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The aim of this study is to evaluate the accuracy of outcome reporting after elective visceral surgery in a low volume district hospital. Outcome measurement as well as transparent reporting of surgical complications becomes more and more important. In the future, financial and personal resources may be distributed due to reported quality and thus, it is in the main interest of healthcare providers that outcome data are accurately collected. Between 10/2020 and 09/2021 postoperative complications during the hospitalisation were recorded using the Clavien–Dindo classification (CDC) and comprehensive complication index by residents of a surgical department in a district hospital. After one year of prospective data collection, data were retrospectively analyzed and re-evaluated for accuracy by senior consultant surgeons. In 575 patients undergoing elective general or visceral surgery interns and residents reported an overall rate of patients with complications of 7.3% (n = 42) during the hospitalization phase, whereas a rate of 18.3% (n = 105) was revealed after retrospective analysis by senior consultant surgeons. Thus, residents failed to report patients with postoperative complications in 60% of cases (63/105). In the 42 cases, in which complications were initially reported, the grading of complications was correct only in 33.3% of cases (n = 14). Complication grades that were most missed were CDC grade I and II. Quality of outcome measurement in a district hospital is poor if done by unexperienced residents and significantly underestimates the true complication rate. Outcome measurement must be done or supervised by experienced surgeons to ensure correct and reliable outcome data. [ABSTRACT FROM AUTHOR]

Background: In primarily unresectable liver tumors, ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged hepatectomy) may offer curative two-stage hepatectomy trough a fast and extensive hypertrophy. However, concerns have been raised about the invasiveness of the procedure. Full robotic ALPPS has the potential to reduce the postoperative morbidity trough a less invasive access. The aim of this study was to compare the perioperative outcomes of open and full robotic ALPPS. Methods: The bicentric study included open ALPPS cases from the University Hospital Zurich, Switzerland and robotic ALPPS cases from the University of Modena and Reggio Emilia, Italy from 01/2015 to 07/2022. Main outcomes were intraoperative parameters and overall complications. Results: Open and full robotic ALPPS were performed in 36 and 7 cases. Robotic ALPPS was associated with less blood loss after both stages (418 ± 237 ml vs. 319 ± 197 ml; P = 0.04 and 631 ± 354 ml vs. 258 ± 53 ml; P = 0.01) as well as a higher rate of interstage discharge (86% vs. 37%; P = 0.02). OT was longer with robotic ALPPS after both stages (371 ± 70 min vs. 449 ± 81 min; P = 0.01 and 282 ± 87 min vs. 373 ± 90 min; P = 0.02). After ALPPS stage 2, there was no difference for overall complications (86% vs. 86%; P = 1.00) and major complications (43% vs. 39%; P = 0.86). The total length of hospital stay was similar (23 ± 17 days vs. 26 ± 13; P = 0.56). Conclusion: Robotic ALPPS was safely implemented and showed potential for improved perioperative outcomes compared to open ALPPS in an experienced robotic center. The robotic approach might bring the perioperative risk profile of ALPPS closer to interventional techniques of portal vein embolization/liver venous deprivation. [ABSTRACT FROM AUTHOR]

Background: Robotic pancreaticoduodenectomy (RPD) is an emerging alternative to open pancreaticoduodenectomy (OPD). Although RPD offers various theoretical advantages, it is used in less than 10% of all pancreaticoduodenectomies. The aim of this study was to report our 10-year experience and compare RPD outcomes with international benchmarks for OPD. Methods: A retrospective review of a prospectively maintained institutional database was performed of consecutive patients who underwent RPD between January 2011 and December 2021. Patients were categorized into low-risk and high-risk groups according to the selection criteria set by the benchmark study. Their outcomes were compared to the international benchmark cut off values. Outcomes were then evaluated over time to identify improvements in practice and establish a learning curve. Results: Of 201 RPDs, 36 were low-risk and 165 high-risk patients. Compared to the OPD benchmarks, outcomes of low-risk patients were within the cutoff values. High-risk patients were outside the cutoff for blood transfusions (26% vs. ≤ 23%), overall complications (78% vs. ≤ 73%), grade I–II complications (68% vs. ≤ 62%), and readmissions (22% vs ≤ 21%). Oncologic outcomes for high-risk patients were within benchmark cutoffs. Cases at the end of the learning curve included more pancreatic cancer (42% from 17%) and fewer low-risk patients (10% from 24%) than those at the beginning. After 41 RPD there was a decline in conversion rates and operative time. Between 95 and 143 cases operative time, transfusion rates, and LOS declined significantly. Complications did not differ over time. Conclusion: RPD yields results comparable to the established benchmarks in OPD in both low- and high-risk patients. Along the learning curve, RPD evolved with the inclusion of more high-risk cases while outcomes remained within benchmarks. Addition of a robotic HPB surgery fellowship did not compromise outcomes. These results suggest that RPD may be an option for high-risk patients at specialized centers. [ABSTRACT FROM AUTHOR]

