In the 20 years since the establishment of our Department of Surgery in 1973, 551 patients with hepatocellular carcinoma (HCC) have been treated by hepatectomy. Based on this experience results of clinical as well as basic studies on the pathogenesis of HCC and its surgical treatment have been accumulated. Approximately 90% of patients with HCC in Japan are associated with liver cirrhosis or precirrhotic chronic hepatitis, resulting in a high mortality rate after hepatectomy. A multiple regression equation predicting the safety limits of hepatectomy in patients with compromised liver function was devised at the end of 1980, after which the mortality rate for posthepatectomy liver failure fell rapidly to almost 0%. Since then, we have clarified that not the hepatic vein but the portal vein bears the draining system for HCC and that tumor hemodynamics together with elevated intratumoral pressure lead to the early development of intrahepatic metastasis. Based on these observations, we devised a new technique of anatomical segment-or subsegmentectomy preceeded by hilar ligation of portal pedicles. Portal vein invasion, intrahepatic metastasis and DNA ploidy patterns of HCC as well as the curability of applied hepatectomy were the cardinal factors that influenced the 5-year survival rate. However, curability itself was the main factor that influenced 10-year survival rate.

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Hemorrhagic acute gastric mucosal lesions (AGML) were classified as postoperative hemorrhagic AGML (postoperative AGML) and other hemorrhagic AGML (other AGML), and its therapeutic results was studied. In postoperative AGML, the rates of the presence of exposed vessels and the rate of going into shock were higher than in the other AGML. The rate of hemostasis, rebleeding and mortality for postoperative AGML was, however, no significant difference compared with other AGML. That is, there was no difference in the intensity of stressor between these two groups. The result of operation was extremely poor, namely, the mortality of surgical therapy for postoperative AGML was 100%. Accordingly, it seems that conservative therapy consisting mainly of intermittent intravenous infusion of H₂ receptor antagonist or continuous intravenous infusion of secretion was most effective in treating postoperative hemorrhagic AGML.

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We reviewed the records of 15 patients with remnant gastric cancer (R-cancer) who had survived more than 10 years after the first gastrectomy, compared with 123 patients with primary gastric cancer which was suspected to originate in the upper third of the stomach (C-cancer). Twenty-two percent of the cases of R-cancer were early cancer and there was no significant difference in the percentage of early cancers between the cases of R-cancer and C-cancer. The histologically differentiated type acounted for 67% of the R-cancer cases and INFa for 31% which was slightly higher than that of C-cancer case. But the resectability of R-cancer was 87%, significantly lower than that of C-cancer, 92%. In R-cancer cases the rate of curative resection was 67%, not significantly different from that of C-cancer cases. The survival rate for R-cancer patients was poorer than that for C-cancer patients until 1.5 years after the operation, but the long-term prognosis was almost equal for the two types. As the macroscopic forms of R-cancer cases were found to be Borrman 2 or 3, if the subjects were limited to those with Borrman 2 or 3, the prognosis for R-cancer patients was poorer. If they were limited to absolute curative cases, the prognosis was also poorer for the patients with R-cancer. By flow cytometry, aneuploid patterns were found in 75% of R-cancer patients and the mean value of the S-phase fraction (SPF) was 25%. Those values were higher than those of C-cancer and those reported for primary gastric cancer. These findings are thought to explain the high malignancy and poor prognosis of R-cancer.

