Prognostic factors and a value of 2009 FIGO staging system in vulvar cancer.

OBJECTIVE: In 2009, International Federation of Gynecology and Obstetrics (FIGO) modified staging of vulvar cancer-the prognostic significance of the new classification relative to the prior system as well as to the commonly recognized prognostic factors has not been assessed. The aim of this study was to test prognostic ability of 2009 staging in a cohort of uniformly treated and staged cases with long-term follow-up. METHODS: Pathologic characteristics were obtained by blind review of the original tissue samples. 76 patients who qualified for surgery on the basis of the same criteria, with full clinical history, were included in the study. The histological analyses were performed on 76 and 35 paraffin-embedded tissue samples from primary tumors and lymph nodes, respectively. Survival analyses included the Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: Univariate analysis has demonstrated that age (p = 0.0170), lymph node metastasis (p = 0.0393), tumor grade (p = 0.0086) and FIGO1994 stage (p = 0.001) were the significant prognostic factors for overall survival. Multivariate analysis has demonstrated that growing age (HR 2.25, 95 % CI 0.79-3.71, p = 0.0321), tumor grade (G1 vs. G2 and G3) (HR 1-3.11, 95 % CI 1.6-4.62, p = 0.0057) and FIGO1994 stage (HR 1.78, 95 % CI 0.55-3.01, p = 0.0061) are independent prognostic factors with respect to overall survival. CONCLUSIONS: The results indicate the prognostic advantage of the 1994 FIGO staging as it has become an independent prognostic factor in contrast to the new FIGO system. This should be tested in future larger cohort studies. Differentiation grade turned out to be a very valuable independent prognostic factor and should be incorporated as a routine component of the histopathologic reports in vulvar cancer.

Expression of indoleamine 2,3-dioxygenase predicts shorter survival in patients with vulvar squamous cell carcinoma (vSCC) not influencing on the recruitment of FOXP3-expressing regulatory T cells in cancer nests.

OBJECTIVE: Regulatory T cells (Tregs), and the enzyme indoleamine 2,3-dioxygenase (IDO), have potential regulatory properties for immune escape in cancer. Inhibitors of IDO are available and could potentially be used in vulvar cancer if IDO was proved to drive progression of the disease. The aim of this study was to evaluate the expression of factor forkhead boxP3 (FOXP3), a marker of Tregs, and IDO in vulvar squamous cell carcinoma (vSCC), and to verify their prognostic significance. METHODS: 76 primary tumors and 35 lymph node metastases derived from 76 patients with full clinical history were analyzed. The intratumoral infiltration of Tregs and IDO expression within cancer were evaluated by immunohistochemistry. RESULTS: The number of Tregs in primary tumor and in corresponding lymph node metastasis was significantly correlated. Intensity of Treg infiltrates in the primary and metastatic sites was not correlated to IDO expression and had no influence on the overall patient survival. High IDO expression was associated with significantly worse overall survival among vSCC patients and was found to be an independent prognostic factor similarly to the tumor grade and patient's age. CONCLUSIONS: The degree of intratumoral Treg infiltrates is an individual feature and remains stable throughout the course of the disease without impact on the patient's survival. IDO expression predicts shorter survival of vSCC patients. If immunologic tolerance of the tumor is promoted by the overexpression of IDO it will not influence the number of intratumoral Tregs. IDO expression seems to be an independent prognostic factor in patients with vSCC.

Prognostic significance of CD4+ and CD8+ T cell infiltration within cancer cell nests in vulvar squamous cell carcinoma.

