[Strategies to Optimise R0 Resection for Hilar Cholangiocarcinoma]. / Strategien zur Optimierung der R0-Resektionsrate von zentralen Gallengangskarzinomen.

BACKGROUND: Retrospective analyses have shown a 20-40 % incidence of R1 resection in hilar cholangiocarcinoma, which therefore represents a significant issue to be addressed. METHODS: We have reviewed the literature on the impact of R1 resection in hilar cholangiocarcinomas and on possible surgical options to increase the rate of complete tumour resections. RESULTS: To minimise the rate of R1 resections a preoperative risk assessment concerning the predisposed anatomic locations is required. During planning of the surgical strategy, liver function plays a central role prior to right-sided hemihepatectomies. Due to the loss of a high amount of functional liver parenchyma, contralateral portal vein embolisation is often used prior to right trisectionectomies. For left-sided hepatectomies the management of the right hepatic artery is fundamental. The right hepatic artery has a very close contact to the tumour region, although arterial invasion is rarely seen. However, the risk of manifest or occult R1 resection is relatively high along the right artery. In selected cases an arterial resection might be considered, but this increases the risk of postoperative complications. Arterial resection might be performed either via direct anastomosis or by using an interposition graft. As reserve procedures preoperative embolisation of the hepatic artery without reconstruction or an arterialisation of the portal vein are available. However, the latter two procedures come along with an increased rate of biliary complications. In selected lymph-node negative patients with irresectable hilar cholangiocarcinoma liver transplantation might be considered. CONCLUSION: Despite significant advances in surgical technique, R1 resection remains a problem, which is aggravated by the lack of evidence-based adjuvant measures.

Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Everolimus and early calcineurin inhibitor withdrawal: 3-year results from a randomized trial in liver transplantation.

The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open-label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI-based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft-Gault) at month 11 post randomization. A 24-month extension phase followed 81/114 (71.1%) of eligible patients to month 35 post randomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval [CI] -1.3, 21.5 mL/min, p = 0.082) in favor of CNI-free versus CNI using Cockcroft-Gault, 9.4 mL/min/1.73 m(2) (95% CI -0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four-variable) and 9.5 mL/min/1.73 m(2) (95% CI -1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI-free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy-proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI-free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus-based CNI-free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.

Technical feasibility of liver transplantation without cold storage.

PURPOSE: The success of liver transplantation (LT) is accompanied by an increased need for organs. The wider use of older donors and marginal organs with risk factors such as steatosis has lead to a new interest to improve the outcome with marginal organs. We herewith report a novel technique for LT with in situ preparation and immediate warm-ischemia liver transplantation (WI-LT). The aim of our study was to demonstrate the technical feasibility and report the transplant course. METHODS: Six patients underwent WI-LT at our institution. Hepatectomies during procurement and LT were both performed in parallel by different surgical teams. Technical factors and postoperative allograft function were analyzed. RESULTS: All six WI-LTs were performed without intraoperative complications with a mean warm-ischemia time (WIT) of 29.0 min. No patient developed primary non-function or required retransplantation. Mean alanine aminotransferase (194.0 ± 170.4 U/l) and aspartate aminotransferase (316.3 ± 222.1 U/l) values on the first postoperative day were low, indicating a low ischemia/reperfusion injury and an excellent liver function. CONCLUSIONS: These results demonstrate that WI-LT is a safe and technically feasible approach for LT with possibly reduced IRI and an excellent postoperative allograft quality. WI-LT may therefore be considered in individual patients especially with extended criteria donors to eventually improve postoperative allograft quality.

[Impact of time of occurrence of liver metastases (synchronous vs. metachronous) on early postoperative outcome and long-term survival of colorectal cancer patients]. / Einfluss des Metastasierungszeitpunkts (synchron vs. metachron) im Hinblick auf das frühpostoperative Outcome sowie das Langzeitüberleben von Patienten nach Resektion kolorektaler Lebermetastasen.

