Personal experience of four decades of evolution of colorectal cancer treatment is reported. Before 1961, abdominoperineal resection with sigmoid colostomy was the sole surgical treatment for 90% of rectal cancers. After 1962, endorectal pull-through (Jinnai), invagination and anterior resection was used for 46% of the patients. In the 1980's instrumentally stapled anterior resection was performed for 75% of the patients. To improve the anal functions after very low anterior resection, such as colo-anal anastomosis, the functional outcome of the colonic J-pouch was compared with end-to-end anastomosis. The colonic J-pouch showed improvement of anal function and the 5-cm pouch resulted in contended function. There is unfortunately a discrepancy between extended surgery for cancer radicality and preservation of organ functions. As a result of pelvic node examination by the clearing method, disease-free survival and postoperative pelvic organ function, the pelvic node dissection should be limited to T3 and T4 cancers of the lower rectum and anal canal. Also there is only a 26% 5-year survival rate and a 48% local recurrence rate in patients with pelvic node metastasis. Therefore adjuvant therapies are considered to be essential. Total preservation of the autonomic nerve resulted in sufficient bladder function and erection; however, ejaculation cannot be completed. As for partial preservation, urination was satisfactory, but sexual functions were poor. Liver metastasis is the largest factor in determining the prognosis of colorectal cancer. The effect of hepatic resection for solitary metastasis was discussed, and hepatic arterial infusion with Interleukin-2, MMC, 5-FU for unresectable metastasis gave a response rate as high as 76% including 20% complete response, and a 5-year survival rate of 28%. Locoregional immunochemotherapy is effective for liver metastasis, because the liver is an extramedullary hematopoietic organ.

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It is well known that deficiency of vitamin B12 or folic acid results in megaloblastic anemia in post-gastrectomized patients. However, there are some patients who exhibit macrocytic anemia in spite of normal levels of both vitamin B12 and folic acid. This study was conducted to investigate the relationship between the occurrence of anemia and changes in the levels of vitamin B12 binding protein in gastrectomized patients. Anemia was seen in 105 of 151 post-gastrectomized patients and macrocytic anemia was observed in 35 of the 105 patients. Serum levels of vitamin B12-binding protein in the patients with macrocytic anemia were higher than those of normal volunteer controls. This increase was seen even in the patients with normal levels of vitamin B12. Transcobalamin II, the only protein that can transport vitamin B12 into the tissues from the serum, was not decresed, however, the serum levels of holotranscobalamin II, a form of transcobalamin II binding to vitamin B12, was decreased in gastrectomized patients. These results may suggest that functional deficiency of vitamin B12 might be present in the gastrectomized patients even with normal serum levels of vitamin B12.

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Thirty-six mongrel dogs underwent 70% partial hepatectomy (HTX), and splenic arterial-portal venous shunt (AP-shunt) was performed for partial portal arterialization. The experimental groups were as follows: group I, 70% HTX; group II, 70% HTX+ splenectomy; group III, 70% HTX+splenectomy+ AP-shunt. The effect of splenic AP-shunt on hepatic function and hepatic regeneration after 70% HTX was determined. Arterial ketone body ratio was higher in group III than in group I and group II on the first postoperative day (POD) (p<0.05). Hepaplastin levels were also higher in group III than in group I and group II on POD 7 (p<0.05). Hepatic DNA synthesis was markedly increased in group III on POD 4, 7 compared to group I and group II (p<0.05) and significantly increased expresion of MIB-1 staining as an indicator of mitosis was found in group III. It is concluded that partial portal arterialization by splenic AP-shunt might enhance hepatic regeneration and hepatic functional revovery after 70% HTX through increased oxygen supply to the remaining liver.

