Results of breast conserving therapy for early breast cancer and the role of mammographic follow-up.

PURPOSE: The following article is a review of 23 years of breast-conserving therapy in our hospital. This study was performed to assess and improve the follow-up care of women with early breast cancer and to evaluate whether or not biannual mammogram is useful. METHODS AND MATERIALS: Between 1972 and December 1995, 3072 women with pathological size pT1 and pT2 breast cancer were treated with conservative surgery and radiation therapy. Eighty-five patients developed a recurrence in the treated breast as the first site of failure, 12 of which had positive axillary nodes. In the following patient study, those with an noninvasive recurrence were excluded. A retrospective assessment of the entire mammographic course was made, starting with the mammogram at the time of original diagnosis to the mammogram of the recurrence. RESULTS: In our study group the probability for local failure ranged from 1 to 2% per year. At 5 and 10 years the actuarial rates were 5 and 10%. The median time to recurrence was 41 months (range 8-161). Twenty-six (31%) recurrences were detected by mammography alone, 10 (12%) by clinical examination only, and 35 (41%) by both methods. For the patients with an ipsilateral recurrence, the overall actuarial 5- and 10-year survival after treatment was 87 and 70%, respectively. The 5-year actuarial rate of survival from salvage mastectomy was 61%. CONCLUSION: Considering the high percentage of recurrences detectable by mammography and the possibility of detection within a short-term interval, we think biannual mammographic follow-up is appropriate for the first years following breast-conserving therapy.

Therapeutic effects of antibodies against adhesion molecules in murine collagen type II-induced arthritis.

Adhesion molecules play important roles in immune reactions and inflammatory processes and may constitute attractive targets for immunomodulatory approaches. In this study, blocking mAbs against a series of adhesion molecules were tested for their therapeutic effect on developing arthritis in a mouse model. MAbs were given for a period of 4 weeks at the time of exspected incidence of visible disease symptoms, i.e. 4 weeks after priming with collagen type II. A significant reduction of incidence down to values of 13% and 29% of the controls was obtained with mAbs against CD44 and alpha 4-integrin, respectively, during an observation time of 13 weeks. MAbs against CD4 and LFA-1 resulted only in weaker, non-significant effects or a delay in the incidence. MAbs against other molecules including L-selectin, ICAM-1 or VCAM-1 were not effective. The development of antibodies against collagen type II, collagen type I, proteoglycans and the immunogen, bovine collagen type II was affected by mAb treatment to a different extent. In this case, the anti CD4 mAb was the most effective, followed by the anti alpha 4-antibodies in most cases, whereas anti CD44 showed less clear effects on the development of humoral responses. In a skin delayed type hypersensitivity model analyzed for comparison, mAbs against LFA-1/ICAM-1 and alpha 4-integrin showed the largest effects on ear swelling. These data show that mAbs against several adhesion molecules are able to block selectively distinct aspects of immune reactions, and that CD44 and alpha 4-integrins could be promising targets for an immunotherapy of rheumatoid arthritis with receptor-interfering agents.

Relation between receptor status and ultrastructure in breast cancer: E+P+ versus E-P-.

Invasive breast cancer specimens were selected, which were either estrogen and progesterone receptor positive (E+P+), (30 cases) or both negative (E-P-). Light microscopical typing and grading were performed. From electron microscopic sections 27 nuclear and cytoplasmic features were recorded. Both estrogen and progesterone receptor content were evaluated using agar gel electrophoresis. As regards grading, highly differentiated tumors were significantly associated with E+P+ receptor status. Among the nuclear ultrastructural features, marked polymorphia, irregular chromatin distribution and multiple nucleoli were associated with lack of receptors. E+P+ tumors more often had surface structures which establish cell interconnection, such as desmosomes, halfdesmosomes and membrane interdigitations, and structures indicating special membrane differentiation, such as microvilli and intracytoplasmic ductuli. Most correlations with receptor content were observed in the assortment of cytoplasmic organelles studied. E-P- tumors were rich in organelles which indicate high metabolic activity, such as mitochondria and ribosomes. A polar organization and smooth ER were more frequent in E+P+ tumors. The biochemical-ultrastructural correlations presented in this study support the hypothesis that the formation of steroid receptors runs parallel to the individual degree of cytoplasmic and nuclear organization and is independent of the histological tumor type. The functional integrity of the complete estrogen response mechanism in E+P+ tumors is indicated by high grades of ultrastructural organization.

