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Background/aims: The association between transfusion and recurrence after resection for hepatocellular carcinoma (HCC) is still under debate. The influences of perioperative blood transfusion on survival and recurrence after curative hepatic resection for HCC and prognostic factors in patients with blood transfusion were evaluated., Methodology: Curative hepatectomy was performed in 210 patients (57%) with and 158 (43%) without perioperative blood transfusion. Prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model., Results: Multivariate analysis revealed that perioperative blood transfusion was an independent predictor for recurrence in patients with serum low albumin level (< 3.5 g/dL). In transfused group, stage IV, large tumor size (> or = 5 cm), high value of ICGR15 (> or = 20%), and old age (> or = 60 year) were independent factors of poor disease-free survival., Conclusions: Perioperative blood transfusion promotes the recurrence of HCC after hepatic resection in patients with hypo-albuminemia. In transfused patients, establishment of strategy for recurrence based on pTNM staging, tumor size, ICGR15, and age may be required to improve survival.

Background/aims: The levels of cell proliferation, apoptosis and angiogenesis were compared histochemically in gastric cancer and its hepatic metastases., Methodology: Tissue samples were taken from 7 patients with gastric cancer associated with synchronous and/or metachronous hepatic metastases. In the 7 gastric cancers and in 4 synchronous and 4 metachronous hepatic metastases, Ki-67 immunostaining was performed to measure the labeling index (Ki-67 LI). Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling was performed to measure the apoptotic index, and immunostaining for factor VIII-related antigen was performed to measure the microvessel density., Results: The Ki-67 LI was higher in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (primary lesions vs. synchronous foci vs. metachronous foci: 47.1% vs. 39.3% vs. 48.0%; P < 0.05). The apoptotic index was lower in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (3.50% vs. 5.01% vs. 2.64%; P < 0.05). The microvessel density was higher in the gastric cancer and the metachronous hepatic metastasis than in the synchronous hepatic metastasis (36.0 vs. 22.2 vs. 34.2; P < 0.05)., Conclusions: The present results suggest that tumor growth as indicated by cell proliferation, apoptosis and angiogenesis is less vigorous in synchronous hepatic metastasis than in primary lesion and/or metachronous hepatic metastasis.

Background/aims: Intrahepatic cholangiocarcinoma is clinicopathologically distinct from hepatocellular carcinoma and hilar cholangiocarcinoma, and the prognostic factors after hepatic resection of these rare tumors are not well documented. The aim of this study was to evaluate prognostic factors of intrahepatic cholangiocarcinoma after hepatic resection., Methodology: We retrospectively studied 20 consecutive patients with intrahepatic cholangiocarcinoma who underwent hepatectomy over a 15-year period from 1984 to 1998. Fifteen prognostic factors were evaluated for their association with overall and disease-free survivals in univariate and multivariate analysis (Cox's proportional hazards model)., Results: Eighty percent of the resected patients had major hepatectomy. Operative morbidity and mortality rates were 30% and 0%, respectively. Four patients (20%) survived more than 5 years without recurrence after hepatic resection. The 1-year, 3-year, and 5-year overall or disease-free survival rate after hepatic resection were 56.0% or 49.5%, 43.8% or 43.3%, and 43.8% or 37.3%, respectively. Univariate analysis showed young age and periductal invasion tumor or the presence of vascular invasion, lymphatic invasion, and lymph node metastasis as significant poor prognostic predictors contributing overall and disease-free survivals. Multivariate analysis revealed only lymph node metastasis as an independent prognostic factor affecting disease-free survival. During the same time, 17 unresectable patients were treated by intrahepatic arterial infusion chemotherapy (12), systemic chemotherapy (4), or radiation (1). Median overall survival time in resected patients (16 months) was significantly better than in unresectable patients (5 months) (P = 0.005)., Conclusions: Hepatic resection remains to be the best current therapeutic option. The prognosis after hepatic resection for intrahepatic cholangiocarcinoma was determined by lymph node metastasis. New adjuvant chemotherapy after surgery is imperative for such patients.

