Loss of heterozygosity at BRCA1/2 loci in hereditary and sporadic ovarian cancers.

Loss of heterozygosity at BRCA1/2 loci in breast and ovarian tumors is a suggested risk factor for germline BRCA1/2 mutation status. We evaluated the presence of losses of selected microsatellite markers localized on chromosomes 17 and 13q in hereditary and sporadic ovarian tumors. 151 consecutive primary ovarian tumors (including 21 with BRCA1/2 mutations and 130 without the mutations) were screened for loss of heterozygosity at loci on chromosomes 17 and 13q. Losses of heterozygosity of at least one microsatellite marker localized on chromosomes 17 and 13q were revealed in 123 (81.5%) and 104 (68.9%) tumors, respectively. Losses of all informative markers on chromosomes 17 and 13 occurred in 30 (19.9%) and 31 (20.5%) tumors, respectively. There was no difference in the frequency of losses at BRCA1 intragenic markers (D17S855 and D17S1323) between BRCA1-positive and BRCA1-negative patients. The frequency of losses on chromosome 17 was higher in high-grade than in low-grade carcinomas. Loss of heterozygosity on chromosomes 17 and 13q is a frequent phenomenon in both hereditary and sporadic ovarian cancers. The frequency of losses at BRCA1 intragenic markers in the ovarian tumor tissue is not strongly related to the presence of BRCA1 germline mutations.

Analysis of the results and long-term follow-up of second-look laparotomy in advanced ovarian cancer.

OBJECTIVE: The goal of the study was to analyze results of 171 second-look laparotomy and compare survival of patients with advanced ovarian cancer depending on SLL results. RESULTS: We obtained the following results: complete pathologic response (CPR)--56.2% (96 patients), microscopic disease (R(micro))--12.8% (22 patients), macroscopic disease (R(marco))--31% (53 patients). In patients with negative SLL results disease recurrence was diagnosed in 38.5%. We compared survival in separate groups of patients depending on SLL results: no difference between the CPR group and R(micro) group. Significantly longer survival of patients in the R(micro) group was found compared to patients with recurrence after negative SLL. There were no differences between the group with recurrence after negative SLL and the R(macro) group. CONCLUSIONS: An important observation is that the survival rate in patients with recurrence after negative SLL was significantly lower compared to patients with microscopic disease. The probable explanation for favorable prognosis in the group with microscopic disease was early administration of chemotherapy after SLL.

Microsatellite instability and HPV genotype in Polish women with cervical cancer.

INTRODUCTION: Human papillomaviruses (HPVs) are associated with anogenital cancer. Little is known about the prevalence of microsatellite instability (MSI) in cervical cancer. The aim of this study was to investigate the incidence of microsatellite instability in cervical cancer and to see whether there is a relation between MSI, HPV and clinicopathological characteristics in the study population. RESULTS: Using three assays (pU1M/2R, GP5+/6+ and E6-nested multiplex PCR) HPV was detected in 110 out of 113 patients with histologically confirmed cervical cancer. The presence of MSI was investigated in 95 of the 113 cases using seven microsatellite loci. In total, 12 out of the 95 patients (12.6%) showed MSI. None of clinicopathological parameters showed a significant difference between microsatellite stable and MSI cases. CONCLUSION: In this population of Polish cervical cancer patients, 12.6% showed microsatellite instability. There was no correlation between MSI positivity and clinicopathological parameters and/or survival.

Combination of intraperitoneal hyperthermic perfusion chemotherapy (IHPC) with intraperitoneal chemotherapy as a treatment modality for persistent ovarian cancer.

Persistent minimal residual disease diagnosed after the first line of chemotherapy during second-look surgery can be an indication for intraperitoneal chemotherapy. Another treatment option is intraperitoneal hyperthermic perfusion chemotherapy (IHPC) where the drug is administrated into the peritoneal cavity with the use of extracorporeal closed circuit perfusate circulation at a temperature of 41-42 degrees C. We have started to perform, as a second-line treatment, a combination of one IHPC procedure and four cycles of standard intraperitoneal chemotherapy. In a patient who had previously undergone three different chemotherapy regimens, stabilization of the disease was achieved. In our opinion combining the IHPC procedure with intraperitoneal chemotherapy can be valuable in patients with small volume residual tumor.

Significance of hypoxia in uterine cervical cancer. Multicentre study.

