Efficacy of tamoxifen ± aminoglutethimide in normal weight and overweight postmenopausal patients with hormone receptor-positive breast cancer: an analysis of 1509 patients of the ABCSG-06 trial.

BACKGROUND: There exists evidence that body mass index (BMI) impacts on the efficacy of aromatase inhibitors in patients with breast cancer. The relationship between BMI and the efficacy of tamoxifen is conflicting. We investigated the impact of BMI on the efficacy of single tamoxifen and tamoxifen plus an aromatase inhibitor in the well-defined prospective study population of the ABCSG-06 trial. METHODS: ABCSG-06 investigated the efficacy of tamoxifen vs tamoxifen plus aminoglutethimide in postmenopausal women with hormone receptor-positive breast cancer. Taking BMI at baseline, patients were classified as normal weight (BMI=18.5-24.9 kg m(-)(2)), overweight (BMI=25-29.9 kg m(-)(2)), and obese (30 kg m(-)(2)) according to WHO criteria. RESULTS: Overweight+obese patients had an increased risk for distant recurrences (hazard ratio (HR): 1.51; Cox P=0·018) and a worse overall survival (OS; HR: 1·49; Cox P=0·052) compared with normal weight patients. Analysing patients treated with single tamoxifen only, no difference between overweight+obese patients and normal weight patients regarding distant recurrence-free survival (HR: 1.35; Cox P=0·24) and OS (HR: 0.99; Cox P=0·97) could be observed. In contrast, in the group of patients treated with the combination of tamoxifen plus aminoglutethimide, overweight+obese patients had an increased risk for distant recurrences (1.67; Cox P=0·03) and a worse OS (1.47; Cox P=0·11) compared with normal weight patients. CONCLUSION: BMI impacts on the efficacy of aromatase inhibitor-based treatment but not single tamoxifen.

Dephasing of exciton polaritons in photoexcited InGaAs quantum dots in GaAs nanocavities.

We present a combined experimental and theoretical study of the emission spectrum of zero dimensional nanocavity polaritons in electrically tunable single dot nanocavities. Such devices allow us to vary the dot-cavity detuning in situ and probe the emission spectrum under well-controlled conditions of lattice temperature and incoherent excitation level. Our results show that the observation of a double peak in the emission spectrum is not an unequivocal signature of strong coupling. Moreover, by comparing our results with theory, we extract the effective vacuum Rabi splitting, the pure dephasing rate, and their dependence on the incoherent optical pumping power and lattice temperature. Our study highlights how coupling to the lattice and dynamical fluctuations in the solid-state environment influence the coherence properties of quantum dot microcavity polaritons and, sometimes, may mask the occurrence of strong coupling.

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.

A prospective randomised trial to study the role of levamisole and interferon alfa in an adjuvant therapy with 5-FU for stage III colon cancer.

The purpose of this trial was to examine the efficacy of the addition of levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5-fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 x 2 factorial study design, 598 patients were randomly assigned to one of four adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year, patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of death were significantly higher for patients treated with LEV compared with those without LEV treatment (HR 1.452, 95% CI 1.135-1.856, P=0.0028; HR 1.506, 95% CI 1.150-1.973, P=0.0027, respectively). No significant impact on survival was observed for therapy with IFN in the univariate analysis. The addition of LEV to adjuvant 5-FU significantly worsened the prognosis of patients with stage III colon cancer. Interferon alfa had no significant influence on survival when combined with adjuvant 5-FU, but increased the toxicity of therapy substantially.

[Poisoning with a podophyllin-containing wart-treating tincture]. / Vergiftung mit Podophyllin-haltiger Warzentinktur.

HISTORY AND ADMISSION FINDINGS: A 57-year-old depressive and alcohol-dependent man was admitted because of frequent nausea and vomiting and abdominal complaints after he had ingested 40 ml of a tincture for treating warts. He was under the influence of alcohol, but normally oriented and without contributory findings other than his gastrointestinal complaints and tachypnea. INVESTIGATIONS: Transaminases were raised (GOT 1197 U/l, GPT 170 U/l, gammaGT 150 U/l, LDH 2047 U/l), as were creatine phosphokinase (426 U/l) and ferritin (12 200 ng/ml). Platelet count was 36000 mm3, Leucocytes count 11 700/mm (3). Gastroscopy showed marked mucosal necrosis along the entire esophagus and the pulled-up small intestine (state after gastrectomy). DIAGNOSIS, TREATMENT AND COURSE: The patient became comatose within 5 hours, acidotic, oliguric, required ventilation and went into severe shock. The symptoms and the fact that podophyllin (pod.) was the main agent in the wart preparation confirmed the suspicion of pod. poisoning. Symptomatic and intensive care measures stabilized his critically grave condition. He was extubated on the 7th day after ingestion and on the 10th day was discharged at his own request in a relatively good general state. When he was re-admitted after 4 weeks he was without psychiatric symptoms but deeply depressed, and he had signs of a polyneuropathy in all limbs, typical of pod. toxin poisoning. CONCLUSION: Pod. toxin, a spindle poison, is the toxic agent of pod., the resin from the roots and rhizomes of various Berberis plants. While the potential toxicity of the resin, taken either orally or applied externally, has been long known, the poorly definied raw product is still being added to anti-wart tinctures.