[Cytophotometric analysis of nuclear DNA-content in so-called obliterating mastopathy with epithelial hyperproliferation]. / Zytophotometrisch ermittelter Kern-DNS-Gehalt in sog. obliterierender Mastopathie mit Epithelhyperproliferation.

INTRODUCTION: Histogenesis, microscopic appearance, and clinical significance of so-called "obliterating mastopathy with epithelial hyperproliferation" are described. This focal lesion, which was recently re-evaluated by Hamperl (1975), may simulate scirrhous carcinoma in X-ray mammography. In histologic specimens similarities to special types of tubular carcinomas may cause problems in differential diagnosis. In order to gain a better insight into their behavior, cytophotometric DNA-analysis was applied to 10 selected cases. MATERIALS AND METHODS: DNA-determination was performed on Feulgen stained sections by means of a Leitz microspectrophotometer MPV 1. The plug technique was used after careful focussing of cell nuclei. Intraductal and extraductal epithelial proliferations have been analyzed in separate series. RESULTS: In four series of extraductal pseudoinfiltration and in six series of intraductal hyperproliferation, normoploid DNA-patterns were found. One series of apocrine metaplasia and one of atypical intraductal proliferation were read as borderline cases, but one case of atypical apocrine metaplasia revealed an aneuploid DNA-pattern, thus indicating the malignant nature of the lesions. DISCUSSION: "Obliterating mastopathy with epithelial hyperproliferation" is regarded a high risk disease which may progress to invasive carcinoma. According to the gross morphologic appearance of the focal lesions, the term "pseudoscirrhus" is proposed. Therapeutic approach depends mainly on the degree of epithelial hyperproliferation and cellular atypia. Focal lesions should be removed by wide excision, whereas in cases of multicentric development, subcutaneous mastectomy and plastic augmentation is recommended.

Paget's disease of the vulva with underlying apocrine adenocarcinoma and local lymph node invasion.

A case of Paget's disease of the vulva with an underlying apocrine adenocarcinoma and local lymph node invasion is reported in a female aged 70. Subjective symptoms of pruritus, burning and pain were associated with typical, but unspecific clinical findings of an erythematous, indistinctly limited, weeping lesion of palm-size with small superficial erosions. Near the right labium majus a solid measuring 2.5 X 1.5 cm in diameter was palpable. The diagnosis was established by microscopic examination of biopsy material, showing intraepidermally the typical Paget's disease with a subjacent, highly differentiated apocrine adenocarcinoma of the sweat glands combined with inguinal lymph node invasion. Other epidermal malignancies were excluded by histochemical reactions. For therapy, telecobalt irradiation combined with high energy electron was applied.

Immunohistochemical demonstration of carcinoembryonic antigen (CEA) in 120 mammary carcinomas and its correlation with tumor type, grading, staging plasma-CEA, and biochemical receptor status.

Antisera to CEA were used for the immunohistochemical localization and quantification of this antigen in 120 Bouin-fixed, paraffin embedded mammary carcinomas. These results were compared to tumor type, grading, staging, biochemical receptor status, cytosolic CEA-levels of the same tumors, and preoperative plasma CEA-levels. Mammary carcinomas were usually characterized by a low percentage of CEA-positive tumor cells: 50.9% of the cases contained more than 5% CEA-positive tumor cells and were therefore defined as being CEA-histopositive in this study. A relation could be shown between CEA-histopositivity and the histologic tumor type. The majority of invasive lobular carcinomas, tubular, and cribriform carcinomas was CEA-negative (72%). Conversely, 70% of invasive ductal carcinomas were CEA-positive. There was a significantly higher percentage of CEA-histopositivity in grade III tumors than in grade I/II carcinomas. The results obtained by quantification of the immunohistochemical staining of CEA were positively correlated with the results obtained by cytosolic CEA-assay. The overall concordance between tissue and plasma determinations of CEA was found to be 57.1%. A positive trend could be found between CEA-positivity and staging. However, no correlation was observed between CEA-positivity and estrogen receptor status.

[Determinants of observer variability in early diagnostic mammography--a ROC analysis]. / Determinanten der Beobachter-Variabilität bei der Früherkennungsmammographie--eine ROC-Analyse.

As part of the German mammographic study, the participating doctors were given test films of 30 histologically confirmed cases. Regarding the indications for biopsy there was good sensitivity (the median amongst 25 doctors was 0.87). Specificity (median 0.86) could be improved. Comparison of individual results with the majority showed considerable variability within the group of doctors performing mammography. ROC analysis indicated that there was considerable observer variability which was independent from the specialty or praxis characteristics of the participants. The inclusion of mammography in an early diagnostic programme requires continuing education of the participants in this technique. This should be supported by further methods of quality assurance.

