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The ingestion and adherence components of the overall phagocytic process have been studied in human peritoneal macrophages (HPM) from cancer or uremic patients and compared with HPM from healthy controls. No difference was found in the studied functions between cancer patients and controls. However, HPM from uremic patients showed a highly significant impairment in the overall phagocytosis and the studied components of this function. In all groups the ingestion phase was significantly depressed after 24 hours of culture. Despite this functional impairment, the total phagocytic process was unchanged, owing to a significant increase in the adherence of test particles.

SUMMARY In a Swedish double-blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2-receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well-matched prior to treatment. Omeprazole was superior to cimetidine in ulcer-healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole- and 45 % of the cimetidine-treated patients were healed (P= 0.02), after 4 weeks 97 and 84% (P= 0.01), and after 6 weeks 100 and 92% (P= 0.02), respectively. There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P= 0.05). Both drugs were well-tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P= 0.02). A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52 % in the cimetidine group. In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

To study some mechanisms involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis.In vitro study.Medical centre hospital, Sweden.Mutagenicity in Ames' test of neutrophils challenged for 2 hours or more by two different strains of H. pylori. One strain designated NCTC 11637 by the National College of Type Cultures activated neutrophils to an oxidative burst and producing vacuolating cytotoxin, the other strain C-7050 lacked these abilities. Mutagenicity was also studied with sterile human gall bladder bile alone added to neutrophils or in combination with both neutrophils and H. pylori.There was no increase in the number of revertants with the crude suspension or the supernatant of neutrophils challenged for 1 hour or less with H. pylori, bile, or the combination of both. However, in 5 out of 19 experiments there was significant mutagenicity after challenge of neutrophils for 2 hours or more with either strain of H. pylori, bile, or the combination of the two. The strongest mutagenicity was obtained after challenge over night (18 hours) with the combination of H. pylori and bile.Mutagenicity occurs when neutrophils are challenged with H. pylori and bile. Factors other than reactive oxygen metabolites seem to be responsible.

The results of case-control studies and anecdotal reports suggest that pancreatitis may be a risk factor for pancreatic cancer, but there have been no studies of sufficient size and power to assess the magnitude of the relation between these two diseases.We undertook a multicenter historical cohort study of 2015 subjects with chronic pancreatitis who were recruited from clinical centers in six countries. A total of 56 cancers were identified among these patients during a mean (+/-SD) follow-up of 7.4 +/- 6.2 years. The expected number of cases of cancer calculated from country-specific incidence data and adjusted for age and sex was 2.13, yielding a standardized incidence ratio (the ratio of observed to expected cases) of 26.3 (95 percent confidence interval, 19.9 to 34.2). For subjects with a minimum of two or five years of follow-up, the respective standardized incidence ratios were 16.5 (95 percent confidence interval, 11.1 to 23.7) and 14.4 (95 percent confidence interval, 8.5 to 22.8). The cumulative risk of pancreatic cancer in subjects who were followed for at least 2 years increased steadily, and 10 and 20 years after the diagnosis of pancreatitis, it was 1.8 percent (95 percent confidence interval, 1.0 to 2.6 percent) and 4.0 percent (95 percent confidence interval, 2.0 to 5.9 percent), respectively.The risk of pancreatic cancer is significantly elevated in subjects with chronic pancreatitis and appears to be independent of sex, country, and type of pancreatitis.

A prospective controlled randomized trial testing adjuvant postoperative combination chemotherapy (5-fluorouracil, lomustine (CCNU) and vincristine) versus no adjuvant therapy in patients operated on for Dukes' C colorectal cancer is reported. In total 334 patients aged less than 70 years were recruited: 205 patients with colonic and 99 with rectal cancer, but there were three protocol violations and these cases are excluded from further consideration. Twenty-seven patients had a limited resection of their cancer. After 5 years' follow-up there was no significant difference in the tumour-free survival rate or in the survival rate between the treated and control groups. Twenty-nine of the 147 patients who started chemotherapy discontinued this treatment because of side-effects, mainly from the gastrointestinal tract. In 30 patients treatment was discontinued because of recurrent disease. The conclusion is that systemic administration of combination chemotherapy for colorectal cancer after operation is not worthwhile in routine clinical practice.

