Wataru Adachi

Survival and recurrence after hepatic resection of 386 consecutive patients with hepatocellular carcinoma.

BACKGROUND Although hepatic resection is one of the most effective treatments for hepatocellular carcinoma (HCC), the longterm results of hepatic resection of this malignancy are far from satisfactory. The potential benefits of hepatectomy for patients with HCC have not been fully delineated. This study aimed to identify surgical outcomes of 386 consecutive patients with HCC undergoing hepatic resection. STUDY DESIGN The retrospective study looked at records of 293 men and 93 women. The mean age was 63.2 years. Preoperative transarterial chemoembolizaton and portal vein embolization were performed in 138 patients (35.8%) and 8 patients (2.1%), respectively. Sixty-two patients (16.1 %) had major hepatectomy and the other 324 (83.9%) had minor hepatectomy. Thirty-seven of 386 patients (9.6%) had a noncurative operation. RESULTS The 30-day (operative) mortality rate was 4.1%, and there were 11 additional late deaths (2.9%). Two hundred fourteen of 327 patients (65.4%) had recurrence after curative resection. Unfavorable factors for survival and recurrence were resection between 1983 and 1990, Child class B or C, cirrhosis, a high value of indocyanine green retention-15, a large amount of intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications. Preoperative transarterial chemoembolization increased the recurrence rate and showed no contribution to prognosis. Currently, 106 patients (27.5%) are alive: 7 (1.8%) after more than 10 years and 43 (11.1%) after more than 5 years. Mean and median overall survivals after operation were 38 months and 29 months, respectively. The 5-year and 10-year overall or disease-free survival rates after hepatic resection were 34.4% and 10.5% or 23.3% and 7.8%, respectively. CONCLUSIONS The longterm survival rate after operation remains unsatisfactory mainly because of the high recurrence rate. Preoperative transarterial chemoembolization should be avoided because of a high risk of postoperative recurrence. Treatment strategies for recurrent HCC may play an important role in achieving better prognosis after operation, especially in patients with more than Child class B, cirrhosis, high values of indocyanine green retention-15, massive intraoperative blood loss, stage IV disease, positive surgical margin, vascular invasion, and postoperative complications.

Hepatic resection for hepatocellular carcinoma in the elderly.

BACKGROUND: Although the number of elderly people undergoing surgery for hepatocellular carcinoma (HCC) has increased because of the prolonged life expectancy rate, potential benefits of hepatectomy for elderly patients with HCC have not been fully delineated. STUDY DESIGN: Using medical records, surgical outcomes of HCC in 103 patients 70 years of age or older undergoing hepatic resection (older group) were clarified and compared with those of 283 patients younger than 70 years of age (younger group) in this retrospective study. Postresection prognostic factors were evaluated by multivariate analysis using Cox’s proportional hazards model. RESULTS: There were no significant differences in postoperative complication, operative mortality, and overall hospital death rates between the two groups. Overall 3- and 5-year survival rates for the older group and the younger group were 51.0% versus 55.2%, and 42.2% versus 40.0%, respectively (p = 0.95). Disease-free 3- and 5-year survival rates for the older group and the younger group were 35.2% versus 37.6%, and 16.6% versus 24.2%, respectively (p = 0.66). Multivariate analysis revealed that the presence of liver cirrhosis and vascular invasion were independently significant factors of poor overall survival. CONCLUSIONS: Selected elderly patients with HCC benefited from resection as much as young patients, and age by itself may not be a contraindication to surgery. Postresection longterm prognosis in the elderly was determined by the presence of liver cirrhosis and vascular invasion.BACKGROUND Although the number of elderly people undergoing surgery for hepatocellular carcinoma (HCC) has increased because of the prolonged life expectancy rate, potential benefits of hepatectomy for elderly patients with HCC have not been fully delineated. STUDY DESIGN Using medical records, surgical outcomes of HCC in 103 patients 70 years of age or older undergoing hepatic resection (older group) were clarified and compared with those of 283 patients younger than 70 years of age (younger group) in this retrospective study. Postresection prognostic factors were evaluated by multivariate analysis using Coxs proportional hazards model. RESULTS There were no significant differences in postoperative complication, operative mortality, and overall hospital death rates between the two groups. Overall 3- and 5-year survival rates for the older group and the younger group were 51.0% versus 55.2%, and 42.2% versus 40.0%, respectively (p = 0.95). Disease-free 3- and 5-year survival rates for the older group and the younger group were 35.2% versus 37.6%, and 16.6% versus 24.2%, respectively (p = 0.66). Multivariate analysis revealed that the presence of liver cirrhosis and vascular invasion were independently significant factors of poor overall survival. CONCLUSIONS Selected elderly patients with HCC benefited from resection as much as young patients, and age by itself may not be a contraindication to surgery. Postresection longterm prognosis in the elderly was determined by the presence of liver cirrhosis and vascular invasion.

