Technical aspects and learning curve of complex laparoscopic hepatectomy: how we do it.

INTRODUCTION: Laparoscopic liver surgery has advanced significantly, offering benefits, such as reduced intraoperative complications and quicker recovery. However, complex laparoscopic hepatectomy (CLH) is technically demanding, requiring skilled surgeons. This study aims to share technical aspects, insightful tips, and outcomes of CLH at our center, focusing on the safety and learning curve. METHODS: We reviewed all patients undergoing liver resection at our center from July 2017 to December 2023, focusing on those who underwent CLH. Of 135 laparoscopic liver resections, 63 (46.7%) were CLH. The learning curve of CLH was also assessed through linear and piecewise regression analyses considering the operation time and intraoperative blood loss. RESULTS: Postoperative complications occurred only in 4.8% of patients, with a 90-day mortality rate of 3.2%. The mean operation time and blood loss significantly decreased after the first 20 operations, marking the learning curve's optimal cut-off. Significant improvements in R0 resection (p = 0.024) and 90-day mortality (p = 0.035) were noted beyond the learning curve threshold. CONCLUSION: CLH is a safe and effective approach, with a relatively short learning curve of 20 operations. Future large-scale studies should further investigate the impact of surgical experience on CLH outcomes to establish guidelines for training programs.

Statin use is associated with the reduction in hepatocellular carcinoma recurrence after liver surgery.

BACKGROUND: Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. METHODS: PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. RESULTS: The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44-0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16-0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15-0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19-0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. CONCLUSION: Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

[Parenchyma sparing or Anatomical Resections for Colorectal Liver Metastases?] / Parenchymsparende Operationen oder anatomische Resektionen bei Lebermetastasen des kolorektalen Karzinoms?

Colorectal cancer is one of the leading causes of death in the Western world. Half of the patients develop colorectal liver metastases (CRLM), while only less than 30% of the patients have surgically resectable metastasis at the time of diagnosis. In case of resectability, classical anatomical (major) hepatectomy offers a high R0 resection rate, but with simultaneously increased perioperative morbidity and mortality. Over the past two decades, the potential benefits of parenchyma-sparing hepatectomy (PSH) for overall oncological outcomes, survival, and re-resection in case of recurrence ("salvageability") have been demonstrated. This article summarizes the current evidence on PSH as a surgical treatment option, and discusses the current "state of the art" in different therapy scenarios.

Intraoperative Increase of Portal Venous Pressure is an Immediate Predictor of Posthepatectomy Liver Failure After Major Hepatectomy: A Prospective Study.

OBJECTIVES: The aim of this study was to assess intraoperative changes of hepatic macrohemodynamics and their association with ascites and posthepatectomy liver failure (PHLF) after major hepatectomy. SUMMARY OF BACKGROUND DATA: Large-scale ascites and PHLF remain clinical challenges after major hepatectomy. No study has concomitantly evaluated arterial and venous liver macrohemodynamics in patients undergoing liver resection. METHODS: Portal venous pressure (PVP), portal venous flow (PVF), and hepatic arterial flow (HAF) were measured intraoperatively pre- and postresection in 67 consecutive patients with major hepatectomy (ie, resection of ≥3 liver segments). A group of 30 patients with minor hepatectomy served as controls. Liver macrohemodynamics and their intraoperative changes (ie, Δ) were analyzed as predictive biomarkers of ascites and PHLF using Fisher exact, t test, or Wilcoxon rank sum test for univariate and logistic regression for multivariate analyses. RESULTS: Major hepatectomy increased PVP by 26.9% (P = 0.001), markedly decreased HAF by 40.7% (P < 0.001), and slightly decreased PVF by 13.4% (P = 0.011). Minor resections had little effects on hepatic macrohemodynamics. There was no significant association of liver macrohemodynamics with ascites. While middle hepatic vein resection caused higher postresection PVP after right hepatectomy (P = 0.04), the Pringle maneuver was associated with a significant PVF (P = 0.03) and HAF reduction (P = 0.03). Uni- and multivariate analysis revealed an intraoperative PVP increase as an independent predictor of PHLF (P = 0.025). CONCLUSION: Intraoperative PVP kinetics serve as independent predictive biomarker of PHLF after major hepatectomy. These data highlight the importance to assess intraoperative dynamics rather than the pre- and postresection PVP values.

