Bernd Gerber

Perioperative screening for metastatic disease is not indicated in patients with primary breast cancer and no clinical signs of tumor spread

AbstractBackground. Is a perioperative metastatic screening program indicated in patients presenting with primary operable breast cancer and no signs of distant metastases? Patients and methods. The impact of staging results (chest X-ray, bone scanning, liver ultrasound) for prognosis, treatment, quality of life and costs was retrospectively analyzed in 1076 patients with an operable breast cancer and no clinical signs of metastases. Results. Staging examinations revealed 30 (2.8%) distant metastases, 130 (12.1%) suspect findings and excluded metastases in 916 (85.1%) patients. Further diagnostic procedures confirmed distant metastases in 7 (5.4%) and excluded them in 123 (94.6%) out of 130 patients with suspect findings. Distant metastases were detected more frequently with increasing pathological tumor size (pT ≤q 2.0 cm: 1.6%, pT 2.1–5.0 cm: 3.0%, respectively pT > 5.0 cm: 15.1%; p < 0.001) and increasing number of involved axillary lymph nodes (pN0: 1.9%, pN1–3+: 1.8%, pN4–9+: 4.0%, pN ≥ 10+: 18.7%; p < 0.001). Due to false positive findings 123 (11.4%) patients had to live for a significant period of time with the psychological distress of suspected metastatic disease. The abandonment of a perioperative screening in 1076 patients saves costs of at least Euro 259,367.68. Conclusions. In breast cancer patients without clinical signs of tumor spread perioperative screening for metastases is not warranted because of low frequency of metastases, false positive findings, missing therapeutic consequences and high costs.

Pathologic Nipple Discharge: Surgery Is Imperative in Postmenopausal Women

BackgroundA total of 10% to 15% of pathologic nipple discharge in women is due to malignant lesions of the breast. The purpose of this study was to discover the rate of breast cancer in women who present with this symptom and undergo ductal excision, to evaluate the different diagnostic methods used before surgery, and to discover whether there are specific factors with regard to dignity.MethodsWe analyzed 118 ductal excisions in 116 patients performed at the women’s hospital of the University of Rostock, Germany, between 1995 and 2002. The discharging duct was identified by preoperative galactography.ResultsThe rate of cancer in these patients was 9.3% (n = 11). The most frequent benign lesion was intraductal papillomatous proliferation (36.4%; n = 43). Solitary papillomas were shown in 21.2% (n = 25), and other specific benign histologic findings were shown in 27.1% (n = 32). Women with malignancies were significantly older (P = .009) and were more often postmenopausal (P = .095) compared with patients with benign histology. Galactography was the method that reached the highest sensitivity (73%), and clinical examination showed the highest specificity (85%) in distinguishing between benign and malignant lesions.ConclusionsBecause 94.1% of all cases presented with specific histological findings causing pathologic nipple discharge, ductal excision combined with preoperative galactography was proven to be a sufficient method for diagnosis and therapy. This procedure should be performed in all postmenopausal women with this symptom because of a cancer rate of 12.7% among this age group and the unsatisfactory quality of other diagnostic methods.

Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases

BackgroundThe number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment.MethodRetrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R0 resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15° of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years.ResultsThe primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients (n=810) and in the lateral hemisphere of the breast in 66.4% (n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location (P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor (P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98).ConclusionWe conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.

Expression of the inhibin/activin subunits alpha (α), beta-A (βA) and beta-B (βB) in benign human endometrial polyps and tamoxifen-associated polyps

BackgroundInhibins (INH) are dimeric glycoproteins, composed of an alpha subunit (INH-α) and one of two possible beta subunits (INH-βA or INH-βB). They have substantial roles in human reproduction and in endocrine-responsive tumours. Therefore, the aims of this study were to determine the frequency and tissue distribution of INH-α, INH-βA and INH-βB in normal human endometrium and glandular-cystic endometrial polyps, and polyps caused by tamoxifen use.Materials and methodsTissue samples were obtained from women in the proliferative, early secretory and late secretory phase as well as glandular-cystic polyps and endometrial polyps associated with tamoxifen use (n=5 each). Immunohistochemistry with specific monoclonal antibodies, a semi-quantitative analysis and statistical evaluation was performed.ResultsINH-α, INH-βA and INH-βB were primarily observed in glandular and luminal epithelial cells, with a variant staining intensity in stromal cells. INH-α in glands was significantly higher during the early secretory phase (p<0.05) and the late secretory phase (p<0.01) than in the proliferative phase with a significant difference between the early secretory and the late secretory phases (p<0.01). INH-βA expression was significantly higher during the late secretory than the proliferative phase (p<0.05) and the late secretory than the early secretory phase (p<0.05), with no significant differences for INH-βB. Glandular-cystic polyps showed significantly lower expression of INH-α and INH-βA than the late secretory endometria (p<0.05 and p<0.01 respectively). Additionally, tamoxifen-associated polyps also demonstrated a significantly lower expression of INH-α and INH-βA than late secretory endometria (p<0.01 and p<0.01 respectively). No statistical differences were observed between tamoxifen-associated and glandular-cystic polyps.DiscussionINH-α, INH-βA and INH-βB were expressed in normal endometrium and endometrial polyps. A cyclical expression of INH-α and INH-βA in normal glands may reflect a functional and hormone-dependent role in human endometrium. Significant differences in staining reaction between the late secretory endometria and polyps suggest that this tissue remains in the proliferating state rather than the secretory state. Therefore, endometrial polyps may be tumours of dysregulation with mainly proliferating characteristics, being unable to synchronise with normal endometrium.

