Cronkhite-Canada syndrome associated with a rectal cancer and adenomatous changes in colonic polyps.

A 52-year-old man with the clinical features of Cronkhite-Canada syndrome developed rectal cancer. Radiologic and endoscopic examinations revealed gastrointestinal polyposis. Histologic examination of the biopsied polyps showed cystic dilatation of glands with an inflammatory stroma. A later biopsy from a rectal polyp proved to be an adenocarcinoma. The totally resected colon and upper rectum had an ulcerated rectal cancer and numerous polyps; most of the polyps showed histological changes typical of the syndrome. Only three polyps had adenomatous changes at their surfaces. Adenomatous and carcinomatous changes of epithelia can occur in non-neoplastic polyposis of Cronkhite-Canada syndrome from which presumably a carcinoma can develop, as in the present case.

Late development of bile duct cancer after sphincteroplasty: a ten- to twenty-two-year follow-up study.

BACKGROUND: Transduodenal sphincteroplasty is designed to destroy the sphincteric muscle fibers, producing a terminal choledochoduodenostomy. In the absence of Oddi's sphincter, intestinal contents with both activated pancreatic juice and bacterial flora are refluxed into the bile duct and remain there for a prolonged time. The long-term effect of producing the reflux has not been evaluated to date. METHODS: One hundred nineteen consecutive patients undergoing transduodenal sphincteroplasty between February 1973 and July 1984 were included in this study. Postoperative clinical courses of 108 patients could be evaluated by means of a retrospective review of the hospital records. Median follow-up was 18 years. RESULTS: Eight cases (7.4%) of primary bile duct cancer were found among the 108 cases at intervals of 1 to 20 years after sphincteroplasty. Two patients had concurrent hepatolithiasis. The patency of sphincteroplasty was confirmed in all cases, and the bile was infected in seven cases. Pathologic specimens obtained demonstrated cholangiocarcinomas and various degrees of atypical hyperplastic lesions under the background of chronic cholangitis. CONCLUSIONS: Chronic cholangitis can be an important causative factor in late development of bile duct cancer after sphincteroplasty. Any patients treated with choledochoduodenostomy should be closely monitored for late cholangiocarcinoma.

Possible role of hepatic bile mucus glycoprotein in development of intrahepatic gallstones.

To study the role played by hepatic bile mucus glycoprotein in the development of hepatolithiasis, mucus glycoprotein, isolated from the bile of patients with intrahepatic gallstones by gel filtration and ultracentrifugation, was examined for precipitability in control hepatic bile obtained postoperatively from patients successfully treated for cholecysto- and/or choledocho-lithiasis. When the mucus glycoprotein was incubated at 38 degrees C for 48 h in the control hepatic bile in the presence of calcium ions, massive precipitation was produced. The precipitation was inhibited by treating the mucus glycoprotein with acid, alkali, a reducing reagent, or protease, the inhibition being most effective with acid, which splits up carbohydrate chains. This suggests that the precipitability of the mucus glycoprotein resides mainly in its carbohydrate chains. These observations imply that the development of intrahepatic gallstones, calcium bilirubinate stones in particular, could be prevented by degrading mucus glycoprotein in hepatic bile.

Regurgitant bile acids and mucosal injury of the gastric remnant after partial gastrectomy.

Three groups, each consisting of seven patients who had undergone either Billroth I, Billroth II, or pylorus-preserving gastrectomies, were evaluated more than 18 months postoperatively in terms of concentration and amount of bile acids in the gastric aspirate and histologic changes in the gastric remnant mucosa. Concentrations of bile acids were determined by gas chromatography and mucosal specimens were obtained by endoscopic biopsy. The total bile acid concentration and all of the individual fractional bile acid levels, whether free or conjugated, were significantly higher in the Billroth II group than in the other two groups. The amount of gastric aspirate was also highest in the Billroth II group. Endoscopic biopsy revealed glandular dysplasia to be predominantly in the Billroth II group. The presence of bile acids in the gastric remnant may contribute to mucosal injury, possibly leading to cancer in the gastric remnant, especially after the Billroth II operation.

