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Biomedical subjects

E Pihl

Publications and source records attributed to E Pihl.

At least 19 recordsLinked to original sources

Lung recurrence after curative surgery for colorectal cancer.

A total of 1578 patients were treated with potentially curative surgical resection for colon and rectal cancer by one surgeon from 1950 to 1982. Follow-up revealed that 117 (11.5 percent) of 1013 patients with rectal carcinoma eventually presented with clinical evidence of pulmonary recurrence, with or without evidence of spread elsewhere; the corresponding figures for the colon were 20 (3.5 percent) of 565 (P less than 0.001). An analysis of the times to recurrence revealed that half of the lung recurrences were clinically obvious within 32 months for rectal tumors and 34 months for colonic, compared to 22 and 21 months, respectively, for liver recurrences, excluding those with other distant metastases. The slower recurrence rate and the longer survival in patients with recurrences in the lung compared to the liver were statistically significant only for rectal primaries (P less than 0.02 and P = 0.001, respectively). Sixteen patients underwent surgery with curative intention for lung recurrences; four of these remain alive at two, six, 11, and 15 years, and one patient was free of recurrence when he died from other causes 15 months after surgery. The conditional probability survival rate for the 16 patients was 38 +/- 13 percent at five years after recurrence operation.

Colonic Neoplasms

Zoned immune suppression of lymph nodes draining malignant melanoma: histologic and immunohistologic studies.

Node-to-node heterogeneity of reaction and recognizable patterns of reaction in node groups draining melanoma were sought. Nodes from 72 patients undergoing lymphadenectomy for high-risk, primary melanoma (57) or node-spread melanoma (15) were accurately oriented to the nearest melanoma. Reactivity of paracortex, follicular areas, and sinuses was assessed on a 0-3+ scale. Reactivity was prominent in paracortex and sinuses but varied from node to node within node groups. Nodes nearest to tumor showed least reaction; nodes at intermediate distances from tumor were most reactive, while those farthest away showed mostly little reaction. Variation of nodal reaction that correlated with the node position relative to the nearest melanoma (zoned reaction) was seen in 92% of patients with nodal metastases of melanoma and in 64% of patients with primary malignant melanoma. Follicular and sinusoidal reactions showed no significant zoning. S-100 protein-positive paracortical dendritic cells (PDCs) in tumor-oriented nodes were quantified. PDCs were infrequent in nodes partly replaced by melanoma or located near to melanoma but were numerous in nodes located farther from tumor. Changes of nodal activity (relative stimulation or suppression) correlate with the distance of the node from the nearest deposit of primary or metastatic melanoma.

Humans

Local recurrence after potentially curative resection for rectal cancer in a series of 1008 patients.

Local recurrence and its related mortality after potentially curative resection for rectal cancer have been analysed in a series of 1008 patients managed by one of the authors. Nine hundred and thirty-four were available for analysis of recurrence. One hundred and seven (11 per cent) patients developed local recurrence without evidence of systemic spread and 84 (9 per cent) both local and systemic recurrence. Local recurrence was less common (14 per cent) after resection of tumours of the upper third of the rectum compared with the middle (21 per cent) (P = 0.02) or lower thirds (26 per cent) (P less than 0.001). Local recurrence was related to both tumour stage and differentiation (P less than 0.001). There was no significant relationship between local recurrence and tumour size or the type of curative resection performed, restorative or non-restorative. The distal margin of clearance after restorative resection did not influence the local recurrence rate. Of patients who developed metastases recurrence was evident within 2 years in 60 per cent. Three hundred and thirty-two patients died from recurrence, 91 (27 per cent) with evidence of local recurrence only, 80 (24 per cent) with combined local and systemic recurrence and 161 (48 per cent) with evidence of systemic spread only. The corresponding median survivals were 35, 34 and 39 months.

Aged

T-antigen expression by peanut agglutinin staining relates to mucosal dysplasia in ulcerative colitis.