Considering extended right lobe grafts as major extended donor criteria in liver transplantation is justified.

The outcomes of split-liver transplantation are controversial. This study compared outcomes and morbidity after extended right lobe liver transplantation (ERLT) and whole liver transplantation (WLT) in adults. MEDLINE and Web of Science databases were searched systematically and unrestrictedly for studies on ERLT and its impact on graft and patient survival, and postoperative complications. Graft loss and patient mortality odds ratios (OR) and 95% confidence intervals (CI) were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Vascular and biliary complications, primary nonfunction, 3-month, 1-, and 3-year graft and patient survival, and retransplantation after ERLT and WLT were analyzed. The literature search yielded 10 594 articles. After exclusion, 22 studies (n = 75 799 adult transplant patients) were included in the analysis. ERLT was associated with lower 3-month (OR = 1.43, 95% CI = 1.09-1.89, P = 0.01), 1-year (OR = 1.46, 95% CI = 1.08-1.97, P = 0.01), and 3-year (OR = 1.37, 95% CI = 1.01-1.84, P = 0.04) graft survival. WL grafts were less associated with retransplantation (OR = 0.57; 95% CI = 0.41-0.80; P < 0.01), vascular complications (OR = 0.53, 95% CI = 0.38-0.74, P < 0.01) and biliary complications (OR = 0.67; 95% CI = 0.47-0.95; P = 0.03). Considering ERLT as major Extended Donor Criteria is justified because ERL grafts are associated with vasculobiliary complications and the need for retransplantation, and have a negative influence on graft survival.

Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Portal vein arterialization as a salvage procedure in hepatopancreatobiliary surgery: a systematic review.

Background: Portal vein arterialization (PVA) is a possible option when hepatic artery reconstruction is impossible during liver resection. The aim of this study was to review the literature on the clinical application of PVA in hepatopancreatobiliary (HPB) surgery. Methods: We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched the PubMed, Embase and Web of Science databases until December 2019. Experimental (animal) studies, review articles and letters were excluded. Results: Twenty studies involving 57 patients were included. Cholangiocarcinoma was the most common indication for surgery (40 patients [74%]). An end-to-side anastomosis between a celiac trunk branch and the portal vein was the main PVA technique (35 patients [59%]). Portal hypertension was the most common longterm complication (12 patients [21%] after a mean of 4.1 mo). The median followup period was 12 (range 1-87) months. The 1-, 3- and 5-year survival rates were 64%, 27% and 20%, respectively. Conclusion: Portal vein arterialization can be considered as a rescue option to improve the outcome in patients with acute liver de-arterialization when arterial reconstruction is not possible. To prevent portal hypertension and liver injuries due to thrombosis or overarterialization, vessel calibre adjustment and timely closure of the anastomosis should be considered. Further prospective experimental and clinical studies are needed to investigate the potential of this procedure in patients whose liver is suddenly de-arterialized during HPB procedures.

