Impact of the axillary nodal status on sentinel node mapping in breast cancer and its relevance for technical proceeding.

OBJECTIVE: The aim of this study is to analyze whether the axillary status influences the lymphatic mapping procedure in malignant breast disease and whether clinically relevant consequences for the technique of Sentinel Node (SN) biopsy may be drawn from this information. MATERIALS AND METHODS: SN biopsy was performed in 150 consecutive patients using a combination of the radioguided and the blue-dye technique. Axillary status was compared with the number of detected nodes. In cases of numerous nodes with tracer uptake, the radioactivity of each radiolabeled node was measured separately in a dose calibrator. We analyzed whether an increased tracer uptake could possibly indicate a 'true' or 'dominant' SN. Blue dye uptake was registered and compared with radioactivity. The findings were related to the histologic results. RESULTS: In patients with a positive axillary status, significantly more radiolabeled nodes were detected than in node negative patients (median 3 vs. 2; p < 0.001). In 54/86 patients with numerous SNs a 'dominant' node with at least twice the radioactivity than other marked nodes could be identified (62.8%). From 26 cases with axillary involvement, 20 patients (76.9%) were identified by the 'dominant' and the remaining six women (23.1%) by others than the seemingly leading SN. CONCLUSION: Axillary lymph node involvement influences the drainage pattern in breast cancer. Patients with numerous SNs have an increased risk of axillary involvement. A high tracer uptake does not permit the identification of a 'true' SN. A lack of surgical accuracy may lead to pitfalls if the axilla is not screened carefully for all radioactive nodes.

Results of a standardized protocol for sentinel node imaging in breast cancer with Tc-99m labeled nanocolloidal albumin.

AIM: Of this study was to evaluate the results of a standardized protocol for sentinel node (SN) detection in breast cancer using Tc-99m labeled nanocolloidal albumin and a combined intra- and subdermal injection technique. METHODS: One hundred and fifty-five women with proven breast cancer (disease stages Tis-T2) were included. Four injections of 10 to 15 MBq of Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the 3, 6, 9 and 12 o'clock positions in the skin overlying the tumor. Planar scintigraphic images in lateral and anterior projections were obtained once between 2.5 and 18 hours after tracer administration. Guided by a gamma probe, all radioactive lymph nodes in the axilla were resected, then complete dissection followed. RESULTS: In 151 of the 155 women (97.4%), nodal tracer uptake (range 1-7 foci, average 2.2) was scintigraphically revealed. In one of these cases, drainage was only to the internal mammary lymphatic chain. Three of the 4 women with detection failure presented with histologically proven tumor infiltration of the lymphatics and axillary involvement. In 49 of the patients with visualized axillary lymph nodes (32.7%), at least one SN was metastatic. In 21 cases, this SN was the only positive node. The remaining 101 patients with negative SN included 4 cases with axillary involvement. The sensitivity of the SN with respect to the histological status of the entire axilla was thus 92.5%, the negative predictive value was 96.0%. The overall accuracy of the method was 97.3%. There was a significant difference between the number of totally detected radioactive nodes in the groups with and without nodal metastases (3.49 vs. 2.57, p < 0.01). CONCLUSION: The described protocol represents an easy reproducible and reliable method for SN detection in breast cancer that additionally allows flexible timing of surgery. Further, we found evidence that the number of scintigraphically visualized nodes also reflects the histological status of the axilla.

Lymphoscintigraphic sentinel node imaging and gamma probe detection in breast cancer with Tc-99m nanocolloidal albumin: results of an optimized protocol.

PURPOSE: The purpose of this study was to aid in the standardization of lymphoscintigraphy for detecting the sentinel node (SN) in breast cancer using Tc-99m-labeled nanocolloidal albumin. MATERIALS AND METHODS: One hundred twenty-three women with proved breast cancer were enrolled. Four injections of 10 to 15 MBq (0.27 to 0.41 mCi) Tc-99m nanocolloid in 0.1 ml physiologic saline were administered intra- and subdermally at the margin of the skin overlying the tumor. Planar scintigraphic images in the lateral and anterior projections were obtained 2.5 to 18 hours after tracer administration. With a gamma probe used as a guide, all radioactive lymph nodes in the axilla were resected. Complete dissection then followed. RESULTS: In 116 of the 123 (94%) women, axillary nodal tracer uptake was revealed. Six of the 7 women in whom detection failure occurred had histologically proved tumor infiltration of the lymphatics and axillary involvement. In 36 (31%) of the patients with visualized lymph nodes, the SN was metastatic. The remaining 80 patients with negative SN included three cases with axillary involvement. The sensitivity of the SN with respect to the histologic status of the entire axilla thus was 92.3%, and the negative predictive value was 96.3%. The overall accuracy of the method was 97.4%. The number of hot nodes in women with and without axillary involvement was significantly different. CONCLUSIONS: The described protocol represents an easily reproduced and reliable method for SN detection in breast cancer. Furthermore, the number of visualized axillary nodes reflects the histologic status of the axilla.