Background/aims: Definitive efficacy of hepatic resection for hepatocellular carcinoma larger than or equal to 10 cm in diameter remains to be resolved., Methodology: The surgical outcomes in 33 consecutive patients with hepatocellular carcinoma in diameter of > or = 10 cm who underwent hepatic resection were retrospectively clarified. Postresection prognostic factors were evaluated by univariate and multivariate analysis using Cox's proportional hazards model., Results: The overall incidence of postoperative complications was 39%, and 5 patients among them had hospital deaths (15%) including 2 (6%) operative deaths. The 3-year, 5-year, and 9-year overall survival rates after hepatic resection were 32%, 27%, and 17%, respectively. Univariate analysis revealed that liver cirrhosis and stage IV-A (pTNM staging) were significant factors of poor overall survival. By Cox's proportional hazards model, liver cirrhosis was an independently unfavorable prognostic factor of long-term survival. Hospital mortality rate in patients with cirrhosis was 31%. The 5-year overall survival rate in patients with cirrhosis (7%) was significantly shorter than that in patients without cirrhosis (43%) (P = 0.006). In addition, the 5-year overall survival rate in patients with stage IV-A (11%) was significantly shorter than that in patients with stage II and III (48%) (P = 0.024). The incidence of stage IV-A in patients with cirrhosis (77%) was significantly higher than those without cirrhosis (35%) (P = 0.032)., Conclusions: Hepatic resection for hepatocellular carcinoma in diameter of > or = 10 cm was effective for patients without liver cirrhosis and with stage II or III. Appropriate selection of the candidates for partial hepatectomy based on the above prognostic factors may play an important role in the improvement of high mortality rate and poor long-term survival for such patients. Prospective randomized trials are needed to define the role of hepatic resection for cirrhotic patients with large HCC.

Background/aims: The aim of this study was to evaluate the inflammatory or antiinflammatory cytokine response to ischemia-reperfusion during hepatectomy and to find a useful marker of injury or surgical stress during hepatic ischemia-reperfusion., Methodology: In 9 patients with liver disease who underwent hepatectomy using the Pringle maneuver, serum cytokines, including alanine transaminase, aspartate transaminase, and hyaluronic acid, were measured just prior to vascular occlusion; 5, 10 and 15 min after initial clamping; and 3 min after initial declamping., Results: The mean concentrations of aspartate transaminase and alanine transaminase did not significantly differ before and after ischemia-reperfusion during hepatectomy. However, mean concentrations of hyaluronic acid after ischemia-reperfusion were significantly (P < 0.03) higher than before clamping. Although there were no significant differences in the mean concentrations of IL-1 beta, IL-6, IL-8, IL-10 and TNF-alpha among, before and after ischemia-reperfusion, the mean concentrations of granulocyte colony-stimulating factor after ischemia-reperfusion and macrophage colony-stimulating factor after reperfusion were significantly (P < 0.05) higher than before clamping., Conclusions: Although hepatic parenchymal cell function was maintained after ischemia-reperfusion during hepatectomy, sinusoidal endothelial cell dysfunction was found. Release of granulocyte colony-stimulating factor and macrophage colony-stimulating factor after ischemia-reperfusion were also found. These cytokines and hyaluronic acid may be useful indicators in the early phase of human ischemia-reperfusion injury during hepatectomy.

As most portal vein occlusion in hilar bile duct carcinoma is caused by tumor invasion to the portal vein, other mechanisms of its occlusion are very rare. We report the case of a 69-year-old man who underwent surgical resection for an advanced hilar bile duct carcinoma associated with unusual portal vein occlusion. Preoperative diagnosis was advanced hilar bile duct carcinoma with liver abscess and right portal vein occlusion due to tumor invasion. Extended right hepatectomy combined with resection of caudate lobe was performed. Intraoperatively, tumor invasion to the portal vein was not evident and resected margin of the right portal vein showed thrombosis and no evidence of malignancy histologically. To our knowledge, this is the first reported case of a patient with a combination of portal vein thrombosis and liver abscess in hilar bile duct carcinoma. Although portal vein occlusion due to thrombosis is an unusual complication in hilar bile duct carcinoma, the presence of liver abscess may be a useful diagnostic implication of this occlusion.

