The significance of resection margins on R0 results in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS: 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS: Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION: Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.

Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection.

Background: Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion: This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.

Prognostic factors of poor postoperative outcomes in gastrectomies.

Background: Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods: 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results: In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion: In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.

One-year Allograft and Patient Survival in Renal Transplant Recipients Receiving Antiplatelet Therapy at the Time of Transplantation.

BACKGROUND: Antiplatelet therapy is common in patients on the waiting list for kidney transplantation. OBJECTIVE: To evaluate the incidence of post-operative bleeding in patients with antiplatelet therapy undergoing kidney transplantation and analyze the impact on the outcome. METHODS: We studied all patients with concomitant antiplatelet therapy undergoing kidney transplantation in our center from January 2007 to June 2012. Data were collected by chart review. Univariate and multivariate logistic regression and Cox proportional hazard model were used to identify risk factors for the long-term outcome. RESULTS: Of 744 kidney transplant recipients during the study period, 161 received oral antiplatelet therapy and were included in the study. One-third of the patients demonstrated signs of bleeding, half of which requiring surgical treatment. Coronary artery disease, deceased donor kidney transplantation, and dual antiplatelet medication were independent risk factors for post-operative bleeding. One-year allograft survival was significantly better in the non-bleeding group (91.4% vs 75.9%, p=0.023). Multivariable analysis found that post-operative bleeding, recipient age, and biopsy-proven rejection were independent risk factors for graft survival. Recipient age and biopsy-proven rejection were also identified as independent risk factors for patient survival. CONCLUSION: This analysis indicated a high risk for post-operative bleeding in renal transplant patients under antiplatelet therapy. The associated negative effect on allograft survival underscored the need to reduce any risk factors for post-operative bleeding.

Assessment of standard laboratory tests and rotational thromboelastometry for the prediction of postoperative bleeding in liver transplantation.

BACKGROUND: Perioperative bleeding remains a major challenge in liver transplantation. We aimed to compare standard laboratory tests with thromboelastometry (ROTEM ® ) with regard to their ability to predict postoperative non-surgical bleeding. METHODS: Data from 243 adult liver transplant recipients from January 2012 to May 2014 were evaluated retrospectively. Upon admission to the intensive care unit, coagulation status was assessed using standard laboratory tests [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count] and ROTEM ® whole blood coagulation assays. Bleeding was defined as transfusion of ≥ 3 units of red blood cells or reoperation for non-surgical bleeding within 48 h after transplantation. Coagulation test results were analysed using receiver operating characteristics (ROC) in order to identify variables predictive of postoperative bleeding. Coagulation management was based on ROTEM ® -guided factor concentrate treatment. RESULTS: The overall incidence of bleeding was 12.3% ( n =30). Twenty-three (9.5%) patients underwent reoperation and seven (2.9%) received ≥3 units of red blood cells and non-operative management. Standard laboratory tests predictive of postoperative bleeding were aPTT and PT [area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive of bleeding with ROTEM ® were CT EXTEM , CFT INTEM , A10 FIBTEM , and MCF FIBTEM , with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen concentration, platelet count, and other ROTEM ® variables failed to demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis-dependent kidney failure, 30 day mortality, and median model for endstage liver disease score were all significantly higher in bleeding patients. CONCLUSIONS: Although both postoperative standard laboratory tests and ROTEM ® assays could identify patients at risk for postoperative bleeding, ROTEM ® assays demonstrated a greater predictive value for impaired fibrinogen polymerization-related coagulopathy.

[Relevance of Ablation Therapies for HCC: "A Real Bridging" for Liver Transplantation?]. / Stellenwert der ablativen Tumortherapie beim HCC: "eine reale Brücke" zur Lebertransplantation?

BACKGROUND: The utilisation of interventional ablation procedures in the context of bridging and downstaging plans for hepatocellular carcinomas before liver transplantation is increasing. The aim of the present study was to summarise current data for the application of bridging and downstaging procedures before liver transplantation. METHODS: The present study is based on an extensive investigation of the literature in PubMed. RESULTS of controlled trials, cohort studies, meta-analyses and reviews were included. RESULTS: Recommendations for the usage of bridging procedures for hepatocellular carcinomas within the Milan criteria and an expected waiting time of more than 6 months until transplantation depend on the size of the lesions and have a low level of evidence. After successful downstaging of hepatocellular carcinomas beyond the Milan criteria into the range of the Milan criteria liver transplantation is recommended with a low level of evidence, as well. CONCLUSION: Randomised controlled trials, clearly proving the success of bridging and downstaging procedures, are not available at the time and are not awaited for ethical reasons. Due to the uncomplicated application and low risk for therapy-associated complications, interventional procedures for bridging and downstaging are accepted and recommended.

[Orthotopic liver transplantation for polycystic liver disease with massive hepatomegaly]. / Orthotope Lebertransplantation bei polyzystischer Leberdegeneration mit massiver Hepatomegalie.

HISTORY: A 51-year-old man (126 kg, 192 cm) with massive hepatomegaly causing cardiopulmonary symptoms was referred to our transplant center 14 years after initial diagnosis of polycystic liver disease. TREATMENT AND COURSE: Uneventful hepatectomy was followed by orthotopic liver transplantation using caval replacement. Donor liver came from a 73-year-old woman (extended criteria donor organ offer). A portocaval shunting was not established during transplantation although the explanted liver weighed 22 kg. 18 months after transplantation liver function is stable and the patient enjoys normal quality of life. CONCLUSION: This case report demonstrates the value and success of transplantation for patients suffering from enormous hepatomegaly due to polycystic liver disease.