Prognostic factors after hepatic resection for hepatocellular carcinoma with hepatitis C viral infection: univariate and multivariate analysis.

OBJECTIVES:Although the incidence of hepatocellular carcinoma (HCC) with hepatitis C virus (HCV) infection is higher than in patients with hepatitis B virus (HBV)–related HCC in Japan, the long-term prognosis and prognostic factors of HCV-related HCC after hepatic resection are poorly understood.METHODS:The surgical outcome of HCV-related HCC in 172 consecutive patients who underwent hepatic resection between 1989 and 1997 was retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Coxs proportional hazards model.RESULTS:The overall incidence of postoperative complications was 23.2%, and 11 patients among that group had hospital deaths (6.4%) including 9 (5.2%) operative deaths. The mean and median overall survivals including hospital death after surgery were 41 months and 33 months, respectively. The 3-, 5-, and 7-yr overall survival rates after hepatic resection were 63%, 52%, and 47%, respectively. The 3-, 5-, and 7-yr disease-free survival rates after hepatic resection were 33%, 20%, and 15%, respectively. Multivariate analysis revealed that serum α-fetoprotein (AFP) of ≥1000 ng/ml and the presence of vascular invasion were independent unfavorable prognostic factors affecting overall survival and that AFP of ≥1000 ng/ml was an independently significant factor of poor disease-free survival.CONCLUSIONS:We found the postresection survival of patients with HCV-related HCC should be stratified by the high value of AFP and the presence of vascular invasion. AFP may be the most powerful predictor of the long-term prognosis and recurrence in such patients.

α-Fetoprotein–producing gastric cancer: histochemical analysis of cell proliferation, apoptosis, and angiogenesis

Objectiveα-Fetoprotein (AFP)-producing gastric cancer has been associated with a poor prognosis. In the present study, the cell proliferation, apoptosis, and angiogenesis of this cancer were studied histochemically to determine its malignant potential.MethodsTissue samples were taken from four patients with AFP-producing gastric cancer and 26 patients with AFP-negative gastric cancer. Cell proliferation was evaluated by Ki-67 immunostaining, and the Ki-67 labeling index (LI) was determined. Apoptosis was studied by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling method, and the apoptotic index was determined. Angiogenesis was evaluated by measuring the microvessel density using factor VIII immunostaining, and immunostainings for vascular endothelial growth factor and thymidine phosphorylase were performed.ResultsThe Ki-67 LI of the AFP-producing gastric cancers was significantly higher than that of the AFP-negative gastric cancers (p < 0.01). The apoptotic index of the AFP-producing gastric cancers was significantly lower than that of the AFP-negative gastric cancers (p < 0.01). The microvessel density of the AFP-producing gastric cancers was significantly higher than that of the AFP-negative gastric cancers (p < 0.01). Vascular endothelial growth factor expression was observed in all four of the AFP-producing gastric cancers, whereas thymidine phosphorylase was not expressed in any of the AFP-producing gastric cancers.ConclusionsThese results suggest that AFP-producing gastric cancers have high malignant potential (high proliferative activity, weak apoptosis, and rich neovascularization) compared with that of AFP-negative gastric cancers. These biological characteristics of AFP-producing gastric cancer reflect the aggressive behavior and the poor prognosis of patients with this type of cancer.