[Therapy studies of the Austrian Breast Cancer Group (ABC)]. / Die Therapiestudien der Austrian Breast Cancer Group (ABC).

The Austrian Breast Cancer Group (ABC) consisting of more than 60 participating centers in Austria has randomized more than 5800 patients in 11 randomized trials since 1984. At present, roughly 30% of all patients with the diagnosis primary breast cancer are accrued in protocols throughout the country. Due to specific activities, the breast conservation rate raised from an initial 20% to more than 60% in the last years. Multicenter trials are not only the basis for progress in medicine but also tools for quality control and quality improvement.

Adjuvant intraperitoneal cisplatin chemotherapy does not improve long-term survival after surgery for advanced gastric cancer.

PURPOSE: The long-term survival probability of patients who undergo surgery for stage 3 and 4 gastric cancer is poor, predominantly due to metastatic spread of the tumor. Depending on the type of tumor histology, the pathway of metastases is mainly peritoneal or hepatic dissemination. Interruption of this mechanism may be possible by intraperitoneal chemotherapy (IPT). PATIENTS AND METHODS: In a prospective randomized trial of 67 patients undergoing surgery for stage 3 and 4 gastric cancer, 33 patients underwent adjuvant postoperative IPT with cisplatin, while 34 control subjects remained untreated. RESULTS: Patients in the treatment group received a median of four IPT perfusions. Apart from frequent nausea, no adverse reactions or complications were noted. The median disease-free survival durations were 12.7 months and 9.7 months in treated patients and controls, respectively (P = .8). After a median follow-up duration of 72 months, 54 patients (80%) had died of primary disease or related complications. The median survival duration for IPT patients was 17.3 months as compared with 16.0 months for controls (P = .6). Autopsies were performed on 12 (18%) of 54 patients who died, and showed tumor spread to the peritoneal cavity and/or to the liver, irrespective of the application of IPT. CONCLUSION: IPT with cisplatin monotherapy does not improve survival probability after surgery for stage 3 and 4 gastric cancer. The reasons for ineffectiveness of IPT may be the choice of an unsuitable chemotherapeutic agent, an inefficient modus of application, or a lack of sufficient drug penetration into the serosa or peritoneal metastasis.

The use of epidemiology for screening and early detection of cancer: examples from Austria.

Reduction of mortality rates and the costs of screening programs have sometimes been discussed on basis of certain therapeutic nihilism especially concerning the treatment of some cancer localizations. Interest of an epidemiological institute should, however, concern specific regions with high cancer risk and in these areas, well defined by epidemiological investigations, screening projects should be performed. A screening program initiated in Oberpullendorf, a district in the federal country of Burgenland in Austria resulted in a rate of 53% Dukes A colorectal cancer stages (0% Dukes D) compared to 27% Dukes A stage (19% Dukes D) without screening. As regards the lung cancer screening programs, these are controversial, due to high costs and no evident influence on mortality rates. The mortality rate for Vienna is about 20% above the Austrian average. In women the discrepancy between the capital and the federal countries is especially high, as in Vienna 44% more women die on lung cancer as compared to the Austrian average. Some promising results in the treatment of lung cancer, especially in small cell carcinoma and combined treatment by chemo- and radiotherapy might justify a screening program for lung cancer. The highest increase of mortality in lung cancer is found in patients at the age of 75 and older. Those patients, however, suffer from other diseases too, therefore "screening programs for polymorbidity" should be discussed.

[Repeat mass screening for fecal occult blood for the diagnosis of colorectal neoplasms in a rural district. Results of an informational campaign]. / Wiederholte Massenscreeninguntersuchung auf okkultes Blut im Stuhl zur Erfassung kolorektaler Neoplasien in einem ländlichen Bezirk. Ergebnisse einer Informationskampagne.