PURPOSE: The aim of the study was to evaluate hypoxia markers (VEGF, GLUT-1, and HIF-1alpha) in cervical cancer tissue depending on staging (FIGO) and grading. We also analyzed the adverse effects of radiotherapy according to expression levels of hypoxic markers in the studied tissue. MATERIAL AND METHODS: Expression of hypoxia-inducible factor-1alpha (HIF-1alpha), glucose transporter 1 (GLUT-1) and vascular endothelial growth factor (VEGF, also known as proangiogenic factor) were estimated in biopsy or surgical specimens from 106 patients diagnosed with uterine cervical cancer. Immunohistochemical methods with EbVision+ complex using monoclonal antibodies anti-VEGF and anti-HIF-1alpha and polyclonal antibody anti-GLUT-1 were applied. RESULTS AND CONCLUSIONS: Hypoxia features measured by percentage of cells undergoing reaction with antibodies anti-HIF-1alpha, anti-GLUT-1 and anti-VEGF were similar in all clinical stages; however the biggest hypoxia features were shown in low differentiated cancers G2 and G3. The 5-year survival for FIGO Stage III patients was shorter in cases with a high expression of hypoxic markers. We observed adverse effects in 45.3% of patients, which occurred more often in patients with higher expression of the studied factors. The presence of hypoxic cells is established as one of the most important factors affecting resistance against tumor radiotherapy and patient prognosis.

Management of massive presacral pelvic bleeding in patients with gynecological malignances: review of the literature.

Hemorrhage has always been a significant potential complication in the field of gynecological oncology. Throughout the years, a variety of medical and surgical modalities aimed at controlling pelvic hemorrhage have been developed. Most recently, these have focused on attempting to decrease the morbidity associated with pelvic bleeding. The effectiveness of and the complications involved in controlling massive hemorrhage by the preemptive method of vascular clamping of the aorta, intraoperative methods, such as the local application of procoagulants and of prolonged compression (pelvic gauze packing, plastic wrapped gauze packing, autograft tissue compression and balloon compression) have all been reviewed. Surgeons are able to acquaint themselves with the choice of methods that can be employed during massive pelvic bleeding resulting from procedures on gynecological malignancies.

The role of pelvic exenteration for treatment of pelvic malignancy--a nine-year experience.

Pelvic exenteration offers the last chance for some women with gynecological and rectal malignancy. A series of 23 patients who underwent pelvic exenteration for local advanced gynecological and rectal malignancies between 1996 and 2004 were retrospectively reviewed. The exenteration was performed because of vulvar cancer in 14 patients and other pelvic malignancies in nine cases: rectal cancer in four cases, in three cases cervical cancer, in one case ovarian cancer and in one case uterine sarcoma. Nine patients developed major complications of the operative field involving the urinary tract or the wound. Early complications included massive bleeding from the sacral plexus in two cases (one patient died during surgery), acute respiratory distress syndrome (ARDS) in one case and thrombophlebitis in one case. Urinary incontinence was observed in two women as a late complication. Only one patient had a complication connected with the gastrointestinal tract. Twenty-two patients were followed-up. In the group of patients with vulvar cancer five women died after 4-29 months because of recurrence of disease. The nine surviving patients are still being followed-up and are without disease; survival time ranges from 6-74 months. In the group of patients with other malignancies four women died.

Differences in the kinetics of the mineralization process in endochondral and intramembranous osteogenesis in human fetal development.

About 300 samples of bone tissue from femoral diaphyses and from parietal bones of calvaria were collected from human fetuses aged from 6-8 to 40-41 weeks in order to compare the kinetics of the mineralization process in endochondral and intramembranous bone formation. The crystallinity of bone mineral was evaluated by the method based on electron spin resonance (ESR) spectrometry, and mineral content was measured after ashing of the samples. Highly significant differences in the kinetics of deposition of mineral (ash content) and maturation of deposited mineral (crystallinity coefficient) were found between parietal bones and femoral diaphyses in the course of fetal development. In the early stages of development (6-8 to 10-12 weeks), the content of mineral and its crystallinity in parietal bones were significantly lower than in femoral diaphyses. In the parietal bones a gradual increase in both values was observed until they reached a plateau at the age of 30 weeks. On the other hand, in femoral diaphyses of 6-8-week-old fetuses mineral content was high and deposited mineral showed a high degree of crystallinity. Both these values did not change significantly until birth. The differences in kinetics of the mineralization process between the weight-bearing bones and bones that are not exposed to the influence of strong external forces are most probably genetically conditioned. The collected data supply embryological information and might be used in the future for evaluation of pathologic changes in skeletal development.

