Preclinical research approaches to esophageal cancer using cultured human esophageal cancer cells include 1) hyperthermia experiments, 2) chemotherapy experiments, 3) chemo-hyperthermia experiments, 4) combining TNF with hyperthermia, 5) combining TNF with Δ¹² prostaglandin J2, 6) appearance of fibrinolytic factor and fibrinolysis inhibitor factor, 7) chromosome analysis of esophageal carcinoma cultured cell lines and 8) production of water in oil in water-type lipiodol emulsion. In the clinical treatment of esophageal cancer, I employed esophageal reconstruction prior to esophagectomy as a standard surgical procedure. In this procedure, two separate teams perform the operation in the cervical and abdominal regions simultaneously, and thorough lymph node dissection is performed in each area. From 1985, taking advantage of this surgical procedure, we have employed three-field dissections in carefully selected cases. Since the founding of our institute, we have performed 242 esophagectomies with an operative death rate of 2.5% and 5-uyear-survival rate of 21.7%.

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The cell kinetics of epithelium in the gastric remnant were studied using several parameters including S phase cell population, PCNA labeling index and ODC activity in terms of portion, operative procedure (Billroth I or II) and duration after operation in 64 patients. PCNA LI and ODC activity in the stomal mucosa were significantly higher than in the greater curvature. This difference was especially pronounced in the group with the B-II procedure. Significantly higher PCNA LI and ODC activity of the stomal mucosa was recognized in the group with the B-II procedure than in that with the B-I procedure. PCNA LI and ODC activity of the stomal mucosa in B-II were significantly higher 5 or more years after surgery than less than 5 years after surgery, however those with B-I showed a contrasting tendency. Parameters in the group with a duration of 5 or more years with the B-II procedure showed significantly higher levels than the group with the B-I procedure. The present study showed that the cell kinetics of stomal mucosa in the gastric remnant were high, especially in the group with a duration of 5 or more years after surgery with the B-II procedure, sugesting that stomal mucosa in the gastric remnant reconstructed with the B-II procedure may have a high risk of promoting carcinogenesis.

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We investigated the indications for conservative surgery in 351 early gastric cancers according to the relationship between lymph node metastasis and the clinicopathological factotrs. The incidence of lymph nodes metastasis in cases of mucosal cancer (m ca.) and submucosal cancer (sm ca.) were 5.4% and 18.0%, respectively. The rate of lymph node metastasis of sm ca. was slightly higher than that of m ca. for each clinicopathological factor. Furthermore, the presence of lymph node metastasis was determined by multivariate analysis using the type II quantification method. Lymph node metastasis of gastric cancer had a closer relationship to histological type, tumor size and gross findings than to depth of invasion, location of the tumor, or preoperative CEA value. The rates of lymph node metastasis were significantly higher for tumors 4 cm or larger, por on histological type, advanced type and elevated + depressed type on the gross findings. Rates were lower for the flat type on gross findings, and for tumors less than 3 cm in diameter. The accuracy rate in discriminating between the two groups was 71.7%. Conservative surgery is performed on cases that scored lower than the cutoff point. However, when the score is below the cutoff point in cases involving por or UI (+), findings should be reviewed carefully. This analysis may be useful for predicting the presence of lymph node metastasis before surgery, and helpful in determining whether to perform conservative surgery.

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Of 61 patients with Borrmann type 4 gastric cancer (B4GC) the 1-and 3-year survival rates of curability A patients (n=18) were 94 and 60%; those of curability B (n=9), curability C (n=24), and no resection (n=10) patients were 56 and 11%, 46 and 0%, and 0 and 0%, respectively. The survival curve of the curability A group was significantly better than any other groups (p<0.01). In prophylactic continuous hyperthermic peritoneal perfusion (CHPP) for B4GC with serosal invasion and PO or P1 peritoneal seedings, 2-and 4-year survival rates of the CHPP (+) group were 90 and 56%, significantly higher than the 67 and 27% of the CHPP (-) group (p=0.02). In therapeutic CHPP for B4GC with P2 or P3 peritoneal seedings, the survival curve of the CHPP (+) group was significantly better than that of the CHPP (-) group (p=0.04). But no patient with P2 or P3 peritoneal seedings survived over 3 years. These results suggested that curability A or B resection and prophylactic CHPP for PO or P1 peritoneal seedings prolonged survival in B4GC, but the prognosis of B4GC with P2 or P3 peritoneal seedings was not ameliorated by therapeutic CHPP. New treatment modalities, such as neoadjuvant chemotherapy, need to be developed against severe peritoneal seedings.

