Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy.

OBJECTIVES: Chemotherapy-induced peripheral neuropathy (CIPN) is a common chemotherapy side effect, but its prevention and treatment remains a challenge. Neurotoxicity may lead to dose limitation or even treatment discontinuation, and therefore potentially affect the efficacy of anticancer treatment and long term outcomes. The practice to administer gabapentin for neuropathy may be applicable, but is limited by insufficient studies. The aim of our study was to assess the presence of chemotherapy-induced peripheral neuropathy in ovarian cancer patients treated with first-line paclitaxel and carboplatin chemotherapy and evaluate the effectiveness of gabapentin in treatment of this condition. MATERIAL AND METHODS: 61 ovarian cancer patients treated with first line chemotherapy were included in the study. The first phase of the study was to assess neurological condition of each patient by: neuropathy symptoms scale, McGill's scale, neurological deficit and quality of life, during the chemotherapy. In the second phase of the study we evaluated the response to gabapentin treatment in a group of patients who developed neuropathy. RESULTS: 78.7% of the patients developed chemotherapy related neuropathy. During the course of chemotherapy these patients experienced significant exacerbation of neuropathy symptoms (p < 0.0001), neuropathic pain (p < 0.0001), neurologic deficit (p < 0.0012) and worsening of quality of life (p < 0.0002). Patients who were qualified to undergo the gabapentin treatment observed improvement in symptoms (p < 0.027), pain (p < 0.027) and neurologic deficit (p < 0.019). Quality of life did not change significantly after gabapentin treatment (p < 0.128). CONCLUSIONS: Chemotherapy substantially deteriorates the neurologic condition of the patients and the quality of life. Paclitaxel and carboplatin treated patients may benefit from gabapentin therapy in chemotherapy-induced peripheral neuropathy.

The role of HE4 in differentiating benign and malignant endometrial pathology.

OBJECTIVES: The incidence of endometrial cancer is constantly growing. More aggressive types of endometrial cancer as well as the incidence in younger women is being observed. More than 80% of cases is diagnosed in early stages due to early symptoms like abnormal bleeding. The remaining 20% of asymptomatic cases of endometrial cancer as well as the cases of false negative histopathological diagnoses are mostly the incidences of serous endometrial cancer and are a true diagnostic and therapeutic challenge. This was the reason of our study in which we proposed investigation of HE4 levels as a complementary diagnostic method in management and diagnosing of EC. MATERIAL AND METHODS: Serum HE4 level was measured in 92 patients with abnormal vaginal bleeding. Based on histhology after curretage the study group was divided into the benign and malignant endometrial pathology groups. Statistical analysis was performed using Mann-Whitney test RESULTS: The difference of serum HE4 level between benign endometrial pathology and cancer was significant (p = 0.000) and the cut-off for identification of patients with endometrial cancer was 58.08 pmol/l. There was a significant difference between G2 and G3 endometrial cancer, and G1 and G3. (p = 0,4 and p = 0,008 respectively) Patients who needed lymphadenectomy had significantly higher HE4 level than those who had no indications for this procedure (p = 0,001). CONCLUSIONS: HE4 is a useful biomarker in diagnosing endometrial cancer. HE4 is associated with high grade endometrial cancer. It can also serve as an useful preoperative counseling tool to identify patients, who may require pelvic and paraaortic lymphadenectomy.

[Ovarian cancer during pregnancy--presentation of three cases and current diagnostic and treatment algorithms]. / Rak jajnika w ciazy--opisy trzech przypadków oraz aktualne algorytmy postepowania diagnostyczno-terapeutycznego.

INTRODUCTION: Malignant tumors are rarely diagnosed during pregnancy and their incidence ranges from 2.4% to 5.7%. Ovarian cancer is ranked fifth among all cancer types and second among all genital cancers diagnosed during pregnancy The course of the disease is asymptomatic in most cases and the initial diagnose is typically made during a routine ultrasound examination. Management of ovarian cancer during pregnancy presents a considerable challenge due to the absence of clear standards of treatment. OBJECTIVES: We present three clinical cases of patients suffering from ovarian cancer diagnosed during pregnancy a review of the literature, as well as possible therapeutic options. RESULTS: Three different clinical scenarios in patients with ovarian cancer diagnosed during pregnancy have been presented. In addition, we reviewed current diagnostic and therapeutic algorithms for patients with ovarian cancer and co-existing pregnancy. CONCLUSIONS: Approximately 5% of ovarian tumors diagnosed in pregnancy are malignant. There are no treatment standards for ovarian cancer diagnosed during pregnancy. Surgical treatment and the subsequent chemotherapy in the 2nd trimester of pregnancy appear to be safe for both, the mother and the child. However, the potential risks and benefits associated with the treatment have to be thoroughly analyzed on a case-by-case basis, to establish optimal diagnostic and treatment algorithms.