Contexte: L'artérialisation de la veine porte (AVP) est une option envisageable lorsqu'il est impossible de reconstruire l'artère hépatique au moment d'une résection du foie. Le but de cette étude était de faire le point sur la littérature concernant l'application clinique de l'AVP en cours de chirurgie hépatopancréatobiliaire (HPB). Méthodes: Nous avons procédé à une revue systématique selon les directives PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons interrogé systématiquement les bases de données PubMed, Embase et Web of Science jusqu'à décembre 2019. Les études expérimentales (chez l'animal), les articles de synthèse et les lettres ont été exclus. Résultats: Vingt études regroupant 57 patients ont été incluses. Le cholangiocarcinome était la plus fréquente indication de la chirurgie (40 patients [74 %]). L'anastomose terminolatérale d'une branche du tronc cæliaque avec la veine porte a été la principale technique d'AVP (35 patients [59 %]). L'hypertension portale a été la plus fréquente complication (12 patients [21 %] après une moyenne de 4,1 mois). Le suivi médian a été de 12 mois (éventail, 1­87 mois). Les taux de survie moyens à 1, 3 et 5 ans ont été de 64 %, 27 % et 20 %, respectivement. Conclusion: L'artérialisation de la veine porte peut être considérée comme une option de dernier ressort pour améliorer l'état des patients victimes d'une désartérialisation hépatique aiguë lorsque la reconstruction artérielle est impossible. Pour prévenir l'hypertension portale et les lésions au foie dues à la thrombose ou à l'hyperartérialisation, il faut veiller à ajuster le calibre vasculaire et fermer rapidement l'anastomose. D'autres études expérimentales et cliniques prospectives s'imposent afin d'analyser le potentiel de cette intervention chez les patients dont le foie se trouve subitement désartérialisé durant une chirurgie HPB.

First Long-term Oncologic Results of the ALPPS Procedure in a Large Cohort of Patients With Colorectal Liver Metastases.

OBJECTIVES: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients with colorectal liver metastases (CRLM) undergoing ALPPS. BACKGROUND: ALPPS is a two-stage hepatectomy variant that increases resection rates and R0 resection rates in patients with primarily unresectable CRLM as evidenced in a recent randomized controlled trial. Long-term oncologic results, however, are lacking. METHODS: Cases in- and outside the International ALPPS Registry were collected and completed by direct contacts to ALPPS centers to secure a comprehensive cohort. Overall, cancer-specific (CSS), and recurrence-free (RFS) survivals were analyzed along with independent risk factors using Cox-regression analysis. RESULTS: The cohort included 510 patients from 22 ALPPS centers over a 10-year period. Ninety-day mortality was 4.9% and median overall survival, CSS, and RFS were 39, 42, and 15 months, respectively. The median follow-up time was 38 months (95% confidence interval 32-43 months). Multivariate analysis identified tumor-characteristics (primary T4, right colon), biological features (K/N-RAS status), and response to chemotherapy (Response Evaluation Criteria in Solid Tumors) as independent predictors of CSS. Traditional factors such as size of metastases, uni versus bilobar involvement, and liver-first approach were not predictive. When hepatic recurrences after ALPPS was amenable to surgical/ablative treatment, median CSS was significantly superior compared to chemotherapy alone (56 vs 30 months, P < 0.001). CONCLUSIONS: This large cohort provides the first evidence that patients with primarily unresectable CRLM treated by ALPPS have not only low perioperative mortality, but achieve appealing long-term oncologic outcome especially those with favorable tumor biology and good response to chemotherapy.

Prognostic Impact of Ventral Versus Dorsal Tumor Location After Total Mesorectal Excision of Rectal Cancer.

BACKGROUND: Multidisciplinary treatment of rectal cancer, including neoadjuvant treatment, total mesorectal excision, and adjuvant chemotherapy, have improved oncological outcome. Preoperative radiation therapy is advocated by national and international guidelines in all patients with AJCC stage II and III rectal cancer. Although this treatment reduces local recurrence rates with no effect on overall survival, there are possible short- and long-term side effects of radiation exposure, so patients should be carefully selected for neoadjuvant radiation therapy. METHODS: We analyzed whether ventral or dorsal tumor location affects local recurrence rates following radical rectal resection. Patients who underwent radical rectal resection for mid or low rectal cancer in our department between October 2001 and December 2013 were included. Prognostic indicators for local recurrence were analyzed using univariate and multivariate analyses. RESULTS: Overall, 480 patients met the inclusion criteria. Univariate analysis identified surgical procedure (hazard ratio [HR] 1.9, p = 0.006), ventral tumor location (HR 3.8, p < 0.001), and a pathologic circumferential resection margin (pCRM) (HR 9.3, p < 0.001) as prognostic factors of local recurrence. Multivariate analysis revealed tumor location (HR 3.5, p < 0.001) and pCRM (HR 6.0, p = 0.002) as independent factors for local recurrence. Neoadjuvant treatment of AJCC stage II and III tumors reduced the local recurrence rate at ventral but not at dorsal tumor locations (p < 0.001). CONCLUSIONS: Ventral versus dorsal tumor location is an independent prognostic factor for local recurrence. Tumor location may aid in patient selection for neoadjuvant treatment.