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In the present study immunohistochemical staining was used to detect for fibronectin (FN) in 53 primary pancreatic cancers (including 9 mucin-producing pancreatic cancers), 26 metastatic lesions and 22 benign diseases. Its expression was examined in regard to its relation to the clinicopathological factors and the patients' prognosis. FN was present in the basement membrane (BM) in 11% of primary pancreatic cancers (6/53), 8% of metastatic lesions (2/26) and 22% of benign diseases (4.22). Five of the six cases of primary pancreatic cancer in which FN was positive in the BM were mucin-producing pancreatic cancers, which are well known to have a relatively good prognosis in general. The rate of positive BM-FN in mucin-producing pancreatic cancers was significantly higher than that in non producing common invasive ductal carcinomas. But there were no significant differences in the rate of positive FN in the cytoplasm among the three groups. The rate of positive FN in the extracellular matrix of benign diseases was significantly higher than those of primary pancreatic cancers and metastatic lesions. The rate of positive BM-FN in low-stage cancers was significantly higher than that in high-stage cancers. Among the patients whose primary pancreatic cancers had been resected, the long-term survivors were seen in the BM-FN-positive groups. These results suggest that FN may play an important role in inhibiting the invasion and metastasis of pancreatic cancer.

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To evaluate the efficacy and safety of recombinant human erythropoietin (r-HuEPO) for gastrointestinal cancer surgery, we performed preoperative blood donation in 19 patients (7 with gastric cancer, 8 with rectal cancer, 4 with esophageal cancer), who were to undergo elective surgery. These patients were divided into two groups according to their initial hemoglobin concentration. Nine patients with hemoglobin concentrations from 11.0g/dl to 13.0g/dl (Group I), donated 800ml of autologous blood preoperatively with r-HuEPO (24, 000 U) administration once a week subcutaneously. Ten patients with hemoglobin concentrations more than 13.0g/dl (Group II), donated 800ml of blood without r-HuEPO administration. All the patients were given ferrous sulphate (210mg of iron) orally every day for three weeks before the operation. There were no significant differences in the background between the two groups except hemoglobin concentration. The amount of donated autologous blood (755.6±83.1 vs 760.0±120.0), and operative blood loss (780.4±418.7 vs 979.0±247.5) were similar in the two groups. Only one patient in group II required additional homologous blood transfusion. Hemoglobin concentration was significantly (p<0.001) reduced in group II by blood donation, but in group I the hemoglobin concentration did not decrease after donation. The reticulocyte count and serum erythropoietin concentration were significantly (p<0.001, p<0.01) higher in group I; therefore r-HuEPO can accelerated the erythropoietic reaction and red cell production in anemic cancer patients. Iron kinetic examination revealed that a disorder in ferrous sulphate utilization in cancer patients. Serum protein reduction and the prolongation of anticoagulant time (PT, APTT) were observed in both groups, although these changes were not significant. None of the 19 patients showed any adverse effects or abnormal laboratory data attributable to r-HuEPO administration. This study indicates the safety of autologous blood donation in gastrointestinal cancer surgery, and effectiveness of r-HuEPO administration in anemic patients.

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In order to elucidate the mechanism of cytokine induction by biological response modifiers (BRM), the expression of cytokine mRNA in human peripheral blood mononuclear cells (PBMC) cultured with OK-432 or polysaccharide K (PSK) was serially analyzed by the reverse transcription-polymerase chain reaction (RT-PCR) method. IL-1β, IL-6 and TNF-α mRNAs were induced within one hour after stimulaion. IL-2 and IFN-γ mRNAs were induced three hours later in OK-432-stimulated PBMC, whereas they were not induced up to 24 hours later in PSK-stimulated PBMC. Production of cytokine proteins increased 1 to 3 hours after mRNA induction. It is important to consider various host factors when BRM therapy is employed. To investigate individual differences in response to BRM, cytokine mRNA induction in PBMC from OK-432-treated patients was analyzed. In 4 out of 34 intradermally injected patients, multiple cytokine mRNAs were strongly induced. We speculate that these patients may have shown good responses to BRM therapy.