BACKGROUND: Today, liver resection represents the only curative treatment option for patients with resectable colorectal liver metastases. Large studies could show that liver surgery can be performed safely in specialised centres, but most of those studies did not differentiate between resection of synchronous and metachronous metastases. The aim of this study was to evaluate the impact of the time of the occurrence of colorectal liver metastases on the early postoperative course as well as the long-term survival. PATIENTS AND METHODS: Two groups of 30 patients each who underwent liver surgery due to synchronous or metachronous colorectal liver metastases at our centre between 2000 and 2010 were included in a matched-pairs analysis. Early postoperative course as well as long-term survival were assessed and compared between both groups. Matching criteria included: age, sex, number of metastases and size of largest metastasis. RESULTS: Postoperative morbidity for the entire study cohort was 23.3 % with a mortality of 0 %. No significant difference could be shown between synchronous and metachronous metastases with regard to incidence and severity of postoperative complications (20 vs. 26.7 %, p = 0.54). The median survival of the synchronous group was 38.9 months (95 % CI 26.4-51.6) compared to 47.9 months (95 % CI 21.4-74.4 %) in the metachronous group, but no significant difference could be detected in the univariate analysis (p = 0.425). CONCLUSION: According to the present results, liver surgery can be performed safely in a specialised centre. The time of occurrence of the metastases (synchronous vs. metachronous) does not seem to have any impact on the early postoperative course as well as on the long-term survival in patients undergoing curative resection of colorectal liver metastases. However, larger studies appear necessary to confirm the results of the present study.

Biliary complications after liver transplantation: old problems and new challenges.

Due to a vulnerable blood supply of the bile ducts, biliary complications are a major source of morbidity after liver transplantation (LT). Manifestation is either seen at the anastomotic region or at multiple locations of the donor biliary system, termed as nonanastomotic biliary strictures. Major risk factors include old donor age, marginal grafts and prolonged ischemia time. Moreover, partial LT or living donor liver transplantation (LDLT) and donation after cardiac death (DCD) bear a markedly higher risk of biliary complications. Especially accumulation of several risk factors is critical and should be avoided. Prophylaxis is still a major issue; however no gold standard is established so far, since many risk factors cannot be influenced directly. The diagnostic workup is mostly started with noninvasive imaging studies namely MRI and MRCP, but direct cholangiography still remains the gold standard. Especially nonanastomotic strictures require a multidisciplinary treatment approach. The primary management of anastomotic strictures is mainly interventional. However, surgical revision is finally indicated in a significant number of cases. Using adequate treatment algorithms, a very high success rate can be achieved in anastomotic complications, but in nonanastomotic strictures a relevant number of graft failures are still inevitable.

Twenty-year longitudinal follow-up after orthotopic liver transplantation: a single-center experience of 313 consecutive cases.

With excellent short-term survival in liver transplantation (LT), we now focus on long-term outcome and report the first European single-center 20-year survival data. Three hundred thirty-seven LT were performed in 313 patients (09/88-12/92). Impact on long-term outcome was studied and a comparison to life expectancy of matched normal population was performed. A detailed analysis of 20-years follow-up concerning overweight (HBMI), hypertension (HTN), diabetes (HGL), hyperlipidemia (HLIP) and moderately or severely impaired renal function (MIRF, SIRF) is presented. Patient and graft survival at 1, 10, 20 years were 88.4%, 72.7%, 52.5% and 83.7%, 64.7% and 46.6%, respectively. Excluding 1-year mortality, survival in the elderly LT recipients was similar to normal population. Primary indication (p < 0.001), age (p < 0.001), gender (p = 0.017), impaired renal function at 6 months (p < 0.001) and retransplantation (p = 0.034) had significant impact on patient survival. Recurrent disease (21.3%), infection (20.6%) and de novo malignancy (19.9%) were the most common causes of death. Prevalence of HTN (57.3-85.2%, p < 0.001), MIRF (41.8-55.2%, p = 0.01) and HBMI (33.2-45%, p = 0.014) increased throughout follow-up, while prevalence of HLIP (78.0-47.6%, p < 0.001) declined. LT has conquered many barriers to achieve these outstanding long-term results. However, much work is needed to combat recurrent disease and side effects of immunosuppression (IS).