[Endoscopic therapy of adnexa tumors using endobag extraction]. / Endoskopische Therapie von Adnextumoren unter Verwendung der Endobag-Extraktion.

Evidence of 39 treated cases of cystic adnexal tumours of unclarified quality indicates that laparoscopic resection with subsequent extraction of the entire tumour in an endobag could provide the possibility of an endoscopic operation even in cases of indistinct tumours or of patients with enhanced perioperative risks. In particular patients with increased morbidity due to immobilisation might especially benefit from the technique.

[Clinical relevance of nucleic acid detection of human papillomaviruses (HPV) in cells from smears of the cervix uteri]. / Beitrag zur klinischen Relevanz des Nukleinsäurenachweises der humanen Papillomviren (HPV) in Abstrichzellen der Cervix uteri.

Cervical smears from 516 women were investigated cytologically and for the presence of papilloma virus (HPV) type 16/18 DNA sequences. From the cytologically normal smears (Pap I, II, IIw) 57/424 (13%) 16/18 were found HPV positive and from the pathological ones (Pap III, IIID, IVa, IVb, V), 30/92 (33%). The age prevalence of the HPV infection--provided a cytologically normal smear--appears compatible with the period of sexual activity, but persistence of the HPV infection has to be considered as a complicating factor. Our investigations on successive smears nevertheless permit the hypothesis that an HPV infection may disappear. The use of biotin-labeled nucleic acid probes yields results at least as reliable as those obtained with radioactive probes. The test for HPV positivity appears at present to be of limited diagnostic and prognostic benefit, particularly for the individual case. Investigations on fundamental oncogenic mechanisms are a different matter.

Use of biotinylated DNA probes in screening cells obtained from cervical swabs for human papillomavirus DNA sequences.

A nonradioactive DNA-detection procedure using biotinylated DNA probes in the screening of cells from cervical swabs for DNA sequences homologous to human papillomavirus (HPV) DNA was tested. This alternative DNA-detection method yielded results comparable to those obtained with radioisotope-labeled DNA probes in 32 cases tested. This procedure obviates the special precautions required for radioisotope materials. Accordingly, this technique can be made available to many laboratories, and conclusive evidence as to the relation of HPV infection to cervical cancer may thus be accumulated.

[Clinical and pathomorphologic studies of the precancerous significance and prognostic assessment of epithelial changes in the vulva]. / Klinische und pathomorphologische Untersuchungen zur präkanzerösen Bedeutung und prognostischen Wertung epithelialer Vulvaveränderungen.

For an observation period of 19 years the authors compiled the relevant clinical and pathomorphological data of patients of the Department of Gynaecology of the University of Cologne to assess the epithelial alterations in the vulva. Particular attention was given to the simultaneous or earlier presence of other genital carcinomas and of genital precancerous growths, especially to the high coincidence rate of malignant and premalignant lesions of the cervix uteri. Metric measurements were performed on histological section preparations to determine the extent and dimensions of microinvasions, i.e. of microcarcinomas. Histological examination of the epithelial alterations adjacent to invasive vulvar carcinomas revealed a carcinoma in situ in only 35% of the cases, in contrast to the situation at the cervix uteri. No definite answer can as yet be given to the question of the concrete risk of malignant degeneration of the carcinoma in situ of the vulva.

[Steroid hormone receptors in normal, dystrophic, dysplastic and carcinomatous vulva tissues]. / Steroidhormon-Rezeptoren in normalen, dystrophischen, dysplastischen und karzinomatösen Vulvageweben.

We employed the agar gel electrophoresis method to determine in 63 samples of vulva tissue the cytoplasmatic receptors for oestradiol, dihydrotestosterone and dexamethasone. Tissues with a binding capacity of more than 5 femtomol/mg (fmol = 10(-15) mol) cell proteins were considered receptor positive. The study comprised 17 normal tissues of the vulva, 13 vulva biopsies at the end of the pregnancy period, 7 dystrophically changed tissues, 11 premalignant changes of the vulva and 15 squamous cell carcinomas. In normal as well as in benign or malignantly changed vulva, specific receptors were found for all the four steroids (ER, PR, DHTR, DExaR). Receptors were most frequent in normal vulva tissue (ER = 94%, PR = 54%, DHTR = 38%, DexaR = 83%) with binding-capacities of 8-650 fmol/mg cell proteins. ER levels were higher during the postmenopausal period than during the premenopausal period. In dystrophia the receptor pattern was almost the same as in healthy tissue. Biopsies conducted at the end of the pregnancy period showed in all cases despite the high endogenous oestrogen levels positive ER values up to 875 fmol/mg cell proteins, whereas PR and DTHR were present in only 20% or 25% with low binding capacities. Loss of receptors, particularly of PR, was seen in premalignant changes (dysplasia of vulva, carcinoma in situ) and in case of squamous cell carcinomas. On comparing the receptor distribution of clinically changed vulva tissue with healthy tissue we found only differences by degree but no fundamental differences in principle.(ABSTRACT TRUNCATED AT 250 WORDS)

[Experiences with CA 125, a tumor marker for malignant epithelial ovarian tumors]. / Erfahrungen mit CA 125, einem Tumormarker für maligne epitheliale Ovarialtumoren.