Biomarkers are powerful clinical diagnostics and predictors of patient outcome. However, robust measurements often require time and expensive laboratory equipment, which is insufficient to track rapid changes and limits direct use in the operating room. Here, this study presents a portable spectrophotometric device for continuous real‐time measurements of fluorescent and non‐fluorescent biomarkers at the point of care. This study measures the mitochondrial damage biomarker flavin mononucleotide (FMN) in 26 extended criteria human liver grafts undergoing hypothermic oxygenated perfusion to guide clinical graft assessment. Real‐time data identified seven organs unsuitable for transplant that are discarded. The remaining grafts are transplanted and FMN values correlated with post‐transplant indicators of liver function and patient recovery. Further, this study shows how this device can be used to monitor dialysis patients by measuring creatinine in real‐time. Our approach provides a simple method to monitor biomarkers directly within biological fluids to improve organ assessment, patient care, and biomarker discovery. [ABSTRACT FROM AUTHOR]

Background: Inconsistent definitions of complications and unexpected events have limited accurate analysis of surgical outcomes. Perioperative outcome classifications currently used for adult patients have limitations when used for children. Methods: A multidisciplinary group of experts modified the Clavien--Dindo classification to increase its utility and accuracy in paediatric surgery cohorts. Organizational and management errors were considered in the novel Clavien--Madadi classification, which focuses on procedural invasiveness rather than anaesthetic management. Unexpected events were prospectively documented in a paediatric surgery cohort. Results of the Clavien--Dindo and Clavien--Madadi classifications were compared and correlated with procedure complexity. Results: Unexpected events were prospectively documented in a cohort of 17 502 children undergoing surgery between 2017 and 2021. The results of both classifications were highly correlated (ρ = 0.95), although the novel Clavien--Madadi classification identified 449 additional events (organizational and management errors) over the Clavien--Dindo classification, increasing the total number of events by 38 per cent (1605 versus 1158 events). The results of the novel system correlated significantly with the complexity of procedures in children (ρ = 0.756). Furthermore, grading of events > grade III according to the Clavien--Madadi classification showed a higher correlation with procedure complexity (ρ = 0.658) than the Clavien--Dindo classification (ρ = 0.198). Conclusion: The Clavien--Madadi classification is a tool for the detection of surgical and non-medical errors in paediatric surgery populations. Further validation in paediatric surgery populations is required before widespread use. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypoxia is a key feature of the tumor microenvironment involved in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC). In this review we will highlight hypoxia's integral role in shaping genomic instability and the tumor immune microenvironment in this disease. We will further present strategies currently being investigated to alleviate hypoxia and those that can be applied for its diagnosis and therapy in patients with PDAC. Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, and it is a disease of dismal prognosis. While immunotherapy has revolutionized the treatment of various solid tumors, it has achieved little success in PDAC. Hypoxia within the stroma-rich tumor microenvironment is associated with resistance to therapies and promotes angiogenesis, giving rise to a chaotic and leaky vasculature that is inefficient at shuttling oxygen and nutrients. Hypoxia and its downstream effectors have been implicated in immune resistance and could be contributing to the lack of response to immunotherapy experienced by patients with PDAC. Paradoxically, increasing evidence has shown hypoxia to augment genomic instability and mutagenesis in cancer, suggesting that hypoxic tumor cells could have increased production of neoantigens that can potentially enable their clearance by cytotoxic immune cells. Strategies aimed at relieving this condition have been on the rise, and one such approach opts for normalizing the tumor vasculature to reverse hypoxia and its downstream support of tumor pathogenesis. An important consideration for the successful implementation of such strategies in the clinic is that not all PDACs are equally hypoxic, therefore hypoxia-detection approaches should be integrated to enable optimal patient selection for achieving improved patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To assess the predictive value of intraoperative indocyanine green (ICG) test in patients undergoing staged hepatectomy. Methods: We analyzed intraoperative ICG measurements of future liver remnant (FLR), preoperative ICG, volumetry, and hepatobiliary scintigraphy in 15 patients undergoing associated liver partition and portal vein ligation for staged hepatectomy (ALPPS). Main endpoints were the correlation of intraoperative ICG values to postoperative complications (Comprehensive Complication Index (CCI®)) at discharge and 90 days after surgery, and to postoperative liver function. Results: Median intraoperative R15 (ICG retention rate at 15 min) correlated significantly with CCI® at discharge (p = 0.05) and with CCI® at 90 days (p = 0.0036). Preoperative ICG, volumetry, and scintigraphy did not correlate to postoperative outcome. ROC curve analysis revealed a cutoff value of 11.4 for the intraoperative R15 to predict major complications (Clavien-Dindo ≥ III) with 100% sensitivity and 63% specificity. No patient with R15 ≤ 11 developed major complications. Conclusion: This pilot study suggests that intraoperative ICG clearance determines the functional capacity of the future liver remnant more accurately than preoperative tests. This may further reduce the number of postoperative liver failures, even if it means intraoperative abortion of hepatectomy in individual cases. [ABSTRACT FROM AUTHOR]

