Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer.

BACKGROUND: Cytokeratins are specific markers of epithelial cancer cells in bone marrow. We assessed the influence of cytokeratin-positive micrometastases in the bone marrow on the prognosis of women with breast cancer. METHODS: We obtained bone marrow aspirates from both upper iliac crests of 552 patients with stage I, II, or III breast cancer who underwent complete resection of the tumor and 191 patients with nonmalignant disease. The specimens were stained with the monoclonal antibody A45-B/B3, which binds to an antigen on cytokeratins. The median follow-up was 38 months (range, 10 to 70). The primary end point was survival. RESULTS: Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presence of micrometastases in bone marrow was associated with the occurrence of clinically overt distant metastasis and death from cancer-related causes (P<0.001), but not with locoregional relapse (P=0.77). Of 199 patients with occult metastatic cells, 49 died of cancer, whereas of 353 patients without such cells, 22 died of cancer-related causes (P<0.001). Among the 301 women without lymph-node metastases, 14 of the 100 with bone marrow micrometastases died of cancer-related causes, as did 2 of the 201 without bone marrow micrometastases (P<0.001). The presence of occult metastatic cells in bone marrow, as compared with their absence, was an independent prognostic indicator of the risk of death from cancer (relative risk, 4.17; 95 percent confidence interval, 2.51 to 6.94; P<0.001), after adjustment for the use of systemic adjuvant chemotherapy. CONCLUSIONS: The presence of occult cytokeratin-positive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer.

Successful treatment of malignant placental site trophoblastic tumor with combined cytostatic-surgical approach: case report and review of literature.

OBJECTIVE: Although rare among gestational trophoblastic diseases, the clinical relevance of malignant placental site trophoblastic tumor (PSTT) derives from its potential malignancy associated with early systemic tumor cell dissemination and manifestation of fatal metastases. Because of the low number of cases reported so far worldwide, several treatment strategies have been under consideration, which will be debated following this case report. METHOD: We present the case of a 33-year-old female with PSTT and metastases to the vagina and lung. A 9-month delay in accurate diagnosis was caused by a misinterpretation of her symptoms as signs of a spontaneous abortion. Specialized pathological examination finally led to the diagnosis of PSTT. Primary surgical treatment consisting of abdominal hysterectomy and unilateral salpingo-oophorectomy was followed by multiple resections of recurrent vaginal disease. After the completion of six cycles of EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine) chemotherapy, hCG titers stayed within the normal range. The patient is without evidence of disease 39 months after primary diagnosis. RESULT: This is the third case of documented long-term remission (>1 year) in metastatic PSTT after combined cryostatic-surgical treatment. CONCLUSION: Since the few previously reported cases with prolonged remission have been treated with the described combined cytostatic-surgical approach consisting of cytoreductive surgery and adjuvant chemotherapy, this approach may be recommended for metastatic PSTT.

Evaluation of mammographic breast lesions with Tc-99m sestamibi scintimammography and contrast enhanced MRI.

Scintimammography using Tc-99m sestamibi and contrast enhanced MRI were performed in order to determine the accuracy of both methods in the diagnostic work up of patients with suspicious or indeterminate preliminary diagnosis. 25 controls and 56 patients (14 with suspicious and 42 with indeterminate preliminary diagnoses), in whom physical examination and/or mammography warranted breast biopsy, underwent prone planar scintimammography. Sestamibi uptake was scored visually and measured using the ROI technique to enable semiquantitative evaluation. The patient group additionally underwent plain and contrast enhanced MRI. Visually determined signal increase following application of Gd-DTPA was compared with scintigraphic findings and final histopathologic results. Sensitivity and specificity of semiquantitative scintimammography for diagnosing breast cancer was 88% and 87%, respectively. Based on ROC analysis a target/non target ratio R > 1.3 was shown to be the optimal threshold for separating benign from suspicious scintigraphic diagnoses. MRI reading provided a slightly higher sensitivity (91%), but a considerable lower specificity (52%) due to contrast enhancement of different benign lesions. In the clinically important patient subpopulation with indeterminate results from previous diagnostic procedures, sensitivity of scintimammography fell to 79%, while specificity remained at 87%. MRI revealed a higher sensitivity of 89% and a lower specificity of 52%. Our data indicate that semiquantitative scintimammography using Tc-99m sestamibi provides a comparable sensitivity to contrast enhanced MRI in the assessment of breast cancer. The latter does not reduce the number of biopsies yielding benign results due to the high number of false positive diagnoses. Therefore, scintimammography seems to be the preferable tool in the diagnostic work-up of patients with indeterminate mammographic diagnoses.

