Sequential bevacizumab and oral cyclophosphamide for recurrent ovarian cancer

Objective

Test the safety and efficacy of sequentially blocking angiogenesis by adding oral cyclophosphamide to bevacizumab following cancer progression on bevacizumab in patients with recurrent ovarian cancer.

Methods

Eligibility included ≤ 2 lines of treatment for recurrence and measurable cancer by RECIST 1.0. Patients received bevacizumab (15 mg/kg every 3 weeks IV) and upon RECIST progression, oral cyclophosphamide (50 mg orally daily) was added. Objectives included safety, toxicities, 3- and 6-month PFS rates, response rate, PFS, and OS.

Results

20 patients were enrolled. Overall response rate was 10%, and 65% of patients had confirmed stable disease (SD). Thirteen of 20 patients received oral cyclophosphamide added to bevacizumab upon bevacizumab progression. Of these 13 patients, 1 patient subsequently achieved a PR (this patient had SD as best response during bevacizumab) and 3 patients had a confirmed SD. For all patients, median PFS was 8.41 months, 6 month PFS rate was 65%, duration of response (DOR) was 7.3 months, and median OS was 22.72 months. Median DOR for patients receiving both bevacizumab and cyclophosphamide was 8.4 months. Most toxicities were grades 1 and 2 and manageable. Grades 3 and grade 4 toxicities included 1 myocardial infarction, 1 gastrointestinal perforation (GIP), and 12/20 patients (60%) developed grade 3 HTN.

Conclusions

Addition of oral cyclophosphamide to bevacizumab at the time of cancer progression on bevacizumab appears to have continued anti-cancer effects in a subgroup of patients and appears to be safe. Randomized trials testing combination versus sequential anti-angiogenic therapy for recurrent ovarian cancer are warranted.     

Circulating tumor cells predict progression free survival and overall survival in patients with relapsed/recurrent advanced ovarian cancer

Objective

Serial circulating tumor cell (CTC) counts have demonstrated predictive and prognostic value in patients with metastatic breast, colorectal, and prostate cancer. In a phase III study of pegylated liposomal doxorubicin (PLD) with trabectedin vs. PLD for relapsed ovarian cancer, we evaluated the correlation, if any, between numbers of CTCs and progression free survival, (PFS) and overall survival (OS).

Methods

CTCs were isolated from peripheral blood (10 mL) using the CellSearch system and reagents (Veridex). A CTC is defined as EpCAM+, cytokeratin+, CD45−, and is positive for the nuclear stain DAPI. The normal reference range for CellSearch is < 2 CTC/7.5 mL of blood. Hazard ratios adjusted for known prognostic factors were estimated by Cox regression.

Results

Two-hundred sixteen patients had baseline CTC measurements of which 111 (51.4%) were randomized to the trabectedin + PLD arm; 143/216 patients (66.2%) were platinum-sensitive. Thirty-one of 216 patients (14.4%) had 2 or more CTCs detected prior to the start of therapy (range 2-566). Univariate Cox regression analyses indicated that patients with ≥ 2 CTCs prior to therapy had 1.89- (p = 0.003) and 2.06-fold (p = 0.003) higher risk for progression and death respectively. Multivariate analyses that include baseline CA-125, platinum sensitivity status, largest diameter lesion, number of tumor lesions, ECOG PS, and tumor grade show that patients with elevated baseline CTC had 1.58- (p = 0.058) and 1.54-fold (p = 0.096) higher risk for progression and death respectively.

Conclusions

Results from this study indicate that elevated numbers of CTCs impart an unfavorable prognosis for ovarian cancer patients.     

A phase II clinical trial of pegylated liposomal doxorubicin and carboplatin plus bevacizumab in patients with platinum-sensitive recurrent ovarian, fallopian tube, or primary peritoneal cancer

Objective

To assess the safety and efficacy of pegylated liposomal doxorubicin (PLD), carboplatin, plus bevacizumab in patients with ovarian, fallopian tube, or primary peritoneal cancer.

Methods

Patients with platinum-sensitive, recurrent disease received PLD 30 mg/m² and carboplatin area under the curve (AUC) 5 on Day 1 plus bevacizumab 10 mg/kg on Days 1 and 15 of every 28-day cycle, for a maximum of 10 cycles. The primary endpoint was objective response rate (ORR) [complete + partial response]; additional endpoints were safety, duration of response, progression-free survival (PFS), and time to progression (TTP).