The targeted delivery of cytotoxic drugs to cancer patients is intended to optimize therapeutic efficacy and reduce side effects. Early results from pioneer work in Boston using a clockwork drive were positive and led to development of the Chronometric Infusor [2]. This external pump was linked to a percutaneous arterial or venous catheter. It was carried in a foam-rubber pouch to dampen the ticking of the clockwork and attached by straps around the patient’s neck and chest. The plastic drug reservoir of the pump had a capacity of 25 ml, and the system allowed a delivery rate of 5 ml per 24 h. The clockwork required winding after 8–12 h.

Various congenital malformations of the testis and the seminal pathways are illustrated by 10 cases. Though these malformations are often free from symptoms, an increasing number of them are now being discovered in connection with investigations of male infertility. In cases of azoospermia where testicular biopsies show complete spermatogenesis, surgical exploration is indicated. Some of these malformations may then be treated by surgery, with fairly good prospects of restored fertility.

Lipid islands in the gastric mucosa are macroscopically well demarcated white or yellow-white patches, microscopically composed of accumulations of lipid-filled macrophages. The occurrence of lipid islands has not previously been linked to gastric surgery. This study presents the prevalence of lipid islands after Billroth I and Billroth II resection as well as in a nonoperated control group. Gastroscopy and multiple biopsies were performed at selected intervals after surgery. The occurrence of single or multiple lipid islands increased with the postoperative time, independent of the original ulcer disease or the type of operation performed. In nonoperated patients, lipid islands were found in 6.3%, and approximately the same prevalence was found 1 to 3 years after gastric surgery. A much higher prevalence was found 10 to 15 years postoperatively, and 23 years after Billroth II resection 60% of the patients demonstrated lipid islands. At repeated gastroscopic examinations over a period of 1 to 2 years, no certain changes in number, size, or distribution of the lipid islands were seen. The etiology of lipid islands is unknown, but intestinal-gastric reflux may be the most plausible etiological factor.

Bleeding is a potential but rare complication after endoscopic biopsies of the gastric mucosa in non-operated patients. The resected stomach, however, seems to run an increased risk of this complication. In a retrospective study comprising 1843 consecutive biopsy examinations of the gastric remnant, 15 bleeding episodes were recorded (0.8%). The frequency of bleeding was 1.1% for the Billroth-II-resected stomach and 0.2% for the Billroth-I-resected stomach. In two patients the bleeding was excessive, requiring emergency surgery. Six other patients required blood transfusions. The observed frequency of bleeding was probably a minimal estimate, suggested by a 20% occult bleeding found in a small prospective study. When planning follow-up examination of patients who have had a gastrectomy, the risk of bleeding should be taken into account, and the patients should be appropriately informed and supervised.

The distribution and metabolism of [5-3H]N'-nitrosonornicotine ([5-3H]NNN) was studied in three 18-day-old miniature pigs. [5-3H]NNN was administered by intracardiac administration into the right ventricle of the heart to mimic uptake by the lung. Whole body autoradiograms taken 15-220 min after treatment showed high levels of radioactivity in the mandibular and parotid salivary glands, Harder's gland, lacrimal glands, glands of the snout and respiratory part of the nasal cavity, and the melanin of the eyes and skin. Bound radioactivity was most abundant in the nasal mucosa and liver. Analysis of tissues by h.p.l.c. showed the presence of high levels of [5-3H]NNN in the mandibular glands and Harder's gland. Levels of [5-3H]NNN and its metabolites were determined in arterial and venous serum, 0.5-220 min after injection. The disappearance of [5-3H]NNN from serum was biphasic. 4-Oxo-4-(3-pyridyl) butyric acid, a metabolite of [5-3H]NNN resulting from 2'-hydroxylation, which is a suspected activation pathway, was detected 0.5 min after injection and appeared to reach a steady state 2-220 min after injection. 4-Hydroxy-4-(3-pyridyl)butyric acid, from 5'-hydroxylation of [5-3H]NNN, and norcotinine, from denitrosation, were also rapidly formed. These experiments are the first in which the appearance of NNN metabolites in blood has been measured. The ratio of 2'-hydroxylation to 5'-hydroxylation varied from 0.27 to 0.60 in arterial serum and from 0.33 to 0.49 in venous serum in the period from 2-220 min. [5-3H]NNN accumulated in the stomach contents such that its levels were greater than those in arterial or venous serum, 60 min after injection. The results of this study demonstrate that the miniature pig is a useful model for the investigation of nitrosamine metabolism and indicate some similarities and differences in metabolism and distribution compared with the rat.