Semiquantitative evaluation of hepatic fibrosis by measuring tissue hydroxyproline.

BACKGROUND/AIMS: It is important to evaluate the degree of hepatic fibrosis when diagnosing and treating hepatic cirrhosis. We focused on hydroxyproline, which is detected specifically in collagen, which plays a major role in hepatic fibrosis. The correlations between liver tissue hydroxyproline residue levels and the degree of hepatic fibrosis were examined in dogs with dimethylnitrosamine-induced fibrotic livers. METHODOLOGY: Dimethylnitrosamine was administered to dogs to establish experimental hepatic fibrosis. Paraffinized sections of liver specimens, stained with hematoxylin-eosin and azan, were examined and the degree of hepatic fibrosis was graded. About three-milligram samples of liver tissue were loaded onto a fully automated liquid chromatograph and the levels of hydroxyproline residues were measured. RESULTS: The liver tissue hydroxyproline appeared to reflect the degree of hepatic fibrosis. The liver tissue hydroxyproline levels and pathological hepatic fibrosis grades correlated significantly (p<0.05). CONCLUSIONS: Tissue hydroxyproline appears to be a more useful fibrosis marker, because hydroxyproline is influenced less by other factors. Furthermore, our results demonstrate that a very small amount of liver tissue (wet weight 3 mg) was enough to enable the levels of hydroxyproline residues to be measured by an automated amino acid analyzer (JLC-3000) and hepatic fibrosis is expressed as the numerical value by this analysis.

[Five cases of rectal cancer showing remarkable response to suppository administration of tegafur].

Five cases of rectal cancer, one male and 4 females, were preoperatively treated with Tegafur suppositories at 1,500 mg per day, for 8 to 21 days (mean, 14 days). These tumors were 2 early cancers and 3 advanced cancers, the configuration of which were one IIa type, one IIa + IIc type and 3 Borrmann 2 types. Their size ranged from 1.3 to 4.2 cm in diameter. Curative resections were performed in all cases, and the examination of the resected specimen revealed marked effects of Tegafur as follows: 1) Reduction of tumor size, 2) disappearance of cancer wall, 3) degeneration of cancer cells and destruction of cancer glands accompanied by fibrous stroma with infiltration of lymphocytes and plasma cells, 4) formation of xanthogranulomatous tissue with foamy histiocytes, which were characteristic findings showing that cancer tissue had been present there. As a result, rectal cancer clearly showed remarkable response to suppository administration of Tegafur for only about two weeks, if the tumor cells were sensitive to the drug.

[A case of unresectable pancreatic cancer successfully treated with continuous venous daily infusion of 5-FU and low-dose CDDP].

This case was a 61-year-old male diagnosed with pancreatic cancer who had a celiotomy. The tumor invasion involved the pancreas body and head. Ultrasonograph examination revealed that all the celiac artery, supramesenteric artery, and portal vein were occluded in the tumor. Because of the unresectability of the tumor, a palliative operation was carried out, and during the following 9 months he was given UFT 300 mg daily. Because abdominal ascites accompanied the tumor growth, the patient underwent combination chemotherapy of cisplatin 5 mg/day x 5/week and continuous infusion of 5-fluorouracil 250 mg/day for 4 weeks. Remarkable reduction of the abdominal ascites and decline of the tumor markers (CEA, CA19-9) was observed in the course of the chemotherapy. Bone marrow function was suppressed by the agents, but granulocyte colony stimulating factor (G-CSF) was very effective for recovery from the damage. Two months after discharge, abdominal ascites recurred. The patient received the same serial chemotherapy for 6 weeks, and now is followed as an outpatient.

[A case of gastric cancer with Borrmann type 4 responding to 5-FU-MMC combined chemotherapy].

A 70-year-old man with advanced Borrmann type 4 was preoperatively treated with 5-FU-MMC combined chemotherapy. The primary tumor including a palpable mass in the abdomen was diminished, and eventually the patient underwent curative resection. This preoperative regimen for advanced Borrmann type 4 gastric cancer might be recommended from the standpoint of less adverse effects of chemotherapy. The patient died suddenly of cardiac infarction in 9 months without recurrent signs.