p73, a geme related to p53, is not mutated in esophageal carcinomas

A novel gene, termed p73, encodes a protein with a significant homology to p53 and has been mapped at chromosome 1p36.3, which is a locus of multiple suppressor genes for tumors including neuroblastoma and other cancers. Since the 1p36 locus is reported to be deleted and p53 is frequently mutated in esophageal carcinomas, we examined loss of heterozygosity (LOH) and mutation of the p73 gene in 48 untreated esophageal tumors, as well as mRNA expression in 8 tumors. We screened the P1 genomic library to obtain a P1 clone containing the p73 gene and found a polymorphic short tandem CT repeat site at intron 9. Intragenic sequences for 14 PCR primer sets and a primer pair flanking the repeat were also determined for the analysis of PCR single‐strand conformation polymorphism (SSCP) and LOH studies, respectively. Expression of p73 mRNA was detectable but at low levels in all 8 tumor tissues by reverse transcriptase PCR. We did not find any type of mutation other than polymorphisms in the 48 esophageal carcinomas, though aberration of the p53 gene on the PCR‐SSCP gels was observed in 15 of 38 (39%) tumors of the same set. In addition, LOH for p73 was found in only 2 of 25 (8%) tumors. These results suggest that, at least in esophageal carcinomas, allelic loss or mutation of p73 may not be a main genetic event for the tumorigenesis as it is with p53. Int. J. Cancer 78:437–440, 1998.

Involvement of vascular endothelial growth factor and urokinase-type plasminogen activator receptor in microvessel invasion in human colorectal cancers.

To evaluate the association among known angiogenic growth factors or factors related to the plasminogen activation system and clinicopathological factors in patients with colorectal cancer, we examined the expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor‐α (TGF‐α), urokinase‐type plasminogen activator (u‐PA), u‐PA receptor (u‐PA‐R) and plasminogen activator inhibitor‐1 (PAI‐1) in clinical specimens of colorectal cancers by Northern blot analysis. In comparison with the expression of these angiogenesis‐related genes in 7 paired samples of colorectal cancers and the adjacent normal mucosa, VEGF mRNA level was significantly higher in the cancer tissues than in the adjacent normal mucosa (p < 0.05). We analyzed expression of these genes in 44 cases of primary colorectal cancers. Among the 3 angiogenic growth factors we examined, VEGF mRNA expression was significantly higher in the cancer tissues with blood vessel invasion or with lymphatic vessel invasion than in those without, respectively (p < 0.05). On the other hand, u‐PA‐R mRNA expression was significantly higher in the cancers with blood vessel invasion than in those without (p < 0.05). In addition, there was a correlation between the expression levels of VEGF and u‐PA‐R mRNA in the cancer tissues we have examined. Using immunohistochemistry, strong staining of VEGF or u‐PA‐R was observed in the cancer cells invading the microvessels. Our findings suggest that malignant transformation might accompany the upregulation of VEGF expression in colorectal cancers and that VEGF and u‐PA‐R might contribute cooperatively to increase angiogenesis around the tumor as well as the metastasis via microvessels. Int. J. Cancer (Pred. Oncol.) 79:179–186, 1998.© 1998 Wiley‐Liss, Inc.

Hepatic resection for large hepatocellular carcinoma

BACKGROUND Long-term survival and prognostic factors after hepatic resection for large hepatocellular carcinoma (HCC) remain to be proved. METHODS The surgical outcome in 133 consecutive patients with HCC in diameter of > or = 5 cm (large HCC; L group) undergoing hepatic resection was retrospectively clarified and compared with that of 253 patients with HCC in diameter of < 5 cm (small HCC; S group). Postresection prognostic factors were evaluated by univariate and multivariate analysis using Coxs proportional hazards model. RESULTS The disease-free 3- and 5-year survival rates between L group and S group were 26% versus 42% and 20% versus 25%, respectively (P = 0.0032). The overall 3- and 5-year survival rates between L group and S group were 38% versus 67% and 28% versus 47%, respectively (P < 0.0001). Multivariate analysis revealed that large amount of intraoperative blood transfusion was an independently significant factor of poor disease-free and overall survivals. CONCLUSIONS Long-term survival in patients with large HCC remains unsatisfactory compared with that in patients with non-large HCC. Restriction of intraoperative blood transfusion may play an important role in the improvement of survival and recurrence in such patients.