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Fifty-seven patients with unresectable gastric cancer that received palliative gastrojejunostomy (36 cases of conventional type: group A, 21 cases of gastric exclusion: group B) were retrospectively examined as to their postoperative quality of life (QOL) and outcome. The frequency of postoperative gastrointestinal bleeding and blood transfusion (ml/month) were significantly lower in group B (500 ml/m) than in group A (1, 288 ml/m). These advantages enabled group B to achieve a better QOL as indicated by prolongation of the period of both postoperative oral intake (97 days vs 201 days) and home stay (97 days vs 178 days). The prognosis also improved, and the 50% survival period in group B was 189 days, whereas that in group A was 111 days. In conclusion, we recommend gastric exclusion as a useful operation for the Iower or middle third of unresectable gastric cancer.

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We studied quality of life (QOL) after gastrectomy in 87 patients with gastric cancer with referenceto patient's knowledge of the diagnosis. QOL was assessed by a questionnaire consisting of 12 itemsdivided into physical, psychological and social factors. The results were scored from 1 to 5 and the totalscore (from 12 to 60) represented the QOL of the patients. The QOL of the patients who had knowledgeof their cancer was significantly better than that of patients without such knowledge (49.4 vs 45.7, p=0.0067). The background of the two groups was different in time after operation and operative methods.However, the QOL of the patients with knowledge of their diagnosis longer than 6 months after distal gastrectomy was also better than that in patients without such information (51.6 vs 45.3, p=0.0014).Knowledge of the diagnosis raised the physical and social assessment, but did not raise the psychological assessment. In particular, the score for uneasiness about the disease in patients with knowledge of theircancer was significantly worse within 6 months after surgery (p=0.0136). It was suggested that psychological support was essential for patients who were told their diagnosis.

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In the present study we investigated the influence of the extent of hepatic resection on postoperativeprognosis for solitary hepatocellular carcinoma (HCC) smaller than 2cm in diameter. Forty two patientswith small primary HCC underwent curative hepatic resection without any operative deaths. Twenty-eight of these 42 patients underwent minor hepatic resection limited to subsegmentectomy, and theremaining 14 patients underwent major hepatic resection more extensive than segmentectomy. Background and postoperative prognosis were compared between these two groups. There were no statisti-cally significant difference between the two groups in background factors including reserve of liverfunction, stage of disease and various factors related to the operative procedure. There was no statisti-cally significant difference in the incidence of postoperative complications between the two groups. Thesurvival rates at 3 and 5 years in the group with minor hepatic resection were 88% and 54%, respectively.They were 100% and 75%, respectively, in the other group. The survival rate of the latter group tended to be better than that of the former group. However, the difference did not reach statistical significance.The rate of recurrence was not significantly different between the two groups. In conclusion, if limitedhepatic resection is expected to be sufficiently curative, it should be considered for small solitary HCC in the early stage.

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The significance of second hepatectomy for recurrent liver metastases from colorectal carcinomawas analyzed in this study. One hundred and seven patients underwent resection of the liver for colorectalcarcinoma metastases between May 1979 and July 1994, ten of whom received a second hepatectomy forrecurrent disease in the residual liver. Although the disease-free interval, size of the tumor, and numberof metastases did not correlate with the prognosis after second hepatectomy, patients with multiplelesions in the bilateral hepatic lobe showed relapse to the remaining liver and died within several monthsof surgery. On the other hand, patients with recurrent lesions in the same hepatic lobe as the metastasesat the first resection survived longer than 4 years without disease. The overall survival rates after secondhepatectomy at 1, 3 and 5 years were 75.0%, 42.8% and 42.8%, and the disease-free survival rates were66.7%, 33.3% and 33.3%, respectively, which were comparable to the result of the first hepatectomy.Therefore, second hepatic resection for liver metastases from colorectal cancer is very beneficial andshould be aggressively performed in selected patients under careful diagnosis.

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An experimental liver micrometastatic model of colorectal carcinoma was developed and the effectsof combination therapy with OK-432 and γIL-2 by splenic injection to inhibit liver metastasis, a criticalelement of prognosis of colorectal carcinoma, were determined. Micrometastasis in the liver was observed on day7 after transportal inoculaiton of colon 26 cells, which are murine colon carcinoma cells.Although the mice were treated with drugs after the development of micrometastasis in the liver, both treatment with each drug singly and in combination resulted in significant inhibition of the developmentof liver metastasis compared with the control (p<0.005). Combined treatment significantly inhibited thedevelopment of liver metastasis compared with OK-432 alone (p<0.025). The anti-tumor activity of splenic cells injected with drugs became stronger. These results suggest that intrasplenic drug injection was effective in inhibiting liver metastasis.

