Randomised trial: One cycle of anthracycline-containing adjuvant chemotherapy compared with six cycles of CMF treatment in node-positive, hormone receptor-negative breast cancer patients.

AIM: A randomised, controlled clinical trial was initiated in 1984 to test whether 1 cycle of anthracycline-containing adjuvant chemotherapy improves the outcome of breast cancer patients presenting with stage II disease and negative oestrogen and progesterone receptors (ER, PgR), as compared with 6 cycles of dose-reduced CMF. PATIENTS AND METHODS: Within 7 years 263 women with stage II breast cancer were randomised either to receive 1 cycle of doxorubicin, vinblastine, cyclophosphamide, methotrexate and 5- fluorouracil (AV-CMF) or to receive 6 cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients were stratified for tumour stage, nodal stage, menopausal status, type of surgery and participating centre. RESULTS: After a median follow-up of 100 months, neither disease-free (DFS) nor overall survival (OS) differed significantly between the two groups. CONCLUSIONS: Compared to 6 cycles of a non-standard low-dose CMF regimen 1 cycle of anthracycline- containing adjuvant chemotherapy failed to improve the outcome in women with stage II receptor-negative breast cancer in terms of DFS and OS.

The affinity of MCF7 breast cancer cells to hyaluronan substrates of different molecular weight and concentrations in an in vitro model.

The affinity of MCF7 breast cancer cells to hyaluronan (HA) was investigated in an in vitro model. The cells form a tightly adhering monolayer on native HA with a concentration of 5 mg/ml. On native HA at higher concentrations the cells reduce their adhesion to the substrate in favor of increased intercellular bonds, resulting in a cluster-like aggregate that tends to detach from the substrate. Aggregate formation is accomplished after 12 h incubation. The phenomenon is independent of the CD44 receptor. Degradation of native HA by hyaluronidase abolishes aggregate formation even at high HA concentrations in favor of formation of a firmly adhering monolayer. This model may help to understand tumor spread on HA tissue structures and may explain therapy successes with hyaluronidase in tumor patients.

Randomized trial of low-dose chemotherapy added to tamoxifen in patients with receptor-positive and lymph node-positive breast cancer.

PURPOSE: To evaluate the outcome in patients with stage II hormone receptor-positive breast cancer treated or not treated with low-dose, short-term chemotherapy in addition to tamoxifen in terms of disease-free and overall survival. PATIENTS AND METHODS: A total of 613 patients were randomized to receive either low-dose chemotherapy (doxorubicin 20 mg/m(2) and vincristine 1 mg/m(2) on day 1; cyclophosphamide 300 mg/m(2); methotrexate 25 mg/m(2); and fluorouracil 600 mg/m(2) on days 29 and 36 intravenously) or no chemotherapy in addition to 20 mg of tamoxifen orally for 2 years. A third group without any treatment (postmenopausal patients only) was terminated after the accrual of 79 patients due to ethical reasons. RESULTS: After a median follow-up period of 7.5 years, the addition of chemotherapy did not improve the outcome in patients as compared with those treated with tamoxifen alone, neither with respect to disease-free nor overall survival. Multivariate analysis of prognostic factors for disease-free survival revealed menopausal status, in addition to nodal status, progesterone receptor, and histologic grade as significant. Both untreated postmenopausal and tamoxifen-treated premenopausal patients showed identical prognoses significantly inferior to the tamoxifen-treated postmenopausal cohort. Prognostic factors for overall survival in the multivariate analysis showed nodal and tumor stage, tumor grade, and hormone receptor level as significant. CONCLUSION: Low-dose chemotherapy in addition to tamoxifen does not improve the prognosis of stage II breast cancer patients with hormone-responsive tumors. Tamoxifen-treated postmenopausal patients show a significantly better prognosis than premenopausal patients, favoring the hypothesis of a more pronounced effect of tamoxifen in the older age groups.

Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.

A randomised clinical trial was performed to test whether or not low-dose chemotherapy lasting only 35 days improves the outcome of breast cancer patients with stage I disease and negative oestrogen and progesterone receptors (ER-, PgR-). Between 1984 and 1990, 277 stage I breast cancer patients with tumours negative for both oestrogen and progesterone receptors were randomised to receive either low-dose short-term chemotherapy or no chemotherapy. Chemotherapy consisted of one cycle of doxorubicin, vincristin (AV) and one cycle of cyclophosphamide, methotrexate, fluorouracil (CMF). Patients were stratified for tumour stage, type of surgery, menopausal status and participating centre. Results were analysed both by univariate and multivariate statistical. After a median length of follow-up of 84 months, disease-free (DFS) and overall survival (OS) did not differ significantly between patients having received adjuvant chemotherapy and the control group. Uni- and multivariate analysis did not show any significant prognostic or therapy related factor. A low-dose short-term adjuvant chemotherapy is insufficient to improve the prognosis of patients with breast cancer stage I with ER-, PgR-tumours.

