Surgical cytoreduction in recurrent ovarian carcinoma in patients with complete response to paclitaxel-platinum.

AIM: The objective was to analyse the impact of secondary cytoreductive surgery in patients with recurrent ovarian carcinoma. METHODS: Retrospective review of 572 consecutive patients with primary ovarian carcinoma. Thirty-eight patients with intraabdominal/pelvic recurrence consisted the study group. Clinical variables affecting tumour resectability and survival were evaluated. RESULTS: Complete tumour resection was obtained in 42% of patients. A solitary tumour recurrence was independently associated with complete tumour resection (p=0.009). Median survival for patients with complete and incomplete tumour resection was 51.8 and 19.9 months. The parameter, residual tumour, was found independently correlated with survival after the relapse surgical procedure (p=0.02). However, including also the parameter, number of relapse tumour sites, in the multivariate analysis, the parameter, residual tumour, was no longer significantly associated with survival. CONCLUSIONS: Complete tumour resection following secondary cytoreductive surgery is associated with improved survival in selected groups of patients with recurrent ovarian cancer. However, other clinical factors than surgical cytoreduction are of considerable significance in determining the outcome of the salvage treatment.

DEMS - a second generation diabetes electronic management system.

Diabetes electronic management system (DEMS) is a component-based client/server application, written in Visual C++ and Visual Basic, with the database server running Sybase System 11. DEMS is built entirely with a combination of dynamic link libraries (DLLs) and ActiveX components - the only exception is the DEMS.exe. DEMS is a chronic disease management system for patients with diabetes. It is used at the point of care by all members of the diabetes team including physicians, nurses, dieticians, clinical assistants and educators. The system is designed for maximum clinical efficiency and facilitates appropriately supervised delegation of care. Dispersed clinical sites may be supervised from a central location. The system is designed for ease of navigation; immediate provision of many types of automatically generated reports; quality audits; aids to compliance with good care guidelines; and alerts, advisories, prompts, and warnings that guide the care provider. The system now contains data on over 34000 patients and is in daily use at multiple sites.

Towards an optimal model for community-based diabetes care: design and baseline data from the Mayo Health System Diabetes Translation Project.

The objective of the Mayo Health System Diabetes Translation Project is to assess the impact of three different models of care on the overall quality of diabetes care in the community. The unit of study is the primary care practice with a different model of care implemented at each of three sites. The design incorporates a comparison of a diabetes guideline implementation team initiative (Practice model A), a guideline initiative combined with clinical use of a Diabetes Electronic Management System (DEMS) by primary care providers (Practice model B) and a guideline initiative combined with DEMS utilization combined with electronic review of DEMS patient encounters by an endocrinologist (Practice model C). Administrative data sets were used to define the patient population at each practice. Patients were designated as new, attending or non-attending based on their pattern of visits over the preceding 12 months. A random sample of 200 charts from attending patients at each site was audited at baseline for diabetes-related process and outcome measures. This audit will be repeated yearly during the 2 years of the project. Baseline data revealed significant differences across sites in adherence to certain key indicators of the quality of diabetes care including: frequency of documentation of eye examinations (19, 39 and 37% for sites A, B and C, respectively), haemoglobin A1c monitoring (64, 89 and 77%) and microalbumin monitoring (3, 15 and 6%). The interventions being assessed in this study include traditional (diabetes education; guideline implementation) and modern (DEMS; telemedicine specialist review) methods for improving the quality of diabetes care. In spite of variation in baseline quality indicators, the setting and design should lead to broad applicability of the results and help determine an optimal model of diabetes care in the community.

Prospectively measured red cell folate levels in methotrexate treated patients with rheumatoid arthritis: relation to withdrawal and side effects.

