Endoglin, VEGF, and its receptors in predicting metastases in endometrial carcinoma.

Preoperative evaluation of the risk for metastases in endometrial carcinoma is challenging. The growth of new vessels, angiogenesis, is important for tumor growth and purported to be involved in the metastatic process. The aim of this study was to evaluate the significance of preoperative serum levels and immunohistochemical expression of angiogenic markers in predicting a metastasized disease. Preoperative sera from 98 consecutive women presenting with endometrial carcinoma were collected. Serum concentrations of VEGF, sFLT1, and CD105 were assessed by enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of CD105, VEGF, FLT1, and KDR. The results were correlated to the presence of metastases, presence of deep (≥50%) myometrial invasion, and the histological grade of the tumor. Tumors with other than endometrioid histology were excluded. Of the 80 evaluable patients, 11 had a metastasized disease. The serum concentration of VEGF was higher in the group with metastases than in the group without metastases (median [range], 743 pg/mL [546-1,183 pg/mL] vs. 383 pg/mL [31-1,524 pg/mL], p < 0.001, respectively). In the multivariable analysis, the concentration of VEGF was the sole independent, albeit weak predictive factor for the presence of metastases (odds ratio, 1.004, 95% confidence interval, 1.002-1.007; p = 0.001). The immunohistochemical expression of the markers was not associated with any of the clinicopathological features of the tumors. The results of the present study suggest that preoperative serum VEGF concentration correlates with the presence of metastases in endometrioid endometrial carcinoma.

Predictive value of serum human epididymis protein 4 and cancer antigen 125 concentrations in endometrial carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the performance of preoperative serum levels of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) in the prediction of the presence of metastases in endometrial carcinoma. STUDY DESIGN: Preoperative sera were collected from 98 women with a diagnosis of endometrial carcinoma. The concentrations of HE4 and CA125 were assessed by enzyme-linked immunosorbent assay and correlated with the results of the final histopathologic report. RESULTS: Fourteen patients had metastases (≥stage IIIA, International Federation of Gynecology and Obstetrics 2009 classification). The serum concentrations of HE4 and CA125 were higher in the group with metastases than in the group without metastases (median [interquartile range], 148.6 pmol/L [71.6-219.1 pmol/L] vs 77.2 pmol/L [52.9-99.3 pmol/L]; P = .001; and 20.0 U/mL [10.1-70.8 U/mL] vs 4.3 U/mL [2.9-10.4 U/mL]; P < .001, respectively). By a multivariate analysis, the combination of HE4 and CA125 (a risk score algorithm) was the only predictive factor for the presence of metastases (odds ratio, 21.562; 95% confidence interval, 5.472-84.963; P < .001), and the grade was the predictor for a deep (≥50%) myometrial invasion by the tumor (odds ratio, 2.005; 95% confidence interval, 1.123-3.581; P = .019). The sensitivity, specificity, positive predictive value, and negative predictive value for the combination of the markers to predict the presence of metastases were 71.4%, 89.5%, 55.6%, and 94.4%, respectively. CONCLUSION: A combination of preoperative HE4 and CA125 seems to be a better predictor of metastatic disease than either 1 alone in endometrial carcinoma.

[Update on current care guidelines: ovarian cancer]. / Munasarjasyöpä.

Ovarian cancer is the most lethal gynaecological cancer. It appears that seemingly ovarian or primary peritoneal carcinomas, in fact, originate from fimbriae. BRCA1/2 mutation carriers are recommended for the removal of ovaries and fimbriae, to reduce the risk of cancer. Treatment of epithelial ovarian cancer is based on the combination of surgery and chemotherapy. The residual tumour volume at the primary operation is the most important predictive factor of survival. The best response at the primary treatment is observed with combination chemotherapy with taxane and platinum. Adding bevacitzumab to first line chemotherapy may improve survival.

[Update on current care guidelines. Diagnosis, treatment and follow-up of cytological changes in the cervix, vagina and vulva]. / Kohdunkaulan, emättimen ja ulkosynnytinten solumuutokset--diagnostiikka, hoito ja seuranta.

Approximately 150 cervical cancer cases are diagnosed in Finland annually. Both incidence and mortality have decreased by 80% since organised screening began. Recently, screening based on primary HPV-testing with Pap-smear triage has been shown to be more sensitive and more specific among women over 35 years old in randomised studies and thus may be implemented in routine. Abnormal findings in Pap smears indicate management. Confirmed CIN1 lesions are followed up and CIN2 and worse lesions treated. Follow-up after treatment should be reliably arranged, because elevated risk of cancer remains over 20 years after treatment. Quality control is of utmost importance.

Transverse myocutaneous gracilis flap reconstruction is feasible after pelvic exenteration: 12-year surgical and oncological results.