Nodal involvement in cancer of the uterine cervix: value of lymphography and MRI.

In this study the preoperative staging of lymph node involvement in cervical cancer was analyzed retrospectively in 155 cases. All results were correlated with lymph node histology. One hundred and three patients underwent preoperative lymphography. Twelve of them were investigated by lymphography and MRI (magnetic resonance imaging). One patient was staged Ia, 10 patients were staged Ib and one patient was staged IIb. All patients underwent surgery; 18.5 lymph nodes were removed on average. Histologically lymph node involvement was found in 3 cases. Lymphography was able to detect lymph node involvement correctly in one case (33% sensitivity). We got two false positive results by lymphography (67% specificity). By MRI all cases were classified as nodal negative. MRI did not have advantage over bipedal lymphography in detecting lymph node involvement in our study, even though the results of lymphography were also poor.

[Therapeutic consequences of early detection of locoregional recurrences in breast cancer]. / Therapeutische Konsequenzen der Früherkennung lokoregionärer Rezidive beim Mammakarzinom.

The value of follow-up investigations depends on the therapeutic consequences of early detection of recurrences and metastatic disease. After breast conservation early detection of recurrent disease by physical and apparative examinations has to be aimed for due to a possible curation by salvage surgery. Also in recurrences of the chest wall a great deal of local controls can be achieved when detected early and at smaller sizes. While axillary recurrences can be controlled by surgery and radiation therapy the prognosis is poor in the case of a supraclavicular and retrosternal lymph node involvement. Diagnostic and therapeutic options will be discussed for these five types of recurrences.

[Post-operative complications following Caesarean section. A comparative study of the years 1957-1958 and 1977-1978]. / Postoperative Komplikationen nach Sectio caesarea. Eine vergleichende Analyse der Jahre 1957/1958 und 1977/1978.

104 Caesarean sections of the Obstetric Department of the University in Hamburg-Eppendorf of the years 1957-1958 were compared with 399 Caesarean sections of the years 1977-1978 in a retrospective study. An attempt was made to correlate the post-operative complications with possible causes. There was a marked rise in wound infections, endometritis, post-operative pyrexia and a decrease of thromboembolic complications and retained lochia. Differences in the old and new years were in the management of labour, the operative technique and the post-operative treatment. In the Caesarean sections of 1977 to 1978 a clear cut correlation between wound infections uterine complications and pyrexia and the number of vaginal examination following rupture of the membranes the duration of rupture of the membranes and the length of labour was found. To reduce the post-operative complication rate at attempt should be made to reduce the number of vaginal examinations, to be stringent in the indications for rupture of the membranes and to avoid delay in inevitable Caesarean sections.

[Split-course neutron and photon irradiation of experimental tumors: the importance of the sequence and interval lengths]. / Zweizeitige Neutronen- und Photonenbestrahlung experimenteller Tumoren: Bedeutung von Sequenz und Intervallänge.

In a split course mixed beam experiment we have investigated the influence of the interval and beam-quality on tumour growth delay. Fast growing sarcomas (SaF) in grey CBA-mice were irradiated with different sequences of neutrons (N) and photons (X) varying the length of time interval from 0 up to 300 minutes between two doses. The tumours were treated with isoeffective doses of X-rays and/or neutrons (XX, NN, NX, XN). In order to achieve a homogeneous radiosensitive cell population, tumours were reversibly made hypoxic by clamping ten minutes prior and during irradiation. Tumour growth delay is dependent on the sequence and on the interval. As expected the growth delay in tumours treated with neutrons only was less dependent on the interval than after pure photon irradiation. Beyond an interval of 30 minutes in the mixed beam schedules the one giving neutrons first was more effective than the one giving photons first.

[Radiotherapy in primary radically operated ovarian cancer]. / Die Strahlentherapie beim primär radikal operierten Ovarialkarzinom.

The basis of primary treatment is consequent surgery. Radiation therapy is not necessary for borderline tumors. An effect has been seen in stages Ib to III with a small amount of post-operative residual tumor. A comparison with the value of alternative chemotherapy has not yet been made. Instillation of the radioisotopes is effective. The value of radiation therapy after successful chemotherapy of stages III/IV has not yet been investigated enough. The results of radiation therapy after surgical and chemotherapeutical failure are poor.