Intraoperative placement of external biliary drains for prevention and treatment of bile leaks after extended liver resection without bilioenteric anastomosis.

BACKGROUND: Improved surgical techniques, substantial preoperative diagnostics, and advanced perioperative management permit extensive and complex liver resection. Thus, hepatic malignancies that would have been considered inoperable some years ago may be curatively resected today. Despite all this progress, biliary leakage remains a clinically relevant issue, especially after extended liver resection. Intraoperative decompression of bile ducts by means of distinct biliary drains is controversial. Although drainage is rarely used as a routine procedure, it might be useful in selected patients at high risk for biliary leakage. METHODS: We describe surgical management of long-segment exposed or injured bile ducts after extended parenchymal resection with concomitant lymphadenectomy. Because blood supply to the bile duct may be impaired, the risk of biliary necrosis and/or leakage is significant. Internal splinting of the bile duct to ensure optimum decompression plus guidance might be helpful. Thus, in selected cases after trisectionectomy we inserted an external-internal or internal-external drain into long-segment exposed bile ducts. For internal-external drains the tube was diverted via the major duodenal papilla into the duodenum and then transfixed after the duodenojejunal flexure through the jejunal wall by means of a Witzel's channel. RESULTS: Because the entire bile duct is splinted, this technique is superior to bile duct decompression with a T-tube. This is supported by the course of a patient suffering biliary leakage after extended right-sided hepatectomy for colorectal metastasis. Initially, a T-tube was inserted for decompression, but biliary leakage persisted. After inserting transhepatic external-internal drainage, bile leakage stopped immediately. The patient's course was then uneventful. Five other patients (mostly with locally advanced hepatocellular or cholangiocellular carcinoma) treated similarly were discharged without complications. Drain removal 6 weeks postoperatively was uncomplicated in five of the 6 patients. In the sixth patient, external-internal drainage was replaced by a Yamakawa-type prosthesis for a biliary stricture. None of the patients suffered severe complications during long-term follow-up. CONCLUSIONS: The bile duct drainage technique presented in this study was useful for preventing and treating bile leakage after long-segment exposure of extrahepatic bile ducts during major hepatectomy. Transhepatic or internal-external drains are often used for bilioenteric anastomoses, but similar drainage techniques have not been reported for the native bile duct. T-tubes are generally used in this situation. In particular cases, however, inner splinting of the bile duct and appropriate movement of the bile via a tube can be helpful.

[Diagnosis of and therapy for hepatocellular carcinoma]. / Diagnostik und Therapie des hepatozellulären Karzinoms.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.

A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation--PROTECT.

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal-sparing alternative. In this randomized 1-year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post-LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft-Gault formula (-2.9 mL/min in favor of EVR, 95%-CI: [-10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (-7.8 mL/min, 95%-CI: [-14.366; -1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy-proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx that deserves further investigation in terms of nephroprotection.

Feasibility of surgery after systemic treatment with the humanized recombinant antibody bevacizumab in heavily pretreated patients with advanced epithelial ovarian cancer.

BACKGROUND: The aim of this study was to assess operative feasibility and outcome after bevacizumab treatment (BT) in ovarian cancer (OC) patients. PATIENTS AND METHODS: We retrospectively identified all OC patients operated between April 2006 and September 2010 after BT. RESULTS: We identified 733 OC operations, 10 of which (1.36%) were performed in a mean time of 134 days (range, 10-288) after BT. Indication was secondary cytoreduction in 3 patients (mean days after BT, 181; range, 82-256) and palliation in 7 due to bowel obstruction and/or intestinal perforation or fistula (mean days after BT, 114; range, 10-288). All but 1 acutely operated patients developed a secondary wound healing, but none of the 3 patients after planned cytoreduction did. Of these 3 patients, 1 suddenly died on the 36th postoperative day, presumably of thromboembolism. None of the patients developed postoperatively a gastrointestinal morbidity; however, in 1 patient operated 21 days after BT due to a vesicointestinal fistula the bladder reconstruction could not heal and developed a permanent fistula. CONCLUSIONS: Emergency surgery after BT due to bowel obstruction and/or fistulas seems to be associated with an impaired wound healing in advanced heavily pretreated platinum-resistant OC patients, while this does not appear the case in planned cytoreduction. Prospective evaluations are warranted to assess surgical safety after BT in this special patients' collective.

