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[Aorto-bi-iliac resection, of the 3rd part of the duodenum and the left colon, for recurrence of colonic cancer].

An aorto-bi-iliac resection was performed in a patient with recurrent cancer of the left colon. Implantation of a Dacron vascular prosthesis was combined with left iliac colostomy and resection of 3rd part of duodenum. Based on this case and a review of the literature, the possibility and value of resection of an invaded vascular axis is emphasized. The revascularization procedure, either by a prosthesis in situ or associated extra-anatomical by-pass, is discussed.

Adenocarcinoma↗

Phenotypical and functional characteristics of tumor-infiltrating lymphocytes from colon carcinomas stimulated with rIL-2 and rIL-4 in vitro: comparison with lymphocytes of the normal colon mucosa and the peripheral blood.

The phenotypical composition of tumor-infiltrating lymphocytes (TIL) from colorectal carcinomas was compared with that of intraepithelial lymphocytes of the autologous normal colon mucosa (IEL) and autologous peripheral blood lymphocytes (PBL). The CD4+/CD8+ ratios of the freshly isolated TIL, IEL and PBL were comparable and always > 1. CD25+, HLA-DR+ and CD56+ cells accumulated significantly in the TIL, while CD45RA+ cells were less frequent compared to the autologous IEL and PBL. CD29+ memory-cells were found with the highest frequency in the TIL. Stimulation with rIL-2 in vitro induced an outgrowth of CD56+ cells in the TIL. Concordantly the expression of CD3+ and the alpha/beta T-cell receptor was low. In a standard 51Cr-release assay these phenotypically LAK-cells representing effectors displayed an unspecific lytic activity against the autologous tumor as well as against allogeneic K562 and Daudi targets. The number of CD56+ cells could be reduced in TIL and PBL by simultaneous stimulation with rIL-2 and rIL-4, while the number of CD3+ cells increased.

Adult↗

O6-Alkylguanine-DNA alkyltransferase in normal colon tissue and colon cancer.

O6-Alkylguanine-DNA alkyltransferase (AGT) is a DNA repair protein that reverses alkylation damage produced by chloroethylnitrosoureas and is a major determinant of cellular resistance to adjuvant chemotherapy with these drugs. AGT activity was measured in 119 samples from 69 patients, including normal, tumor, and diseased tissue, and 42 patients in which both normal and tumor tissue were assayed. The activity varied among individuals, but there was no statistically significant difference in average AGT activity among tumor, normal, and diseased tissue, or between men and women, or between young and old patients (< 70 or > 70 years). Few (3/49) tumor samples showed an absence of AGT activity (Mer- phenotype). The results indicate that nearly all colon cancers have significant AGT activity, and adjuvant chloroethylnitrosoureas chemotherapy must be modified, perhaps by the use of AGT biochemical modulators, to overcome this natural drug resistance.

Adolescent↗

Multiple 'serrated adenocarcinomas' of the colon with a cell lineage common to metaplastic polyp and serrated adenoma. Case report of a new subtype of colonic adenocarcinoma with gastric differentiation.

A 70-year-old woman underwent right hemicolectomy and six carcinomas were recognized in the resected colon. These carcinomas were considered to be of a cell lineage common to serrated adenoma (SA) and hyperplastic (metaplastic) polyp (H/MP), because of the occurrence of multiple SAs and H/MPs around the carcinomas, as well as the co-existence of SA and H/MP areas within the carcinomas. These carcinomas had the following common histological and immunohistochemical features: a serrated structure resembling SA; a lace-like structure; infiltrative growth within the muscularis propria, with dedifferentiation at the invasive front; and immunohistochemical expression of pS2 and human gastric mucin. Based on these features, a new subtype of carcinoma is proposed, with a cell lineage common to SA and H/MP. It would also seem that p53 is involved in the serrated adenoma-carcinoma sequence.

Adenocarcinoma↗

The results of surgical treatment of cancer of the colon at the Cleveland Clinic from 1965-1975: classification of the spread of colon cancer and long-term survival.

Between the years 1965-1975, 564 patients underwent surgical treatment for cancer of the colon. The primary tumour was removed in 502 patients (89%) in all cases with a "no touch isolation" technique. The 5-year survival rate corrected for age was 64% in 546 operative survivors, and 82% in 413 patients operated with intent to cure. Survival analyses are presented classifying the spread of the tumour by the clinico-pathological method of Turnbull, the TNM method, the Astler-Coller method, Dukes' method. The results suggest that the Astler-Coller classification offers no advantage over that of Dukes' when predicting survival for patients after operation for cure, and that separating those patients considered to have evidence of invasion of an adjacent organ at operation (Turnbull's classification) from those patients without evidence of contiguous growth, is only justified if invasion of cancer is confirmed by histological examination of the resected specimen.

