Prognostic impact of BRCA1 pathogenic and BRCA1/BRCA2 unclassified variant mutations in patients with ovarian carcinoma.

BACKGROUND: The clinical relevance of BRCA1/2 alterations in ovarian carcinoma patients is debatable. Our aim was to determine factors influencing the risk of recurrence and death in ovarian carcinoma patients with BRCA pathogenic and unclassified variant mutations. METHODS: A consecutive series of 205 women with primary ovarian carcinoma were screened for mutations in BRCA1 and BRCA2 genes using a conformational sensitive gel electrophoresis and direct sequencing. Data regarding medical and familial history were collected using questionnaires. Clinical and pathologic data were extracted from medical records. RESULTS: Unclassified variant mutations in BRCA1 or BRCA2 genes were found in 16 (8%) patients, and BRCA1 pathogenic mutations were found in 18 (9%) patients. No pathogenic mutation was found in BRCA2 gene. Multivariate analysis showed that BRCA1 pathogenic mutation was an independent predictor of reduced risk of relapse and death (Hazard ratios [HR] 0.52 [confidence interval {CI} 0.28-0.98] and 0.38 [CI 0.10-0.96], respectively). Unclassified variant mutation did not affect recurrence and survival (HR 0.84 [CI 0.43-1.66] and 0.94 [CI 0.48-1.82], respectively). Other factors associated with reduced risk of relapse and death were complete pathologic remission at second-look laparotomy and family history of breast and ovarian carcinoma, respectively. Recurrence and death outcomes among unclassified variant mutation carriers did not differ significantly from those in sporadic cases. CONCLUSIONS: Patients with BRCA1 pathogenic mutation seem to have reduced risk of recurrence and death. These results should be interpreted with caution as they may be influenced by more intensive treatment, better response to cisplatin, and younger age of mutation carriers. Clinical relevance of BRCA1/2 unclassified variant mutations warrants further studies.

Prevalence and clinical correlations of BRCA1/BRCA2 unclassified variant carriers among unselected primary ovarian cancer cases - preliminary report.

The objective of this study was to determine the prevalence of BRCA1 and BRCA2 gene mutations in unselected ovarian cancer patients, and to analyse clinical and pathological features of ovarian cancer unclassified variant mutation carriers in comparison with BRCA1 pathogenic mutation carriers and sporadic cases. A consecutive sample of 205 women with primary ovarian cancer was screened for mutations in the BRCA1 and BRCA2 genes using a direct test for small deletions and insertions, conformational sensitive gel electrophoresis and direct sequencing. Data regarding medical and familial history were collected using questionnaires. Clinical and pathological data were extracted from medical records. Unclassified variants and polymorphic mutations accounted for 8% (n = 16) and 6% (n = 13) of all cases, respectively. BRCA1 pathogenic mutations were found in 18 (9%) patients. None were found in BRCA2. The mean age of onset for BRCA1-associated tumours was 43.1 years (standard deviation (SD: 7.3) whereas in the patients with an unclassified variant, polymorphism, or no detectable gene changes, the mean age of onset ranged from 49.5-56.4 years. The most significant predictors for pathogenic or unclassified variant changes in BRCA1 in ovarian cancer patients were a younger age of onset and a history of hyperthyroidism and infertility. Except for infertility and hyperthyroidism, unclassified variant-linked ovarian tumours share features with sporadic tumours rather than with BRCA1 pathogenic mutations.

[Hereditary ovarian cancer as a separate clinical entity]. / Dziedzicznie uwarunkowany rak jajnika--odrebna jednostka chorobowa?

Family history of ovarian cancer has been regarded as the most important risk factor in developing this type of tumor. Recent identification of cloning of specific tumor suppressor genes responsible for hereditary ovarian cancer syndromes, resulted in the surge of enthusiasm and optimism regarding the practical application of genetic information. Many investigators believe that natural history of hereditary ovarian may significantly differ from sporadic cases. Some independent findings have shown that serous adenocarcinoma was the most frequent histological type in hereditary ovarian cancer patients, whereas the mucinous and the borderline were underrepresented in this group. Also, patients with hereditary ovarian cancer tend to develop the disease at younger than expected age. At the present moment, it remains unknown if environmental/lifestyle factors play a role in penetrance and expression of specific tumor suppressor genes in mutation carriers. The era of molecular genetics has raised hopes not only for a better understanding of biology and natural history of hereditary ovarian tumors but also a rapid breakthrough in prevention and management of this disease.

[Lymph node metastasis as a prognostic factor in cervical carcinoma]. / Przerzuty do wezlów chlonnych jako czynnik prognostyczny raka szyjki macicy.

MATERIAL AND METHODS: 499 patients with cervical carcinoma at stage I and IIa after radical hysterectomy were included in the study. Diagnosis was based on gynecological examinations and cervical biopsies. Clinical staging was determined by FIGO classification. Pelvic lymph nodes were routinely removed on hysterectomy. RESULTS: Metastatic nodes were observed in 26.3% (131 patients). We found no metastatic nodes at stage Ia. In the group of 410 patients with stage Ib cervical cancer metastases in lymph nodes were found in 24.6% (101 patients). In the group of 78 patients with stage IIa cervical cancer metastatic nodes were observed in 38.5% (30 patients). In our finding metastases were located in one group of lymph nodes in 64.4% (64 patients) with stage Ib and 43.3% (13 patients) with stage IIa. Metastatic involvement of more than one group of lymph nodes was observed in 36.6% (37 patients) of stage Ib and 56.7% (17 patients) of stage IIa. The most frequent pattern of lymph nodes metastatic involvement comprised common iliac and obturatorious nodes. 5 year survival in the group without metastases in lymph nodes was estimated at 82.2%, and in the group with nodal metastases--50.8% (p = 0.005). CONCLUSIONS: 1. Metastases to pelvic lymph nodes are significant prognostic factor of long-term survival in patients with cervical cancer. 2. Patients with metastases in lymph nodes and no subsequent postoperative radiotherapy had significantly worse long-term survival.

