The importance of self-observation of fecal blood in indicating a proper bowel examination.

This study presents a new model of screening for colorectal cancer. Persons aged 50 or over in a city of 160,000 inhabitants were encouraged by a newspaper campaign to act on signs of fecal blood and to come forward for examination. A quantitative immunological human hemoglobin (Hb)-specific test method was employed, and, as a simple discriminatory help to minimize perianal contamination, a constringent local ointment was used. The group of fecal bleeders was examined by colonoscopy. Altogether, 1638 persons came forward to request screening. Of these, 168 were submitted for colonoscopy, and, among those 18 colorectal cancers (11% of colonoscopies) were found. Of the cancers a significant part 28% were early cases (Dukes' A). In addition 28 adenomas were detected. The results show that there exists in the population a group of neglected fecal bleeders. Increasing the population's awareness of this symptom as a possible sign of colorectal cancer combined with prompt and proper medical investigations would lead to the detection of early cases of colorectal cancers.

Finding colorectal tumours with an immunological faecal occult blood test in symptomatic primary health care patients.

The aim of this prospective study was to investigate whether an immunological double faecal occult blood test (Fecatwin-S/FECA-EIA) can be used in screening patients with symptoms suggestive of colonic or rectal origin in primary health care. Altogether 523 patients were referred to the study by general practitioners. Three kits were used for the faecal samples and each time the sample was taken from two places of the faeces. If the guaiac test (Fecatwin-S) was positive, the immunological test (FECA-EIA) was performed. All 71 patients with an immunotest absorbance value of over 0.8 were investigated with colonoscopy and this group had 13 cancers, eight adenomas and one hyperplastic polyp. A control group of 41 consecutive patients with an absorbance value under 0.8 had one adenoma and three hyperplastic polyps. The uninvestigated FECA-EIA negative patients had no malignant colorectal tumours in the mean follow-up period of 2.2 years according to hospital records. All cancers had very high absorbance values, the mean value being 2.461. With adenomas the mean absorbance value was 1.912 and with hyperplastic polyps 0.814. Most of the diagnosed cancers and adenomas were in patients over 65 years of age. The study indicates that the immunological occult blood test is a useful tool for a general practitioner in finding bleeding colorectal tumours. The number of needless clinical examinations can be lowered which is important especially among elderly patients. However, the test-negative patients should be retested or investigated if symptoms continue.

Adenoma residua in colorectal cancer. A study of 34 colorectal cancers detected by an immunological occult blood test.

A retrospective histological study was made searching for adenoma remnants in 34 colorectal cancer specimens detected by the quantitative and human Hb-specific immunological FECA-EIA test for occult blood in the faeces. As a control group, 34 colorectal cancer preparations from routine hospital material were studied in a similar manner. A difference was found between these materials, 12 out of 34 study cancers showing adenoma residua compared with only two in the control group. Even if a proportion of colorectal cancers is apparently not associated with adenomas, it is suggested that the existence of adenoma remnants is a sign of biologically early tumour development and consequently, it might correlate with a favourable prognosis.

Gastric cancer associated structure in mucus glycoproteins shown as a clinically useful marker.

A new monoclonal antibody has been developed which is capable of detecting structures in gastric mucus glycoproteins expressed in the fetus and in adult gastric mucosa in conditions such as gastric carcinoma. Cancer associated monoclonal antibodies were selected by testing them against various mucous glycoprotein samples from the alimentary tract, including salivary glycoproteins from both secretory and non-secretory subjects, and cancerous and normal gastric juice glycoproteins. They were tested against 1000 samples of gastric juice from an unselected population. Immunochemical characterisation suggested that the glycoproteins picked up by P4 and i11 include one of the compounds reacting with rabbit anti-fetal sulphoglycoprotein antigen serum. On the basis of a clinical trial and immunohistological evaluation further evidence was obtained of P4 as the most promising antibody for further experimentation. A total of 302 gastric juice specimens from patients with various gastric symptoms were analysed using the enzyme linked immunosorbent assay technique and P4 antibody. Of 10 gastric cancers, nine had P4 in the gastric juice. A positive correlation was found between gastric ulcer and the appearance of P4. Duodenal ulcers were not correlated to P4. Atrophic gastritis and P4 coincided less frequently. Raised P4 values were found in between 3% and 9% of subjects, depending on the population. Cancer cases showed high P4 values, which allows adjustment of the lower limit of a positive result to high level whereby a considerable number of non-cancerous P4 positives are omitted.