Markers of liver regeneration-the role of growth factors and cytokines: a systematic review.

BACKGROUND: Post-hepatectomy liver failure contributes significantly to postoperative mortality after liver resection. The prediction of the individual risk for liver failure is challenging. This review aimed to provide an overview of cytokine and growth factor triggered signaling pathways involved in liver regeneration after resection. METHODS: MEDLINE and Cochrane databases were searched without language restrictions for articles from the time of inception of the databases till March 2019. All studies with comparative data on the effect of cytokines and growth factors on liver regeneration in animals and humans were included. RESULTS: Overall 3.353 articles comprising 40 studies involving 1.498 patients and 101 animal studies were identified and met the inclusion criteria. All included trials on humans were retrospective cohort/observational studies. There was substantial heterogeneity across all included studies with respect to the analyzed cytokines and growth factors and the described endpoints. CONCLUSION: High-level evidence on serial measurements of growth factors and cytokines in blood samples used to predict liver regeneration after resection is still lacking. To address the heterogeneity of patients and potential markers, high throughput serial analyses may offer a method to predict an individual's regenerative potential in the future.

Impact of Surgeon's Experience on Vascular and Haemorrhagic Complications After Kidney Transplantation.

OBJECTIVE: The aim of this study was to investigate the independent risk factors of vascular and haemorrhagic complications after kidney transplantation (KTx) and to evaluate how the surgeon's experience affects the rate of vascular and haemorrhagic complications. METHODS: After exclusion of paediatric and multi-organ transplantations, 1462 KTx operations between 2000 and 2016 were analysed. Independent risk factors were evaluated by multivariable logistic regression analysis. The generalised estimating equation logit model was used to display learning curve progression and determine the best cut off number of KTx operations to reduce vascular and haemorrhagic complications. RESULTS: Vascular and haemorrhagic complications occurred in 38 KTx cases (2.6%). Renal vein thrombosis was the most common complication (0.6%). Graft loss occurred in 11 of 38 (28.9%) cases. Donor age of >60 years (OR 3.687, 95% CI 1.663-8.175, p = 0.001), recipient cardiovascular disease (CVD) (OR 2.270, 95% CI 1.071-4.810, p = 0.032), and surgeon's experience (OR 0.875, 95% CI 0.783-0.977, p = 0.018) were independent predictors of vascular and haemorrhagic complications. Twenty-six previous KTx operations are needed to decrease predicted probability of post-KTx vascular and haemorrhagic complications below 2.6%. CONCLUSIONS: The surgeon's experience is an independent risk factor for vascular and haemorrhagic complications after KTx. Acceptable post-operative vascular and haemorrhagic complications are achieved after a minimum of 26 KTx. As a donor age of >60 years and recipient CVD are also independent risk factors for vascular and haemorrhagic complications, it is suggested that these patients should preferably be operated on by surgeons who have performed more than 26 KTx operations.

Beyond the visible: preliminary evaluation of the first wearable augmented reality assistance system for pancreatic surgery.