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The relation between prostaglandins, c-erbB-2 and DNA ploidy pattern was investigated in 55patients with colon cancer (11 with hepatic metastasis and 44 without hepatic metastasis) to assess malignant potential. The c-erbB-2 oncoprotein was immunohistochemically stained using a polyclonalantibody. Prostaglandin E₂ and D₂ were determined by the DCC method. DNA ploidy was determinedfrom formalin-fixed, paraffin-embedded tissue using an Epics-751 flow cytometer. The positive stainingrate of c-erbB-2 oncoprotein in the positive metastatic group was higher than that in the negative group.The DNA aneuploidy rate and mean of D.I. in the positive staining group were higher than those in thenegative staining group. There fore, it is suggested that c-erbB-2 might be an indicator for assessing themalignant potential of colon cancer. PGE₂ and D₂ tissue concentrations were lower in the positive metastatic group and/or positive oncoprotein cases. These findings suggest that PGs might play a role ininhibiting hepatic metastasis in colon cancer.

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To investigate the therapeutic efficacy of G-CSF in treating peritonitis, we examined its effect on themortality and function of polymorphonuclear leukocytes (PMN) in a rat peritonitis model. E. coli wasadministered intraperitoneally. G-CSF and/or an antibiotic (LMOX) were given to rats after the onset ofperitonitis. The mortality rate was decreased by simultaneous administration of G-CSF. Moreover, theadministration of G-CSF in combination with LMOX induced a marked increase in the survival rate (100%), and resutlted in improvement of the peripheral leukocyte count. The ability of PMN to generate O₂^- in the LMOX+G-CSF treated group was significantly enhanced as compared with that of the othertreated groups. The plasma endothelin-1 (ET-1) level was shown to be the lowest in the group treated with LMOX+G-CSF and to correlate with a decrease in the rat mortality in contrast with the endotoxin level.The combined use of G-CSF in treatment did not induce the findings of acute lung injury. These resultssuggest that G-CSF may have a protective effect on survival and also provide excellent support toantibiotics in the treatment of severe peritonitis. In addition, in this series of experiments, the plasma ET-1 level, regardless of endotoxin, was a useful indicator of the severity of peritonitis.

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An extremely rare case of Alport-leiomyomatosis syndrome in a 23-year-old woman who had complained of dysphagia and chest oppression since 1986 is reported. She was admitted to our hospital because of a mediastinal mass on a chest radiograph in October 1990. We diagnosed the mass as a diffuse type of the esophageal leiomyoma. Subtotal esophagectomy was performed under the left thoracotomy followed by reconstruction using a gastric tube. The tumors in the upper and lower thoracic portion of the esophagus measured 8.5cm×5.5cm and 13.9cm×7.8cm in diameter, respectively, with no invasive findings. Pathological examination revealed diffuse hypertrophy of the internal circular muscle the esophagus. Also the microscopic findings of leiomyomatous changes were found in the middle thoracic portion and oral surgical margin of the esophagus in which we could not detect a tumor rnacroscopically. No malignant signs were observed, The cases of diffuse leiomyomatosis of the esophagus accompanied by disorders found in the Alport syndrome was well analysed in recent yeas by Garcia-Torres and Orozco ⁴⁾, and they have reported as a new syndrome naming Alport-leiomyomatosis syndrome. This case had a hereditary history, nephropathy, clitoral hypertrophy and bilateral myopia co-existed.

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We report two cases of morbid obesity accompanied with obstructive sleep apnea syndrome (SAS) and obesity hypoventilation syndrome (OHS). Pulmonary function test and overnight sleep study by polysomno-graphic recording were performed before and after surgery. Satisfactory weight control was obtained without surgical complications after vertical banded gastroplasty (VBG).With the reduction in weight, the symptoms of SAS and OHS, as well as several other complications caused by the severe obesity, disappeared. Quality of life also improved remarkably, as exhibited by activity performance and disappearance of irritability at waking. The improvement in hypoventilation was attributed to a reduc-tion in excessive fatty deposition in the neck and pharyngeal wall, the chest wall and the abdomen. Thus it appeared that VBG is efficacious in the treatment of morbid obesity with sleepapnea and hypoventila-tion.