Role of mannose-binding lectin-2 polymorphism in the development of acute cellular rejection after transplantation for hepatitis C virus-induced liver disease.

UNLABELLED: The development of liver and graft disease is suspected to be affected by genetic diversity. Mannose-binding lectin-2 (MBL-2) is an important immunomodulatory factor that is involved in complement activation. The aim of our study was to elucidate the role of MBL-2 genotypes after liver transplantation (LT) for hepatitis C virus (HCV)-induced liver disease regarding the incidence of acute cellular rejection (ACR), graft inflammation, fibrosis development, and antiviral treatment response. METHODS: A group of 149 patients who underwent LT for HCV-induced liver disease were genotyped for MBL-2 (rs7096206; G/C) by TaqMan genotyping assay. We evaluated 518 post-LT protocol biopsies and at least 98 urgent liver biopsies regarding graft fibrosis stages, inflammation grades, and evidence for rejection within MBL-2 genotype groups. RESULT: No association of MBL-2 polymorphisms was observed regarding inflammation, fibrosis, and antiviral treatment outcome. However, the C allele of the MBL-2 gene (P = 0.001) and gender compatibility (P = 0.012) were factors significantly associated with the incidence of ACR. CONCLUSION: MBL-2 polymorphisms and gender are involved in the development of ACR after LT. CC genotype and gender match may be regarded as risk factors for ACR in HCV-positive graft recipients. Further studies are needed to confirm and verify this observation in non-HCV groups as well.

Tumor necrosis factor alpha inhibitors as immunomodulatory antirejection agents after intestinal transplantation.

We reported the successful administration of infliximab for late-onset OKT3-resistant rejection in two patients, who presented persistent ulcerative inflammation of the ileal graft after intestinal transplantation (ITX). Based on this experience, the present study demonstrated our long-term experience with infliximab for different types of rejection-related and inflammatory allograft alterations. Infliximab administration (5 mg/kg body weight (BW)) was initiated at a mean of 18.2 ± 14.1 months after transplantation. The number of administrations per patient averaged 8.4 ± 6.7. Repeat dosing was timed according to clinical signs and graft histology in addition to serum-levels of tumor necrosis factor alpha (TNFα), lipopolysaccharide binding protein (LBP) and C-reactive protein (CRP). Infliximab was successful in the following patients: patients with late-onset OKT3- and steroid-refractory rejection who presented persistent ulcerative alterations of the ileal graft (n = 5), patients with ulcerative ileitis/anastomositis, who did not show typical histological rejection signs (n = 2), and one patient with early-onset OKT3-resistant rejection. Infliximab was not successful in one patient with early-onset OKT3-resistant rejection that was accompanied by treatment-refractory humoral rejection. In conclusion, infliximab can expand therapeutic options for late-onset OKT3- and steroid-refractory rejection and chronic inflammatory graft alterations in intestinal allograft recipients.

Management and outcomes of haemorrhage after pancreatogastrostomy versus pancreatojejunostomy.

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a major cause of morbidity and mortality after pancreaticoduodenectomy (PD). It remains unclear whether performance of a pancreatogastrostomy (PG) instead of a pancreatojejunostomy (PJ) improves outcomes owing to better endoscopic accessibility. METHODS: A large retrospective analysis was undertaken to compare outcomes of PPH, depending on whether a PG or PJ was performed. The primary outcome was the rate of successful endoscopy. A secondary outcome was the therapeutic success after adding surgery. RESULTS: Of 944 patients who had a PD, 8·4 per cent developed PPH. Endoscopy was the primary intervention in 21 (81 per cent) of 26 patients with a PG and 34 (64 per cent) of 53 with a PJ; it identified the bleeding site in 35 and 25 per cent respectively (P = 0·347). Successful endoscopic treatment was more common in the PG group (31 versus 9 per cent; P = 0·026). Surgery was performed for PPH in 15 patients (58 per cent) with a PG and 35 (66 per cent) with a PJ (P = 0·470). The majority of haemorrhages that required surgery were non-anastomotic intra-abdominal haemorrhages (12 of 15 versus 21 of 35; P = 0·171). Endoscopic or conservative treatment for PPH was successful in 42 per cent of patients with a PG and 32 per cent with a PJ (P = 0·520). The success rate increased to 85 and 91 per cent respectively when surgery was included in the algorithm (P = 0·467). CONCLUSION: The type of pancreatic anastomosis and its inherent effect on endoscopic accessibility had very little impact on the outcome of PPH. This was because haemorrhage frequently occurred from intra-abdominal or non-anastomotic intraluminal lesions.