[Continuous arterial infusion therapy of recombinant interleukin-2 and cyclophosphamide in hepatoma and liver metastasis].

The continuous arterial infusion of only recombinant interleukin-2 (rIL-2) was used in 9 patients with unresectable liver metastasis of colorectal or biliary cancer. This therapy was undertaken for the activation of tumor infiltrating lymphocytes (TIL), but was not effective. Then we tried continuous arterial infusion of rIL-2 and low-dose cyclophosphamide (CY) for liver metastasis. 3 of the patients who received rIL-2 and CY showed partial remission of disease. This therapy was possibly effective because of the activation of TIL and the suppression of tumor infiltrating suppressor lymphocytes.

[Continuous hyperthermic peritoneal perfusion (CHPP) therapy in advanced gastric cancer].

In CHPP therapy for advanced gastric cancer, a perfusate containing 20 mg CDDP and 8 mg MMC in 1,000 ml physiologic saline warmed at 47 degrees C was infused at a constant rate of 200 ml/min into the pouch of Douglas. The intraperitoneal temperature at the supra-pancreatic region was around 39.0 degrees C. To obtain a more stable and higher intraperitoneal temperature, the infusing rate was increased to 400 ml/min. This yielded a 3 degrees C higher temperature (42 degrees C) at the same measuring site. However, the temperature recorded at various intraperitoneal sites did not always reach such an effective range. The maximal plasma concentrations of MMC determined during CHPP at the 200 and 400 ml/min infusion were 0.09 +/- 0.03 and 0.11 +/- 0.03 microgram/ml, and those of CDDP 1.6 +/- 0.4 and 1.7 +/- 0.3 microgram/ml, respectively, all of which were not significantly different. When an intraperitoneal dosage of 20 mg MMC was given to 3 patients, the portal venous blood, at 10 min after the administration, produced a 1.7 times higher concentration of the agent than did the peripheral venous blood. This discrepancy between the two concentrations was much smaller than found by other investigators in animal experiments.

[Facilitation of hepatic metastasis by surgical stress in mice].

An experimental model for hepatic metastasis with a transplantation route of free-pedicled subcutaneous-embedded spleen was established in BALB/c mice. Colon-26 tumor cells to produce hepatic metastasis were inoculated into the spleen and the influence of surgical stress by means of a 20-min exposure of the abdominal cavity on the incidence of hepatic metastasis was examined. Hepatic metastasis was more promoted by the surgical stress in order when it was given on the same day, the 7th day and the 3rd day of the inoculation. Administration, without surgical stress, of ASGM 1, a specific inhibitor of the natural killer activity, also facilitated the hepatic disease. Administration of OK-432 prior to the surgical stress or ASGM 1 was at least partly effective for prevention of the hepatic metastasis and prolonged the survival of the inoculated mice. Preoperative immunotherapy utilizing OK-432 might be a possible means to prevent hepatic metastasis triggered in colorectal surgery for cancer.

[An experimental study on development of gallstone disease after curative gastrectomy for cancer--postoperative alteration of the composition of canine gallbladder bile after subtotal gastrectomy with truncal vagotomy].

In connection with gallstone (GS) formation after gastrectomy for cancer, we examined alteration of the composition of gallbladder bile after subtotal gastrectomy with truncal vagotomy. Of 11 mongrel dogs with cholecystostomy, 3 underwent B-I and 4 B-II gastrectomy. Four dogs without gastrectomy were served as controls. Bile was collected for 12 months. Bile acids were quantified by GLC. The bile was cultured for bacteriology. TBA did not significantly differ among the three groups of the dogs. In the two gastrectomized groups, CDA (a secondary bile acid) kept a higher level and CA (a primary bile acid) maintained a lower concentration compared with those in the controls. A remarkable increase of non-conjugated bile acids was recognized in both gastrectomized groups. Lithogenicity was low for all of the 3 groups. All but 1 control dog incurred bile infection that persisted long. Black pigment stones containing calcium bilirubinate developed in 1 of the 3 B-I and 2 of the 4 B-II dogs but none in the controls. The bile infection seemed to be involved in the development of GS. As the alteration of bile composition and GS occurred solely in the gastrectomized dogs, subtotal gastrectomy with truncal vagotomy might precipitate the GS formation.

