[Pancreas resection in cancer. Reduced mortality but morbidity is still high].
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Adult↗
Biomedical subjects
L Domellöf
Publications and source records attributed to L Domellöf.
[WHO meeting on stomach cancer. Dissection of the glands can be a suitable measure].
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Germany↗
Prognosis of chronic pancreatitis: an international multicenter study. International Pancreatitis Study Group.
OBJECTIVES: The aim of this study was to determine which factors predict mortality in a cohort of patients with chronic alcoholic and nonalcoholic pancreatitis. Patients with chronic pancreatitis are known to have a reduced life expectancy, but the quantitative relationship between various clinical features and survival is unclear. METHODS: We evaluated survival among 2015 subjects with chronic pancreatitis treated at seven centers located in six countries. RESULTS: Mean age at diagnosis was 46 +/- 13 yr and mean duration of follow-up was 7.4 +/- 6.2 yr. Overall survival at 10 yr was 70% (95% confidence interval (CI), 68-73%) and at 20 yr was 45% (95% CI, 41-49%). Survival was significantly less than in the background population. There were 559 deaths observed among those with chronic pancreatitis compared with an expected number of 157.4, yielding a standardized mortality ratio (SMR) of 3.6 (95% CI, 3.3-3.9). Older subjects and those with alcoholic pancreatitis had a significant reduction in survival. In a multivariate analysis, mortality of middle-aged and older subjects was 2.3 (95% CI, 1.8-2.8) and 6.3 (95% CI, 4.7-8.3) times greater than subjects less than 40 yr at diagnosis. Smoking (hazard ratio, 1.4; 95% CI, 1.0-1.9), drinking (hazard ratio, 1.6; 95% CI, 1.2-2.2), or development of cirrhosis (hazard ratio, 2.5; 95% CI, 2.0-3.2) increased the risk of death during the observation period, but we observed no survival difference in operated vs. nonoperated patients. CONCLUSIONS: Age at diagnosis, smoking, and drinking are major predictors of mortality in patients with chronic pancreatitis.
Age of Onset↗
Adjuvant chemotherapy with 5-fluorouracil, vincristine and CCNU for patients with Dukes' C colorectal cancer. The Swedish Gastrointestinal Tumour Adjuvant Therapy Group.
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.
Antineoplastic Combined Chemotherapy Protocols↗
Effect of therapeutic concentrations of anthracyclines on monocyte phagocytosis of yeast cells.
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.
Antibiotics, Antineoplastic↗
Gallstone growth, size, and risk of gallbladder cancer: an interracial study.
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.
Adult↗
Pharmacokinetics and central haemodynamic effects of doxorubicin and 4'epi-doxorubicin in the pig.
The relationship between the cardiotoxicity and the haemodynamics/pharmacokinetics of clinical concentrations of doxorubicin and 4'epi-doxorubicin was studied. Twelve pigs were randomized to receive i.v. infusions of either drug of 50 mg/m2 over 3.0 min. Aortic, pulmonary arterial, coronary sinus and central venous plasma concentrations of the agents were determined until 180 min after the infusion. The V5 ECG, left ventricular dP/dT, aortic, pulmonary arterial and right atrial pressures were recorded continuously, cardiac output and coronary sinus blood flow were recorded intermittently. No haemodynamic changes were recorded after administration of either drug. Pharmacokinetic data indicated myocardial extraction, followed by myocardial release of both drugs. This release was higher after administration of 4'epi-doxorubicin than after doxorubicin, within the range 2-4 min and 20-40 min after the infusion. The tendency of greater myocardial release of 4'epi-doxorubicin may explain its lower cardiotoxicity.
Animals↗
Pharmacokinetics of intra-arterial mitomycin C with or without degradable starch microspheres (DSM) in the treatment of non-resectable liver cancer.
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.
Adult↗
Cystadenocarcinoma of the pancreas 9 years after a pancreatic cyst operation: report of a case.
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.
Cystadenocarcinoma↗
Cardiopulmonary hemodynamics and pharmacokinetics after hepatic intraarterial infusion of 5-fluorouracil (5-FU). An experimental study in the pig.
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.
Animals↗
A cytostatic drug (taxol) which does not inhibit monocyte phagocytosis.
Taxol is a new cytotoxic agent which arrests cell division in the G2 and the M phases, due to its unique property of inhibiting microtubule function by stabilization. In contrast to other microtubule antagonists except griseofulvin, taxol did not inhibit monocyte phagocytosis. It is suggested that lack of interference with the function of mature leukocytes may reduce the immunosuppression induced by a cytotoxic agent.
Alkaloids↗
Therapeutic concentrations of melphalan do not affect yeast cell phagocytosis by monocytes.
The effect of melphalan on monocyte phagocytosis was assessed by studying the uptake of fluorescent yeast cells by glass-adherent monocytes (a fluorescence-quenching technique). In contrast to several other cytotoxic agents, melphalan did not inhibit monocyte phagocytosis. Although the main immunosuppressive side effect of most cytotoxic drugs appears to be due to bone marrow depression with reduction of leukocyte counts, it is reasonable to assume that lack of interference with the function of mature leukocytes is a favourable feature of an antineoplastic drug.
Humans↗
The effects of omeprazole and cimetidine on duodenal ulcer healing and the relief of symptoms.
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.
Adolescent↗
Splenic release of amino acids in man assessed by arterial and venous blood sampling in situ.
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.
Amino Acids↗
Role of actin polymerization in monocyte phagocytosis of yeast cells effect of cytochalasin B.
The role of the cortical actomyosin-like contractile system in monocyte phagocytosis was studied by means of inhibition with cytochalasin B. Monocyte phagocytosis of yeast cells was assayed with a fluorescence extinction technique of surface-located phagocytosis which distinguishes between adherence and ingestion phases of total phagocytosis. Cytochalasin B, 10 micrograms/ml, inhibited monocyte phagocytosis by 20-30%. The cytochalasin inhibition was significant and restricted to the ingestion phase. The finding supported the hypothesis that the contractile structures of the cell have a contributory role in IgG-mediated monocyte phagocytosis on a surface. It is suggested that the cytochalasin effect reflected the role of chemotaxis in monocyte phagocytosis assayed by the present technique.
Actins↗
Arterial bullet embolism with radiologic demonstration of vessel entrance site.
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Adult↗
Distribution and metabolism of N'-nitrosonornicotine in the miniature pig.
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.
Animals↗