Axillary Dissection in the Case of Positive Sentinel Lymph Nodes: Results of the Innsbruck Consensus Conference.

The prognosis of breast cancer is most heavily influenced by the status of the axillary nodes. Until a few years ago, this knowledge was gained through radical axillary lymph node clearance. In the meantime, sentinel lymph node clearance has become an established part of the surgical treatment of breast cancer. With the development of this procedure, the morbidity caused by axillary dissection has been reduced significantly. Although comprehensive prospective, randomised data regarding the safe use of the sentinel concept are only now available, the focus currently, however, is on the question of whether in the case of positive sentinel lymph nodes, an axillary dissection can be done away with altogether without having any negative impact on the risk of loco-regional recurrence or on progression-free survival and overall survival. The results of the American ACOSOG-Z001 study have changed the fundamental perspective of this. In this study on the advantages of axillary dissection following the confirmation of tumour tissue in the sentinel lymph nodes, there were no statistically significant advantages from axillary dissection for women with a favourable overall risk profile who had received radiotherapy and systemic therapy. If this concept takes hold, the surgical treatment of node-positive breast cancer, at least in the axilla, would be reduced to a minimum, and the focus of treatment would in future lie more on the systemic treatment of this condition. As part of an interdisciplinary consensus meeting, a standardised approach for Austria with regard to this question was decided upon.

Does hysteroscopy facilitate tumor cell dissemination? Incidence of peritoneal cytology from patients with early stage endometrial carcinoma following dilatation and curettage (D & C) versus hysteroscopy and D & C.

BACKGROUND: In several case reports, distension and irrigation of the uterine cavity during fluid hysteroscopy was suspected to cause tumor cell dissemination into the abdominal cavity in patients with endometrial carcinoma. It was the aim of this study to compare the incidence of positive peritoneal cytology in patients who underwent dilatation and curettage (D & C) with or without previous hysteroscopy. METHODS: The authors conducted a multicentric, retrospective cohort analysis. One hundred thirteen consecutive patients with endometrial carcinoma treated between 1996 and 1997 were included. Endometrial carcinoma had to be limited to the inner half or less than the inner half of the myometrium (pathologic Stage IA,B). Positive peritoneal cytology was obtained during staging laparotomy. Patients underwent D & C either with or without prior diagnostic fluid hysteroscopy. No selection or randomization was applied to the two groups. Positive peritoneal cytology, defined as malignant or suspicious, was considered the primary statistical endpoint. RESULTS: Peritoneal cytology was suspicious or positive in 10 of 113 patients (9%). The presence of suspicious or positive peritoneal cytology was associated with a history of hysteroscopy (P = 0.04) but not with myometrial invasion (P = 0.57), histologic subtype (P = 1.00) or grade (r = 0.16, P = 0.10), or the time between D & C and staging laparotomy (r = 0.04, P = 0.66). CONCLUSIONS: Based on the limited extent of endometrial carcinoma in the current analysis, our data strongly suggest dissemination of endometrial carcinoma cells after fluid hysteroscopy. Determining whether a positive peritoneal cytology affects the prognoses of patients without further evidence of extrauterine disease will require longer follow-up.

Impact of hysteroscopy on disease-free survival in clinically stage I endometrial cancer patients.

Recent data strongly suggest tumor cell dissemination of endometrial carcinoma cells in the course of fluid hysteroscopy. In patients who had endometrial cancer which was (except for peritoneal cytology) confined to the uterus, the disease-free survival (DFS) of 135 patients who underwent hysteroscopy prior to staging laparotomy was compared with the DFS of 127 patients without hysteroscopy. After a median follow-up of 23 months, 10 patients experienced tumor recurrence. Although there was a trend towards a higher incidence of positive peritoneal cytology at laparotomy in patients who underwent hysteroscopy, this difference did not achieve statistical significance (P = 0.47). For 5 years, the DFS was 92.4% in patients with hysteroscopy and 84.7% in patients without hysteroscopy before laparotomy (log-rank, P = 0.782). Our data therefore suggest a similar short-term DFS in endometrial cancer patients with and without hysteroscopy prior to laparotomy.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage I and II endometrial cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastasis in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated endometrial cancer. METHOD: A sample of 103 paraffin-embedded tumor specimens of surgical treated endometrial cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 95% (98/103), 87% (89/103), and 80% (82/103) of the tumour samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.28 (p = 0.004), 0.05 (p = 0.6), and -0.03 (p = 0.73), respectively. In the univariate analysis, the expression of MMP-1 (log-rank test, p = ns), MMP-2 (log-rank test, p = ns), and TIMP-2 (log-rank test, p = ns) were not associated with overall survival. CONCLUSION: MMP-1, MMP-2, and TIMP-2, detected by immunohistochemistry are not helpful in predicting the prognosis of endometrial cancer patients.

