HE4 is an independent prognostic marker in endometrial cancer patients

Objective

To evaluate the prognostic value of pretherapeutic serum HE4 in endometrial cancer in comparison to CA125.

Methods

HE4 and CA125 serum levels were analyzed by means of chemiluminescent microparticle immunoassays in 183 patients with endometrial cancer treated at the Department of Obstetrics and Gynecology, Innsbruck Medical University, between 1999 and 2009. The Kaplan-Meier method and Cox's proportional hazards analysis were performed to determine the prognostic significance of HE4, CA125 and the combination of both markers.

Results

In univariate analysis both markers, HE4 and CA125, were of prognostic value for overall survival (p < 0.001 and p = 0.028) and disease-free survival (p = 0.015 and p = 0.045). In multivariate analysis HE4 was seen to have independent prognostic value in overall survival (HR 2.407, p = 0.017) in contrast to CA125. The combination of both markers showed a higher hazard ratio (HR 4.04, p = 0.023) for overall survival in comparison to HE4 alone. In the subgroup endometrioid histological type (n = 132) only HE4 was of prognostic value for overall survival in univariate (p = 0.001) and multivariate analysis (p = 0.023).

Conclusions

Pretherapeutic serum HE4 levels alone and in combination with CA125 are an independent prognostic marker in endometrial cancer patients.     

CA 125 normalization with chemotherapy is independently predictive of survival in advanced endometrial cancer

Objective

Changes in CA 125 with chemotherapy predict outcome for epithelial ovarian cancer. There is no such data for advanced endometrial cancer.

Method

Retrospective review of all women receiving carboplatin and paclitaxel for advanced endometrial cancer at any of the institutions of the British Columbia Cancer Agency between September 1995 and September 2006.

Results

185 newly diagnosed women were treated. Univariable analysis for progression-free survival identified as adverse predictors: grade 3, positive residual, age > 60, deep myometrial invasion, increasing stage/substage, papillary serous subtype, presence of cervical involvement, ECOG 1 or greater, CA 125 above 35 either preoperatively or at start of cycle 1 and CA 125 greater than 24 at the start of cycle 3. Upon multivariate analysis, CA 125 above 24 at cycle 3, grade 3 and positive residual remained as independent predictors. The single most important factor identified by decision tree analysis was CA 125 level at cycle 3.

Conclusion

As with epithelial ovarian cancer, changes in CA 125 are highly predictive of outcome for advanced, chemotherapy treated endometrial cancer.     

The feasibility of carboplatin-based intraperitoneal chemotherapy in ovarian cancer

Objective

To reduce toxicities in cisplatin-based intraperitoneal (IP) chemotherapy, we substituted carboplatin for cisplatin. The purpose of this study was to provide preliminary toxicity data of carboplatin-based IP chemotherapy and to evaluate the feasibility of this chemotherapy regimen in patients with ovarian cancer after primary debulking surgery.

Study design

The toxicity data of 19 primary ovarian cancer patients (IP group) who underwent carboplatin-based IP and intravenous (IV) combination chemotherapy (IP carboplatin AUC 5 on day 1, IV paclitaxel 175 mg/m² on day 2, and IP paclitaxel 60 mg/m² on day 8) after primary debulking surgery were retrospectively analyzed and compared to 34 patients (IV group) who were treated with standard platinum-based IV chemotherapy during the same period.

Results

The toxicity data in a total of 118 cycles were analyzed. Grade 3 or 4 leukopenia, neutropenia, and pain were more common in the IP group than the IV group. There were seven catheter-related complications. Fourteen patients (73.7%) were able to complete six cycles or more of IP chemotherapy. Survival results in the IP group were compared with those from the IV group; a prolonged progression-free survival was observed (26.6 vs. 20.7 months; p = 0.038). Compared to the previous results with cisplatin-based IP chemotherapy, there was no significant difference in hematologic events. However, gastrointestinal, neurologic, and metabolic events in this study were definitely lower compared to those of cisplatin-based IP chemotherapy.

