Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology.

PURPOSE: Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles (M-CH) in preventing intraabdominal recurrence following curative surgery for gastric cancer. The Austrian Working Group for Stomach Cancer, a subgroup of the Austrian Working Group for Surgical Oncology, initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen. PATIENTS AND METHODS: A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were randomly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound (n = 46) or served as a surgical control group (n = 45). Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment. RESULTS: After a median observation period of 597 days (range, 72 to 1,096), a significantly higher postoperative complication rate was observed in the M-CH group (35%) compared with the control group (16%) (P < .02). In accordance with this finding, the postoperative (60 days) mortality rate was also significantly elevated in the M-CH group (11% v 2% in the control group). Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy, the protocol committee decided to stop further recruitment of patients onto this study. CONCLUSION: Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications. However, no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial.

Human plasma lipid peroxide levels show a strong transient increase after successful revascularization operations.

This study was performed to evaluate the hypothesis that oxygen radicals/lipid peroxidation are involved in reperfusion injury in humans. The study included 37 patients, who underwent surgical revascularization operations for kidney transplantation (9 subjects) or limb salvage (28 subjects). Peripheral venous blood samples were taken 30 min before starting reperfusion (baseline) and 1, 2, 3, 4, and occasionally 6 to 18 h after revascularization. The amount of plasma malonaldehyde formed in the reaction with thiobarbituric acid (MDA-TBA) was determined by high-performance liquid chromatography (HPLC). The baseline MDA-TBA values of the patients were very close to the value determined for 20 age-matched healthy subjects (i.e. mean +/- SD 0.689 +/- 0.294 nmol/mL plasma [range 0.2 to 1.37] vs. 0.700 +/- 0.209 nmol/mL plasma [range 0.385 to 1.29]). All patients responded to successful revascularization with significant increase of the plasma MDA-TBA within about 1 h after onset of reperfusion. Thereafter the values decreased nearly to the preoperative state. The mean increase of MDA-TBA was 107% in kidney transplantation and 54% in limb revascularization. In a few patients with severe arteriosclerosis, revascularization was not optimal and no increase in the MDA-TBA value occurred. The results of this study indicate that therapeutic intervention to prevent lipid-peroxidation-mediated reperfusion injury is confined to a rather narrow time window and must be undertaken either prior to or immediately after revascularization.

Elevated serum neopterin levels in atherosclerosis.

Plasma levels of neopterin were determined in patients with different clinical stages of atherosclerosis. Non-hospitalized patients with atherosclerosis had serum and plasma neopterin levels within the normal range of the assay (6 +/- 2 nM). These values were not significantly different from those reported for healthy blood donors (5 +/- 2 nM). In contrast, about 50% (29 out of 61) of hospitalized patients undergoing conservative or surgical therapy had neopterin plasma levels, which exceeded the normal range (greater than 10 nM) up to 10-fold. The two groups differ on a significance level of P less than 0.01. For further evaluation hospitalized patients were subgrouped according to neopterin levels. In the subgroup with elevated neopterin levels patients with higher Frederickson types of atherosclerosis were overrepresented compared to patients with normal neopterin levels. Type 4 differed significantly from patients without pathological changes of lipoprotein (P less than 0.05). Only 3 patients suffered from minimal skin necrosis, two of them had elevated neopterin levels. Significantly more patients with peripheral artery occlusions had elevated neopterin levels than patients with occlusions of central arteries (P less than 0.05). All other criteria used for comparison (sex, age, smoking, antioxidant status, diabetes, hypertension, adipositas, hyperuricemia) did not vary significantly in both subgroups. These data indicate that neopterin plasma levels might be a valuable parameter in activity staging and therapeutic follow up of atherosclerotic patients. Additionally, an involvement of the nonspecific immune system in atherogenesis is suggested by the increased plasma neopterin concentrations.

Normothermic liver ischemia and antioxidant treatment during hepatic resections.

The purpose of our study was to evaluate the clinical impact of reperfusion injury after normothermic ischemia during major liver resections and the effect of an intraoperative antioxidant infusion. This prospective randomized study comprised 50 patients; half of them (treatment group) were given an antioxidant infusion containing tocopherol and ascorbate immediately prior to reperfusion onset. Venous blood samples for the determination of MDA-TBARS (malondialdehyde-thiobarbituric acid reactive substances) by a HPLC-based test as a marker of lipid peroxidation were taken prior to ischemia, 30 min after reperfusion onset and at the end of the operation. In the control group there was a significant increase of MDA-TBARS (p = 0.001) at 30 min after reperfusion onset. At the end of the operation the values had returned to the initial level. The treatment group showed only a marginal increase (p-value for the difference between the two groups: 0.007). After exclusion of the patients with histologically proven advanced cirrhosis the increase in the control group (p < 0.001) and the difference between the increase in the two groups (p = 0.001) became more significant. Prothrombin time was also significantly better in the treatment group (p = 0.003). Postoperative complications such as prolonged liver failure, bleeding disorders and infections were seen more often in the control group. In our study MDA-TBARS was increased after liver ischemia, but in patients with advanced cirrhosis the effect was smaller or even absent. This increase and possible clinical consequences of reperfusion injury could be reduced by intraoperative administration of an antioxidant infusion.

