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Purpose: The International Study Group of Liver Surgery (ISGLS) defined post-hepatectomy biliary leakage as drain/serum bilirubin ratio > 3 at day 3 or the interventional/surgical revision due to biliary peritonitis. We investigated the definition's applicability., Methods: A retrospective evaluation of all liver resections over a 6-year period was performed. ROC analyses were performed for drain/serum bilirubin ratios on days 1, 2, and 3 including grade A to C (analysis I) and grade B and C biliary leakages (analysis II) to test specific cutoff values., Results: A total of 576 patients were included. One hundred nine (18.9%) postoperative bile leakages occurred (19.6% of the whole population grade A, 16.5% grade B/C). Areas under the curve (AUC) for analysis I were 0.841 (day 1), 0.846 (day 2), and 0.734 (day 3). The highest sensitivity (78% on day 1/77% on day 2) and specificity (78% on day 1/79% on day 2) in analysis I were obtained for a drain/serum bilirubin ratio of 2.0. AUCs for analysis II were similar: 0.788 (day 1), 0.791 (day 2), and 0.650 (day 3). The highest sensitivity (73% on day 1/71% on day 2) and specificity (74% on day 1/76% on day 2) in analysis II were detected for a drain/serum bilirubin ratio of 2.0 on postoperative day 2., Conclusion: Biliary leakages should be defined if the drain/serum bilirubin ratio is > 2.0 on postoperative day 2., (© 2023. The Author(s).)

Objective: The aim of this study was to evaluate the survival benefit of sirolimus in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC) (exploratory analysis of the SiLVER-trial)., Summary and Background Data: Patients receiving LT) for HCC are at a high risk for tumor recurrence. Calcineurin inhibitors have shown evidence to promote cancer growth, whereas mammalian target of rapamycin (mTOR) inhibitors like sirolimus have anticancer effects. In the SiLVER-trial (Clinicaltrials.gov: NCT00355862), the effect of sirolimus on the recurrence of HCC after LT was investigated in a prospective randomized trial. Although the primary endpoint of improved disease-free survival (DFS) with sirolimus was not met, outcomes were improved for patients in the sirolimus-treatment arm in the first 3 to 5 years. To learn more about the key variables, a multivariate analysis was performed on the SiLVER-trial data., Patients and Methods: Data from 508 patients of the intention-to-treat analysis were included in exploratory univariate and multivariate models for overall survival (OS), DFS and a competing risk analysis for HCC recurrence., Results: Sirolimus use for ≥3 months after LT for HCC independently reduced the hazard for death in the multivariate analysis [hazard ratio (HR): 0.7 (95% confidence interval, CI: 0.52-0.96, P = 0.02). Most strikingly, patients with an alpha-fetoprotein (AFP) ≥10 ng/mL and having used sirolimus for ≥3 months, benefited most with regard to OS, DFS, and HCC-recurrence (HR: 0.49-0.59, P = 0.0079-0.0245)., Conclusions: mTOR-inhibitor treatment with sirolimus for ≥3 months improves outcomes in LT for HCC, especially in patients with AFP-evidence of higher tumor activity, advocating particularly for mTOR inhibitor use in this subgroup of patients., Clinical Trial Registration: EudraCT: 2005-005362-36 CLINICALTRIALS.GOV:: NCT00355862.

Background: Liver transplantation (LT) is a complex yet curative treatment for a subset of patients with hepatocellular carcinoma (HCC). Due to donor organ shortage, patients with HCC need to be carefully selected for LT. In European countries, selection of patients is based on the Milan criteria, and donor organs are allocated by Eurotransplant. In order to optimize the utilization of available liver grafts, the outcome of HCC patients after LT needs to be closely monitored and evaluated., Methods: We assessed the outcome of 304 HCC patients who underwent LT at a tertiary medical center over a period of nearly 20 years (February 1998 until June 2017)., Results: The 5-, 10- and 15-year survival rates were 62, 47 and 30%, respectively. The strongest survival-determining factor was tumour recurrence. Apart from a high tumour grading, the pre-LT MELD score was significantly and negatively associated with survival after LT., Conclusion: Our results confirm the importance of recurrence for the outcome of HCC patients after LT and highlight the relevance of HCC patients' liver function before LT. Our findings encourage efforts to identify prognostically relevant factors for LT in HCC with the overall goal of refining the organ allocation system and maximizing the survival benefit after LT., (Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC)., Methods: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint., Results: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874)., Conclusions: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