PURPOSE: The retroperitoneal nature of the pancreas, marked by minimal intraoperative organ shifts and deformations, makes augmented reality (AR)-based systems highly promising for pancreatic surgery. This study presents preliminary data from a prospective study aiming to develop the first wearable AR assistance system, ARAS, for pancreatic surgery and evaluating its usability, accuracy, and effectiveness in enhancing the perioperative outcomes of patients. METHODS: We developed ARAS as a two-phase system for a wearable AR device to aid surgeons in planning and operation. This system was used to visualize and register patient-specific 3D anatomical models during the surgery. The location and precision of the registered 3D anatomy were evaluated by assessing the arterial pulse and employing Doppler and duplex ultrasonography. The usability, accuracy, and effectiveness of ARAS were assessed using a five-point Likert scale questionnaire. RESULTS: Perioperative outcomes of five patients underwent various pancreatic resections with ARAS are presented. Surgeons rated ARAS as excellent for preoperative planning. All structures were accurately identified without any noteworthy errors. Only tumor identification decreased after the preparation phase, especially in patients who underwent pancreaticoduodenectomy because of the extensive mobilization of peripancreatic structures. No perioperative complications related to ARAS were observed. CONCLUSIONS: ARAS shows promise in enhancing surgical precision during pancreatic procedures. Its efficacy in preoperative planning and intraoperative vascular identification positions it as a valuable tool for pancreatic surgery and a potential educational resource for future surgical residents.

Promising Results of Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy for Perihilar Cholangiocarcinoma in a Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: ALPPS popularity is increasing among surgeons worldwide and its indications are expanding to cure patients with primarily unresectable liver tumors. Few reports recommended limitations or even contraindications of ALPPS in perihilar cholangiocarcinoma (phCC). Here, we discuss the results of ALPPS in patients with phCC in a systematic review as well as a pooled data analysis. METHODS: MEDLINE and Web of Science databases were systematically searched for relevant literature up to December 2023. All studies reporting ALPPS in the management of phCC were included. A single-arm meta-analysis of proportions was carried out to estimate the overall rate of outcomes. RESULTS: After obtaining 207 articles from the primary search, data of 18 studies containing 112 phCC patients were included in our systematic review. Rates of major morbidity and mortality were calculated to be 43% and 22%, respectively. The meta-analysis revealed a PHLF rate of 23%. One-year disease-free survival was 65% and one-year overall survival was 69%. CONCLUSIONS: ALPPS provides a good chance of cure for patients with phCC in comparison to alternative treatment options, but at the expense of debatable morbidity and mortality. With refinement of the surgical technique and better perioperative patient management, the results of ALPPS in patients with phCC were improved.

Surgical therapy for major lung parenchymal damage from late coronavirus disease complication: case report and literature review.

Background: Coronavirus disease [severe acute respiratory syndrome coronavirus disease 19 (SARS COVID-19)] has emerged as one of the most challenging diseases of recent decades. After the pandemic outbreak, our knowledge of the virus has expanded and developed, but we face a new wave of atypical complications that require special attention. In addition to the acute complications of COVID-19 infection, late complications of the disease are taking an increasingly important part in the management of affected patients, which are grouped under the collective term "Long COVID". In this work, we present our therapy strategy in three cases of pulmonary cavity as a late complication after COVID-19, as well as perform a literature review of published articles in this matter. Case Description: This study includes 3 cases of pulmonary cavities as a late COVID complication. Among them only one patient was vaccinated. The mean duration between the occurrence of Long COVID and SARS COVID-19 disease was 4 weeks in our patients. All patients underwent adequate medical therapy after Long COVID. However, due to the disease progression and significant elevated infections parameters, all patients underwent surgical therapy. One patient underwent uniportal video-assisted thoracoscopic surgery (VATS) lobectomy and decortication of the empyema, whereas we performed thoracotomy for other patients. All patients treated successfully and discharged shortly after the operation. Our literature review provides a total of 12 publications with only 50 patients. No patients received vaccination. The mean interval time between acute infection and the appearance of pulmonary cavities was about 4 weeks. The results showed that most patients were treated with conservative therapies. Only two patients were treated using invasive therapies. Both patients were successfully treated and recovered from the procedures. Conclusions: This group of late complications COVID patients requires individualized treatment strategy. In the case of an underlying pulmonary cavities, depending on the findings, despite increased perioperative risks, very good results can be achieved by presentation to a specialized and experienced thoracic surgery center.