Conclusions

Carboplatin-based IP and IV combination chemotherapy is feasible in patients with ovarian carcinoma after primary debulking surgery.     

Prognostic value of elevated preoperative serum CA125 in ovarian tumors of low malignant potential: a multinational collaborative study (ANZGOG0801)

Objective

Previous studies on prognostic factors in ovarian tumors of low malignant potential (LMP) were too small for robust conclusions. We examined the prognostic impact of preoperative serum CA125 ≥ 50 U/ml levels in patients diagnosed with ovarian LMP tumors in a large multinational cohort.

Methods

This retrospective study included 940 patients with ovarian LMP tumors diagnosed between 1985 and 2008 at six gynecologic cancer centers. Patients either had radical treatment (bilateral salpingo-oophorectomy with or without hysterectomy) or conservative, fertility-sparing treatment. Multivariate Cox proportional hazard models were used to determine independent prognostic factors for disease-free (DFS) and overall survival (OS). Based on receiver operating characteristic curve (ROC), a preoperative serum CA125 level ≥ 50 U/ml was considered “elevated”.

Results

CA125 was more often elevated in serous than in mucinous tumors and in advanced FIGO stages (2 to 4) compared to stage1. DFS at 5 years was 89% and 95% in patients with elevated and normal CA125 levels (p < 0.05). Similarly, the 5-year OS was 90% among patients with elevated CA125 compared to 95% among patients with normal levels (p < 0.05). For both DFS and OS elevated CA125 levels and advanced stages of the disease were independent prognostic factors. Analysis of subgroups revealed that CA125 was only prognostic in serous LMP tumors.

Conclusions

In the context of serous ovarian LMP tumors, elevated preoperative serum CA125 represents a biomarker independently associated with impaired disease-free and overall survival. CA125 is available in most centers and could inform surgeons about the risk of treatment failure.     

Patterns of recurrence in advanced epithelial ovarian, fallopian tube and peritoneal cancers treated with intraperitoneal chemotherapy

Objectives

To examine the distribution and outcomes of recurrent disease in patients with ovarian, fallopian tube and peritoneal cancers after optimal cytoreduction and adjuvant intraperitoneal (IP) chemotherapy.

Methods

All patients diagnosed with ovarian, fallopian tube, or peritoneal cancer between 2004 and 2009 who underwent optimal cytoreductive surgery and received adjuvant intravenous (IV) and IP chemotherapy with paclitaxel and a platinum-based agent were eligible. Age, performance status, tumor origin, stage, and grade were recorded. First recurrences were identified using CA125 values, radiographic studies, operative notes, and pathology reports. Sites of recurrence were classified as intraperitoneal (IP), extraperitoneal (EP) or distant. Kaplan-Meier estimates and Cox multivariate regression models were used to assess the associations between recurrent disease distribution and progression-free survival (PFS) and overall survival (OS).

Results

One hundred forty-three patients met the criteria for inclusion. The majority were Stage III (86%) and serous histology (77%). Eighty-four (58.7%) received IV/IP paclitaxel/cisplatin per GOG-172 and 59 (41.3%) received IV/IP paclitaxel/carboplatin. Seventy-two percent completed 6 cycles. Ninety (62.9%) patients manifested a recurrence. One-hundred twelve sites of recurrence were identified with 70 (62.5%) IP and 42 (37.5%) EP and distant sites. Nineteen (21%) recurred in more than one site, i.e. both IP and EP locations. Site of recurrence did not impact OS, however, patients who recurred in multiples sites had significantly worse OS (p < 0.001).

Conclusion

Approximately 40% of patients treated with IP chemotherapy have a first recurrence outside the peritoneal cavity. Though site of recurrence did not affect OS those with multi-focal recurrence demonstrate worse survival.     

Carbetocina vs. oxitocina para la prevención de hemorragia posparto en pacientes grandes multíparas: estudio aleatorizado controlado

Objective

Carbetocin is a long-acting oxytocin analogue that can be used as a uterotonic agent in the management of postpartum hemorrhage. The purpose of this study was to compare the effectiveness of carbetocin (100 μg IV) with that of oxytocin (20 U IV) in the prevention of postpartum bleeding in grand multiparous patients (five or more pregnancies).

