Selective hypertrophy of the lobus caudatus as a novel approach enabling extended right hepatectomy in the presence of a non-perfused left lateral liver lobe.

INTRODUCTION: Portal vein embolization (PVE) is a well-established technique to enhance functional hepatic reserves of segments II and III before curative extended right hepatectomy for tumors of the right liver lobe. However, an adequate hepatopetal flow of the left lateral portal vein branches is required for a sufficient PVE-associated hypertrophy. CASE REPORT: Here, we report a 65-year old patient suffering from a locally advanced intrahepatic cholangiocarcinoma in the right liver lobe and segment IV. A curative extended right hepatectomy after preoperative PVE of liver segments IV-VIII was initially impossible because of partial thrombosis of the left lateral portal vein branches resulting in an ischemic-type atrophy of segments II and III. However, due to a massive hypertrophy of the caudate lobe following PVE of liver segments IV-VIII, subsequent extended right hepatectomy with intraoperative thrombectomy of segments II and III was made possible. CONCLUSIONS: To our knowledge this is the first case in which an extended right hepatectomy for a liver malignancy, in the presence of atrophic left lateral section, was made possible by a massive PVE-associated hypertrophy of the caudate lobe.

Alveolar echinococcosis-spreading disease challenging clinicians: a case report and literature review.

Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging.

Horseshoe kidney for transplantation: technical considerations.

Owing to the ongoing shortage of cadaver organs, kidneys with an atypical anatomy such as horseshoe kidneys must be considered for transplantation. Owing to its low prevalence, experience with the transplantation of a horseshoe kidney is very limited. This article reports on the transplantation of a horseshoe kidney to a 58-year-old man with renal failure from chronic glomerulonephritis. Because of a relatively thick isthmus, which indicated a complex urinary collecting and intrarenal vessel system, the kidney was transplanted en bloc. Together with optimal placement of the kidney, only adequate length and positioning of the vessels, especially the venous drainage, could prevent postoperative complications such as kinking of the vessels and thrombosis. These problems could be solved by cutting the renal veins without using a vena cava patch. Careful positioning of the kidney within the intraperitoneal cavity is also necessary. The decision to transplant the kidney en bloc or after separation depends on many factors and should be made individually.

Experience Since MELD Implementation: How Does the New System Deliver?

Because of increasing waiting-list mortality, the MELD (Model for End-Stage Liver Disease) allocation system was implemented within most countries of the Eurotransplant area on December 16, 2006. Five years have now passed, and we review in this paper the effects of the MELD-based allocation upon the waiting list for liver transplantation, on peri-operative management and on postoperative outcome. Giving priority to sicker patients on the waiting list has resulted in a significant increase in mean MELD score at the time of organ allocation. Consequently, there has also been a significant reduction in waiting-list mortality. However, in Germany a worsening in postoperative outcome, mainly in the group of high-MELD recipients (≥30 points), has been reported. This paper presents comprehensive results following liver transplantation within the MELD era. Especially for the group of high-risk recipients, risk factors for impaired survival are presented and discussed.

Clinical outcome of patients with advanced ovarian cancer after resection of liver metastases.

AIM: Hepatic resection has become the standard treatment for patients with primary or metastatic liver malignancies. The aim of our study was to evaluate the clinical outcome of hepatic resection in patients with advanced ovarian cancer (AOC). PATIENTS AND METHODS: All patients undergoing hepatic resection for AOC in our institution between 11/1991 and 02/2007 were evaluated by a validated intraoperative documentation tool. RESULTS: Seventy patients were evaluated (median age=59 years; range=29-76 years). Forty-one (58.6%) patients underwent liver resection; 29 patients had unresectable disease. Additional multivisceral procedures performed were: colic resection (51.4%), small bowel resection (32.9%), gastric resection (5.7%), pancreatic resection (4.3%), splenectomy (5.7%). The median survival of patients with R0 resection was 42 months (95% confidence interval (CI)=17-66 months), 4 months for R1, 6 months (95% CI=0-11 months) for R2, and 5 months (95% CI=0-9 months) for those without liver resection. In multivariate analysis, postoperative residual tumor mass was the strongest predictor of survival. CONCLUSION: Our data indicate that complete macroscopical tumor resection remains the strongest predictor of survival in patients with liver metastases from AOC.

Successful liver transplantation with continued dual antiplatelet therapy.

