic Appendectomy: Is There a Norse Shield-Maiden Effect?

BACKGROUND: Gender bias may represent a threat to resident assessment during surgical training, and there have been concerns that women might be disadvantaged. There is a lack of studies investigating gender differences in 'entry-level' real-life procedures, such as laparoscopic appendectomy. We aimed to explore potential gender disparities in self-evaluation and faculty evaluation of a basic surgical procedure performed by junior surgical residents in general surgery. METHODS: A structured training program in laparoscopic appendectomy was implemented before undertaking evaluation of real-life consecutive laparoscopic appendectomies by junior residents in general surgery. Resident and faculty gender-pairs were assessed. Intraclass correlation coefficient (ICC) was calculated using a single-rater, consistency, 2-way mixed-effects model. RESULTS: A total of 165 paired sessions were completed to evaluate resident-faculty scores for the procedure. Overall, 19 residents participated (43% women) and 26 faculty (42% women) were involved. The overall correlation between faculty and residents was good (ICC > 0.8). The female-female pairs scored higher for most steps, achieving excellent (ICC ≥ 0.9) for several steps and for overall performance. Female residents were more likely to give a higher self-evaluated score on own performance particularly if evaluated by a female faculty. Also, female trainees had highest correlation-score with male faculty. CONCLUSIONS: This study found higher performance scores in female surgical residents evaluated during real-time laparoscopic appendectomy. No negative gender bias toward women was demonstrated. Better insight into the dynamics of gender-based interaction and dynamics in both training, feedback and influence on evaluation during training is needed when evaluating surgical training programs.

Structured and Systematic Team and Procedure Training in Severe Trauma: Going from 'Zero to Hero' for a Time-Critical, Low-Volume Emergency Procedure Over Three Time Periods.

BACKGROUND: Resuscitative emergency thoracotomy is a potential life-saving procedure but is rarely performed outside of busy trauma centers. Yet the intervention cannot be deferred nor centralized for critically injured patients presenting in extremis. Low-volume experience may be mitigated by structured training. The aim of this study was to describe concurrent development of training and simulation in a trauma system and associated effect on one time-critical emergency procedure on patient outcome. METHODS: An observational cohort study split into 3 arbitrary time-phases of trauma system development referred to as 'early', 'developing' and 'mature' time-periods. Core characteristics of the system is described for each phase and concurrent outcomes for all consecutive emergency thoracotomies described with focus on patient characteristics and outcome analyzed for trends in time. RESULTS: Over the study period, a total of 36 emergency thoracotomies were performed, of which 5 survived (13.9%). The "early" phase had no survivors (0/10), with 2 of 13 (15%) and 3 of 13 (23%) surviving in the development and mature phase, respectively. A decline in 'elderly' (>55 years) patients who had emergency thoracotomy occurred with each time period (from 50%, 31% to 7.7%, respectively). The gender distribution and the injury severity scores on admission remained unchanged, while the rate of patients with signs on life (SOL) increased over time. CONCLUSION: The improvement over time in survival for one time-critical emergency procedure may be attributed to structured implementation of team and procedure training. The findings may be transferred to other low-volume regions for improved trauma care.