Design

Prospective, randomized controlled trial.

Population

Patients with vaginal deliveries of singleton pregnancies (≥28 weeks).

Methods

A total of 135 patients were selected to receive 100 μg of carbetocin in a single IV dose or 400 mU oxytocin/min (LR 1000 cc+20 U oxytocin, 100 cc/h) at the end of the third stage of labor.Main outcome measures: Postpartum hemorrhage despite the medication used, requiring the use of alternative measures.

Results

There were no statistically significant differences in the frequency of therapeutic failures or the need to transfuse blood products. The use of carbetocin was associated with a lesser need to manually explore the uterus (RR: 0.12; 95% CL 0.03-0.48). The incidence of adverse effects was similar in both groups. There were no differences in the effects of drugs on breastfeeding.

Conclusions

The use of a single IV dose of carbetocin is as effective as 20 IV units of oxytocin in the prevention of postpartum hemorrhage in grand multiparous women after vaginal delivery. The incidence of adverse effects and complications was similar in the two groups. Carbetocin should be considered a useful alternative to conventional uterotonics in the prevention of postpartum bleeding in grand multiparous patients.     

Does intraperitoneal chemotherapy benefit optimally debulked epithelial ovarian cancer patients after neoadjuvant chemotherapy?

Objective

To compare survival of ovarian cancer patients treated with neoadjuvant chemotherapy followed by intraperitoneal (IP) versus intravenous (IV) chemotherapy after optimal interval debulking.

Methods

Optimally debulked patients after neoadjuvant IV platinum paclitaxel based chemotherapy followed by postoperative IP chemotherapy were reviewed. A similar cohort of patients treated postoperatively with IV platinum paclitaxel based chemotherapy was chosen as control. Patient and disease-related demographics were abstracted from electronic hospital medical records. Associations between categorical variables were determined using Chi square test. Cox regression and Kaplan-Meier method estimated progression-free and overall survival.

Results

Fifty-four IV and 17 IP treated patients after interval debulking were studied. The majority of patients had serous histology and grade 3 tumours. There was no significant difference between the two groups with respect to age and proportion of microscopic residual disease. Patients with macroscopic residual disease had a significantly worse prognosis (HR = 2.17, 95% CI = 1.23-3.85, p = 0.008). Clinical complete response after primary treatment was 67% and 88% in the IV and IP group, respectively (p = 0.36). Estimated mean progression-free survival was 18 months in the IV group and 14.1 months in the IP group (p = 0.42). IP chemotherapy was not predictive of progression-free survival in the Cox model adjusted for age and residual disease status (HR = 1.22, 95% CI = 0.62-2.4, p = 0.56). Estimated mean survival was 68.9 months in the IV group and 37.5 months in the IP group (p = 0.85).

Conclusions

Survival benefit associated with IP chemotherapy after optimal upfront surgery may not translate to the neoadjuvant setting.     

Proteomic biomarkers apolipoprotein A1, truncated transthyretin and connective tissue activating protein III enhance the sensitivity of CA125 for detecting early stage epithelial ovarian cancer

Objective

The low prevalence of ovarian cancer demands both high sensitivity (> 75%) and specificity (99.6%) to achieve a positive predictive value of 10% for successful early detection. Utilizing a two stage strategy where serum marker(s) prompt the performance of transvaginal sonography (TVS) in a limited number (2%) of women could reduce the requisite specificity for serum markers to 98%. We have attempted to improve sensitivity by combining CA125 with proteomic markers.

Methods

Sera from 41 patients with early stage (I/II) and 51 with late stage (III/IV) epithelial ovarian cancer, 40 with benign disease and 99 healthy individuals, were analyzed to measure 7 proteins [Apolipoprotein A1 (Apo-A1), truncated transthyretin (TT), transferrin, hepcidin, ß-2-microglobulin (ß2M), Connective Tissue Activating Protein III (CTAPIII), and Inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4)]. Statistical models were fit by logistic regression, followed by optimization of factors retained in the models determined by optimizing the Akaike Information Criterion. A validation set included 136 stage I ovarian cancers, 140 benign pelvic masses and 174 healthy controls.