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We experienced a case of resected intrahepatic cholangiocarcinoma, which did not form a mass in the liver but was growing only in the intraductal lumen. A 62-year-old woman was admitted to our hospital for an operation for intrahepatic cholangiocarcinoma. Abdominal ultrasonography and CT revealed a 4-cm tumor, including the dilated intrahepatic duct, in the right hepatic lobe. The lobe was resected under intraoperative ultrasonography. But the resected specimen did not contain a mass and many tumor thromboses were found in the dilated hepatic duct. Histologically the bile duct wall and the tumor showed well differentiated adenocarcinoma. Clinical fiundings of the tumor growing intraductally without forming a mass are now meaning not clear. It is difficult for an intrahepatic cholangiocarcinoma with intraductal growth to be diagnosed precisely and it is necessary for us to decide on the range of resection carefully.

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A 75-year-old woman who complained abdominal pain and vomiting and had no previous laparotomy was diagnosed as having ileus. A long tube was placed to decompress of the intestine. After symptoms were disappeared, she began oral intake. After that she had a fever, right hip joint pain, and swelling of the right femoral area. She received an incision in that area because of the phlegmon. Then, a continuous fecal discharge was observed from this incision. Fistulography showed a fecal fistula connected to the small bowel through the femoral cananl. Therefore we made a diagnosis of perforation of small intestine by incarcerated femoral hernia caused necrotizing fasciitis of the right thigh. At the operation, the incarcerated part of the ileum wall was necrosed and perforated into the femoral canal. Partial resection of the ileum and debridement of the right thigh were performed. Nineteen days after the operation, skin plantation was done. No complications occurred postoperatively. Diagnosis of Richter hernia is likely to be late, since there are often no marked local findings. This suggests that Richter's hernia should be considered in a case of intestinal obstruction without previous laparotomy.

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It is well known that an unused intestinal tract after colostomy or ileostomy for various conditionsshows atrophic changes. We investigate histopathologically the case of an external fistula of the ileum with ileum and colon unused for 50 years. A 73-year-old woman, who had a past history of surgical treatment of an ovarian disease and ileus at another hospital, had the complication of an external fistula of the ileum for 50 years. We performed laparotomy and resected the fistula, surrounding adhesive ileum, the distal ileum and the cecum for a length of the about a meter. Macroscopical findings of the resected specimen were marked atrophy of the wall and muscle layer of the distal ileum to the fistula and the colon. In histological sections of the surgical specimen, we found almost normal villi and crypts with brush border/microvilli, but low density and short length of tubules in the distal ileum to the fistula. We refer to a paper which reported that a total abstinence from food made brush border/microvilli be lost in the mucosa of an unused alimentary canal, a continued oral diet was important to maintain absorbing function (brush border/microvilli). Histologically, there was marked chronic inflammatory cell infiltration in the unused colonic mucosa, however, these findings disappeared at the colonic biopsy specimen a year after the operation. We propose that a form of nonspecific colitis is one of the cause of absorbing dysfunction.

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We report surgical case of probable intestinal Behcet's disease with perforating multiple ulcers in the right colon. A 46-year-old woman visited our clinic complaining of abdominal pain and fever on March 25, 1994. She had recurrent aphthoid ulcers of the oral cavity and lips. An emergency operation was performed under a diagnosis of perforating peritonitis on day 5 after admission. There were multiple perforations in the cecum and ascending and transverse colon. Right extensive hemicolectomy was performed. Macroscopic examination of the resected colon revealed multiple discrete and punched-out ulcers and erosions. These ulcers were shaped like a spindle and perforations were seen in at least 15 points in the resected specimen. Microscopically there was a nonspecific inflammatory infiltrate in the neighborhood of the ulcers. These ulcers penetrated through the mucosa into the muscularis proria or serosa. According to the postoperative study of HLA types, HLA-B5 and HLA-Bw51 were detected and genital aphthoid ulcers also appeared postoperatively. Therefore intestinal Behcet's disease was suspected. A case like this was thought to be very uncommon because of the multiple perforations due to the characteristically shaped ulcers in the colon.

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