CA 125 (Cancer Antigen 125) is an antigen identified by means of a monoclonal antibody on the surface of epithelial ovarian carcinoma cells. The serum concentration levels of CA 125 were measured in 41 women with benign and 95 patients with malignant tumours of the ovary. Immunoradiometric determination was effected by means of a kit supplied by Centocor. 35 U/ml was assumed as limit values of the standard range. Enhanced serum concentrations of CA 125 were seen in 5 per cent of the healthy volunteers of a standard group of persons, in 17 per cent of women with benign and in 78 per cent of women with malignant ovarian tumours. Patients without recurrence of tumour after successful primary treatment showed values above 35 U/ml in only 3 per cent of the cases. The incidence of pathological CA 125 serum concentration levels depended upon the histological type of the ovarian tumour and was highest in women with epithelial carcinomas, especially those with serous cystadenocarcinomas (87 per cent). In follow-up examinations of 30 patients with ovarian carcinoma over a period of one to 60 months, CA 125 concentrations correlated with the disease pattern in 90 per cent of the cases. The increases in CA 125 values preceded clinical diagnosis of the relapse by 1-8 months in seven out of twelve women. Routine determination of CA 125 appears advisable in the control of patients with ovarian carcinoma on account of the high sensitivity and specificity during follow-up.

Clinical significance of cancer antigen 125 (CA 125) in ovarian cancer.

Cancer antigen 125 (CA 125), a new ovarian cancer-associated antigen, was studied by radioimmunological determination of serum concentrations in 58 healthy blood donors, in 31 women with benign tumors, and 100 patients with malignant tumors of the ovary. Elevated CA 125 levels were found in 5% of normal controls, in 13% of women with benign tumors, and in 78% of patients with ovarian cancer. After successful antineoplastic treatment, false positive CA 125 values were observed in 4% of tumor-free patients. The incidence of pathological CA 125 serum levels was found to depend on the histogenetic origin of the ovarian tumors and was highest in patients with epithelial serous cystadenocarcinomas (85%). Sequential determinations of CA 125 in 27 patients with ovarian cancer under therapy showed a concordance in 89% of cases between serum concentrations and clinical courses. Elevations of CA 125 were already observed 1-6 months before objective evidence of recurrence. Therefore, the determination of serum CA 125 is recommended in the surveillance of patients with ovarian cancer.

[HBs-antigen determination during pregnancy with reference to prevention of a postnatal infection in the newborn infant]. / HBs-Antigennachweis in der Schwangerschaft unter dem Gesichtspunkt der Prävention einer postnatalen Infektion des Neugeborenen.

In 1980 and 1981 the blood samples of 2040 pregnant women from the Department of Obstetrics of the University Hospital of Cologne have been examined for HBs-antigen. In 37 samples (1.8%) HBs-antigen was detected. As there are considerable racial as well as geographic differences in the frequency of HBs-antigenemia, we differentiated between German and foreign women. In 10 out of 1519 (0.7%) German and in 27 out of 521 (5.2%) foreign women, respectively, HBs-antigen could be demonstrated. Only 1 woman was known to be HBs-antigen positive. Until now, 38 children have been born in the University Hospital to 33 HBs-antigen-positive mothers. After birth, 35 children received hepatitis B immune globulin (HBIG). So far, none of these immunised children exhibited signs of a hepatitis B infection--22 children have been followed up 5-19 months, and 13 children 1-4 months. Three newborns did not receive HBIG: One child was already infected at time of birth, the 2 other children were erroneously not given HBIG. One of these 2 children fell ill at the age of 5 months with clinical and serological manifestations of hepatitis B, the other child appears healthy up to date (11 weeks).

[Criteria for the definition of early cancer of the breast (author's transl)]. / Kriterien zur Abgrenzung von Frühfällen des Mammakarzinoms.