Results

In a training set analysis, the 3 most effective biomarkers (Apo-A1, TT and CTAPIII) exhibited 54% sensitivity at 98% specificity, CA125 alone produced 68% sensitivity and the combination increased sensitivity to 88%. In a validation set, the marker panel plus CA125 produced a sensitivity of 84% at 98% specificity (P = 0.015, McNemar's test).

Conclusion

Combining a panel of proteomic markers with CA125 could provide a first step in a sequential two-stage strategy with TVS for early detection of ovarian cancer.     

A phase I study with an expanded cohort to assess the feasibility of intravenous paclitaxel, intraperitoneal carboplatin and intraperitoneal paclitaxel in patients with untreated ovarian, fallopian tube or primary peritoneal carcinoma: a Gynecologic Oncology Group study

Objective

To define the maximum tolerated dose (MTD) and assess the feasibility of intravenous (IV) paclitaxel, intraperitoneal (IP) carboplatin, and IP paclitaxel in women with newly diagnosed Stages II-IV ovarian, fallopian tube, or primary peritoneal carcinoma.

Methods

Patients received escalating doses of paclitaxel IV and carboplatin IP on day 1 and paclitaxel IP 60 mg/m² on day 8. A standard 3 + 3 design was used in the escalation phase. A two-stage group sequential design with 20 patients at the MTD was used in the feasibility phase. Patient-reported neurotoxicity was assessed pre and post treatment.

Results

Patients were treated with paclitaxel 175 mg/m² IV and carboplatin IP from AUC 5-7 on day 1 and paclitaxel 60 mg/m² IP on day 8. The MTD was estimated at carboplatin AUC 6 IP and 25 patients enrolled at this dose level. Within the first 4 cycles, seven (35%) of twenty evaluable patients had dose-limiting toxicities (DLTs) including grade 4 thrombocytopenia (1), grade 3 neutropenic fever (3), > 2 week delay due to ANC recovery (1), grade 3 LFT (1), and grade 3 infection (1). De-escalation to paclitaxel 135 mg/m² IV was given to improve the safety. After six evaluable patients completed 4 cycles without a DLT, bevacizumab was added and six evaluable patients completed 4 cycles with one DLT (grade 3 hyponatremia).

Conclusions

Paclitaxel at 175 mg/m² IV, carboplatin AUC 6 IP day 1 and paclitaxel 60 mg/m² IP day 8 yield 18-56% patients with DLTs. The tolerability of the regimen in combination with bevacizumab was indicated in a small cohort.     

Patterns of first recurrence following adjuvant intraperitoneal chemotherapy for stage IIIC ovarian cancer

Objective

Adjuvant intraperitoneal (IP) platinum-based chemotherapy has been shown to improve outcome for patients with advanced ovarian cancer. We hypothesize that patients who have received adjuvant IP chemotherapy more commonly recur first at extraperitoneal sites than patients who have received adjuvant intravenous (IV) chemotherapy.

Methods

Patients with newly diagnosed stage IIIC optimally debulked serous ovarian cancer were identified from institutional databases. Patterns of recurrence were compared between patients who received IV and IP chemotherapy using standard two-sided statistical tests.

Results

Of the 104 patients who met inclusion criteria, 60 received IV chemotherapy and 44 received IP chemotherapy. Patients in the IV group had a first recurrence more commonly in the lower abdomen or pelvis than the IP group. Patients in the IP group more commonly recurred in the upper abdomen and extra-abdominal lymph nodes. More patients in the IP group than the IV group recurred at extra-abdominal sites (45.5% versus 23.3%, P = 0.018).

Conclusions

Patients receiving adjuvant IP chemotherapy are less likely to first recur in the lower abdomen or pelvis and more likely to recur outside of the abdominal cavity. The data suggest that IP chemotherapy is highly effective in the anatomic areas of peritoneal distribution.     