Background: Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week. Methods: Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long‐term liver perfusion machine and moreover supportive in the biomedical engineering process. Results: Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 ("poor" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver). Conclusion: Knowing the feasible ranges (upper‐ and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs. [ABSTRACT FROM AUTHOR]

Background: Enhanced Recovery After Surgery (ERAS) has been widely applied in liver surgery since the publication of the first ERAS guidelines in 2016. The aim of the present article was to update the ERAS guidelines in liver surgery using a modified Delphi method based on a systematic review of the literature. Methods: A systematic literature review was performed using MEDLINE/PubMed, Embase, and the Cochrane Library. A modified Delphi method including 15 international experts was used. Consensus was judged to be reached when >80% of the experts agreed on the recommended items. Recommendations were based on the Grading of Recommendations, Assessment, Development and Evaluations system. Results: A total of 7541 manuscripts were screened, and 240 articles were finally included. Twenty-five recommendation items were elaborated. All of them obtained consensus (>80% agreement) after 3 Delphi rounds. Nine items (36%) had a high level of evidence and 16 (64%) a strong recommendation grade. Compared to the first ERAS guidelines published, 3 novel items were introduced: prehabilitation in high-risk patients, preoperative biliary drainage in cholestatic liver, and preoperative smoking and alcohol cessation at least 4 weeks before hepatectomy. Conclusions: These guidelines based on the best available evidence allow standardization of the perioperative management of patients undergoing liver surgery. Specific studies on hepatectomy in cirrhotic patients following an ERAS program are still needed. [ABSTRACT FROM AUTHOR]

Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen. The patient rapidly recovered a normal quality of life without any signs of liver damage, such as rejection or injury to the bile ducts, according to a 1-year follow up. This inaugural clinical success opens new horizons in clinical research and promises an extended time window of up to 10 days for assessment of viability of donor organs as well as converting an urgent and highly demanding surgery into an elective procedure. A human liver is transplanted successfully after preservation for 3 days via machine perfusion. [ABSTRACT FROM AUTHOR]

In patients with extensive colorectal liver metastases (CRLM) and insufficient future liver remnant (FLR) a faster and more effective FLR augmentation than portal vein embolization is the associating liver partition and portal vein ligation in staged hepatectomy (ALPPS). Before ALPPS, the presence of arterial blood supply to the subsequently resected hemiliver must be ensured. We present a case with neoadjuvant-treated CRLM and insufficient FLR who developed a large intrahepatic hematoma after liver biopsy. For continuous bleeding, the right hepatic artery was embolized. Fortunately, an accessory right hepatic artery arising from the superior mesenteric artery was present, which enabled the ALPPS procedure to be performed. After ALPPS, the patient did not experience liver failure. The case exemplifies that preoperative evaluation of the vascular supply of the liver is of paramount importance in advanced hepatic surgery such as ALPPS. [ABSTRACT FROM AUTHOR]