[Incidence of primary malignant lesions in clinically benign teratoma: on the problem of adequate surgical procedure]. / Die Häufigkeit primärmaligner Herde in klinisch gutartigen Teratomen: Zur Frage eines adäquaten chirurgischen Vorgehens.

The Problem of an Adequate Surgical Approach: Frequency of malignant teratomas is, according to the literature, 2%-10%. Examining 194 own cases (1983-1993) it was 1.5%. We found one squamous cell carcinoma (0.5%). Additionally we found 2 immature teratomas (1%). We point out the different biological behaviour of malignant mature teratomas and immature teratomas. We agree with the majority of authors that the method of choice is the intact removal of all teratomas without iatrogen rupture or contamination of the abdominal cavity by contents of the teratoma. This adequate surgical procedure can and should be performed by laparotomy or laparoscopy with endobag. The often practised method of cutting open the cyst during laparoscopy, sucking off the contents or cutting the teratoma into pieces, has been proven to lead to implantation and worsening the prognosis in case of a malignant teratoma. Even the rinsing of the abdominal cavity, usually carried out with this method, could not compensate always for the disadvantage of this "dirty" endoscopical method compared with usual oncological standards. This is pointed out by case reports in the literature and the first analysis of a German survey with early-follow-up of 192 laparoscopically managed ovarian malignancies [11a]. The principle of intact removal of every teratoma should again be kept in mind.

[Ano-genital injuries in female victims of sexual assault]. / Ano-genitale Verletzungen bei weiblichen Opfern von Sexualdelikten.

Sexual assault continues to represent the most rapidly growing violent crime in the USA. Statistics prove a persistent rise in rape incidence with poor conviction rates. This knowledge, along with the vast multitude of emotional sequilae of rape and self-perceived inferior legal status of the involved females results in a high percentage of unreported cases. This presented paper reports of ano-genital trauma in case of sexual assault. Under 2970 victims of sexual assault, examined and treated between 1967-1985 in the Department of Gynecology and Obstetrics Charlottenburg (Free University of Berlin), a percentage of almost 40% was represented by children in the age of 0-14. Therefore, only 1696 patients with complete gynecological examination with correct case history examination for injuries and traces of sperm, infections could be presented. The total rate of injuries was: Perineum 8.4%, vulva 5.4%, vagina 1.8%, pelvis/thighs 14.2%. The highest risk to be injured in case of sexual assault had the age group of victims over 55 years (nearly 50%). The lowest rate of injury has been encountered in the age groups 0-5 years, 6-10 years, 26-35 years: Under 10%. A solitary anal-injury has not been found. Specific training in emergent and chronic care for the victims, both physical and mental, in conjunction with preventive measures to genital infections and pregnancy, are necessary when the gynecologist is involved.

[Carcinoma in situ of the breast--is axillary lymphadenectomy necessary?]. / Carcinoma in situ der Mamma--ist eine axilläre Lymphadenektomie notwendig?

Between 1963 and 1993, 3720 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg and at the I. Frauenklinik der Universität München for a malignant condition of the breast. 187 of these (5%) exhibited stage p Tis, 102 (54.5%) of whom had an axillary lymphadenectomy. One patient had a micrometastasis (pN1a). During the observation period of up to 24 years, 11 patients (5.9%) developed local recurrence. In none of the patients a regional or generalised recurrence could be observed within this period. On the basis of our own results and those from the literature, we conclude that, under the aspect of a risk-adapted tumour surgery, axillary lymphadenectomy is no longer necessary under certain conditions: an invasive carcinoma should be excluded with high certainty in the tumourectomy specimen as well as in the remaining breast. Therefore, a histological work-up in serial sections must be provided to exclude multifocality (multicentricity) and a tumour diameter larger than 25 mm.

Intraductal carcinoma (DCIS) of the breast. Risk-adapted tumor surgery with axillary lymphadenectomy?