The value of serological markers in the diagnosis and prognosis of endometriosis: a prospective case-control study

Objective

We analyzed selected well-known and less well-known serum markers that have been proposed for diagnosis and severity assessment of endometriosis, in a case-control study.

Study design

This prospective study was carried out in a Clinical Department of Gynecology in Iasi, Romania. Study participants included endometriosis patients, and controls in whom laparoscopy had excluded endometriosis. Each case and control was investigated for serum levels of CA125, TNF, IL-1, IL-6 and IL-8. The data were correlated with clinical symptoms and revised American Fertility Society (rAFS) score and stage, and interpreted by Mann-Whitney U-test and ANOVA regression analysis.

Results

Over the course of 1 year, 24 cases of endometriosis and 24 controls of matched age were selected. The rAFS stages were: stage I, 12.5%; stage II, 16.7%; stage III, 58.3%; and stage IV, 12.5%. CA125 levels were over the cut-off of 35 IU/l in 54% of patients (versus 8% of controls), averaging 67.5 (CI95: ±17.5). The sensitivity and specificity were 54% and 91%, respectively, with a p value of <0.001 (statistically significant). For IL-6, 71% of cases and 87% of controls were above the cut-off of 2 pg/ml, with an average of 11.83 ± 7. The sensitivity and specificity were 71% and 12%, respectively, but the difference was not statistically significant, p = 0.071. Other tested serum markers had no discrimination value. A correlation with severity of endometriosis was seen for CA125 (p = 0.03) but not for IL-6, by ANOVA.

Conclusion

CA125 correlated with endometriosis screening and severity, indicating its superiority as a marker for further, larger studies.     

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained. Continuous variables were evaluated by Student's t test or Wilcoxon-Mann-Whitney test.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively. Comparing patients with NRD v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1). There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001). In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.     

The impact of pretreatment thrombocytosis and persistent thrombocytosis after adjuvant chemotherapy in patients with advanced epithelial ovarian cancer

Objective

To evaluate the impact of both pretreatment thrombocytosis, and platelet count reduction post-adjuvant chemotherapy, on survival in patients with advanced epithelial ovarian cancer.

Methods

Records of 179 women who underwent cytoreductive surgery for FIGO stage III or IV epithelial ovarian cancer and received six cycles of platinum/paclitaxel-based chemotherapy between July1998 and March 2009 were retrospectively reviewed. Platelet ratio was defined as the preoperative platelet count divided by the platelet count after chemotherapy. The prognostic significance of thrombocytosis and platelet ratio, together with various clinicopathological factors, were evaluated by multivariate analysis.

Results

Sixty-two of 179 (34.6%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis had greater elevations of CA-125 (p < 0.0001) and a greater volume of ascites (p = 0.007). On multivariate analysis, thrombocytosis and CA-125 elevation retained significance as indicators of poor prognosis in patients with stage III or IV disease. In patients with normal CA-125 after chemotherapy, a high platelet ratio was an independent risk factor for reduced survival (p = 0.05).

Conclusions

Preoperative thrombocytosis and a high platelet ratio appear to be poor prognostic factors of survival in patients with advanced epithelial ovarian cancer who were treated with cytoreductive surgery and adjuvant platinum/paclitaxel-based chemotherapy.     

Progression-free and overall survival of a modified outpatient regimen of primary intravenous/intraperitoneal paclitaxel and intraperitoneal cisplatin in ovarian, fallopian tube, and primary peritoneal cancer

Objective

GOG study 172 demonstrated improved progression-free (PFS) and overall (OS) survival for patients with stage III optimally debulked ovarian and peritoneal carcinoma treated with IV/IP paclitaxel and IP cisplatin compared to standard IV therapy. The inpatient administration, toxicity profile, and limited completion rate have been blamed for the lack of acceptance and widespread use of this regimen. We sought to evaluate the PFS, OS, toxicity, and completion rate of a modified outpatient IP regimen.

