Preoperative transforming growth factor-beta 1 (TGF-beta 1) plasma levels in operable breast cancer patients.

OBJECTIVES: The aim of this project was to search for new risk prognostic markers in the early stage of breast cancer. We tested preoperative plasma transforming growth factor - beta 1 (TGF- beta 1) levels in patients with operable breast cancer. Correlation with traditional prognostic markers and with positivity/negativity sentinel lymph node was evaluated. MATERIALS AND METHODS: Between 2003 and 2005, 36 patients with operable breast cancer (T1-2, N0-1, M0) with positive or negative sentinel lymph nodes were evaluated for their plasma TGF-beta 1. Twenty-seven healthy individuals (9 premenopausal and 18 postmenopausal) served as controls. Patients were evaluated for the traditional prognostic markers including tumor characteristics, positivity and negativity of sentinel lymph node, TNM, tumor grade, expression of tumor markers CA 15-3 and CEA, hormonal status (pre- or postmenopausal patients, estrogen and progesteron receptor expression), ERB and p53 expression. Predictive value of TGF-beta 1 level and correlation with either of the assessed parameters was tested by one way ANOVA analysis. RESULTS: Measurements of preoperative plasma TGF-beta 1 levels in patients with operable breast cancer were significantly higher compared with healthy individuals (median 15293 and 3983 pg/ml p < 0.0001). TGF-beta 1 level in plasma of patients with a positive sentinel lymph node was significantly higher than in patients with negative sentinel lymph nodes (high vs low, median 18,9 and 14,5 ng/ml, respectively, p = 0.05). CONCLUSION: The determination of TGF-beta 1 status might help to identify a high-risk population early in tumor progression, for which a more appropriate therapy should be established. In the node-negative population, the up-regulation of TGF-beta 1 might constitute an early event that promotes further progression of breast tumors.

[The clinical significance of sentinel lymph node micrometastases in breast cancer]. / Klinický význam mikrometastáz karcinomu prsu v sentinelové uzline.

OBJECTIVE: The advent of sentinel lymph node biopsy and improvements in histopathological and immunohistochemical analysis has increased the rate at which micrometastases are identified. However their significance has been the subject of much debate. Published studies have reported divergent results regarding the significance and implications of axillary lymph node micrometastases. Some studies demonstrate no associations, whilst others have found these to be indicators of poor prognosis, associated with non-SLN involvement, in addition to local and distant failure. The objective of our study was to evaluate the impact of sentinel lymph node micrometastatic cancer to prognosis of the disease. DESIGN: Retrospective study. SETTING: Departments of Gynecology and Obstetrics, Faculty Hospital, Prague. METHODS: From January 2000 to December 2006 in 87 cases with sentinel axillary node negative cancer we reexamined the axillary tissue blocks by serial sectioning, haematoxilin-eosin staining and immunohistochemistry. Additional 15 cases of micrometastatic sentinel node involvement detected by frozen section were included. The overall and disease free survivals of patients with sentinel negative status (N0-67 cases) and with sentinel node micrometastases (Nmic-35 cases) were evaluated. The median follow-up was 60 months (24-96 months). RESULTS: Micrometastases (Nmic) were found in 20 cases (23%). From the group of 67 nodes negative patients (N0) in 7 cases (10.5%) developed tumor recurrence and from the group of 35 Nmic in 5 cases developed five tumor recurrences (13.3%). In the group of N0 patients developed 2 regional recurrences and 3 patients died, but 2 patients died of other causes. In the group of Nmic developed one regional recurrence and 3 patients died of generalization of disease. CONCLUSION: Our study demonstrated that the presence of sentinel node micrometastases is associated with risk of development of distant metastases and generalization of the disease, but not with higher risk of regional recurrence.

[Detection of postoperative lymphoedema in patients with breast cancer]. / Detekce pooperacního lymfedému u pacientek s karcinomem prsu.

OBJECTIVE: Lymphoedema is a severe postoperative complication after treatment of many malignancies. It is a pathological accumulation of extracellular water (ECW). Early diagnostic tool is needed. Multifrequency bioimpedance analysis (MFBIA) is a method for detection of changes in ECW. TYPE OF STUDY: Prospective study. SETTING: Dept. of Obstetrics and Gynaecology of the 2nd Medical Faculty, Charles University, Prague. METHODS: We measured a control group of 72 women and a group of 74 patients undergoing a breast cancer surgery during 18 month after the surgery by MFBIA and circumferency. Characteristics of the patients were recorded. The detection of lymphoedema was done using MFBIA, circumferency measurement and upon the symptoms of the patients. RESULTS: The average age in the controll and tested group was 40,1 and 58,9 years. The average size of the tumour, grade and positivity if oestrogen receptors was 15,1 mm, 2,04 and 43%. In 23 patients (21%) complete lymphadenectomy was performed, in 51 patients (79%) a detection of sentinel lymph node was performed. Lymphoedema was detected in 8 women (11%). In these patients MFBIA detected lymphoedema 9 month earlier in total than other methods. CONCLUSION: MFBIA is a low-cost and precise method for the detection od early stage postoperative lymphoedema. We recommend to incorporate MFBIA into standard dispensatory plan of every patient combined with circumferency measurement.