This is the first matched pair analysis on the puzzling clinical problem of whether to perform liver transplantation (LT) or liver resection (LR) for Child's A hepatocellular carcinoma (HCC) patients. A total of 201 patients diagnosed with HCC and Child's A liver cirrhosis were treated with LT transarterial chemoembolization (TACE) or LR between 1998 and 2012. To achieve the most accurate study design, two groups of 57 patients were matched retrospectively according to their tumor characteristics detected by the initial computerized tomography (CT) scan. Sixteen of 57 LT candidates were not transplanted due to tumor progress during pre-treatment (TACE). Nevertheless, the retrospective analysis of the matched pairs according to the intention-to-treat principle resulted in a better five-yr overall survival (OS) rate of 54.3% for the group of LT candidates compared with 35.7% for those receiving LR (p = 0.19). In patients meeting the University of California, San Francisco (UCSF) criteria, five-yr OS reached 58.4% after LT and 45.1% after LR (p = 0.56). For Milan criteria (MC) patients, LT resulted in 57.9% and LR in 42% five-yr OS rate (p = 0.29). In conclusion, the finding of a better OS rate in LT was not statistically significant. There was also a selection bias in favor of LT, which may have influenced the OS. Therefore, particularly in regard to organ scarcity, LR remains a viable treatment option for respectable HCC in Child's A cirrhosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background & Aims: Liver transplantation is a curative treatment option for patients with hepatocellular carcinoma (HCC) and liver cirrhosis. To date, patient selection for transplantation is based on size and number of nodules as assessed by imaging before listing. We hypothesized that changes in tumour features resulting from pre-transplant transarterial chemoembolisation (TACE) is a superior criterion to predict tumour recurrence., Methods: 136 patients with HCC in cirrhosis with two or more cycles of pre-transplant TACE were included in this study. According to the surgical specimens, 46 patients exceeded the Milan criteria., Results: Tumour recurrence occurred in 21 patients (15%). Classification of Milan criteria according to the imaging at referral was not predictive for recurrence (p=0.58), whereas the Milan criteria in the imaging immediately before transplantation reflected changes after pre-transplant TACE and were highly predictive (p<0.0001). Of the 99 patients constantly within Milan or downstaged to within Milan, 88% were recurrence-free after 5 years, compared to 55% of the patients exceeding the Milan criteria despite pre-transplant TACE. Five-year absence of recurrence was better predicted by the criterion "Progressive Disease" according to RECIST (p<0.0001). If progression was defined as any progression (including less than 20% of the sum of target lesions or new measurable lesions), predictability of recurrence in the receiver operating characteristic was 0.86., Conclusions: Imprecise assessment of size and number of tumour lesions limits prognostic importance of initial imaging. Characteristics of tumour response to TACE are reliably recognized and allow identification of suitable patients for transplantation. Future selection criteria for LT in HCC should consider this aspect., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC)., Materials and Methods: 273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical (n = 130), TACE (n = 32), and systemic chemotherapy/best supportive care (n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively., Results: The 1-, 3-, and 5-year survival rates in patients after surgical resection were 60%, 40%, and 23%, respectively. Recurrence occurred in 63 percent of patients after R0 resection. Median time of recurrence-free survival was 14 months. Univariate analysis revealed nine significant risk factors for overall survival in the resection group: major surgery, extrahepatic resection, vascular and bile duct resection, lymph node invasion, poor tumour differentiation, positive surgical margin, multiple lesions, tumour diameter, and UICC-Stage. Multivariate analysis showed that lymph node metastasis (P < 0.001), poor tumour differentiation (P = 0.002), and positive resection margins (P = 0.001) were independent prognostic factors for survival. Median survival as well as overall survival rates of TACE patients were comparable to those of lymph node positive patients and patients with tumour positive surgical margins., Conclusions: R0 resection in patients with negative lymph node status remains the best chance for long-term survival in patients with IHC. There is no significant survival benefit of surgery in lymph node positive patients or patients with positive resection margin over TACE., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Objectives: To report the outcome of patients with hepatocellular carcinoma (HCC) in non-cirrhotic liver depending on the mode of primary treatment and to define clinicopathological factors influencing patients' prognosis., Methods: A retrospective analysis of an unselected cohort of 105 patients was performed. Overall survival (OS) was estimated by the Kaplan-Meier method and potentially prognostic factors were analyzed in Cox regression models., Results: OS of the whole cohort at 1, 3, and 5 years was 66%, 47%, and 29%, respectively. Tobacco consumption, ECOG >0, macroscopic vascular invasion, continuous tumor diameter, and treatment other than resection were predictors of decreased OS in the whole cohort. Resection was performed in 64% of patients with 1-, 3-, and 5-year OS rates of 84%, 69%, and 42%, respectively. Siderosis and BCLC stage were associated with decreased OS after resection. Recurrence occurred in 57% of patients with 1-, 3-, and 5-year disease-free survival (DFS) rates of 63%, 39%, and 31%, respectively. Viral hepatitis and macroscopic vascular invasion were associated with decreased DFS. One-, 3-, and 5-year OS rates in patients with non-surgical approaches (transarterial chemoembolization, systemic therapy, best supportive care) were 38%, 11%, and 7%, respectively. Tobacco consumption and Okuda stage were associated with decreased OS in these patients., Conclusions: OS and DFS of patients with HCC in non-cirrhotic liver depend most notably on tumor-related, demographic, and etiological factors. Features of the non-neoplastic liver tissue play only a minor role. Liver resection leads to a significantly better prognosis than non-surgical treatment approaches.