Correction: Oweira et al. Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepaRG Tumor Cells. J. Clin. Med. 2022, 11, 4794.

There was an error in the original publication [...].

Declined Organs for Liver Transplantation: A Right Decision or a Missed Opportunity for Patients with Hepatocellular Carcinoma?

BACKGROUND: Liver transplantation is the only promising treatment for end-stage liver disease and patients with hepatocellular carcinoma. However, too many organs are rejected for transplantation. METHODS: We analyzed the factors involved in organ allocation in our transplant center and reviewed all livers that were declined for transplantation. Reasons for declining organs for transplantation were categorized as major extended donor criteria (maEDC), size mismatch and vascular problems, medical reasons and risk of disease transmission, and other reasons. The fate of the declined organs was analyzed. RESULTS: 1086 declined organs were offered 1200 times. A total of 31% of the livers were declined because of maEDC, 35.5% because of size mismatch and vascular problems, 15.8% because of medical reasons and risk of disease transmission, and 20.7% because of other reasons. A total of 40% of the declined organs were allocated and transplanted. A total of 50% of the organs were completely discarded, and significantly more of these grafts had maEDC than grafts that were eventually allocated (37.5% vs. 17.7%, p < 0.001). CONCLUSION: Most organs were declined because of poor organ quality. Donor-recipient matching at time of allocation and organ preservation must be improved by allocating maEDC grafts using individualized algorithms that avoid high-risk donor-recipient combinations and unnecessary organ declination.

Promising Outcomes of Modified ALPPS for Staged Hepatectomy in Cholangiocarcinoma.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage procedure that can potentially cure patients with large cholangiocarcinoma. The current study evaluates the impact of modifications on the outcomes of ALPPS in patients with cholangiocarcinoma. In this single-center study, a series of 30 consecutive patients with cholangiocarcinoma (22 extrahepatic and 8 intrahepatic) who underwent ALPPS between 2011 and 2021 was evaluated. The ALPPS procedure in our center was modified in 2016 by minimizing the first stage of the surgical procedure through biliary externalization after the first stage, antibiotic administration during the interstage phase, and performing biliary reconstructions during the second stage. The rate of postoperative major morbidity and 90-day mortality, as well as the one- and three-year disease-free and overall survival rates were calculated and compared between patients operated before and after 2016. The ALPPS risk score before the second stage of the procedure was lower in patients who were operated on after 2016 (before 2016: median 6.4; after 2016: median 4.4; p = 0.010). Major morbidity decreased from 42.9% before 2016 to 31.3% after 2016, and the 90-day mortality rate decreased from 35.7% before 2016 to 12.5% after 2016. The three-year survival rate increased from 40.8% before 2016 to 73.4% after 2016. Our modified ALPPS procedure improved perioperative and postoperative outcomes in patients with extrahepatic and intrahepatic cholangiocarcinoma. Minimizing the first step of the ALPPS procedure was key to these improvements.

Risk Factors of Rejection in Renal Transplant Recipients: A Narrative Review.

Multiple factors influence graft rejection after kidney transplantation. Pre-operative factors affecting graft function and survival include donor and recipient characteristics such as age, gender, race, and immunologic compatibility. In addition, several peri- and post-operative parameters affect graft function and rejection, such as cold and warm ischemia times, and post-operative immunosuppressive treatment. Exposure to non-self-human leucocyte antigens (HLAs) prior to transplantation up-regulates the recipient's immune system. A higher rate of acute rejection is observed in transplant recipients with a history of pregnancies or significant exposure to blood products because these patients have higher panel reactive antibody (PRA) levels. Identifying these risk factors will help physicians to reduce the risk of allograft rejection, thereby promoting graft survival. In the current review, we summarize the existing literature on donor- and recipient-related risk factors of graft rejection and graft loss following kidney transplantation.

Kynurenine Is the Main Metabolite of Tryptophan Degradation by Tryptophan 2,3-Dioxygenase in HepG2 Tumor Cells.

