Recurrence of Hepatocellular Carcinoma After Liver Transplantation is Associated with Episodes of Acute Rejections.

PURPOSE: The impact of acute rejection (AR) after liver transplantation (LT) for hepatocellular carcinoma (HCC) on patient outcome is uncertain. This aim of this study is to investigate whether AR is associated with HCC relapse and overall survival. PATIENTS AND METHODS: Patients undergoing LT for HCC between 2001 and 2015 were retrospectively analyzed with regard to histopathological proven AR within the median time until recurrence. Cox's regression analysis was conducted revealing risk factors for HCC recurrence. RESULTS: HCC recurred in 47 of 252 analyzed patients with a median time to recurrence of 20 months. Patients with AR (28.6%) had a significantly higher frequency of recurrence compared to patients without AR (13.0%, p=0.002). Multiple Cox regression analyses identified AR within 20 months to be an independent risk factor for HCC recurrence both as dichotomized (HR=2.91, 95%CI: 1.30-6.53; p=0.009) and as a continuous variable (HR=1.81, 95%CI: 1.28-2.54; p=0.001). HCC recurrence and AR were associated with higher grades of liver fibrosis one year after LT, when compared to patients without AR (p=0.019). CONCLUSION: Our results demonstrate an association of AR with HCC recurrence after LT with implications for intervals of monitoring in tumor surveillance. Graft fibrosis and immune mechanisms are potentially related and causal interactions are worth further investigation.

Laparoscopic Liver Resection for Intrahepatic Cholangiocarcinoma: A Single-Center Experience.

Background: Despite recent advances in the field of laparoscopic liver surgery, intrahepatic cholangiocarcinoma (iCC) as an entity has been nearly exempted from the new approaches because of proposed technical difficulties in achieving lymphadenectomy (LAD) and beneficial oncologic outcomes. Materials and Methods: Clinical courses of all consecutive patients (n = 159) undergoing liver resection for iCC at the Department of Surgery, Charité-Universitätsmedizin between January 2015 and October 2019 were studied. Ultimately, after applying selection criteria 27 laparoscopic liver resections were compared with 31 open liver resections. Results: Preoperative patient characteristics were similar with regard to general health and tumor characteristics. However, patients in the laparoscopic group tended to have more advanced liver fibrosis. When LAD was performed laparoscopically, a median of eight lymph nodes were resected, complying with current AJCC treatment guidelines. Patients undergoing laparoscopic resection showed lower overall morbidity contributing at least in part to a markedly decreased hospital stay. Conclusions: Herein, we report on one of the largest series of laparoscopically resected iCC, with a high proportion of major resections. Our data show laparoscopic resection to achieve noninferior outcomes to open resection despite impaired preoperative liver function.

Laparoscopic liver surgery in cirrhosis - Addressing lesions in posterosuperior segments.

BACKGROUND: Minimal-invasive liver resection has gained considerable attention in recent years, assuming a weighty position in the field of HPB surgery. Even lesions in posterosuperior segments, the technically most challenging localization, have been resected while achieving comparable outcomes to laparotomy. The objective of this study is to evaluate whether the similar beneficial results can be conveyed through minimal-invasive techniques for patients with liver cirrhosis. MATERIALS AND METHODS: We retrospectively analyzed all consecutive patients undergoing laparoscopic liver resection with at least one lesion in the posterosuperior liver segments (IVa, VII, VIII) at our center between January 2012 and July 2018. Patients were separated in two groups based on the presence (n = 43) or absence (n = 115) of liver cirrhosis. RESULTS: Preoperative patient characteristics showed that patients with cirrhosis were older (p < 0.001), had more frequently diabetes (p < 0.005) and a history of alcohol consumption (p < 0.0005). Preoperative liver function, as assessed by LiMAx score was markedly decreased in patients with liver cirrhosis (p < 0.005). While a similar percentage in both groups had anatomical resection, significantly more major resections were performed in patients without cirrhosis (cirrhosis: 23.3% vs. no cirrhosis 55.7%; p < 0.0005). Consequently, surgeries were markedly longer in the no cirrhosis group (p < 0.0005). There was no difference with regard to the need for perioperative transfusion or conversion to laparotomy. There was no differences found between both groups with regard to the postoperative course showing similar ICU- and hospital stays. Complication rate, both with regard to minor and major complications, as well as rate of clear resection margins were similar between the two groups as well. CONCLUSION: Patients with liver cirrhosis and a lesion in the posterosuperior liver segments are amenable to the minimal-invasive approaches as no significant differences can be observed with regard to safety and oncologic sufficiency. As these procedures are from a technical perspective challenging, they should be performed in specialized centers.

