Somatic mutations detected by mini- and microsatellite DNA markers reveal clonal intratumor heterogeneity in gastrointestinal cancers.

We investigated clonal intratumor heterogeneity by comparing different areas of each tumor in 20 gastrointestinal cancers from female patients (1 esophageal cancer, 5 stomach cancers, and 14 colorectal cancers). In all 19 cases informative for X-inactivation analysis with the M27 beta and/or the phosphoglycerate kinase probes, the tumors were clonal. Separate areas from a given tumor showed identical X-inactivation patterns, providing evidence for its single-cell origin. Of 20 cancers, 11 showed p53 gene mutations (base pair insertions, point mutations, and one case of a base pair deletion) in exons 5-8. A particular p53 gene mutation was identical in all tumor areas investigated per case. The minisatellite probes detected loss of heterozygosity or new mutant alleles at 1p33, 1q21, 5q35, 17p13, or 18q21. In seven cases mutations at particular loci were restricted to one or two areas per tumor, while in another seven cases they were common to all tumor areas. Loss of heterozygosity or new alleles detected at the microsatellite loci D2S123, D3S1611, D5S107, D17S261, or D18S34 [(CA)n repeats] were common to all tumor areas in 7 of 19 cases. In another seven cases, however, microsatellite mutations at these loci were restricted to one to three areas per tumor. Tracing clonal intratumor heterogeneity would permit one to study the hierarchy of mutational events in cancers where no premalignant lesions can be harvested. Most important, our study indicates that clonal intratumor heterogeneity might lead to sampling errors in the molecular diagnosis of cancer biopsy specimens when using mini- or microsatellite markers.

Early hematological toxicity of adjuvant perioperative intraportal and intravenous chemotherapy with fluorouracil, mitomycin and heparin in colorectal cancer. Swiss Group for Clinical Cancer Research.

BACKGROUND: From 1987 to 1993 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III adjuvant trial in patients with colorectal adenocarcinoma with the objective of comparing intraportal versus intravenous perioperative chemotherapy. PATIENTS AND METHODS: Patients younger than 75 years had a curative en bloc resection of their cancer and were then randomized into three arms: 1. adjuvant perioperative portal liver infusion with fluorouracil, mitomycin and heparin, 2. adjuvant subclavian intravenous infusion with the same regimen and 3. no adjuvant treatment. The hematological toxicity was evaluated by hemoglobin determination and leucocyte and thrombocyte counting before and during ten days after surgery. RESULTS: Hemoglobin showed a median decrease of 22% in the control group. This decrease is aggravated significantly by 3% through the chemotherapy. Leucocytes showed a median decrease of 7% in the control group. Perioperative chemotherapy caused a significantly higher median drop; 23% when given into the liver through the portal vein and 34% when given systemically through a subclavian catheter. Thrombocytes revealed a median decrease of 25% in the control group. Chemotherapy was not associated with a significant additional drop. CONCLUSIONS: Adjuvant perioperative chemotherapy with fluorouracil, mitomycin and Heparin as given in this study is associated with a significant mild drop in hemoglobin and leucocytes during the first 10 postoperative days. If drug dose increases are planned in future trials the addition of hematopoietic growth factors might be considered.

[Morphological and biochemical examinations of different suture materials in colon anastomosis in the rat]. / Morphologische und biochemische Untersuchungen mit verschiedenen Nahtmaterialien an der Kolonanastomose der Ratte.

Histological, mechanical and biochemical examinations in the one layer colon anastomosis of the rat have shown that the synthetic resorbable suture material as Dexon and Vicryl are as good or even better than silk or catgut chromic. The most favourable histological reaction is observed with Dexon. Collagenolytic activity and collagen content are not influenced by the suture material during the first 14 postoperative days.

[Operative procedure guidelines for the treatment of colonic volvulus]. / Operationstaktische Richtlinien für die Behandlung des Kolonvolvulus.

In Western Europe volvulus of colon is a very rare disease. We observed only 15 cases within 15 years among more than 70,000 patients. In comparison with the literature we try to give some recommendations for the treatment of colonic volvulus. If the intestine is without disturbance of blood supply a two stage proceeding is proposed: first derotation of the intestinal loop and in a second step elective resection. If there is gangrene or perforation incontinuity resection without primary anastomosis is recommended.