OBJECTIVE: To investigate whether red cell folate (RCF) levels relate to side effects, withdrawals, or disease activity during treatment with the folic acid antagonist methotrexate (MTX) for rheumatoid arthritis (RA). METHODS: Side effects were recorded monthly, RCF levels were measured by lactoglobulin binding radioassays, and 8 variables for disease activity were measured in a placebo controlled double blind trial of 28 weeks' duration comparing efficacy of MTX (n = 23) and D-penicillamine (n = 23). RESULTS: From Week 20 RCF levels decreased only in the MTX group (p < 0.02), and 5 MTX treated patients withdrew due to side effects. Withdrawals had lower RCF values at Weeks 0 and 9 compared to the remaining patients (p < 0.05). Folate deficiency evolved in 5 patients; 2 of these developed cytopenia. Aberrations in the scheduled dosage increase were related to lower pretreatment values of RCF (p = 0.007). Side effect scores were inversely correlated to RCF values at Weeks 0, 9, and 28 (p < 0.05). RCF levels measured concomitantly with liver enzyme elevation were lower than the remaining values (p < 0.001). When side effects were reported, 96% of concomitantly measured RCF values were below 800 nmol/l. RCF values at entry did not correlate to improvement in any variable for disease activity, or a graded overall improvement. CONCLUSION: RCF levels decrease during MTX treatment and relate to side effects, withdrawals, liver enzyme elevations and aberrant MTX dosage increase, but not to the therapeutic effect. RCF above 800 nmol/l protects against side effects.

[Optimization of radiotherapy of cervical cancer. Introduction of an extern radiotherapy based on CT and low-dosage afterload technique at the Rikshospitalet]. / Optimering af strålebehandling af cervixcancer. Introduktion af ekstern strålebehandling baseret på CT og lav dosishastigheds afterloading-teknik på Rigshospitalet.

In September, 1987 remote controlled afterloaded caesium in treatment of carcinoma was introduced at the Department of Oncology, Copenhagen University Hospital. All patient data, treatment, complications and deaths were registered prospectively. This study describes treatment results of the first 178 consecutively treated patients. The four year survival rates for patients stage I, II and III were 70%, 68% and 43%, respectively. The stage I patients were all considered unfit for surgery due to age or other medical conditions. During the observation period 13 patients developed severe complications requiring surgery, and three of these patients died. It was concluded that treatment with afterloaded caesium for carcinoma of the cervix has reduced radiation of the medical personnel to an almost unmeasurable dose, that the treatment results were comparable to those of the larger centres in the world and that the new treatment technique suggests further improvement in the treatment of cervical carcinoma.

The value of CA 125 measurement before second-look laparotomy in patients with ovarian carcinoma.

Serum CA 125 levels were evaluated in 71 patients undergoing second-look laparotomy for primary epithelial ovarian cancer. With a cut-off limit of 35 U/ml, 17 of 45 patients with residual disease (38%) were CA 125-positive. All of 26 patients with pathological complete response were marker-negative. Second-look laparotomy may be avoided in a select group of patients with elevated CA 125 values.

[Whipple disease. A rare systemic disorder with multiple manifestations]. / Mb. Whipple. En sjoelden systemsydom med multiple manifestationsformer.

Mb. Whipple is a rare systemic disorder with multiple manifestations. We present a case-story demonstrating the typical course: migrating, non-deforming arthralgies are years later followed by diarrhoea, loss of weight, fatigue and pronounced biochemical disturbances. Intestinal biopsy shows numerous PAS-positive, diastaseresistent macrophages, and antibiotic treatment is initiated. After a somewhat prolonged course, complicated with Giardiasis and endocarditis, the patient recovers. Four months after the cessation of antibiotic treatment, however, the patient shows clinical signs of relapse, and treatment is restarted. The etiological agent has recently been identified as a gram-positive actinomycete called Tropheryma Whippleii. There are some, but not unequivocal, signs of a cellular immunodeficiency, perhaps predestinating certain patients to the disease. The course is usually favourable, when treated with relevant antibiotics. Relapse is not uncommon, and is very problematic when the CNS is involved. Therefore, a combination treatment with good penetration of the blood-brain barrier is recommended--e.g. two weeks treatment with parenterally administered streptomycin and benzylpenicillin followed by sulphamethoxazole-trimethoprim orally for one year.