Immunohistochemical detection of matrix metalloproteinases (MMP) 1 and 2, and tissue inhibitor of metalloproteinase 2 (TIMP 2) in stage IB cervical cancer.

OBJECTIVE: Matrix metalloproteinases (MMPs) are a family of zinc-dependent metalloendopeptidases which participate in the degradation of collagen and other extracellular matrix macromolecules. Expression of gelatonic MMPs, such as MMP-2 has been linked to enhanced tumor invasion and metastases in in vitro and in vivo model systems. It was the aim of this study to determine whether the expression of MMP-1, MMP-2, and TIMP-2 correlates with survival in patients with surgically treated cervical cancer stage IB. METHODS: A sample of 154 paraffin-embedded tumor specimens of surgical treated FIGO stage IB cervical cancer was immunohistochemically investigated. RESULTS: MMP-1, MMP-2, and TIMP-2 were detected by immunohistochemistry in 74% (113/154), 32% (49/154), and 80% (107/154) of the tumor samples, respectively. Correlation coefficients for MMP-1/MMP-2, MMP-1/TIMP-2, MMP-2/TIMP-2 were 0.14 (p = 0.12), 0.37 (p = 0.0001), and 0.17 (p: 0.005), respectively. A significant correlation was found between MMP-1 and lymph node status (P < 0.01) and lymphvascular space invasion (P < 0.05). The expression of MMP-1 (log-rank test, p = 0.6), MMP-2 (log-rank test, p = 0.8), and TIMP-2 (log-rank test, p = 0.15) were not correlated with overall survival. CONCLUSION: MMP-1, detected by immunohistochemistry, seems to play a role in the development of lymphvascular space invasion and lymph node metastases, but is not helpful in predicting the prognosis of cervical cancer patients.

Endometrial cancer: accuracy of the finding of a well differentiated tumor at dilatation and curettage compared to the findings at subsequent hysterectomy.

The objective of this study was to examine the accuracy of the finding of a histologically well differentiated endometrial carcinoma at dilatation and curettage (D & C) prior to hysterectomy. A retrospective multicentric chart review of 137 endometrial cancer patients was conducted, including all patients in whom a well differentiated endometrial carcinoma had been diagnosed by D & C. Histopathologic grading as determined by D & C was compared with the grading established at the final histologic examination after hysterectomy. Seventy-eight percent of all cases in which a well differentiated tumor was diagnosed with D & C were confirmed as well differentiated endometrial carcinomas, whereas 20.4% had to be upgraded as moderately differentiated tumors after evaluation of the hysterectomy specimen. In one case in which a uterine adenocarcinoma was diagnosed by D & C, a well differentiated adenocarcinoma was found to be combined with a carcinosarcoma in the hysterectomy specimen. In order to avoid false findings of a well differentiated tumor, the histologic grade should be confirmed by intraoperative frozen section examination. This is especially important in cases in which surgical staging was not planned initially.

p53 protein overexpression: a strong prognostic factor in uterine papillary serous carcinoma.

