2012, Vol 10, No 4
The immunohistochemical analysis of metallothionein in complete hydatidiform mole and in decidual cells in correlation with the applied therapy of surgery alone or surgery followed by chemotherapy
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 261-269
ABSTRACT

Introduction: The presence of metallothionein in both the endometrium and decidua is associated with the resistance of both endometrial and decidual cells to immunemediated apoptosis. Consequently, the aim of the present study has been to typify metallothionein immunoreactivity within the molar lesions of both the patients who were treated with surgery alone and those who were also given chemotherapy. Methods: We analyzed the immunoreactivity of metallothionein in both the trophoblast and decidual cells derived from patients on whom curettage was performed due to a diagnosis of complete molar pregnancy. These patients were then divided into two subgroups according to whether or not they required chemotherapy following the surgical procedure. Results: We observed a statistically significantly lower metallothionein immunoreactivity levels within the trophoblast cells derived from the complete hydatidiform mole patients who had had surgery alone in comparison to the levels found in those patients for whom surgery was followed by chemotherapy. Conclusion: Resistance to apoptosis linked with metallothionein intracellular immunoreactivity may influence the clinical course of hydatidiform mole.

Keywords: metallothionein, complete hydatidiform mole, chemotherapy, decidua, endometrium
DOWNLOAD ARTICLE (PDF)
Genital malignant tumors and precancerous conditions in female carriers of constitutional BRCA1 gene mutations undergoing prophylactic adnexectomy
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 270-285
ABSTRACT

Aim of paper: Assessment of incidence of genital malignant tumors and precancerous conditions in females undergoing prophylactic PBSO/RRSO surgery (prophylactic bilateral salpingo-oophorectomy/risk reducing salpingo-oophorectomy). Material and methods: Study population consisted of 209 women affected with one of three BRCA1 gene mutations most common in the Polish population (5382insC, 4153delA and C61G), undergoing prophylactic genital resection. Procedures were performed in asymptomatic patients and unremarkable findings in ancillary diagnostic tests. Surgeries have been performed over 11 years (since 15.09.1999 thru 31.12.2010). Analysis included number and type of malignant tumors and precancerous conditions detected at surgery as well as patients’ age at the time of diagnosis, compared with mean age of all patients in the study group. Assessed parameters included oncologic data, e.g. clinical stage, histological diagnosis, histological type and morphological malignancy grade correlated with type of constitutional mutation of the BRCA1 gene. Suggested surgery has been accepted by 81.96% (209/255) of the patients. Mean interval between consent for surgery and its execution was 13.27 months (median 4 months). Mean patients’ age at the time of preventive surgery was 48.21 years (median 49 years). In 88.99% of the cases (185/209) adnexectomy was expanded to include the uterine corpus (sparing of the cervix) or the entire uterus. Positive history of oncologic surgery was obtained in 42.11% of the cases (88/209), thereof 40.67% (85/209) operated on due to breast cancer. Results: Histological study of surgical specimens revealed the following oncologic conditions: 8 cases of asymptomatic ovarian cancer, 2 cases of primary peritoneal cancer and 2 cases of primary fallopian tube cancer (12/209 – 5.74%). Thereof, 6 ovarian cancers were at FIGO stage I and 2 at FIGO stage II. One case of asymptomatic endometrial cancer and one case of CIN3 (carcinoma in situ) cervical cancer was detected. Intraepithelial neoplasia (dysplasia) within the fallopian tubes was detected in 8.13% (17/209) of the patients. Overall, early forms of malignant tumors were detected in 7.18% (15/209) of the patients. Most cancers (73%; 11/15) were poorly differentiated (G3) of the serous type. No cases of FIGO stage III and IV disease were noticed. Most patients (62.5%) with malignant tumors and precancerous conditions harbored the insC5382 mutation. Only a single case of cancer has been diagnosed in a patient under 45 – 6.67% (1/15). Conclusions: 1) Prophylactic surgery enables detection of early clinical stages of malignant tumors in female carriers of constitutional mutations of the BRCA1 gene. 2) Preventive genital resection in female carriers of BRCA1 gene mutations is an effective way to detect asymptomatic forms of genital malignancy. 3) Fallopian tube intraepithelial neoplasia (dysplasia) is a relatively frequent condition seen at preventive surgery in BRCA1 gene mutation carriers. 4) Scope of preventive genital tract resection must be tailored depending on individual patient’s situation.