[The thromboprophylactic effect of low molecular weight heparin (Fragmin) in hip fracture surgery. A placebo controlled trial]. / Den tromboprofylaktiske effekt af lavmolekylaer heparin (Fragmin) ved hoftefrakturkirurgi. En placebokontrolleret undersøgelse.

A prospective, randomized, double-blind trial concerning prophylaxis of thrombosis in 82 patients undergoing hip fracture surgery was conducted to compare a new low-molecular-weight heparin (Fragmin) with a placebo. Deep venous thrombosis (DVT) was detected by I125-fibrinogen uptake test followed by ascending phlebography when positive. Sixty-eight patients completed the study and a 50% reduction in the incidence of DVT was demonstrated: 9/30 (30%) patients in the treatment group and 22/38 (50DVT. This significant difference was achieved by one daily dose of 5.000 IU Fragmin subcutaneously, commencing preoperatively and continuing for six days. No differences in bleeding nor other complications in the two groups were observed. Fragmin administered once daily offers an effective and safe prophylaxis of thrombosis in hip fracture surgery.

Trends in the incidence of cancer of the kidney, pelvis, ureter and bladder in Denmark 1943-88.

Temporal trends in the incidence of cancer of the renal parenchyma, renal pelvis, ureter, bladder, urethra and Wilm's tumor in the period 1943-88 were described. Log-linear Poisson models were used to estimate the changes over time and the geographical variations. We have found a steep increase in the incidence of pelvis and ureter cancer; and to some extent also for bladder cancer in men. The incidence of cancer of the renal parenchyma has increased more moderately while the rates of Wilm's tumor have been virtually stable throughout the period. These findings suggest that tumors in the urinary system differ with respect to risk factors and should be grouped by their histological origin as well as topographical site.

Pharmacokinetics of ticlopidine during chronic oral administration to healthy volunteers and its effects on antipyrine pharmacokinetics.

1. The pharmacokinetics of ticlopidine, a novel antithrombotic agent, have been investigated in 10 healthy volunteers dosed orally with the drug (250 mg 12 hourly for 21 days), to determine the basic pharmacokinetic parameters in humans, to investigate its accumulation during repeated administration, and to assess its effects on hepatic drug-metabolizing enzymes. 2. After the first dose, peak plasma concentrations (median 0.31, range 0.08-0.80 mg/l) were generally found at 2 h. The levels decreased rapidly to a median concentration of 0.087 mg/l by 4 h then declined to 0.022 (range less than 0.005-0.128) mg/l at 12 h after administration, with apparent half-lives of approx. 4 h. The median AUC value for this first dosage interval (AUC tau) was 0.97 (range 0.41-3.49) mg h l-1. 3. Pre-dose plasma concentrations indicated that steady state was reached after 5-10 days, and then remained essentially unchanged through to the end of the study. From 30 h after the final dose, drug levels declined exponentially with a median half-life of 28.8 (range less than or equal to 20-50) h. 4. Following the final dose, the median peak concentration and AUC tau were 0.99 (range 0.22-2.12) mg/l and 4.06 (range 0.90-15.2) mg h l-1 respectively. Based on AUC values, the mean accumulation factor +/- SD was 3.73 +/- 1.14. 5. The metabolic status of subjects was assessed by administration of single doses of antipyrine (700 mg orally) 7 days before the first dose of ticlopidine and 2 days after the final dose. Treatment with ticlopidine decreased antipyrine clearance, demonstrating that it inhibited drug-metabolizing enzymes. Significant correlations (r2 = 0.84, p less than 0.01) were found between the AUC values for ticlopidine and antipyrine, indicating that the interindividual variation in the pharmacokinetics of ticlopidine are explained by differences in metabolic clearance.