Background: Recurrence of hepatocellular carcinoma after orthotopic liver transplantation not amenable to surgical approaches is associated with poor outcome., Aims: Retrospective evaluation of the safety and efficacy of sorafenib in patients with post-transplant hepatocellular carcinoma recurrence., Methods: Patients with post-transplant hepatocellular carcinoma recurrence were treated with sorafenib. Adverse events were assessed using National Cancer Institute Common Toxicity Criteria of AEs version 3.0, tumour response was evaluated according to Response Evaluation Criteria in Solid Tumours., Results: First-line therapy after recurrence was surgery (n=6), radiation therapy (n=1), chemotherapy (n=1), and sorafenib (n=3). Finally, 11 patients were treated with sorafenib. Nine patients (82%) received an additionally targeted therapy with sirolimus as part of their immunosuppressive regimen. Most common grade 3 adverse events included diarrhoea (46%), hand-foot skin reaction (27%), nausea, fatigue, and leucopoenia (all 18%). Sorafenib had to be discontinued in two patients due to adverse events and six additional patients required a dose adjustment. No deterioration of liver graft function occurred. Median time to progression was 4.1 months; however, patients were treated with ongoing sorafenib in case of clinical benefit (median 8.9 months). Median overall survival after initiation of sorafenib treatment was 20.1 months., Conclusion: Sorafenib in combination with immunosuppression including sirolimus may be administered to patients with post-transplant hepatocellular carcinoma recurrence with acceptable toxicity and without deterioration of liver graft function., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC)., Methods: OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs., Results: Real time PCR showed a downregulation of SLC22A1 and SLC22A3 in HCC compared to TST (p ≤ 0.001). A low SLC22A1 expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, SLC22A1 was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low SLC22A1 expression (< median) showed a higher SLC22A3 expression compared to HCC with high SLC22A1 expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the SLC22A3 expression.In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC., Conclusion: The downregulation of OCT1 is associated with tumor progression and a worse patient survival.

Purpose: Prognosis after resection of liver metastases of colorectal cancer is influenced by a variety of clinical factors. For more than 20 years, efforts have been made to restructure and simplify prognostic parameters into clinical scores. We evaluated the influence of various clinical and pathological factors on survival and recurrence and developed a simple model for risk stratification., Methods: We have analyzed a total of 13 prognostic factors in 382 consecutive and prospectively enrolled R0-resected patients and applied our data set to ten published prognostic scoring systems. Prognostic factors that influenced disease-specific and disease-free survival were included into a model clinical risk score., Results: The 5- and 10-year observed survival rates were 43% and 28%, respectively, for all 382 patients. The disease-specific 5- and 10-year survival rates were 49% and 37%, respectively; the 5- and 10-year recurrence rates were 68% and 70%, respectively. For patients with synchronous liver metastases, survival was not affected by the timing of liver resection. The prognosis after treatment of any recurrence was best after the accomplishment of a repeated R0 situation, independent of the location of the recurrence. In the multivariate analysis, the disease-specific survival and recurrence rates were statistically significantly influenced by more than three lymph node metastases of the primary tumor, more than two lesions within the liver, and the presence of extrahepatic tumor., Conclusions: From these data, we have developed a simple score for the risk stratification which may be useful for future studies on interdisciplinary management of colorectal liver metastases.

