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.

Selective decrease of serum immunoglobulin G1 as marker for early stages of invasive breast cancer.

The diagnostic value of the decrease in percentage of immunoglobulin G1 (%lgG1) in breast cancer was analyzed with special emphasis on early tumor stages. IgG1 and total IgG were preoperatively measured in the sera of a total of 801 individuals using a modified quantitative affinity chromatography. Group A consisted of 174 healthy individuals of both sexes, group B of 324 female patients with benign breast disease, and group C of 303 patients with invasive and non-invasive breast cancer. Within group C, 13 patients presented with intraductal carcinoma, and 22 patients with a pT1a-tumour (diameter less than 0.5 cm). The %IgG1 values were compared among groups A, B and C. In addition, correlations were sought between %IgG1 values of group C and tumor size, stage (UICC), histopathological grade and oestrogen (ER) and progesteron receptor (PR) expression. The mean value of %IgG1 in group A was 63.3 +/- 0.5 s.e.m., in group B 57.75 +/- 0.4 s.e.m. and in group C 52.37 +/- 0.5 s.e.m. The differences of mean values were highly significant between all three groups. Sensitivity and specificity of %IgG1 to discriminate between group A and C were 75% and 87%, and between group B and C 62% and 63%, respectively. The significant decrease of %IgG1 in total serum IgG is able to distinguish patients with breast cancer of more than 5 mm in diameter from healthy controls and patients with benign breast diseases. Finally, calculated posterior probabilities revealed that within certain concentration limits %lgG1 may provide predictive information with high probabilities.

[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.

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.

Anterior and upward displacement of the inferior mesenteric vein:a new diagnostic clue to left paraduodenal hernias?

A 26-year-old man with acute deterioration of recurrent abdominal pain was admitted to the hospital. Plain film (abdominal radiographs), spiral computed tomography (CT), and barium contrast studies were performed. A left paraduodenal hernia causing acute jejunal obstruction was identified on upper gastrointestinal barium studies and spiral CT. Pre- and postsurgery examinations were compared, and relevant radiological findings were identified. Spiral CT provided excellent visualization of the pathognomonic displacement of the inferior mesenteric vein.

Multiphasic helical CT in diagnosis and staging of hilar cholangiocarcinoma.

OBJECTIVE: The purpose of our study was to assess the potential of thin-section multiphasic helical CT in diagnosis and staging of hilar cholangiocarcinomas. SUBJECTS AND METHODS: Identically collimated helical CT studies were performed before and during the hepatic artery dominant phase and during the portal vein dominant phase of contrast enhancement in 29 consecutive patients with proven hilar cholangiocarcinomas. Differences in attenuation between the tumor and the liver were calculated in each case by subtracting the average attenuation of the tumor from that of the liver. A four-point scale termed a "lesion conspicuity score" was used to determine rates of tumor detection. CT findings were correlated with surgically assessed extent of tumor, histologic findings, or both in all cases. RESULTS: Ten (34%) of the 29 hilar cholangiocarcinomas were detected on unenhanced images. All hilar cholangiocarcinomas (100%) were seen on hepatic artery dominant phase scans, and 25 (86%) of 29 hilar cholangiocarcinomas were seen on portal vein dominant phase scans, regardless of the morphologic appearance. An infiltrating stenotic lesion was found in 17 (59%) of 29 patients, an exophytic hilar lesion was found in 11 patients (38%), and one patient (3%) had an intraluminal polypoid lesion. Mean differences in enhancement between infiltrating stenotic lesions and the liver were significantly greater on hepatic artery dominant phase scans (28 +/- 10 H) than on portal vein dominant phase scans (10 +/- 8 H), whereas the mean difference in enhancement between the exophytic lesions and the liver was statistically greater during the portal vein dominant phase (p < .01). Two of the hilar cholangiocarcinomas were resectable at surgery, and 18 were not. The overall accuracy of helical CT for assessing resectability was 60%. In 10 (56%) of 18 patients, unresectable disease was correctly diagnosed with helical CT (sensitivity, 56%). Eight (44%) of 18 patients considered to have resectable tumors with helical CT had unresectable tumors at surgery. A resectable tumor was correctly diagnosed in two patients with helical CT. CONCLUSION: Multiphasic helical CT can be used to detect and classify hilar cholangiocarcinomas. However, the exact proximal tumor extent along bile ducts tends to be underestimated with helical CT; therefore, helical CT is inaccurate for determining resectability.

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.

Selective decrease of serum immunoglobulin G1 as a marker of malignant transformation in colorectal tissue.