The thromboprophylactic effect of a low-molecular-weight heparin (Fragmin) in hip fracture surgery. A placebo-controlled study.

A prospective, randomized, double-blind trial concerning thromboprophylaxis in 82 patients in whom hip fracture surgery was performed was conducted to compare a new low-molecular-weight heparin (Fragmin) with placebo. Deep venous thrombosis (DVT) was detected by 125-I-fibrinogen uptake test followed by ascending phlebography when positive. Sixty-eight patients completed the study, and a 50% reduction in the incidence of DVT was demonstrated: nine of 30 patients in the treatment group (30%) and 22 of 38 patients in the placebo group (58%) developed DVT. This significant difference was achieved by one daily dose of 5000 IU Fragmin subcutaneously, commenced preoperatively and continued for six days. There were no differences in bleeding or other complications in the two groups. Fragmin given once daily offers an effective and safe thromboprophylaxis in hip fracture surgery.

Metastasis from squamous carcinoma of the cervix stage 1B to a borderline cystadenoma of the ovary.

A case of metastasis from squamous carcinoma stage 1B of the cervix to a borderline cystadenoma of the ovary is described. In addition, the patient had atypical endometrial hyperplasia. The patient underwent a radical hysterectomy with no adjuvant postoperative treatment and has resumed work, with no sign of recurrence one year postoperatively. The aspects of the metastasis to the ovary, multiple tumors in the genital tract and tumor-to-tumor metastasis are discussed. Reports on ovarian metastasis in low-stage squamous carcinoma of the cervix are few and it still seems justified to spare the ovaries at surgery in the young patient.

[Intracavitary irradiation of esophageal cancer]. / Intrakavitaer strålebehandling af cancer esophagi.

Intracavitary irradiation (ICI) of esophageal cancer is a technique where the radioactive source is placed in the lumen of the esophagus thereby delivering a high local radiation dose to the tumor. ICI is used as single modality therapy for palliation of dysphagia or as a supplement to external irradiation. Dysphagia is hereby relieved in more than 90% of the patients and it appears that survival is improved. The side effects are dose dependent and consist of esophagitis, esophageal ulceration and benign stricture. Fistulae do not seem to occur with increased frequency after ICI, but an existing fistula is claimed to be a contraindication to ICI. The mortality connected with ICI is considerably lower than with tubulation or laser extirpation. It is concluded that ICI is a promising treatment in esophageal cancer both as palliative and curative treatment in combination with other treatment modalities.

Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery. A placebo controlled study.

In a double-blind, randomised study of thromboprophylaxis in patients undergoing total hip replacement, we compared a low-molecular-weight heparin with a placebo. Of the 120 patients enrolled, 112 completed the trial; 58 in the treatment group and 54 in the placebo group. Nine (16%) patients in the treatment group and 19 (35%) in the placebo group developed deep venous thrombosis, diagnosed by the 125I-fibrinogen uptake test (p < 0.02). Verification was obtained by phlebography in 86% of the patients. Prolonged surgery increased the risk of thrombosis in the placebo group but not in the treatment group (p < 0.05). There were significantly more cases of deep venous thrombosis in the placebo group during the first four postoperative days (p < 0.02). The groups did not differ with respect to peroperative and postoperative bleeding. Low-molecular-weight heparin offers safe and easily administered thromboprophylaxis in total hip replacement.

[Renal cancer in Denmark in 1943-1986. Cancer statistics number 27]. / Nyrecancer i Danmark 1943-1986. Kraeftstatistik nummer 27.

During the past 45 years, the number of new cases of parenchymatous renal cancer have increased from approximately 230 to over 500 per annum. The incidence of renal cancer increased until the middle of the nineteen seventies, after which it stagnated. Parenchymatous renal cancer is nearly twice as frequent in men. During the entire period, Wilms' tumour and sarcoma have been very rare with only few new cases every year.