Background/aims: The use of intraoperative blood salvage autotransfusion (IBSA) during surgical approaches may contribute to tumour cell dissemination. Therefore, IBSA should be avoided in cases of malignancy. However, the risks of IBSA might be acceptable in liver transplantation (LT) for selected small hepatocellular carcinoma (HCC)., Methods: In total, 136 recipients of LT with histologically proven HCC in the explanted liver were included in this analysis. With regard to tumour recurrence, 40 patients receiving IBSA despite HCC (IBSA group) were compared to 96 patients without IBSA (non-IBSA group)., Results: Milan criteria as assessed in the explanted liver were fulfilled in 24 of 40 IBSA patients and 58 of 96 non-IBSA patients (p = 0.85). Five of 40 patients in the IBSA group and 18 of 96 patients in the non-IBSA group experienced tumour recurrence (p = 0.29). In spite the theoretical risk of tumour cell dissemination, the recurrence rate was not increased in the IBSA group., Conclusion: Our results indicate that IBSA does not modify the risk of HCC recurrence. Therefore, in highly selected HCC patients undergoing LT, the use of IBSA appears to be justified., (Copyright © 2011 S. Karger AG, Basel.)

Hepatocellular carcinoma and cholangiocarcinoma are relatively rare tumors of the gastrointestinal tract in western Europe but their incidence has been increased in recent years. Newly diagnosed intrahepatic lesions or intrahepatic cholestasis require extensive laboratory tests and imaging studies in order to confirm the diagnosis of hepatocellular carcinoma, intrahepatic or extrahepatic cholangiocarcinoma. The treatment options range from liver resection or liver transplantation to conservative measures (in cases of non-resectable lesions). This review article aims to provide an overview on the diagnostic options and the subsequent treatment.

Background: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC., Methods/design: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating., Discussion: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC., Trial Register: Trial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36).

Objective: Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery., Summary Background Data: Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment., Methods: According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n=28). Resection (n=82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible., Results: Local recurrence at the site of ablation or resection occurred in 32% and 4% (P<0.001), new metastases apart from the site of previous treatment in 50% and 34% (P=0.179), and systemic recurrence in 32% and 37% (P=0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P=0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P=0.93., Conclusions: Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.

Hepatic resections represent a standard procedure for both benign and malignant liver diseases. Nevertheless, typical complications arise follow-ing hepatic surgery. Besides common problems, such as bile leakage or impaired wound healing, rare complications, like progressive liver failure or portal vein thrombosis are observed. Mortality and morbidity after liver resection depend on the preoperative constitution of the patient, on the state of the liver parenchyma and on the re-main-ing liver volume. In particular, a marked steatosis increases both morbidity and mortality of hepatic resections. The advances of modern chemotherapy increases the number of surgical patients, who were previously not resectable. However, the chemotherapy induced hepatotoxicity implies additional problems, thus increasing the morbidity of liver resections. Therefore, before planning hepatic surgery, the individual situation of the patient has to be evaluated in order to maximise the security of the operative procedure.

Background: Gastric cancer is one of the most frequent malignancies worldwide. More than 50% of all patients present with advanced stage of disease, with long-time survival of less than 5%. In selected subgroups, palliative gastric resection seems to be beneficial for survival and improved quality of the remaining life time, but is still controversially discussed., Patients and Methods: We report 3 cases of patients with intestinal-type advanced gastric cancer. All patients presented preoperatively with stage IV disease with liver metastases. The patients underwent palliative gastric resection and subsequent palliative chemotherapy. We performed a genome-wide DNA analysis of 9 gastric cancer tissue specimens using the DNA microchip array technique., Results: 4 and 6 years after palliative surgery and chemotherapy, 2 of the patients show no signs of recurrence, while the third patient shows stable disease under third-line chemotherapy 4 years after the initial diagnosis. Comparative genetic analysis of 9 gastric cancer tissue specimens suggested that the degree of chromosomal aberration was closely related to survival for intestinal-type gastric cancers., Conclusions: Palliative gastric resection is beneficial for survival and quality of life in selected patients. Determination of the degree of chromosomal aberrations might be helpful in predicting the response on multimodal treatment in intestinal-type gastric cancer. A better understanding of molecular biology is needed to define prognosis markers and molecular targets., (Copyright © 2010 S. Karger AG, Basel.)

