Surgical therapy of celiac axis and superior mesenteric artery syndrome.

INTRODUCTION: Compression syndromes of the celiac artery (CAS) or superior mesenteric artery (SMAS) are rare conditions that are difficult to diagnose; optimal treatment remains complex, and symptoms often persist after surgery. We aim to review the literature on surgical treatment and postoperative outcome in CAS and SMAS syndrome. METHODS: A systematic literature review of medical literature databases on the surgical treatment of CAS and SMAS syndrome was performed from 2000 to 2022. Articles were included according to PROSPERO guidelines. The primary endpoint was the failure-to-treat rate, defined as persistence of symptoms at first follow-up. RESULTS: Twenty-three studies on CAS (n = 548) and 11 on SMAS (n = 168) undergoing surgery were included. Failure-to-treat rate was 28% for CAS and 21% for SMAS. Intraoperative blood loss was 95 ml (0-217) and 31 ml (21-50), respectively, and conversion rate was 4% in CAS patients and 0% for SMAS. Major postoperative morbidity was 2% for each group, and mortality was described in 0% of CAS and 0.4% of SMAS patients. Median length of stay was 3 days (1-12) for CAS and 5 days (1-10) for SMAS patients. Consequently, 47% of CAS and 5% of SMAS patients underwent subsequent interventions for persisting symptoms. CONCLUSION: Failure of surgical treatment was observed in up to every forth patient with a high rate of subsequent interventions. A thorough preoperative work-up with a careful patient selection is of paramount importance. Nevertheless, the surgical procedure was associated with a beneficial risk profile and can be performed minimally invasive.

Enterothorax After Hepatic Surgery: A Single-Center Experience.

BACKGROUND: Enterothorax (ET) is a rare complication after hepatic surgery. The literature in this field is limited and mainly based on case reports. The aim of this study was to review our department's experience. PATIENTS AND METHODS: We retrospectively analyzed 602 patients who underwent hepatic resection between November 2008 and December 2016. Major hepatic surgery (n = 321) was defined as right or extended right hepatectomy (n = 227), left or extended left hepatectomy (n = 63), trisegmentectomy (n = 13), and living donor liver transplantation (n = 18). ET cases were identified by analyzing clinical courses and radiological imaging. RESULTS: ET was observed in five out of 602 patients (0.8%). All patients developed the complication after major hepatic surgery (five out of 321, 1.6%). ET exclusively occurred after right (n = 3) or extended right hepatectomy (n = 2). Median time to diagnosis was 22 months. Radiological imaging showed herniation of small (n = 2), large bowel (n = 2), or omental fat (n = 1) with a median diaphragmatic defect of 3.9 cm. Two patients presented with acute incarceration and underwent emergency surgery, one patient reported recurrent pain and underwent elective repair, and two patients refused surgery. Follow-up imaging in two operated patients showed no recurrence of ET after 36 and 8 months. CONCLUSIONS: Patients after right hepatectomy have a substantial risk of ET. Acute right upper quadrant pain and/or dyspnea after hepatectomy should be investigated with adequate radiological imaging. Elective surgical repair of ET is recommended to avoid emergency surgery in case of incarceration.

Short Chemotherapy-Free Interval Improves Oncological Outcome in Patients Undergoing Two-Stage Hepatectomy for Colorectal Liver Metastases.

BACKGROUND: In patients undergoing two-stage hepatectomy (TSH) for colorectal liver metastases (CRLM), chemotherapy is discontinued before portal vein occlusion and restarted after curative resection. Long chemotherapy-free intervals (CFI) may lead to tumor progression and poor oncological outcomes. OBJECTIVE: The aim of this study was to investigate the impact of the length of CFI on oncological outcome in patients undergoing TSH for CRLM. PATIENTS AND METHODS: Overall, 74 patients suffering from bilobar CRLM who underwent ALPPS (associating liver partition with portal vein ligation for staged hepatectomy; n = 43) or conventional TSH (n = 31) at two tertiary centers were investigated. The impact of CFI on long-term outcomes was analyzed by univariable and multivariable analysis. RESULTS: Preoperative chemotherapy was administered in 91 % (67/74) of patients, and chemotherapy was resumed postoperatively in 69 % (44/64) of patients who completed TSH. The use of postoperative chemotherapy was significantly associated with improved mean overall survival (36 ± 3 vs. 13 ± 3 months; p < 0.001). Overall, the median CFI from surgery to postoperative chemotherapy was 16 weeks (interquartile range 11-31) and was significantly shorter in the ALPPS group when compared with the conventional TSH group (10 vs. 21 weeks; p < 0.001). Multivariable analysis revealed a CFI ≤ 10 weeks as an independent factor associated with improved overall survival (p = 0.006) and disease-free survival (p = 0.010). CONCLUSION: A short CFI is associated with improved oncological outcome in patients undergoing TSH for CRLM. Decreased interstage intervals after ALPPS may facilitate the timely resumption of chemotherapy.

