Evidence for different expression profiles for c-Met, EGFR, PTEN and the mTOR pathway in low and high grade endometrial carcinomas in a cohort of consecutive women. Occurrence of PIK3CA and K-Ras mutations and microsatellite instability.

Molecular and genetic investigations in endometrial carcinogenesis may have prognostic and therapeutic implications. We studied the expression of EGFR, c-Met, PTEN and the mTOR signalling pathway (phospho-AKT/phospho-mTOR/phospho-RPS6) in 69 consecutive tumours and 16 tissue microarrays. We also analysed PIK3CA, K-Ras mutations and microsatellite instability (MSI). We distinguished two groups: group 1 (grade 1 and 2 endometrioid cancers) and group 2 (grade 3 endometrioid and type II clear and serous cell cancers). We hypothesised that these histological groups might have different features. We found that a) survival was higher in group 1 with less aggressive tumours (P⟨0.03); b) EGFR (P=0.01), PTEN and the AKT/mTOR/RPS6 signalling pathway were increased in group 1 versus group 2 (P=0.05 for phospho-mTOR); c) conversely, c-Met was higher (P⟨0.03) in group 2 than in group 1; d) In group 1, EGFR was correlated with c-Met, phospho-mTOR, phospho-RPS6 and the global activity of the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway. In group 2, EGFR was correlated only with the phospho-AKT/phospho-mTOR/phospho-RPS6 pathway, whereas c-Met was correlated with PTEN; e) survival was higher for tumours with more than 50% PTEN-positive cells; f) K-RAS and PIK3CA mutations occurred in 10-12% of the available tumours and MSI in 40.4%, with a loss of MLH1 and PMS2 expression. Our results for endometrial cancers provide the first evidence for a difference in status between groups 1 and 2. The patients may benefit from different targeted treatments, anti-EGFR agents and rapamycin derivatives (anti-mTOR) for group 1 and an anti c-MET/ligand complex for group 2.

Out-of-hospital follow-up after low risk breast cancer within a care network: 14-year results.

The delegation of low-risk breast cancer patients' follow-up to non-hospital practitionners (NHP), including gynaecologists and general practitioners, has been assessed prospectively within a care network in the Paris region. Patients with early stage breast cancer were eligible. The follow-up protocol was built according to international guidelines. By 2012, 289 NHPs were following 2266 patients treated in 11 centres. Median follow-up time was 7.4 years. The mean intervals between two consecutive consultations were 9.5 [9.2-9.8] months for women supposed to be monitored every 6 months and 12.5 [12.2-12.8] for those requiring annual monitoring. The relapse rate was 3.2% [2.1-4.3] at 5 years and 7.8% [5.9-9.7] at 10 years. Seventy one percent of relapses were diagnosed on a scheduled assessment. Only 6% were lost-to-follow-up. Delegating follow-up after low risk breast cancer to NHPs in a care network is feasible, well accepted and provides an alternative to follow-up in specialized centres.

Malignant transformation of superficial peritoneal endometriosis lesion.

A 63-year-old woman with no medical history underwent an abdominal surgery with hysterectomy and bilateral salpingo-oophorectomy for a 10 cm peritoneal cyst with increased cancer antigene-125. A large suspicious tumour of the Douglas space, with contact to the uterus and the rectal wall was described. The rest of the exploration was normal, specially the rest of the peritoneum. Histopathology revealed a malignant transformation of a superficial peritoneal endometriosis. Secondary surgery was thus completed by laparoscopy with bilateral pelvic and para-aortic lymph node dissections, omentectomy and multiple peritoneal biopsies. All staging samples were free of cancer; therefore no complementary therapy was administered. After 18 months of follow-up, consisting of clinical examination and pelvis magnetic resonance imaging every 6 months, we did not observe any recurrence. Malignant transformation of superficial peritoneal endometriosis is a rare disease and surgical management seems to be the main treatment.

The exportability of the ACOSOG Z0011 criteria for omitting axillary lymph node dissection after positive sentinel lymph node biopsy findings: a multicenter study.