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Between 1982 and 1991, a total of 710 patients underwent gastrectomy for gastric cancer in the First Department of Surgery, Nara Medical University. Of these, 78 elderly patients aged 75 and older were divided into two age groups: 54 patients aged between 75 and 79 (defined Group A) and 24 patients aged 80 and older (defined Group B). Preoperative organ dysfunctions, operation method, postoperative complications and prognosis were compared in these two groups. As preoperative organ dysfunctions, cardiac dysfunction and diabetes mellitus were more frequently seen in Group B than in Group A. In Group B, the extent of gastrectomy and lymphnode dissection were minimized in so far as possible to obtain a shorter operation time and less intraoperative blood loss. The incidence of postoperative morbidity was 50.0% in Group A and 70.8% in Group B. As complications, cardiac insufficiency, pulmonary disease and delirium were more frequently seen in Group B than in Group A. The main cause of death was due to cancer recurrence in Group A, while it was other diseases and postoperative complications in Group B. These results suggest that, in elderly gastric cancer patients, aggressive surgery fo curative resection is recommended in patients under 80, but an adequate procedure with special care should be selected to prevent postoperative complications in patients aged 80 and older.

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In order to establish a policy regarding extended radical dissection of lymph nodes located beyond Group 3 in patients with advanced cancer of the lower stomach with duodenal invasion, I started with the hypothesis that the extent of metastasis to these groups of lymph nodes would be proportional to the tumor volume invading into the duodenum. Metastasis to the lymph nodes of Groups 3 and 4 was studied with respect to the following four factors, which could be evaluated by preoperative imaging diagnosis: 1) the length of tumor invasion into the duodenum, 2) the depth of invasion on the pyloric ring, 3) the circumferential extent of pyloric ring invasion, and 4) the pattern of invasion into the duodenum. The following results were obtained.(1) The rate of metastasis to the lymph nodes of Groups 3 and 4 was high when the length of duodenal invasion was over 10 mm, the depth of invasion on the pyloric ring was pm or greater, the circumferential extent of pyloric ring invasion was over 50%, and the pattern of invasion into the duodenum was the deep or full type.(2) When a score was assigned to each of these four factors, the following formula was able to predict metastasis to the lymph nodes of Groups 3 and 4: Z (X) =0.23X1 + 0.27X2 + 1.19X3 + 0.61X4.623, where X1 is the length of duodenal invasion, X2 is the depth of invasion on the pyloric ring, X3 is the circumferential extent of pyloric ring invasion, and X4 is the pattern of invasion into the duodenum. In the future, it should be possible to determine each factor by preoperative imaging studies, obtain a value for Z (X) by scoring the factors, and thus estimate the risk of metastasis to lymph nodes beyond Group 3. In conclusion, it wasconsidered possible to preoperatively determine the need for extended radical dissec tion of the lymph nodes of Group 3 and 4 by concomitant use of imaging diagnosis.

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We studied the relationship between reduction rate of serum bilirubin level, factors in prolonged jaundice and serum type IV collagen (7S domain) (7S) levels in 24 patients with obstructive jaundice due to various diseases. The mean value of 7S before the drainage operation in 24 patients was significantly higher than that in normal controls (p<0.001). There is no significant difference in value of 7S by sex or age, and the value was not influenced by differences either in location or duration of the obstruction. We divided 24 patients into 3 groups on the basis of the reduction rate “b”, which were a “good group”, b<-0.09; a “fair group”, -0.09≤b<-0.05; and a “poor group”, -0.05≤b.The mean value of 7S in the“poor gmup” was significantly higher than that in the“good group” (p<0.01), and the value of 7S was significantly correlated with the reduction rate“b” (p<0.01). The value of 7S inpatients with positive bacterial cultures of the bile was higher than that in those with negative cultures (p<0.05). Furthermore, the white blood cell counts correlated well with the value of 7S (p<0.01). However we did not find the significant changes in the value of 7S after the drainage operation in each of the 3 groups. These results suggest that the value of 7S before the drainage operation is one of the factors in prolonged jaundice even after that is successfully carried out, under the influence of bile infection. Thus we concluded that the measurement of serum 7S domain level before the biliary decompression is clinically useful for predicting prolonged jaundice.