Epidural analgesia and perioperative kidney function after major liver resection.

BACKGROUND: Epidural analgesia (EDA) is a common analgesia regimen in liver resection, and is accompanied by sympathicolysis, peripheral vasodilatation and hypotension in the context of deliberate intraoperative low central venous pressure. This associated fall in mean arterial pressure may compromise renal blood pressure autoregulation and lead to acute kidney injury (AKI). This study investigated whether EDA is a risk factor for postoperative AKI after liver surgery. METHODS: The incidence of AKI was investigated retrospectively in patients who underwent liver resection with or without EDA between 2002 and 2012. Univariable and multivariable analyses were performed including recognized preoperative and intraoperative predictors of posthepatectomy renal failure. RESULTS: A series of 1153 patients was investigated. AKI occurred in 8·2 per cent of patients and was associated with increased morbidity (71 versus 47·3 per cent; P = 0·003) and mortality (21 versus 0·3 per cent; P < 0·001) rates. The incidence of AKI was significantly higher in the EDA group (10·1 versus 3·7 per cent; P = 0·003). Although there was no significant difference in the incidence of AKI between patients undergoing minor hepatectomy with or without EDA (5·2 versus 2·7 per cent; P = 0·421), a substantial difference in AKI rates occurred in patients undergoing major hepatectomy (13·8 versus 5·0 per cent; P = 0·025). In multivariable analysis, EDA remained an independent risk factor for AKI after hepatectomy (P = 0·040). CONCLUSION: EDA may be a risk factor for postoperative AKI after major hepatectomy.

Liver transplantation in recipients receiving renal replacement therapy: outcomes analysis and the role of intraoperative hemodialysis.

The Model for End-Stage Liver Disease (MELD) system has dramatically increased the number of recipients requiring pretransplant renal replacement therapy (RRT) prior to liver transplantation (LT). Factors affecting post-LT outcomes and the need for intraoperative RRT (IORRT) were analyzed in 500 consecutive recipients receiving pretransplant RRT, including comparisons among recipients not receiving IORRT (No-IORRT, n = 401), receiving planned IORRT (Pl-IORRT, n = 70), and receiving emergent, unplanned RRT after LT initiation (Em-IORRT, n = 29). Despite a median MELD of 39, overall 30-day, 1-, 3- and 5-year survivals were 93%, 75%, 68% and 65%, respectively. Em-IORRT recipients had significantly more intraoperative complications (arrhythmias, postreperfusion syndrome, coagulopathy) compared with both No-IORRT and Pl-IORRT and greater 30-day graft loss (28% vs. 10%, p = 0.004) and need for retransplantation (24% vs. 10%, p = 0.099) compared with No-IORRT. A risk score based on multivariate predictors of IORRT accurately identified recipients with chronic (sensitivity 84%, specificity 72%, concordance-statistic [c-statistic] 0.829) and acute (sensitivity 93%, specificity 61%, c-statistic 0.776) liver failure requiring IORRT. In this largest experience of LT in recipients receiving RRT, we report excellent survival and propose a practical model that accurately identifies recipients who may benefit from IORRT. For this select group, timely initiation of IORRT reduces intraoperative complications and improves posttransplant outcomes.

Major challenges limiting liver transplantation in the United States.

