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.

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.

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.

Successful outcome of severe adenovirus hepatitis of the allograft following liver transplantation.

Here we report the first adult patient who survived severe adenoviral hepatitis of a liver graft, in contrast to 4 previously reported cases in adults, all of which had a fatal outcome. Early diagnosis was based on the immunohistological detection of adenoviral protein in the context of biopsy-proven hepatitis. Dramatic reduction of immunosuppression along with supportive care were the treatment strategies in this case. Adenoviral infection of the allograft should always be considered as a differential diagnosis when clinical signs of severe hepatitis are present after liver transplantation. Accurate diagnosis with immunohistochemical detection of viral proteins in the liver graft is of paramount importance for the early diagnosis and management of this uncommon, severe, and probably underdiagnosed entity.

How useful is PET/CT imaging in the management of post-transplant lymphoproliferative disease after liver transplantation?

Post-transplant lymphoproliferative disease (PTLD) is a serious and potentially life-threatening complication after solid organ transplantation. Here, we report our first experience with the use of PET/CT (positron emission tomography combined with computed tomogram) for the management of patients with PTLD after liver transplantation. Four patients with histologically proven PTLD were analyzed. Conventional work-up included physical examination and head-to-pelvis CT. PET/CT was used in one patient for initial staging and in all patients for follow-up. PET/CT positive findings underwent biopsy. Information provided by PET/CT resulted in a change of medical management in three of the four patients. Conventional work-up missed residual disease after surgery in one and failed to detect a tumor relapse in another patient. However, one patient disclosed a false positive PET/CT finding in the lungs. In conclusion, PET/CT may be a useful tool for staging and therapy monitoring of PTLD after liver transplantation.

[Surgical therapy of colorectal liver metastases]. / Metastasentherapie: Resektion von kolorektalen Lebermetastasen.

The liver is the most common organ of distant colorectal metastases. Liver resection currently represents the best and only potentially curative treatment for metastatic colorectal cancer isolated to the liver. Five-year survival rates of 30 to 40% are reported after curative liver resection. Unfortunately, only 10 to 20% of patients with liver metastases without extraheaptic disease are amenable to surgical resection. Novel therapy strategies to improve respectability such as neoadjuvant chemotherapy, portal vein embolisation or ligature, resection combined with ablation and two-stage hepatectomy are currently evaluated. The overall goal of these treatments is to increase the proportion of patients with isolated colorectal liver metastases that can undergo curative resection. Despite curative resection, 60 to 70% of patients will develop recurrent disease. In case of isolated recurrence to the liver that is resectable, repeat liver resection is the treatment of choice. Adjuvant chemotherapy is directed to reduce the risk of recurrence after resection. Despite few encouraging randomised trials on adjuvant chemotherapy, there are no definitive recommendations for adjuvant chemotherapy.

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.

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.

Functional interaction between fluorodeoxyuridine-induced cellular alterations and replication of a ribonucleotide reductase-negative herpes simplex virus.

G207 is an oncolytic herpes simplex virus (HSV) which is attenuated by inactivation of viral ribonucleotide reductase (RR) and deletion of both gamma(1)34.5 genes. The cellular counterparts that can functionally substitute for viral RR and the carboxyl-terminal domain of ICP34.5 are cellular RR and the corresponding homologous domain of the growth arrest and DNA damage protein 34 (GADD34), respectively. Because the thymidylate synthetase (TS) inhibitor fluorodeoxyuridine (FUdR) can alter expression of cellular RR and GADD34, we examined the effect of FUdR on G207 bioactivity with the hypothesis that FUdR-induced cellular changes will alter viral proliferation and cytotoxicity. Replication of wild-type HSV-1 was impaired in the presence of 10 nM FUdR, whereas G207 demonstrated increased replication under the same conditions. Combined use of FUdR and G207 resulted in synergistic cytotoxicity. FUdR exposure caused elevation of RR activity at 10 and 100 nM, whereas GADD34 was induced only at 100 nM. The effect of enhanced viral replication by FUdR was suppressed by hydroxyurea, a known inhibitor of RR. These results demonstrate that the growth advantage of G207 in FUdR-treated cells is primarily based on an RR-dependent mechanism. Although our findings show that TS inhibition impairs viral replication, the FUdR-induced RR elevation may overcome this disadvantage, resulting in enhanced replication of G207. These data provide the cellular basis for the combined use of RR-negative HSV mutants and TS inhibitors in the treatment of cancer.

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.

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.

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.

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.

Relevance of locoregional chemotherapy in patients with liver metastases from colorectal primaries.

Progression of colorectal cancer can occur primarily isolated in the liver. But, only the minority of the affected patients is eligible for surgery. Initially, systemic chemotherapy was ineffective in the treatment of unresectable hepatic metastases. For this reason, intraarterial chemotherapy was introduced as treatment alternative to the systemic chemotherapy. Long-term intraarterial chemotherapy regimens with FUDR in patients with colorectal liver metastases, using implantable pumps and ports, resulted in improved response rates, which was confirmed by several randomized trials. However, an improvement in median survival has not yet been demonstrated after regional chemotherapy of hepatic metastases. Since the intraarterial therapy with floxuridine (FUDR) had been reported to result in a high rate of local toxicity, 5-fluorouracil (5-FU) was introduced into regional chemotherapy of the liver. A randomized trial demonstrated superiority of intraarterial 5-FU versus intraarterial FUDR therapy. Despite these reports about high response rates, the benefit of intraarterial chemotherapy remains questionable, because it has not yet resulted in a prolongation of median survival. For this reason, long-term regional chemotherapy cannot be considered as standard treatment and should therefore not be conducted outside controlled clinical trials. Further evaluations on this technique should only be performed in experienced centers.