Uterine papillary serous carcinoma (UPSC) is an uncommon but aggressive type of endometrial cancer associated with rapid progression of disease and poor prognosis. We investigated 23 cases of UPSC. p53 expression was studied in archival paraffin-embedded tissue by immunohistochemistry. Eleven tumors (47.8%) showed p53 overexpression whereas 12 tumors (52.2%) were p53 negative. One of 8 stage I/II (12.5%) and 10/15 stage III/IV (66.6%) tumors revealed p53 staining (P = 0.027). The median overall survival was 43.3 months. Patients with advanced-stage (III, IV) disease had a 5-year overall survival probability (5-year OS%) of 24% compared to 100% in those in stages I and II (log-rank, P = 0.018). Myometrial invasion, lymphatic space invasion, or lymph node involvement did not correlate with the 5-year OS of these patients. Patients whose tumors overexpressed p53 had a significantly shorter survival than those whose tumors did not (P = 0.033). This study confirms the influence of p53 overexpression on survival in UPSC patients.

Influence of postoperative treatment on survival in patients with uterine papillary serous carcinoma.

BACKGROUND: Uterine papillary serous carcinoma (UPSC) is an uncommon, aggressive type of endometrial cancer associated with an advanced stage at initial presentation, rapid progression of disease, and poor prognosis. METHODS: Twenty-three patients with UPSC were included in this study. History, treatment, follow-up, and 5-year overall survival probability (5-yr OS%) were evaluated. RESULTS: All women underwent total hysterectomy and bilateral salpingo-oophorectomy. Positive lymph nodes were found in 10 of 17 patients who underwent pelvic lymphadenectomy. Eight patients had FIGO Stage I/II, whereas 15 patients showed Stage III or IV tumors. After surgery 5 women underwent radiotherapy, 5 chemotherapy, and 8 both radiotherapy and chemotherapy. Chemotherapy consisted of cisplatin/carboplatin plus cyclophosphamide. Adjuvant irradiation consisted of vault and external beam irradiation. The median duration of follow-up was 39.4 months (25th and 75th percentiles; 26. 1, 68.1). The median overall survival was 43.3 months (12.9, 75th percentile not reached). Three of 10 patients who received only chemotherapy or radiotherapy are alive, whereas 7/8 patients who received a combination of both are alive with no evidence of disease at the time of reporting. The 5-yr OS% was 80% in those who received radio- and chemotherapy and only 30% in those who were treated with radiotherapy alone (log rank = 0.05). CONCLUSION: These results stress the need to study and evaluate the usefulness of combined chemo- and radiation therapy in patients with uterine serous papillary cancer.

The significance of determining CA 15-3 in the cytosol of breast cancer.

The identification of tumor markers in patients who had undergone operation for breast cancer provides important information in the follow-up in addition to evaluation by clinical and visual methods. The aim of our study was to determine the clinical prospective value of CA 15-3, mucin-like carcinoma-associated antigen and carcinoembryonic antigen in preoperative measurement of serum samples in patients with primary breast cancer, and to determine CA 15-3 and steroid receptors in the cytosol of the tumor. The results show that the most exact correlation occurred between serum CA 15-3 and the different stages of the tumor. However, there is no conclusive evidence for the prognosis and the course of the disease from preoperative findings of tumor markers in serum samples or in the cytosol of the tumor in patients with breast cancer.

[Heat flux measurements of the fetal scalp and cardiotocography in predicting acidosis states sub partu--a comparison of 2 methods]. / Wärmeflussmessungen vom fetalen Skalp und Kardiotokographie zur Vorhersage von Azidosezuständen sub partu--ein Vergleich zweier Methoden.