BACKGROUND: Liver transplantation in patients with dual antiplatelet therapy is considered high-risk procedure due to possible bleeding complications. However, withdrawal of antiplatelet therapy can lead to major adverse cardiac events such as stent thrombosis and even fatal myocardial infarction. CASE REPORT: We report on a 61-year-old male patient with nutritive toxic liver cirrhosis who underwent liver transplantation at our hospital in March 2010. Following two strokes he received secondary prophylaxis with aspirin and clopidogrel, which was continued at time of liver transplantation. The transplantation was performed successfully without withdrawal of the antiplatelet therapy. No cardiac event and no major bleeding complication occurred. CONCLUSIONS: This is, to our knowledge, the first report of a liver transplantation under dual antiplatelet therapy with aspirin and clopidogrel. It shows that even major procedures such as liver transplantation, with its associated high risk of surgical bleeding, can be safely performed with an appropriate risk.

Oncological superiority of hilar en bloc resection for the treatment of hilar cholangiocarcinoma.

PURPOSE: Long-term results after liver resection for hilar cholangiocarcinoma are still not satisfactory. Previously, we described a survival advantage of patients who undergo combined right trisectionectomy and portal vein resection, a procedure termed "hilar en bloc resection." The present study was conducted to analyze its oncological effectiveness compared to conventional hepatectomy. PATIENTS: During hilar en bloc resection, the extrahepatic bile ducts were resected en bloc with the portal vein bifurcation, the right hepatic artery, and liver segments 1 and 4 to 8. With this "no-touch" technique, preparation of the hilar vessels in the vicinity of the tumor was avoided. The long-term outcome of 50 consecutive patients who underwent curative (R0) hilar en bloc resection between 1990 and 2004 was compared to that of 50 consecutive patients who received curative conventional major hepatectomy for hilar cholangiocarcinoma (perioperative deaths excluded). RESULTS: The 1-, 3-, and 5-year survival rates after hilar en bloc resection were 87%, 70%, and 58%, respectively, which was significantly higher than after conventional major hepatectomy. In the latter group, 1-, 3-, and 5-year survival rates were 79%, 40%, and 29%, respectively (P = 0.021). Tumor characteristics were comparable in both groups. A high number of pT3 and pT4 tumors and patients with positive regional lymph nodes were present in both groups. Multivariate analysis identified hilar en bloc resection as an independent prognostic factor for long-term survival (P = 0.036). CONCLUSIONS: In patients with central bile duct carcinomas, hilar en bloc resection is oncologically superior to conventional major hepatectomy, providing a chance of long-term survival even in advanced tumors.

Renal autotransplantation--a possibility in the treatment of complex renal vascular diseases and ureteric injuries.

BACKGROUND: We report our contemporary experiences with renal autotransplantation in patients with complicated renal vascular diseases and/or complex ureteral injuries. Since its first performance, renal autotransplantation has been steadily improved and become a safe and effective procedure. MATERIAL/METHODS: Between 1998 and 2006, 6 renal autotransplantations in 6 patients were performed at the University Medical Center of Leipzig. After nephrectomy and renal perfusion ex vivo, the kidney was implanted standardized in the fossa iliaca. The vessels were anastomized to the iliac vessels, the ureter was reimplanted in an extravesical tunneled ureteroneocystostomy technique according to Lich-Gregoir. Demographic, clinical, and laboratory data of the patients were collected and analyzed for pre-, intra-, and postoperative period. RESULTS: Indications for renal autotransplantation were complex renovascular diseases in 2 patients (1 with fibromuscular dysplasia and 1 with Takayasu's arteritis) and in 4 patients with complex ureteral injuries. The median duration of follow-up was 9.7 years (range: 5.6-13.3). The laboratory values of our 6 patients showed improvements of creatinine, urea and blood pressure levels in comparison to the preoperative status at the end of follow-up period. CONCLUSIONS: The present study reports excellent results of renal autotransplantation in patients with renovascular disease or complex ureteric injuries. After a median follow-up of 9.7 years all 6 patients present with stable renal function as well as normal blood pressure values. Postoperative complications were observed with a rate comparable to other studies.

Impact of microvessel density on lymph node metastasis and survival after curative resection of pancreatic cancer.