INTRODUCTION: Pelvic exenteration (PE) is the only curative treatment for certain locally advanced intrapelvic malignancies. PE has high morbidity, and optimal reconstruction of the pelvic floor remains undetermined. MATERIALS AND METHODS: A retrospective chart review was performed at a tertiary university center to assess the surgical and oncological outcomes of 39 PE procedures over a 12-year period. The majority of patients (n = 25) underwent transverse musculocutaneous gracilis (TMG) flap reconstruction for pelvic floor reconstruction. RESULTS: The 1- and 5-year overall survival (OS) was 72% (95%CI 58%-86%) and 48% (95%CI 31%-65%), respectively. In multivariate analysis, lymph node metastasis (HR 3.070, p = 0.024) and positive surgical margins (HR 3.928, p = 0.009) were risk factors for OS. In this population, 71.8% of the patients had at least one complication. The complication rate was 65.4% and 84.6% for patients with versus without flap reconstruction, respectively (p = 0.191). The length of stay was longer for patients with a major complication 16,0 ±â€¯5,9 days vs. 29,4 ±â€¯14,8 days, p = 0,001, but complications did not affect OS. CONCLUSION: For selected patients, PE is a curative option for locally advanced, residual, or recurrent intrapelvic tumors. Pelvic floor and vulvovaginal defects can reliably be reconstructed using TMG flaps. TMG flaps are favored in our institution over abdominal-based flaps because the donor site morbidity is reasonable and TMG does not interfere with enterostomy.

Ultrasonographic assessment of weight of the myomatous uterus: a pilot study using a new combined geometrical formula.

OBJECTIVE: To evaluate the accuracy of a formula combining the prolate ellipsoid (uterine corpus) and cylinder (uterine cervix) formulas in estimating the preoperative weight of the total uterus using a transvaginal ultrasound probe to obtain the uterine dimensions for the formulas. STUDY DESIGN: Three dimensions of the uterine corpus (length, width and anteroposterior diameter) and cervical length and cervical anteroposterior diameter were preoperatively determined using a transvaginal ultrasound probe in 12 women with symptomatic leiomyomas scheduled to undergo hysterectomy. In two patients whose uteruses were the largest, part of the measurements had to be taken with a transabdominal ultrasound. Three investigators repeated all the rounds of measurements three times, producing in total 108 of findings (12 subjects x 3 investigators x 3 rounds of measurements). The geometric formula of prolate ellipsoid was compared to a formula combining the ellipsoid and cylinder formulas for accuracy in predicting overall uterine size (corpus and cervix) through correlation with hysterectomy specimens. The weight of the uterus in grams was directly derived from the volume of the uterus. RESULTS: All measurements of the uterine corpus and cervix could be obtained preoperatively with a transvaginal ultrasound probe except in two patients who had the largest uteruses. The plain, traditional formula for the prolate ellipsoid overestimated the weight of the uterus and differences between the estimated and the true weight were statistically significant. The difference was not significant when the formula combining the formulas of the prolate ellipsoid and cylinder was used. CONCLUSION: The new formula combining the prolate ellipsoid and cylinder formulas is more accurate in predicting the true total weight of the uterus than the plain prolate ellipsoid formula. The transvaginal ultrasound probe proved useful in evaluating the dimensions of the uterine corpus and cervix.

Ultrasonographic-guided pervaginal cul-de-sac cytology in the follow-up of ovarian carcinoma.

UNLABELLED: The aim of this study was to compare, prospectively, traditional pervaginal cul-de-sac aspiration cytology with an ultrasonographic-guided aspirate in the detection of residual or recurrent ovarian carcinoma. PATIENTS AND METHODS: Fifty-one patients with ovarian carcinoma were monitored during chemotherapy (21 patients) or follow-up (30 patients) after first-line treatment. All patients underwent both traditional blind pervaginal cul-de-sac aspiration cytology and an ultrasonographic-guided pervaginal aspirate. The samples were classified as class 0 or insufficient when no mesothelial cells were detected in the aspirate. The results of cytological classification of the aspirates were compared with each other according to sampling order. RESULTS: Samples were classified as class 0 in 56% when the traditional cul-de-sac aspiration was taken first, and in 73% when ultrasonographic-guided aspiration was taken first (p = 0.249, Fisher's exact test). The number of class 0 samples was smaller among those taken second than among those taken first (22 (44%) vs. 33 (65%), p = 0.046). Four recurrences were detected during the mean follow-up of six months (range 2-11 months) in 30 patients who were followed-up after the first-line treatment. In one case, a positive cul-de-sac cytology was the first and only early indication of recurrence. CONCLUSION: The use of ultrasonography did not improve the accuracy of the cul-de-sac aspiration. The greater amount of fluid in the cul-de-sac during the second sampling might contribute to achieving a better result.

A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Reconstruction of the pelvic floor and the vagina after total pelvic exenteration using the transverse musculocutaneous gracilis flap.