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In order to examine the effects of obstructive jaundice on respiratory dysfunctions induced from acute peritonitis, change of dead space rate (VD/VT) (VD: dead space volume. VT: single ventilation volume) was measured. We also studied the ameliorative effects of dobutamine hydrochloride on the pulmonary dysfunction. 30 adult male mongrel dogs were separated into four groups. Ligation of the common bile duct was performed followed by making diffuse peritonitis after one week (Group I). Next 10 dogs were underwent only the operation to make the peritonitis (Group II). VD/VT of these dogs were continuously monitored for 6 hours. To see the effect of dobutamine, 8μg/kg/min. of dobutamine were administrated to half of Group I (Group III) or Group II dogs (Group IV) after onset of peritonitis. Peritonitis for 6 hours showed significant increase to 42.0±13.0% in Group I, whereas that of Group II dogs was kept stable at 3.2±8.7% (p<0.001). Administration of dobutamine significantly suppressed the increase of VD/VT Group III dogs (p<0.005). It was concluded that when peritonitis is associated with obstructive jaundice, VD/VT increases in the early phase of the pulmonary dysfunction and is a useful indicator of the dysfunction. In addition, dobutamine administration is effective for the treatment of pulmonary dysfunction due to obstructive jaundice and peritonitis.

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The expression of c-erbB-2 protein was examined immunohistochemically in a total of 75 freshly frozen specimens of colorectal cancer, and correlations between its expression and clinicopathological variables were analyzed. Seventy-five cases were scored by assessing the intensity of staining (strongly positive, weakely positive and negative). The incidence of strongly positive staining of c-erbB-2 protein among the 75 cases was 29.3%, and strongly positive staining was significantly correlated with lymph node metastasis, lymphatic or vascular invasion, liver or lung metastasis and Dukes' stage. These results suggest that the expression of c-erbB-2 protein may serve as a useful biological marker in colorectal cancer.

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The purpose of this study was to examine the changes in plasma endotoxin levels in the perioperative period, and to investigate the effect of nutritional status on endotoxin levels. Portal blood samples were obtained from 37 patients who underwent abdominal surgery, and the endotoxin levels were measured. The relationship between portal blood endotoxin level and preoperative serum albumin level was examined. In the 17 consecutive patients enrolled in this study, preoperative levels of several rapid transport proteins were measured, and their relation to portal blood endotoxin levels was determined. Furthermore, perioperative changes in the peripheral venous plasma endotoxin level were examined. No significant correlation was found between preoperative serum albumin level and portal blood endotoxin level, but the preoperative serum level of the third component of complement or haptoglobin was negatively correlated with the portal blood endotoxin level. The endotoxin level in plasma obtained during surgery were about 3 times higher than the preoperative values. These data suggest that malnutrition predisposes patients to increased endotoxin levels in portal blood during the abdominal surgery.

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A novel ploidy typing of flow cytometric DNA histograms by measurement of single mixed specimens was devised for accurate detection of intratumoral DNA heterogeneity. The results were compared with those obtained by static cytofluorometry (SCM) to investigate the accuracy of this method, and its relationship to clinicopatho logical findings and prognosis in 30 cases of colon cancer was investigated. To simulate the DNA histogram by computer, the aneuploid pattern was divided into A1 and 42 patterns by the coefficient of variation of the aneuploid peak. Nine of ten diploid pattern cases (90%) showed homogeneity by SCM, and ten of 12 lt2 pattern cases (83.3%) showed heterogeneity by SCM. The results with this method were consistent with the results obtained by SCM. Tumors with the A2 pattern showed a tendency toward higher frequency of liver metastasis, lymph node metastasis and a more advanced stage. This ploidy typing might be useful for detection of heterqgeneity and investigation of the relationship to clinicopathological findings and prognosis.