Liver transplantation for alcohol-related cirrhosis: a single centre long-term clinical and histological follow-up.

BACKGROUND: Alcohol-induced liver cirrhosis is one of the leading indications for liver transplantation today. Due to the general organ shortage and continuous deaths on the waiting list there has been some debate on the issue of indication and ethical problems. It was the aim of this study to critically analyse the outcome of patients with alcoholic cirrhosis transplanted at our centre with special emphasis on alcohol-recurrence frequency and long-term histological follow-up. METHODS: Three hundred five patients who received LT for alcoholic cirrhosis at our institution were followed over a period of 3-10 years after transplantation. Biopsies were taken 1, 3, 5, and 10 years after LT. Specimens were analysed and staged concerning inflammation, rejection, fatty involution, and fibrosis/cirrhosis. Clinical characteristics as well as serological parameters, immunosuppressive protocols, rejection episodes, and patient and graft survival were recorded. RESULTS: Recurrence of alcohol abuse occurred in 27% of all patients analysed. Regardless of alcohol consumption, 5-year graft and patient survival were excellent; after 10 years abstinent patients showed significantly better survival (82% vs. 68%; P=0.017). Histological changes were slightly more pronounced among recurrent drinkers, no significant difference regarding inflammation or fibrosis was detected. CONCLUSION: Patients undergoing LT for alcohol-induced cirrhosis show excellent long-term survival rates with stable graft function. Alcohol recurrence impairs long-term prognosis; however, compared to other patient sub-populations (HCC, HCV) results are clearly above average.

[Current developments in liver transplantation in Germany: MELD-based organ allocation and incentives for transplant centres]. / Aktuelle Entwicklungen der Lebertransplantation in Deutschland: MELD-basierte Organallokation und "incentives" für Transplantationszentren.

Liver transplantation represents a successful and well-established therapeutic concept for patients with advanced liver diseases. Organ donor shortage continues to pose a significant problem. To ensure fair and transparent allocation of too few post-mortem grafts, the model of end-stage liver disease (MELD)-based allocation was implemented in December 2006. This has decreased waiting list mortality from 20 to 10 % but at the same time has reduced post OLT survival (1-year survival from almost 90% to below 80%), which is largely due to patients with a labMELD score > 30. Following MELD introduction the regular allocation threshold has increased from a matchMELD of initially 25 to meanwhile 34. At the same time the quality of donor organs has seen a continuous deterioration over the last 10 - 15 years: 63% of organs are "suboptimal" with a donor risk index of > 1.5. Moreover, the numbers of living-related liver transplantations have decreased. In Germany incentives for transplant centres are inappropriate: patients with decompensated cirrhosis, high MELD scores and high post-transplant mortality as well as marginal liver grafts are accepted for transplantation without the necessary consideration of outcomes, and against a background of the still absent publication and transparency of outcome results. The outlined development calls for measures for improvement: (i) the increase of donor grafts (e. g., living donation, opt-out solutions, non-heart beating donors), (ii) the elimination of inappropriate incentives for transplant centres, (iii) changes of allocation guidelines, that take the current situation and suboptimal donor grafts into account, and (iv) the systematic and complete collection of transplant-related data in order to allow for the development of improved prognostic scores.

[Perioperative anesthesia management of extended partial liver resection. Pathophysiology of hepatic diseases and functional signs of hepatic failure]. / Perioperatives anästhesiologisches Management bei ausgedehnten Leberteilresektionen. Pathophysiologie der Lebererkrankungen und funktionelle Zeichen des Leberversagens.