[Two cases of intussusception of appendiceal mucocele: diagnostic value of preoperative ultrasonography].

Mucocele of the appendix was first described and named "Hydrops processus vermiformis" by Rokitansky in 1866. Intussusception of a appendiceal mucocele is very rare and we have been able to find only 14 previously reported cases. We present two cases with preoperative ultrasonography which is valuable for its diagnosis. Case 1: A 5-year-old male was admitted to Kahoku Hospital because of right lateral colic abdominal pain and tumor. Ba-enema examination revealed intussusception to the colon and ultrasonography showed the cystic mass of the appendix. Case 2: A 51-year-old female was admitted because of right lower abdominal pain. Ultrasonography was helpful showing the cystic tumor at the base of the appendix. Recent reports say that ultrasonography is valuable examination for its diagnosis. Also in our two cases preoperative ultrasonography was performed and gave us valid information for its qualitative diagnosis.

[Timing of surgical intervention in ulcerative colitis].

Ulcerative colitis is a borderline disease between medicine and surgery and ultimate evaluation of medical or surgical therapy remains to be settled. Except for the absolute indication for operation (toxic dilatation, perforation, bleeding and etc.), it is not always easy to consider surgery for this disease because so many factors influence its clinical course. Nevertheless, a prudent decision regarding surgery seems mandatory for a reasonable surgical therapy with a low mortality and high curability that enables an earlier rehabilitation and more complete social activity. The total number of primary operative cases of ulcerative colitis in our clinic over a period of March 1954 through the end of December 1983 was 30. A comparison of our experience up to the end of 1965 and since then has shown an operative mortality of 2/14 in the first and 1/16 in the second period, and that all these 3 deaths were through an emergency operation but not through 29 cases of elective surgery. It is emphasized that one of the most important factors influencing outcome of operation is whether or not it is undertaken as an urgent surgery during a hard time of the disease that has failed to respond to intensive medical treatment.

[Role of bile glycoprotein in intrahepatic calculus formation].

To clarify the etiology of intrahepatic calculus formation, we examined the components of hepatic bile, particularly glycoprotein, in 20 controls and 10 patients with intrahepatic calculi. The results obtained were summarized as follows: 1) The yield of delipidized bile powder was approximately 2.5 times higher in intrahepatic calculosis than in control. Quantitative analysis revealed that protein and neutral sugar were significantly increased in intrahepatic calculosis as compared with those in control. In SDS-PAGE of the powder, both intrahepatic calculosis and control groups demonstrated almost similar patterns except for difference in stainability between groups. This indicates that glycoprotein, that had been already present in control bile, was markedly increased in hepatic bile in intrahepatic calculosis. SDS-PAGE also demonstrated a thick and deep-stained band near the starting point only in intrahepatic calculosis. 2) Chromatography obtained from gel filtration on Sepharose CL-6B revealed 2 large peaks, one in void volume (macromolecular) and the other in total volume (micromolecular) region. In chemical analysis, macromolecular fraction in intrahepatic calculosis was rich in galactosamine, fucose and sialic acid, and characterized by prominent serine and threonine, which indicated that it was composed mainly of mucin type sialoglycoprotein. The micromolecular fraction in both groups were rich in aspartic acid and mannose, which indicated that they were composed mainly of serum type glycoprotein.

[Treatment of intrahepatic gallstone].

The postoperative outcomes in patients with hepatolithiasis are greatly affected by the presence of residual stones. One hundred and seventeen patients with hepatolithiasis treated in our clinic were analysed. The indication of hepatectomy for hepatolithiasis was determined by the degree of stricture of intrahepatic bile duct. The rate of residual stones was reduced from 54.5% to 14.5% by the introduction of choledochoscopical lithotomy. Thus, pre- and postoperative choledochoscopical examination and lithotomy are shown to play an important role in treatment of the patients with hepatolithiasis.