Screening of colorectal tumours using an improved faecal occult blood test. Quantitative aspects.

A recently developed double test for detecting faecal occult blood (a sensitive guaiac test combined with a quantitative immunological human haemoglobin test), was adapted to population screening. The study involved an unselected population of 10,343, aged 49-74 years. There was 66.5% participation. 174 colonoscopies were done, yielding seven adenocarcinomas, 44 adenomas and four hyperplastic polyps. By eliminating benign anal tract bleeding, the number of endoscopies decreased from 340 to 174. Most tumours showed an absorbance over 0.80, and it is suggested that by setting the lower limit of positivity at the 0.80 absorbance level, the number of clinical examinations could fall to about 1%, without substantially missing tumours.

Canine gastric glycoprotein antigens in early carcinogenesis.

The effect of one single dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) on the antigenic structures of gastric juice glycoproteins, was studied in dogs. Antisera to glycoproteins of the fetal alimentary canal were raised. Histologic mucosal specimens and glycoprotein fractions of gastric juice which were taken from four dogs during a 15.5-month period after MNNG administration, were examined immunohistologically and by immunodiffusion for the appearance of fetal-like antigens. Fetal-like structures appeared in a stepwise manner in both the acid and neutral glycoprotein fractions of the gastric juice, and showed gradual crossreactivity between macromolecules obtained from gastric juice samples obtained during the observation period. Eight immunizations carried out using physicochemically different glycoprotein fractions of fetal canine alimentary canal mucosa, produced a similar response, thus indicating that the same antigenic structures are incorporated into all mucus glycoproteins, even though they do differ physicochemically. It is suggested that this "omnipotential" incorporation picture could also be found after exposure to MNNG and is, by its nature, typically fetal.

Clinicopathological study of gastric cancers and precancerous states detected by fetal sulfoglycoprotein antigen screening.

A clinicopathological analysis is presented of gastric cancer cases detected in a mass screening trial in Finland, using the oncofetal antigen, fetal sulfoglycoprotein antigen, as a marker. The survey covered a population of 53,020 between the ages of 40 and 70, the percentage of participation being 74.8%. Of these participants, 3,508 subjects (8.8%) were found to be fetal sulfoglycoprotein antigen secretors, and among them 36 gastric cancers, one gastric carcinoid, and 10 tubular adenomas were detected. Both main histological types of gastric cancer, intestinal and diffuse, were represented. There were 15 early cancers. In addition, there were three widely spread superficial cancers. Because of early diagnosis, the prognostic view for these cases is clearly better than that found in the clinic by conventional means, curative resection being carried out in 28 cases (78%).

The purification procedure for human gastric juice FSA and its chemical composition.

A purification procedure for a gastric cancer-associated glycoprotein FSA is described. This substance was considered to be sulphated but is now found to derive its charge from carboxylic groups and has been renamed foetal sialoglycoprotein. The chemical composition is similar to blood group substances with differences which may reflect its origin from gastric cancer. The molecular size differs from that of the carcinoembryonic antigen. The calculation of the yield based on dry weight measurements is not possible until a radioimmunoassay technique becomes available and development of such an assay is now in progress in our laboratory.

Occurrence of influenza A viruses and their antibodies in migratory birds in Finland.

A Finnish material of 455 cloacal specimens from 24 species of small migratory birds and of 54 cloacal specimens from 10 species of waterfowl was investigated for the occurrence of A type influenza virus. Influenza A virus was isolated in only one specimen, originating from a mallard (Anas platyrhynchos). Parallely, yolk material from 109 waterfowl representing 9 species was investigated for the occurrence of influenza A antibodies by complement fixation and immunodiffusion tests. In three yolk specimens, one from a widgeon (Anas penelope), one from a common gull (Larus canus) and one from a lesser blackbacked gull (Larus fuscus), positive reactions with low titres of 1:2--1:4 were obtained. The study shows that waterfowl can carry influenza A virus, but the role of small migratory birds in this respect seems to be negligible in Finland.