The importance of partial liver resection as a therapeutic option to cure hepatic tumors has increased over the last decades. This has been influenced on the one hand by advances in surgical and anesthetic management resulting in a reduced mortality after surgery and on the other hand by an increased incidence of hepatocellular carcinoma. Nowadays, partial resection of the liver is performed safely and as a routine operation in specialized centers. This article describes the pathophysiological changes secondary to liver failure and assesses the perioperative management of patients undergoing partial or extended liver resection. It looks in detail at the preoperative assessment, the intraoperative anesthetic management including fluid management and techniques to reduce blood loss as well as postoperative analgesia and intensive care therapy.

[Current status of multimodal therapy for colorectal liver metastases]. / Kolorektale Lebermetastasen: Aktueller Stand der multimodalen Therapie.

Surgical resection is the only chance of cure for patients with colorectal liver metastases und significantly improves patient survival. The percentage of patients who can undergo curative resection as well as the survival after liver resection can be increased by using modern multimodal treatment algorithms. This has been achieved by not only innovations in pre- and postoperative chemotherapy but also by new surgical and interventional techniques and last but not least by individualisation of chemotherapeutic regimens. Due to the high number of new treatment modalities, a generally accepted treatment algorithm cannot be provided so far for all subgroups of the inhomogeneous group of patients with colorectal liver metastases. In the present review the current status of multimodal therapy is outlined and the pending questions mentioned.

The impact of carbon dioxide pneumoperitoneum on liver regeneration after liver resection in a rat model.

BACKGROUND: In recent years, laparoscopic hepatic resection is performed by an increasing number of surgeons. Despite many advantages of the laparoscopic procedure, it is unclear whether the pneumoperitoneum affects the postoperative liver regeneration after liver resection. The current study aimed to investigate the influence of a carbon dioxide (CO(2)) pneumoperitoneum on liver regeneration in a rat model. METHODS: In this study, 60 male Wistar rats were subjected to 70% partial hepatic resection. Of these 60 animals, 30 underwent preoperative pneumoperitoneum at 9 mmHg for 60 min. After hepatic resection, the rats were killed at 12, 24, and 48 h, and on days 4 and 7. The outcome parameters were hepatocellular injury (plasma aminotransferases), oxidative stress (plasma malondialdehyde), interleukin-6 (IL-6), and liver regeneration (mitotic index, KI-67; regenerating liver mass). RESULTS: The mitotic index was significantly lower in the pneumoperitoneum group than in the group without pneumoperitoneum at all time points (p < 0.05). In the pneumoperitoneum group, KI-67 was significantly lower on day 4 (p < 0.05). The liver regeneration rate was significantly lower for the animals with pneumoperitoneum on days 2 and 4 (p < 0.05). The postoperative hepatocellular injury was significantly greater after pneumoperitoneum at 12, 24, and 48 h (p < 0.05). Plasma malondialdehyde and IL-6 were significantly higher in the pneumoperitoneum group at 24 h and on day 4 (p < 0.05). CONCLUSION: This study showed that pneumoperitoneum before extended liver resection impaired postoperative liver regeneration. Oxidative stress reaction and hepatocellular damage was markedly higher after pneumoperitoneum. Further investigations, especially with patients that have impaired liver function, are necessary for clinical consequences to be drawn from these results.

Advances in image guided conventional and minimal invasive liver surgery.

Technological developments, advances in perioperative medicine and ongoing scientific research have led to reduced rates of mortality and morbidity in patients undergoing major liver surgery. Under these conditions, the frontier of resectability is constantly in movement towards more complex cases with extended tumor spread and potentially minimized remnant liver volume. A promising technique to support oncological correct and safe liver surgery is the introduction of preoperative computer based planning models and intraoperative navigation systems. Whereas three-dimensional (3D) liver models are commercially available and have been clinically implemented, the use of navigation systems is currently under evaluation by different groups using a variety of techniques. This manuscript is meant to give the reader an overview on current developments, difficulties and future aspects of image guided liver surgery.