[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.

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.

Complications and surgical interventions during 4 years of biliary extracorporeal shockwave lithotripsy.

BACKGROUND/AIMS: Extracorporeal shockwave lithotripsy (ESWL) of renal concrements, a revolutionary therapeutic concept, was introduced into clinical routine in the early 1980s. In this study, complications and surgical interventions of biliary extracorporeal shockwave lithotripsy were investigated. MATERIAL AND METHODS: Two hundred-eighty patients with gallbladder stones underwent extracorporeal shockwave lithotripsy during a 4 year (January 1990-December 1993) investigation period. Two hundred four patients were female, and 76 patients were male with a mean age of 48 years. All patients were symptomatic. Selection was carried out following the "Munich criteria" and the selection rate was 15.3% of all referred patients (n = 1831). One hundred eighty-eight patients had solitary stones, 92 patients presented with multiple stones (maximum 3 stones), with an average of 1.7 stones and a mean stone volume of 2.4 cm3 and stone diameter of 16.5 mm. Shockwave lithotripsy was performed with a second generation electrohydraulic lithotriptor with a mean of 2.1 sessions. Mean duration of one session was 50 min, 1331 discharges were applied on average with a mean power of 22.7 kV. RESULTS: Analgesia, with Alfetanil (mean 2.3 mg), was necessary in 68% of all treatment sessions. Fragmentation could be achieved in 81% of the cases, stone clearance was observed in 172 cases (66.4%) out of 258 patients after 12 months. Twenty-two patients were treated in 1993 and are still under observance. Side effects such as colic after treatment were observed in 88 cases (31.4%). In seven cases, severe complications such as impaction of fragments in the papilla of Vater followed by serochemical pancreatitis were seen. An urgent endoscopic sphincterotomy was necessary in these 7 cases (2.5%). Within 4 weeks after shockwave treatment in 4 cases 1.4% emergency cholecystenomy had to be performed. Elective cholecystectomy was done in 16 patients (5.7%). There were no deaths observed during the investigation period. CONCLUSION: Based on the results of our series, we do not recommend biliary ESWL in patients with stone volumes exceeding 14 cm3 (3cm), the high fragment volume after sufficient fragmentation by shockwaves indicates long term oral dissolution therapy. The probability of complications will be increased by the presence of larger fragments.

The influence of trauma on changes in neutrophil granulocyte function assessed by an analysis of granulocyte migration.

We examined the effects of trauma on polymorphonuclear leucocyte (PMN) migratory parameters and PMN elastase release, with the aim of tracing an acute inflammatory reaction from its very beginning to the phase of recovery. Fifteen patients who underwent monotrauma surgery, followed by uneventful healing, served as inflammation model. PMN activation was studied by measuring their readiness to migrate (TMI) and their penetration potency (DC) in a whole blood membrane filter device, in which a chemoattractant depot (FMLP) was integrated. Control chambers lacking FMLP provided parameters of the spontaneous migration. In healthy controls (n = 64), the numbers of invading PMNs decreased continuously from the outermost layer towards the interior of the filter device. FMLP did not influence the mobilization rate of PMNs immigrant from the blood into the filter, but those cells that did migrate penetrated deeper (P < 0.05). After trauma, the spontaneous and FMLP-stimulated DC was increased (P < 0.05). Trauma also tended to inhibit PMN migratory activity episodically; depression of the unspecific immune function (low TMI values) was found on the 3rd (P < 0.0001) and 12th (P < 0.01) postsurgical days. There was no correlation between the migratory parameters and the inflammation parameter, PMN elastase release. Preliminary results indicate that analyses of PMN migratory parameters by a whole blood membrane filter assay could provide a valuable adjunct in monitoring trauma-associated immunologic changes.

Results of irradiation treatment in patients with non-resectable oesophageal cancer.