Staining of 326 rectal mucosal biopsies from ulcerative colitis patients with peanut agglutinin (PNA), which binds to the T-blood group antigen and has been claimed to reflect a cancer-associated mucin alteration, showed highly significant direct associations with mucosal dysplasia (P less than 0.001), disease activity (P less than 0.001), and subsequent development of rectal cancer in a smaller series of patients (P = 0.005). Staining for normal colonic mucin by the Dolichos biflorus (DBA) lectin related significantly and inversely to dysplasia. Intense normal colon mucin staining by DBA related significantly (P less than 0.025) to long disease duration and to subsequent development of cancer (P = 0.02). The latter association is based on a small number of patients only and is not considered conclusive evidence, but may provide a link with goblet-cell hyperplasia. The authors conclude that although T-antigen expression relates to dysplasia, the findings of "false" positive and negative rates of 22 and 33 percent respectively, make it unlikely that staining of biopsy sections for the T-antigen by peanut agglutinin will contribute materially to routine assessment for dysplasia and cancer risk prediction in patients with ulcerative colitis.

Adult

Changes in lymphocyte status and responsiveness in pregnancy detected by a fluorescent cell probe.

Lymphocyte reactivity assessed by a fluorescent lipophilic probe test of responsiveness to concanavalin A (con A) was shown to differ from normal in early pregnancy. The difference was most marked in multiparas. Abnormal reactivity was detected in the earliest pregnancy examined (5 weeks' gestation) and up to about the 20th week; after 20 weeks, reactivity was normal in all of the multiparas and most of the nulliparas studied. However, in pregnancy induced hypertension (PIH), a disorder of late pregnancy, the same responsiveness as in early pregnancy was found. When unstimulated lymphocytes were examined, abnormal reactivity associated with increased fluorescence was observed in early pregnancy and in PIH, compared with normal late pregnancy, reflecting alteration in lymphocyte membrane phospholipids. It is postulated that pregnancy is associated with sequential change in immunity, disturbance of which may result in immunologically-determined obstetric morbidity.

Adult

Promoting effect of beer and ethanol on anti-tumour cytotoxicity: unaffected growth of a transplantable rat tumour.

The effects of beer and alcohol (4.8% ethanol v/v) were studied on (i) the growth of a syngeneic colonic carcinoma transplantable in male D/A rats, (ii) levels of blood B and T-lymphocyte classes, (iii) antibody-dependent cellular cytotoxicity (ADCC), and (iv) direct lymphocyte anti-tumour cytotoxicity. Beer and alcohol had no effect on tumour growth, but led to significant increases in non-specific anti-tumour cytotoxicity in the levels of blood lymphocytes labelled by the monoclonal antibody OX/8 (cytotoxic/suppressor cells) and in the levels of total T-lymphocytes; ADCC was not affected. It is concluded that alcohol stimulates non-specific cell-mediated immunity (CMI) but that it either does not affect tumour growth or that the increased CMI is compensatory for a tumour-growth stimulatory effect of alcohol.

Animals

Altered blood lymphocyte subclasses in patients with ulcerative colitis.

Peripheral blood lymphocytes were studied by flow cytofluorimetry and monoclonal antibody techniques in 107 patients with ulcerative colitis and in 20 healthy controls of similar ages. Total T, T helper (TH), and T cytotoxic/suppressor (TC/S) lymphocytes were defined by the monoclonal antibodies OKT3, OKT4 and OKT8, respectively, while B lymphocytes were defined by surface immunoglobulin. Patients had a significantly (P less than 0.05) lower proportion of TC/S lymphocytes than the controls, and patients with quiescent disease had a reduced proportion of B lymphocytes compared to controls and those with active disease. Patients with marked mucosal dysplasia had a significantly (P less than 0.025) lower proportion of TH lymphocytes and a higher (P less than 0.01) proportion of B lymphocytes than those without dysplasia. There were no significant associations between lymphocyte levels and any other clinicopathological features assessed.

Adult

Lymphocyte subclasses in pregnancy induced hypertension.