[Acute appendicitis in non-contrast spiral CT: a diagnostic luxury or benefit?]. / Akute Appendizitis im Nicht-Kontrast-Spiral-CT: diagnostischer Luxus oder Nutzen?

PURPOSE: To evaluate the diagnostic accuracy of thin collimated unenhanced spiral-CT in patients with clinically suspected acute appendicitis and to determine the impact on patient management and overall costs. METHOD: Unenhanced focussed appendiceal spiral-CT was performed in 56 patients (23 women and 33 men) with clinically suspected acute appendicitis. Scans were obtained from the L4 level to the symphysis pubis using 5 mm collimation, 7.5 mm table feed (pitch 1.5) and 4 mm increment without i.v., oral, or rectal contrast material. Prospective diagnoses based on CT findings were compared with surgical (and histopathological) results and clinical follow-up. The effect of spiral-CT on patient management and clinical resources was assessed. RESULTS: 29 patients (10 women and 19 men) underwent appendectomy. Unenhanced spiral-CT was an accurate imaging technique for the initial examination of patients with suspected acute appendicitis with a sensitivity of 95.4% and a specificity 100%, an accuracy of 98.2%, a positive predictive value of 100%, and a negative predictive value of 97.1%. In 27 patients with no evidence of acute appendicitis, an alternative diagnosis could be made in 24 patients by unenhanced spiral-CT. CONCLUSION: Unenhanced spiral-CT is an accurate test to diagnose or to exclude acute appendicitis. Routine appendiceal spiral-CT can improve medical care and reduce the overall costs for patients suspected of having acute appendicitis.

[Fatal Candida mycosis following leukemia therapy]. / Tödliche Candida-Mykose im Gefolge der Leukämiebehandlung.

The authors report a case of fatal Candida septicaemia in a seven year-old female patient who had been undergoing cytostatic therapy for the previous four years for acute lymphoblastic leukaemia. The condition was histologically identified by means of special staining methods and immunocytochemistry. Since secondary mycoses--like in the present case--are frequently missed clinically, this report serves to emphasize their great importance.

A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer.

The purpose of this trial was to investigate the efficacy of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) in stage II colon cancer. Patients with stage II colon cancer were randomised to either adjuvant chemotherapy with 5-FU/LV (100 mg m(-2) LV+450 mg m(-2) 5-FU weekly, weeks 1-6, in 8 weeks cycles x 7) or surveillance only. Five hundred patients were evaluable for analyses. After a median follow-up of 95.6 months, 55 of 252 patients (21.8%) have died in the 5-FU/LV arm and 58 of 248 patients (23.4%) in the surveillance arm. There was no statistically significant difference in overall survival (OS) between the two treatment arms (hazard ratios, HR 0.88, 95% CI 0.61-1.27, P=0.49). The relative risk for tumour relapse was higher for patients on the surveillance arm than for those on the 5-FU/LV arm; however, this difference was not statistically significant (HR 0.69, 95% CI 0.45-1.06, P=0.09). Consequently, disease-free survival (DFS) was not significantly different between the two trial arms. In conclusion, results of this trial demonstrate a trend to a lower risk for relapse in patients treated with adjuvant 5-FU/LV for stage II colon cancer. However, in this study with limited power to detect small differences between the study arms, adjuvant chemotherapy failed to significantly improve DFS and OS.

[Therapy-refractory pelvic vein thrombosis in pregnancy as a sequela of protein S deficiency]. / Therapierefraktäre Beckenvenenthrombose in der Schwangerschaft als Folge eines Protein S-Mangels.

Protein S (PS) serves as a cofactor for activated Protein C, which has anticoagulative activity. PS deficiency (inherited or acquired) leads to spontaneous, recurrent thromboembolic complications in adulthood. PS level is significantly reduced during pregnancy and puerperium and during use of oral contraceptives. We report on our experience with a 26 year old pregnant woman, who developed a descending iliofemoral venous thrombosis in the 39th week of gestation. She underwent venous thrombectomy with a temporary arteriovenous fistula. Recurrent thrombosis occurred a few days after parturition. Redothrombectomy was performed successfully, but 2nd recurrent thrombosis occurred 10 days later. Further, lysis therapy did not reopen the venous system. Functional PS activity of 34% (IL-Instrumentation Laboratory Protein S-test, normal range 60-140%) was markedly reduced, which was the only pathological finding of coagulation analysis. For 20 years, the patient's mother has been undergoing coumarin therapy because of recurrent thromboembolic complications. We can therefore assume an inherited PS deficiency in the young mother.