PURPOSE: The roles of angiogenesis and the most prominent angiogenic vascular endothelial growth factor (VEGF) in diseases of the pancreas remain controversial. We compared microvessel density (MVD) and VEGF status in normal pancreatic, chronic pancreatic, and pancreatic cancer (PC) tissues to establish their prognostic relevance. METHODS: Eighty samples of PC tissue, 32 samples of normal pancreatic tissue, and 20 samples of chronic pancreatitis (cP) tissue were immunostained with monoclonal anti-CD31 and polyclonal anti-VEGF antibody. The MVD was correlated with clinicopathological features and survival. RESULTS: Microvessel density was higher in PC than in cP (P < 0.001). Residual tumor status was highly predictive for survival (P < 0.001). After stratification for residual tumor status, we identified lymph node metastasis (LNM) in more than two lymph nodes (P < 0.04) and high MVD (P < 0.03) as risk factors for mortality. Multivariate analysis revealed only a high MVD (P = 0.03, odds ratio 0.441, 95% confidence interval 0.211-0.821) as an independent predictor of poor survival. Vascular endothelial growth factor was found over stromal cells in cP and over ductal adenocarcinoma cells in PC. Vascular endothelial growth factor expression status was not predictive of survival (P < 0.07). CONCLUSION: This study confirms the role of angiogenesis in PC and identifies MVD as an independent prognostic factor in patients with curatively resected PC.

Impact of the MELD allocation after its implementation in liver transplantation.

OBJECTIVE: On 16 December 2006, most Eurotransplant countries changed waiting time oriented liver allocation policy to the urgency oriented Model for End-stage Liver Disease (MELD) system. There are limited data on the effects of this policy change within the Eurotransplant community. PATIENTS AND METHODS: A total of 154 patients who had undergone deceased donor liver transplantation (LT) were retrospectively analyzed in three time periods: period A (1-year pre-MELD, n = 42) versus period B (1-year post-MELD, n = 52) versus period C (2 years after MELD implementation, n = 60). RESULTS: The median MELD score at the time of LT increased from 16.3 points in period A to 22.4 and 20.4 in periods B and C, respectively (p = 0.007). Waitlist mortality decreased from 18.4% in period A to 10.4% and 9.4% in periods B and C, respectively (p = 0.015). Three-month mortality did not change significantly (10% each for periods A, B and C). One-year survival was 84% for the MELD 6-19 group compared with 81% in the MELD 20-29 group and 74% in the MELD ≥30 group (p = 0.823). Analyzing MELD score and previously described prognostic scores [i.e. survival after liver transplantation (SALT) score and donor-MELD (D-MELD) score] with regard to 1-year survival, only a high risk SALT score was predictive (p = 0.038). In our center, 2 years after implementation of the MELD system, waitlist mortality decreased, while 90-day mortality did not change significantly. CONCLUSION: Up to now, only the SALT score proved to be of prognostic relevance post-transplant.

Balanced management of hepatic trauma is associated with low liver-related mortality.

BACKGROUND: Hepatic trauma is a rare surgical emergency with significant morbidity and mortality. Therapeutic strategies have been controversially discussed during the last decades. METHODS: The medical records of 47 consecutive patients with hepatic trauma treated at the University Hospital of Leipzig between 2004 and 2008 were retrospectively reviewed for the severity of liver injury, management, morbidity, and mortality and compared to a preceding cohort. Logistic regression analysis was performed to identify risk factors influencing mortality. RESULTS: Compared to 63 patients treated between 1993 and 2003, moderate liver injuries (grades I-III) occurred more frequently (p = 0.0006), and the proportion of patients that were managed operatively decreased from 68.9% to 37.5%. Twenty patients (42.6%) were treated conservatively (all grades I to III) and 27 surgically (47.4%). In detail, five patients were treated by hepatic packing alone, 13 by suture or coagulation, five by atypical resection, and four by hemihepatectomy. The overall mortality was 8.5% with a liver-related mortality rate of 2.1%. According to severity grades I-III, IV, and V, mortality rates were 0%, 18.2%, and 50.0%, respectively. Univariate analysis identified Injury Severity Score (ISS) >30, Moore grades IV and V, hemoglobin at admission <6.0 mmol/L, and need for transfusion of >12 erythrocyte concentrates to be significant risk factors for early posttraumatic death, while multivariate analysis only ISS >30 revealed to be of prognostic significance for early postoperative survival. CONCLUSION: Compared to a previous cohort in the same hospital, more patients were treated conservatively. Management of liver injuries presented with a low liver-related mortality rate. Grades I-III injuries can safely be treated by conservative means with excellent results. However, complex hepatic injuries may often require surgical treatment ranging from packing to complex hemihepatectomy. Hence, for selection of appropriate therapeutic options, patients with hepatic injuries should be treated in a specialized institution.