Although the efficacy of electronic foetal heart rate (FHR) monitoring and intermittent scalp blood sampling is well established, these methods still result in a considerable number of false positive and negative predictions. Consequently, methods, which improve the accuracy of prediction, are still under study. Heat flux measurements from the foetal scalp have been shown to relate to the metabolic condition of the foetus during delivery. In this study, we investigated the predictive power of measuring scalp heat flux and monitoring the FHR electronically, and the combination of both. In 136 foetuses the scalp heat flux was measured by means of a heat flux transducer, 2.5 cm in diameter, attached to the foetal scalp after the cervix had dilated to greater than 2.5 cm. Heat flux was regarded as abnormal, if the heat flux was less than 10 w/m2 or greater than 21 w/m2, or fell by more than 20% of its initial value during the last 30 min before delivery. FHR tracings were considered abnormal, if they resulted in therapeutic consequences like oxygen mask for the mother, scalp blood sampling or immediate operative delivery. Foetuses were considered acidotic, if their pH in the arterial cord blood was less than 7.20. Accuracy of prediction was described by appropriate parameters. The scalp heat flux method resulted in a higher specificity (80.4% vs. 72.5%), positive predictive value (59.2% vs. 51.7%), and overall accuracy (82% vs. 77%) than FHR monitoring. Sensitivity of FHR monitoring was slightly higher than the one of heat flux method (88.2% vs 85.3%). Combining both methods resulted in a sensitivity of 100% thus detecting all acidotic foetuses, but specificity fell to 62%.(ABSTRACT TRUNCATED AT 250 WORDS)

The metoclopramid-provocation test for prediction of transient hyperprolactinemia during cycle stimulation.

The predictive value of the metoclopramid-provocation test to detect transient hyperprolactinemia during cycle stimulation was assessed. Patients developing hyperprolactinemia during cycle stimulation showed a significantly higher PRL response to the metoclopramid-provocation test before cycle stimulation. The current study confirms previous reports that hyperprolactinemia during cycle stimulation can interfere with follicular and oocyte maturation. The use of the metoclopramid-test can detect an enhanced responsiveness to PRL stimulators and offers the possibility of treatment during cycle stimulation.

Squamous cell carcinoma (SCC) antigen in patients with invasive cervical carcinoma during primary irradiation.

In a prospective study, serum concentrations of squamous cell carcinoma (SCC) antigen were determined by radioimmunoassay from 74 healthy volunteers and 54 patients with cervical carcinoma who underwent irradiation therapy. 5.4% of the controls had SCC levels greater than 3.0 ng/ml, which was considered as upper limit of the normal range. 31/54 (57.4%) patients and 60% of the patients with SCC had elevated pretreatment levels. In all patients with pretreatment serum levels above 3.0 ng/ml, SCC serum levels decreased during irradiation therapy. 4/5 patients with posttreatment levels greater than 0.5 ng/ml developed recurrence or persistence of tumor, 1 patient could not be followed up. Good conformity was found between SCC antigen serum levels and therapy response. SCC antigen determinations during and after therapy provide a useful tool in detecting progression and persistence of tumor.

Use of CA 125 monoclonal antibody to monitor patients with ovarian cancer.

The monoclonal antibody (mAb) OC 125 reacts with an antigen on human ovarian carcinoma (OVCA) cells that is also shed into the body fluids and can be detected in patients' sera and/or ascites with a radioimmunometric assay. For the present study, serum CA 125 levels of patients (n = 36) with different stages of OVCA were investigated. Serum levels seem to correlate with tumor burden. In stages I and II (n = 12), 33% of patients were CA 125 positive, whereas 70% of stage III and IV patients (n = 24) were CA 125 positive. Mean serum levels were in 93 U/ml (stages I, II) and 279 U/ml (stages III, IV). CA 125 levels in ascites and in pleural effusions were manyfold higher than serum levels of the same patients (P less than 0.0001). Immunohistochemical investigations of CA 125 in different ovarian tumors (n = 91) revealed that 85% of malignant and 75% of borderline serous cystadenocarcinomas had detectable CA 125 surface expression. Furthermore, 71% of benign tumors showed the CA 125 epitope, whereas mucinous tumors were negative for this marker. One of six ovarian cancer cell lines was CA 125 positive, whereas in 6 of 11 patients, ascites-derived ovarian cancer cells (fresh and gradient isolated) were positive for this marker. The proportion of positive cells ranged from 10 to 90% in these samples. Intraperitoneal recombinant interferon-gamma (rIFN-gamma) therapy resulted in an increase in the number of cells reacting with CA 125. The results of monitoring in patients receiving different therapeutic regimens and/or agents demonstrate the usefulness of this marker.

CA 19-9, CA 125 and CEA in the endometrial mucosa during the menstrual cycle, in atypical hyperplasia and endometrial carcinoma.