[Bone loss in women with malignant genital neoplasms]. / Utrata masy kostnej u pacjentek z notwtworami zlosliwymi narzadów plciowych.

Nowadays, women with genital cancers live longer due to early diagnosis and better treatment schemes. Only few studies assessed bone mass in patients with genital cancer Osteoporosis is a condition characterized by progressive loss of bone mass, weakening of the spatial structure of the bone, and increased susceptibility to fractures. Osteopenia is a condition of reduced, but not yet reaching the pathological values, bone density in relation to norms for age and sex. Metastases are the primary cause of death in cancer patients. It is estimated that approximately half of people dying due to cancer have bone metastases. Osteoporosis in neoplastic disease may occur due to bone metastases or therapy-related adverse effects, i.e. reduced bone mineral density (BMD). Bone microenvironment provides a good medium for the growth of cancer cells. BMD of the femur and spine should be measured by DXA. Computed tomography (CT) and magnetic resonance imaging (MRI) are the techniques used to detect bone metastases. Lifestyle is the key to improving the quality of life and maximize any pharmacological treatment in cancer patients. It is proposed that treatment of cancer without bone metastases does not require therapy increasing bone mass. Further studies in women treated for gynecological malignancies undergoing oophorectomy and adjuvant treatment are needed to elucidate the mechanisms associated with bone loss.

COX-2 expression pattern is related to ovarian cancer differentiation and prognosis, but is not consistent with new model of pathogenesis.

OBJECTIVE: Numerous studies suggest that cyclooxygenase-2 (COX-2) is overexpressed in cancer. Our objective was to investigate the relationship between COX-2 expression in ovarian carcinoma and clinicopathological factors. An emphasis was put on the association with the new pattern of tumorigenesis that divides tumors into type I--less aggressive, and type II--more aggressive one. The prognostic significance of COX-2 expression was evaluated. METHODS: Ovarian cancer tissues were obtained from 65 patients in FIGO III stage (23 with type I and 42 with type II ovarian cancer). COX-2 expression was evaluated by immunohistochemistry. The statistical analysis was performed in order to assess the connection between COX-2 expression and characteristic factors of ovarian cancer patients as well as the new division for type I and type II ovarian cancer RESULTS: COX-2 expression was detected in 91% of tissue samples. It was markedly elevated in well differentiated tumors (p = 0.0041). The platinum-resistant tumors had significantly higher expression of COX-2 (p = 0.0337). There was no difference between COX-2 expression in type I and type II ovarian cancer (p = 0.6720). The COX-2 staining was not associated to age, CA125 level, the presence of ascites or any special histological type. An increased expression of COX-2 was an unfavorable prognostic factor for overall survival (p = 0.0369) and progression-free survival (p = 0.0218). Multivariate analysis confirmed that COX-2 overexpression is an independent unfavorable prognostic factor of shorter progression-free survival (p = 0.048). CONCLUSIONS: COX-2 expression is an unfavorable prognostic factor for progression-free survival and overall survival in ovarian cancer There is no relationship between COX-2 expression in ovarian cancer tissue and the examined model of ovarian cancer pathogenesis.

The 3020insC NOD2 gene mutation in patients with ovarian cancer.

OBJECTIVE: There is an increasing evidence that genetic factors play a role in the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are responsible for an increased risk of ovarian cancer. The role of mutations in NOD2 gene in this type of neoplasm is still under investigation. THE AIM: The aim of this study was to determine: 1. incidence of NOD 2 3020insC constitutional mutation in a group of consecutive women with ovarian cancer, 2. risk of developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and pathological features of ovarian cancer in NOD2 gene mutation carriers. PATIENTS AND METHODS: Clinical and pathological data were collected from 257 non-selected patients with primary epithelial ovarian cancer. The researches identified NOD2 3020insC gene mutation. On the basis of patient source documentation we obtained the data concerning the age of patients at diagnosis, histopathological recognition, FIGO stage and morphological grade G. RESULTS: 19 out of 257 women were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An increased risk of ovarian cancer in NOD2 mutation carriers was not revealed (OR=1.01; p=0.928; 95% Cl=0.61-1.66). The mean age at diagnosis of patients with NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2). The difference between these frequencies was statistically irrelevant (p=0.550). Clinical and pathological profile of ovarian cancer was made. We assessed the following features: age at disease onset, histopathology, FIGO stage and morphological grade G. For NOD2 mutation carriers no statistically significant features of ovarian cancer were revealed. CONCLUSION: 1. Despite high frequency of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer, genetic testing seem not to be justified in all women diagnosed with this disease. 2. Due to a lack of increased risk of ovarian cancer in NOD2 gene mutation carriers, proceedings for them may not differ from recommendations for general population. 3. It is difficult to determine characteristic clinical and pathological features of ovarian cancer for NOD2 gene mutation carriers.