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Ischemic necrosis of the gastric remnant is a rare and serious complication of distal gastrectomy. The authors report one case after distal gastrectomy without splenectomy, and a review of the literature. The patient was a 61-year-old woman who had recieved distal gastrectomy for early gastric cancer. On the 6 th postoperative day, the patient developed peritonitis due to perforation of the gastric remnant. At uregent laparotomy, a large necrotic area was found at the short gastric vessels of the gastric remnant. Total gastrectomy and abdominal drainage were performed. Seven months aftersurgery, the patient remains well. The overall mortality in a review of these cases was 70%. It is hoped that earlier diagnosis will lead to lower morbidity and mortality.

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A case of α-fetoprotein (AFP) producing gastric carcinoma with portal venous tumor thrombosis was experienced. The patient was a 72-year-old man diagnosed as having gastric carcinoma, whose serum level of AFP was markedly elevated to 20, 780 ng/ml. In laparotomy, gastric carcinoma was T₃, N₃, P₀, H₀, M₀, Stage IV a according to the General rules for the gastric cancer study. We found out an induration in the portal vein and performed the portogram. It revealed complete obstruction of the portal vein. We performed total gastrectomy, removal of the tumor thrombus and insertion the catheter into the portal vein. Histological examination showed that some tissues resembled hepatocellular carcinoma. Immuno-histochemical study revealed that the gastric carcinoma, tumor thrombus and metastatic lymph node were positively stained with AFP-antiserum. Postoperative chemotherapy has been performed with 5-fluorouracil, mitomycin C and cisplatin, the patient is still alive for 5 months after operation.

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A case of hyperammonemia and coma induced by sodium valproate (VPA) after hepatectomy for liver metastasis is reported.A 50-year-old man who suffered from cerebral infarction in the past, had been taking VPA as an anti-convulsant drug.The course after hepatectomy wasuneventful, and food intake was begun from the 4th postoperative day with lactulose and VPA. Four days after the interruption of lactulose, he complained of general malaise. Five days after the interruption of lactulose, he fell into coma.Although there were no abnormalities in liver function examinations and brain computed tomography, the ammonia level was so high that we suspected the coma was due to hyperammonemia induced as a possible side effect of the drug.He regained consciousness 2 days after the interruption of VPA and administration of lactulose and morihepamine. Ammonia was high on the preoperative day when VPA was administrated. Ammonia decreased during transient elevation just after the operation when VPA was interrupted, and became elevated with VPA re-administration. Analysis of amino acids revealed a decrease in arginine with VPA administration. The above suggests that coma resulted from inhibition of the urea cycle, which was induced by VPA and hepatectomy.

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A 53-year-old man with jaundice was diagnosed with hepatic hilum cancer of the bile duct. He had tarry stool 13 days after PTCB performed for relief from jaundice. Emergency angiography confirmed the aneurysm at a branch of the right hepatic artery, and we embolized the right hepatic artery for massive hemobilia. Post-TAE angiography did not indicate hemorrhage, but his anemia progressed slowly, angiography performed on the next day again showed no massive hemobilia and showed the extravasation of contrast medium from a proximal branch of the right hepatic and the gastroduodenal arteries. TAE of the proper hepatic artery was attempted, and continuous intraarterial infusion of pitressin at the gastroduodenal artery was started. Subsequently, his physical condition improved without hemorrhage, and eventually hepatopancreaticoduodenectomy could be performed. Thus, it is concluded that TAE plus continuous intraarterial infusion of pitressin were usefull in the management of hemobilia due to bile duct cancer.

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We report a case of Alonso-Lej II (diverticilum type) congenital choledochal cyst with bile duct stone. The patient was a 63-year-old man with the chief complaint of epigastralgia. A few hyperechoic masses in the gallbladder were detected by ultrasonography. Faint filling defects and extracanal pooling of contrast medium in the terminal common bile duct were revealed by ERG. ChoIecystectomy, chloledocholithotomy and transduodenal papilloplasty were performed. A small diverticulum of the common bile duct and blackc stones in it and the gallbladder were noted. Diverticulum of the common bile duct has been reported in 22 cases in the Japanese literatures. Adult cases numbered 13. These cases showed clinical aspects of bile duct stone, pancreatitis, and bile duct cancer, as well as Alonso-Lej I cyst.