PURPOSE: To determine the exportability of the criteria defined by the American College of Surgeons Oncology Group Z0011 trial for selecting patients who are eligible for omitting completion axillary lymph node dissection (cALND) after a positive sentinel lymph node (SLN) biopsy result and to investigate whether not following the Z0011 criteria might affect patient outcomes. METHODS: From a multicenter database, we selected 188 patients with positive SLNs and then excluded patients with positive SLNs on immunohistochemistry only. We retrospectively applied the Z0011 criteria and grouped the patients as eligible or ineligible for omitting cALND. The eligible group was compared with the cohort included in the Z0011 trial and with the ineligible group. Kaplan-Meier survival curves were calculated for each group, and univariate analyses assessed associations between the groups and clinicopathological variables. RESULTS: The final analysis involved 125 patients with positive SLNs. Eighty-seven patients (69.6 %) were potentially eligible for omitting cALND. The estrogen receptor status, T stage, grade, and number of positive non-SLNs were not statistically different between the eligible group and the Z0011 cohort. The ineligible group had significantly more positive non-SLNs (P = 0.01) and a lower 5-year overall survival rate than the eligible group (P < 0.001). CONCLUSIONS: The similarity of clinical characteristics between the Z0011 trial cohort and our eligible group confirms the exportability of these criteria to another population. The worse prognosis of patients who did not meet the Z0011 criteria suggests prudence before disregarding or enlarging broadening the indications for omitting cALND.

Selection of patients with advanced-stage cervical cancer for para-aortic lymphadenectomy in the era of PET/CT.

BACKGROUND: The aim of this study was to report the false-negative rate of positron-emission tomography (PET) /Computed Tomography (CT) for para-aortic (PA) lymph node (LN) metastasis and to examine if PA lymphadenectomy could be omitted when PET/CT of the pelvic area is negative. PATIENTS AND METHODS: Patients without evidence of extrapelvic disease on preoperative imaging or in the PA area were included. Each patient underwent a laparoscopic PA lymphadenectomy. RESULTS: A total of 61 patients were included. Seven patients (11%) had PALN metastasis. The false-negative rate of PET/CT was 11%. When PET/CT was positive for pelvic nodes, the risk for PA metastasis was 18% versus 8% when PET/CT was negative in the pelvic area (p=0.24). CONCLUSION: The apparent low sensitivity of the PET/CT does not make it a relevant alternative to surgical LN staging when no uptake is visualized in the PA area. However, for patients in whom PET/CT is negative in the pelvic area, the risk of metastasis in the PA area is low.

Hypoxia imaging of uterine cervix carcinoma with (18)F-FETNIM PET/CT.

PURPOSE: Our aims were to assess the feasibility of imaging hypoxia in cervical carcinoma with (18)F-fluoroerythronitroimidazole ((18)F-FETNIM) and to compare (18)F-FETNIM uptake with metabolic uptake of (18)F-FDG. PATIENTS AND METHODS: We included 16 patients with cervical carcinoma. After imaging with FDG, (18)F-FETNIM PET/CT was performed and tumor-to-muscle (T/M) ratio uptake was assessed. (18)F- FETNIM uptake was correlated to FDG uptake and osteopontin (OPN), a marker of hypoxia, and patients' outcomes. RESULTS: All tumors were detected by (18)F-FDG PET. (18)F-FETNIM T/M ratios ranged from 1.3 to 5.4. There was no significant correlation between (18)F-FETNIM and (18)F-FDG uptake. High (18)F-FETNIM uptake (T/M > 3.2) was associated with reduced progression-free survival (log-rank = 0.002) and overall survival (log-rank = 0.02). Osteopontin ranged from 39 to 662 µg/L (median, 102.5 µg/L). Patients with OPN greater than 144 µg/L had reduced progression-free survival compared with those with OPN less than 144 µg/L (log-rank = 0.03). We found no significant correlation between (18)F-FETNIM uptake and OPN blood levels. CONCLUSIONS: Our preliminary results showed that a high uptake of (18)F-FETNIM was associated with a worse progression-free and overall survival.

Axillary Padding without Drainage after Axillary Lymphadenectomy - a Prospective Study of 299 Patients with Early Breast Cancer.

BACKGROUND: After lymphadenectomy for early breast cancer, seroma formation is a constant event requiring a suction drainage. This drainage is the strongest obstacle to reducing the hospital stay. Axillary padding without drainage appears to be a valuable option amid the various solutions for reducing the hospital stay. METHODS: We conducted a comparison between 114 patients with padding and 185 patients with drainage. Data were obtained from 2 successive prospective studies. RESULTS: The mean hospital stay was 2.4 days (range 1-4) in the padding group and 4.2 days (range 2-9) in the drainage group (p < 0.05). There were fewer needle aspirations for seroma in the padding group (8.8 vs. 23%, p < 0.05). At 6 weeks, only 28% (32/114) of the patients in the padding group reported pain versus 51% (94/185) in the drainage group. The mean pain intensity at 6 weeks was 3 and 4.3 respectively (p < 0.0001). CONCLUSION: Axillary padding without drainage was associated with a better post-operative course than suction drainage in this historical comparison, and the hospital stay was significantly shortened. There are only few series published on this new technique but they all indicate good feasibility and good tolerance. A large randomised multicentric evaluation is now warranted.

Impact of infertility drugs after treatment of borderline ovarian tumors: results of a retrospective multicenter study.