Background/aims: Prostaglandin E1 has been used in hepatectomy based on a few limited clinical studies suggesting that PGE1 improves liver function. The aim of this study was to evaluate the effects of PGE1 administration during hepatectomy for cirrhotic hepatocellular carcinoma., Methodology: Forty-three patients undergoing hepatectomy for cirrhotic hepatocellular carcinoma were divided into 2 groups: hepatectomy with Prostaglandin E1 treatment (PG group; n = 19) and without Prostaglandin E1 treatment (control group; n = 24). Prostaglandin E1 (0.02-0.07 microgram/kg/min) was administered intravenously from beginning to end of surgery in the PG group., Results: There were no significant differences between groups with respect to age, gender, preoperative liver and renal function, or intraoperative variables such as blood loss, weight of resected liver and total clamping time by the Pringle maneuver. No patient had severe postoperative complications. Initial postoperative maximum concentrations of serum total bilirubin, creatinine, and blood urea nitrogen in the PG group were significantly lower than those in the control group., Conclusions: Prostaglandin E1 administration during hepatectomy for cirrhotic heptocellular carcinoma resulted in improved renal and hepatic function.

Background/aims: Little information regarding synchronous gastric cancer (GC) associated with hepatocellular carcinoma (HCC) is available. The aim of this study was to clarify the clinicopathologic features of synchronous GC associated with HCC, and we also discuss the diagnostic and therapeutic issues regarding them., Methodology: In a series of 396 patients with GC and 340 patients with HCC, we investigated the clinicopathologic features of the patients with synchronous GC associated with HCC (HCC group; n=10). They were compared to the patients with resected GC without HCC (non-HCC group) which was divided into 2 groups: with chronic hepatic disease (CHD: CHD group; n=15) and without CHD (Control group; n=345)., Results: The HCC group consisted of 10 of the 396 patients with GC (2.6%), and of 340 with HCC (2.9%). Eight node-negative early GC and 2 advanced GC cases were observed in the HCC group. Nine of these GC (90%) were well-differentiated adenocarcinoma. The tumor sizes of the HCC group were significantly smaller than those of the control group (p<0.05). The incidences of intestinal type and early GC in the HCC group were significantly higher than those in the control group, (p<0.05). However, there were no significant differences in any parameters between the HCC group and CHD group. With regard to early GC, there were no significant differences in any parameters, excluding the site of GC in the CHD group, between the HCC group and non-HCC group. Eight in the HCC group were surgically resected, and the post-operative period of these patients was uneventful. Although there were no significant differences in survival after surgery among the 3 groups, the survival of the patients with early GC in the HCC group was significantly worse than that in the control group (p<0.01)., Conclusions: The clinicopathologic features of synchronous GC associated with HCC are not very aggressive in most patients probably because of the early detection, and those of early GC with HCC appeared to resemble that of GC with CHD. Since early GC may not influence the clinical outcome of HCC patients, limited gastric resection can be recommended even when curative surgery for HCC is performed. By contrast, when advanced GC is present, curative gastrectomy with lymphadenectomy would be advisable to improve the long-term survival.

We report on a patient with small cell carcinoma of the esophagus treated with effective combination chemotherapy followed by surgical resection. A 69 year-old male had an ulcerated tumor in the middle part of the esophagus, which was microscopically diagnosed as small cell carcinoma of the esophagus. After combination chemotherapy, endoscopy showed that the esophageal tumor had changed into a shallow ulcer. No cancer cell was found in the biopsy specimen of the ulcer. A subtotal esophagectomy with regional lymph node dissection was performed. Histological examination showed that a few cancer cells remained in a microvessel of the submucosal layer in the removed esophagus and no cancerous lesion was found in regional lymph nodes. The patient was well and was able to remain at home. However, he eventually died 21 months after first detection of the carcinoma due to progression of multiple lung and mediastinal lymph node metastases. After complete or partial remission is achieved by the combination chemotherapy, surgical resection may be recommended as the second therapy that occasionally produces long-term remission and possibly long-term survival for patients with small cell carcinoma of the esophagus, such as the present case.

Background/aims: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis. The aim of this study was to clarify the significance of VEGF expression in esophageal squamous cell carcinoma (SCC)., Methodology: Tissues samples were taken from 52 patients with esophageal SCC after surgery. VEGF expression in these SCCs was examined immunohistochemically. Microvessels in the tumor stained for Factor VIII-related antigen were counted. Ki-67 antigen as a proliferative marker was immunostained with MIB-1, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed for the evaluation of apoptosis. Ki-67 labeling index (LI) and apoptotic index were then calculated., Results: VEGF expression was observed in 30 of the patients (57.7%). The microvessel count was significantly higher (p = 0.007), and the apoptotic index was significantly lower (p < 0.0001) in the SCC with VEGF expression than in the SCC without it, but no significant difference was observed in the Ki-67 LI between these groups. There was an inverse correlation between the microvessel count and the apoptotic index (p = 0.007). In the clinicopathologic factors, histologic venous invasion of cancer cells (p = 0.039) and lymph node metastasis (p = 0.049) were significantly correlated with VEGF expression. The survival rate after curative surgery was better in the patients without VEGF expression (p < 0.05), and distant organ metastasis after surgery was frequently observed in the patients with VEGF expression (p = 0.023)., Conclusions: These results suggest that VEGF expression is associated with angiogenesis in esophageal SCC, and may be a prognostic factor in patients with esophageal SCC. Furthermore, apoptosis may be influenced by angiogenesis in esophageal SCC.