Tumor-associated angiogenesis and lymphangiogenesis correlate with progression of intrahepatic cholangiocarcinoma.

OBJECTIVES: Little is known about the function of tumor-associated neovascularization in the progression of intrahepatic cholangiocarcinoma (IHC). This study was conducted to evaluate the influence of tumor-associated angiogenesis and lymphangiogenesis on progression of IHC. METHODS: We analyzed tissue specimens of IHC (N=114) by immunohistochemistry using the endothelial-specific antibody CD31 and the lymphendothelial-specific antibody D2-40 and subsequently quantified microvessel density (MVD) and lymphatic microvessel density (LVD). To analyze the influence of tumor-associated angiogenesis and lymphangiogenesis on tumor progression, tumors were allocated according to mean MVD and LVD, respectively, into groups of "high" and "low" MVD and LVD, respectively, and various clinicopathological characteristics as well as recurrence and survival data were analyzed. RESULTS: IHC revealed an induction of tumor-associated angiogenesis and lymphangiogenesis. Tumors of "high" MVD displayed more frequently advanced primary tumor stages and multiple tumor nodes. Furthermore, patients with tumors of "high" MVD had an inferior curative resection rate and suffered more frequently from recurrence. A "high" LVD was correlated with increased nodal spread, and patients with "high" LVD tumors more frequently developed recurrence. In the univariate analysis, MVD and LVD revealed significant influence on survival, and MVD was identified as an independent prognostic factor for survival in the multivariate analysis. The 5-year survival of patients with "low" MVD tumors was 42.1%, compared with 2.2% in patients with "high" MVD tumors (P<0.001). CONCLUSIONS: This study suggests a critical function of tumor-associated angiogenesis and lymphangiogenesis for progression of IHC. Therefore, antiangiogenic and antilymphangiogenic approaches may have therapeutic potency in this tumor entity.

Prognostic significance of the DNA-index in liver transplantation for hepatocellular carcinoma in cirrhosis.

OBJECTIVE: This study was conducted to evaluate the prognostic significance of the tumor DNA index in patients receiving liver transplantation for hepatocellular carcinoma (HCC) in cirrhosis. BACKGROUND: In patients suffering from HCC in cirrhosis, the current selection for liver transplantation does not optimally achieve the goal to simultaneously maximize the number of viable transplant candidates and reject the smallest number of those who could have benefited. This is the first report on the prognostic significance of the tumor DNA index. PATIENTS AND METHODS: From 1988 to 2007, liver transplantation for HCC in cirrhosis was performed in 246 consecutive patients. The DNA-index was determined by Feulgen staining and semiautomatical image analysis. Interpretation of DNA histograms followed the recommendations outlined in the European Society for Analytical Cellular Pathology consensus report on diagnostic DNA image cytometry. RESULTS: A DNA-index

Extended bile duct resection and [corrected] liver and transplantation in patients with hilar cholangiocarcinoma: long-term results.

For patients with irresectable hilar cholangiocarcinoma, liver transplantation (LT) is currently being reassessed because of promising data for neoadjuvant radiochemotherapy. For increased radicality, hepatectomy in combination with pancreatic head resection [extended bile duct resection (EBDR)] was performed for irresectable hilar cholangiocarcinoma during our initial experience. EBDR and LT was performed in 16 patients between 1992 and 1998. No neoadjuvant or adjuvant treatment was performed. The Union Internationale Contre le Cancer stages were I (n = 6), IIA (5), IIB (3), and IV (2). To evaluate the suspected increase in surgical radicality, a matched pair analysis was performed with 8 patients undergoing LT for hilar cholangiocarcinoma without partial pancreatoduodenectomy. The 1-, 5-, and 10-year patient survival rates after EBDR were 63%, 38%, and 38%, respectively. Twelve patients died: 2 died because of postoperative complications, 8 died because of tumor recurrence, and 2 died while recurrence-free more than 10 years after transplantation. Among the 6 stage I patients, only 1 developed tumor recurrence, but 2 died because of postoperative complications. The following factors showed a trend toward inferior survival: distant metastases, positive lymph nodes, high carbohydrate antigen 19-9 levels, and preoperative percutaneous transhepatic cholangiodrainage. When all lymph node-negative patients were considered after the exclusion of perioperative deaths, 10-year survival was 56%. In conclusion, the overall long-term survival was relatively low in our inhomogeneous cohort but favorable in patients without metastases. However, because of the increased perioperative mortality, EBDR is not recommended as a standard procedure for hilar cholangiocarcinoma instead of LT alone. To further improve the results, other approaches such as (neo)adjuvant therapy have to be increasingly investigated.