Adult↗

Impact of different betalactam antibiotics on the normal human flora, and colonization of the oral cavity, throat and colon.

Phenoxymethylpenicillin was given orally in doses of 800 mg twice daily for seven days to six patients, and bacampicillin was given in doses of 400 mg three times per day for seven days to another six patients. Saliva, throat and faecal specimens were taken for cultivation of aerobic and anaerobic bacteria. Only small changes in the normal saliva and throat flora were observed, and no changes in the faecal flora were noticed during the observation period. Cefoxitin was administered parenterally in doses of 2 g at 6 h intervals for 12 h to six other patients. Pronounced changes in the colon flora occurred. Of the aerobic bacteria, enterobacteria decreased and cefoxitin-resistant enterococci increased in number; of the anaerobic bacteria, gram-negative rods decreased in number. At the end of the administration period, all cefoxitin-resistant strains decreased, and suppressed enterobacteria and bacteroides increased in number.

Adult↗

Natural history of minute sessile colonic adenomas based on radiographic findings. Is endoscopic removal of every colonic adenoma necessary?

PURPOSE: With the development of colonoscopy and double-contrast barium enema, detection of minute sessile colonic adenomas has increased. We evaluated progression of these lesions radiologically and attempted to clarify the natural history. METHODS: A total of 125 minute sessile adenomas (< or = 5 mm in size) with histologic confirmation were examined by double-contrast barium enema at an interval of more than one year. The average follow-up period was 24 (range, 12-36; standard deviation, 9.4) months. To allow for differences in magnification, adenomas increasing in size by 2 mm or more were defined as growing, and the other lesions were defined as unchanged. RESULTS: Eighty-six adenomas showed no interval change in size. Four adenomas decreased 1 mm in size, and 27 adenomas increased 1 mm in size. The remaining eight adenomas (6 percent) increased by 2 or 3 mm in size. None of the adenomas showed any morphologic changes. There was also no difference in degree of histologic atypia between growing and unchanged adenomas. None of the adenomas developed into carcinomas during the follow-up period. CONCLUSIONS: These data show that most minute sessile adenomas remain unchanged in size and morphology over the long term. Accordingly, these adenomas probably should be followed up radiologically or endoscopically to avoid excessive polypectomy.

Adenoma↗

The establishment of two rat colonic carcinomas in tissue culture. A basic prerequisite for standardized experiments on the biology of colonic carcinomas in vivo.

Two rat colonic carcinomas (DMH-Co-1 and DMH-Co-2) derived from dimethyl-hydrazine-induced metastasizing adenocarcinomas were established as permanent cell lines. By means of electron microscopy, immunofluorescence microscopy and biochemical analysis of cytoskeletal components, it has been shown that both tumor cell lines retain in vitro the phenotypic characteristics of the primary tumors. The in vitro growth properties revealed only minor differences between the two cell lines. After retransplantation in vivo, DMH-Co-2 gave rise to moderately differentiated adenocarcinomas, whereas the tumors arising from DMH-Co-1 exhibited a continuum of differentiation encompassing adenocarcinomas, undifferentiated carcinomas and squamous cell carcinomas. These permanent cell lines offer the opportunity for isolating divergent subpopulations by in vitro cloning and facilitate standardized experiments on their biological behaviour in vivo.

Adenocarcinoma↗

Secondary placement of a voice prosthesis after total pharyngolaryngectomy with colon interposition: voice restoration in colon interposition.

We present a patient treated by a total pharyngolaryngoesophagectomy and postoperative radiotherapy for a hypopharyngeal T4N2bM0 squamous cell carcinoma. The upper digestive tract was reconstructed with a pedicled left colon interposition through the posterior mediastinum. A voice prosthesis was placed 9 months after the initial treatment, following measurement of the tracheo-neopharyngeal wall thickness by sonography. Fifteen months after the total pharyngolaryngectomy, the patient remains free of recurrent disease and has successfully resumed speaking with the voice prosthesis.

Carcinoma, Squamous Cell↗

Degenerative behavior of epithelial cells in the colonic crypt of the mouse following administration of colonic carcinogen, 1,2-dimethylhydrazine.