BACKGROUND: The clinicopathological significance of the local spontaneous immune reaction in vulvar squamous cell carcinoma remains unclear. The purpose of this study was to clarify the role of the subtypes of tumor-infiltrating lymphocytes, both individually and synergistically. METHODS: Seventy-six patients with verified histopathological data and complete clinical history were included into the study. We collected 76 paraffin-embedded samples of the primary tumor. The presence of CD4+ and CD8+ T cells was evaluated by immunohistochemistry and compared with commonly recognized prognostic factors. The primary end point analyzed was the overall survival. RESULTS: CD4+ and CD8+ T cells were detected both within the nests of carcinoma and in the stroma, but only the infiltration within cancer cell nests was further analyzed. There was significant positive correlation (Spearman rho test R = 0.282, P = 0.014) between the number of intratumoral CD4+ and CD8+ T cells. No correlation was observed between the number of tumor-infiltrating CD4+ and CD8+ T cells and the patients' survival. Patients were classified into the following 4 groups (CD4+/CD8+, CD4⁻/CD8⁻ CD4+/CD8⁻, CD4⁻/CD8+), but none of them correlated with overall survival. CONCLUSIONS: These data support the statement that CD4⁻ and CD8+ T cells cooperate within cancer cell nests, but this spontaneous immune reaction is an individual feature not influencing the prognosis. Intratumoral CD4+ T cells might control or reflect the immune responses against cancer cells, whereas CD8+ T cells do not seem to work as sufficient effectors in tumor tissues.

Clinical significance of VEGFR-2 and VEGFR-3 expression in ovarian cancer patients.

The vascular endothelial growth factor (VEGF) family and VEGF receptors (VEGFR) play an essential role in angiogenesis and lymphangiogenesis. The aim of this study was to clarify the prognostic significance of VEGFR expression in ovarian carcinoma. Levels of VEGFR-2 and VEGFR-3 tissue expression in human ovarian tumours were assayed by immunoblotting and the correlations between analysed factors and clinicopathological features were examined. Tissue samples consisted of 42 benign and 10 borderline (low malignant potential - LMP) tumours, 76 ovarian carcinomas, 8 Krukenberg tumours and 32 normal ovarian tissues. The highest relative level of VEGFR-2 was detected in cases with at the early stages of cancer development. The highest level of VEGFR-3 was detected advanced cancer stages and those with Krukenberg tumours. Overexpression of VEGFR-3 was found to correlate with the debulking status (p = 0.02) and positive response to chemotherapy (p = 0.04). A statistically significant longer progression free survival (PFS) was observed in women with a low than with a high expression of VEGFR-3 (p = 0.01). Increased levels of VEGFR-2 expression at the early stages of ovarian cancer may indicate the significance of neoangiogenesis at these stages. Overexpression of VEGFR-3 reflects the aggressiveness of ovarian carcinoma spread and has a predictive value for identifying high-risk patients with poor prognosis.

[Insertion of IUD after extrauterine mislocation of the previous one]. / Powtórne zalozenie wkladki wewnatrzmacicznej po nierozpoznanym przemieszczeniu poprzedniej do jamy brzusznej.

We present a case report of a 37-year-old woman with accidental finding of two IUDs--one inserted correctly and the other one located in the abdomen.

Characteristic features of recurrences of squamous cell carcinoma of the vulva.

AIM: The objective of this study was to find prognostic factors for the development of recurrences in patients who had undergone surgical treatment of vulvar cancer. METHODS: The records of patients with primary vulvar cancer (n=104) treated at the Department of Gynaecological Oncology of the Medical University of Gdansk between 1998 and 2001 were reviewed to identify those with squamous histology. Of the 93 thus identified 27 were excluded because of lack of standard treatment and 7 because of lack of radical surgery. A total number of 59 patients with squamous cell carcinoma were finally analyzed. For each record the age of the patient, size of the lesion, depth of invasion, margins of resection and lymph node status were analyzed. All patients were staged according to FIGO (1996). Recurrences were recorded by localization, whether local, groin or distant, and compared with a group of patients without any recurrences after radical surgery (n=59). RESULTS: Recurrence was recorded in 19 cases (28.8%). A local (vulvar/perineal) recurrence was diagnosed in 10 patients (10/59, 16.9%), while 5 (5/59, 8.5%) developed groin recurrence and 4 (4/59, 6.8%) had distant recurrences. Multifocality of the primary tumour is an independent risk factor for local recurrence (HR: 3.12; 95% CI: 0.84-11.6). A metastatic node was the only independent prognostic risk factor for groin or distant recurrence (HR: 3.16; 95% CI: 0.94-10.2). CONCLUSION: Close follow-up of patients treated for vulvar cancer is recommended to detect recurrences at an early and potentially curable stage. Deep inguinal-femoral lymphadenectomy could be replaced with superficial inguinal groin dissection.