The use of oncofetal antigen FSA in discrimination between benign and malignant gastric ulceration.

Discrimination between histologically confirmed benign and malignant gastric ulcerations was studied, using an oncofetal antigen (FSA) as the parameter of malignant transformation. In chronic gastric ulcer FSA could be found in 54.2% as compared with 20.0% in duodenal ulcer patients. 91.1% of gastric cancers were FSA positive. A current epidemiological study on a non-selected population gives 8.8% FSA secretors. The study supports the earlier conception that chronic gastric ulcer must be considered a precursor of cancer, and indicates the need, especially in cases showing FSA secretion, for active surgical therapy or a long-term follow-up with endoscopic biopsies.

Prolonged BCG treatment of melanoma: does it suppress the immune capacity?

The immunological status of seven patients with disseminated melanoma during BCG scarification was followed. As parameters, the total peripheral blood leukocyte and lymphocyte counts, serum immunoglobulin levels, natural ABO blood group antibodies, lymphocyte responses in vitro to PHA and PPD, and skin reactivity against PPD and candidin were followed during a period of 2--36 months. The EAC-rosette-forming cells increased and the E-rosette-forming cells decreased during prolonged BCG therapy. The skin reactions and lymphocyte responses showed in most patients conversion from negative to positive or augmentation at the start of the therapy. Later on, however, the values in most patients dropped before disseminated disease became clinically apparent. In the only surviving patient the values first increased, remained high, and after 100 weeks treatment decreased. After 140 weeks' treatment immunological parameters are similar to pre-treatment levels. The possibility that prolonged intensive BCG treatment might eventually suppress the immune system, and thus result in an enhanced risk of dissemination of the disease, is discussed.

Intestinal-type carcinoma of gallbladder. A histochemical and immunologic study.

Two intestinal carcinomas of the gallbladder are presented. In both carcinomas the structure was papillary in superficial parts; the deeper ones also tended to an adenomatous structure. One of the tumors was bordered by a mucosa, with both intestinal- and antral-type metaplastic islands. The tumor was mainly a typical papilloma with malignant degeneration and infiltrative growth. The intestinal structure was morphologically clear in the papillary area of both carcinomas, but not distinct in the invasive part of the tumor. In both tumors, goblet cells and columnar cells with a distinct brush border were noted. Histochemical and immunologic methods were used in the identification of the glycoproteins of the tumor cells. With both methods the intestinal character of the tumor could be shown. A positive fluorescence was achieved with an intestinal antiserum in well-differentiated tumorous areas containing goblet cells, as well as in the intestinal metaplastic areas. In the same areas the gallbladder-specific antigen was negative. The antiserum isolated from the normal gastric mucosa and corresponding to neutral glycoprotein gave a positive fluorescence only in the nontumorous metaplastic gastric superficial-type epithelium and in the metaplastic antral-type glands.

Electrophysiological findings in diphenyl poisoning.

The fungistatic agent diphenyl caused fatal poisoning with signs of neurotoxicity in a worker in a Finnish paper mill. This initiated a neurophysiological study of 24 workers occupationally exposed to diphenyl. Ten men showed EEG abnormalities, mainly diffuse or generalized ones. The abnormalities persisted on re-examination one and two years later. Nine subjects had EMG abnormalities; seven also exhibited fibrillations in some muscles. One subject showed a long rhythmic series of fasciculations similar to the spontaneous activity described in infantile spinal muscular atrophy. Nerve conduction velocity, especially that of slower motor fibres, was reduced in several cases. Electroneuromyographic abnormalities also persisted on re-examination. Although diphenyl is considered a comparatively safe chemical, it showed evidence of neurotoxicity when workers were exposed to concentrations in excess of the presently accepted threshold limits. Electrophysiological methods should be applied for the early detection of occupational hazards.