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A 56-year-old man visited our department for examination of type I early gastric cancer of the upper body of the stomach, which was indicated in a mass examination. Thorough examination revealed superficial and distinctly depressed early esophageal cancer of the lower intra-thoracic esophagus. The patient was admitted to our department under the diagnosis of early synchronous double cancer of esophagus and stomach, and underwent subtotal esophagectomy, cardiectomy, and reconstruction with a gastric tube. Early synchronous double cancer of esophagus and stomach is rare, and only 37 cases, including ours, have been reported inJapan. These 37 cases were reviewed and were clinically investigated in this study. The patients were 32 males and 4 females with an average age of 62 years. Many of the esophageal cancers were of the superficial and protruding type, or superficial and distinctly depressed type of the middle and lower intra-thoracic esophagus with sm invasion, and many of the gastric cancers were of the IIc type of area A. The incidence of multiple cancers was high: multiple esophageal cancers in 3 (8%) and multiple gastric cancers in 8 (22%). Subtotal esophagectomy or total gastrectomy was frequently performed (21 patients, or 57%), performed. Four (19%) of the 23 patients in whom the outcome was followed up died within one year after the operation. In operating on early synchronous double cancer of esophagus and stomach, it is important to select a surgical procedure that can yield a cure with minimal surgical stress.

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A 53-year-old woman with a huge benign liver cyst in the right lobe underwent a deroofing operation. The preoperative serum CA 19-9 level was 37.8 U, /ml. Per-cutaneous cystic needle aspiration showed serous fluid with an extremely high CA 19-9 level (135, 400 U/ml). The postoperative serum CA 19-9 increased to 438, 00 U, /ml and gradually normalized. Immunohistochemical staining of the epithelium of the cyst wall was positive for CA 19-9 The efficacy of measuring CA 19-9 in cystic fluid is under discussion. In this case the CA 19-9 level was extremely high, although benign in nature.

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Five cases of ectopic liver, a rare liver anomaly, are reported with the clinicopathological findings. The patients ranged from 34 to 65 years of age; 2 were male and 3 were female. All were asymptomatic, and the condition was found incidentally during surgery for gallbladder stone or early gastric cancer. The location was around the gallbladder in 4 cases and at the hepatoduodenal ligament in 1 case. In every case only one ectopic liver was found, and the sizes ranged from 7 to 17mm. Pathologically, the liver tissue was normal in al cases and possessed Glisson's sheath and central vein and showed stricture of the hepatic lobule. Ectopic liver is encountered incidentally during surgery, autopsy, or laparoscopy, and seldom shows clinical symptoms. Most are located around the liver, especially around the gallbladder, and are generally singular and less than 5 cm in size. Pathologically, many cases show normal liver tissue that possessed hepatic lobule. More cases will be found by precise intraoperative research and with the progress of imaging diagnosis.

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Six cases of partial hepatectomy for hepatocellular carcinoma (HCC) in hemodialysis patients are presented. All patients were male and the mean age was 52 years. Three patients had associated chronic hepatitis and the other 3 had liver cirrhosis, but liver function had not greatly deteriorated. The systemic pressure fluctuated sharply during the operation, especially in two patients with total hepatic vascular occlusion. Catheterization witha Swan-Ganz catheter and micminfusion of catecholamine were very effective for management of the intra-and post-operative circulatory status. Hemodialysis was performed without any problems using anti-oagulants, and all patients were transferred to dialysis centers about a week after the operation. Two patients had severe hemorrhagic gastritis, one with a chronic infectious fistula and the other was on hepatic arterial infusion chemotherapy. All patients survived f6r more than 1 year after the operation but 4 patients died, Three of the 4 patients who died had associated recurrent HCC. We conclude that partial hepatectomy in a hemodialysis patient may be performed successfully under careful management with due care for minimal operative invasion and prevention of gastrointestinal bleeding.

