Immune reactivity in patients with colorectal cancer: assessment of biologic risk by immunoparameters.
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Biomedical subjects
Publications and source records attributed to M Stearns.
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A retrospective analysis of 1,826 cases (924 colon, 902 rectal) from ten institutions provided the basis of this study on the staging of cancer of the colon and rectum. The general rules of the American Joint Committee on the relationship between times and the staging of cancer have been followed. These represent modifications of the originally formulated TNM system of the Union Internationale Contre Le Cancer (UICC) which has been designed as a clinical-diagnostic classification, not applicable to cancer of inaccessible sites or structures requiring postsurgical treatment pathologic assessment of therapeutically removed specimens. Inadequacies of the clinical data requested for our study required adoption of the pTNM evaluation method of classification. Multiple regression analysis of the data demonstrated a relationship between survival and the following: depth of penetration (T), status of regional lymph nodes (N), and presence or absence of distant metastasis (M). This was similar for both sites. Basically, for the rectum it was in consonance with the original Dukes' classification (A, B, and C), and was remarkably applicable to the colon. The survival data for the two sites were so similar as to suggest the use of one set of pTNM categories not only for the postsurgical-treatment pathologic evaluation, but also for the stage grouping definitions. Strongly recommended for cancer of all sites is the development of General Oncology Data Forms to be included in the clinical charts and records of all patients with cancer.
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Adult Sprague-Dawley rats weighing approximately g were fed bovine serum albumin and sodium bicarbonate by gavage. Serum was obtained at intervals after feeding and tested for immunoreactive bovine serum albumin by radioimmunoassay. Nanogram amounts of immunoreactive bovine serum albumin were detected in serum; peak values were obtained after 4 and 6 hr. The influence of intestinal inflammation on protein uptake was examined in two model systems. Infection of rats with Nippostrongylus brasiliensis was accompanied by partial villous atrophy in the intestinal segments harboring adult worms and mild systemic anaphylaxis in the rat was accompanied by increased intestinal vascular and mucosal permeability. Enhanced uptake of BSA was observed before and shortly after self-cure of infection and during mild systemic anaphylaxis. The molecular size of immunoreactive bovine serum albumin approximated that of the administered bovine serum albumin; no small fragments of bovine serum albumin bearing antigenic determinants were detected.
We examined the relation of carcinoembryonic antigen levels to time, site and extent of recurrence in 358 patients with colorectal cancer. The recurrence rate was higher in patients with Dukes' B and Dukes' C lesions who had preoperative levels higher than 5 ng per milliliter. There was a linear inverse correlation between preoperative levels and estimated mean time to recurrence in patients with Dukes' B and C lesions, ranging from 30 months for a level of 2 to 9.8 months for a level of 70 ng per milliliter. In patients with Dukes' C lesions the median time to recurrence was 13 months if preoperative levels were higher than 5 ng per milliliter, and 28 months if they were lower. Preoperative carcinoembryonic antigen levels in patients with resectable Dukes' B and C cancer provided an additional criterion for allocating these patients to groups at high or low risk for recurrence.
The usefulness of the CEA as an indicator of recurrence and a guide to selected second-look surgery was evaluated from a retrospective analysis of 358 patients with colorectal cancer and from a prospective experience with 16 patients all of whom had been admitted for second-look surgery because of postoperative elevations of CEA only. Our previous experience had shown that after curative resection the CEA usually returned to normal levels (less than 5 ng/ml) within one month, but became elevated at time of clinically obvious recurrence being very high in patients with liver metastases, but only moderately elevated or normal in patients with local recurrence. All 16 patients had previously had curative resection of colorectal cancer; 13 in the rectum or rectosigmoid and three in the right colon. There were 13 Dukes' C and three Dukes' B cancers. All had been followed clinically and by CEA testing at three monthly intervals and were considered free of disease (NED) at time of CEA elevation. The median disease free interval was 13 months (range 4-57 months) and the median CEA prompting admission for second-look operation was 21 ng/ml (range 10-56 ng/ml). The sites of recurrence were liver in six, lung in two and localized disease in six. Two patients had negative exploration for recurrence and were found to have cholelithiasis only (one of these later died of metastases). Resection for cure was done in seven and palliative resection or biopsy only was done in nine patients. At this time, four patients are NED (12-37 months), five are living with disease (10-16 months) and seven have died of disease (2-12 months). The CEA test provides a method of early detection of recurrence and may permit surgical retrieval in selected patients and earlier initiation of palliation in other patients. The longterm effects in patient salvage remain to be defined.