Between 1963 and April 1994, 3823 women were treated both at the Universitäts-Frauenklinik Berlin-Charlottenburg as well as at the I. Frauenklinik der Universität München, for a malignant condition of the breast gland. 161 of these (4.2%) exhibited an intraductal carcinoma stage pTis, whilst 99 (61.5%) were axillary lymphadenectomised. During the observation time-span of up to 24 years, 9 patients (5.6%) developed local recurrence. In neither patients of the group with axillary nor without axillary dissection could a regional recurrence be observed within this period. Also, a generalisation of this condition was not recorded in any patient. On the basis of our own results and those from the literature we postulate that, under the auspices of a risk adapted tumor surgery, axillary lymphadenectomy is no longer necessary under certain conditions in non-invasive breast carcinoma.

[Laparoscopic preliminary surgery of ovarian malignancies. Experiences from 127 German gynecologic clinics]. / Laparoskopisches "Anoperieren" von ovariellen Malignomen. Erfahrungen aus 127 deutschen Frauenkliniken.

A controversial discussion has arisen between endoscopists and oncologists about laparoscopic management of ovarian cancer and borderline tumours. A questionnaire was mailed to 273 German Departments of Gyn./Obst. A response rate of 46% (127 hospitals) was obtained concerning the endoscopical technique used, the kind and delay of post-endoscopical cancer operation and the early findings (follow-up) in cases of ovarian cancer, dysgerminoma, malignant teratoma, tubal cancer and borderline tumours of the ovary. In this German survey it could be shown that laparoscopic management of malignant ovarian tumours was not uncommon between 1991-1994. Totally, 61% of ovarian cancer stage Ia and 84% of ovarian borderline tumours stage Ia have been reported without any pathological finding in laparotomy subsequent to laparoscopic management of the lesions. The 192 cases cited here are undoubtedly an underestimate of the real present frequency of endoscopically managed ovarian malignancies. Patients with this early "negative" report should be followed up carefully and may not permit conclusions that laparoscopic management of ovarian malignancies may be harmless for them. In 16% of the stage Ia borderline tumours and in 39% of the stage Ia ovarian cancer early spread has been found totally, demonstrating that implantations and metastases subsequent to the endoscopical procedure can be found even in an early follow-up phase. In 92.4% laparoscopic capsule rupture, tumour morcellement with intraabdominal spilling, subsequent cystectomy or adnectomy had been the technique of choice with additional rinsing of the intraabdominal cavity. This was harmful for the majority of patients if the subsequent cancer surgery by laparotomy was delayed for more than 8 days. Early progression of these cases to stage I c has been reported in 20% (7/36 cases) and to stage II-III in 53% (19/36 cases). Only in 7.4% the endobag procedure was used in laparoscopic management of ovarian cancer stage Ia. In ovarian cancer stage Ic-III (n = 50) an early seeding in the laparoscopic tract was reported in 52% (13/25) if subsequent cancer surgery by laparotomy was delayed more than 8 days. The endoscopical techniques and the early findings after an endoscopical management are reported in detail. In conclusion, in respect of common oncological standards the actual practice in laparoscopic management of ovarian malignancy is considered poor surgery. Capsule rupture, tumour morcellement and unprotected "biopsy" in the intraabdominal cavity and an additional delay of adequate cancer surgery are the main pitfalls of that procedure. For the overwhelming majority of patients undergoing such endoscopical procedures very early implants and metastases in the pelvis, the abdominal cavity or the laparoscopic tract have been found. It seems necessary that laparoscopic management of ovarian malignancies and borderline tumours under the present technical conditions are given up and that we should return to reliable standards of oncological surgery comparable to laparotomy. This should be discussed urgently.

[Risk of hematogenous metastasis of cancer of the uterine cervix]. / Uber das Risiko der hämatogenen Fernmetastasierung beim Karzinom der Cervix uteri.

Metastasis development in cervical cancer was analysed retrospectively to determine whether haematogenic metastases occurred with higher frequency in younger women than in older women. Based on clinical and morphologic data, parameters for the identification of a high-risk group for the development of haematogenic metastases were established. The data of 533 patients who underwent therapy at the University Women's Hospital Berlin-Charlottenburg from 1970 to 1984 were evaluated. 11.8% of these patients developed haematogenic metastases. No significant difference was found in the 5-year risk for development of haematogenic metastases between different age groups. Furthermore, no increase in the incidence of haematogenic metastases was found in women under 35 years in the course of time. The influence of pretreatment characteristics for the development of haematogenic metastases was assessed in 185 patients who underwent surgery for cervical cancer from 1979 to 1984. Univariate as well as multivariate regression analysis of histopathologic characteristics in the surgical specimens revealed blood vessel invasion, tumour grading, dissociated tumour growth, and number of mitoses as important parameters for the occurrence of haematogenic metastases. In this study group, patient age strongly influenced the occurrence of haematogenic metastases. In contrast, prognostic parameters for the development of local recurrence of the disease were derived from morphologic data which described the locoregional spread of the tumour (staging, tumour growth beyond the cervix, involvement of the corpus uteri, and lymph node involvement).(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhuman practices in gynecology in national socialism and its victims. Study of concrete results]. / Uber inhumane Praktiken der Frauenheilkunde im Nationalsozialismus und ihre Opfer. Untersuchung zu konkreten Ereignissen.