Background: Transmission of donor-derived cancer by organ transplantation is rare, but the risk has been increasing due to the aging donor pool. Undifferentiated neuroendocrine small-cell carcinoma is an aggressive tumor with the tendency to spread. Herein we have demonstrated different approaches to treat organ recipients with transmitted tumors., Methods and Results: Grafts were retrieved from a decreased donor without any history of previous diseases. Autopsy was not performed after donation. The recipient of the liver graft presented with suspected nodules on routine abdominal ultrasound. After computed tomography (CT) scan, biopsy confirmed the diagnosis of a small-cell carcinoma. Donor origin was unequivocally identified by DNA fingerprinting. Despite chemotherapy the patient died 7 months after orthotopic liver transplantation (OLT). All involved transplantation centers were informed immediately following diagnosis. The male kidney recipient underwent detailed diagnostic work-up to exclude tumor transmission. One year after transplantation, liver metastases caused by a histologically proven small-cell carcinoma from the same donor were apparent. Chemotherapy was immediately started and the graft was removed. Despite continued treatment the tumor progressed and the patient died after repeated intestinal complications. The pathological examination of the explanted second kidney graft did not show any tumor infiltration., Conclusion: Therapeutic regimens in recipients suffering from donor-derived carcinoma differ depending on the transplanted organ. Graft removal of non-life-sustaining organs and discontinuation of immunosuppressive medication should result in complete tumor rejection. Minimizing the risk of tumor transmission, a CT scan might be advisable in donors of more advanced age.

Tumor recurrence is a major problem after orthotopic liver transplantation (OLT) in patients with hepatocellular carcinoma (HCC). In 60 patients OLT was performed for HCC after pretreatment by repeated transarterial chemoembolization (TACE). Forty-four recipients exceeded the Milan criteria. Recurrence-free 5-year survival was 65.2% and 5-year freedom from recurrence was 73.2%. During the waiting time, 14 patients experienced minimal change, which did not fulfill the definition of tumor progression according to official oncological criteria. Five-year freedom from recurrence among patients with stable compared with progressive disease was 93.3% versus 28.1%, respectively (P = .0001). A strict TACE pretreatment protocol may select patients with obviously biologically less aggressive tumors, who are suitable for OLT even if the HCC exceeds the commonly accepted listing criteria.

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5-year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P < 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n = 39) with progress-free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n = 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P = 0.0017). Progress-free course of TACE during the waiting time (P = 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P = 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number., ((c) 2006 AASLD.)

Selection of patients suffering from hepatocellular carcinoma (HCC) in cirrhosis for liver transplantation is based upon the number and diameter of tumor nodules but not with vascular invasion. From 1989 to 2003, 1619 liver transplantations were performed in 1471 patients, including 163 patients with an HCC in cirrhosis. Selection criteria were a maximal diameter of up to 5 cm when the tumor appeared to be uninodular, or up to 3 cm in the case of two or three nodules and no vascular invasion prior to transplantation. The postoperative mortality rate was 1.7%. One-, 5- and 10-year survivals were 88%, 62%, and 51%, respectively. Among 1307 transplantations without HCC, the rates were 90%, 84%, and 76%, respectively (P < .0001). Multivariate analysis identified histopathological grading and vascular invasion to predict survival. A subgroup analysis showed 5-year survivals of 67% and 57% for well versus moderately differentiated tumors with vascular invasion. Liver transplantation is a safe and effective long-term treatment for small HCC in cirrhosis. Exeptions from the morphometric rules may be justified for patients with HCC in cirrhosis who show well or moderately differentiated tumors with vascular invasion.

Liver resection combined with the resection and reconstruction of the vena cava represents the only potential curative therapy for malignant hepatic tumors with invasion of the vena cava. We performed a liver resection with segmental replacement of the retrohepatic vena cava by synthetic grafts in 29 patients. In three cases, the additional presence of central involvement of all three hepatic veins required ex situ tumor resection. Four patients underwent a simultaneous exstirpation of the primary tumor (kidney or suprarenals). The remaining hepatic veins were reimplanted into the graft in three cases, and in two cases the renal veins were reimplanted. There was no perioperative mortality. A distal arteriovenous fistula was not applied. Five patients revealed postoperative transient liver insufficiency, requiring temporary dialysis in three cases. Two of these patients developed a transient multiorgan failure with the need of mechanical ventilation. 18 patients died during the course of follow-up, 17 of these cases due to recurrent metastases of the primary disease. Infection or thrombosis of the prosthetic vascular graft have not been observed. Beside tumor exstirpation, extended liver resection and concomitant vena cava replacement may prevent embolism as well as the obstruction of the vena cava with lower extremity swelling and the possibility of developing a Budd Chiari syndrome. We were able to achieve a long-term survival for surgically treated patients even in cases with advanced tumor stages.