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A cholangiocellular carcinoma arising in the left lobe of liver in a 64-year-old man remained unresectable because of infiltration to the hepatic duct of the anterior segment of the right lobe. During a period of 6 months after surgery, the tumor invaded the anterior abdominal wall and caused extensive cutaneous induration and ulcer, without demonstrating further progression towards the hepatic hilum or causing obstructive jaundice. Histological examination of the lesion revealed well-differentiated tubular adenocarcinoma. Radiotherapy, hyperthermia and intra-arterial infusion chemotherapy via the bilateral internal thoracic arteries achieved no remarkable effect, the patient died 1 year and 8 months after the surgery. This type of extension of cholangiocellular carcinoma seems to be extremely rare and has seldom been reported in the domestic literature.

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A 23-year-old woman underwent pancreatoduodenectomy for pancreatic acinar cell carcinoma in October 1980. As usrgery was absolutely curative, adjuvant chemotherapy was not administered. Chemotherapy with 5-FU, CDDP and OK-432 was started when pulmonary and hepatic metastases were detected inoctober 1984. Pulmonary metastatic lesions disappeared on an X-ray image five months after chemotherapy, while hepatic metastatic lesions showed minor response. In February 1987, pulmonary metastatic lesions appeared again, however, the second chemotherapy with 5-FU, ADM and MMC failed to show any effect. The lesions were confirmed to be the metastatic lesions of acinar cell carcinoma by open lung biopsy. The patient's condition gradually deteriorated, and she died in January 1987

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We report a case of mucinous cystadenocarcinoma of the appendix that was diagnosed preoperatively. A 76-year-old woman visited our hospital complaining of pain in the umbilical region. The barium enema study revealed extrinsic compression in the ileocecal region. Abdominal ultrasonography showed a cystic tumor with a papillary elevated lesion in the right lower quadrant. Abdominal computed tomography showed a 7×5 cm cystic mass with curvilinear calcification in the ileocecal region. Colonoscopy showed a disk-like protrusion of the cecal mucosa around the orifice of the appendix, and whitish mucus drained through the orifice of the appendix. Based on these findings, we diagnosed this case as mucinous cystadenocarcinoma of the appendix and performed ileocecal resection with lymph node dissection. Histological findings demonstrated mucinous cystadenocarcinoma infil-trating the appendix wall. In Japan only 7 cases, including our case, have been diagnosed preoperatively as mucinous cystadenocarcinoma of the appendix. Ultrasonographic examination of the tumor cavity was most useful to diagnose our case.

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We experienced a case of digestive mycosis with Aspergillus. The patient was a 62-year-old woman who was introduced to our center for shock that developed 2 days after the appearance of abdominal pain. Ileocaecal resection was performed for strangulated ileus. On day 7, bloody flux occurred and endoscopy revealed sigmoid psudomembranous formation. On day 14, re-operation was performed for persistent digestive hemorrage. Ischemic changes observed in the descending and sigmoid colonic regions were resected, with an artificial anus being prepared. From about this time, β-glucan became positive and was as high as 310pg/ml on day 22, leading to the diagnosis of deep seated mycosis. The contemporaneous microbiological examination revealed the involvement of aspergillus, and the pathohistological examination revealed colonic ulceration and worm bodies of Aspergillus in the ulcer base. Following the present case, β-glucan was also effective in mycosis with other than Candida like Aspergillus, and its measurement was confirmed to be effective for the diagnosis of fungemia.

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A case of primary malignant lymphoma of the cecum which formed a large mass occupying the pelvic cavity is reported. A 17-year-old man complaining of fainting was sent to our department with a diagnosis of anemia and pelvic tumor of unknown origin. Abdominal echogram and computed tomography showed a large mass involving the intestine in the pelvic cavity. Barium enema study demonstrated stenosis of the ascending colon. Colonscopy showed a tumor with granular surface in the ascending colon, and the biopsy specimen revealed malignant lymphoma, diffuse medium cell type. Angiogram showed that the tumor was fed by the ileocolic artery. He underwent right hemicolectomy and lymph node dissection. Macroscopic examination of the resected specimen showed that the tumor originated in the cecum, and histological study revealed malignant lymphoma, diffuse medium B cell type. He underwent chemotherapy and is being followed up as an outpatient.

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