Background/aims: The aim of this study was to clarify risk factors associated with intra-operative blood loss in hepatectomized patients with giant cavernous hemangioma (GCH) of the liver., Methodology: Twenty patients with GCH of the liver were treated by hepatectomy. Eleven patients with intra-operative blood loss > 2000 ml (mean: 7145 +/- 7080 m; Group 1) were reviewed retrospectively and compared to 9 patients with intra-operative hemorrhage < 2000 ml (mean: 918 +/- 429 ml; Group 2)., Results: Although there were no significant differences in pre-operative AST, ALT, and ICG-15 or fibrinogen and platelets between the two groups, pre-operative total bilirubin and fibrin degradation product (FDP) in Group 1 was significantly higher than in Group 2. Mean operation time and intra-operative blood transfusion in Group 1 versus Group 2 were 433 min vs. 213 min (p < 0.0001) and 3036 ml vs. 422 ml (p = 0.0072), respectively. The weight of resected liver (r = 0.821, p < 0.0001), maximum diameter of tumor (r = 0.782, p < 0.0001) and operation time (r = 0.748, p < 0.0001) were the most highly correlated with intra-operative blood loss, followed by pre-operative total bilirubin (r = 0.605, p = 0.0038), FDP level (r = 0.576, p = 0.0068) and intra-operative blood transfusion (r = 0.561, p = 0.0089)., Conclusions: These findings suggest that pre-operative management to reduce the tumor size, total bilirubin and FDP levels may be essential to minimize intra-operative hemorrhage and blood transfusion.

Background/aims: Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor which is an angiogenic factor. We attempted to clarify the significance of dThdPase expression in esophageal squamous cell carcinoma (SCC)., Methodology: Tissues samples were taken from 50 patients with esophageal SCC after curative surgery. The expression of dThdPase was immunohistochemically examined using a monoclonal antibody to dThdPase (clone 654-1). Microvessels in SCC stained for Factor VIII-related antigen were counted. Vascular endothelial growth factor (VEGF) was immunostained with R11. Ki-67 antigen was immunostained with MIB-1, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end labeling was performed, and Ki-67 labeling index (LI) and apoptotic index were calculated., Results: The expression of dThdPase was observed in 30 patients (60%). Between the SCC with and without dThdPase expression, significant differences were found in microvessel count (p < 0.001) and VEGF expression (p < 0.01), but not in Ki-67 LI and apoptotic index. With regard to the clinicopathologic factors, significant differences were observed in histologic venous invasion (p < 0.01) and lymph node metastasis (p < 0.05). Survival rate after surgery was better in the patients with dThdPase-negative SCC (p < 0.05), and distant organ metastasis after surgery was frequently observed in the patients with dThdPase-positive SCC (p < 0.05)., Conclusions: These results suggest that dThdPase expression may be associated with angiogenic promotion and may be one of the prognostic factors in esophageal SCC.

A case of Zollinger-Ellison syndrome produced by gastrinoma in the duodenum accompanied by multiple endocrine neoplasia type-1 (MEN-1) is reported. A 46 year-old female underwent distal gastrectomy due to gastric ulcer 5 years ago. As ulceration of the residual stomach recurred, further examination was performed. Hyperprolactinemia, hypergastrinemia, primary hyperparathyroidism, pancreatic tumor, and duodenal carcinoid were evident, and the diagnoses of Zollinger-Ellison syndrome and MEN-1 were established. The origin of the gastrin secretion was suspected to be from the pancreatic tumor, so sampling of the portal blood was performed. As lesion on the gastrinoma in the pancreas could not be identified, total parathyroidectomy was performed for primary hyperparathyroidism. The level of the gastrin secretion, however, remained high. Partial resection of the duodenum for the duodenal carcinoid and a distal pancreatectomy were carried out concurrently. Immunohistochemical study of the anti-gastrin antibody revealed duodenal tumor cells. Initially, the gastrinoma was thought to be in the pancreas, however, the lesion accompanied with MEN-1 and the Zollinger-Ellison syndrome had occurred in the duodenum.