Background Donation after circulatory death (DCD) represents up to 40% of used kidney grafts. While studies have shown similar outcomes compared with donation after brain death (DBD) in the short term and mid-term, no data on long-term outcomes exist. Methods We retrospectively analysed patients transplanted at our institution between January 1985 and March 2000. All DCD recipients were matched one-to-one with patients transplanted with DBD grafts during this period according to sex, age and year of transplantation and followed up until December 2020. During this period, 1133 kidney transplantations were performed, of which 122 were with a DCD graft. Results The median graft survival after 35 years of follow-up was 23 years [277 months {95% confidence interval (CI) 182–372}] in DBD recipients and 24.5 years [289 months (95% CI 245–333)] in DCD recipients (P = 0.65; hazard ratio 0.91). Delayed graft function occurred in 47 patients in the DCD group compared with 23 in the DBD group (P < 0.001), albeit without a significant long-term outcome difference in graft or patient survival. We could not show any difference in graft function in terms of creatinine levels (133 versus 119 µmol/L), proteinuria (370 versus 240 mg/24 h) and glomerular filtration rate slope (–0.6 versus –0.3 mL/min/year) between the two groups for graft survival >20 years. Conclusions This is the first study to show similar graft survival and function in DCD kidneys compared with DBD kidneys after 35 years of follow-up. DCD grafts are a valuable resource and can be utilized in the same way as DBD grafts. [ABSTRACT FROM AUTHOR]

Background: The perforated duodenal diverticulum remains a rare clinical entity, the optimal management of which has not been well established. Historically, primary surgery has been the preferred treatment modality. This was called into question during the last decade, with the successful application of non-operative therapy in selected patients. The aim of this systematic review is to identify cases of perforated duodenal diverticula published over the past decade and to assess any subsequent evolution in treatment. Methods: A systematic review of English and non-English articles reporting on perforated duodenal diverticula using MEDLINE (2008–2020) was performed. Only cases of perforated duodenal diverticula in adults (> 18 years) that reported on diagnosis and treatment were included. Results: Some 328 studies were identified, of which 31 articles met the inclusion criteria. These studies included a total of 47 patients with perforated duodenal diverticula. This series suggests a trend towards conservative management with 34% (16/47) of patients managed non-operatively. In 31% (5/16) patients initially managed conservatively, a step-up approach to surgical intervention was required. Conclusion: Conservative treatment of perforated duodenal diverticula appears to be an acceptable and safe treatment strategy in stable patients without signs of peritonitis under careful observation. For patients who fail to respond to conservative treatment, a step-up approach to percutaneous drainage or surgery can be applied. If surgery is required, competence in techniques ranging from simple diverticulectomy to Roux-en-Y gastric diversion or even Whipple's procedure may be required depending on tissue friability and diverticular collar size. [ABSTRACT FROM AUTHOR]

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion. In this study, we analysed coagulation parameters during one week ex situ perfusion at 34℃. Eight discarded human livers were perfused with blood‐based, heparinised perfusate for one week; perfusions in a further four livers were terminated on day 4 due to massive ongoing cell death. Coagulation parameters were well below the physiologic range at perfusion start. Physiologic levels were achieved within the first two perfusion days for factor V (68.5 ± 35.5%), factor VII (83.5 ± 26.2%), fibrinogen (2.1 ± 0.4 g/L) and antithrombin (107 ± 26.5%) in the livers perfused for one week. Despite the increased production of coagulation factors, INR was detectable only at 24h of perfusion (2.1 ± 0.3) and prolonged thereafter (INR > 9). The prolongation of INR was related to the high heparin level in the perfusate (anti‐FXa > 3 U/mL). Intriguingly, livers with ongoing massive cell death also disclosed synthesis of factor V and improved INR. In summary, perfused livers were able to produce coagulation factors at a physiological level ex situ. We propose that single coagulation factor analysis is more reliable for assessing the synthetic function of perfused livers as compared to INR when using a heparinised perfusate. [ABSTRACT FROM AUTHOR]