BACKGROUND: Total pelvic exenteration (TPE) is a rare operation in which the pelvic contents are removed entirely. Several options for pelvic floor and vaginal reconstruction have been described including transverse rectus abdominis musculocutaneous (TRAM) or deep inferior epigastric perforator (DIEP) flaps. The transverse musculocutaneous gracilis (TMG) flap has been introduced for breast reconstruction as a free flap. We adopted the pedicled TMG flap for reconstructions after TPE. To the best of our knowledge, this is the first report of this method in the literature. METHODS: Between November 2011 and February 2014, 12 patients underwent TPE and reconstruction with unilateral (six patients) or bilateral (six patients) pedicled TMG flaps. Five patients underwent vaginal reconstruction with bilateral TMG flaps. We describe the operative procedure and the outcome of the operation in these patients. RESULTS: The total mean operative times for TPE with or without vaginal reconstruction were 467 ± 12 and 386 ± 59 min, respectively. The TMG flaps had enough vascular tissue and mobility for reconstructing the TPE defects. There was distal edge necrosis in one out of 18 flaps, while the rest survived completely. During the follow-up, complete wound healing with no signs of weakening of the pelvic floor was observed in all cases. CONCLUSIONS: Soft-tissue reconstructions are needed to reduce complications associated with TPE, to secure the pelvic floor and to reconstruct the vagina in select patients. The TMG flap is a logical flap choice that does not lead to functional deficits, complicate the abdominal ostomies or weaken the abdominal wall. It reduces the length of operation compared to that of abdominal flaps. LEVEL OF EVIDENCE: IV, therapeutic.

Ovarian manifestations in women with autosomal dominant polycystic kidney disease.

BACKGROUND: Ovarian cysts are found in some premenopausal women with autosomal dominant polycystic kidney disease (ADPKD). Liver cysts are the major extrarenal manifestations, frequently found in postmenopausal women. Female steroid hormones may regulate hepatic cystogenesis, but ovarian manifestations in postmenopausal women are unknown. The aim of the present study is to investigate possible ovarian manifestations associated with ADPKD in premenopausal and postmenopausal women. METHODS: The study group included 19 premenopausal or postmenopausal women with ADPKD and 19 age- and parity-matched control women with no history of renal disease. Ovarian structures and volumes were measured by means of transvaginal ultrasonography. RESULTS: Three of 8 premenopausal and 1 of 11 postmenopausal women with ADPKD had a small unilateral single ovarian cyst; there were none in controls. Eight women with ADPKD and 8 controls of premenopausal age had similar ovarian volumes (4.92 +/- 2.97 versus 3.92 +/- 2.60 cm3). Eleven postmenopausal women with ADPKD had an increased mean ovarian volume compared with 11 postmenopausal controls (4.11 +/- 2.60 versus 1.66 +/- 0.96 cm3; P < 0.01). Ovarian volume was not associated with the use of hormonal replacement therapy or impaired renal function in postmenopausal women with ADPKD. CONCLUSION: ADPKD is not associated with cystic ovaries, although single ovarian cysts are occasionally found. Equal ovarian volumes between premenopausal and postmenopausal women with ADPKD suggest a possible indirect effect of polycystic kidneys on gonads in aging women.

Hematological toxicity of salvage treatment after high-dose chemotherapy and conventional chemotherapy of ovarian cancer.

BACKGROUND: To compare the toxicity of salvage chemotherapy (CT) given for recurrent or progressive ovarian cancer (OC) after either high-dose chemotherapy (HDC) or conventional CT. PATIENTS AND METHODS: HDC supported by autologous stem cell transplantation was given to ten OC patients. Seven of them were treated with salvage CT for recurrent disease and were included in this study (Group A). Seven patients with recurrent OC treated primarily with conventional CT (Group B) were matched for age (+/- 3 years), stage and histology. The hematological toxicity of treatment was graded according to the WHO criteria. RESULTS: During salvage CT, grade 3-4 neutropenia was seen in nine out of 81 courses (11.1%) in Group A and in six out of 85 courses (7.1%) in Group B (p <0.1). The use of G-CSF was more common in Group A than in Group B, both during first-line and salvage CT. When the mobilisation courses were excluded in Group A, the use of G-CSF was more common during salvage treatment than during primary treatment (27 out of 81 vs. 16 out of 85, p < 0.05). Also, in Group B the use of G-CSF was more common during salvage CT than during primary treatment (10 out of 85 vs. 0 out of 73, p < 0.01). Grade 3-4 thrombocytopenia was seen in nine out of 81 courses (11.1%) in Group A but in none of the 85 courses (0%) in Group B (p<0.05). No platelet transfusion was needed during salvage treatment. The mean interval of courses in salvage CT was 27.7 days (range 19-71) in Group A and 27.5 days (range 18-120) in Group B (p = ns). Overall survival was 40.4 months in Group A and 33.0 months in Group B (p < 0.1). CONCLUSION: Salvage treatment after HDC was well-tolerated when given with G-CSF support. Salvage chemotherapy could be carried out with the same doses and intervals both for patients treated earlier with HDC and conventional CT.