Results

Of the 54 patients enrolled, 15 (27.8%) completed the study treatment as planned. Intent-to-treat (all enrolled patients) ORR was 72.2% (95% CI: 58.4, 83.5). Median duration of response was 11.9 months (95% CI: 9.3, not estimable) and median TTP was 13.9 months (95% CI: 11.4, 16.0). PFS was virtually the same as TTP. Three (5.6%) patients discontinued therapy due to disease progression, and another 3 (5.6 %) patients discontinued therapy due to serious adverse events (Grade 4 thrombocytopenia, Grade 3 small/large intestinal obstruction/small intestinal perforation, and Grade 3 abdominal abscess). Fifty (92.6%) patients had ≥ 1 adverse event of interest, most commonly neutropenia (42.6%), hypertension (37.0%), stomatitis (37.0%), proteinuria (37.0%), and palmar-plantar erythrodysesthesia (27.8%). No appreciable decreases in left-ventricular ejection fraction were observed.

Conclusion

Most patients responded to PLD, carboplatin, and bevacizumab combination therapy. The safety profile was consistent with the known toxicities of these agents. These findings present a potential treatment option for women with ovarian, fallopian tube, or primary peritoneal cancer.     

Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian cancer trial

Objective

To describe and analyze observed hypersensitivity reactions (HSR) from the randomized, multicenter phase III CALYPSO trial that evaluated the efficacy and safety of the combination of carboplatin and pegylated liposomal doxorubicin (CD) compared with standard carboplatin-paclitaxel (CP) in patients with platinum-sensitive relapsed ovarian cancer (ROC).

Methods

HSR documented within case report forms and SAE reports were specifically analyzed. Analyses were based on the population with allergy of any grade and for grade > 2 allergy.

Results

Overall 976 patients were recruited to this phase III trial, with toxicity data available for 466 and 502 on the CD and CP arms, respectively. There was a 15.5% HSR rate associated with CD (2.4% grade > 2) versus 33.1% with CP (8.8% grade > 2), p < 0.001. HSRs occurred more often during first cycle in the CD (46%) arm than in the CP arm (16%). Multivariate predictors of allergy were chemotherapy regimen and age; patients randomized to CD and patients ≥ 70 years old on CP had less allergy. Few patients (< 6%) stopped treatment due to allergy. Allergy rates were higher in patients who did not receive prior supportive treatment; however there was no relationship between allergy and the type of carboplatin product received, or response rate.

Conclusions

Use of PLD with carboplatin instead of paclitaxel and older age were the only 2 factors predicting a low rate of HSRs in patients with ROC. CD has previously demonstrated superior progression-free survival and therapeutic index than CP. Taken together these data support the use of CD as a safe and effective therapeutic option for platinum-sensitive ROC.     

Significance of age and comorbidity on treatment modality, treatment adherence, and prognosis in elderly ovarian cancer patients

Background

Age is associated with poor prognosis in ovarian cancer patients. Reasons could be increased comorbidity, more advanced stage, or nonoptimal surgery or chemotherapy. Objectives of this study were to evaluate the significance of comorbidity and age ≥ 70 years on receiving cytoreductive surgery, standard combination chemotherapy (TC), adherence to TC treatment, and prognosis.

Methods

A retrospective cohort study of all women registered in a nation-wide database with ovarian or peritoneal cancer in 2005-2006. Logistic regression was employed for determining the predictive value of age and comorbidity (ASA score) on receiving cytoreductive surgery and TC, and on adhering to TC. Kaplan-Meier method and Cox proportional hazards analysis were employed for survival analyses.

Results

Of 961 patients, 348 (36.2%) were elderly. Age ≥ 70 years was independently predictive of not receiving surgery, OR 0.2(95% CI 0.1-0.5) and TC treatment, OR 0.03 (95% CI 0.01-0.1). Comorbidity was also independently predictive of not receiving standard treatment: OR for receiving surgery with ASA score of ≥ 3 was 0.2 (95% CI 0.1-0.5), and for receiving TC it was 0.03 (95% CI 0.01-0.1). Overall, age ≥ 70 was a poor prognostic factor in OS and PFS, but the effect of age ceased after 16 months. Comorbidity was a poor prognostic factor throughout the study period but with time-varying effect. For patients treated with TC, age was not a prognostic factor, whereas ASA score ≥ 3 was.