Forty-eight patients with non-resectable cancer of the oesophagus and oesophagogastric junction (Group A: Stage I/II, 32; Group B: Stage III/IV, 16) underwent intraluminal Iridium-192 high dose-rate afterloading therapy (5-7 Gy/session, total dose: 5-21 Gy, mean: 12.4 Gy) and external beam irradiation (Karnofsky > or = 80% 50-60 Gy/2 Gy per day; Karnofsky 60-79%: 30 Gy/3 Gy per day). Durable satisfactory palliation (intake of at least semi-solid food) was demonstrated in 96% of patients. The mean survival for group A was 19.1 months and that for group B, 6.9 months, with a 12-month survival rate of 66% (group A) and 0% (group B) (P < 0.001). Local tumour response and complication rate were significantly dose-related with a predicted response rate of 70.5%, and a complication rate of 50% at ERD 129.3 Gy.

Mutant p53 expression and DNA analysis in human breast cancer comparison with conventional clinicopathological parameters.

Scientific research evaluates the prognostic importance of 53 expression and DNA flow cytometry controversially. To evaluate the prognostic relevance of mutant p53 protein overexpression and DNA flow cytometry in primary breast cancer we correlated these factors with the common prognostic parameters such as tumor size, lymph node status, grading, menopausal status and receptor status. Human breast cancer specimens from 180 previously untreated patients were collected and deep frozen. On each specimen DNA-analysis by Geohde's technique (Partec PAS II) and immunohistochemical evaluation of mutant p53 protein (PAb 1801 and 240, Novocastra Lab., Great Britain) were performed. Besides TNM- and histological classification, estrogen (ER)- and progesterone (PgR) receptor content was recorded. Overexpression of mutant p53 protein was found in 34 (19%) of all specimens. All these 34 tumors were aneuploid (p = 0.007), 86% of them were receptor negative (p 0.0001), 79% had a high tumor grade (p 0.0001), 73% a high S-phase-fraction (SPF) (p = 0.045) and 53% were premenopausal (p 0.0001). Tumor size and node status did not correlate significantly with p53 expression. 27 (15%) out of 180 carcinomas were diploid. There was a significant correlation between ploidy and the tumor grade (p = 0.003) and SPF (p 0.0001), but not correlation between ploidy and tumor size (p = 0.21), node status (p = 0.33) or receptor status (p = 0.18). A low SPF was predominantly found in tumors less than 2 cm in diameter (p 0.0001); no significant correlation was found between SPF, receptor status, tumor grade, node and menopausal status. Mutant p53 protein expression and DNA analysis in combination with common prognostic parameters might help to detect prognostically unfavourable subgroups of breast cancer patients.

Ossifying fibromyxoid tumour of the neck clinically mimicking a primary neoplasm of the thyroid gland.

We present a 50-year-old male patient with an ossifying fibromyxoid tumour (OFMT) of the prethyroidal soft parts infiltrating the thyroid gland in coincidence with recurrent goitre, 20 years after strumectomy. The tumour, initially misdiagnosed as thyroid carcinoma and malignant schwannoma respectively, was histologically composed of typical solid cell-formations and shelly-like mature bone at the periphery. In addition, in the tissue adjacent to the tumour some foreign body granulomas with suture material and small proliferating nerves were present as a residual of the preceding strumectomy. We regard this finding as an indication of nerve sheat origin of OFMT. Follow up of 3 years after total thyroidectomy and local irradiation shows the patient free of recurrent and metastatic disease.

[Epithelioid leiomyosarcoma of the stomach. Clinical experiences with a rare stomach tumor]. / Das epithelioide Leiomyosarkom des Magens. Klinische Erfahrungen mit einem seltenen Magentumor.

Gastric epithelioid leiomyosarcoma (epLMS), which generally occurs in mid- or late adult life, is a rare smooth muscle tumor of the stomach. Out of 25 soft tissue tumors of the stomach operated at the Department of Surgery, University of Graz, two epLMS were diagnosed. This paper presents the case of a 67-year-old male with an epLMS in the corpus and of a 80-year-old female with an epLMS in the fundus of the stomach. The tumors were not diagnosed by gastroscopy; they were localized by sonography and CT-scan. In both cases the tumor was completely removed surgically, using a TA 90 4.8 mm respectively a TA 55 4.8 mm stapler. Diagnosis was reached by histological and immunohistochemical examination of the tumor tissue. Surgical excision with wide tumor-free resection margins is the therapy of choice in this tumor group.

Malignant schwannoma of the breast.

Malignant schwannoma (MS) is a tumor of the Schwann or nerve sheath cells, most frequently occurring in the lower and upper extremities, trunk and head region. We report the third known case of MS of the breast, which occurred in a 27-year-old woman. The palpable tumor, about 1.2 cm in diameter, was localized in the upper inner quadrant of the right breast. After ultrasonography, mammography and fine needle aspiration cytology, the tumor was removed surgically.