The effect of griseofulvin on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to other microtubule antagonists, grisofulvin did not inhibit monocyte phagocytosis. It is suggested that the lack of griseofulvin interference with essential leukocyte functions is a possible explanation for the fact that the microtubule antagonist griseofulvin serves as a comparatively safe and harmless drug.

To investigate gallstone size, growth, and the relation between stone size and gallbladder cancer we have used cholecystectomy reports from 1676 female subjects (169 Whites, 531 Blacks, and 976 Native American Indians). Although the prevalence of gallstones differs markedly in these groups it appears that the estimated growth rate of gallstones in younger subjects, 2.0 mm per year (95% confidence interval: 1.7-2.3 mm) is homogeneous for all three groups. In both Indian and non-Indian populations the proportion of small stones diminished and the proportion of large stones increased over time. We found a strong relationship between gallstone size and gallbladder cancer. Large stones (greater than or equal to 3 cm) were found in 40% of patients with gallbladder cancer but in only 12% of all subjects of similar age. The relative risk for gallbladder cancer in subjects with stones greater than or equal to 3 cm was 9.2 compared with subjects with stones less than 1 cm. (95% confidence interval: 2.3-37). We estimate that one-third of all gallbladder cancers in subjects with calculi will be associated with large (greater than or equal to 3 cm) stones. We believe that stone size might be used to determine the risk of gallbladder cancer in patients with gallstones.

Possible promotion of MNNG-induced gastrointestinal carcinogenicity was evaluated in male Wistar rats exposed to unconjugated bile acid given as gavage or as obtained through truncal vagotomy plus pyloroplasty. No significant difference was found compared with the relevant control groups. Even though gastroduodenal erosions were found more frequently in the bile acid gavage and MNNG groups than in MNNG-treated controls, secondary deconjugated bile acids apparently did not reach optimal promoting concentrations. In contrast to partial gastrectomy, vagotomy and pyloroplasty does not increase the tumor yield in the rat.

The phagocytic and metabolic functions of the reticuloendothelial system (RES) were studied in 20 postoperative cancer patients undergoing long-term combination chemotherapy. Each course included vincristine, methyl-CCNU (day 1) and 5-fluorouracil (days 1-5) every sixth week. The RES-test was performed prior to each course, using /sup 125/I-labeled microaggregated human serum albumin. Total leukocytes, mononuclear cells and platelets were monitored before, during and after each treatment. A significant, initial impairment of the catabolic function of the RES was found (2P . 0.006). A similar, nonsignificant trend was observed in the phagocytic function. The normalization may mirror the large metabolic capacity of the RES. This is further demonstrated by the fact that splenectomized (N . 9) and nonsplenectomized patients did not differ. A significant decrease was also found in total leukocytes and mononuclear cells (2P less than 0.001). Combination chemotherapy induced a similar myelosuppression in both groups, but did not further reduce the mobile RES in asplenic individuals.

The nutrient intake, fecal neutral sterol concentration, and bile acid concentration of populations with a varied risk for colon cancer development were investigated. High‐risk populations in the metropolitan New York area and Malmo, Sweden, were compared with an intermediate‐risk population in Umea, Sweden. The mean daily intake of protein and fat was comparable in all groups, but the total daily fiber intake was higher in Umea, as was the total daily stool output. There was no difference in the total fiber intake and stool output between Malmo and metropolitan New York. The fecal secondary bile acid concentration was lower in Umea than in the other two areas; no difference was observed between Malmo and metropolitan New York. These results suggest that high fiber intake may be considered protective against colon cancer even in a population with a high fat intake. A high dietary fiber intake may limit colon cancer risk by increasing stool bulk, and thus diluting and/or binding tumor promoters.

The effects of degradable starch microspheres (DSM) on mitomycin C pharmacokinetics and bone marrow toxicity were studied in a phase II multicenter study. Sixty-three patients with non-resectable primary or secondary liver cancer were randomized to receive either i.a. mitomycin C 15 mg/m2 first, followed 5 weeks later by mitomycin C 15 mg/m2 plus DSM 360 mg administered into the hepatic artery (group I) or the same treatments in the opposite sequence (group II). In 36 out of 47 patients who received at least 2 treatments, peripheral venous blood samples were analyzed for mitomycin C pharmacokinetics on a minimum of 2 paired courses. In all patients, the area under the concentration time curve (AUC) was significantly lower when the drug was co-administrated with DSM, but the terminal half-life (t1/2) of mitomycin C was unchanged. In group I the addition of DSM resulted in a significantly lowered AUC, but not in group II. The discrepancy between the 2 groups is probably due to differences in DSM-induced intra-hepatic shunting. The addition of DSM resulted in significantly higher platelet nadir values, but unchanged white blood cell count nadir value. In conclusion, DSM reduce the systemic exposure of mitomycin C and seem to lessen the haematologic toxicity judged from a less pronounced decrease in platelets.