Conclusion

Elderly patients and patients with comorbidity less often receive optimal surgical and medical treatment. For those receiving optimal treatment, age ≥ 70 is not an independent poor prognostic factor, whereas severe comorbidity is.     

Evaluation of two doses of recombinant human luteinizing hormone supplementation in down-regulated women of advanced reproductive age undergoing follicular stimulation for IVF: a randomized clinical study

Objectives

To evaluate the effects of mid-follicular recombinant human luteinizing hormone (rhLH) supplementation in down-regulated women of advanced reproductive age undergoing in vitro fertilization (IVF).

Study design

This was a prospective, randomized parallel-group study (allocation 1:1) including 187 normogonadotrophic infertile patients aged ≥35 years. Subcutaneous triptorelin was used for pituitary desensitization, and ovarian stimulation was achieved with recombinant human follicle-stimulating hormone (rhFSH) either alone (Group 1) or in combination with rhLH in one of two daily doses: 37.5 IU (Group 2) or 75 IU (Group 3). Ovarian stimulation characteristics and IVF outcome were evaluated. The main outcome was pregnancy rate.

Results

A total of 62, 62 and 63 patients were randomized to groups 1, 2 and 3 respectively, and 56, 54 and 55 patients respectively were available for final analysis of the results. Follicular development and oocyte yield were significantly higher in group 1 patients compared with patients in groups 2 and 3. Oocyte maturity and number of oocytes fertilized were also higher in group 1 patients; this difference almost reached statistical significance. No significant difference in implantation and clinical pregnancy rates was found among the three treatment groups.

Conclusions

rhLH supplementation is not a useful tool for patients of advanced reproductive age in ovarian stimulation protocols using an appropriate gonadotrophin-releasing hormone agonist and a step-down regimen of rhFSH.     

Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer

Objective

Weekly paclitaxel has been shown to be an effective cytotoxic regimen for recurrent epithelial ovarian cancer (EOC), and may act through inhibition of angiogenesis. Bevacizumab, a potent angiogenesis inhibitor, has also been shown to have activity in patients with EOC. Therefore, we sought to determine if the addition of bevacizumab to weekly paclitaxel led to an increased survival compared to weekly paclitaxel alone.

Methods

A single institutional review was conducted for patients with recurrent EOC treated with weekly paclitaxel (60-70 mg/m²) on days 1, 8, 15, and 22 of a 28 day cycle and those treated with weekly paclitaxel and bevacizumab (10-15 mg/kg on day 1 and 15). Response rates (RR) were calculated, and progression-free survival (PFS), and overall survival (OS) were compared using Kaplan-Meier survival analysis.

Results

Twenty-nine patients treated with weekly paclitaxel and 41 patients treated with paclitaxel/bevacizumab were identified. The groups were similar in demographics, initial optimal cytoreduction, stage, histology, grade, platinum sensitivity, and median number of previous regimens (4 vs. 4, p = 0.69).The overall response rate (ORR) was 63% (complete response (CR) 34% and partial response (PR) 29%) for paclitaxel/bevacizumab and 48% (CR 17% and PR 31%) for weekly paclitaxel (p = 0.23). Improvement in PFS was seen in those treated with paclitaxel/bevacizumab in comparison to weekly paclitaxel alone (median PFS 13.2 vs. 6.2 months, p < .01). There was a trend towards improved OS for paclitaxel/bevacizumab (median OS 20.6 vs. 9.1 months; p = 0.12). Toxicities were similar between the two regimens although more bowel perforations (2 vs. 0) were seen in the paclitaxel/bevacizumab group.

Conclusion

A significant increase in PFS with a trend towards improved OS was demonstrated in this heavily pretreated population treated with paclitaxel/bevacizumab as compared to weekly paclitaxel alone. This data should be helpful in guiding future trials to determine the optimal care for women with recurrent EOC.     