[Colorectal cancer]. / Kolorektales Karzinom.

Incidence of colorectal cancer is increasing during the last years. 5% of the population get affected. From these a group of patients with a higher carcinoma risk must be separated: that with adenomas, familial polyposis and ulcerative colitis. Nourishment seems to be one of the main factors for the development of cancer. Although all important principles of radical surgery are realized, this 5-year survival rate for colorectal cancer is less than 40%. Prophylaxis, early diagnosis and the effect of irradiation and drug therapy must improve the relatively poor prognosis of colorectal cancer, which has reached in Germany the highest mortality and even -- with the exception of skin cancer -- the highest morbidity of all malignant neoplastic diseases.

[Experience with 50 clinical manifestations of small intestine tumors]. / Erfahrung mit 50 klinisch manifesten Dünndarmtumoren.

During the last 20 years we have seen 50 tumors of the small bowel, of which 28 were malignant. The low 5-year survival rate of 33.8% was due to a high operative mortality because of an advanced stage of the disease with ensuing complications such as perforation. In 50% of all obstructive tumors, associated peptic ulcerative lesions have been observed in the stomach or duodenum probably induced by stasis in the upper bowel. Therefore, the small bowel should always be inspected carefully during operation for peptic ulcer which did not heal with conservative treatment.

[Animal experimental study with different suture materials in colonic anastomosis in rats]. / Tierexperimentelle Studie mit verschiedenen Nahtmaterialien an der Kolonanastomose der Ratte.

On colon anastomoses of the rat four different suture materials were tested under standardized conditions. The tensile strength was determined by means of a microtraction apparatus. As a result it became evident that there are significant differences in the behaviour of the various suture guts.

[Stercoraceous perforation of the colon (author's transl)]. / Sterkorale Kolonperforation.

Stercoraceous perforation of the colon is mainly observed in patients with chronic renal failure. Pathophysiology and clinical feature is demonstrated on the basis of the experience with 10 patients. Prophylaxis of stercoraceous formations is important, for after the perforation prognosis is very poor: only 1 patient survived. Surgical therapy consists of resection of the whole involved colon with out primary anastomosis.

[Amebiasis as surgical emergency]. / Amöbiasis als chirurgischer Notfall.

Report of 2 cases of systemic complications many years after inappercept infection with amoeba histolytica. Amoebiasis being a rare affection in Switzerland, diagnosis was missed and not revealed till operation. One case with multiple liver abscesses, healed after drainage and chemotherapy with metronidazol and dehydroemetine. In the other case with colonic perforation and multiple liver abscesses combined surgical and drug therapy failed, the patient died in hepatotoxic coma. Short cut of clinics and therapy in amoebiasis, pointing out that surgery is reserved for the complications as great liver abscess, colonic perforation or fistula between abdominal and pleural cavity.

[Tumor surgery: principles of radical treatment (author's transl)]. / Radikalitätsprinzipien in der Tumorchirurgie (Colon- und Rectumcarcinom).

The 5-year survival rate for curative radical resections of colorectal cancer including Dukes' stages A-C has not improved during the last 20 years. The main principles of surgical treatment have now been realized: en-bloc resection of the tumor together with its lymph drainage system, primary high ligature of the supplying blood vessels, prophylaxis of peroperative metastases and a high total resection rate with low operative mortality. In the future, an improved prognosis must come from prophylaxis, early diagnosis, and improved methods of irradiation and chemotherapy, because the limits of surgical treatment have been reached.

[Development of small intestinal neomucosa]. / Entwicklung von Dünndarm-Neomukosa.

Under certain conditions epithelium grows on the peritoneal surface. By folding the colon of the rat the authors constructed a seromuscular tunnel of which the two ends were sutured to the transsected ileum, making normal small bowel passage possible. 6-12 weeks after the operation a pouch was found on which a one-layer cylindric epithelium had developed showing evidence of disaccharidase activity. Clinically the model could be used to enlarge the mucosal surface of the remaining small bowel following extensive resection.