It has been postulated that reflux of bile into the stomach promotes gastric carcinogenesis. Bilestained aspirates from 50 asymptomatic patients, partially gastrectomized more than 10 years earlier, were examined bacteriologically and with regard to conjugated and deconjugated bile acids. Endoscopic biopsies showed atrophic gastritis in all patients, cancer in two and severe dysplasia in another two. pH in the reflux aspirates was 7.3 ± 0.4 (mean ± standard deviation). Bacterial cultures were positive in all patients studied. Fecal type flora, mostly E. coli, klebsiella and Clostridium perfringens, was found in 85 percent of the patients. Total bile acids were found to be 2.6 ± 2.0 mg/ml, 23 percent of which were deconjugated. Deoxycholic acid, known to promote carcinogenesis in animals, amounted to 27 percent of total bile acids and deconjugated deoxycholic acid was 5 percent of total bile acids. The mostly anaerobic microflora and the presence of mainly free secondary and primary bile acids may contribute to the high incidence of cancer in the gastric remnant observed after Billroth I or II operations.

The effect of CCNU on human monocyte phagocytosis of yeast cells was measured in vitro. ‘Therapeutic’ CCNU concentrations had no measurable effect on monocyte phagocytosis. Higher concentrations of CCNU had a slight but statistically significant effect on the engulfment phase of monocyte phagocytosis. The results suggest that CCNU treatment is of minor importance for monocyte function.

Carcinoma of the gastric remnant after resection for benign ulcers is regarded as a rare complication after Billroth I resection. In seventy-four patients reexamined by gastroscopy and multiple biopsies ten to twenty-two years after gastric resection four cases of cancer of the gastric stump were diagnosed and the patients operated on. Another eight patients had regenerative polyps and one patient had a tubular adenoma. The histologic findings in gastroscopic biopsy specimens from the gastric stoma and fundus are compared. Possible precancerous changes and etiologic aspects are discussed briefly. Repeated gastroscopy is recommended starting about ten years after gastric resection for benign ulcers.

A case of embolism of a .22 caliber revolver bullet to the left deep femoral artery after penetrating the abdominal aorta is described. The case is discussed in relation to previous reports with special reference to the surgical intervention. The importance of whole body fluoroscopic search for all bullets not accounted for is emphasized. When the bullet entrance site is in the abdominal aorta, emboli should be expected to locate to the lower extremities.

The role of cytoplasmic microtubules in the phagocytosis of yeast cells by blood monocytes was studied by means of therapeutic concentrations of the Vinca alkaloids vincristine, vinblastine, and vindesine. Phagocytosis was measured in a monolayer of glass-adherent monocytes fed with fluorescein-labelled yeast cells. Phagocytosis was composed of two sequential processes, yeast cell adherence to the monocyte and yeast cell engulfment by the monocyte. Monocyte phagocytosis was significantly inhibited by the Vinca alkaloids, mainly due to inhibition of engulfment but probably also due to inhibition of adherence. Since the Vinca alkaloids are microtubule antagonists it is reasonable to assume that monocyte phagocytosis, both adherence and engulfment, are partially microtubule-dependent processes. It is suggested that Vinca alkaloid inhibition of monocyte phagocytosis is of value in the treatment of type II-III autoimmune disorders, such as idiopathic thrombocytopenic purpura and autoimmune haemolytic anaemia.

The environmental carcinogens N-nitrosopyrrolidine (NPYR) and N'-nitrosonornicotine (NNN) were incubated with human liver microsomes to test for the presence of enzymes catalyzing alpha-hydroxylation, which is likely to be an activation mechanism for these compounds. Both nitrosamines underwent alpha-hydroxylation; rates were higher for NPYR than for NNN, as observed in rats. The results indicate that both NPYR and NNN can be metabolically activated by human liver microsomes.