Background: Liver surgery and transplantation currently represent the only curative treatment options for primary and secondary hepatic malignancies. Despite the ability of the liver to regenerate after tissue loss, 25–30% future liver remnant is considered the minimum requirement to prevent serious risk for post-hepatectomy liver failure. Purpose: The aim of this review is to depict the various interventions for liver parenchyma augmentation–assisting surgery enabling extended liver resections. The article summarizes one- and two-stage procedures with a focus on hypertrophy- and corresponding resection rates. Conclusions: To induce liver parenchymal augmentation prior to hepatectomy, most techniques rely on portal vein occlusion, but more recently inclusion of parenchymal splitting, hepatic vein occlusion, and partial liver transplantation has extended the technical armamentarium. Safely accomplishing major and ultimately total hepatectomy by these techniques requires integration into a meaningful oncological concept. The advent of highly effective chemotherapeutic regimen in the neo-adjuvant, interstage, and adjuvant setting has underlined an aggressive surgical approach in the given setting to convert formerly "palliative" disease into a curative and sometimes in a "chronic" disease. [ABSTRACT FROM AUTHOR]

Suppressing serotonin to enhance immunotherapy: The neurotransmitter serotonin is known to be involved in cell proliferation and cancer, but its role in the tumor microenvironment has been unexplored. Here, Schneider et al. used syngeneic mouse models of pancreatic and colorectal cancer to show that genetic knockdown of peripheral serotonin enhanced CD8+ T cell accumulation in tumors and reduced tumor growth. In addition, the pharmacological serotonin inhibitors fluoxetine and telotristat were able to enhance the effects of anti–PD-1 therapy to induce long-term tumor control in mice. These FDA-approved drugs suggest a promising combination treatment to improve cancer immunotherapy that warrants further clinical investigation. Platelet-derived peripheral serotonin has pleiotropic effects on coagulation, metabolism, tissue regeneration, and cancer growth; however, the effect of serotonin on the tumor microenvironment remains understudied. Peripheral serotonin–deficient (Tph1−/−) mice displayed reduced growth of subcutaneous and orthotopically injected syngeneic murine pancreatic and colorectal cancers with enhanced accumulation of functional CD8+ T cells compared to control C57BL/6 mice, resulting in extended overall survival. Subcutaneous and orthotopic syngeneic tumors from Tph1−/− mice expressed less programmed cell death 1 ligand 1 (PD-L1), suggesting serotonin-mediated regulation. Serotonin enhanced expression of PD-L1 on mouse and human cancer cells in vitro via serotonylation, which is the formation of covalent bonds between glutamine residues and serotonin, resulting in activation of small G proteins. Serotonin concentrations in metastases of patients with abdominal tumors negatively correlated to the number of CD8+ tumor-infiltrating T cells. Depletion of serotonin cargo or inhibition of serotonin release from thrombocytes decreased growth of syngeneic pancreatic and colorectal tumors in wild-type mice, increased CD8+ T cell influx, and decreased PD-L1 expression. Pharmacological serotonin depletion with oral fluoxetine or intraperitoneal injection of the TPH1 inhibitor telotristat augmented the effects of programmed cell death protein 1 (PD-1) checkpoint blockade and triggered long-term tumor control in mice subcutaneously inoculated with syngeneic colorectal and pancreatic tumors. Overall, peripheral serotonin weakens effector functions of CD8+ T cells within tumors. Clinically approved serotonin targeting agents alone or in combination with PD-1 blockade provided long-term control of established tumors in murine models, warranting further investigation of the clinical translatability of these findings. [ABSTRACT FROM AUTHOR]