Human Stem Cells Promote Liver Regeneration After Partial Hepatectomy in BALB/C Nude Mice.

BACKGROUND: Mesenchymal stem cells (MSCs) have been suggested to augment liver regeneration after surgically and pharmacologically induced liver failure. To further investigate this we processed human bone marrow-derived MSC according to good manufacturing practice (GMP) and tested those cells for their modulatory capacities of metabolic alterations and liver regeneration after partial hepatectomy in BALB/c nude mice. METHODS: Human MSCs were obtained by bone marrow aspiration of healthy donors as in a previously described GMP process. Transgenic GFP-MSCs were administered i.p. 24 h after 70% hepatectomy in BALB/c nude mice, whereas control mice received phosphate-buffered saline. Mice were sacrificed 2, 3, and 5 d after partial hepatectomy. Blood and organs were harvested and metabolic alterations as well as liver regeneration subsequently assessed by liver function tests, multianalyte profiling immunoassays, histology, and immunostaining. RESULTS: Hepatocyte and sinusoidal endothelial cell proliferation were significantly increased after partial hepatectomy in mice receiving MSC compared to control mice (Hepatocyte postoperative day 3, P < 0.01; endothelial cell postoperative day 5, P < 0.05). Hepatocyte fat accumulation correlated inversely with hepatocyte proliferation (r2 = 0.4064, P < 0.01) 2 d after partial hepatectomy, with mice receiving MSC being protected from severe fat accumulation. No GFP-positive cells could be detected in the samples. Serum levels of IL-6, HGF, and IL-10 were significantly decreased at day 3 in mice receiving MSC when compared to control mice (P < 0.05). Relative body weight loss was significantly attenuated after partial hepatectomy in mice receiving MSC (2 d and 3 d, both P < 0.001) with a trend toward a faster relative restoration of liver weight, when compared to control mice. CONCLUSIONS: Human bone marrow-derived MSC attenuate metabolic alterations and improve liver regeneration after partial hepatectomy in BALB/c nude mice. Obtained results using GMP-processed human MSC suggest functional links between fat accumulation and hepatocyte proliferation, without any evidence for cellular homing. This study using GMP-proceeded MSC has important regulatory implications for an urgently needed translation into a clinical trial.

[Laparoscopic Liver Surgery - a Single Centre Series of 250 Consecutive Cases]. / Laparoskopische Leberchirurgie ­ Berliner Zentrumserfahrungen aus 250 konsekutiven Fällen.

BACKGROUND: In spite of convincing results from internationally prominent liver centres, laparoscopic liver surgery is not widely used in Germany. A structured program to develop laparoscopic liver surgery was established in 2015 at the Department of Surgery, Charité Hospital, Berlin, in order to provide support for establishing this approach in German hospitals. METHODS: We now report the results of our centre for 250 consecutive laparoscopic liver resections between 12/2013 and 1/2018. A retrospective analysis was performed with respect to indications, patient characteristics, complexity of the operations and postoperative results. The development of the program was analysed by comparing period 1 (1/2014 - 12/2015) and period 2 (1/2016 - 12/2017). RESULTS: In comparison with period 1 (n = 16, 25% of patients), patients in period 2 (n = 75, 50% of patients) included a significantly greater percentage of patients with a high ASA score (3/4; p = 0.001). Hepatocellular carcinoma was the most frequent indication (n = 76, 30.4%), followed by colorectal liver metastases (n = 63, 25.2%). Malignant tumours increased over the years from 53.8% in period 1 to 75.7% in period 2 (p = 0.001). 72 major (≥ 3 segments) and 178 minor resections (< 3 segments) were performed, with an increase in major resections (n = 12, 17.9%) in period 1 to period 2 (n = 56, 33.1%, p = 0.02). In spite of the significantly higher percentage of complex operations in period 2, the rate of major complications (Dindo-Clavien ≥ III a) in period 2 was 16% (27 patients) was not significantly higher than in period 1, with 11.9% (8 patients, p = 0.432). 67 patients (26.8%) suffered from liver cirrhosis; the postoperative complication rate (Dindo-Clavien ≥ III a) was not significantly different between patients with (12%) and without cirrhosis (15.8%, p = 0.424). CONCLUSION: Aside from appropriate expertise in conventional open liver surgery, minimally invasive surgery and intraoperative sonography, it is necessary to develop a structured program for the reliable implementation of laparoscopic liver surgery in German hospitals. Because of the convincing results, conventional open liver surgery will be largely replaced in Germany by laparoscopic techniques in the coming years.