Orthotopic liver transplantation in patients with portal vein thrombosis in the absence of hepatocellular carcinoma.

BACKGROUND: Liver transplantation (OLT) in the setting of portal vein thrombosis (PVT) has been a matter of controversy in the past. We herein report our experience with OLT for PVT in the absence of hepatocellular carcinoma. PATIENTS AND METHODS: Data from patients undergoing OLT for end-stage liver disease, having a documented PVT before OLT, were reviewed. RESULTS: Twenty-five patients were included for the period July, 2003 to December, 2009. There were 20 men and 5 women of median age 57 years. Median values for waiting time and Model for End-Stage Liver Disease score were 150 days and 18, respectively. PVT was classified as grade II (n = 6), IIIa (n = 7), IIIb (n = 9), or IVa (n = 3). Partial portal vein resection/reconstruction, operative thrombectomy, and eversion thromboendovenectomy were performed in 2, 16, and 7 instances, respectively. After a median follow-up of 18 months, 14 patients are alive. Survival rates at 3, 6, 9, and 12, months and 3 years post-OLT were 68%, 64%, 61%, 61%, and 61%, respectively. PVT grade was a negative predictor of survival by Cox proportional hazard analysis (P = .0253). CONCLUSION: Despite the technical innovations in recent years, PVT grade correlated with poor patient survival irrespective of the surgical technique.

Stented ureterovesical anastomosis in renal transplantation: does it influence the rate of urinary tract infections?

OBJECTIVE: Our objective was to evaluate the impact of routine use of double-J stents on the incidence of urinary tract infection after renal transplantation. METHODS: We conducted a retrospective-comparative single-centre study in 310 consecutive adult deceased donor kidney recipients transplanted from 2002 to 2006. Patients were divided in two groups, with or without urinary stent implantation. To evaluate the predictive factors for UTI, donor and recipients pre- and post-transplantation data were analysed. Early urological complications and renal function within 12 months of transplantation were included as well. RESULTS: A total of 157 patients were enrolled to a stent (ST) and 153 patients to a no-stent (NST) group. The rate of urinary tract infection at three months was similar between the two groups (43.3% ST vs. 40.1% NST, p = 0.65). Of the identified pathogens Enterococcus and Escherichia coli were the most common species. In multivariate analysis neither age nor immunosuppressive agents, BMI or diabetes seemed to have influence on the rate of UTI. When compared to males, females had a significantly higher risk for UTI (54.0% vs. 33.5%). CONCLUSION: Prophylactic stenting of the ureterovesical anastomosis does not increase the risk of urinary tract infection in the early postoperative period.

Transplantation after blunt trauma to the liver: a valuable option or just a "waste of organs"?

OBJECTIVE: Liver injury due to trauma is a rare indication for transplantation. The main indications in such cases were uncontrollable bleeding and insufficient hepatic function. Because of poor results, liver transplantation in these patients is occasionally described as "waste of organs", however based on insufficient data. This study aims to report our experience and to critically question the indication of transplantation in these patients. METHODS: All liver transplantations at our institution were reviewed retrospectively. This covered 1,529 liver transplants between September 1987 and December 2008. Of them, 6 transplants were performed due to motor-vehicle accidents which caused uncontrollable acute liver trauma in 4 patients. The patients' peri-operative course, short- and long-term outcomes were analyzed. RESULTS: Five deceased-donor liver transplantations (4 full size, 1 split) and 1 living donor (right) transplantation were performed. The median GCS score was 9/15; the median MELD score was 15. Postoperative complications were observed in 3 patients, requiring re-operation in 2. After a median (range) follow-up of 32.95 (10.3-55.6) months, 2 patients are alive and remain well on immunosuppression. CONCLUSION: Liver transplantation in patients with otherwise surgically uncontrollable acute liver injury can be indicated as a life saving procedure and can be performed successfully in highly selected cases.

Effect of low-dose rapamycin on tumor growth in two human hepatocellular cancer cell lines.

AIM: Liver transplantation is the best treatment for patients with early hepatocellular carcinoma (HCC) and cirrhosis. A limiting factor for long-term survival remains posttransplant tumor recurrence. Thus, there is widespread discussion about the role of various immunosuppressive agents. The newly developed immunosuppressive drug rapamycin may aid to lower recurrence rates. We investigated the efficiency of rapamycin as compared with previous immunosuppressants in a tumor cell model. METHODS: We studied two HCC cell lines for cell-cycle and proliferation analyses after treatment with rapamycin or other immunosuppressants. To elucidate the underlying molecular signaling pathway, we performed Western blotting for phosphorylated p70 S6 kinase protein expression. RESULTS: Low-dose rapamycin inhibited tumor cell growth at doses of 1, 5, and 10 ng/mL, while standard immunosuppressants stimulated growth. A rapamycin dose of 20 ng/mL showed a marked decrease in the growth inhibition of both HCC cell lines compared to low-dose administration. CONCLUSION: Rapamycin in low doses inhibited the growth of two HCC cell lines in vitro. Inhibition of tumor cell growth was observed with a high dose of rapamycin (20 ng/mL), which appears to be the dividing line between growth and inhibition. We postulated that at higher doses the immunosuppressive effect of rapamycin is overrode by its antitumor effects.