[Breast cancer in the man: a report of 30 patients]. / Das Mammakarzinom des Mannes: Ein Bericht über 30 Patienten.

A retrospective review of male patients suffering from breast cancer seen over an 18-year period was carried out at the Department of Clinical Oncology of the University Hospital of Graz. Thirty evaluable cases were analysed. Eight patients had Stage I, 11 had Stage II, 8 had Stage III, and 3 had Stage IV disease. Local control was achieved in the majority, 29/30 (97%), by either surgery alone or combined surgery and radiation therapy. Local recurrence developed in 2 (7%) patients. Further 7 (23%) patients developed distant metastases and were treated in accordance with policies developed for the appropriate stage of the disease in females, with hormonal manipulation for hormone receptor-positive and -unknown patients and chemotherapy for hormone receptor-negative patients. The corrected five-year survival (Kaplan-Meier) is 83% for the entire group, 100% for patients with Stage I disease, 86% in Stage II, and 67% in Stage III and IV disease, respectively. This corresponds well with the results in recently published series. Stage of disease at initial presentation was a significant factor determining survival in our investigation. Our own data as well as recent data from literature suggest that with respect to TNM Stages in mammary carcinoma, there is no prognostic difference between men and women. To what extent improved local control by adequate local therapy or systemic adjuvant treatment modalities may improve overall survival remains to be discussed.

A phase I/II study of 4'-O-tetrahydropyranyl-doxorubicin, 5-fluorouracil, and high-dose leucovorin as first-line therapy in advanced breast cancer patients.

A total of 50 patients were treated weekly with 5-fluorouracil (FU), leucovorin (LV), and 4'-O-tetrahydropyranyl-doxorubicin (THP) as first-line chemotherapy for advanced breast cancer (ABC). In phase I the doses of LV (500 mg/m2, day 1) and FU (350 mg/m2, day 1) were held constant, while the dose of THP (day 1) was escalated, from the initial dose of 10 mg/m2 up to the maximum tolerated dose (MTD). Twenty-eight patients entered phase I, and MTD for THP was defined as 35 mg/m2 in this combination. Dose-limiting toxicities were myelosuppression and hepatotoxicity. In phase II, another 22 patients were treated with THP at a dose level of 30 mg/m2. Including 4 patients already treated at this dose in the first part, 25 patients were evaluable for response: 1 patient obtained a complete response (CR) and 13 showed a partial response (PR), giving an objective response rate of 56%. The median duration of response was 9.1+ months and median survival, 15.5+ months. Side effects were generally mild, with ECOG grade I and II leukopenia in 51% of all cycles and grade III in 3% of the courses. Other toxicity included nausea and vomiting (54% and 8%, respectively) and alopecia (24%), all restricted to ECOG grade I and II. Our results suggest that weekly THP/LV-FU represents an active regimen for first-line treatment of ABC with relative low toxicity.

[Degree of substitution and volume expanding effect of various medium molecular weight hydroxyethyl starch solutions]. / Substitutionsgrad und volumenexpandierender Effekt unterschiedlicher mittelmolekularer Hydroxyäthylstärke (HAES)-Lösungen.

Hydroxyethylstarch (HES) is today one of the most frequently used artificial plasma substitutes in prehospital, as well as in clinical settings. However, there are no studies comparing the volume effect of different HES solutions. The goals of the present study therefore were to compare the volume effect of three HES solutions, which are similar with regard to mean molecular weight but different in concentration and degree of substitution. The obtained results enable guidelines for fluid resuscitation in hypovolemia to be laid down. In 30 patients fulfilling the ASA physical status classification I and II 500 ml of either 10% HES 200/0.5, 6% HES 200/0.5 or 6% HES 200/0.6-0.66 were infused within 30 min. The effect of each solution was evaluated using the mechanical oscillator technique (MOT). This technique measures precisely density changes of blood and plasma and allows-using standard formulae-calculation of blood and plasma volume changes. All 3 HES solutions showed similar effects in increasing plasma volume. Immediately after the end of infusion plasma volume was increased by about 800 ml with 10% HES and by about 650 ml with 6% HES 200/0.5. The volume expanding effect of 6% HES 200/0.6-0.66 amounted to 700 ml. The volume expanding effect of all starches decreased only slightly during the following two hours; an interesting detail observed was a second volume effect of HES (about 20% of the volume infused). We conclude that for the correlation of fluid deficits due to trauma, hemorrhage and shock HES solutions seem to be most effective artificial plasma substitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Weekly 5-fluorouracil and high-dose folinic acid in combination with epidoxorubicin as first-line therapy in advanced breast cancer: a phase II study.