Thrombolytic therapy of cerebral arterial occlusion with recombinant tissue plasminogen activator.

This report describes three patients, with acute cerebral arterial occlusion, treated with recombinant tissue plasminogen activator (rt-PA). In one patient with basilar artery occlusion thrombolytic treatment was initiated 12 h after onset of the symptoms. In two patients with angiographically verified occlusion of the middle cerebral artery, the treatment was initiated approximately 4.5 h after onset of the symptoms. Recombinant tissue plasminogen activator 80-120 mg, was infused intra-arterially over 90-100 min via a catheter the tip of which was close to the occlusion. This regimen resulted in recanalization in all the patients; however, in two patients it was verified by repeat CT scan only. In two patients the thrombolytic treatment was successful (the patients improved clinically); the third patient died of massive cerebral infarct-related oedema. In none of the patients did significant bleeding or other obvious side-effects occur. From this preliminary report it is concluded that angiographically proven thrombolytic recanalization in acute cerebrovascular occlusion is possible with rt-PA. In some patients, however, the treatment is initiated too late. Further investigation of the possible indication for thrombolytic therapy in stroke is needed.

The Copenhagen case-control study of renal pelvis and ureter cancer: role of analgesics.

Analgesic intake was investigated for 96 patients with cancer of the renal pelvis and ureter (including papillomas) and 294 hospital controls. In comparison with persons who never used analgesics, increased relative risks (RR) were seen for users of phenacetin-containing drugs after adjustment for smoking and high-risk occupational exposure (men: RR = 2.4; women: RR = 4.2). A significant relative risk for aspirin use among women was also observed. There was an indication of a dose-effect relationship for both types of analgesics. The influence of phenacetin and aspirin on the development of renal pelvis and ureter tumours could not be separated since in this study the two compounds occurred so frequently in the same formulation. Experimental studies and phenacetin metabolism makes it biologically most relevant to attribute the observed association in the present study to the phenacetin component of the drugs.

The Copenhagen case-control study of bladder cancer. V. Review of the role of urinary-tract infection.

During the years 1979-1981, a population-based study of 388 patients with bladder cancer, including papilloma, and of 790 controls was conducted in Greater Copenhagen. No pronounced difference between cases and controls of either sex was observed for bladder infection, kidney infection or bladder stones. Women with kidney stones had a significantly elevated relative bladder cancer risk (RR = 3.7; 95% CI = 1.2-12.1); the risk for bladder cancer was also increased (RR = 1.5), although not significantly so, in women who had ever had a 'kidney disease'. A review of the existing studies in humans and in animals of the association between bladder infection and cancer reveals a need for studies to determine whether urinary-tract infections increase either the true risk for bladder tumours or only complications of early bladder cancer before a clinical diagnosis has been made.

Platelet function in classic migraine during attack-free periods.

It has been reported that migraine sufferers have an enhanced platelet activity, as well as an enhanced thromboembolic risk. In this study, 12 subjects with classic migraine were compared with 12 age- and sex-matched controls. The following parameters were tested: platelet aggregation; platelet content of ADP, ATP and cyclic-AMP (cAMP); plasma levels of cAMP, 6-keto-PGF1 alpha and thromboxane B2, serum levels of TxB2 and lipids. ADP- and adrenaline-induced platelet aggregation, platelet content of ADP, ATP and cAMP did not differ significantly between the groups. Platelets from migraine subjects, however, showed a decreased beta-adrenoceptor response to stimulation with isoprenaline when determined as platelet cAMP production in vitro. The prostacyclin metabolite 6-keto-PGF 1 alpha was significantly decreased in the migraine group. No difference were observed in TxB2. Plasma lipids were similar, except that the migraine cases had higher levels of LDL-cholesterol. These data do not confirm a general platelet malfunction in migraine patients, but suggest a decreased functional capacity of platelet beta-adrenoceptors and an altered metabolism of prostacyclin and LDL-cholesterol.