The development of morphological changes in the body mucosa after partial gastrectomy for ulcer disease according to Billroth I and II was studied early (within 3 years) and late (10-24 years) postoperatively with gastroscopy and forceps biopsies. The morphological findings in the body mucosa of the operation specimens and biopsies from the stomas were compared. The effect of time, ulcer disease, operation procedure, sex, and age was studied. In duodenal ulcer patients, with significantly less pronounced inflammatory mucosal changes in the operation specimen, partial gastrectomy caused acute and chronic gastritis to the same degree as seen in gastric ulcer patients within 3 years postoperatively. Duodenal ulcer patients also developed mucosal atrophy, cystic dilatation of the gastric glands, and intestinal metaplasia by time to an extent not significantly different from what was found in gastric ulcer patients. No correlation could be found between the mucosal changes and factors like age, sex, or operation procedure. Mucosal atrophy, chronic gastritis, and intestinal metaplasia are regarded as possible features of malignant transformation. If this concept is true, our findings may explain why stump carcinoma is frequently reported with the same incidence independent of preoperative ulcer disease or anastomotic procedure.

In order to diagnose early stump carcinoma 20 years after Billroth II resection an endoscopic follow-up was performed in 214 of 459 patients primarily resected for benign ulcer disease. A further aim was to study the localization of macro- and microscopic mucosal changes. Three patients with stump carcinoma were found among 140 patients dead at the follow-up. Six carcinomas, among which two were early carcinomas, were diagnosed in the follow-up group. All carcinomas were found in men. Moreover, 1 patient with multifocal precancerous alterations of the stoma, 2 with tubular adenoma, and 20 with regenerative polyps (9.3%) were found. No significant difference was found in the ratio of original duodenal-gastric ulcer in patients with carcinoma or polyps when compared to other patients. The macro- and microscopic changes were most severe in the stoma, which seems to be a preferential site for carcinoma. The histological changes, however, did not differ in patients with or without carcinoma and polyps. At present no evidence has been found indicating that histological findings such as chronic atrophic gastritis, intestinal metaplasia, or cystic dilatation of the gastric glands, can be regarded as an early indicator of malignant transformation. In order to achieve early detection of stump carcinoma, repeated gastroscopic examinations are recommended from 10 to 15 years after surgery.

The immunosuppressive effect of chemotherapy associated with surgery is poorly understood. The effect of combination chemotherapy--fluorouracil, adriamycin and mitomycin (FAM)--on monocyte phagocytosis was tested in patients operated on for gastric cancer. The adherence, engulfment and total phagocytic process were studied with a fluorescence-quenching technique 1 hour, 24 hours and 1 week after 19 FAM treatments in nine patients. The engulfment of yeast cells and the total phagocytosis were significantly impaired 1 hour post-treatment (p less than 0.05 and less than 0.01, respectively). These functions had normalized after 24 hours, but after 1 week the engulfment step was significantly depressed (p less than 0.05). Significantly increased adherence of yeast cells (p less than 0.05) was found at the same time. The initial, transient depression of monocyte phagocytosis probably was related to inactivation of cell-surface receptors. The late (1 week) depression probably was due to bone-marrow toxicity. This functional impairment of the blood monocytes was not reflected as clinical liability to infections.

The dietary pattern, fecal bile acid and neutral sterol concentrations, and the bacterial beta-glucuronidase activity of 2 population groups with a varied risk for colon cancer development (i.e., a high-risk population in the metropolitan New York area and an intermediate-risk population in Umea, Sweden) were investigated. The average daily intake of dietary protein was the same in the 2 groups, but the fat intake was higher in Umea than in New York. The daily total fiber intake was also higher in Umea, as was the daily total stool output. The concentration of fecal secondary bile acids and beta-glucuronidase activity was lower in Umea than in New York, but the total daily excretion of these constituents was the same in both groups. The data suggest that one of the factors contributing to the lower risk of colon cancer in Umea, despite the high dietary fat intake, is the high intake of dietary whole grain and cereal fiber, which leads to an increase in stool bulk, thus diluting and/or binding promoters.

A very unusual case of incarcerated afferent loop in a postoperative diaphragmatic hernia after a Billroth II operation and a subsequent thoraco-abdominal resection of a benign oesophago-cardial stricture is presented. Insufficient closure of the diaphragm combined with long loops after a gastro-jejunostomy seemed to be the predisposing factor to this unusual postoperative complication. The risk of rare cases of incarcerated diaphragmatic hernia should be considered after proximal gastric resection.