Liver transplantation is the gold standard of care in patients with end-stage liver disease and those with tumors of hepatic origin in the setting of liver dysfunction. From 1988 to 2009, liver transplantation in the United States grew 3.7-fold from 1713 to 6320 transplants annually. The expansion of liver transplantation is chiefly driven by scientific breakthroughs that have extended patient and graft survival well beyond those expected 50 years ago. The success of liver transplantation is now its primary obstacle, as the pool of donor livers fails to keep pace with the growing number of patients added to the national liver transplant waiting list. This review focuses on three major challenges facing liver transplantation in the United States and discusses new areas of investigation that address each issue: (1) the need for an expanded number of useable donor organs, (2) the need for improved therapies to treat recurrent hepatitis C after transplantation and (3) the need for improved detection, risk stratification based upon tumor biology and molecular inhibitors to combat hepatocellular carcinoma.

Systematic review and meta-analysis of interferon after curative treatment of hepatocellular carcinoma in patients with viral hepatitis.

BACKGROUND: A combined antiviral and tumoricidal effect of interferon (IFN) is assumed to occur after resection or ablation of hepatocellular carcinoma (HCC). METHODS: An electronic search of the Medline, Embase and Central databases from January 1998 to October 2007 was conducted to identify randomized controlled trials evaluating adjuvant effects of IFN after curative treatment of HCC. A meta-analysis was performed to estimate the effects of IFN on 2-year outcome. RESULTS: Seven trials enrolling a total of 620 patients were included in the meta-analysis. Adjuvant treatment with IFN significantly reduced the 2-year mortality rate after curative treatment of HCC, with a pooled risk ratio of 0.65 (95 per cent confidence interval 0.52 to 0.80); P < 0.001) in absence of any significant heterogeneity (I(2) = 0 per cent, P = 0.823 for chi(2)). The effect on reduction of tumour recurrence was less pronounced but still significant (pooled risk ratio 0.86 (95 per cent c.i. 0.76 to 0.97); P = 0.013). IFN had to be discontinued in 8-20 per cent of patients. CONCLUSION: IFN has a significant beneficial effect after curative treatment of HCC in terms of both survival and tumour recurrence.

Use of phosphorous-31 nuclear magnetic resonance spectroscopy to determine safe timing of chemotherapy after hepatic resection.

Liver resection induces accelerated growth of residual hepatic micrometastases. Adjuvant chemotherapy may improve outcome if administered early after resection but may prove lethal if initiated prior to completion of DNA synthesis in regenerating liver. This study investigates phosphorus-31 nuclear magnetic resonance ((31)P-NMR) as a noninvasive tool for measuring energy changes reflective of hepatic DNA synthesis and for predicting safe timing of chemotherapy after 70% hepatectomy. To evaluate metabolic changes in regenerating liver, quantitative three-dimensional (31)P-NMR was performed, using the technique of chemical shift imaging at various time points after 70% hepatectomy in adult male Fischer rats. Animals receiving a course of 2'-deoxy-5-fluorouridine (FUDR; 100 mg/kg, i.p. four times per day x 5), initiated at the time of operation, were also evaluated to observe the effects of chemotherapy on liver regeneration. Forty-eight hours after resection, hepatic nucleoside triphosphate (NTP), which reflects ATP content, fell 37% (P < 0.03) in animals undergoing hepatectomy alone. By contrast, animals receiving FUDR after hepatectomy demonstrated a mitigated NTP response, with a drop of only 17% (P = not significant), suggesting that interruption of DNA synthesis leads to a reduced consumption of ATP. Direct measures of DNA synthesis and nuclear proliferation were correlated with NMR findings. [(3)H]Thymidine incorporation and Ki67 immunohistochemistry were performed on liver samples from rats undergoing 70% hepatectomy with and without FUDR. Both [(3)H]thymidine incorporation and Ki67 expression were inhibited significantly at 48 h in animals receiving hepatectomy and FUDR, compared with those not treated with FUDR. To determine whether NMR changes could be used to identify safe timing of chemotherapy after hepatectomy, rats were treated with a 5-day course of FUDR initiated either prior to or after NMR changes normalized. Animals treated with FUDR at the point of NTP normalization (72 h) showed significantly improved survival over those that began treatment at operation (75 % versus 17 %; P = 0.0005, log rank test). FUDR inhibits hepatic DNA synthesis and influences mortality if administered too early after hepatectomy. Chemical shift imaging is a noninvasive tool that can identify metabolic changes coinciding with DNA synthesis and nuclear proliferation after hepatectomy. (31)P-NMR may be useful for determining safe timing of chemotherapy after liver resection.

Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability.