Peripheral blood lymphocyte subclasses were studied by flow cytofluorimetry and monoclonal antibodies in 21 women with Pregnancy Induced Hypertension (PIH), 20 healthy women in their third trimester of pregnancy and in 20 nulliparous, nonpregnant women. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to define total T cells, T helper cells (Th) and T suppressor-cytotoxic cells (Ts/c) respectively. B lymphocytes were defined by their surface immunoglobulin. Absolute numbers of total T cells and Ts/c cells were significantly decreased (p less than 0.05) in patients with PIH compared to either control group. The proportion of B lymphocytes was significantly (p less than 0.01) increased and absolute numbers were marginally increased. These findings reflect an immune disturbance which may be of prime importance in the pathogenesis of this disease.

Adolescent

Significance of lymphocyte fluorescence polarization changes after phytohemagglutinin stimulation in cancer and noncancer conditions.

The double-zone fluorescein fluorescence polarization (FFP) "cancer" test was used to study 540 blood lymphocyte samples from 341 donors, of whom 158 had confirmed cancer: The other donors were noncancer patients, pregnant women, and normal individuals. The FFP response in cancer patients was the reverse of that in normal individuals, but an abnormal response was also obtained in some noncancer conditions, including the chronic inflammatory disorders--rheumatoid arthritis, cholecystitis, and diverticulitis--and in early pregnancy or pregnancy-induced hypertension. Thus the cancer discriminatory value of the test is limited. Examination of its biologic basis suggests that the positive FFP response in cancer and other conditions is due to altered immune status of blood lymphocytes, with associated change in cytoplasmic fluidity affecting the polarization of fluorescence. Incubation of normal blood lymphocytes with cyclic GMP induced an abnormal, cancer-like FFP response.

Cyclic AMP

High-fat diet promotes and causes distal shift of experimental rat colonic cancer--beer and alcohol do not.

Intestinal cancer was induced in inbred male D/A rats by 1,2-dimethylhydrazine, and the interrelationships between a high-fat (33.5% w/w) diet, beer and alcohol (4.8% v/v) ingestion, and tumor location and incidence were examined. The number of tumors per animal was significantly greater in both the small and large intestines of rats on the high-fat diet, as opposed to the standard diet. The 6-fold increase in incidence of colorectal cancer occurred almost exclusively in the distal half of the large bowel; i.e., there was a highly significant (p less than 0.005) shift, similar to that seen in man in countries adopting high-fat Western-type diets. Neither alcohol nor beer ingestion affected the incidence of intestinal cancers, but beer was associated with a more distal distribution of small-intestinal cancers in animals on the high-fat diet. However, this was not considered sufficient evidence for any material effect of beer on experimental intestinal carcinogenesis.

1,2-Dimethylhydrazine

Metastatic 'early' colorectal cancer.

If colorectal carcinomas where the primary tumours are confined to the wall are considered 'early', the likelihood of lymph node metastasis in these tumours is 21% and for those that do not extend beyond the submucosa it is 13%. Because of the renewed interest in local treatment of small accessible rectal tumours and the use of colonoscopy for the removal of 'polyps' with invasive carcinoma, we analysed our long-term cancer survival figures for 'early' cancers in this combined surgical series spanning more than 30 years. The presence of regional lymph node metastasis in 'early' rectal cancer was associated with a significantly (P = 0.001) reduced proportion of long-term survivors (56%) compared to those without nodal involvement (79%). Long term survival in 'early' colonic cancer was less influenced (P less than 0.05) by whether lymph node metastasis was present (73%) or not (77%). The authors conclude that until more information is available with regard to the risk of lymph node spread from 'early' tumours, resection is advised for all invasive tumours of the colon in good risk patients, but the indications for local excision of 'early' rectal cancers can be extended in view of the ease of careful follow-up and the use of salvage procedures in those with recurrence.

Colonic Neoplasms

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. I. Favorable prognosis in female patients.