Analysis of hMLH1 and hMSH2 expression in cisplatin-treated ovarian cancer patients.

BACKGROUND: Loss of DNA mismatch repair may result in resistance to platinum- based anticancer drugs. The hMLH1 and hMSH2 proteins play a critical role in the maintenance of genome integrity and are involved in resistance to platinum-based therapy in colorectal cancer, which is deficient in hMLH1 protein and endometrial cancer, as well as in hMSH2 protein. However, the predictive value of MLH1 and MSH2 expression in ovarian cancer cisplatin-resistance is still to be determined. OBJECTIVE: The aim of this study was to investigate the expression of hMLH1 and hMSH2 proteins in ovarian carcinoma specimens and to evaluate their prognostic significance by means of overall survival (OS) and progression-free survival rates (PSF). MATERIAL: Ovarian cancer tissues were obtained from 61 patients: 45 platinum-sensitive and 16 platinum-resistant. hMLH1 and hMSH2 proteins expression was evaluated by immunohistochemistry, with the use of mouse monoclonal antibodies clone 14 for hMLH1 and clone FE11 for hMSH2. The log-rank test and Kaplan-Meier statistics were used to analyze the relationship between proteins expression and progression free survival, as well as the overall survival. RESULT: No significant correlation was found between hMLH1 and hMSH2 expression and overall survival and progression free survival in the group of patients sensitive and resistant to cisplatin. No significant difference was found in proteins expression intensity between the two compared groups of patients. Age of patients, type of cancer histology, FIGO staging, grading, clinical response and CA 125 did not reveal correlation with the expression of the analyzed proteins. CONCLUSION: The immunohistochemical expression of hMLH1 and hMSH2 proteins in ovarian cancer has no predictive value in resistance to cisplatin.

Retrospective Evaluation of Thromboembolism Risk in Ovarian Cancer Patients Treated with Bevacizumab.

BACKGROUND: Bevacizumab is used in addition to standard, platinum-based chemotherapy to treat advanced-stage ovarian cancer patients. Thrombosis is a well-documented adverse effect of bevacizumab. OBJECTIVE: The aim of this study was to identify predictive parameters for thromboembolic events in ovarian cancer patients and to explain how bevacizumab increases the risk of these events. PATIENTS AND METHODS: Fifty-seven FIGO stage III ovarian cancer patients who underwent cytoreductive surgery and chemotherapy were identified and included in this retrospective study. Twenty-six patients were treated with carboplatin and paclitaxel (CP) only (control group), and 31 patients received CP with bevacizumab (study group). The two groups were compared with regard to thrombosis risk factors and laboratory parameters (total leukocytes, platelet count, hemoglobin, APTT, prothrombin time, INR, fibrinogen levels, D-dimer concentration) before treatment, after each course of chemotherapy, and during thromboembolic events. RESULTS: Only patients in the group receiving bevacizumab experienced venous thromboembolism (VTE) (p=0.03, χ² test). VTE occurred on average at the 13th cycle of chemotherapy. Patients who experienced VTE had increased BMI before chemotherapy as compared to patients with no thromboembolic event (27.2 vs. 23.3, p=0.005, Mann-Whitney test). D-dimer concentration before treatment was also elevated more in patients affected by VTE (3132.5) than in the non-VTE group (956.43) (p=0.0007, Mann-Whitney test). During the first four administrations of chemotherapy in patients with future VTE, there was a reduction in D-dimer concentration and an extension of APTT. A D-Dimer level higher than 485 ng/mL prior to first chemotherapy indicates for a risk of VTE with 94% sensitivity and 36% specificity. CONCLUSIONS: An elevated D-dimer level and high BMI before chemotherapy are risk factors for VTE in ovarian cancer patients receiving bevacizumab. Bevacizumab possibly increases the risk for VTE.