[The clinical importance of protein C and S deficiency for surgical patients]. / Die klinische Bedeutung von Protein-C- und -S-Mangelzuständen für das chirurgische Patientenkollektiv.

Protein C and S are important factors in blood coagulation reported in many papers about people who suffered from thromboembolic diseases related to inherited or acquired deficiencies. Homozygous protein C/S deficiency is lethal in most cases without therapy. Heterozygous deficiency is moderate and complications occur between the 20.-50. year of age. Acquired protein C/S deficiency is a strong parameter for liver function. The typical clinical manifestations of protein C/S deficiencies are superficial and deep leg vein thrombosis, thrombosis of the mesenterial, cerebral, renal and axillary veins, portal vein thrombosis and pulmonary embolism. Most of the affected people live disease free over a longer period and develop thromboembolic complications during and after trauma, surgical interventions, pregnancy and puerperium. We report our experience with a 60 years old male who had developed a severe bilateral iliofemoral vein thrombosis with signs of pulmonary embolism after total hip replacement. An extended functional protein C deficiency (type II) was investigated by coagulation tests (Protein C Reagent, coagulometric from Behring Institute). A second female patient developed a descending iliofemoral vein thrombosis during pregnancy. Venous thrombectomy with arteriovenous fistula was performed, but reocclusion occurred after delivery. Redo-surgery was undertaken and a second reocclusion took place 10 days later. Further lysis therapy was not able to reopen the venous system. Whereas immunological and functional protein C levels showed normal ranges, the functional protein S level was markedly reduced (IL-Instrumentation Laboratory Protein S-Test).

["Pseudothrombosis" of the lower leg, induced by a ruptured Baker's cyst]. / "Pseudothrombose" des Unterschenkels, hervorgerufen durch eine rupturierte Baker-Zyste.

A sudden onset of unilateral swelling and tenderness on pressure of the calf with no history of trauma is suggestive of vein thrombosis. Baker cysts, especially if ruptured, mimic the clinical picture of deep vein leg thrombosis. The examination method of choice is duplex sonography. We report on a 30-year-old man who was admitted to our hospital with signs of deep vein leg thrombosis. Phlebography revealed normal venous circulation. Examination by duplex sonography showed a ruptured Baker cyst. No intra-articular lesions of the knee joint were revealed by arthroscopy. Histological examination of the biopsy specimens of the synovia showed no specific pathologic condition. The clinical signs improved with conservative treatment.

Antioxidative vitamin treatment: effect on lipid peroxidation and limb swelling after revascularization operations.

The objective of this study was to evaluate the antioxidative properties of the multivitamin cocktail Omnibionta (alpha-tocopherol, ascorbic acid, retinol, vitamin B complex) in terms of diminishing lipid peroxidation with improvement of leg edema performance after limb revascularization operations in humans. Fifty-one subjects were selected; the control group contained 27 patients and the treatment group 24 patients, who received the vitamin cocktail intravenously before the start of reperfusion. All patients suffered from acute or chronic arterial occlusive disease, except two subjects with arterial trauma. MDA-TBARS in plasma, quantified by HPLC, taken as a measure of lipid peroxidation was significantly increased (p < 0.001) in the control group 1 hour after reperfusion onset and decreased to its baseline value within the following 2 hours (0.73 +/- 0.26, 1.21 +/- 0.48, 0.99 +/- 0.48, 0.73 +/- 0.33 nmol/ml). In contrast, in the treatment group MDA-TBARS did not exceed the baseline value during the reperfusion period (0.93 +/- 0.30, 0.70 +/- 0.29, 0.65 +/- 0.23, 0.70 +/- 0.37 nmol/ml). Leg edema, expressed by extremity circumference, was significantly (p < 0.008) elevated in the control group (30.7 +/- 4.04 cm versus 35.35 +/- 4.12 cm) compared to a lack of increase in the treatment group (29.25 +/- 5.13 cm versus 29.76 +/- 5.70 cm). These results suggest that antioxidative vitamin treatment might be valuable in preventing lipid peroxidation and decreasing extremity edema.

[Established and new surgical procedures in the therapy of breast cancer]. / Etablierte und neue chirurgische Verfahren in der Therapie des Mammakarzinoms.