Introduction: The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week. Methods: Porcine livers (n = 42) were procured and perfused with blood at 34°C following aseptic technique and standard operating procedures. The antimicrobial prophylaxis was adapted and improved in a step‐wise manner taking into account the pathogens that were detected during the development phase. Piperacillin‐Tazobactam was applied as a single dose initially and modified to continuous application in the final protocol. In addition, the perfusion machine was improved to recapitulate partially the host's defense system. The final protocol was tested for infection prevention during one week of perfusion. Results: During the development phase, microbial contamination occurred in 27 out of 39 (69%) livers with a mean occurrence of growth on 4 ± 1.6 perfusion days. The recovered microorganisms suggested an exogenous source of microbial contamination. The antimicrobial agents (piperacillin/tazobactam) could be maintained above the targeted minimal inhibitory concentration (8‐16 mg/L) only with continuous application. In addition to continuous application of piperacillin/tazobactam, partial recapitulation of the host immune system ex situ accompanied by strict preventive measures for contact and air contamination maintained sterility during one week of perfusion. Conclusion: The work demonstrates feasibility of sterility maintenance for one week during ex situ normothermic liver perfusion. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate if the time of day a cholecystectomy was performed affects in-hospital complication rates and mortality. Methods: A national quality measurement database was retrospectively studied. Study period was 2010 to 2017. The inclusion criteria were operatively treated cholecystitis or another benign disease of the gallbladder. Further, the time of day the operation was performed must have been documented. We defined nighttime as all interventions performed between 7PM until 6AM. A total of 11′459 patients were included. Development of any complication during hospitalization and in-hospital mortality was the main outcomes. The first part of the study was solely descriptive. In the second part, we applied a 1:1 case–control-matching. A matched group of 274 pairs were further investigated. Results: Only 8.4% of the procedures were performed during nighttime. Complications occurred in 6.7% of all patients. We found twice as many complications in the nighttime group compared to the daytime group. Mortality was 0.56% during daytime and 0.52% during nighttime. In a matched-pair analysis, however, we found no significant differences in the overall mortality rate nor in the occurrence of complications when comparing day- vs. nighttime operations. Conclusions: We found twice as many complications in the nighttime group (12%) compared to the daytime group (6.1%), mainly related to patient risk factors. In contrast to common apprehension, however, nighttime cholecystectomies were not associated with higher mortality rates. [ABSTRACT FROM AUTHOR]

Hypoxia is prominent in solid tumors and a recognized driver of malignancy. Thus far, targeting tumor hypoxia has remained unsuccessful. Myo-inositol trispyrophosphate (ITPP) is a re-oxygenating compound without apparent toxicity. In preclinical models, ITPP potentiates the efficacy of subsequent chemotherapy through vascular normalization. Here, we report the results of an unrandomized, open-labeled, 3 + 3 dose-escalation phase Ib study (NCT02528526) including 28 patients with advanced primary hepatopancreatobiliary malignancies and liver metastases of colorectal cancer receiving nine 8h-infusions of ITPP over three weeks across eight dose levels (1'866-14'500 mg/m2/dose), followed by standard chemotherapy. Primary objectives are assessment of the safety and tolerability and establishment of the maximum tolerated dose, while secondary objectives include assessment of pharmacokinetics, antitumor activity via radiological evaluation and assessment of circulatory tumor-specific and angiogenic markers. The maximum tolerated dose is 12,390 mg/m2, and ITPP treatment results in 32 treatment-related toxicities (mostly hypercalcemia) that require little or no intervention. 52% of patients have morphological disease stabilization under ITPP monotherapy. Following subsequent chemotherapy, 10% show partial responses while 60% have stable disease. Decreases in angiogenic markers are noted in ∼60% of patients after ITPP and tend to correlate with responses and survival after chemotherapy. Restoring oxygenation in hypoxic tumors might lead to favorable oncological outcome of patients if combined with standard multimodal therapy regimens. Here the authors report a phase Ib clinical trial of anti-hypoxic myo-inositol trispyrophosphate (ITPP) in hepato-pancreato-biliary neoplasms. [ABSTRACT FROM AUTHOR]

Purpose: The relevance of pancreatic texture for pancreatic fistula (POPF) formation after distal pancreatectomy (DP) remains ill defined. Recent POPF definition adjustments and common subjective pancreatic texture assessment are further drawbacks in the investigation of pancreatic texture as a factor for POPF development after DP. Methods: The predictive value of pancreatic texture by histologic assessment was investigated for POPF formation after DP, respecting the updated 2016 fistula definition. Histologic evaluation at the resection margin included amount of steatosis, degree of fibrosis, and pancreatic duct size. Results: A total of 102 patients who underwent DP were included. Thirty-six patients developed POPF. There was no difference in histologic variables in patients with and without POPF. In the univariate analysis, none of the three histologic features showed significant correlation with POPF formation. The ROC (receiver operating characteristic) curve demonstrated poor utility for the grade of steatosis 0.481 ± 0.058 (p = 0.75) and grade of fibrosis 0.466 ± 0.058 (p = 0.57) as predictive factors for POPF formation. Conclusion: Results indicate that pancreatic texture does not predict POPF formation following DP. This is particularly relevant in the context of the increasing use of robotic and laparoscopic approaches for DPs with limited clinical pancreatic texture assessment by palpation. [ABSTRACT FROM AUTHOR]