The degenerative behavior of cells following administration of 1,2-dimethylhydrazine was analyzed in its target organ, the distal colon of the mouse. Within 3-6 h after carcinogen treatment, an increasing number of epithelial cells in the proliferative compartment of the crypt degenerated. Degenerating cells were present most frequently as phagosomes in the neighboring epithelial cells, and infrequently as pyknotic nuclei being extruded from the epithelial lining in the crypt. Epithelial cells prelabeled with [3H]thymidine degenerated first, followed by those not prelabeled, indicating that the carcinogen-induced degeneration of cells occurred after passage of cells through the DNA synthesis phase.

1,2-Dimethylhydrazine↗

Anti-colon/ovarian tumor antigen: localization of colon cancer xenografts in athymic rats.

Tumor localization studies in athymic rats bearing human colon tumors were performed using the radioiodinated monoclonal antibody SP-21 and its F(ab')2. Antibody preparations isolated from ascitic fluid and antibody from bioreactor effluent were used in these studies with similar radioimmunolocalization results. The intact antibody had an optimal localization time of 4-8 days after injection, while the F(ab')2 fragments had an optimal localization time of 3-4 days. Whole-body autoradiography, whole-body immunohistochemistry, and scintigraphy confirmed that the intact antibody and the antibody fragments localized preferentially in the tumor. The antibody distribution within the tumor was uniform, and not confined to the periphery, nor to focal areas within the tumor. Dose-response studies were performed with the intact antibody over a range of 10-100 micrograms/kg of total body weight with no clear-cut relationships observed. Comparisons of different radio-iodination methods indicated that the chloramine-T-based methods resulted in preparations with higher tumor uptake.

Animals↗

Endoscopic mucosal resection of superficially spreading colonic neoplasms larger than 5 cm in the right colon after injection of dilute sodium hyaluronate: report of two cases.

Submucosal injection is the most important procedure for the safe performance of endoscopic mucosal resection in the large intestine while avoiding the risk of perforation. We used dilute sodium hyaluronate containing Bosmin and achieved safe piecemeal resection of large superficial tumors in the right colon in two patients. Piecemeal snare resection is considered to be acceptable if all the tissue pieces can be collected for histopathological diagnosis.

Colonic Neoplasms↗

Intercellular junctions, apical differentiation, and infiltrative features in colon cancer: an ultrastructural study. The Colon Cancer Team at IMAS.

Changes in the structure and number of cell junctions have been related to the infiltrative and metastatic potential of tumor cells. Apparently, the loss of cell adhesion should be coordinated with significant changes in the apical and basal cell domains. The authors have performed a sequential ultrastructural study of cells in the superficial, middle, and deep regions of well- and moderately differentiated colon adenocarcinomas. This was to investigate the differences in the organization of different membrane domains among tumor cells in the in situ areas, the advancing, infiltrative edge of the tumors, and the infiltrating zones between these two extreme zones. The results of the study suggest that the organization of these domains is not strictly coordinated, and that, for each infiltration level, both a settling and an infiltrating cell population can be found. These findings could explain the fact that apparently well-differentiated tumors are able to seed distant tissues with individual cells, rather than with well-differentiated glandular aggregates that would hardly be able to reach the vessel lumina without significantly modifying their organization.

Actin Cytoskeleton↗

The synthetic colon peptide pyroGlu-His-GlyOH inhibits growth of human colon carcinoma cells (HT-29) transplanted subcutaneously into athymic mice.

Growth inhibitory tripeptide, pyroGlu-His-GlyOH colon mitosis inhibitor (CMI), was recently isolated from water extracts of mouse intestine. In the present study, it was demonstrated in two different experiments that i.p. injections of CMI, daily or 3 times a week, could inhibit the long-term s.c. growth of HT-29 cells in athymic mice. The growth inhibitory effect was most pronounced initially with approximately 50-90% growth inhibition, and declined terminally with approximately 40-60% growth inhibition. A bell-shaped dose-response curve with maximal effect at 1 pmol/animal/injection was seen.

Animals↗

T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. I. Significant bispecific lysis of syngeneic colon carcinoma CC531 is critically dependent on prolonged preactivation of effector T-lymphocytes by immobilized anti-T-cell receptor antibody.