Comparative Analysis Between the HER2 Status in Primary Breast Cancer Tissue and the Detection of Isolated Tumor Cells in the Bone Marrow

The presence of isolated tumor cells in the bone marrow (ITC-BM) of breast cancer patients is an independent prognostic parameter, indicating hematogenous tumor cell dissemination. While the HER2 status of breast cancer tissue has predictive value for the efficacy of different therapies, its prognostic relevance is controversial. To investigate the relationship between HER2 and ITC-BM, we retrospectively analyzed tumor tissues of 327 patients who underwent bone marrow aspiration at primary diagnosis or during the disease-free interval. Screening for ITC-BM was performed immunocytochemically, using the anti-cytokeratin antibody A45 B/B3. HER2 was determined by immunohistochemistry (IHC) with the antibody CB 11 (n= 277) and by fluorescence in situ hybridization (FISH, PathVision, Vysis, n= 206).ITC-BM were found in 83 of 327 patients (25.4%), with a median of 2.0 per 2 × 106mononuclear cells. HER2 positivity (2+/3+) was demonstrated in 18.8% of the tumors, amplification by FISH in 56 of 206 cases (27.2%). Established pathological parameters,tiviathological parameters, such as tumor size (p= 0.15), lymph node status (p= 0.93) and HER2 did not predict the presence of ITC-BM. After a median follow-up of 49months (1–255), the presence of ITC-BM was a significant prognostic factor for distant disease free and overall survival, as well in univariate (log-rank-test, p= 0.024) as in multivariate analysis (cox-regression, p= 0.033 ). This also was confirmed in subgroups of patients by aease free survival (p= 0.013) and local recurrence (p= 0.003).The detection of ITC-BM is superior in predicting overall survival, compared to the HER2 status of the primary tumor. The direct identification of HER2 on ITC-BM is the aim of ongoing research, potentially synergizing the prognostic relevance of ITC-BM and the predictive value of the HER2 status.

Treatment of pregnancy associated gynaecological malignancies

Pregnancy, leading to new life, on one hand, and life threatening malignancies an the other hand, are per se diametric subjects. Symptoms of malignancies are ignored more frequently during pregnancy by patients and physicians, often resulting in delayed diagnosis. Diagnosis and treatment of gynaecological malignancies, however, are increasingly important for four reasons: the peak incidence of several malignancies occurs during the reproductive age; late pregnancies present more often in an age group with increased risk for cancer, intensified care for pregnant women leads to more thorough diagnosis, and, curative treatment of malignancies gives women the potential chance for becoming pregnant. For these reasons, special features of the diagnosis and treatment of gynaecological malignancies will regularly part of routine patient care. This review article covers certain practice related features of gynaecological malignancies.

Immunhistologischer Tumorzellnachweis an Lymphknoten beim nodal-negativen Mammakarzinom: Korrelation mit “etablierten” und “neueren” Prognosefaktoren

Fragestellung: Die Bedeutung von immunhistologisch detektierten Tumorzellen in axillAren Lymphknoten und ihre Beziehung zu anderen Prognoseparametern werden untersucht. Methoden: 1807 axIllAre Lymphknoten von 122 pT1-2N₀M₀-Patientinnen wurden mit einem Panzytokeratin-AntikOrper untersucht. Klinische Daten, histologische Befunde, etablierte und neuere Prognoseparameter wurden zudem bestimmt. Die mittlere Nachbeobachtungszeit betrAgt 50 Monate. Ergebnisse: Der immunhistologische Tumorzellnachweis in den Lymphknoten von 16 der 122 (13,1 %) Patientinnen war mit einem kUrzerem krankheitsfreien Uber-leben (p = 0,03) verbunden. In der multivariaten Analyse mit dem Cox-Regressionsmodell wurden TumorgrOΒe, Grading, GefAΒinvasion und S-Phase als unabhAngige Prognoseparameter, nicht jedoch der Tumorzellachweis bestAtigt. SchluΒfolgerung: Immunhistologisch nachgewiesene Tumorzellen in axillAren Lymphknoten sind prognostisch und therapeutisch bedeutsam, stellen jedoch keinen unabhAngigen Prognoseparameter dar.

Port-site metastasis after diagnostic laparoscopy for presumably benign ruptured ovarian cyst: disseminated intraperitoneal metastasis of a Krukenberg tumor

The occurrence of port-site metastasis (PSM) has been reported largely after surgical laparoscopy for gastrointestinal and gynecological carcinomas, mainly ovarian and cervical neoplasia. We present an uncommon case of a port-site metastasis after diagnostic laparoscopy for presumably benign ruptured ovarian cyst, which turned out to be a disseminated intraperitoneal metastasis of a Krukenberg tumor. Although such tumors are rare, every surgeon should be aware of their incidence, especially in relation to the clinical presentation, the younger patient age and peritoneal metastasis of an unknown primary tumor. Since the risk related to PSM after laparoscopic surgery for malignancy still has to be determined, preventive measures should be encouraged when laparoscopy is carried out and intraoperatively ascites or peritoneal carcinosis is being diagnosed.