Naohiko Koide

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.

Significance of macrophage chemoattractant protein-1 expression and macrophage infiltration in squamous cell carcinoma of the esophagus

OBJECTIVES:Macrophage chemoattractant protein-1 (MCP-1) is a chemokine-inducing infiltration of macrophages, which can play several roles in tumor growth and metastasis. We have attempted to clarify the relationship between MCP-1 expression and macrophage infiltration in esophageal squamous cell carcinoma (SCC).METHODS:Paraffin-embedded sections of tissue samples taken from 56 patients with esophageal SCC after curative surgery were immunohistochemically stained for MCP-1, CC chemokine receptor 2 (CCR-2), and thymidine phosphorylase (TP). Macrophage recruitment in SCC was evaluated by monocytic count based on CD68 immunostaining. Microvessels immunostained for Factor VIII-related antigen were counted in SCC, and microvessel density (MVD) was determined. Ki-67 labeling index was calculated based on Ki-67 immunostaining, and an apoptotic index was calculated based on the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling.RESULTS:MCP-1 was expressed in cancer cells of 31 SCC (55.4%) and in stromal cells mainly identified as macrophages of 16 SCC (28.6%). CCR-2 was expressed in stromal cells of all SCC and in vascular endothelial cells of 15 SCC (26.8%). There was a significant correlation between the expression of MCP-1 in cancer cells and of CCR-2 in stromal cells. TP was expressed in stromal cells in 76.7% of the SCC. Monocytic count, MVD, and Ki-67 LI in SCC with MCP-1 expression in cancer cells were higher than that without, and apoptotic index in SCC with MCP-1 expression in cancer cells were lower than that without. Furthermore, the monocytic count was positively correlated with MVD, while it was inversely correlated with apoptotic index. Clinicopathologically, MCP-1 expression in cancer cells was correlated with venous invasion, distant metastasis, and lymph node metastasis. Monocytic count in SCC with venous invasion, distant metastasis, or lymph node metastasis was higher than that without them. Five-year survival rate in the patients with high monocytic count or MCP-1 expression was worse than that with a low monocytic count or without MCP-1 expression.CONCLUSIONS:These results suggest that MCP-1 expression and macrophage infiltration is associated with angiogenic promotion in esophageal SCC. MCP-1 expression may be interactively associated with macrophage infiltration in esophageal SCC; MCP-1 may play an important role in tumor angiogenesis through production of angiogenic factors, such as TP, by recruited macrophages in esophageal SCC. Furthermore, CCR-2 expression in vascular endothelial cells may participate partially in angiogenesis. Clinicopathologically, esophageal SCC patients with MCP-1 expression have no favorable prognosis.

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.

Stromal tumor of the pancreas with expression of c-kit protein: Report of a case

Abstract We report on a case of a stromal tumor, similar to a gastrointestinal stromal tumor, originating from the pancreas. The patient was a 54‐year‐old woman, who was seen at the Kofu Municipal Hospital because of an abdominal tumor. On abdominal computed tomography and splenic arteriography, the tumor was detected in the pancreatic tail. The patient underwent distal pancreatectomy with splenectomy. Macroscopically, the cut surface of the tumor showed almost completely surrounded by the normal pancreatic tissue. Microscopically, the tumor composed of spindle‐shaped cells that were immunoreactive for vimentin, CD34, and c‐kit protein. Therefore, the tumor was diagnosed as a stromal tumor of the pancreas. The expression of c‐kit protein suggests that this pancreatic stromal tumor may originate from primitive mesenchymal cells which can be a logical candidate for the origin of gastrointestinal stromal tumors and extra‐gastrointestinal stromal tumors.

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.

Surgical treatment for anorectal malignant melanoma: report of five cases and review of 79 Japanese cases

IntroductionAnorectal malignant melanoma (AMM) is a relatively rare disease. Because of its poor prognosis, the optimal surgical treatment for AMM is still controversial and difficult to determine. In this paper, we report five cases of AMM that have been treated by surgery and/or other methods at Shinshu University Hospital within the last decade. We also review the present five cases along with 74 other Japanese cases reported between 1997 and 2006 and discuss the role of surgery in the treatment of AMM.Results and discussionAmong our AMM patients, two who underwent radical abdominoperineal resection had long survival, while the other three patients who underwent palliative surgery had a poor outcome. On the total of 79 AMM patients, those who underwent curative surgery had a better outcome than those who underwent palliative surgery (p < 0.0001). Furthermore, the outcome of AMM patients at stages 0 and I was better than that of AMM patients at stages II, III, and IV (p < 0.0001). There was no significant difference in survival between AMM patients with and without adjuvant chemotherapy.ConclusionIn conclusion, AMM patients treated by curative surgery can expect long-term survival, although the usefulness of adjuvant chemotherapy for AMM patients is controversial.

Usefulness of Preoperative Endobronchial Ultrasound for Airway Invasion around the Trachea: Esophageal Cancer and Thyroid Cancer

Background: It is important to confirm preoperative tracheobronchial invasion to enable the selection of the most appropriate treatment. Objective: This study was performed to compare the usefulness of computed tomography (CT), magnetic resonance image (MRI) and bronchoscopy by endobronchial ultrasonography (EBUS) for the assessment of invasion of thyroid or esophageal cancer in cases with suspected tracheobronchial invasion. Methods: In cases with suspected contact between the tumor and tracheobronchial wall, CT, MRI and EBUS indicated deformity of the tracheobronchial wall due to the adjacent mass. The final diagnosis was based on surgical and histological results, and/or clinical follow-up. Results: Fifty-four patients were included in this study. Based on the findings of CT, MRI and EBUS, invasion was suspected in 29, 28 and 25 patients, respectively. Seventeen patients did not undergo surgery based on the results of CT, MRI and bronchoscopy with EBUS. Final diagnosis was intact trachea or bronchial adventitia in 26 patients and invasion in 28 patients. The sensitivity and specificity of CT, MRI and EBUS for invasion were 59 and 56, 75 and 73, and 92 and 83%, respectively. The accuracy of EBUS was significantly greater than that of CT in the present study (p = 0.0011). The accuracy of EBUS was significantly different from that of CT and MRI in the surgically treated patients (p = 0.005 and p = 0.032, respectively). Conclusion: EBUS is the most useful technique for determining the depth and extent of tumor invasion into the airway wall. The combination of MRI and EBUS will contribute to surgical planning in patients with esophageal and thyroid cancer.

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.