OBJECTIVE: To evaluate safety and fertility outcome after the use of infertility drugs in patients who were treated conservatively for a borderline ovarian tumor (BOT). DESIGN: A retrospective multicenter study. SETTING: Centers participating in the French National Register on In Vitro Fertilization registry. PATIENT(S): Thirty patients who were treated for BOT who underwent ovarian induction (OI). INTERVENTION(S): Ovarian induction was performed in 25 patients for infertility after conservative surgery and before surgery for recurrent disease in 5 patients with a single ovary (emergency cases). MAIN OUTCOMES MEASURE(S): Fertility and recurrences rates. RESULT(S): The mean number of cycles of OI per patient was 2.6 (range, 1-10 cycles). The median follow-up time after treatment of the BOT was 93 months (range, 26-276 months). After a median follow-up time of 42 months after OI, 4 recurrences were observed (initial management was simple cystectomy in 3 of them). All recurrences were borderline tumors on a remaining ovary that had been treated by surgery alone. All patients are currently disease-free. Thirteen pregnancies were observed (10 pregnancies (40%) in the group of 25 patients who were treated for infertility). CONCLUSION(S): These results suggest that infertility drugs could be used safely in patients who experience infertility after conservative management of an early-stage BOT.

Results of hysterectomy in patients with bulky residual disease at the end of chemoradiotherapy for stage IB2/II cervical carcinoma.

BACKGROUND: We assessed the clinical outcome after hysterectomy in patients with bulky residual disease after chemoradiotherapy for stage IB2/II cervical carcinoma. METHODS: Subjects were 10 patients who had bulky (>2 cm) residual disease in the cervix after external radiotherapy (45 Gy) combined with concomitant chemotherapy (cisplatin 40 mg/m2/week) and uterovaginal brachytherapy (15 Gy). RESULTS: Extrafascial hysterectomy was performed in three patients, type II radical hysterectomy was performed in six patients, and pelvic exenteration was performed in one patient. Pelvic lymphadenectomy was performed in eight patients, and para-aortic lymphadenectomy was performed in eight. Five patients had nodal involvement (pelvic nodes in four and para-aortic nodes in four), and six had lymphovascular space involvement. Surgical margins were free in nine patients. Seven patients developed grade 2 (n = 3) and/or grade 3 (n = 4) complications. The median duration of follow-up after surgery was 22 months (range, 1-37 months). With follow-up available in nine patients, seven relapsed, and only two remained disease free. CONCLUSIONS: This series confirms the high rate of nodal spread in patients with bulky residual cervical disease after chemoradiotherapy. Furthermore, patients who underwent hysterectomy had a high complication rate. Only two patients are alive and disease free. The results of surgery are disappointing; surgery does not seem to improve the survival of these patients.

Anatomy of pelvic and para-aortic nodal spread in patients with primary fallopian tube carcinoma.

BACKGROUND: To describe characteristics of patients with nodal spread and the anatomy of pelvic and para-aortic node involvement in primary fallopian tube carcinoma. STUDY DESIGN: Between 1985 and 2003, 19 women with primary fallopian tube carcinoma underwent systematic bilateral pelvic and para-aortic lymphadenectomy up to the level of the left renal vein. Initial lymphadenectomy (without chemotherapy) was performed in 6 patients and in 13 patients lymphadenectomies were performed after chemotherapy at the time of second-look operation. RESULTS: Nine patients had nodal involvement: four in the pelvic area and eight in the para-aortic nodes. Two, one, and six patients had stages I, II, or III disease, respectively. When para-aortic nodes were involved, the left para-aortic chain above the level of the inferior mesenteric artery was the site most frequently involved (six patients). CONCLUSIONS: In patients with primary tubal carcinoma, the left para-aortic chain above the level of the inferior mesenteric artery is the most frequently involved. Lymphadenectomy should involve all pelvic and para-aortic chains up to the level of the left renal vein, even in patients with stage I disease.

The suburethral sling for female stress urinary incontinence: a retropubic or obturator approach?