Background: Unresectable cholangiocarcinoma has a poor prognosis and treatment options are limited. Combined systemic and intrahepatic chemotherapy may improve local control and enable downsizing. The aim of this study was to determine the maximum tolerated dose (MTD) of intravenous gemcitabine combined with intravenous cisplatin and hepatic arterial infusion (HAI) with floxuridine (FUDR) in patients with unresectable intrahepatic or hilar cholangiocarcinoma. Methods: Twelve patients were treated within a 3 + 3 dose escalation algorithm with 600, 800, or 1,000 mg/m2 gemcitabine and predefined doses of cisplatin 25 mg/m2 on days 1 and 8, q21, for 4 cycles, and FUDR 0.2 mg/kg on days 1–14 as continuous HAI, q28, for 3 cycles. Safety and toxicity as well as resectability rates after 3 months and preliminary survival data are reported. Results: The determined MTD for gemcitabine was 800 mg/m2. Dose limiting toxicities were neutropenic fever and biliary tract infections. In total, 27% of the patients showed partial remission and 73% stable disease. Although none of the patients achieved resectability after 3 months, the 3-year overall survival rate was 33%, median overall survival 23.9 months (range 1–49), and median progression-free survival 10.1 months (range 2–40). Conclusions: Intravenous gemcitabine/cisplatin plus HAI-FUDR is feasible and appears effective for disease control. Larger prospective studies evaluating this triplet combination are warranted. [ABSTRACT FROM AUTHOR]

Objective: With the growing demand for livers in the field of transplantation, interest in normothermic ex situ machine perfusion (NMP) has increased in recent years. This may open the door for novel therapeutic interventions such as repair of suboptimal grafts. For successful long-term NMP of livers, blood glucose (BG) levels need to be maintained in a close to physiological range. Methods: We present an “automated insulin delivery” (AID) system integrated into an NMP system, which automatically adjusts insulin infusion rates based on continuous BG measurements in a closed loop manner during ex situ pig and human liver perfusion. An online glucose sensor for continuous glucose monitoring was integrated and evaluated in blood. A model based and a proportional controller were implemented and compared in their ability to maintain BG within the physiological range. Results: The continuous glucose sensor is capable of measuring BG directly in human and pig blood for multiple days with an average error of 0.6 mmol/L. There was no significant difference in the performance of the two controllers in terms of their ability to keep BG in the physiological range. With the integrated AID, BG was controlled within the physiological range on average in 80% and 76% of the perfusion time for human and pig livers, respectively. Conclusion: The presented work offers a method and shows the feasibility to maintain BG in the physiological range for multiple (up to ten) days during ex situ liver perfusion with the help of an automated AID. Significance: Maintaining BG within the physiological range is required to enable long-term ex situ liver perfusion. [ABSTRACT FROM AUTHOR]

Infection with Echinococcus granulosus is a common helminthic disease worldwide with endemic in a region with high endemic areas in Africa, Asia, Middle East, South America and southern Europe. We report a rare case of a young patient with cystic echinococcal disease of the liver invading the pericardium. The patient initially presented with life-threatening cardiac tamponade, which resulted in the discovery of the underlying parasitic disease. He successfully underwent en-bloc hepatic pericystectomy and pericardiac resection with closure of the pericardial defect using a xenogeneic patch. After this procedure, he recovered well and had no cardiac complications in the long term. Under treatment with albendazol, the patient showed no signs of recurrent disease. Cases of complex cystic echinococcosis, which invade adjacent organs or body cavities, often need radical surgery for definitive treatment embedded in a multidisciplinary approach in highly specialized centers. [ABSTRACT FROM AUTHOR]