Angiotensin II type I receptor and miR-155 in endometrial cancers: synergistic antiproliferative effects of anti-miR-155 and losartan on endometrial cancer cells

Objective

MicroRNA-155 (miR-155) is one of the micro RNAs (miRNA) most consistently involved in neoplastic diseases, and it is known to repress the angiotensin II type 1 receptor (AGTR1). The aim of the present study was to evaluate the expressions of miR-155 and AGTR1, and to clarify the potential efficacy of anti-miR-155, alone and in combination with AGTR1 blocker losartan in endometrial cancers.

Methods

Expressions of miR-155 and AGTR1 were evaluated using real-time PCR and immunohistochemistry. And the MTT assay was performed in endometrial cancer cells following anti-miR-155 and AGTR1 blocker (losartan) treatment, alone and in combination.

Results

miR-155 was over-expressed and AGTR1 was underexpressed in endometrial carcinoma tissues. AGTR1 immunoreactivity was found in six of ten (60.0%) normal endometrium, 11 of 14 (78.6%) endometrial hyperplasia, and 27 of 62 (43.5%) endometrial carcinoma tissues (P = 0.051), and patients with AGTR1 expression showed trend towards improved survival after multivariate analysis (P = 0.08). We checked that abolishing the function of miR-155 and AGTR1 by anti-miR-155 or losartan inhibited cell survival of endometrial carcinoma cells, respectively, and furthermore, combined treatment showed synergistic effects.

Conclusions

In this study, we characterized the expressions of miR-155 and AGTR1 in endometrial tissues. The combined treatment with anti-miR-155 and losartan has a synergistic antiproliferative effect and an improved understanding is required to clarify whether miR-155 and AGTR1 can be used as a novel therapeutic target in endometrial 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.     

Unraveling the two entities of endometrioid ovarian cancer: a single center clinical experience

Objective

Due to the increasing prevalence of the benign condition, ovarian carcinoma arising from endometriosis is emerging as a relevant clinical entity with an unclear biological signature. We have investigated clinical and histologic features of endometriosis-associated endometrioid ovarian cancer using an institutional retrospective database.

Methods

Patients diagnosed with endometrioid ovarian cancer at our institution were divided into two groups according to the fulfillment or not of Sampson's and Scott's criteria for the detection of endometriosis-associated ovarian cancer. Clinical and histological data were reported and compared. Survival analysis was obtained using the log-rank test in an unadjusted Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model to establish independent factors associated with endometriosis-associated endometrioid ovarian cancer and to identify predictors of survival. The degree of concordance was evaluated by Cohen's Kappa measures.

Results

Patients with endometriosis-associated endometrioid ovarian cancer were significantly younger, had a lower disease stage (62% vs 23%; p = 0.003), a less prevalent high grade tumor (38% vs 82%; p = 0.002) and a higher prevalence of squamous and mucinous metaplasia. The rate of endometrial cancer diagnosis was significantly higher in women with endometriosis-associated endometrioid ovarian cancer (33%) than in other patients (11%) (p = 0.04) with a 92% concordance between ovarian and endometrial histologic tumor grade. A significant difference in survival rate could not be demonstrated between patients with or without endometriosis.

Conclusions

The analysis of a retrospective endometrioid ovarian cancer database may allow to suggest a 40 molecular, morphological and clinical parallelism between endometrial and endometrioid ovarian cancers.     

Reliability of sentinel node assay in vulvar cancer: the first Croatian validation trial

Objectives

To evaluate patterns of recurrence in 1988 FIGO stage IC endometrioid endometrial adenocarcinoma.

Methods

A prospectively maintained endometrial cancer database was utilized to identify all patients with stage IC endometrioid endometrial adenocarcinoma treated between 2/93 and 6/09. Patterns of recurrence and risk factors were analyzed.

Results

One hundred thirty-four patients with stage IC endometrial cancer were identified. Median age was 66 years (range, 31-91 years). All patients were initially treated surgically, and 79% underwent comprehensive surgical staging with lymphadenectomy. Median number of lymph nodes removed was 18 (range, 1-45). Fifty-one patients (38%) had FIGO grade 1 tumors, 55 (41%) had grade 2 tumors, and 28 (21%) had grade 3 tumors. The majority of patients (91%) received adjuvant radiation therapy. With a median follow-up of 36 months (range, 0.6-141.4 months), 10 patients recurred. Of these, 2 (20%) were grade 1, 2 (20%) were grade 2, and 6 (60%) were grade 3. Nine (90%) of these recurrences had a distant component and 7 (70%) were fatal. Overall, the 3 year cumulative incidence failure rate for grade 1/2 tumors was 5.4%; for grade 3 tumors it was 28.9% (P < 0.001). Age, BMI, and lymphovascular invasion were not associated with an increased risk of recurrence.