[Paclitaxel hypersensitivity reactions in patients with advanced ovarian carcinoma]. / Reakcje nadwrazliwosci na paklitaksel u chorych z zaawansowanym rakiem jajnika.

OBJECTIVES: The purpose of our study was to analyze the rate of hypersensitivity reactions (HSRs) to paclitaxel in patients with advanced ovarian carcinoma. We also analyzed the possibility of re-administration paclitaxel with adequate treatment after hypersensitivity reactions. MATERIALS AND METHODS: The incidence of HSRs was analyzed retrospectively in 112 patients who received 24-hr infusions of paclitaxel (135 mg/m2) for advanced ovarian cancer at the Department of Gynecology Medical University of Gdansk between the January 2000 and the February 2002. Before each course of the paclitaxel administration patients received orally dexamethasone (20 mg p.o., 12 and 6 hours prior to the chemotherapy) and thirty minutes prior to the infusion of paclitaxel all patients received, diphenhydramine (50 mg), and cimetidine (300 mg) intravenously (i.v.). When HSR was observed administration of paclitaxel was temporally stopped and before the re-challenge additional intravenous dosage of hydrocortisone (200-500 mg) and diphenhydramine (25 mg) was given. RESULTS: Severe hypersensitivity reactions occurred in 9 patients (8%) and the administration of paclitaxel was withdrawn. Mild hypersensitivity reactions were observed in 8 patients (7%) and all of these patients were successfully retreated with paclitaxel without HSRs. CONCLUSION: We conclude that this premedication and treatment strategy provides lower hypersensitivity reactions rate and allows for continuing administration of paclitaxel in patients with advanced ovarian carcinoma.

[Evaluation of surgical complications connected with intraperitoneal chemotherapy in ovarian cancer]. / Analiza powiklan chirurgicznych wystepujacych w przebiegu chemioterapii dootrzewnowej u chorych na raka jajnika.

OBJECTIVES: From a theoretical viewpoint, the use of intraperitoneal therapy (i.p.) in patients with ovarian cancer (a malignancy, which remains mainly confined to the peritoneal cavity) is logical. Intraperitoneal catheters have moved to the forefront as a delivery system in cancer treatment. Authors described complications during the placement, usage, and evacuation of Tenckhoff catheters. Some of them report much too high number of surgery complications connected with i.p. DESIGN: We report a number of complications connected with insertions, functions, and evacuations of Tenckhoffa catheter. MATERIAL AND METHODS: From January 1996 to January 2002, 92 patients with recurrent or persistent ovarian cancer, after surgery and first line chemotherapy, have had catheter insertion performed, but only 79 have had performed catheter evacuation: because of: not complete therapy (7 patients), three patients died during i.p. therapy, in three cases intraperitoneal catheter has spontaneously fold out. RESULTS: During insertion total number of complications 9(9.78%), 6 bowel incision, 1 bladder incision, 1 hernia of the linea alba, 1 incision of bowel and bladder. During catheter evacuation total number of complications 9 (11.39%), 8 bowel incisions 1 hernia of the linea alba. Complications connected with catheter function: only 8 of 92 (8.70%) required cessation of chemotherapy prior to its expected completion, 2 fistula of the catheter to vagina, 2 fistulas to bowel, in two cases intraperitoneal catheter has spontaneously fold out due to abscess, one after citostatics flow under the skin, one because of abscess in peritoneal cavity, and problems with citostatics inflow one because of subileus. CONCLUSION: The surgical complications occurring during IPC are not dangerous for patients. IPC is valid and safe way of treatment patients with ovarian cancer. The frequency of complications occurring during insertion of Tenckhoff catheter depends on the way of placement.

[Comparison of quality of life in patients with advanced ovarian cancer treated with intraperitoneal or intravenous cisplatin and cyclophosphamide as a second line of therapy]. / Porównanie jakosci zycia chorych zaawansowanym rakiem jajnika otrzymujacych w drugiej linii leczenia cisplatyne z cykofosfamidem dootrzewnowo oraz dozylnie.

OBJECTIVES: The study aimed to compare the effect of second line intravenous and intraperitoneal chemotherapy on physical and psychological aspects of quality of life in patients with advanced ovarian cancer. MATERIALS AND METHODS: Quality of life was measured with EORTC QLQ-C30 (version 3.0) questionnaire. 42 sample patients with histologically confirmed diagnosis of advanced epithelial ovarian cancer treated with second line intravenous or intraperitoneal chemotherapy were included in the study. RESULTS: Higher score of global quality of life and less side-effects of chemotherapy were observed in the group of patients treated with intraperitoneal chemotherapy. In this group constipation and dyspnoea were less common. CONCLUSION: Intraperitoneal chemotherapy has less negative influence on quality of life than intravenous drug delivery.