Background/aims: Basaloid squamous carcinoma (BSC) of the esophagus has been associated with poor outcome after surgery. In this study, apoptosis and cell proliferation of BSC were studied to evaluate the malignant potential of this cancer., Methodology: In tissue samples from 4 out of 5 BSC patients (1 patient with pre-operative radiotherapy was excluded) and from 30 patients with squamous cell carcinomas (SCCs) of the esophagus, apoptosis was studied by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and cell proliferation was evaluated by the immunostaining of proliferating cell nuclear antigen (PCNA). Two of the 5 patients with BSC died of recurrence and the remaining 2 patients are alive without recurrence., Results: TUNEL-positive cells and PCNA-positive cells were observed to exist randomly and independently in the BSC samples. In the well- and moderately differentiated SCCs, TUNEL-positive cells and PCNA-positive cells were locally observed. The apoptotic index was significantly lower in the BSC than in the SCC tissues, and the PCNA labeling index was significantly higher in BSC than in SCC., Conclusions: These results suggest that BSC of the esophagus has great proliferative activity and weak apoptosis. These characteristics may reflect the aggressive behavior and poor prognosis of esophageal BSC. Early detection of this tumor, as in the present 2 cases, will contribute to a better prognosis.

Cases of esophageal cancer with intramural metastasis to the stomach and esophageal cancer with metastasis to an intramural lymph node of the stomach are herein reported. The former patient was a 52 year-old male. Squamous cell carcinoma (SCC) of the lower esophagus with an intramural metastasis located at the gastric cardia and a small leiomyoma at the fornix were resected. The latter patient was a 70 year-old female. SCC of the lower esophagus and an intramural lymph node metastasis located at the anterior wall of the gastric cardia were resected. The patient died nevertheless of multiple liver metastases. These gastric involvements were detectable by endoscopy before surgery. The clinicopathological features of these esophageal cancers were characterized; the sites were the lower part of the esophagus, and extreme lymphatic and vascular invasions were shown histologically. The gastric tumors were located in the upper third of the stomach, and the findings revealed submucosal tumors. It is therefore important to discriminate other gastric tumors, and to resect them simultaneously with esophageal cancer when a gastric tube has been used for reconstruction after esophagectomy.

We herein describe a patient with a giant mixed hepatocellular carcinoma and cholangiocarcinoma (MHC) surrounding the inferior vena cava (IVC). The patient was treated by extended left hepatic lobectomy with resection of the main right, left and middle hepatic veins and preservation of the inferior right hepatic vein (IRHV) after hepatic arterial infusion (HAI) chemotherapy. The patient died of distant metastases 4 years after initial HAI chemotherapy. As there is no hope of cure with HAI alone in the patients with MHC, this operative procedure even after HAI is recommended for patients with reduced liver function, tumor involving the RHV and surrounding the IVC.

Background/aims: In order to improve the management of patients of gastric cancer with synchronous hepatic metastasis, their records were retrospectively studied., Materials and Methods: From January 1981 to July 1993, 558 gastric cancer patients were admitted in our institute. Twenty-five with synchronous hepatic metastasis were used in this study. Among these 25 patients, six had hepatic metastasis alone and nineteen had some other additional noncurative prognostic factors. For the primary lesion, 12 patients received gastrectomy (total or distal subtotal) and 13 patients did not. For the hepatic metastasis, 12 patients had regional therapy (hepatectomy or hepatic arterial chemotherapy) and 13 had not. Both gastrectomy and regional therapy for hepatic metastasis were carried out in 6 patients who had hepatic metastasis alone., Results: Five year cumulative survival rate was 9%. Survival rate of patients with hepatic metastasis alone was significantly better than the patients with additional noncurative factors (p < 0.05). The two long term survivors in this study had no other noncurative factors except hepatic metastasis., Conclusions: Neither gastrectomy nor regional therapy for hepatic metastasis had beneficial effects on the patients with additional noncurative factors. Gastrectomy and regional therapy for hepatic metastasis should be performed in patients without additional noncurative factors.