Methods

Using a prospectively maintained database, we evaluated the outcomes of patients who underwent primary optimal cytoreduction for stage III ovarian, tubal, or peritoneal carcinoma followed by IV/IP chemotherapy from 1/05-3/09. Our modified regimen was as follows: IV paclitaxel (135 mg/m²) over 3 h on day 1, IP cisplatin (75 mg/m²) on day 2, and IP paclitaxel (60 mg/m²) on day 8, given every 21 days for 6 cycles.

Results

We identified 102 patients who initiated the modified IV/IP regimen and completed chemotherapy. The median follow-up was 43 months. The median age at diagnosis was 57 years (range, 23-76). Primary disease site was: ovary, 77 (75%); fallopian tube, 13 (13%); peritoneum, 12 (12%). FIGO stage was: IIIA, 8 (8%); IIIB, 4 (4%); IIIC, 90 (88%). Residual disease after cytoreduction was: none, 58 (57%); ≤ 1 cm, 44 (43%). The most frequent grade 3/4 toxicities were: neutropenia, 12 (12%); gastrointestinal, 8 (8%); neurologic, 6 (6%). Eighty-two (80%) of 102 patients completed 4 or more cycles of IV/IP therapy; 56 (55%) completed all 6 cycles. The median PFS and OS were 29 and 67 months, respectively.

Conclusions

By modifying the GOG 172 treatment regimen, convenience, toxicity, and tolerability appear improved, with survival outcomes similar to those of GOG 172. This modified IV/IP regimen warrants further study.     

Effects of bevacizumab and pegylated liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers

Objectives

Currently, pegylated liposomal doxorubicin (PLD) is regarded as one of the standard treatment options in recurrent ovarian cancers (ROC). Bevacizumab has shown significant antitumor activity for ROC in single-agent or in combination with cytotoxic agents. We have conducted a preliminary study to investigate effects of combination of bevacizumab and PLD for heavily pretreated patients with ROC.

Methods

Thirty patients with ROC were treated with combination therapy with weekly bevacizumab and PLD, 2 mg/kg of continuous weekly bevacizumab and 10 mg/m² of PLD (3 weeks on, 1 week off). The treatment was continued until development of disease progression, or unmanageable adverse effects. Response evaluation was based upon Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and Gynecologic Cancer Intergroup (GCIG) CA125 response criteria. Adverse effects were analyzed according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

Results

Overall response rate was 33%, and clinical benefit rate (CR + PD + SD) was 73%. Median progression-free survival was 6 months (range: 2-20 months), and a 6-months progression-free survival was 47%. Any hematological toxicities more than grade 3 were not observed. Two cases developed non-hematologic toxicities more than grade 2; a case with grade 3 hand-foot syndrome, another with grade 3 gastrointestinal perforation (GIP). The case with GIP was conservatively treated and recovered after 2 months, and there was no case with treatment-related death.

Conclusion

The present investigation suggested that combination therapy with bevacizumab and PLD was active and well tolerated for patients with ROC. We recommend the regimen be evaluated in further clinical studies.     

Measurement of the minimum apparent diffusion coefficient (ADCmin) of the primary tumor and CA125 are predictive of disease recurrence for patients with endometrial cancer

Objective

The purpose of this study was to evaluate whether preoperative measurements of the minimum apparent diffusion coefficient (ADCmin) on magnetic resonance imaging (MRI) and the tumor marker CA125 are correlated with the clinical characteristics and prognosis of patients with endometrial cancer.

Methods

The distribution of cases that scored positive for each of the biological parameters examined and the correlations with the ADCmin of the primary tumor and the serum tumor marker CA125 were examined for 111 patients with preoperative assessment of primary endometrial cancer.

Results

There were significant correlations between the ADCmin of the primary tumor and the FIGO stage (P = 0.001), depth of myometrial invasion (P < 0.001), cervical involvement (P = 0.003), lymph node metastasis (P = 0.027), ovarian metastasis (P < 0.001), peritoneal cytology (P = 0.027) and tumor maximum size (P < 0.001). The disease-free survival (DFS) rate of patients with high serum CA125 was significantly lower than that of patients with low serum CA125 (P = 0.0395). The DFS rate of patients with a low ADCmin of the primary tumor was significantly lower than that of patients with a high ADCmin of the primary tumor (P < 0.001). In particular, the ADCmin of the primary tumor was an independent factor for disease recurrence in a multivariate analysis (P = 0.019).