For reasons that are not known, the incidence of stomach cancer is declining in most countries. In contrast, cancer of the gastric remnant after partial gastrectomy for peptic ulcer disease seems to be increasing. "Stump cancer" has been claimed to be a separate disease entity and has recently been mentioned as an iatrogenic cancer. Alkaline bile reflux, dietary surfactants and maybe the abuse of tobacco are postulated as promoting or initiating agents, in causing malignant transformation of the operated as well as non-operated stomach. Variations in gastric pH, microflora and emptying rate may be of importance in the carcinogenic process. The decline in cancer incidence in the non-operated stomach has mainly been restricted to the intestinal type of cancer. Thus, it is important to note that stump cancer often is of the diffuse type. Different target cells and/or modes of carcinogen exposure may be of etiological importance in these histologically and clinically separate neoplastic diseases.

Selective angiography of the testicular artery was performed in 12 boys (age 3–14 yr) with nonpalpable testis. The angiographic, operative, and microscopic findings are described. True aplasia was diagnosed in seven patients. In three patients previously operated upon, the second exploration was facilitated by angiography. This method might be a valuable diagnostic aid in selected cases previously operated for gonadal disorders or inadequately explored for cryptorchism in order to avoid more extensive surgical explorations.

Carcinoembryonic antigen (CEA) was studied by the three-layer bridge immunoperoxidase technique in gastric biopsy specimens taken from 49 patients, 13--20 years after partial gastrectomy. Routine histological examination revealed various degrees of chronic atrophic gastritis in all patients. A positive CEA reaction was found in 6 out of 9 with malignant or premalignant mucosal changes and in 4 out of 40 without these changes. In two cases of carcinoma the biopsies revealed a positive CEA reaction. In 4 patients with carcinoma diagnosed 1--2 years after the first examination the initial nonmalignant biopsies were CEA-positive in one case. All biopsies from mucosa with severe dysplasia and adenomatous polyps were CEA-positive. Four patients without malignant or premalignant changes in the gastric mucosa had CEA-positive biopsies. No carcinoma has been found in these patients at re-examinations after 1 year. The results indicate that the occurrence of immunohistochemically detectable CEA may be associated with malignant transformation of the gastric mucosa. The value of this method in screening patients at increased risk of gastric carcinoma will be further explored.

The effect of therapeutic concentrations of doxorubicin, epirubicin, and mitoxanthrone on mature leukocyte function has been examined by measuring phagocytosis of yeast cells by surface-bound monocytes, using a fluorescence-quenching method. There was a 10% inhibition of monocyte phagocytosis by doxorubicin, but epirubicin and mitoxanthrone had no effect on monocyte phagocytosis. Anthracyclines may have a major immunosuppressive effect due to bone marrow depression. The lack of interference with mature monocyte function by epirubicin and mitoxanthrone provides a potential advantage in comparison with the parent compounds.

Reported 5-FU-induced cardiac side effects may be explained by drug-induced hemodynamic changes and/or by direct myocardial toxicity due to regional drug uptake. This question was studied in 11 animals given constant infusions and 6 animals given bolus 5-FU infusions into the hepatic artery. Six animals, which received normal saline infusion, served as controls. A second aim was to study possible pulmonary drug clearance. Aortic, pulmonary arterial, and coronary sinus plasma 5-FU concentrations were determined during constant and after the bolus infusions of 5-FU. The V5 ECG, aortic, pulmonary arterial, and right atrial pressures were recorded continuously, and cardiac output and coronary sinus blood flow were recorded intermittently in all animals. No significant alterations in hemodynamic variables were seen during constant infusion. After the bolus infusion, an increased arterio-mixed venous oxygen content difference was recorded. Pharmacokinetic data after 3-min infusions indicated pulmonary drug uptake and release; during constant infusions, the data indicated myocardial drug uptake. As there were no alterations in myocardial oxygen demand or supply or in systemic hemodynamics during this myocardial drug uptake, it is likely that the cardiotoxicity is related to the direct effects of the drug on cardiac myocytes.

The continuity of the T tube tract on removal of the drain was studied by fluoroscopic examination in 51 patients. Leakage was found in 25 cases (abdominal cavity 7, wound drain 6, local cavity 11, combined abdominal and wound drain leakage 1). No correlation was found between the incidence of pyrexia or pain and the presence of leakage. These complications, noted in 10 patients, are probably explained by bacterial contamination of the bile in combination with the trauma caused by extraction of the tube.