Keywords: prophylactic bilateral salpingo-oophorectomy, risk reducing salpingo-oophorectomy, BRCA1, asymptomatic cancers, ovarian cancer, tubal cancer, peritoneal cancer, intraepithelial neoplasia
DOWNLOAD ARTICLE (PDF)
Intraoperative radiotherapy in early breast cancer: effectiveness and toxicity assessment
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 286-295
ABSTRACT

Introduction: Breast-conserving therapy (BCT) with adjuvant radiotherapy in the management of patients with breast cancer is an effective alternative for mastectomy. A standard adjunct to BCT is irradiation of the entire breast for 5-7 weeks. Aim of paper: Evaluation of treatment effectiveness, analysis of early and delayed radiation-induced reactions, cosmetic effect and quality of life. Material and methods: Analysis encompassed 150 patients undergoing BCT, intraoperative radiotherapy (IORT) and external beam radiotherapy (EBRT) followed up for at least one year. Follow-up examination 1 month, 6 months, 12 months and 24 months after completion of treatment included: physical examination, breast photography, analysis of early and delayed post-radiation reactions. Nuclear magnetic resonance mammography and sonography of the breasts was obtained after 6 months of observation. Results: No cases of local recurrence have been noticed. Acute radiation-induced reaction of the skin (grade 1 and 2) developed in 21.2% patients. No cases of grade 3 and 4 reactions have been noticed. Very good and good cosmetic effect was obtained in 81.5% of the patients. Breast pain has been reported by 20.6% of the patients, and skin hyperesthesia – by 17% of them. Breast edema was seen in 81.3% of the patients 1 month, in 63.4% 6 months, in 54.9% 12 months and in 56% 2 years after completion of radiotherapy. Altered skin pigmentation was noticed in 67.8% of the patients 1 month, in 44.1% 6 months, in 37.8% 1 year and in 31% 2 years after completion of radiotherapy. Conclusion: No cases of local recurrence or severe (high-grade) radiation-induced reactions were noticed during follow-up. Intraoperative radiotherapy reduced duration of treatment by one week, enabling inclusion the entire planning target volume (PTV) by a homogenous radiation dose and reduced the risk of geographic error.

Keywords: breast cancer, intraoperative radiotherapy, treatment-related toxicity, quality of life, radiation-induced reaction
DOWNLOAD ARTICLE (PDF)
Analysis of selected problems of sentinel lymph node biopsy in patients with breast cancer
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 296-306
ABSTRACT

Sentinel lymph node biopsy in patients with early-stage breast cancer is an example of a surgical procedure which, despite its long history, has had no uniform standard of performance implemented. This is a problem which concerns both the indications and limitations of this method as well as many of the technical aspects connected with the procedure. This paper is an attempt to resolve some of the controversies mentioned above based on the clinical experience of the authors. Material and method: The group consisted of 974 patients suffering from breast cancer and treated from January 2004 through October 2011 in the Clinical Department of Breast Cancer and Reconstructive Surgery of the Oncology Center in Bydgoszcz who were also scheduled for sentinel lymph node removal. Data regarding the preoperative diagnosis of the primary tumor, such as minimally invasive methods (FNAB, core biopsy, and mammotome biopsy) or open surgical biopsy (tumorectomy, quadrantectomy, or past breast operations with no relation to the current treatment) of the location of the lesion and the sentinel lymph node identification method (combined isotope-dye, isotope, or dye method) was analyzed. Results: Ninety-four point five percent of all sought nodes were detected. The detection rate for the combined SLN marking and isotope methods amounted to 94.4% each, whereas in the case of the dye method, it amounted to 100%. Of all the patients who underwent surgery for the first time, 95.0% had the sentinel lymph node location isolated during the operation, whereas in the case of patients who had previously undergone surgical treatment of the breast or surgical biopsy of a tumor it was 92.1%. Moreover, the location of the tumor within the breast did not have a significant impact on the success of the sentinel lymph node biopsy. Conclusions: The surgical biopsy of the primary lesion preceding the removal of the sentinel lymph node does not have a significant impact on the possibility of the detection of the node sought. The situation is similar with regard to the selected method of sentinel lymph node detection and the location of the primary tumor. As a result, it is possible to extend the usage of the sentinel lymph node biopsy into a wider range of cases.