Purpose: Historically, invasion of the inferior vena cava (IVC) represented advanced and often unresectable hepatic disease. With surgical and anesthetic innovations, IVC resection and reconstruction have become feasible in selected patients. This review assesses technical variations in reconstructive techniques and post-operative management. Methods: A comprehensive literature search was performed according to PRISMA. Inclusion criteria were (i) peer-reviewed articles in English; (ii) at least three cases; (iii) hepatic IVC resection and reconstruction (January 2015–March 2020). Primary outcomes were reconstructive technique, anti-thrombotic regimen, post-operative IVC patency, and infection. Secondary outcomes included post-operative complications and malignant disease survival. Results: Fourteen articles were included allowing for investigation of 351 individual patients. Analysis demonstrated significant heterogeneity in surgical reconstructive technique, anti-thrombotic management, and post-operative monitoring of patency. There was increased utilization of ex vivo approaches and decreased use of venovenous bypass compared with previously published reviews. Conclusion: This review of literature published between 2015 and 2020 reveals persistent heterogeneity of hepatic IVC reconstructive techniques and peri-operative management. Increased utilization of ex vivo approaches and decreased use of venovenous bypass point towards improved operative techniques, peri-operative management, and anesthesia. In order to gain evidence for consensus on management, a registry would be beneficial. [ABSTRACT FROM AUTHOR]

Background: Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown.Methods: An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1.Results: A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1.Conclusion: This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications. [ABSTRACT FROM AUTHOR]

Background: Robotic hepatopancreaticobiliary (HPB) procedures are performed worldwide and establishing processes for safe adoption of this technology is essential for patient benefit. We report results of the Delphi process to define and optimize robotic training procedures for HPB surgeons. Methods: In 2019, a robotic HPB surgery panel with an interest in surgical training from the Americas and Europe was created and met. An e-consensus–finding exercise using the Delphi process was applied and consensus was defined as 80% agreement on each question. Iterations of anonymous voting continued over three rounds. Results: Members agreed on several points: there was need for a standardized robotic training curriculum for HPB surgery that considers experience of surgeons and based on a robotic hepatectomy includes a common approach for "basic robotic skills" training (e-learning module, including hardware description, patient selection, port placement, docking, troubleshooting, fundamentals of robotic surgery, team training and efficiency, and emergencies) and an "advanced technical skills curriculum" (e-learning, including patient selection information, cognitive skills, and recommended operative equipment lists). A modular approach to index procedures should be used with video demonstrations, port placement for index procedure, troubleshooting, and emergency scenario management information. Inexperienced surgeons should undergo training in basic robotic skills and console proficiency, transitioning to full procedure training of e-learning (video demonstration, simulation training, case observation, and final evaluation). Experienced surgeons should undergo basic training when using a new system (e-learning, dry lab, and operating room (OR) team training, virtual reality modules, and wet lab; case observations were unnecessary for basic training) and should complete the advanced index procedural robotic curriculum with assessment by wet lab, case observation, and OR team training. Conclusions: Optimization and standardization of training and education of HPB surgeons in robotic procedures was agreed upon. Results are being incorporated into future curriculum for education in robotic surgery. [ABSTRACT FROM AUTHOR]

Background: The landscape of surgical training has been subject to many changes over the past 15 years. This study examines resident satisfaction, determinants of satisfaction, demographics, working hours and the teaching rate of common operations in a longitudinal fashion with the aim to identify trends, shortcomings and possible ways to improve the current training system. Methods: The Swiss Medical Association administers an annual survey to all Swiss residents to evaluate the quality of postgraduate medical training (yearly respondents: 687–825, response rate: 68–72%). Teaching rates for general surgical procedures were obtained from the Swiss association for quality management in surgery. Results: During the study period (2003–2018), the number of surgical residents (408–655 (+61%)) and graduates in general surgery per year (42–63 (+50%)) increased disproportionately to the Swiss population. While the 52 working hour restriction was introduced in 2005 reported average weekly working hours did not decline (59.9–58.4 h (−3%)). Workplace satisfaction (6 being highest) rose from 4.3 to 4.6 (+7%). Working climate and leadership culture were the main determinants for resident satisfaction. The proportion of taught basic surgical procedures fell from 24.6 to 18.9% (−23%). Conclusions: The number of residents and graduates in general surgery has risen markedly. At the same time, the proportion of taught operations is diminishing. Despite the introduction of working hour restrictions, the self-reported hours never reached the limit. The low teaching rate combined with the increasing resident number represents a major challenge to the maintenance of the current training quality. [ABSTRACT FROM AUTHOR]