Coexpression of vascular endothelial growth Factor and p53 protein in squamous cell carcinoma of the esophagus

OBJECTIVE:p53 plays a role in tumor angiogenesis, and vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of the present study was to clarify how expression of p53 protein participates in angiogenesis, and whether the coexpression of VEGF and p53 protein has a significance for angiogenesis and the clinicopathological features in esophageal squamous cell carcinoma (SCC).METHODS:Tissues samples were taken from 60 patients with esophageal SCC after surgery. The expression of VEGF and p53 protein in these SCC was examined immunohistochemically. Microvessel density (MVD) was determined by counting microvessels in tumor sections stained for Factor VIII-related antigen. Ki-67 labeling index (LI) was calculated, based on Ki-67 antigen immunostaining, as a proliferative marker. Apoptotic index (AI) was calculated, based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling, to evaluate apoptosis.RESULTS:VEGF expression was observed in 58.3%, and p53 protein expression was observed in 61.7% of the 60 patients. VEGF and p53 protein were significantly coexpressed in 26 (43.4%). Histological venous invasion (p < 0.01) and distant metastasis (p < 0.05) were significantly correlated with p53 protein expression. The two parameters were more frequently observed in the SCC with VEGF/p53 coexpression than in those without the coexpression. The MVD and Ki-67 LI were significantly higher (p < 0.01 and p < 0.001), and the AI was significantly lower (p < 0.001) in the SCC with p53 protein expression than in the SCC without it. The MVD and Ki-67 LI were higher, and the AI was lower in the SCC with VEGF/p53 coexpression than in those without the coexpression. The 5-yr survival rate in patients with the coexpression was poorer than in the other patients.CONCLUSION:These results suggest that mutant p53 expression is associated with angiogenesis and distant metastasis in esophageal SCC, and that the coexpression of p53 and VEGF may play an important role in angiogenesis, and have important clinical significance.

Laparoscopic resection of a retroperitoneal schwannoma.

Although laparoscopic surgery for retroperitoneal diseases has been widely performed, there are few reports of laparoscopic resection for retroperitoneal tumors. We present the case of a 5-cm retroperitoneal tumor compressing the right common iliac vein and inferior vena cava that was successfully resected using a laparoscopic technique. Dissection between the tumor and the large vessels was performed safely using a harmonic scalpel and an ultrasonic surgical aspirator. Histopathology of the resected tumor showed a benign schwannoma. Laparoscopic surgical techniques should be considered for treatment of selected retroperitoneal tumors.

Immunohistochemical expression of bcl-2 protein in squamous cell carcinoma and basaloid carcinoma of the esophagus

In the present study, the expression of bcl-2 protein in esophageal squamous cell carcinoma (SCC) and basaloid carcinoma (BC) was immunohistochemically examined, and its relation to tumor progression and postoperative survival was determined in SCC.A total of 42 SCC and 4 BC tumor samples were fixed with formalin, embedded in paraffin, and stained using monoclonal bcl-2 protein antibody, clone 124. Immunoreactivity was semiquantitatively scored, and the staining results were compared with the pathologic features and survival rates. The cytoplasm of basal cells from the normal esophageal epithelium was stained. In some well- and moderately differentiated SCCs, bcl-2 protein-positive reaction was observed in the peripheral part of the tumor cord, but in poorly differentiated SCC, the cells were weakly or hardly stained. However, in BC, the cells were strongly stained. The immunoreactivity was positive in 45.2% of the SCCs and all of the BCs. There were no significant differences in pathological features or patient survival between the bcl-2 protein-positive and protein-negative SCCs. In conclusion, the expression was not related to tumor progression and had no prognostic significance in SCC. Conversely, BC had strong immuno-histochemical expression, probably associated with the differentiation of carcinoma cells simulating the basal cells of the esophagus.