CA 19-9, CA 125 and CEA were demonstrated by immunohistochemistry in 58 tissue samples of normal mucosa, 21 samples of atypical hyperplasia and 74 samples of endometrial carcinoma. CA 19-9 was mainly detected in the mid phase of secretion (8/11). CA 125 in the mid (6/11) and in the late phase (8/9). As opposed to CEA, both tumor markers are secretion products of the normal endometrium and are not expressed in the endometrial glands during the proliferation phase. CA 125 expression does not correlate with the degrees of differentiation or malignancy. The percentage of CA 19-9 positive cases rises with increasing differentiation. In atypical hyperplasia, however, this percentage is as small as in undifferentiated carcinoma. 93% of the endometrial carcinomas were CA 19-9, 65% CA 125 and 58% CEA positive.

Ovarian tumors of low malignant potential (borderline tumors): immune morphology and current status.

CA 125, CA 19-9 and CEA were demonstrated in tissue samples of 30 ovarian borderline tumors by immunohistochemistry. Of the 21 serous and 9 mucinous borderline tumors, 23 were in stage I and 7 stage III. None of the patients died of disease. All mucinous borderline tumors were CA 125 negative, 89% CA 19-9 positive and 44% CEA positive. 62% of the serous borderline tumors were CA 125 positive, 52% CA 19-9 and 19% CEA positive. Tumors of low malignant potential responded to CA 19-9 like invasive carcinomas. The incidence of positive responses to CA 125 ands CEA fell between that of benign and malignant tumors. The marker pattern did not correlate with tumor stage and cytological grading. The biological behavior of ovarian borderline tumors ranges between that of benign tumors and invasive carcinomas and cannot be classified as definitely belonging to either group. It is plausible that they are primarily of the borderline type, and not benign tumors that undergo malignant degeneration.

Tissue expression of CA 125 in benign and malignant lesions of ovary and fallopian tube: a comparison with CA 19-9 and CEA.

Sections of formalin-fixed and paraffin-embedded tissue specimens of 11 normal ovaries and tubes, 13 tubo-ovarian abscesses, 3 tubal carcinomas, and 115 ovarian tumors were investigated by immunohistochemistry. CA 125 and CA 19-9 were demonstrated with monoclonal antibodies, CEA with polyclonal antibodies. The tissue expression was visualized by the avidin-biotin method. In the germinal epithelium of all ovaries no tumor marker was confirmed. In 4 out of 11 tubes the epithelium was CA 125 positive, in 2 out of 11 cases CA 19-9 positive. Nine out of 13 tubo-ovarian abscesses were CA 125 and 5 out of 13 were CA 19-9 positive in their epithelium. Elevated serum levels of these markers might be due to expression via the epithelial cell of the inflamed tube. All normal and inflammatory adnexal tissues were CEA negative. In serous tumors and undifferentiated carcinomas, CA 125 was most frequently confirmed (85 and 70%, respectively). All mucinous tumors were CA 125 negative. The most frequently confirmed tumor marker was CA 19-9 (77%). In endometrioid tumors, CEA was most frequent (44%). In 42% of the borderline tumors and carcinomas only one marker was demonstrated, in 7% none. Here, immunohistochemistry may indicate the most adequate marker. Tumor marker expression was markedly heterogenous: tumor areas with strong, weak, and no reaction were adjacent. The tumor markers revealed no specificity for malignancy or disease.

[Assessment of edema in pregnancy]. / Die Bewertung von Odemen in der Schwangerschaft.

The clinical evaluation of oedemata during pregnancy is more or less subjective and not reproducible. There is no common factor to the relevance of its presence. The aim of this investigation was to check systematically the frequency and degree of generalised Oedemata and their clinical relevance. 184 pregnant women were examined for their finger circumference between the 16th and 36th week of gestation. According to the change in the circumference, three significantly different groups of oedemata were found. The group with strongly marked oedemata showed increased hypertensive complications and the highest rate of growth retarded children. This objective and simple method of measuring the finger circumference, is suggested for antenatal care.