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A 52-year-old woman with a fibrous polyp of the gallbladder is reported. The patient had an upper abdominal pain, so she underwent gastrofiberscopy and ultrasonography. The latter showed a polypoid lesion which had both hyperechoic and solid echo elements. Subsequently drip-infusion cholangiography revealed a nodular spherical filling defect in the fundus. Under suspicion of carcinoma of the gallbladbladder, a cholecystectomy with dissection of the lymnph node around the common bile duct was performed. We found a pedunculated polyp, 17×25×17mm in size, on the fundus and normal mucosa. The polyp was composed of loose connective tissue with inflammatory infiltration and a vascular network. There was no evidence of a malignancy. These findings were consistent with those of a fibrous polyp. These polyps tend to enlarge more than 10mm in size. In ultrasonography they are shown small nodular or granular surface and solid element. Our case is the second largest one of the 22 fibrous polyps ever reported.

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A case of necrotic Meckel's diverticulum due to torsion at its neck, resulting in perforative peritonitis, is reported. The patient, a 32-year-old man was admitted with the complaint of lower abdominal pain. Emergency laparotomy was performed under the diagnosis of acute peritonitis; Meckel's diverticulum, 8.5×5.0cm in size, was found to protrude from the lateral wall of the ileum about 50cm proximal to Bauhin's valve, and was voluvulated about 360 degrees clockwise at its neck and necrotized. Perforation, 2mm in diameter, was present at the body of the diverticulum, causing acute pan-peritonitis. Partial resection of the ileum and peritoneal lavage were performed. Torsion is a rare complication of Meckel's diverticulum, and we found only 9 reported cases, including ours, in Japan. Those cases were also large in size, greater than 6cm (mean 11.5cm) in length, and had a narrow neck of the diverticulum. It is thought that large size and a narrow neck of the diverticulum may be an anatomical factor in torsion of Meckel's diverticulum.

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Two cases of goblet cell carcinoid of the appendix were reported with a review of the Japanese literature. Both patients were male, one 46 and the other 41 years old. They had symptoms consistent with acute appendicitis and underwent appendectomy. Pathological examination revealed goblet cell carcinoid in addition to acute inflammation of the appendix. Both patients subsequently underwent right hemicolectomy. No neoplastic cells were detected histologically in either specimen. One was well 2 years and 2 months, the other was well 2 years after the operation. Thirty-one cases including these two were collected from the Japanese literature. Most of them had surgery after a diagnosis of acute appendicitis, though an ileocecal tumor was suspected in a few advanced cases. Appendectomy alone with postoperative follow up, ileocecal resection or right hemicolectomy were choise of the treatments in them. Metastasis or recurrence was observed in a few cases, suggesting of necessity of aggressive surgical treatment.

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Perianal Paget's disease is rare. Only twenty cases, including ours, have been reported in Japan, and almost all of them have been associated with malignant tumors. We describe one case of Paget's disease with anal cancer originating from anal glands. A 79-year-old man came to our hospital with chief complaints of anal tumor and bleeding. We found an anal tumor on the dentate line and perianal erosion. Biopsy of the anal tumor reveraled signet ring cell carcinoma, and abdominoperineal resection was performed. Histologically, the anal tumor was mucocellular carcinoma with mucous lake, and the perianal erosion was due to the intraepidermal spread of signet ring cells, i.e., Paget's cells. Based on the literature, we report that perianal Paget's disease shows a relationship with anaI cancer originating from anal glands.

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Extended hepatic surgery and hepatic transplantation under total vasuclar exclusion technique has been established. We applied this technique to a patient with tumor thrombus extending to the retrohepatic vena cava and arising from advanced renal cell carcinoma. After left nephrectomy, we carried out thrombectomy under total hepatic vascular exclusion with partial extracorporeal circulation using a Bio-pumpe^® (BP-80), because the tumor thrombus reached the level of the main hepatic outlet. In addition, hypothermic perfusion of the liver using 1000ml of Lactate Ringer solution at 4°C was performed to preserve liver function. Total ischemic time of the liver was 36 minutes. The duration of the critical level of arterial ketone body ratio (<0.4) was 30minutes during this operation. Serum GOT and GPT levels rose to 255 and 170 KU on the first postoperative day and returned to normal by the 14th postoperative day. Extensive tumor thrombus in the inferior vena cava could be removed safely without any additinal damage to the liver under partial extracorporeal circulationand the hypothermic perfusion technique.

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