Maspin overexpression correlates with positive response to primary chemotherapy in ovarian cancer patients.

OBJECTIVE: Maspin is a member of the serine protease inhibitor superfamily. Experimental studies revealed that maspin suppresses tumor growth, angiogenesis, invasion and metastasis. We examined maspin expression in human ovarian tumors and relation between maspin expression and clinicopathological features as well as the role of maspin in predicting clinical outcome in patients with ovarian cancer. METHODS: Tissue samples consisted of 42 benign tumors, 10 borderline (LMP) tumors, 76 ovarian carcinomas, 8 Krukenberg tumors and 32 normal tissues. Immunoblot analysis was performed to evaluate the relative expression of maspin/beta-actin. RESULTS: Relative maspin level was significantly higher in patients with LMP tumors (median 0.74) and early stages ovarian cancers (median 0.46) when compared with healthy tissues (median 0.03), those with benign (median 0.23) and metastatic tumors (median 0.22). Overexpression of maspin was found to correlate with the early stage of the disease (p=0.001), non-serous subtype of ovarian cancer (p=0.03) and positive response to chemotherapy (p=0.02). A statistically significant longer PFS was seen in women with high as compared with low expression of maspin (p=0.03). CONCLUSIONS: Maspin is upregulated in borderline tumors and the early stages of ovarian carcinoma and then significantly downregulated with malignant transformation. High expression may paradoxically promote the invasion and metastasis of ovarian carcinomas. Our study revealed that maspin expression could play an important role in predicting the results of treatment of ovarian cancer patients.

Expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes in primary endometrial cancer.

The HtrA family of serine proteases takes part in cellular stress response including heat shock, inflammation and cancer. Downregulation of human HtrA1 and HtrA3 genes has been reported in some cancers, including endometrial cancer (EC), suggesting a tumor-suppressor role for both genes. The mechanism of the HtrA function is not known, however, evidence exists showing that both HtrA1 and HtrA3 regulate biological processes by modulating TGF-beta signaling. In the presented study the expression of human HtrA1, HtrA2, HtrA3 and TGF-beta1 genes was examined in 124 endometrial tissue specimens including 88 cancers and 36 normal endometria. The expression of the tested genes was evaluated at mRNA and protein levels by semi-quantitative RT-PCR and western blotting methods, respectively. Our results showed significant decrease of HtrA1 and HtrA3 mRNA and protein levels in EC compared to normal tissues. The most dramatic decrease was found for HtrA3 at both mRNA and protein levels (3.2- and 5.6-fold, respectively). Moreover, the HtrA3 protein (short isoform) was not detected in 19% of the cancers, and its level decreased from the premenopausal to the postmenopausal group. The HtrA2 protein levels were significantly lower in EC tissues compared to normal tissues. We also found a significant increase of the TGF-beta1 protein level in EC as well as a significant negative correlation between HtrA1/2/3 and TGF-beta1 relative protein levels. Our results showing downregulation of HtrA1 and HtrA3 gene expression support previous studies suggesting a tumor suppressor role for these genes. Furthermore, our data suggest that HtrA2 may be involved in EC development as well as suggest the involvement of HtrA1, HtrA2 and HtrA3 in the inhibition of TGF-beta signaling in endometrial tissues.

Second line platinum-based intraperitoneal chemotherapy for advanced ovarian cancer.