Conclusions

Patients with stage IC, grade 3 endometrial cancer had a significantly increased risk of recurrence (28.9%). All of these recurrences had a distant component and the majority were fatal. Further investigation into the addition of adjuvant systemic therapy in these high-risk patients is warranted.     

A prospective study of the factors associated with the success rate of external cephalic version for breech presentation at term

Objective

To determine the factors associated with the success rate of external cephalic version (ECV) for breech presentation at term.

Methods

A prospective analysis of 500 ECV maneuvers. The variables maternal age, maternal weight, body mass index, previous cesarean delivery, gestational age, parity, amount of amniotic fluid, placental location, and type of breech were studied using logistic regression analysis.

Results

The success rate of ECV was 52.2% (n = 261). The variables significantly associated with success were parity, placental location, amount of amniotic fluid, and type of breech (P < 0.05). A parity of 2 had a 3.74-times higher probability of success than nulliparity (95% CI, 2.37-5.90); a posterior placenta increased the success rate by 2.85 times compared with an anterior placenta (95% CI, 1.87-4.36); and double footling breech presentation had a 2.77-times higher success rate compared with a frank breech presentation (95% CI, 1.16-6.62). The area under the ROC curve showed a predictive ability of 73.6% (95% CI, 69.2%-77.9%) for these 3 variables.

Conclusion

Parity, placental location, amount of amniotic fluid, and type of breech presentation were associated with the success rate of ECV.     

Effect of prenatal and perinatal antibiotics on maternal health in Malawi, Tanzania, and Zambia

Objective

We assessed the effect of prenatal and peripartum antibiotics on maternal morbidity and mortality among HIV-infected and uninfected women.

Methods

A multicenter trial was conducted at clinical sites in 4 Sub-Saharan African cities: Blantyre and Lilongwe, Malawi; Dar es Salaam, Tanzania; and Lusaka, Zambia. A total of 1558 HIV-infected and 271 uninfected pregnant women who were eligible to receive both the prenatal and peripartum antibiotic/placebo regimens were enrolled. Pregnant women were interviewed at 20-24 weeks of gestation and a physical examination was performed. Women were randomized to receive either antibiotics or placebo. At the 26-30 week visit, participants were given antibiotics or placebo to be taken every 4 hours beginning at the onset of labor and continuing after delivery 3 times a day until a 1-week course was completed. Logistic regression and Cox proportional hazards models were used.

Results

There were no significant differences between the antibiotic and placebo groups for medical conditions, obstetric complications, physical examination findings, puerperal sepsis, and death in either the HIV-infected or the uninfected cohort.

Conclusion

Administration of study antibiotics during pregnancy had no effect on maternal morbidity and mortality among HIV-infected and uninfected pregnant women.     

Induction of labor with vaginal misoprostol plus oxytocin versus oxytocin alone

Objective

To compare the effect of an oxytocin infusion alone or preceded by an intravaginal application of misoprostol for labor induction in women with term pregnancies and a low Bishop score.

Methods

This study randomized 100 multiparous women with singleton pregnancies over 38 weeks and a Bishop score less than 6 to receive either a single 50-µg dose of misoprostol intravaginally 3 hours before initiation of the oxytocin infusion or only an oxytocin infusion. The time from induction to delivery, the route of delivery, and maternal and fetal outcomes were analyzed.

Results

The mean time from induction to delivery was 9.36 ± 1.97 hours in the misoprostol plus oxytocin group and 11.08 ± 3.23 in the oxytocin alone group (P = 0.002). The rates of vaginal delivery, 1- and 5-minute Agpar scores, placental abruption, and postpartum hemorrhage were similar between the 2 groups, as were the rates of admission to the neonatal intensive care unit. There were no cases of perinatal asphyxia.

Conclusion

A 50-µg intravaginal application of misoprostol before starting the oxytocin infusion is a more effective method of labor induction than an oxytocin infusion alone for our study population.     