Conclusions

The present findings indicate that a low preoperative ADCmin of the primary tumor is an important predictive factor for identifying endometrial cancer patients with a risk of disease recurrence.     

Bilateral uterine artery ligation plus B-Lynch procedure for atonic postpartum hemorrhage with placenta accreta

Objective

To assess the effectiveness of bilateral uterine artery ligation followed by B-Lynch compression suturing in women with atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta.

Method

This protocol was followed in 26 women undergoing cesarean delivery for placenta accreta.

Results

Two women died from disseminated intravascular coagulopathy. In the remaining 24 women, placental remnants completely disappeared within 8 months and ovulation resumed after a mean ± SD of 51.6 ± 3.2 days. Moreover, 18 women (75%) became pregnant within 12 months.

Conclusion

Atonic postpartum hemorrhage and placental site bleeding due to adherent placenta accreta can be safely controlled by bilateral uterine artery ligation followed by B-Lynch compression suturing in women who desire to remain fertile.     

A nomogram for estimating the probability of ovarian cancer

Objective

Accurate preoperative estimates of the probability of malignancy in women with adnexal masses are essential for ensuring optimal care. This study presents a new statistical model for combining predictive information and a graphic decision support tool for calculating risk of malignancy.

Methods

The study included 153 women treated with definitive surgery for adnexal mass between 2001 and 2007 with preoperative ultrasound testing and a serum CA125. Multivariable logistic regression was used to develop a statistical model for estimating the probability of ovarian cancer as a function of age, ultrasound score, and CA125 value, with adjustments for nonlinear and interactive relationships.

Results

A total of 20 cases of pathologically confirmed cancer (13 invasive malignancies, and 7 tumors of low malignant potential) were identified (20/153 = 13%). The model obtained excellent discrimination (ROC area = 0.87), explained nearly half of the observed variation in the risk of malignancy (R² = 0.43), and was well calibrated across the full range of malignancy probabilities. The model equation is represented in the form of a nomogram, which can be used to calculate preoperative probability of malignancy. At a 5% risk of malignancy threshold, the model has a sensitivity of 90% and a specificity of 73%.

Conclusions

Statistical models for estimating the probability of adnexal mass malignancy are substantially improved by including adjustments for non-linear relationships among key variables. A clinically relevant nomogram provides an objective tool to further aid clinicians in counseling patients and ensuring proper referral to surgical sub-specialists when indicated.     

Improved quality of life is partly explained by fewer symptoms after treatment of fibroids with mifepristone

Objective

To examine mediators of mifepristone treatment on improvements in health-related quality of life (HRQOL) among women with symptomatic fibroids.

Methods

The study sample included women with symptomatic uterine fibroids who were treated with 5 mg or 2.5 mg of mifepristone or placebo. Assessments of uterine size (ultrasound), pain (McGill pain questionnaire), bleeding (diary), anemia (gm/dL), and HRQOL measured using the uterine fibroid symptom quality of life scale were done at baseline, 3 months, and 6 months. The improvements in HRQOL that could be explained by changes in these clinical factors were assessed.

Results

The final sample included 62 women. Treatment with mifepristone was associated with significant improvement in HRQOL, which was explained in part by reduction in pain (28%, P < 0.001) and bleeding (18%, P < 0.001). Reduction in uterine volume was of marginal significance (P = 0.05) and was associated with a decrease in HRQOL (7%). Much of the impact of treatment on HRQOL (61%) remained unexplained in this model.

Conclusions

Improvements in HRQOL after treatment with mifepristone are partly explained by improvements in pain and bleeding, but not uterine size. However, most of the improvement in HRQOL is not explained by improvements in these clinical parameters.