Nonresponse to pre-operative chemotherapy does not preclude long-term survival after liver resection in patients with colorectal liver metastases.

BACKGROUND: Liver resection is the only curative treatment offering a chance of long-term survival in patients with colorectal liver metastases (CRM). Recent data indicated that liver resection in patients with tumor progression while receiving chemotherapy was associated with poor outcome. The aim of the study was to identify risk factors for poor outcome in patients with pre-operative chemotherapy of CRM. METHODS: We analyzed 160 patients after liver resection for CRM with preoperative systemic. chemotherapy. Three groups of patients were identified: 44 patients (27.5%) had a tumor response, 20 (12.5%) showed stable disease, and 96 (60%) patients had tumor progression while on chemotherapy. Median follow-up was 2.4 years (range, 6 days-11.1 years). All available clinicopathologic variables possibly associated with outcome were evaluated. RESULTS: Survival was 88%, 53%, and 37% at 1, 3, and 5 years. Noncurative resection, carcinoembryonic antigen levels >200 ng/ml, tumor grading, size of the largest tumor >5 cm, and number of metastases were associated with poor patient outcome. In the multivariate analysis, tumor free margin and tumor grading correlated with the outcome. Tumor progression while on chemotherapy had no influence on the long-term survival. CONCLUSION: Liver resection offers a long-term survival benefit for patients with CRM, even when tumor growth proceeds during pre-operative chemotherapy.

Distinct temporospatial expression patterns of glycolysis-related proteins in human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) represents the sixth most frequent human cancer worldwide and is characterized by rapid progression as well as resistance to systemic chemotherapy. Recently, glycolysis has emerged as a potent driving force of tumor growth and therapy failure. The precise role of glycolysis for the pathogenesis of human HCC has not been elucidated thus far. Therefore, we have conducted a comprehensive analysis of the expression patterns of central glycolysis-related factors [glucose transporter-1 and -2 (Glut-1 and Glut-2), phosphoglycerate kinase-1 (PGK-1) and hypoxia-inducible factor-1alpha (HIF-1alpha)] in a large cohort of benign and malignant human liver samples. PGK-1 protein and gene expression was scant in normal liver, elevated in cirrhotic livers and most intense in HCC. Strong immunoreactivity of Glut-2 was noted in cirrhotic livers, whereas in HCC it was only expressed in 50% of examined cases. Strikingly, PGK-1 as well as Glut-2 protein expression was indicative of poor patient prognosis. Glut-1 protein was absent in neoplastic hepatocytes but prominent in tumor-associated endothelial cells. Specific nuclear staining of HIF-1alpha was noted in only 12% of HCC samples. Our data point toward a tumor-promoting function of glycolysis in HCC and establish PGK-1 as an independent prognostic parameter. Furthermore, the endothelial-specific expression of Glut-1 makes a special dependence of vessels on glucose reasonable to assume. In summary, we believe our analysis warrants the validation of glycolytic inhibitors as innovative treatment approaches of human HCC.

Extended liver resection for intrahepatic cholangiocarcinoma: A comparison of the prognostic accuracy of the fifth and sixth editions of the TNM classification.