Keywords: breast cancer, sentinel node, sentinel lymph node biopsy, nodal metastases, lymphoscintigraphy
DOWNLOAD ARTICLE (PDF)
Immune phenomena associated with the development and treatment of female genital malignancies
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 307-316
ABSTRACT

A prerequisite for the development of a malignant tumor is the occurrence of a series of mutations in suppressor genes, so that cells acquire a malignant phenotype. There is no single molecular alteration that would lead a cell through a complex process of carcinogenesis. In the case of late-stage ovarian cancer, the next necessary step is the escape of these genetically altered cells from the supervision of the host immune system. Initially, the process of evasion from immune control is merely one of “cheating” the immune system. However, as the tumor increases in size, it takes control over the immune system, at least on a local scale, and the escalation of this phenomenon may result in generalized immune suppression. First, a cancer cell masks its presence, then it inhibits the non-specific immune system as well as the specific immune response by (among other things) initiating the apoptosis of the cytotoxic cells infiltrating its microenvironment. Finally, cancer cells modify their microenvironment so that it supports their development and by accumulating immunosuppressive Treg lymphocytes inhibits the immune response against them. Understanding the principles governing this phenomenon would thus appear to be key to being able to, but also to counteract it. The resulting knowledge might allow us to supplement the standard combination of antitumor treatment and immune therapy, thus improving its efficacy. Currently one of the most promising forms of immune therapy is the removal of Treg cells from the tumor microenvironment.

Keywords: immune therapy, ovarian cancer, immune tolerance, Treg, macrophages
DOWNLOAD ARTICLE (PDF)
Ovarian cancer: does it always require surgery?
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 317-325
ABSTRACT

The paper presents key aspects associated with modern approach to surgical treatment of women with ovarian cancer. It should be emphasized that the best treatment outcomes depend on optimal surgical resection and adjuvant chemotherapy based on taxanes and platinum derivatives. Primary surgical treatment includes determination of clinical stage and total excision of the tumor. If this is impossible, e.g. due to far-advanced disease, the only viable option is maximal cytoreduction. In spite of significant progress in surgical techniques and improved response to first-line chemotherapy, failure of combined treatment over the first 2 years are seen in about 40-50% of the cases. Effectiveness of treatment of recurrent disease is poor and depends on response to first-line treatment, treatment-free survival and patient’s general condition. In exceptional situations, ovarian cancer patients may undergo fertility-preserving sparing procedures. This may be an option with unilateral tumor at FIGO stage IA and IC, patient is young, plans pregnancy and willing to accept close postoperative surveillance. Treatment of ovarian cancer is an area with a tremendous potential for improvement and should remain an ongoing challenge for modern science. In such a complex therapeutic process, surgical treatment still plays a crucial role – it is always indicated in ovarian cancer patients, while its scope and technique depend on individual requirements and condition of women treated.

Keywords: ovarian tumor, ovarian cancer, surgical treatment, sparing surgery, combined treatment
DOWNLOAD ARTICLE (PDF)
Rare clinical types of breast cancer
CURR. GYNECOL. ONCOL. 2012, 10 (4), p. 326-336
ABSTRACT

Paget’s disease of the nipple may exist as an isolated condition or may be associated with breast cancer. Paget’s disease-associated breast cancer may be intraductal or invasive; depending on location, it may be retromamillary or peripheral. Surgical treatment consists in sparing procedure or breast amputation. Patients with Paget’s disease coexisting with an infiltrating breast cancer, should undergo sentinel node biopsy or axillary lymphadenectomy. Bilateral breast cancer is diagnosed in women diagnosed with primary cancer in both breasts. This definition does not include metastases of unilateral breast cancer to contralateral breast. Recommended type of surgical treatment is bilateral mastectomy and bilateral biopsy of sentinel node or axillary lymphadenectomy. Sparing treatment is a therapeutic option applicable in reference centers only. Isolated metastases of other tumors to the breasts are very rare. The usual origin of breast metastases is contralateral breast cancer. Less frequent are secondary foci of lymphoma and melanoma. Management strategy depends on what type of malignant tumor was the source of metastases. The cornerstone of treatment is usually systemic treatment, if available. Surgical treatment is limited to surgical biopsy or palliative treatment (e.g. mastectomy due to bleeding from the tumor). Occult breast cancer is diagnosed in women with metastases of adenomatous cancer, non-differentiated or non-classified to axillary lymph nodes, when neither physical nor radiological examination reveal a primary breast cancer. The most probable origin of axillary metastases is breast cancer. Surgical treatment consists in axillary lymphadenectomy and mastectomy. One may withhold from mastectomy if spared breast will undergo total radiotherapy. Breast cancer in the elderly, i.e. persons over 70, accounts for over 30% of all breast cancer cases. Surgical treatment of elderly women with breast cancer should be based on standard protocols (mastectomy or sparing treatment; biopsy of sentinel node and/or axillary lymphadenectomy). Standard treatment protocol can and should be modified when treatment-associated risk exceeds expected benefits thereof.

Keywords: Paget’s disease of the nipple, bilateral breast cancer, isolated metastases of other tumors to the breast, occult breast cancer, breast cancer in the elderly
DOWNLOAD ARTICLE (PDF)