The surgical rectus sheath block for post-operative analgesia: a modern approach to an established technique

Objective

To describe the surgical rectus sheath block for post-operative pain relief following major gynaecological surgery.

Technique

Local anaesthetic (20 ml 0.25% bupivacaine bilaterally) is administered under direct vision to the rectus sheath space at the time of closure of the anterior abdominal wall.

Study design

We conducted a retrospective case note review of 98 consecutive patients undergoing major gynaecological surgery for benign or malignant disease who received either standard subcutaneous infiltration of the wound with local anaesthetic (LA, n = 51) or the surgical rectus sheath block (n = 47) for post-operative pain relief.

Main outcome measures

(1) Pain scores on waking, (2) duration of morphine-based patient controlled analgesia (PCA), (3) quantity of morphine used during the first 48 post-operative hours and (4) length of post-operative stay.

Results

The groups were similar in age, the range of procedures performed and the type of pathology observed. Patients who received the surgical rectus sheath block had lower pain scores on waking [0 (0-1) vs. 2 (1-3), p < 0.001], required less morphine post-operatively [12 mg (9-26) vs. 36 mg (30-48), p < 0.001], had their PCAs discontinued earlier [24 h (18-34) vs. 37 h (28-48), p < 0.001] and went home earlier [4 days (3-4) vs. 5 days post-op (4-8), p < 0.001] [median (interquartile range)] than patients receiving standard subcutaneous local anaesthetic into the wound.

Conclusions

The surgical rectus sheath block appears to provide effective post-operative analgesia for patients undergoing major gynaecological surgery. A randomised controlled clinical trial is required to assess its efficacy further.     

Comparing effectiveness of combined transobturator tension-free vaginal mesh (Perigee) and transobturator tension-free vaginal tape (TVT-O) versus anterior colporrhaphy and TVT-O for associated cystocele and urodynamic stress incontinence

Objective

To evaluate the efficacy and safety of transobturator tension-free vaginal mesh (Perigee) and concomitant transobturator tension-free vaginal tape (TVT-O) for treating cystocele with urodynamic stress incontinence (UDSI).

Study design

A retrospective study of 115 patients with symptomatic stages 2-3 cystocele and UDSI who were treated with a Perigee system (Group I, n = 68) plus TVT-O procedure or traditional anterior colporrhaphy (Group II, n = 47) plus TVT-O procedure. All patients were followed up for more than one year. Objective and subjective symptoms were evaluated at one year postoperatively. Statistical analysis was performed using SPSS software.

Results

The objective cure rates for cystocele at one year were significantly higher in Group I than in Group II (98.5% and 86.9%, P = 0.018), respectively. The cure rates for UDSI in the two groups were 91.0% vs. 91.3% (P = 1.000). Symptomatic improvement of frequency was better in Group I than Group II (87.7% vs. 70.0%, P = 0.030). There were no significant differences with regard to intraoperative and postoperative complications between the two groups.

Conclusions

The combination of the Perigee system and TVT-O offers a safe and effective treatment for cystocele with UDSI and may be performed as first-line treatment.     

Short vs long second stage of labour: is there a difference in terms of postpartum anal incontinence?

Objective

Our purpose was to determine if prolonged second-stage labour independently increases postpartum anal incontinence.

Study design

360 primiparous women were studied retrospectively after vaginal delivery of term cephalic singletons, including a group with short second-stage labour (<30 min, n = 163) and a group with a prolonged second stage (>90 min, n = 197). A quality of life questionnaire on anal incontinence (FIQOL) was sent out at 15 months after delivery.

Results

184 women (96 with short second-stage labour and 88 with a prolonged second stage) answered the questionnaire (response rate 51%). Flatus incontinence was reported after prolonged second-stage labour in 9.1% of women vs 15.6% after short second stage (p = 0.18). Fecal incontinence was reported after prolonged second-stage labour in 2.3% vs 5.2% after a short second stage (p = 0.45).

Conclusion

We suggest that prolonged second stage of labour should not be associated with an increased risk of postpartum incontinence.     

Comparison of the TVT SECUR System “hammock” and “U” tape positions for management of stress urinary incontinence

Objective

To assess the efficacy and complications associated with use of the TVT SECUR System device with placement of the tape in either a “hammock” or “U” position for management of stress urinary incontinence (SUI).