In an immunological study of 288 colorectal carcinoma patients, we investigated the relationship between survival and preoperative in vitro antibody-dependent cellular cytotoxicity (ADCC) against the colonic carcinoma cell line HT-29. A highly significantly favorable (p = 0.001) association was found in the 20 female patients with ADCC. Nearly all (97%) of the 66 patients with ADCC were blood group O, but blood group per se did not relate to survival, nor could staging explain the survival association with ADCC. The mechanism whereby ADCC or its in vivo expression confers a survival advantage is unknown but we suggest that it derives from immunoreactivity against blood group A antigens produced inappropriately in the carcinomatous epithelium of the group O and B patients.

ABO Blood-Group System

Antibody-dependent cellular cytotoxicity (ADCC) in colorectal carcinoma. II. Blood group association.

Colorectal carcinoma patients' sera with ADCC antibody reacting with the HT-29 cell line (blood group A) generally (88%) cross-reacted with another group A cell line (COLO-394) but much less frequently (6-33%), with six tumor cell lines that did not express ABO blood group antigens. The findings suggested the possibility that the ADCC reactivity against the HT-29 cell line particularly by patients of blood group O is generally via "A" or "A-like" antigenicity of the target cells. This was supported by absorption studies that showed that the ADCC reactivity could be removed by blood group A but never by group B erythrocytes. Our results suggest that the prognostically favorable ADCC antibody in colorectal carcinoma patients' sera is of anti-blood group A specificity or cross reactivity.

ABO Blood-Group System

Mucosal dysplasia. A major predictor of cancer following ileorectal anastomosis.

Fifty patients with ulcerative colitis managed by colectomy and ileorectal anastomosis had rectal biopsies performed in the period 1967 to 1972. Follow-up information was available on all patients. Thirty-nine patients were reviewed and rectal biopsies performed in the 1980 to 1982 period. Three patients had developed rectal cancer in the period 1975 to 1980, and two rectal cancers were detected in the 1980 to 1982 follow-up period. All cancers occurred in patients with a diagnosis of moderate or severe dysplasia in biopsy specimens from the 1969 to 1972 period. The probability of developing rectal cancer after a diagnosis of moderate or severe dysplasia in this series reached 42 per cent at nine years from diagnosis.

Adult

T helper lymphocyte depression in early human pregnancy.

Peripheral blood lymphocyte subclasses were determined in 60 women with normal pregnancies, 20 from each trimester, and in 20 controls using automated flow cytofluorimetry. The cells were stained with the monoclonal antibodies OKT3, OKT4 and OKT8 to stain total T cells, T helper and T suppressor-cytotoxic lymphocytes, respectively. A polyvalent rabbit anti-human Ig serum was used to stain B lymphocytes. Absolute numbers of T lymphocytes were significantly reduced in both the first and second trimesters. This was due to a significant decrease in T helper lymphocytes and a smaller, statistically not significant, reduction in the number of T suppressor lymphocytes. There was no significant change in lymphocyte subclasses during the third trimester. Total lymphocyte numbers were normal throughout pregnancy.

Antibodies, Monoclonal

Monoclonal antibodies to human colon and colorectal carcinoma.

A series of monoclonal antibodies was produced by immunizing mice with fresh carcinoma of the colon and with the cell line HT-29. These antibodies could be classified into 3 different groups: (a) those which were HT-29 specific and reacted with no other cell line or fresh colon carcinoma samples; (b) antibodies which reacted with HT-29 and were also reactive with a number of other in vitro cell lines; and (c) antibodies which appeared to be specific for carcinoma of the colon cell lines in that they reacted selectively with colon carcinoma cell lines and not with carcinoma lines derived from other tissues. It was clearly shown by immunoperoxidase staining of both normal and neoplastic cells of the gastrointestinal mucosa, from stomach to colon, that these antibodies were not tumour-specific. Indeed, one antibody (250-30.6) has a remarkable specificity for secretory epithelium of any tissue whether it be found in the gastrointestinal tract, respiratory system or urinary system. We question the existence of tumour-specific antigens detected by monoclonal antisera described thus far, and comment on the remarkable specificity of some of the sera produced, emphasized by the secretory cell-specific antibody described herein.

Animals