HPV and histological status of pelvic lymph node metastases in cervical cancer: a prospective study.

AIMS: The purpose of this prospective study was to describe the incidence and distribution pattern of human papillomavirus (HPV) DNA in intraoperative dissected lymph nodes and to relate this to the pathological confirmation of metastasis. METHODS: Samples of primary cervical cancer lesions and dissected lymph nodes were obtained from women undergoing surgical treatment. The presence of HPV DNA was detected by the polymerase chain reaction. RESULTS: Tissue from 79 tumours and 365 lymph nodes was analysed. Metastasis to the lymph nodes was found in 19 cases. Metastasis correlated with the volume of the primary lesion, the depth of cervical and vaginal invasion, and with invasion of the corpus. HPV DNA was found in 60 of the primary lesions and 31 of the lymph nodes. The presence of HPV DNA in the lymph nodes correlated with the volume of the primary lesion and vaginal invasion. CONCLUSIONS: The incidence of HPV DNA in lymph nodes is twice as high as that of histopathologically confirmed metastases. The risk of the presence of HPV DNA and histopathologically confirmed metastases in lymph nodes is related to certain features of the primary tumour.

Pharmacological characterization of the contractile effects of galanin (1-29)-NH2, galantide and galanin (1-14)-(alpha-aminobutyric acid8)scyliorhinin-I in the rat gastric fundus.

Porcine galanin (1-29)-NH2, galantide (M15) and galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I used in concentrations of 300, 1,000 and 3,000 nM respectively caused contractions of rat fundus strips. The contractile responses to galanin(1-29)-NH2 were not modified by atropine (10 microM), guanethidine (10 microM), naloxone (1 microM), a mixture of propranolol (10 microM) and phentolamine (10 microM), indomethacin (10 microM), a mixture of mepyramine (10 microM) and cimetidine (10 microM), saralasin (10 microM), and spantide (100 microM). The effects of M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I were significantly decreased by atropine for 36 and 18% and by spantide for 37 and 26% respectively. Indomethacin inhibited the muscle response to M15 without influence on the galanin (1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I-induced action. These results support findings that galanin (1-29)-NH2 contracts rat gastric fundus strips by stimulating specific receptors localized on the surface of smooth muscle cells. M15 and galanin(1-14)-(alpha-aminobutyric acid8)-scyliorhinin-I seem to contract smooth muscles not only by acting at galanin receptors, but by interacting with muscarinic or tachykinin receptors or modulating the release of acetylcholine and substance P. Diltiazem (EC50 825 nM), dantrolene (EC50 30.2 microM) and the phospholipase C inhibitors U-73122 (EC50 549 microM) and U-73343 (EC50 751 microM) lowered the contraction to galanin(1-29)-NH2 in a concentration-dependent manner. These observations imply that though the extracellular Ca2+ influx plays a major role in the action of galanin(1-29)-NH2, the release of Ca2+ ions from the intracellular stores contributes to the response of smooth muscles of galanin(1-29) NH2. Norepinephrine (30, 60, 100 and 300 nM) concentration-dependently reduced the Emax to galanin (1-29)-NH2 and reduced the slopes of the concentration-contraction curves, without a notable change in EC50. Pertussis toxin pre-treatment (10 and 30 mg/kg intravenous [i.v.]), 120 h before the experiment, notably increased the maximal response of the rat gastric fundus to galanin(1-29)-NH2, without a significant change in the properties of the concentration-contraction curves (EC50, slopes). The observations may suggest that pertussis toxin-sensitive GTP-binding proteins are involved in the modulation of the excitatory effects of galanin(1-29)-NH2 in the rat gastric fundus.

Acute renal failure after anterior pelvic exenteration: a case report and review of the literature.

This is a report of a case of advanced cervical carcinoma in a 34-year-old woman treated with anterior pelvic exenteration at the Department of Gynecology of the Medical University in Gdansk. Despite annual gynecological check-ups, the patient presented with profuse bleeding from the genital tract. IVa cervical carcinoma according to the International Federation of Gynecology and Obstetrics (FIGO) staging was diagnosed. A vesicovaginal fistula was confirmed. In the postoperative period acute renal failure occurred. Twenty-four days after the operation when normal renal parameters had been restored, the patient was transferred to the Department of Radiotherapy for supplementary treatment. Pelvic exenteration offers the last chance for some women with gynecological malignancy and can provide a good chance of long-term survival in carefully selected patients with gynecological cancer.