OBJECTIVE: To report the results of ovarian cancer treatment, where a regimen of intravenous cyclophosphamide followed by intraperitoneal cisplatin or carboplatin was administered as second line treatment. DESIGN: Retrospective observational study on 198 women with stage I-IV histologically documented epithelial ovarian cancer after one or more prior regimens of chemotherapy. SETTING: University tertiary referral clinic, Gdansk, Poland. METHODS: The study group was recruited from among 593 ovarian cancer patients treated between January 1996 and December 2006. Conditions of inclusion for intraperitoneal treatment were: relapse or recurrence of disease after surgery followed by first line treatment. Recurrences were confirmed through re-staging laparotomy or second-look laparotomy. Patients received 90 mg/m(2) cisplatin, or carboplatin AUC 6 intraperitoneally and cyclophosphamide 750 mg/m(2) intravenously. Four or six courses were planned for each patient. MAIN OUTCOME MEASURES: Response to treatment defined as complete or partial response, or progressive disease, and survival rates. RESULTS: There were 67 (34%) with complete and 61 (31%) with partial response, while 69 (35%) developed progressive disease. Median survival from the initiation of intraperitoneal chemotherapy (IP) was 51 months and significantly longer for patients who received four cycles of IP: 78 months vs. 20 months for patients who received six intraperitoneal cycles. CONCLUSIONS: IP can be used in second line treatment of ovarian cancer, but six treatment cycles appear associated with worse results compared to four.

Twenty-four-hour and conventional blood pressure components and risk of preterm delivery or neonatal complications in gestational hypertension.

Gestational hypertension is a recognized risk factor for the development of complications during pregnancy. The present study retrospectively assessed the respective values of blood pressure components derived from conventional and 24-h recordings (ABPM) as predictors of premature delivery in women with gestational hypertension based on office readings from 26th week of gestation onwards. Blood pressures were measured conventionally and over 24 h. Standard medical and obstetric history, and standard laboratory work-up were taken into account. The mean (+/- standard deviation, SD) age of 123 women was 29 +/- 6 years. Current pregnancy was, on average, the second. The conventional systolic (SBP)/diastolic (DBP) blood pressure averaged 140 +/- 19/92 +/- 14 mmHg, and pulse pressure (PP) and mean arterial pressure (MBP) averaged 48 +/- 10 and 108 +/- 15 mmHg. The corresponding values derived from ABPM were 135 +/- 16/90 +/- 11, 47 +/- 9 and 105 +/- 12 mmHg. The 24-h blood pressures had better prognostic value than the conventional blood pressures. The 24-h SBP predicted risk of premature delivery and was inversely related to the duration of pregnancy and birth weight. After the exclusion of 41 women with white-coat hypertension, the highest predictive value was associated with PP. PP wider by 1SD was associated with 66% higher risk of premature delivery, and was associated with shortening of pregnancy by 2 weeks and 400 g lower birth weight, even after adjustment for SBP. In conclusion, ABPM is superior to conventional blood pressure measurements in predicting adverse outcome of pregnancy. Twenty-four-hour PP, of all classic indices, seems to be most closely related to increase of that risk.

Comparative clinical studies of fertility and infertility in women with endometriosis.

OBJECTIVE: To compare clinical characteristics of infertile and fertile patients with endometriosis. MATERIAL AND METHODS: We evaluated medical records of women who underwent surgical treatment of endometriosis (n=284) between January 1999 and December 2003. Our study included only cases of histopathologically proven pelvic endometriosis (n=269). These patients were categorized into two groups named after infertile (n=45) and fertile cases (n=224). Clinical data were compared. RESULTS: Infertile patients are younger (t student. P=0.0000), have lower weight (Wilcoxon test P=0.0150), lower blood pressure--either systolic (Wilcoxon test P=0.0006) or diastolic (Wilcoxon test P=0.0007), separate noncystic endometriotic leasions occur frequently among these cases (Pearson chi-square P=0.000). CONCLUSION: Noncystic endometriotic implants are more strongly related to infertility than endometriomas. The relationship between blood pressure and infertility requires further investigation. endometriosis.

[Phalanges necrosis--a rare manifestation of "hand-foot" syndrome induced by gemcitabine used in the second--line therapy for progressive ovarian cancer. A case report]. / Zespól dloniowo-podeszwowy pod postacia martwicy palców rak. Przypadek rzadkiego powiklania w nastepstwie zastosowania gemcytabiny u chorej z zaawansowanym rakiem jajnika.