Gastric cancer is highly refractory to DNA-damaging therapies. We therefore studied both gene mutation and protein expression of p53 and Bax in a cohort of 116 patients with gastric cancer who underwent R0-resection with a curative intent. Bax mutation was independent from severe microsatellite instability (MSI), that is, global mismatch repair deficiency as determined by analysis of BAT-25/BAT-26 microsatellite markers. Thus, Bax-frameshift mutation is a feature of tumors with low MSI. In contrast and as expected, no p53 mutations were observed in the microsatellite instable tumors. p53 Mutation or p53 overexpression did not have an impact on disease prognosis. p53-Inactivation was, however, associated with an extremely poor prognosis in the subgroup of patients with Bax-mutated tumors. Thus, we show for the first time that the combined mutation of p53 and Bax, two key regulators of the mitochondrial apoptosis pathway, results in an extremely aggressive tumor biology and poor clinical prognosis.

Analysis of the p53/BAX pathway in colorectal cancer: low BAX is a negative prognostic factor in patients with resected liver metastases.

PURPOSE: To determine the prognostic value of the central downstream apoptosis effector BAX in relation to its upstream regulator p53 in R0-resected hepatic metastases of colorectal cancer. PATIENTS AND METHODS: Retrospective analysis of 41 patients who underwent potentially curative resection of liver metastases from colarectal cancer was performed. Tumor DNA was screened for p53 mutations by single-stranded conformational polymorphism polymerase chain reaction and for BAX frameshift mutations by fragment length analysis. Protein expression of BAX, p21, and p53 was investigated by immunohistochemistry. RESULTS: Overall median survival was 40.2 months. Tumors with BAX frameshift mutations were considered microsatellite mutator phenotype-positive and were excluded from further prognostic analyses. Patients with high BAX protein expression had a median survival of 53.6 months compared with 35.4 months for patients with low BAX expression (P < .05). The negative prognostic value of low BAX expression was more evident in those patients with wild-type p53 (median survival, 54.0 v 23.3 months for BAX-negative tumors; P < .01). Low BAX expression was an independent negative prognostic marker in multivariate regression analysis for all patients independent of the p53 status (relative risk, 3.03, P = .03), especially for p53 wild-type tumors (relative risk, 8.21; P = .0095). CONCLUSION: We conclude that low BAX expression is an independent negative prognostic marker in patients with hepatic metastases of colorectal cancer. The best survival was seen in patients with an intact p53-to-BAX pathway; ie, wild-type p53- and BAX-positive tumors. Thus, analysis of apoptosis signaling pathways (here, p53 in concert with its downstream death effector, BAX) might yield more prognostic power in future studies as compared with analysis of single genes such as p53 alone.

Analysis of p53/BAX/p16(ink4a/CDKN2) in esophageal squamous cell carcinoma: high BAX and p16(ink4a/CDKN2) identifies patients with good prognosis.

PURPOSE: We have previously shown that loss of BAX expression is a negative prognostic factor in metastatic colorectal cancer. In the present study, we addressed the prognostic relevance of BAX and its upstream regulator p53 in squamous cell carcinoma (SCC) of the esophagus. Analysis of p16(ink4a/CDKN2) was included because p16(ink4a/CDKN2) and p53 were shown previously to cooperate during induction of cell cycle arrest and apoptosis. PATIENTS AND METHODS: Retrospective analysis of 53 patients with curative intended R0 resection of esophageal SCC was done. Protein expression of BAX, p53, and p16(ink4a/CDKN2) was investigated by immunohistochemistry. In addition, tumor DNA was screened for BAX frameshift mutations by fragment length analysis and for p53 mutations by single-strand conformation polymorphism-polymerase chain reaction. RESULTS: Overall median survival was 13.7 months. Patients with high BAX protein expression had a median survival of 19.5 months versus 8.0 months with low BAX expression (P <.005). High p16(ink4a/CDKN2) protein expression was associated with a median survival of 23.8 months versus 9.7 months with low p16(ink4a/CDKN2) (P =.011). The best survival (median, 45.8 months) was seen in a subgroup of 12 patients whose tumors bore the combination of both favorite phenotypes (ie, high BAX and high p16(ink4a/CDKN2) protein expression). CONCLUSION: In this retrospective investigation, the combined analysis of BAX and p16(ink4a/CDKN2) shows subgroups in SCC of the esophagus with favorable (p16(ink4a/CDKN2)/BAX high expressing) or poor prognosis (loss of p16(ink4a/CDKN2)/loss of BAX). We suggest that such a multimarker analysis of apoptosis pathways could be useful for individualization of therapeutic strategies in the future, and suggest prospective studies to confirm these results.