Methods

A prospective study of patients with SUI allocated into one of two groups: “hammock” or “U” tape placement. Preoperative urodynamic results were compared with results at the 6-month and 1-year follow up. Outcome measures were objective cough test assessment and subjective patient responses to a questionnaire at follow up.

Results

Of 82 patients included in the study, 43 comprised the “hammock” group and 39 comprised the “U” group. The objective cure rate at 1-year follow up was 62.8% (n = 27) in the “hammock” group and 71.8% (n = 28) in the “U” group. At 1-year follow up, the subjective cure, improvement, and failure rates for the “hammock” group were 60.5%, 13.9%, and 25.7% respectively, and 69.2%, 12.8%, and 17.9% respectively, for the “U” group.

Conclusion

The efficacy of the TVT SECUR System was lower (< 72%) than the cure rates reported for other TVT procedures; further studies are required.     

Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer ≤ 70 years

Objective

Lynch syndrome (LS) is a hereditary syndrome that predisposes to multiple malignancies including endometrial cancer (EC). We aimed to evaluate a diagnostic strategy for LS based on routine analysis of microsatellite instability (MSI) and immunohistochemical (IHC) staining for mismatch repair (MMR) proteins in tumour tissue of all newly diagnosed EC patients ≤ 70 years.

Methods

Consecutive EC patients ≤ 70 years were included prospectively in eight Dutch centres. EC specimens were analysed for MSI, IHC of four MMR proteins, MMR gene methylation status and BRAF-mutations. tumours were classified as; 1) likely to be caused by LS, 2) sporadic MSI-H, or 3) microsatellite stable (MSS).

Results

Tumour specimens of 179 patients (median age 61 years, IQR 57-66) were analysed. In our study 92% of included patients were over 50 years of age. Eleven EC patients were found likely to have LS (6%; 95% CI 3-11%), including 1 patient suspected of an MLH1, 2 of an MSH2, 6 of an MSH6 and 2 of a PMS2 gene defect. Germline mutation analyses revealed 7 MMR gene germline mutations. Ten patients likely to have LS (92%) were older than 50 years. In addition, 31 sporadic MSI-H tumours with MLH1 promoter hypermethylation (17%; 95% CI 13-24%) were identified.

Conclusions

Molecular screening for LS in patients with EC diagnosed ≤ 70 years, leads to identification of a profile likely to have LS in 6% of cases. New screening guidelines for LS are needed, including recommendations for EC patients older than 50 years of age.     

Do uterine risk factors or lymph node metastasis more significantly affect recurrence in patients with endometrioid adenocarcinoma?

Objectives

Controversy continues over the importance of lymph node (LN) status in treating and predicting recurrence in endometrial cancer. Several predictive models are available which use uterine factors to stratify risk groups. Our objective was to determine how LN status affects recurrence and survival compared to uterine factors alone.

Methods

A retrospective review was performed of patients undergoing complete surgical staging for clinical stage 1 endometrioid adenocarcinoma of the uterus. Patients were assessed based on PORTEC 1 high intermediate risk (H-IR) criteria (2 factors : age > 60, grade 3, > 50% DOI), GOG-99 H-IR criteria (age > 70 + 1 factor, age 50-70 + 2 factors, any age + 3 factors: grade 2 or 3, LVSI, > 50% DOI), and PORTEC 2 criteria. Rates of nodal involvement, recurrence rates, PFS, and OS were compared.

Results

We identified 352 clinical stage I patients with positive LN in 24% (87). 175 patients met PORTEC 1 eligibility and 66 met H-IR criteria. Rates of LN positivity were similar among groups (18.4% vs 19.7%, p = 0.83) but recurrence rates were dissimilar (7.4% vs 27.3%, p = 0.0004). Only 93 met PORTEC 2 criteria for treatment with no association between LN status, recurrence, and eligibility. 188 patients met H-IR eligibility criteria for GOG-99 with LN positive and recurrence rates higher in the H-IR group compared to GOG-99 eligible (34.6% vs 16.3%, p = 0.0004, 28.3% vs. 10.6%, p = 0.0002).

Conclusions

Patients with H-IR disease based on uterine characteristics alone have substantial risk of nodal involvement. Knowledge of LN status may better define risk, prognosis, and postoperative treatment.