"Hand-foot" syndrome is a well-documented, dermatologic reaction after several chemotherapeutic agents with wild spectrum of symptoms. To the best of our knowledge, palmar-plantar erythrodysesthesia syndrome--presented as irreversible cytotoxic side effect induced by gemcitabine alone--has not been reported so far. We present a case of a patient with a history of peripheral sensory neuropathy who developed a painless finger necrosis caused by gemcitabine used in the second-line therapy for progressive ovary cancer.

High frequency of BRCA1/2 germline mutations in consecutive ovarian cancer patients in Poland.

BACKGROUND: We estimated the prevalence of BRCA1/2 germline mutations in consecutive ovarian cancers and correlated the mutation status with clinicopathological features. METHODS: 151 consecutive primary ovarian cancer patients were screened for BRCA1/2 germline mutations. RESULTS: We identified BRCA1/2 germline mutations in 21 (13.9%) patients. Seventeen (81%) of carriers have BRCA1 and four (19%) have BRCA2 mutation. BRCA1/2 carriers have a distinctly longer overall survival than sporadic cases (log-rank, p=0.014). CONCLUSIONS: The relatively high proportion of BRCA1/2 carriers among unselected ovarian cancer patients indicates the necessity of searching for recurrent BRCA mutations in each case of ovarian carcinoma. This routine screen should be widened to include denaturing high performance liquid chromatography (DHPLC) analysis of both exons 11 of BRCA1 and BRCA2 genes in women with positive family history.

[A rare case of post-partum urethrovaginal fistula. Management of obstetric complications]. / Przetoka cewkowo-pochwowa jako powiklanie przedluzonego porodu.

A rare case of a 22-year old patient with obstetric urethrovaginal fistula, resulting in urinary incontinence, has been reported in the following report The emphasis is put on a number of medical and social consequences related to the formation of the fistula. Authors have presented the diagnostic difficulties. The aim of the report is to draw attention to the probable complications following prolonged labour and the necessity of appropriate treatment.

[Sentinel node identification in cervical cancer patients: a feasibility study]. / Identyfikacja wqzla wartowniczego w inwazyjnym raku szyjki macicy.

OBJECTIVES: According to recommendations, the sentinel node (SN) procedure results causes of less radical treatment and reduction of morbidity. DESIGN: The aim of this study was to determine the feasibility of sentinel lymph node identification using radioisotopic lymphatic mapping with technetium-99m labelled nanocolloid and blue dye injection in patients with early-stage cervical cancer. MATERIAL AND METHODS: 100 patients with FIGO stage from IB1 to IIA primary carcinoma undergoing radical hysterectomy with pelvic lymphadenectomy have been investigated. RESULTS: 84% of the patients have been diagnosed with at least one-sided SN and 66% of them with two-sided SN. The sentinel detection rates, depending on the stages, were as following: 181-96.6%, IB12-66.7%, IIA-62.5%. Successful identification of SN was less likely in patients with tumors > 2cm (54% of SN) compared with those with tumors < or = 2cm (96% of SN). The false negative rate for the SN procedure was 3% (3/100). In all false negative SNs the primary cervical tumor was above 2cm and there was an isthmus infiltration. SN detection had 86.4% sensitivity, 100% specificity, and 95.3% negative predictive value. CONCLUSION: Sentinel node mapping method for cervical cancer patients undergoing primary surgical therapy is a feasible option. The sentinel node detection rate is relatively high and depends on FIGO stage and the tumor size. The appliance of SN into cervical cancer procedures allows us to refrain from a surgery in favor of radiochemiotherapy, seems to be the right course of action in deciding treatment and may result in fewer postoperative complications rate.

[Late recurrence of malignant tumours 20 years after diagnosis and treatment]. / Pózne wznowy nowotworów zlosliwych po 20 latach od rozpoznania i leczenia.

Late recurrence of malignant tumours is very rare phenomenon. Seven cases of late recurrent malignancy (melanoma--2 cases, clear cell renal cancer, stomach sarcoma, breast cancer, basal cell carcinoma, ovarian cancer) after 20-32 (average 22.3) years from diagnosis and treatment were described. The histopathological examination results of primary and recurrent tumours were identical. Six patients died at the age from 40 to 89 (mean 66.8) years. The survival of patients after recurrence was from 4 to 11 (mean 7.3) months.