In 1987/88 and 1988/89 we tested the population (aged greater than or equal to 40) of the district of Oberpullendorf in 2 series for faecal occult blood by means of the Hemdetect Test. In the first test series the test was offered to 18,233 persons and 8235 (45%) persons completed the test; 187 (2.3%) were positive. In the second series 6512 (36%) out of 18,241 completed the test and 472 (7.2%) persons were positive. The persons with positive results were examined by colonoscopy, gastroscopy, and abdominal sonography, in combination with routine investigations. Secondary compliance in these investigations was 92%. The screening method revealed 34 colorectal cancers with the favourable pathological staging: Dukes A 18 (53%), Dukes B 6 (18%), Dukes C 10 (29%), Dukes D 0. 11 polyps showing carcinoma in situ and 174 polyps (70% of which were adenomas) in 124 patients were treated by colonoscopy. In the meantime we have detected 14 "interval" cancers among people with a false negative test result, also at a favourable staging: Dukes A 6 (43%), Dukes B 4 (29%), Dukes C 4 (29%), Dukes D 0. In the non-responders we found 30 colorectal cancers at a much worse staging: Dukes A 7 (23%), Dukes B 10 (33%), Dukes C 8 (27%), and Dukes D 5 (17%). Screening for faecal occult blood in combination with the necessary investigations of the positive persons by colonoscopy is able to detect symptomless colorectal cancers at a less advanced pathological stage and enables the treatment of precancerous adenomatous polyps. An improvement in cumulative sensitivity is expected on annual repetition of screening for faecal occult blood.

Adjuvant intraperitoneal cisplatin therapy in patients with operated gastric carcinoma: results of a randomized trial.

In a multicenter trial the efficacy of intraperitoneal administration of cisplatin after radical or palliative resection of gastric carcinoma with respect to overall survival was investigated. In 64 randomised patients, patients treated with intraperitoneal perfusion did not show a benefit in the overall survival after a median follow-up of 18 months.

[Toxicity results of an adjuvant study with intraperitoneal chemotherapy in patients with stomach cancer. Current status and future prospects of intraperitoneal therapy]. / Toxizitätsergebnisse einer Adjuvansstudie mit intraperitonealer (ip) Chemotherapie bei Patienten mit Magenkarzinom. Derzeitiger Stellenwert und Zukunftsperspektiven der ip Therapie.

The peritoneum is a frequent location of recurrent disease after surgical treatment of carcinoma of the stomach, colon, rectum or ovary. Usually this type of recurrence does not respond very well to systemic chemotherapy. The rational of intraperitoneal (ip) perfusion with cytotoxic drugs is based on a 2- to 3-log-fold increase in ip level over plasma concentration for certain chemotherapeutic agents. Hence, malignant cells in the peritoneal cavity can be exposed to very high concentrations of cytotoxic agents without serious systemic side effects. Remission rates of peritoneal carcinoma after ip perfusion of a range of chemotherapeutic substances varied from between 15 to 50%. Minimal information is available about adjuvant ip perfusion after operation for cure. Toxicity data are presented from our adjuvant trial using ip perfusion after operation for gastric carcinoma for cure with cisplatin in a randomized fashion. Altogether 59 perfusions were performed, with minimal systemic toxicity, no occurrence of peritonitis and only 1 portal infection. Immunological data show that 1 day after ip perfusion the concentration of natural killer cells is increased in 60% of all perfusions, but decreased only in 28%. We conclude that ip perfusion with cisplatin is a safe procedure with limited toxicity. The efficacy of this technique in peritoneal carcinosis is not yet proven in randomized trials. The observation period of our trial in the adjuvant stage after operation for gastric carcinoma is too short as get to assess the usefulness of the procedure.

[Adjuvant chemotherapy in patients with radical resection of stomach cancer: 5-year results of a prospective randomized study]. / Adjuvante Chemotherapie bei Patienten mit radikal reseziertem Magenkarzinom: 5-Jahres-Ergebnisse einer prospektiv randomisierten Studie.

102 patients with operable gastric carcinoma were randomly allocated to untreated control, polychemotherapy, chemoimmunotherapy. At a median follow-up of 5 years, chemotherapy did not improve the overall survival rate. However, in certain subgroups, patients with lymphnode metastases and intestinal tumor type showed a significant survival benefit when treated with adjuvant chemotherapy. Furthermore, we found the site of first recurrence very closely related to the type of tumor histology. Regardless of the positive effect of chemotherapy in retrospective subset-analysis, we do not generally recommend the use of polychemotherapy in operable gastric carcinoma.

[Long-term results of selective proximal vagotomy]. / Langzeitergebnisse der selektiv-proximalen Vagotomie.