Effects of preexisting immunity on the response to herpes simplex-based oncolytic viral therapy.

Herpes simplex viruses (HSV) type 1 are the basis of a number of anticancer strategies that have proven efficacious in animal models. They are natural human pathogens and the majority of adults have anti-HSV immunity. The current study examined the effect of preexisting immunity on the response to herpes-based oncolytic viral treatment of hepatic metastatic cancer in a murine model designed to simulate a clinical approach likely to be utilized for nonneurological tumors. Specifically, the anticancer effects of NV1020 or G207, two multimutated HSV-1 oncolytic viruses, were tested in immunocompetent mice previously immunized with a wild-type herpes simplex type 1 virus. Mice were documented to have humoral as well as cell-mediated immunity to HSV-1. Tumor response to oncolytic therapy was not measurably abrogated by immunity to HSV at the doses tested. The influence of route of viral administration was also tested in models of regional hepatic arterial and intravenous therapy. Route of viral administration influenced efficacy, as virus delivered intravenously produced some detectable attenuation while hepatic arterial therapy remained unaffected. These results demonstrate that when given at appropriate doses and in reasonable proximity to tumor targets, HSV-based oncolytic therapy can still be expected to be effective treatment for patients with hepatic malignancies.

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer.

AIMS: Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS: IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. RESULTS: Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusate's PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). CONCLUSIONS: The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

Relevance of Ki-67 antigen expression and K-ras mutation in colorectal liver metastases.

AIMS: The liver is a frequent site of metastases from colorectal cancer. While these lesions are potentially amenable to surgical resection, they are usually very aggressive, and recurrence is frequent. Mutations of the proto-oncogene K- ras are thought to impart a strong growth signal to tumour cells and are closely associated with the development of malignancies of the colon and rectum. Hepatic metastases from colorectal cancer have notably elevated proliferative rates. The present study was performed to investigate the relationship between proliferation or K- ras mutation and prognosis following curative resection of colorectal liver metastases. METHODS: Colorectal liver metastases from 41 patients undergoing curative hepatic resection were examined for proliferation status and presence of K- ras mutations. The proliferative activity was assessed by Ki-67 immunohistochemistry. DNA from the same tissue samples was screened for point mutations in codon 12 of the K- ras gene using a novel microplate-based allelic-specific hybridization assay. Ki-67 scores and K- ras status were then related with patient survival as determined through retrospective analysis. RESULTS: Median survival was 40 months. Patients with high Ki-67 scores (> or = 50%) had significantly shorter median survival compared with those with low scores (30 vs 44 months, log-rank P=0.02). A high Ki-67 score was an independent negative prognostic factor by multivariate regression analysis (relative risk=3.04, P=0.036). K- ras point mutations were detected in 6/41 patients (15%), but mutational status did not correlate with Ki-67 score or survival. CONCLUSIONS: These findings suggest that the tumour proliferative index is a useful predictor of aggressive tumour behaviour and an indicator of patient survival. The presence of K- ras mutations does not appear to correlate with tumour proliferation status or patient survival.

Effect of fibrin glue occlusion of the hepatobiliary tract on thioacetamide-induced liver failure.

BACKGROUND: Expression and activation of hepatocyte growth factor (HGF) is stimulated by a complex system of interacting proteins, with thrombin playing an initial role in this process. The impact of temporary occlusion of the hepatobiliary tract with fibrin glue (major component thrombin) on the HGF system in acute and chronic liver damage in a rat model was investigated. METHODS: Chronic liver damage was induced in 40 rats by daily intraperitoneal application of thioacetamide (100 mg/kg) for 14 days. After 7 days half of them received an injection of 0.2 mL fibrin glue into the hepatobiliary system. Daily intraperitoneal administration of thioacetamide continued for 7 consecutive days. The rats were then sacrificed for blood and tissue analysis. Acute liver failure was induced in 12 rats by intraperitoneal administration of a lethal dose of thioacetamide (500 mg/kg per day for 3 days) after an injection with 0.2 mL fibrin glue into their hepatobiliary tract. Survival rates and histological outcome were investigated and compared with control animals. RESULTS: Fibrin glue occluded rats showed significantly lower liver enzyme activities and serum levels of bilirubin, creatinine and urea nitrogen. Immunohistochemistry revealed a significant increase in c-met-, HGFalpha- and especially HGFbeta-positive cells. Rats subjected to a lethal dose of thioacetamide survived when fibrin glue was applied 24 hours prior to the toxic challenge. These animals showed normal liver structure and no clinical abnormalities. CONCLUSION: Fibrin glue occlusion of the hepatobiliary tract induces therapeutic and prophylactic effects on chronic and acute liver failure by stimulating the HGF system. Therefore, fibrin glue occlusion might be useful in treating toxic liver failure.