OBJECTIVE: The present study was conducted to analyze the outcome after liver resection for intrahepatic cholangiocarcinoma (IHC) and to compare the prognostic accuracy of the fifth and sixth editions of the TNM classification of malignant tumors. SUMMARY BACKGROUND DATA: A comparison of the prognostic accuracy of the fifth and sixth editions of the TNM classification of malignant tumors is missing for IHC as yet. The present report is, to our knowledge, the largest series on surgical resection of IHC in the world literature and the first comparison of long-term outcome according to the fifth and sixth edition of the TNM classification of malignant tumors. METHODS: From 1988 to 2007, 195 liver resections for IHC were performed in our institution. Staging was performed according to the liver chapters of the fifth and sixth edition of the TNM classification of malignant tumors. RESULTS: In a multivariate analysis of prognostic variables, R0-resection, UICC-stage I/II according to the sixth edition, highly or moderately differentiated IHC, and lymph node negative IHC were identified as favorable prognostic variables. UICC-stage IIIc of the sixth edition, which was almost identical to the group of lymph node positive IHC was identified as unfavorable predictor of postoperative prognosis. Formally, curative resections (R0-resections) were achieved in 138 patients (71%). One- and 5-year survival rates after R0-resections were 72.4% and 30.4%, respectively. CONCLUSIONS: Extended resections for IHC resulted in a favorable rate of R0-resection, which is the most important prognostic variable. Staging of IHC according to sixth edition of the TNM classification is superior in comparison with the fifth edition as indicated by the results of the multivariate analysis.

Tumor-associated lymphangiogenesis correlates with prognosis after resection of human hepatocellular carcinoma.

BACKGROUND: Experimental results from animal models as well as studies of human cancers indicate a critical role for tumor-associated lymphangiogenesis in tumor progression. However, its significance in hepatocellular carcinoma (HCC) is not well established. METHODS: We analyzed tissue specimens from healthy liver (n = 36), cirrhotic liver (n = 24), and HCC (n = 60) by immunohistochemistry, using antibody D2-40 specific for lymphendothelia. We subsequently quantified lymphatic microvessel density (LVD). The LVD was correlated with clinicopathological characteristics of the tumors as well as survival and disease-free survival of the patients. RESULTS: In contrast to healthy as well as cirrhotic liver, lymphangiogenesis was induced in HCC. Lymphatic vessels were detected in the intratumoral septa as well as within the bulk of tumor cells. Tumors with high LVD (24 of 60) had developed significantly more frequently in cirrhotic livers (P = 0.001) and were more frequently restricted to one liver lobe (P = 0.04). Univariate analysis revealed high LVD as a marker for reduced survival and disease-free survival disadvantage (median >60 vs. 21 months, P = 0.018, and 19 vs. 8 months, P = 0.047, respectively). In multivariate analysis, LVD showed a trend toward association with reduced survival (P = 0.059) and represented an independent prognostic factor for disease-free survival (P = 0.017). CONCLUSIONS: Tumor-associated lymphangiogenesis is involved in neovascularization of hepatocellular carcinoma. Quantitative analysis of LVD demonstrated a significant influence of lymphangiogenesis on survival and established LVD as an independent predictor of disease-free survival. Quantification of LVD may be helpful in identifying patients with a high risk of tumor recurrence.

Microvessel density correlates with lymph node metastases and prognosis in hilar cholangiocarcinoma.

BACKGROUND: Neovascularization was shown to be critically involved in the progression of multiple cancers, and treatment approaches targeting tumor-associated neovascularization provide convincing results in recent years in some tumor entities. However, little is known about the tumor-associated neovascularization in hilar cholangiocarcinoma. The present study was conducted to analyze tumor-associated neovascularization in hilar cholangiocarcinoma and to determine its influence on tumor growth, metastasis, recurrence, and prognosis. METHODS: We analyzed tissue specimens of hilar cholangiocarcinoma (n = 60) by immunohistochemistry using the endothelial-specific antibody CD31 and subsequently quantified the microvessel density (MVD). The MVD was correlated with clinicopathological characteristics and recurrence pattern of the tumors as well as survival of patients. RESULTS: Hilar cholangiocarcinoma revealed a high degree of vascularization, with a calculated mean MVD of 28.1 +/- 14.5 vessels. Tumors with a high MVD had a significant higher incidence of lymph node involvement (P = 0.009) and local recurrence (P < 0.001). Furthermore, a high MVD was identified to be a significant overall survival disadvantage (3-year, 28% vs. 93%; 5-year, 8% vs. 78%; P < 0.001) as well as disease-free survival disadvantage (3-year, 7% vs. 88%, 5-year, 7% vs. 72%; P < 0.001), with MVD representing an independent prognostic factor for survival. CONCLUSIONS: Neovascularization is associated with nodal spread as well as local recurrence and serves as an independent prognostic factor for survival after curative resection of hilar cholangiocarcinoma. Therefore, tumor-associated neovascularization seems to be critically involved in the progression of this tumor entity. In addition, neovascularization may represent a potential target in he development of new therapeutic approaches in hilar cholangiocarcinoma.