In order to define cancer of the breast limited to the breast parenchyma 114 infiltrating carcinomas with a maximum size of 1 cm and 88 non-infiltrating carcinomas (without size limitation) were investigated histologically for axillary lymph node metastases. All carcinomas with a size of up to 0.5 cm (25 cases) were free of lymph node metastases. Infiltrating carcinomas with a size of more than 0.5 cm up to 1 cm (108 cases) showed metastases in 25%. Non-infiltrating carcinomas of more than 0.5 cm (69 cases) had lymph node metastases in 1.4%. Considering the excellent prognosis, by histologically criteria infiltrating carcinomas of up to 0.5 cm and all non-infiltrating carcinomas can be considered as cases of "early breast cancer". For detection of these carcinomas mammography is of considerable importance, particularly when micro-calcifications are demonstrated. Among non-invasive carcinomas 74% were thus discovered by this method.

[Mental and somatic findings after subcutaneous mastectomy and augmentation (author's transl)]. / Psychische und somatische Befunde nach subkutaner Mastektomie und Augmentation.

20 women were subjected to clinical follow-ups after subcutaneous mastectomy and augmentation graft, the psycho-social consequences being investigated by means of a semi-structured interview and psychodiagnostic tests. With an average dwelling time of the prostheses of 22.6 months, cosmetic results were rated very good or good in 41.7% only of the cases from an objective viewpoint. However, the patients themselves arrived at a much more favourable subjective evaluation. All women complained of disturbed sensitivity. About one-half of the patients experienced pain as well as a feeling of tension in the breast. In 4 women there was also restricted mobility of the shoulder joint. The women did not feel impaired regarding their social activities, after having overcome an initial feeling of uncertainty. General sexual enjoyment, however, was definitely impaired. With one exception, none of the couples included the operated breast in the sexual foreplay.

[Diagnosis of stromal hyperplasia of the endometrium (author's transl)]. / Zur Diagnose der Stromahyperplasie des Endometriums.

In three cases of endometrial stromal hyperplasia, nuclear DNA-content was determined by Feulgen microspectrophotometry. In two cases DNA-content exhibited the diploid pattern. In the third case values ranged from diploid to tetraploid, also showing an additional peak for hypotetraploid values. The two cases with diploid DNA patterns are considered to have less malignant potential. This corresponds well to clinical follow-up examinations performed three and nine years later, where no progression to malignant growth was established. The pronounced proliferative tendency observed in the third case would make progression to malignancy appear highly probable.

Morphometric and cytophotometric investigations of lobular neoplasia of the breast with ductal involvement.

The two different types, A and B, of in situ lobular neoplasia of the breast can be distinguished by cytomorphological means. DNA-measurements of type A are preponderantly diploid while those of type B vary from diploidy to hyperteraploidy with a maximum in the hyperdiploid range. The results indicate a higher potential of malignancy in type B. Homogenous ductular cell proliferations in the immediate neighbourhood of a lobular neoplasia display virtually the same distribution of DNA-values. Such evidence suggests that ductular changes and concomitant intralobular lesions have a common genesis, showing also a similar tendency towards malignant changes.

X-chromatin (Barr bodies) correlated with the DNA content of lobular neoplasia and invasive lobular carcinoma in the female breast.

Literature relating X-chromatin with the histologic grade in carcinoma of the breast is briefly reviewed. X-chromatin incidence has been determined in 14 cases of lobular neoplasia and 5 invasive lobular carcinomas of the breast and has been correlated with the DNA content in these sections examined by Feulgen microspectrophotometry. In 11 of the cases of lobular neoplasia, the DNA values fell within the diploid range and in the 3 remaining cases within the diploid to tetraploid range, while the 5 invasive lobular carconomas showed a DNA distribution between the diploid and tetraploid ranges. The X-chromatin counts of these cases were variable but did not correlate with the cytophotometrically observed degree of malignancy in lobular neoplasia. No statistically significant differences in X-chromatin count of lobular neoplasia and invasive lobular carcinoma could be seen.

[The significance of prenatal diagnosis of twins (author's transl)]. / Die Bedeutung der pränatalen Zwillingsdiagnose.

By means of ultrasound and fetal electrocardiography the diagnosis of twin pregnancies can be made prenatally without any reservation; the diagnosis is even possible in the first half of pregnancy. Comparative analysis of two approximately equal collectives of in all 602 twin pregnancies--1,45% of all births in the years 1955-1975 at the University Clinic for Gynecology and Obstetrics of the University of Cologne--revealed a better prognosis concerning the course of pregnancy and the new-born by prenatal diagnosis. The earliest possible diagnosis of twins, resulting in more intense clinical observation--and occasional clinical treatment--facilitated a significantly longer duration of pregnancy, leading to a higher percentage of mature twins. Whereas the total number of obstetric operations was reduced because of prenatal diagnosis, selection of highrisk cases led to a distinct increase in Caesarian sections. The prolongation of pregnancy, the higher birth weights and better maturity attained, were accompanied by decrease in perinatal mortality and in improvement in the Apgar-index of the newborn in that collective, in which prenatal diagnosis was achieved.