An improved model for rat liver transplantation including arterial reconstruction and simplified microvascular suture techniques.

For experimental liver transplantation in the rat, the models that have been used most frequently do not include reconstruction of the arterial blood supply to the liver. In these procedures, specially developed cuff anastomoses rather than the conventional microvascular suture technique are used almost exclusively in the recipient operation, so that the anhepatic time is minimized. In this study the technical details of an improved rat model for orthotopic liver transplantation are described. During the donor operation in this experimental method, the liver is prepared with an arterial pedicle that includes the abdominal segment of the aorta, permitting perfusion in situ of the portal vein as well as the hepatic artery. The transplantation of the excised donor organ into the recipient site is carried out with simplified microvascular suture techniques and includes reconstruction of the arterial supply to the liver. Anastomosis of the bile duct is accomplished by choledocho-choledochostomy with a splint technique and supplemental suturing. For the entire procedure, magnifying glasses with 2- to 2.5-fold magnification are sufficient. When this technique has been mastered, the average duration of the anhepatic phase is about 20 min, well below the critical 30-min limit for survival of the experimental animals. As proficiency increased, the perioperative mortality was reduced to 9.2% (n = 130). With the combination of portal and arterial in situ flushing during the donor operation and the rearterialization of the transplant during the recipient operation, the clinical conditions can be approximated more closely than is possible when the transplanted rat liver is supplied only by the portal vein. Use of microvascular suture techniques, without cuff anastomoses, reduces the need for ex situ handling of the donor organ.

[The status of regional long-term chemotherapy in liver metastasis]. / Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen.

In numerous tumors, metastasis can be limited to the liver. In non-resectable patients, regional treatment modalities, especially arterial cytostatic infusion, are favored in contrast to systemic chemotherapy, whereas intraportal or intraperitoneal application is not successful. Improved results with high response rates have been reported after development of intra-arterial (i.a.) long-term regimens with FUdR in patients with colorectal liver metastases using implantable pumps and ports. However, a survival benefit could only be demonstrated in comparison with a control group only treated symptomatically. Because of several reports on major local toxicity of i.a. FUdR treatment (i.e. chemical hepatitis and biliary sclerosis) several other effective i.a. 5-FU regimens have been developed. A randomized study has demonstrated superiority of i.a. 5-FU versus i.a. FUdR. In comparison with systemic treatment, superiority has only been demonstrated in patients with an intrahepatic tumor burden of < 25%. Publications about regional treatment of patients with breast, gastric cancer or carcinoid liver metastases are rare. Despite the high response rates reported, the benefit of arterial chemotherapy remains questionable. Overall, local long-term chemotherapy cannot be recommended outside of studies as a primary treatment. However, extensive experience and new drugs support the idea of conducting further regional studies.

Current surgical management of hilar and intrahepatic cholangiocarcinoma: the role of resection and orthotopic liver transplantation.

Cholangiocarcinoma (CCA) is a rare but devastating malignancy that presents late, is notoriously difficult to diagnose, and is associated with a high mortality. Surgical resection is the only chance for cure or long-term survival. The treatment of CCA has remained challenging because of the lack of effective adjuvant therapy, aggressive nature of the disease, and critical location of the tumor in close proximity to vital structures such as the hepatic artery and the portal vein. Moreover, the operative approach is dictated by the location of the tumor and the presence of underlying liver disease. During the past 4 decades, the operative management of CCA has evolved from a treatment modality that primarily aimed at palliation to curative intent with an aggressive surgical approach to R0 resection and total hepatectomy followed by orthotopic liver transplantation.