A total of 25 patients with advanced breast cancer were treated weekly with i.v. 5-fluorouracil at 350 mg/m2, folinic acid at 500 mg/m2, and epidoxorubicin at 35 mg/m2 as first-line chemotherapy for a maximum of 18 cycles. In all, 24 patients were evaluable for response. Overall, 1 patient achieved a complete response and 11 patients showed a partial response, for an objective response rate of 50%; the median duration of response was 18.3+ months and median survival amounted to 18.8+ months. Side effects were generally mild, with grade II leukopenia occurring in 10 patients and grade III leukopenia, in 1 patient. Other toxicity included nausea and vomiting (82%), diarrhea (48%), stomatitis (48%), and alopecia (92%), all of which were mainly restricted to WHO grades I and II. Our results suggest that leucovorin modulation of 5-fluorouracil can safely be incorporated into combination chemotherapy with epidoxorubicin on the investigated schedule. The observed response rate appears comparable with that obtained with other first-line regimens.

[A 41-year-old woman with recurrent cholangitis after bile duct operation 17 years earlier. A case report]. / Eine 41 jährige Frau mit rezidivierenden Cholangitiden nach Gallenwegsoperation vor 17 Jahren. Ein Fallbericht.

The case of an 41 year old female is reported, who underwent surgical correction of a congenital cyst of the common bile duct 17 years ago. Because of repeated pain attacks in the right upper quadrant in connection with fever and serochemical signs of cholestasis the patient was admitted to our unit. The exploration with ERCP and CT now showed a common channel in combination with a congenital cyst of the common bile duct. The risk of the anomalous pancreaticobiliary junction upon either the biliary tract or the pancreatic duct will be discussed, also the fact of an higher incidence of malignant tumors of the biliary system. The therapeutic procedures will be discussed.

[The place of mammography following breast-conserving therapy of breast cancer]. / Der Stellenwert der Mammographie nach brusterhaltender Therapie des Mammakarzinoms.

This study evaluates the radiographical signs of the breast in 168 patients with breast carcinoma who were treated with lumpectomy and radiation therapy. Two thirds of the postsurgical scars were radiologically seen only up to two years after operation. One-third showed only discrete scarred tissue after this period. The most characteristic sign was the continuous diminution of the post-surgical and post-radiation lesions in the follow-up mammograms (scar densities, fibrosis and architectural distortions). Microcalcification highly suspicious of malignancy developed in 6%; one-third, however, proved to be benign. Acute and chronic edema were the most striking symptoms up to one year after radiotherapy; the final stage of the post-radiation alterations was breast fibrosis which demonstrated in 60% of the cases rather discretely. The recurrence rate was 7%.

[Breast cancer in the catchment area of the Graz Institute of Pathology. Evaluation of morphologic parameters based on 1,510 cases]. / Das Mammakarzinom im Einzugsgebiet des Grazer Instituts für Pathologie. Evaluierung morphologischer Parameter an Hand von 1510 Fällen.

The patient's age, tumour size, histological type and degree of differentiation as well as involvement of axillary lymph nodes are decisive for prognosis and therapy of breast cancer. Moreover these parameters reflect the achievement of early diagnosis and the surgical standard of treatment of breast carcinomas. Therefore we retrospectively reviewed 1510 cases diagnosed from 1984-1987. Non-invasive carcinomas were diagnosed in 4%. 75% of them were classified as intraductal carcinoma and 25% as lobular carcinoma in situ. 96% of the tumours were invasive at time of diagnosis. Invasive ductal carcinoma (NOS-type) was found in 70.2%, invasive lobular carcinoma in 12.3%. 3.2% of the tumours showed both ductal and lobular differentiation and 2.3% corresponded to invasive ductal carcinoma with a predominantly intraductal component. Medullary and mucinous carcinomas were detected in 2.1% and 2% of cases, respectively. Papillary carcinomas were observed in 0.9%, the frequency of other histological types was less than 1%. 44% of the tumours corresponded to UICC-category pT1, 38% to pT2, 6% to pT3 and 8% to pT4. A meaningful correlation of tumour size and axillary lymph node involvement was possible in only 906 cases, in which 10 or more lymph nodes were verified histologically. Lymph node metastases were detected in 23% of tumour category pT1 and in 47% of category pT2. PT3- and pT4-tumours metastasized to axillary lymph nodes in 77 and 86% of cases, respectively.