[A set of patients with breast cancer associated with pregnancy]. / Soubor pacientek s karcinomem prsu v souvislosti s tehotenstvím.

OBJECTIVE: The aim of our study is to follow patients diagnosed with breast cancer associated with pregnancy. DESIGN: Prospective follow-up study. SETTING: Department of Obstetrics and Gynecology of the 2nd Medical Faculty of the Charles University and Faculty Hospital Motol, Prague. METHODS: Between the year 2002 and 2006 12 women were reffered to our department, seven with the diagnosis of breast cancer during pregnancy, three within one year after the delivery, two pregnant after the therapy for breast cancer. A managment was sellected individually with respect to the age of pregnancy, the stage of the disease and to the decision of the women. The average age of the diagnosis, managment, way of delivery, fetal and maternal outcome were recorded. RESULTS: The average age was 31.7 years. Two patients underwent a termination of the pregnancy, other delivered a healthy newborn. Two of our patients are dead, three have a metastatic disease, one was lost for follow-up, the rest are further followed. CONCLUSIONS: Breast cancer diagnosed during pregnancy is a special and rare situation, which needs to be managed individually as there is a lack of information about such patients. These patients should be concentrated in specialized centers.

[Transforming growth factor-beta 1 as a marker in patients with operable breast cancer]. / Transformacní rustový faktor--beta 1 jako marker u pacientek s operabilním karcinomem prsu.

UNLABELLED: OBJECTIVE AND DESIGN OF STUDY: Determination of TGF-beta 1 levels in plasma of patients with operable breast cancer. The correlation of TGF levels with the stage of disease and other prognostic markers. Prospective study. METHODS: There were 36 patients fulfilling the entrance criteria included in the study. The blood samples were taken to set the plasma levels of TGF-beta before the operation, with no adjuvant therapy. 27 age matched healthy volunteers served as controls. The study was approved by ethical board and patients signed informed consent regarding blood sampling and results presentation. Differences between groups were determined using the Mann-Whitney U-test. RESULTS: We proved that TGF-beta 1 levels are elevated in patients with operable breast cancer. Moreover, TGF-beta in plasma of patients with positive sentinel lymph node was significantly higher as compared to patients with negative sentinel node. Most important is the fact that patients involved in our study were in very early stages of disease. CONCLUSION: TGF-beta 1 is marker correlating with breast cancer disease risk factors, especially with positive sentinel lymph node. We conclude that TGF is one of the early markers which may help define the risk of disease progression already before the operation.

Radioguided occult lesion localisation in combination with detection of the sentinel lymph node in non-palpable breast cancer tumours.

PURPOSE OF THE INVESTIGATION: The aim of study was to determine the efficacy of radioguided occult lesion localisation (ROLL) for non-palpable invasive breast cancer combined with sentinel lymph node biopsy (SLNB) and to compare the amount of tissue excised by radioguided navigation versus the hook-wire technique. METHODS: We injected 45 MBq of radiolabelled technetium intratumourally and 15 MBq subdermally 18 hours before surgery in 21 women with bioptically verified non-palpable breast cancer. We identified by gamma probe non-palpable tumours, which were excised, followed by identification and excision of the sentinel lymph node. We compared our results with a group of 12 women with non-palpable lesions marked by hook-wire localisation. RESULTS: ROLL combined with SLNB was successful in 100%; volume of excised tissue was smaller in the hook-wire group but expressed higher variability in volume than in the ROLL group although the difference was not statistically significant. CONCLUSION: The method of ROLL combined with SLNB is technically possible and safe, resulting in minimisation of the surgical intervention and a decrease in postoperative morbidity. ROLL was more precise than the hook-wire procedure even though the amount of tissue excised was the same in both groups.

[New method for detection of nonpalpable breast cancer]. / Nová metoda detekce nehmatných karcinomu prsu.

OBJECTIVE: The objective of the study was to evaluate the feasibility of radio guided occult lesion localization (ROLL) in the cases of nonpalpable breast cancers with sentinel lymph node biopsy. DESIGN: Prospective clinical study SETTING: Department of Gynecology and Obstetrics, 2nd Medical Faculty and Teaching Hospital, Praha METHODS: Thirty-eight patients with nonpalpable breast cancer diagnosed by core cut biopsy underwent an injection of the radiopharmaceutical 18-20 hours before surgery. The dose of the radiopharmaceutical was 45 MBg into tumor and 15 MBg subdermaly. Surgical excision of radioactive breast tissue with nonpalpable tumor was carried out using the hand held gamma probe and the same technique was performed for biopsy of sentinel lymph node. Standard localization technique with hook-wire was performed in the control group of fifty-one patients. RESULTS: Radioguided surgery of nonpalpable tumor was successful in all cases. Surgical margins were clear in all cases, in four cases (10.5%) the margins were only 2 mm. The sentinel node was identified in all cases, in 3 patients (7.9%) the sentinel node was involved by tumor and axillary lymphadenectomy was performed. Infiltrating carcinomas were diagnosed in the "hook-wire" group in 21 cases (41.2%), all with clear margins over 3mm. Proportion of margins status between ROLL and hook-wire was the same. It seems that the health tissue loss around the tumor is in hook-wire technique bigger but it requires next study. CONCLUSION: Simultaneous performance of ROLL and sentinel node biopsy is useful and practicable methods in the management of nonpalpable breast cancer. In comparison to hook-wire, radioguided removal allows reduced excision volume and better lesion centering within the specimen.