[Lobular cancer transformation of the female breast. Mammography diagnosis and clinical relevance]. / Läppchenkanzerisierung der weiblichen Mamma. Mammographische Diagnostik und klinische Relevanz.

Lobular cancerisation was diagnosed in 101 women between 1976 and 1980. Calcification in the mammograms and follow-up without mastectomy were analysed. Therapy was simple biopsy, because the term lobular cancerisation was not established at that time. Surgery was done at the University Clinic for Women and the Elim Hospital at Hamburg. Retrospective analysis of the specimens was performed at the Department of Gynaecological Histopathology of the Hamburg University Clinic. Mammograms were available in 72 cases, showing calcifications in 40 cases. It was impossible to match the calcifications in the mammograms and the histological slides. Hence, a further 23 cases from 1980 to 1990 were analysed, suffering from lobular cancerisation and ductal carcinoma in situ (DCIS). Comparing 13 mammograms showing calcifications, with large-area scans, only two showed corresponding calcifications. Based on these data a specific diagnosis of lobular cancerisation by mammography is impossible. The follow-up of 88 patients with breast-preserving surgery and lobular cancerisation showed ipsilateral invasive carcinoma in three cases (0.35% in a total of 100 follow-up years), ipsilateral DCIS in five, and contralateral invasive breast cancer in one case. The therapy of lobular cancerisation should depend on the coexisting DCIS. There is no additional risk of local recurrence by lobular cancerisation.

[Measurement of the distance of the rectal mucosa from a gynecologic afterloading applicator based on the drop in performance of a cobalt-60-source]. / Messung des Abstandes der Rektumschleimhaut von einem gynäkologischen Afterloadingapplikator über den Dosisleistungsabfall einer Kobalt-60-Quelle.

PURPOSE: Assessment of the distance from a gynecological afterloading applicator to the rectum mucosa. METHODS: The appropriate afterloading applicator for HDR-Ir-therapy is used for that purpose. A Co-60-source (370 MBq) with a guiding wire is positioned at the tip of the applicator and then withdrawn in steps of 1 cm. For each of these points the maximum dose at the rectum mucosa is measured with an ionisation chamber. From a reference curve it is then possible to determine the distance from the rectum mucosa to the applicator and to mark it in the calculated isodose plan. The actual daily dose to the rectum mucosa is planned not to exceed 3.0 Gy in the maximum. RESULTS: Up to now the measurements were performed in 91 patients. The minimal distances of the rectum mucosa from the applicator were found to range from 5 to 18 mm with an average value of 14 mm. CONCLUSIONS: The comparison of the measurement with the readings of the rectum probe during each session showed, that the method is suitable to avoid an overdose at the rectum mucosa.

Radiation therapy of para-aortic lymph nodes in gynaecologic cancers: techniques, results and complications.

From 1965 to 1986 the para-aortic lymph nodes of 141 patients with gynaecologic cancers were irradiated directly after initial treatment of the primary site was completed. Another 32 patients only received para-aortic radiation treatment when para-aortic metastases became clinically apparent some time later. Radiation therapy was performed using a biaxial-four-segmental-rotating-field-technique. Crude survival of the group with initial para-aortic radiation treatment is far better than of the second group. Only five cases of severe complications due to para-aortic treatment were reported. In order to analyze the reason for such a low number of complications, CT-treatment planning for a typical patient was performed for different methods as they have been described in the literature, also referring to treatment data such as success, total dose and dose-distribution, thus influencing the complication rate. Obviously, the biaxial-four-segmental-rotating-field-technique is a method allowing to deposit a certain dose into the target volume without considerably damaging tissues in the vicinity.

Radiation therapy of para-aortic lymph nodes in cancer of the uterine cervix.

From 1965 to 1986, 173 patients with gynaecological cancer received para-aortic radiation treatment using a biaxial-four-segmental-rotating field technique. Seventy-five patients with cervical cancer and proven lymph node involvement were eligible for analysis. Crude survival and disease-free survival in 37 patients with FIGO III and 15 patients with FIGO IVA, receiving initial para-aortic treatment were compared with the corresponding data from patients in whom para-aortic treatment was secondary applied when para-aortic metastases became clinically symptomatic. Five-year survival rates of 37.5% (FIGO III) and 27.3% (FIGO IVA) were encouraging as none of the patients in the secondary group survived for more than 16 months. The number of complications induced by the described method of survived for more than 16 months. The number of complications induced by the described method of para-aortic irradiation appears to be substantially lower than with other methods using equal doses. Five cases of severe but not life-threatening side-effects were observed among 173 treated patients.