The established surgical procedure in the treatment of mammary cancer today is, without any doubt the modified radical mastectomy (Patey, Dyson). The adjuvant radiation therapy, following modified radical mastectomy, could not improve the all over survival of mammary cancer patients. Within the last years the breast conserving surgical procedures went more and more into the field of interest, especially of the patients. That is the reason, why these treatment-schedules should be considered very carefully according to thorough oncological principles. The radiation therapy within the conserving treatment is necessary as primary treatment in addition to surgery.

[Cystic adventitia degeneration of the popliteal artery: sonographic confirmation of the diagnosis]. / Zystische Adventitia-Degeneration der Arteria poplitea: Sonographische Sicherung der Diagnose.

Cystic adventitial disease is a rare condition resulting in arterial occlusive symptoms. The characteristic clinical and angiographic findings suggest the diagnosis cystic adventitial disease. The presented case shows, that sonography can demonstrate the adventitial cyst and the resulting stenosis and confirm the diagnosis.

[Is sphincter-plasty for treatment of fecal incontinence in patients older than 60 justified?]. / Ist die Sphinkterplastik zur Behandlung der Fäkalen Inkontinenz bei Patienten älter als 60 Jahre gerechtfertigt?

Overlapping sphincteroplasty is the method of choice for isolated anterior sphincter defects. Patients over 60 years of age can undergo this operation with similar good results as in younger patients. However, preoperative physiologic assessment of the pelvic floor is necessary for a good postoperative outcome.

Effect of antioxidants on oxidative modification of LDL.

Human low density lipoprotein (LDL) with a molecular mass of 2.5 million contains on average 1300 molecules of polyunsaturated fatty acids (PUFAs) bound in the different lipid classes. The predominant antioxidant in LDL is alpha-tocopherol, with an average of 6 molecules in each LDL particle. The other substances with potential antioxidant activity are: gamma-tocopherol, beta-carotene, alpha-carotene, lycopene, cryptoxanthin, cantaxanthin, phytofluene and ubiquinol-10. Each is present in amounts of only 1/20th to 1/300th of that of alpha-tocopherol. If LDL is exposed to oxidative conditions (Cu++ ions, macrophages) a lag phase precedes the oxidation of PUFAs. During the lag phase the antioxidants disappear with alpha-tocopherol the first to go and beta-carotene the last. The lag phase, which can readily be determined, is an index of the oxidation resistance of LDL. If LDL is loaded with vitamin E in vitro its oxidation resistance increases linearly with its alpha-tocopherol content according to the equation, y = kx+a. The same relationship is applicable if the alpha-tocopherol content of LDL is increased by taking oral vitamin E. Daily doses of 150, 225, 800 and 1200 IU RRR-alpha-tocopherol increased the LDL alpha-tocopherol on average to 138%, 158%, 144% and 215% of the initial value, the oxidation resistance being increased to 118%, 156%, 135% and 175%, respectively. The efficiency of vitamin E-dependent (= k) and the vitamin independent (= a) oxidation resistance seem to be subject specific with strong individual variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Generation, characterization, and histochemical application of monoclonal antibodies selectively recognizing oxidatively modified apoB-containing serum lipoproteins.

To investigate either the role oxidized LDL plays in atherosclerosis or structural changes on the surface of oxidized LDL, monoclonal antibodies (mAbs) are an important tool. After immunizing mice with Cu(2+)-oxidized LDL (oxLDL) and fusion of splenocytes, hybridoma supernatants were screened and cloned. Two mAbs, OB/04 and OB/09 (IgG and IgM), were further characterized. In solid-phase fluorescence immunoassays and Western blot analysis both mAbs reacted with oxLDL, LDL oxidized by a free radical-generating azo compound, or oxVLDL but not with native LDL, acetylated LDL, oxHDL3, azo-oxidized HDL3, or HDL3 modified with malondialdehyde (MDA). In competitive immunoassays with LDL modified by oxidized fatty acid-derived aldehydes, mAb OB/09 strongly reacted with MDA-LDL or MDA-VLDL and LDL modified with 4-hydroxyhexenal followed by 4-hydroxynonenal but not with 4-hydroxyoctenal or hepta-2,4-dienal. mAb OB/04 had a weak affinity for LDL after modification with these aldehydes except for MDA-LDL. LDL modified with arachidonic acid oxidation products (AAOPs) was also recognized by this mAb. However, albumin modified either by the aldehydes applied or by AAOPs did not react with either mAb. Thus, the data indicate that each of the mAbs recognizes a different epitope that is expressed only on apoB-containing lipoproteins upon oxidative modification. An immunostaining with mAb OB/04 was obtained in areas rich in macrophages and in connective tissue of a human atherosclerotic lesion.