Highly selective vagotomy was performed in 361 patients over the past 10 years. The mortality was 0.3% in uncomplicated, and 1.6% in complicated duodenal ulcer. With a mean follow-up period of 52 months the recurrence rate was 7.4%. The known advantages of this operation, namely low mortality and low postoperative morbidity (dumping 0.8%, diarrhoea 0.8%, unintentional weight loss 0%, food intolerance 1.9% and epigastric fullness after meals 1.9%), were confirmed in our patients. The overall clinical result was excellent or good (Visick I or II) in 87% of patients. Clinical failures were most often caused by recurrent ulceration. Highly selective vagotomy is still the operation of choice in uncomplicated duodenal ulcer. It can also be recommended in selected cases of complicated ulcer disease.

[Are fractures of the upper ankle joint to be treated conservatively? (author's transl)]. / Ist die Behandlung der Knöchelfrakturen nach konservativen Gesichtspunkten Uberholt? Spätergebnisse der konservativen Therapie.

By means of 796 fractures of the upper ankle-joint, the treatment and results of the therapy according to the conservative-viewpoints are going to be discussed. Comparing the results after operative treatment, conservative therapy today is only justified with fractures of th type A and B under the presumption that there is no subluxation of the talus of the latter mentioned. Bimalleolar fractures of the type A can also be treated conservatively with good results if the inner-ankle fracture has not resulted in the destruction of the ankle-fork. All other fractures should have open reduction and internal fixation. Special attention shall be paid to the reconstruction of the complex fibula-syndesmosis.

[Prophylaxis of thromboembolism in abdominal surgery. Comparison of low dose heparin, acetylsalicylic acid and their combination (author's transl)]. / Thromboembolie-Prophylaxe in der Abdominalchirurgie. Vergleich von niedrig dosiertem Heparin, Azetylsalizylsäure und deren Kombination.

The aim of the study was to compare the effect of three possibilities of prophylaxis of thromboembolism: low dose heparin, acetylsalicylic acid (ASA) and a combination of the two. The evaluation of the clinical observations showed no significant differences between the three prophylaxis groups. The iodine fibrinogen test showed no different reaction with regard to the leg, a superiority of ASA in the thigh was suggested, at least in our random samples. Whether this observation is the reason why the frequency of fatal pulmonary emboli can be reduced by ASA is discussed. The complete calculation points to a superiority for ASA here. The size of the selected samples is, however, too small for more definite statements.

[Spontaneous mesenteric venous thrombosis, a rare complication of oral contraceptives (author's transl)]. / Primäre Mesenterialvenenthrombose, eine seltene Komplikation oraler Ovulationshemmer.

Spontaneous mesenteric venous thrombosis without recognizable aetiology is a rare condition. Only 10 cases have been described in world literature as a complication of oral contraceptives. The case report is presented of a 51 year-old married woman who had been taking oral contraceptives for 7 years. After abdominal pain for weeks segmental mesenteric venous thrombosis with a gangrenous small bowel loop was diagnosed. The gangrenous small bowel loop was treated by resection. Subsequently after discontinuance of contraceptive medication she was symptom free. The problems of diagnosis are pointed out and it is suggested that immediate discontinuance of oral contraceptives in women with unexplained abdominal pain might prevent gangrene of small bowel.

PIP: A 51-year-old woman who had used the oral contraceptive Lyndiol for 7 years developed severe abdominal pains that lasted for several weeks. There were no unequivocal clinical, laboratory test, or X-ray results to determine the cause of the pains. The patient was operated on for resection of a gangrenous loop of the small intestine, caused by a mesenteric venous thrombosis. It is possible that discontinuation of oral contraceptive use may have prevented the gangrene. Discontinuation of oral contraceptive use is recommended for women with unexplained abdominal pains.

[Exploration of pancreaticojejunal anastomosis by postoperative endoscopic pancreaticography (author's transl)]. / Anwendbarkeit der endoskopischen retrograden Pankreatikografie zur Funktionsprüfung pankreatikojejunaler Anastomosen.

Endoscopic pancreaticography (EP) was performed in 9 patients after pancreaticojejunal anastomosis had been established surgically; in 2 of these patients EP was not successful. The anastomosis could be demonstrated in 5 cases to be functioning 1-6 years after operation; in 3 cases the duct system was found to be dilatated, in 2 cases diameters were normal. EP and clinical symptoms correlated well in 4 of 5 cases.

[Factor XIII and the risk of postoperative impaired wound healing and bleeding (author's transl)]. / Faktor XIII und das Risiko postoperativer Wundheilungsstörungen und Blutungen.

Factor XIII concentration was investigated pre- and postoperatively in the plasma of 139 patients undergoing major abdominal surgery. Postoperative complications (impairment of wound healing and haemorrhage) were significantly more frequently seen in patients with a low concentration of factor XIII. A low preoperative concentration of factor XIII can be interpreted as a high risk factor.