[Sentinel lymphatic node biopsy for breast cancer in practice]. / Biopsie sentinelové lymfatické uzliny u karcinomu prsu v praxi.

OBJECTIVE: This paper reviewed the feasibility and accuracy of sentinel lymph node status in women with breast cancer. DESIGN: Clinical retrospective study. SETTING: Dept. of Obstetrics and Gynecology, 2nd Medical School, Teaching Hospital Motol, Praha. METHODS: Our trial involved 169 patients with breast cancer in the T1 and T2 stage without suspicion for axillary lymph node involvement. Lymphatic mapping was performed by sub dermal or subareolar injection of 99mTc labeled collodial human albumin (Senti-Scint) in the dose of 15 MBg one day before surgery. During the operation lymphatic mapping with vital blue dye (patent blau) was performed. Then the hand-held gamma-ray detector probe was used to locate the sentinel node. From a small axillary incision the blue-stained sentinel node was removed. Both methods of detection were compared, the sentinel lymph node has to be hot-radioactive and blue-stained. Complete axillary lymphadenectomy was then done. All removed lymph nodes were prepared for histopathological examination. RESULTS: Failures of sentinel lymph node detection were in 9 cases (5.3%) of the 169 patients. There was one case of false negative sentinel lymph node biopsy (0.6%). Most failures occurred during the learning phase of lymphatic mapping and were associated with excessive tumor involvement of axillary lymph nodes. Success of sentinel lymph node detection was in 160 cases (94.7%) and in our trial both methods of lymphatic mapping were equally effective. Tumor involvement of sentinel lymph nodes were in 43 patients (26.9%), in 19 (11.9%) of them, the sentinel nodes were the only metastasis nodes, whereas in the remaining 24 (15%) patients other axillary nodes were positive. The concordance between negative sentinel node and axillary lymph node status was in 117 (73.1%) cases. CONCLUSION: The introduction of sentinel lymph node biopsy allows directed and accurate assessment of axillary involvement with minimal morbidity. Sentinel node accurately predicts the status of all axillary nodes in more than 94.7% of cases.

[Hormone replacement therapy, proliferation in the breast and risk of carcinoma]. / Hormonální substitucní lécba, proliferace prsu a riziko karcinomu.

OBJECTIVE: The objective of the study was to investigate the changes of histopathological and immunohistochemical parameters of breast tissue among the HRT users. DESIGN: Prospective, pilot study. SETTING: Departments of Gynecology and Obstetrics, Pathology and Radiology of the 2nd Medical School, Charles University and the Teaching Hospital Motol, Praha 5, Czech Republic. METHODS: The samples of breast issue were obtained by core cut biopsy and during the breast surgery procedures in the study group of HRT users (no = 48) and in the control group of women without HRT (n = 22). Proliferation index (Ki-67), expression of ERB2 oncoprotein and hormonal receptors (ER, PR) were examined in the breast tissue in addition to routine histopathological examinations. RESULTS: We did not record increasing frequency of proliferative and precancerous lesions in the group of HRT users. Ki-67 expression was very low both in HRT users and in the control group of women. The values of estrogen receptors expression in breast tissue samples of women with HRT were similar to the findings in the normal breast. The values of progesterone receptor expression were higher among the HRT users then non-users, but it can be considered as a normal response of breast tissue to hormonal influence. Expression of ERB protein in HRT users was similar to that found in non-users. CONCLUSION: The findings indicate that HRT has not increased the proliferation rate of the breast tissue in our study group, so this mechanism certainly does not increase the risk of breast cancer.

[The role of laparoscopic hysterectomy in the surgical treatment of premalignant and malignant diseases of the uterine cervix and uterus]. / Uloha laparoskopické hysterektomie v chirurgické lécbe premaligních a maligních onemocnení hrdla a tela delohy.

Laparoscopic hysterectomy is a suitable surgical method in women with premalignant changes of the uterine cervix and in premalignant and malignant endometrial diseases in a selected group of women with low or medium risk. The authors consider laparoscopic lymph-adenectomy in patients with endometrial carcinoma as technically feasible, provided careful selection and indication are made. Careful preoperative examination by biopsy, hybridization probes, tumour markers, sonography, computed tomography or magnetic resonance are essential. A minimal invasive approach can be applied not only in benign diseases of organs of the lasser pelvis. Favourable convalescence parameters are the reason for integration of surgical laparoscopy with gynaecological oncology. Multicentric control studies are needed which will provide evidence that endoscopy can improve the results of hitherto used surgical treatment. Training of the modern surgeon in the sphere of gynaecological oncology involves mastering of surgical techniques of open radical operations as well as perfect endoscopic surgery and strategy.