Factors influencing period of time between negative second-look laparotomy and ovarian carcinoma recurrence. Multicenter study in Poland.

OBJECTIVE: The aim of our study was to evaluate factors such as primary clinical stage, presence of ascites, serum CA 125 antigen level, histological type of ovarian cancer, cell differentiation and number of chemotherapy cycles influencing the time of recurrence after negative second-look operations. MATERIAL AND METHODS: Having observed complete clinical remission in 356 patients with ovarian cancer, second-look laparotomy was performed. In 180 patients complete pathologic remission was detected and in 73 recurrence was observed. Correlation analysis between time of recurrence and the above-mentioned prognostic factors was carried out by means of the Mann-Whitney and Kruskal-Wallis tests. RESULTS: The time from the second-look operation till diagnosis of relapse ranged from 7 to 36 months (average 21 months). The statistical analysis showed a correlation between the presence of ascites, increased serum CA 125 antigen level, the administration of six chemotherapy courses and the time of recurrence. In all those cases relapse occurred earlier than in patients without ascites, with normal CA 125 antigen levels and after ten courses of chemotherapy. CONCLUSION: Our findings suggest that the stage of clinical advancement and histologic grading do not influence the time of recurrence. The presence of ascites, increased serum CA 125 antigen level and the administration of fewer chemotherapy courses (6 versus 10) after primary surgery affects the earlier relapse of disease.

[Clinical aspects of intraperitoneal chemotherapy in patients with ovarian carcinoma]. / Kliniczne aspekty chemioterapii dootrzewnowej u chorych z rakiem jajnika.

Ten women with primary ovarian carcinoma in clinical progression grade III degree according to FIGO received intraperitoneal chemotherapy. They all had surgical treatment and 9 of them received after operation intravenous cytostatics PAC or PC. Cisplatin 100-220 mg/m2 was given intraperitoneally through a Tenckhoff catheter for long-term dialysis. Before beginning of intraperitoneal chemotherapy in 6 cases the malignant lesions were under 2 cm in diameter, and in 4 cases the size of these lesions was exceeding 2 cm with far advanced disease. In patients with malignant lesions under 2 cm CR was obtained in 4 cases, SD in 1 case and PR in 1 case. In the group with malignant lesions exceeding 2 cm the results of intraperitoneal treatment were: SD in 2 cases and PD in 2 cases. Intraperitoneal chemotherapy is an effective method in ovarian carcinoma when intravenous chemotherapy is ineffective. This is another method which provides a chance of prolongation of the life of the patients.

[Retrospective assessment of the feasibility of conservative surgery in the vulvar squamous cell carcinoma]. / Retrospektywna ocena mozliwosci zastosowania oszczedzajacych technik leczenia miejscowego u chorych na plaskonablonkowego raka sromu.

OBJECTIVES: Radical vulvar surgery is associated with significant morbidity. DESIGN: The aim of the study was to assess retrospectively the feasibility of less extensive surgery in vulvar cancer patients operated in our institution with radical intent. The feasibility of less extensive surgical procedures was investigated, based on the retrospective analysis of preoperative assessment of tumour location and extent in a group of 162 patients. RESULTS: In the next step, the pathology reports of actually performed extensive operations were carefully reviewed in a search of microscopic evidence of tumour outside the limits of proposed conservative procedures. Conservative surgery was regarded technically possible in 127 patients (85.8%). Macro- or microscopic multifocality was detected in 22 patients (14.9%), of whom in 15 cases conservative surgery was regarded possible on the basis of clinical assessment. However, only in 11 cases tumour was found outside the limits of planned excision, in 9 of those cases--due to multifocal lesions. CONCLUSIONS: Less extensive surgery is technically feasible in a vast majority of vulvar cancer patients, however the selection for conservative procedures based only on clinical assessment of tumour extent is not sensitive enough to assure radical treatment in all patients and better methods of preoperative evaluation, such as vulvoscopy or random vulvar biopsies need to be investigated before the decision on routine use of conservative surgery is made.

[Risk factors for groin lymph node involvement in patients with vulvar cancer]. / Czynniki kliniczno-patologiczne warunkujace ryzyko zajecia pachwinowych wezlów chlonnych u chorych na raka sromu.