Major complications following exenteration in cases of pelvic malignancy: a 10-year experience.

AIM: To analyze the major complications after exenteration of gynecological and rectal malignancies. METHODS: Twenty-two patients with gynecological malignancy and 6 with rectal malignancy underwent pelvic exenteration (PE) between 1996 and 2005. PE was performed for primary malignancy in 71.4% of cases (vulvar cancer in 13, cancer rectal in 5, cervical cancer in 1 and Bartholin's gland cancer in 1 cases respectively and recurrent malignancy in 28.6% of cases (cervical cancer in 5, ovarian cancer in 1, uterine sarcoma in 1 and rectal cancer in 1 cases respectively). Posterior PE, total PE and anterior PE were most often performed. RESULTS: Major complications in the operative field involving the urinary tract infection or the wound dehiscence occurred in 12 patients (42.9%). Early complications included massive bleeding from the sacral plexus, adult respiratory distress syndrome (ARDS), thrombophlebitis, acute renal failure, urinary bladder dysfunction, ureter damage, re-operation and pulmonary embolus. Urinary incontinence was observed in 2 women as a late complication. In 1 patient a nephrostomy was performed in 1 patient due to extensive hydronephrosis and 1 patient had complications connected with the gastrointestinal tract. The mortality rate was 7%, of which inter-operative mortality accounted for 3.5%. Major complications often occurred in advanced primary vulvar cancer affecting those with recurrent malignancies. CONCLUSION: PE is more beneficial to patients with primary vulvar and rectal cancer than to those with recurrent cancer. Knowledge of the inherent complications and morbidity of PE is essential.

[DNA ploidy and results of first line chemotherapy in ovarian cancer patients]. / Wplyw ploidii DNA na rokowanie w zaleznosci od odpowiedzi na chemioterapie i rzutu u chorych na raka jajnika.

AIM OF THE STUDY: The prognostic significance of DNA ploidy in ovarian cancer patients determined by flow cytometric analysis, in correlation with effectiveness of first line chemotherapy. MATERIAL AND METHODS: DNA ploidy by FC was investigated in group of 102 ovarian cancer patients from fresh frozen samples (4 patients was excluded from the study). RESULTS: Positive answer for first line treatment we notified in 64(62,75%) cases, lack of answer 34 (37,25%) patients. Aneuploidy was more frequent in negative group 31(91,18%), diploid tumours occurred in 3(8.82%) cases. In positive group aneuploid tumours occurred in 29(45,31%) and diploid in 35(54,69%) patients (p<0,001). Median survival in positive group--45 months, in negative group 12 months (p<0,0001). In positive group median survival in patients with aneuploid tumours--31 months, in patients with diploid tumours median survival was not reached (p=0,0102). In negative group DNA ploidy has no impact on survival (p=0,1027) CONCLUSIONS: 1. DNA ploidy determined by flow cytometry is prognostic factor in ovarian cancer patients who answered positively for first line treatment. 2. Aneuploid tumours appear much often then diploid in group of patient who did not answer for first line chemotherapy 3. Patients with diploid tumours have better prognosis. 4. Lack of positive answer for first line treatment is bad prognostic factor.

[The course of actinomycosis of female reproductive organs mimicking ovarian cancer--the diagnostic limits and difficulties]. / Promienica narzadu plciowego o przebiegu klinicznym podobnym do raka jajnika--trudnosci i ograniczenia diagnostyczne.

A case of actinomycosis presenting as tubo-ovarian abscess, misdiagnosed as ovarian malignancy in 54-year old woman with IUD is reported. Author presents the diagnostic problems due to uncommon location, no reliable clinical manifestation and nonspecific CT imaging findings, based on current literature. Knowledge of the characteristic features may help one consider the possibility of actinomycetic infection in the differential diagnosis, in patients with a previous history of predisposing factors and treat them appropriately.