STUDY OBJECTIVE: To evaluate the feasibility and safety of the obturator approach for placement of a vaginal suburethral sling indicated for women with stress urinary incontinence. DESIGN: Retrospective cohort analysis (Canadian Task Force classification IV). SETTING: University teaching hospital. PATIENTS: Forty-nine women suffering from stress incontinence. INTERVENTION: Analysis of the suburethral sling according to surgical approach during two consecutive periods: retropubic from January 1, 2001 through September 30, 2001, and obturator from October 1, 2001 through January 31, 2002. MEASUREMENTS AND MAIN RESULTS: During the study period, 25 patients underwent surgery with the retropubic approach and 24 with the obturator approach. The patient characteristics did not differ between the two groups. The obturator approach was feasible in all attempted procedures. The mean operative time was 46 minutes (range 20-90) for the retropubic approach compared with 32 minutes (range 15-50) for the obturator approach (p = .03). Two bladder injuries occurred with the former, none with the latter (although cystoscopy was not routinely performed) (p = .49). Similarly, significantly more patients in the retropubic approach group had difficulty with postoperative voiding compared with those in the obturator approach group (10 [40%] vs 2 [8%], p = .01). Only two patients, both in the retropubic group, had voiding difficulties for longer than 1 week. One month after surgery, continence results did not differ significantly between the two groups (p = .30). In the retropubic approach group, 20 (80%) of the women were cured, and substantial improvement was experienced by 5 (20%). In the obturator approach group, these figures were 20 (83%) and 3 (12.5%), respectively, with one surgical failure (4%). Those initial results were unchanged at last follow-up (mean follow-up was 13.7 +/- 3 months for the retropubic approach group and 7.2 +/- 2 months for the obturator approach group). CONCLUSION: The obturator approach for suburethral slings is feasible and safe and may limit both preoperative and postoperative complications. Our short-term continence results compare well with those achieved with the retropubic approach. A randomized study is now needed to compare these two approaches.

Port-site implantation after laparoscopic treatment of borderline ovarian tumors.

BACKGROUND: The aim of this article is to report 3 cases of port-site implantation after laparoscopic treatment of a borderline ovarian tumor. CASES: Three patients underwent a laparoscopic procedure for a serous (2 patients) or mucinous (1 patient) borderline ovarian tumor. In 2 patients, the port-site implantation was discovered during a later surgical procedure, and one was discovered clinically 11 months after the initial laparoscopic oophorectomy. Surgical resection of the port-site was the only treatment in all cases. These women are currently alive and disease-free 11, 23, and 51 months after the treatment of the scar metastasis. CONCLUSIONS: These results suggest that, unlike port-site metastasis in other gynecologic malignancies, the prognosis in patients with a port-site implantation after laparoscopic management of borderline ovarian tumor is excellent. The treatment of this complication is surgical resection.

Impact of surgical staging in patients with macroscopic "stage I" ovarian borderline tumours: analysis of a continuous series of 101 cases.

The aim of this study was to assess the patient's clinical outcome following complete or incomplete surgical staging in cases treated for an early stage low-malignant-potential ovarian tumour (LMPOT). One-hundred and one patients treated between 1965 and 1998 for a early stage I LMPOT were reviewed according to whether the initial surgical staging was complete (Group 1/defined by peritoneal cytology + peritoneal biopsies + infracolic omentectomy) or incomplete (Group 2/omission of at least one of the peritoneal staging procedures described above). Complete and incomplete surgical stagings were carried out in 48 (48%) and 53 (52%) patients, respectively. Four (8%) LMPOT recurrences were observed in Group 2, all following conservative management, but there were no recurrences in Group 1. No relapses with invasive carcinoma or peritoneal disease and no tumour-related deaths were observed. The absence of complete peritoneal staging in patients with an apparent "stage I" LMPOT increased the recurrence rate. However, this surgical restaging (in cases of incomplete initial surgery) does not modify the survival of patients with apparent "stage I" LMPOT misdiagnosed during the initial surgery. This procedure could probably be omitted: (1) if the peritoneum is clearly reported as "normal" during the initial surgery; (2) in the absence of a micropapillary pattern; and (3) if the patient agrees to be carefully followed-up.

Neovagina construction by combined laparoscopic-perineal sigmoid colpoplasty in a patient with Rokitansky syndrome.

We created a neovagina by sigmoid colpoplasty using a combined laparoscopic-perineal approach in a 19-year-old woman with Rokitansky syndrome. Operating time was 4 hours and 45 minutes. No perioperative or postoperative complications occurred. Hemoglobin level fell by 1 g/dl. Total doses of morphine, nonsteroidal antiinflammatory drugs (NSAIDs), and paracetamol were 20 mg, 350 mg, and 28 g, respectively. Hospital stay was 7 days. The length of the neovagina was 12 cm. By comparison, in the three reported cases of laparotomic-perineal sigmoid vaginoplasty, mean operating time was 5 hours and 40 minutes; 24-hour fall in hemoglobin was 3.2 g/dl (range 2.1-4.3 g/dl); mean doses of morphine, NSAIDs, and paracetamol were 42.6 mg, 300 mg, and 40 g, respectively; mean hospital stay was 11.3 days; and length of neovaginas was 10, 12, and 12 cm. Although sigmoid colpoplasty is a reliable and reproducible technique, it requires experience in laparoscopic colonic surgery. The combined laparoscopic-perineal approach is associated with less analgesic requirement, shorter hospital stay, and similar anatomic results compared with the laparotomic-perineal approach.