In our opinion German gynaecology has failed to adequately face what came to pass during the Nazi period. This can be proved objectively, for there is no evidence that, after 1945, gynaecology had in any way cared to take notice--either thermatically or medically--of the thousands of victims of inhuman practices such as forced termination of pregnancy, compulsory sterilisation and the like. During the past 50 years recollections of enforced sterilisations, compulsory abortions, deliberate and hence criminal negligence and problematic approaches in research and teaching were almost completely banished from the area of conscious awareness and largely suppressed or silently ignored. Most of the medical directors of Departments of Gynaecology of German universities shared this view whenever they were questioned on the connections between gynaecology and Nazism. Now that two generations have passed it seems possible to examine and explore with less guilt feelings and shame the immensely fateful rôle of gynaecology in that context. Accent should be on the fate of the victims of that period. To bring back these events to memory, however, does not permit to conceal the part played by the physicians committing of these inhuman Nazi crimes. Data collected from a psychosomatically oriented examination of victims exemplify that to concretely recall gynaecology during Nazism a1-so offers a chance in several respects. One of the possibilities in this context is to signal "late apology" and regret to patients who had been victims, in one's own area of work, after one has psychically worked over their fate. Besides, a gynaecological-psychosomatic expertise will help e.g. that compulsorily sterilised women are granted financial aid that has at long last become a legal possibility and can be applied for since 1980. However, the relevant patient records do show very clearly that the inhuman practice of gynaecology during the so-called "Third Reich" was not only a collective problem but equally due to a failure of the individual conscience of numerous gynaecologists. Working over this complex may enhance our own sensitivity for psychosomatic and ethic problems and counteract any likelihood of a recurrence of an inhuman gynaecology.

[Late disorders of bladder function after Wertheim operation--an analysis of urodynamic parameters with reference to surgical radicality]. / Späte Blasenfunktionsstörungen nach Wertheim-Operation--eine Analyse von urodynamischen Parametern unter Berücksichtigung der operativen Radikalität.

Permanent disturbances of bladder function are the most unpleasant and least tolerated side effects in patients, who underwent Wertheim hysterectomy because of cervical cancer. The cause of this problem with respect to the radical nature of the operation in relation to the possibly and responsible anatomical structures (sacrouterine ligament, parametrium, paracolpium) has not been completely elucidated. The aim of this prospective study was, to determine this interrelation in 39 (out of 120 radically hysterectomised) patients subjected to urodynamic examination preoperatively and 6-8 months postoperatively after Wertheim hysterectomy. With regard to preserved or lost postoperative bladder sensitivity, no correlation was found to either the length of the vaginal cuff or the parametric tissue. A statistically significant correlation was found between the length of the resected parametric tissue and the onset of postoperative stress urinary incontinence. Furthermore, there was a statistically significant correlation between the length of the resected vaginal cuff and the bladder capacity. The urodynamic parameters of maximum flow-rate, flow-time and residuals correlated rather with the radical nature of removal of the parametrial tissue than with the radicality of the vaginal resection, but that was not significant. The study leads to the conclusion, that within the variations of radical hysterectomy with medium radicality (Wagner-Wertheim procedure), the results presented here are not strikingly different regarding postoperative disturbances of bladder function. To determine such differences, investigations after more radical procedures (e.g. Latzko) would be more suitable.

[Neuroendocrine cancer of the uterine cervix: an especially aggressive form of cancer with clinical, diagnostic and therapeutic characteristics]. / Das neuroendokrine Karzinom der Cervix uteri: Eine besonders aggressive Krebsform mit klinischen, diagnostschen und therapeutischen Besonderheiten.