Theoretically, administration of 5-fluorouracil (5-FU) into the hepatic artery should improve the clinical response rate by high tumor cell extraction of the drug. However, previous studies in animals and man have also found a major extrahepatic elimination route for 5-FU. In the present study of 7 patients with primary and secondary liver cancer, we have found indications that a considerable elimination of 5-FU takes place in the cardio-pulmonary circuit. Thus, the mean AUC in the hepatic vein was 7185 mumol X min X l-1 and 3792 in a peripheral vein.

A patient case with malignant fibrous histiocytoma (MFH) of the gallbladder is presented. This rare malignancy is occasionally found within the abdominal cavity. However, to our knowledge this is the first report of this tumor within the biliary tract. Diagnostic, therapeutic, and etiological aspects are discussed.

Doxycycline has been reported to depress leukocyte functions. The effect of peroral administration of 400 mg doxycycline was evaluated after 24 hours in 18 healthy persons. No inhibitory effect on monocyte phagocytosis was found. There is no evidence that therapeutic concentrations of doxycycline depress leukocyte functions to a degree of clinical significance.

Splenectomies performed in children aged 0-14 during the period 1968-1977 have been reviewed. In 413 cases traumatic rupture of the spleen had occurred. The trauma causing the rupture, preoperative examinations, operative findings and complications have been studied. Most frequently traffic accidents had caused the splenic rupture. Many ruptures were not bleeding at the time of operation. Consequently surgical repair saving the spleen had been possible in several cases. Splenectomized children have a significant increased risk of overwhelming sepsis. In this retrospective material 10 children (2.4%) developed sepsis within eight years. Five of these cases had a fatal outcome. The need for a more conservative attitude in children with splenic rupture is emphasized.

The effect of a therapeutic doxycyline concentration on yeast-cell phagocytosis by blood monocytes was studied in vitro by means of a fluoresence assay. This method allows discrimination between monocyte-adherent yeast cells and ingested yeast cells. The adhesive and phagocytic capacity of 50 monocytes was measured in 16 healthy donors. Yeast-cell adherence was not influenced by doxycycline. In contrast, a slight depression of phagocytosis by doxycycline was suggested. The median difference between doxycyclin-treated and control monocytes was 30% (p = 0.07). It is reasonable to assume that a possible inhibitory effect of doxycycline on monocyte phagocytosis is negligible in healthy individuals. However, a clinically significant effect cannot be excluded in severely immuno-compromised patients.

The splenic arteriovenous differences in plasma amino acid concentrations were assessed in situ by peroperative sampling in 11 patients undergoing splenectomy because of benign and malignant hematologic diseases. The total difference was about 250 mumol/l, which suggests that the spleen contributes about 11 mumol/100 g spleen/min of amino acids to the portal vein. This means that the liver extraction of amino acids may be at least 10% greater than previously believed.

A retrospective and a prospective group of 38 and 20 patients respectively were studied with regard to bacterial strains, clinical effect, toxic side effects and serum concentration of gentamicin in severe surgical infections. A high degree of therapeutic efficacy evaluated as cure or improvement was noted (68 and 75% in the two groups). The serum levels were especially closely checked in the prospective study to keep the gentamicin concentration within the therapeutic range but below toxic levels. This aim was achieved in most cases probably explaining the relatively low incidence of side effects (nephrotoxicity 4 and fungal infection 11 patients). The hazards of gentamicin interactions with drugs like furosemide, penicillins or cephalosporins are discussed.

A patient case with cystadenocarcinoma of the pancreas in a middle-aged woman is described. Nine years prior to the pancreatic malignancy she underwent cystogastrostomy due to a pancreatic cyst presumed to be of non-neoplastic nature. The malignancy occurred at the site of the previous cystogastrostomy and was radically resected. Five years later the patient was well without signs of recurrence. The possibilities of incorrect primary diagnosis or development of a rare pancreatic malignancy in a previous cystogastrostomy are discussed.

A selective angiography of the testicular artery was performed in 7 boys and 7 men without a palpable testicle in order to localize cryptorchid testes or to establish testicular agenesis. The examination could be carried out in all cases, and the angiographic diagnosis was confirmed at operation and at a subsequent microscopy in the 12 cases hitherto operated upon. The width of the artery and its branches are also presented.