Two hundred and thirty-seven patients with carcinoma of the colon and 16 patients with benign lesions of the colon and rectum underwent skin tests with 2-4, dinitrochlorobenzene and a battery of intradermal antigens. The incidence of 2-4, dinitrochlorobenzene reactors decreased with the increasing stage of the disease. Seventy-six per cent of the patients with Dukes' A cancer were 2-4, dinitrochlorobenzene positive compared with 56 per cent of those with Dukes' B cancer and 61 per cent of those with Dukes' C lesions. Of the patients with advanced primary operable cancer, those who have metastases beyond the intestine and its mesentery, only 46 per cent were 2-4, dinitrochlorobenzene positive. Only 42 per cent of the patients with inoperable advanced or recurrent disease reacted to 2-4, dinitrochlorobenzene. Neither age nor sex was a determinate factor in the capacity of the patient to respond to 2-4, dinitrochlorobenzene. Tumor burden appeared to correlate best with the ability of the patient to respond to 2-4, dinitrochlorobenzene. In patients with Dukes' A or B lesions, the clinical follow-up period was too short to gauge prognostic significance of skin tests. In patients with Dukes' C lesions who were observed at 12 months, six of 11 in the 2-4, dinitrochlorobenzene negative group had a recurrence or died of disease compared with only four of 17 in the 2-4, dinitrochlorobenzene positive group, p less than 0.10. In 38 patients with advanced primary operable cancer who were observed for nine months, 40 per cared iwth 28 per cent of 2-4, dinitrochlorobenzene positive group. A similar relationship was observed in a group of patients with advanced or recurrent disease who were observed for nine months in which 58 per cent of the patients in the 2-4, dinitrochlorobenzene negative group were dead of disease compared with 40 per cent of those in the 2-4, dinitrochlorobenzene positive group. Skin testing with 2-4, dinitrochlorobenzene and selected intradermal antigens adds prognostic information to that predicted from the clinicopathologic stage of the disease in instances of carcinoma of the colon and rectum. In general, patients with reactive skin tests have more favorable recurrence and survival rates with each stage of the disease.
Histologic sections from 143 patients treated with surgery for infiltrating adenocarcinoma of the distal large bowel were studied with emphasis on the morphologic characteristics of the regional lymph nodes. Lymph nodes were classified into four groups designated lymphocyte predominance, germinal center predominance, lymphocyte depletion, and unstimulated. Results were correlated with the extent of disease and five year survival data. There was no significant association between the histologic pattern of the lymph nodes and the extent of the primary lesion. There was a higher survival rate in patients whose nodes showed germinal center predominance (71 per cent) compared with those whose nodes showed lymphocyte predominance or the unstimulated pattern (both 54 per cent), but these results were not statistically significant.
Muscle transposition of the innervated omohyoid muscle into the tendon of the paralyzed posterior cricoarytenoid muscle was studied in a small series of subhuman primates. A similar procedure was described previously by King for treatment of bilateral recurrent nerve injuries. Our studies confirm that this procedure adequately enlarges the airway to allow normal activity without a tracheostomy. Histologic studies appear to show nerve ingrowth occurring at 6 months as in other neuromuscular pedicle procedures. The procedure is easily performed and causes no other muscle denervation.
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