There are two main enzymes that convert tryptophan (Trp) to kynurenine (Kyn): tryptophan-2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO). Kyn accumulation can promote immunosuppression in certain cancers. In this study, we investigated Trp degradation to Kyn by IDO and TDO in primary human hepatocytes (PHH) and tumoral HepG2 cells. To quantify Trp-degradation and Kyn-accumulation, using reversed-phase high-pressure liquid chromatography, the levels of Trp and Kyn were determined in the culture media of PHH and HepG2 cells. The role of IDO in Trp metabolism was investigated by activating IDO with IFN-γ and inhibiting IDO with 1-methyl-tryptophan (1-DL-MT). The role of TDO was investigated using one of two TDO inhibitors: 680C91 or LM10. Real-time PCR was used to measure TDO and IDO expression. Trp was degraded in both PHH and HepG2 cells, but degradation was higher in PHH cells. However, Kyn accumulation was higher in the supernatants of HepG2 cells. Stimulating IDO with IFN-γ did not significantly affect Trp degradation and Kyn accumulation, even though it strongly upregulated IDO expression. Inhibiting IDO with 1-DL-MT also had no effect on Trp degradation. In contrast, inhibiting TDO with 680C91 or LM10 significantly reduced Trp degradation. The expression of TDO but not of IDO correlated positively with Kyn accumulation in the HepG2 cell culture media. Furthermore, TDO degraded L-Trp but not D-Trp in HepG2 cells. Kyn is the main metabolite of Trp degradation by TDO in HepG2 cells. The accumulation of Kyn in HepG2 cells could be a key mechanism for tumor immune resistance. Two TDO inhibitors, 680C91 and LM10, could be useful in immunotherapy for liver cancers.

Efficacy of Technical Modifications to the Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy (ALPPS) Procedure: A Systematic Review and Meta-Analysis.

To compare the outcomes of modified-Associating Liver Partition and Portal vein Ligation for Staged hepatectomy (ALPPS) techniques with those of conventional-ALPPS. Background: ALPPS is an established technique for treating advanced liver tumors. Methods: PubMed, Web of Science, and Cochrane databases were searched. The outcomes were assessed by single-arm and 2-arm analyses. Results: Seventeen studies containing 335 modified-ALPPS patients were included in single-arm meta-analysis. The estimated blood loss was 267 ± 29 mL (95% confidence interval [CI], 210-324 mL) during the first and 662 ± 51 mL (95% CI, 562-762 mL) during the second stage. The operation time was 166 ± 18 minutes (95% CI, 131-202 minutes) during the first and 225 ± 19 minutes (95% CI, 188-263 minutes) during the second stage. The major morbidity rate was 14% (95% CI, 9%-22%) after the first stage. The future liver remnant hypertrophy rate was 65.2% ± 5% (95% CI, 55%-75%) and the interstage interval was 16 ± 1 days (95% CI, 14-17 days). The dropout rate was 9% (95% CI, 5%-15%). The overall complication rate was 46% (95% CI, 37%-56%) and the major complication rate was 20% (95% CI, 14%-26%). The postoperative mortality rate was 7% (95% CI, 4%-11%). Seven studies containing 215 patients were included in comparative analysis. The hypertrophy rate was not different between 2 methods (mean difference [MD], -5.01; 95% CI, -19.16 to 9.14; P = 0.49). The interstage interval was shorter for partial-ALPPS (MD, 9.43; 95% CI, 3.29-15.58; P = 0.003). The overall complication rate (odds ratio [OR], 10.10; 95% CI, 2.11-48.35; P = 0.004) and mortality rate (OR, 3.74; 95% CI, 1.36-10.26; P = 0.01) were higher in the conventional-ALPPS. Conclusions: The hypertrophy rate in partial-ALPPS was similar to conventional-ALPPS. This shows that minimizing the first stage of the operation does not affect hypertrophy. Moreover, the postoperative overall morbidity and mortality rates were lower following partial-ALPPS.