The compilation of neuroendocrine carcinomas of the cervix uteri comprises a rare group of carcinomas characterised by particularly aggressive behaviour. These carcinomas can be described and differentiated from similar carcinomas with different biological behaviour by light microscopy and immunohistochemical investigations. We present three patients with neuroendocrine carcinoma of the cervix, stage I b, all of them operated according to Wertheim's operation with pelvic lymphadenectomy and in one case paraaortal lymphadenectomy. In all three cases we found a clinical manifestation of hematogenic metastases. Since we are not aware of any reports on this form of carcinoma in German literature, we would emphasise the importance of diagnostic differentiation between neuroendocrine carcinomas of the cervix and other similar carcinomas of this localisation, in particular since this form of carcinoma requires specific therapeutic procedures.

[Adenocarcinoma and adenosis of the vagina. On the histogenesis, diagnosis and therapy of a rare genital neoplasms]. / Adenokarzinom und Adenose der Vagina. Zur Histogenese, Diagnostik und Therapie einer seltenen Genitalneoplasie.

In the United States, vaginal adenosis and clear-cell carcinoma of the vagina were frequently observed in young women, who had been exposed to the synthetic estrogen diethyl-stilbestrol (DES) during their embryonic development. In Germany, obviously, no such exposure occurred. Clearly, such diseases also develop without the context of intrauterine exposure to certain substances. Our own case of such a partly exophytic, partly endophytic adeno-carcinoma of the vagina with multifocal vaginal adenosis, demonstrates the histogenesis, symptoms, diagnostic procedures and therapy of this rare disease. Since young women during their reproductive years are mostly affected, the possibility of fertility-conserving surgery is discussed despite the current practice of radical cancer surgery (with and without radiation). In the 25-year-old patient, we conducted a colpectomy whilst leaving the uterus and ovaries, and replaced the vaginal defect by a sigmoid transplant anastomosed to the cervix. The patient has regular menstrual cycles, should, however, not become pregnant for 1 to 2 years for oncological reasons.

[Serous papillary adenocarcinoma of the endometrium]. / Das serös papilläre Adenokarzinom des Endometriums.

7 cases of serous-papillary adenocarcinoma of the endometrium (UPSC) were found in a retrospective study of 80 patients which were treated at the Department of Gynaecology of the University of Munich from August 1987 to December 1989 because of endometrial adenocarcinoma. Characteristic histologic findings and prognostic factors of the UPSC were examined by means of large scale sections of the completely worked-up uteri and compared with the usual adenocarcinoma of the endometrioid type (UEC). Despite only minimal myometrial infiltration in some cases, lymphangiosis carcinomatosa was almost always present (6/7) and more than 50% of patients showed evidence of blood vessel involvement. In all patients with pelvic lymph node dissection metastases were found. According to our results in line with the literature, UPSC is a highly malignant and morphologically distinct variant of endometrial adenocarcinoma without promising treatment to date.

[Differentiated operative therapy of endometrial carcinomas]. / Differenzierte operative Therapie des Endometriumkarzinoms.

The traditional surgical procedure to treat operable endometrial cancer is the removal of the uterus and both adnexa. In the trend of modern gynecological oncology this standardized operation should be changed in favour to a more individual procedure adapted to preoperative and intraoperative stage of the disease. A carefully fractioned curettage (of the cervix and the corpus uteri) is necessary to differ stage I (T1) and stage II (T2). Further important prognostic factors as myometrial invasion, nodal status, lymph vessel and blood vessel involvement and the intraabdominal findings (T3) are details of the post-surgical evaluation. A differentiated surgical treatment of the endometrial cancer includes for a stage I disease hysterectomy, bilateral adnectomy and pelvine lymphonodectomy. We recommend this additional procedure in all stages of the disease: The nodal status is for almost all genital cancers and breast cancer the most important prognostic factor. Postoperative adjuvent therapy (radiotherapy, hormonal therapy, chemotherapy) may be indicated by that. The surgical procedure for stage II (corpus and cervix involved) disease is a radical hysterectomy (Wertheim), bilateral adnectomy and pelvine lymphonodectomy. A paraaortal lymphonodectomy may be recommended, but most of the patients are 70 years and more and have a multimorbidity. Therefore, we indicated this additional procedure only in 7.5% of the operated patients. The surgical strategy in the (rare) stage III individual cancer is similar to the procedure in progressive ovarian cancer: Cytoreduction and debulking (e.g. omentum majus, peritoneum, involved bowel) has to be performed subsequent to hysterectomy, bilateral adnectomy and lymphonodectomy to improve the poor prognosis.