OBJECTIVES: Morbidity of vulvar cancer surgery is predominantly related to groin lymph node dissection. DESIGN: The aim of the study was to determine factors influencing the probability of groin lymph node metastases and to select a subgroup of patients in whom the risk of nodal involvement is low and nodal dissection can be omitted. MATERIAL AND METHODS: A retrospective analysis was performed on the group of 123 patients who had undergone full inguino-femoral lymph node dissection as a part of their primary vulvar cancer treatment. RESULTS: The risk of involvement of groin nodes was related to the clinical assessment of the stage of disease according to 1970 FIGO classification (p < 0.001), depth of stromal invasion (p = 0.004), primary tumour diameter (p = 0.009) and to the presence of pain in the vulva (p = 0.028). In multivariate analysis the probability of groin node infiltration was related to the diameter of primary tumour (p = 0.008) and depth of stromal invasion (p = 0.013). CONCLUSION: The analysis allowed for division of vulvar cancer patients into subgroups of similar risk of lymph node involvement.

[Invasive vulvar carcinoma in a sixteen year old patient]. / Inwazyjny rak sromu u szesnastoletniej chorej.

A case of vulvar carcinoma diagnosed in 16 year old patient is described. Presented are steps in diagnosis and multi-stage conservative surgical treatment aimed at cure without unnecessary mutilation of the young woman.

[Neurofibroma plexiforme of the small pelvis: a case report]. / Neurofibroma plexiforme miednicy mniejszej--opis przypadku.

There are reports of rare cases of nerve tissue tumors of the small bowel, ovary, urinary bladder or retroperitoneal space. We report a case of neurofibroma plexiforme of pelvis minoris in 42-year-old woman. The first diagnosis was adnexal tumor. Laparotomy was performed and a big, solid tumor of left parametrium was found. The histology of the tumor was described as neurofibroma plexiforme. There was also an inflammatory tumor of appendix involving right Fallopian tube. The described by other authors cases suggest, that diagnosis of nerve tissue tumors in pelvis minoris is very difficult. Surgery is an adequate way of final diagnosis and management.

[Use of intraperitoneal chemotherapy in patients with clinical stage I ovarian neoplasms]. / Zastosowanie chemioterapii dootrzewnowej u chorych na raka jajnika w I degree zaawansowania klinicznego.

Results of treatment with intraperitoneal cisplatin chemotherapy via Tenckhoff catheter of 14 high-risk stage I ovarian cancer patients are presented. Seven patients had malignant ascites and in 6 a spillage of the tumor occurred before or during surgery. All patients achieved pathological complete remission after IP chemotherapy. During a median follow up of 38.5 months (range: 15-58) one recurrence was noted 16 months after treatment.

[Ectopic pregnancy in the stump of the uterine tube after in vitro fertilization]. / Ciaza ektopowa w kikucie jajowodu po zaplodnieniu pozaustrojowym.

A rare case of ectopic pregnancy in stump of uterine tube after IVF, which was done after bilateral removal of uterine tubes, caused by uterine tube pregnancies was described. Diagnostic difficulties were shown in that case.

[Endometrial carcinoma in patients with family history of neoplasms]. / Rak blony sluzowej trzonu macicy u chorych z obciazonym nowotworowo wywiadem rodzinnym.

OBJECTIVES: The aim of the study was multifactorial clinical analysis of patients with neoplasmatic family history operated because of endometrial carcinoma in 2nd Dept. of Obstetrics and Gynecology Medical University of Gdansk between 1983-1997. MATERIAL AND METHODS: The group of 117 women who answered inquiry forms was analysed. The other data was obtained from case histories. The subgroup of patients with neoplasmatic family history was selected. RESULTS: The subgroup of patients with neoplasmatic family history was 41.9% of all treated women (49 women). The median age was 58.8; most of them were para- and postmenopausal women. In the group of patients with adenocarcinoma of endometrium the neoplasmatic family history was obtained twice more often then in group with adenosquamous carcinoma. The neoplasmatic disease was found in different members of family (parents, sisters, brothers, grandparents, uncles, aunties and other). In 1/3 cases a neoplasmatic disease was found in few members of the family. CONCLUSION: Women with neoplasmatic family history have to be controlled more strictly because of "coexisted" genetic, internal and economic factors.