In order to develop a rat model that reflects human weakly or nonimmunogenic tumor-host relationships and allows investigation of T-cell retargeting with bispecific monoclonal antibodies in vivo, we prepared several mixed hybridomas. One fusion partner was the anti-rat-T-cell receptor (TCR)-framework hybridoma R73 and the others were hybridomas producing antibodies against CC531, a Wag rat colon carcinoma. Stimulation of Wag rat spleen cells with immobilized R73 mAb and rIL-2 yielded predominantly CD8 positive effector T-lymphocytes, which lysed control P815 target cells efficiently in R73-mediated reverse antibody-dependent cellular cytotoxicity (ADCC). The capacity of these effectors to cause significant hybrid antibody-mediated lysis of CC531 emerged several days later, was critically dependent on prolonged stimulation with immobilized R73, and was associated with increased N-alfa-benzyloxycarbonyl-L-lysine thiobenzyl esterase content.

Animals↗

Colon cancer-associated DNA mutations: marker selection for the detection of proximal colon cancer.

This study evaluates the potential ability of a specific panel of DNA mutations to identify right-sided colorectal carcinomas (CRCs) that would be missed by a flexible sigmoidoscopy (FS) screening program. This panel could then be applied to stool DNA analysis for noninvasive proximal CRC detection. A series of resected right-sided CRCs from 101 patients who had no left-sided advanced colonic neoplasms distal to the splenic flexure were analyzed. Tumor DNA was isolated from microdissected tumor sections. Deletions in the BAT-26 locus, a marker of microsatellite instability, and mutations at 19 loci spread among the p53, K-ras, and Apc genes were detected following PCR amplification. Mutations were identified in 83% of successfully amplified samples and were variably present in each of the target sites: p53 (42%), Apc (37%), K-ras (28%), and BAT-26 (24%). Mutations were identified across all Dukes stages (CIS/A 6/8 [75%], B 41/51[80%], C 30/32 (94%), and D 6/9 [67%]). Our data suggest that this 20-marker mutation panel may be associated with more than 80% of cancers undetectable by FS. The adjunctive use of stool DNA mutation analysis using this marker panel in FS CRC screening programs may significantly increase the detection of proximal CRC.

Adenocarcinoma↗

Peroral pneumo colon--a double contrast technique to evaluate distal ileum and proximal colon.

The technique of peroral pneumocolon (POPC) has been found to be simple and easy to obtain excellent double contrast visualization of the distal ileum and proximal colon. Thirty-four patients were subjected to the POPC examination of which 29 had undergone prior barium meal follow through studies. In 86.2% of these cases POPC was found to be superior as compared to conventional studies. In 5 patients who could not retain Ba-enema, POPC was performed as first line of investigation with 100% efficacy.

Barium Sulfate↗

Colonic cell proliferation in two different ethnic groups with contrasting incidence of colon cancer: is there a difference in carcinogenesis?

Most studies on colorectal carcinogenesis suggest a field defect, preceding overt development of cancer. The low incidence of adenomatous polyps in the African population, however, suggests that there may be an alternative route for cancer development. The aim of the study was to discover if the difference in incidence of colorectal cancer in Africans compared with the white population is reflected in a different pattern of cell proliferation. Histological normal mucosa from 30 patients (15 white South African (W), 15 South African Africans (A)) with confirmed colon cancer were examined. Proliferating cells were detected using the Ki-67 antigen. In addition, cell proliferation data were obtained, from 30 age matched controls (15 Africans, 15 white South Africans), without colorectal disease. The African controls were significantly younger (mean (SD) (A: 42 (20), W: 66 (13), p < 0.05)) than the white controls. The second control group had a significantly higher mean (SD) total labelling index (W: 11 (3), A: 6 (4), p < 0.05). In addition the proliferative pattern of the white group without evidence of colorectal cancer showed a comparatively large amount of dividing cells in compartment 2, compared with African controls (mean (SD) (W: 21 (8), A: 9 (8), p < 0.05)). Mucosa from Africans with cancer showed a proliferative pattern with the same increased total labelling index (A: 15 (5), W: 16 (6), p = NS, phase II proliferative lesion) and an even more pronounced upward expansion (phase I proliferative lesion) compared with white cancer patients. This suggests that the mechanism of colorectal carcinogenesis is similar in Africans and the white population. The lack of clinical evidence of the adenoma-carcinoma sequence, and the incidence of cancer at a comparatively young age in Africans may be explained by the fact that colorectal cancer in this ethnic group behaves more aggressively and that adenomatous polyps are rapidly converted into overt cancer before detection.

Adenoma↗