BACKGROUND: Malignant diseases of various origins were previously shown to be associated with a characteristic and highly significant change in the serum pattern of immunoglobulin (Ig)G subclasses, comprised of a decrease in %IgG1 and an increase in %IgG2 relative to and independent of the absolute concentration of total IgG. The goal of the current study was to evaluate this phenomenon as an indirect marker in the primary diagnosis of colorectal carcinoma. METHODS: Using affinity chromatography, IgG1, IgG2, and total IgG were determined in 36 patients with colorectal carcinoma of different stages and compared with 162 apparently healthy controls. RESULTS: It was found that: 1) the mean values for %IgG1 and %IgG2 of all carcinoma patients differed significantly from those of the controls; 2) no quantitative association was found with tumor stages, and four of five patients with incipient adenocarcinoma within a polyp exhibited the characteristic shift in IgG subclasses; 3) based on a calculated cutoff, the specificity and sensitivity of %IgG1 to discriminate between controls and carcinoma patients was found to be 88% and 74%, respectively; and 4) a quantitative correlation between individual %IgG1 values and the probability of correct assignment to carcinoma patients or controls was established. CONCLUSIONS: The significant decrease in %IgG1 accompanied by an increase in %IgG2 in total serum IgG represents an indirect, tissue nonspecific, and early marker of malignant proliferation that distinguishes colorectal carcinoma patients from healthy controls with a specificity of 88% and sensitivity of 74%.

Hemostatic methods for the management of spleen and liver injuries.

The spleen and liver are the most frequently injured organs during blunt and penetrating abdominal trauma. Emergency laparotomy is crucial for early control of bleeding and to prevent "secondary" injury as a result of physiologic splanchnic vasoconstriction and free oxygen radicals. Altogether 98 patients with spleen and liver injuries were treated over an 8-year period. Primary orthotopic spleen preservation could be achieved in 46 of 63 patients. In 58 patients with hepatic trauma, hemostatic treatment was chosen based on the severity of the injury. Nonoperative management was used for four splenic and seven hepatic trauma patients. The most commonly used techniques were fibrin sealing, suturing, and débridement for hepatic injury and mesh splenorrhaphy, fibrin glue, and partial resection with a TA stapler for splenic injury. The death of patients with complex injuries was mainly due to preclinical massive blood loss and multiple organ failure.

[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.

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.

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.

Laparoscopic partial splenic resection.

Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach.

Pyogenic liver abscess: studies of therapy and analysis of risk factors.

Experience with 46 patients diagnosed with liver abscesses over a 13-year period was reviewed to ascertain the impact of percutaneous versus surgical drainage. In most of the cases the abscesses were diagnosed by sonography or computed tomography. The most common pathogenetic mechanism was ascending biliary tract infection. Of the 46 total patients, 27 were primarily treated surgically, whereas 19 underwent percutaneous drainage. In the surgical group five (18.5%) patients required reoperation. Percutaneous drainage failed in four patients (21.1%). Multivariate stepwise logistic regression analysis revealed that a high APACHE II score, low hemoglobin level, and high serum bilirubin level were significant predictors of a complicated clinical course. Death was related more closely to the overall condition of the patient, as expressed by a high APACHE II score, and the underlying disease (malignancy) than to the mode of therapy.

Diagnosis and treatment of carotid body tumors.

Carotid body tumors are rare although they must always remain part of the differential diagnosis of a neck mass. Sonography as the screening method of choice followed by angiography determines the diagnosis. In 11 patients 12 carotid body tumors were extirpated. The reconstruction of the internal carotid artery with an interposition of the greater saphenous vein was necessary in two cases after resection of the tumor. One patient underwent preoperative embolisation because of a huge tumor. Two postoperative radiotherapies were undertaken because of malignancy in one case and a partially extirpated tumor in the other. After a 9 year follow-up period all patients are alive. One patient suffers from a persistent palsy of the hypoglossal nerve and another complains of permanent headache supposedly caused by the reocclusion of the venous interposition of the carotid artery. In conclusion, our data support the diagnostic strategies in patients with suspected carotid body tumors. Regarding the exact therapeutic regimen, we suggest the surgical resection, followed by radiotherapy in cases of confirmed malignancy or partially resectable lesions.

A multivitamin infusion prevents lipid peroxidation and improves transplantation performance.

The objective of this study was to test the hypothesis that ischemia reperfusion damage in kidney transplantation is associated with lipid peroxidation and that inhibition of lipid peroxidation by antioxidants improves the function of the transplanted kidney. Lipid peroxidation was assessed by measuring the plasma malonaldehyde content (as thiobarbituric acid reaction product) with high-performance liquid chromatography. Kidney function was assessed by plasma creatinine and creatinine clearance. Thirty patients of an ongoing series were randomly selected into two groups, with 14 controls and 16 patients in the antioxidant therapy group. Therapy consisted of two ampoules of Omnibionta (which contains vitamins C, E, A and B complex) diluted in 500 ml physiological sodium chloride, which was infused intravenously prior to reperfusion onset. No significant differences existed for the age of the patients in the control (43.00 +/- 9.86 years) and the therapy group (41.56 +/- 14.14 years) nor in the kidney preservation time, which was 24.12 +/- 8.73 and 18.43 +/- 9.97 hours in the control and therapy group, respectively. The controls showed a transient increase of plasma lipid peroxides as measured by malonaldehyde with a peak one hour after onset of reperfusion. Compared to the baseline value of 0.74 +/- 0.26 (mean +/- SD) the one hour malonaldehyde value increased to 1.46 +/- 0.22 nmol/ml (P < 0.001). In the therapy group the plasma malonaldehyde level did not increase, but slightly decreased by about 20% compared to the baseline value. The difference of plasma malonaldehyde between the two groups one hour after reperfusion onset was highly significant (P > 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)