Sebastien Gouy

Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: a French multicentre retrospective cohort study of 566 patients.

BACKGROUND Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patients selection.

Gynaecological cancers in pregnancy

Cervical and ovarian cancers are the most common gynaecological cancers diagnosed during pregnancy. In early-stage cervical cancer during the first and at the beginning of the second trimester, the two main considerations for management of the patient are the tumour size (and stage) and nodal staging. MRI and laparoscopic lymphadenectomy are useful for clinicians planning a potentially conservative approach. The management of patients with locally advanced cervical disease is controversial and should be discussed on a case-by-case basis according to the tumour size, radiological findings, the term of pregnancy, and the patients wishes. Different histological types of malignant ovarian diseases arise during pregnancy and their management depends on the diagnosis (histological subtypes, tumour differentiation, and nodal status), the tumour stage, and the trimester of the pregnancy. In patients with peritoneal spread or high-risk early-stage disease, neoadjuvant chemotherapy with pregnancy preservation could be appropriate.

Nodal-staging surgery for locally advanced cervical cancer in the era of PET

Chemoradiation therapy is deemed the standard treatment by many North American and European teams for treatment of locally advanced cervical cancer. The prevalence of para-aortic nodal metastasis in these tumours is 10-25%. PET (with or without CT) is the most accurate imaging modality to assess extrapelvic disease in such tumours. The true-positive rate of PET is high, suggesting that surgical staging is not necessary if uptake takes place in the para-aortic region. Nevertheless, false-negative results (in the para-aortic region) have been recorded in 12% of patients, rising to 22% in those with uptake during PET of the pelvic nodes. In such situations, laparoscopic surgical para-aortic staging still has an important role for detection of patients with occult para-aortic spread misdiagnosed on PET or PET-CT, allowing optimisation of treatment (extension of radiation therapy fields to include the para-aortic area). Complications of the laparoscopic procedure were noted in 0-7% of patients. Survival of individuals (missed by PET) with para-aortic nodal metastasis of 5 mm or less (and managed by extended field chemoradiation therapy) seems to be similar to survival of those without para-aortic spread, suggesting a positive therapeutic effect of the addition of staging surgery. Nevertheless, the effect on survival of potential delay of chemoradiation owing to use of PET and staging surgery, and acute and late complications of surgery followed by chemoradiation therapy (particularly in case of extended field chemoradiation to para-aortic area), need to be studied.

Borderline ovarian tumour: pathological diagnostic dilemma and risk factors for invasive or lethal recurrence

By comparison with ovarian carcinomas, borderline ovarian tumours are characterised clinically by superior overall survival, even in women with peritoneal spread. In this Review, we aimed to clarify the histological and clinical factors potentially defining a high-risk group in whom disease is likely to evolve to invasive disease. Invasive peritoneal implants (in serous borderline ovarian tumours) and residual disease after surgery were the two factors clearly identified. Other factors are controversial owing to increased risk of invasive recurrence: micropapillary patterns in serous borderline ovarian tumour, intraepithelial carcinoma in mucinous lesions, stromal microinvasion in serous lesions, and use of cystectomy in mucinous borderline ovarian tumours. The pathologist has a pivotal role in assessment of the borderline nature of ovarian tumours and in identification of high-risk criteria, most of which are histological. But, reproducibility of the histological interpretation of some of these potential criteria--eg, classification of peritoneal implants (particularly in desmoplastic subtype), stromal microinvasion, micropapillary patterns, and intraepithelial carcinoma in mucinous borderline ovarian tumours--remains unclear, and should be investigated.

Prospective Multicenter Study Evaluating the Survival of Patients With Locally Advanced Cervical Cancer Undergoing Laparoscopic Para-Aortic Lymphadenectomy Before Chemoradiotherapy in the Era of Positron Emission Tomography Imaging

PURPOSE The aim of this prospective study conducted in three French comprehensive cancer centers was to evaluate the therapeutic impact on survival of laparoscopic para-aortic (PA) staging surgery in locally advanced cervical cancer (LACC) before chemoradiotherapy. PATIENTS AND METHODS We conducted a prospective multicenter study of 237 patients treated from 2004 to 2011 for LACC with negative positron emission tomography (PET) imaging of the PA area and undergoing laparoscopic PA lymphadenectomy. Radiation fields were extended to the PA area when PA nodes were involved. Chemoradiotherapy modalities were homogeneous across institutions. Patients with a poor prognosis histologic subtype or peritoneal carcinosis were excluded. RESULTS Patients had clinical International Federation of Gynecology and Obstetrics stages IB2 (n = 79), IIA (n = 10), IIB (n = 121), III (n = 22), or IVA (n = 5). One hundred ninety-nine patients had squamous carcinoma, and 38 had adenocarcinoma/adenosquamous lesions. Twenty-nine patients (12%) had nodal involvement (false-negative PET-computed tomography [CT] results)-16 with a PA nodal metastasis measuring more than 5 mm and 13 with a nodal metastasis measuring ≤ 5 mm. Event-free survival rates at 3 years in patients without PA involvement or with PA metastasis measuring ≤ or more than 5 mm were 74% (SE, 4%), 69% (SE, 21%), and 17% (SE, 14%; P < .001). CONCLUSION To our knowledge, this is the largest series of patients reported undergoing such a strategy. We obtained the same survival rate for patients with PA nodal metastasis ≤ 5 mm and patients without PA lymph node involvement, suggesting that this strategy is highly efficient in such patients. Conversely, the survival of patients with PA nodal involvement greater than 5 mm remained poor, despite the absence of extrapelvic disease on PET-CT imaging in this subgroup.

Prognostic Impact of Vitamin B6 Metabolism in Lung Cancer

Patients with non-small cell lung cancer (NSCLC) are routinely treated with cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo. By aggravating a bioenergetic catastrophe that involves the depletion of intracellular glutathione, vitamin B6 exacerbates cisplatin-mediated DNA damage, thus sensitizing a large panel of cancer cell lines to apoptosis. Moreover, vitamin B6 sensitizes cancer cells to apoptosis induction by distinct types of physical and chemical stress, including multiple chemotherapeutics. This effect requires pyridoxal kinase (PDXK), the enzyme that generates the bioactive form of vitamin B6. In line with a general role of vitamin B6 in stress responses, low PDXK expression levels were found to be associated with poor disease outcome in two independent cohorts of patients with NSCLC. These results indicate that PDXK expression levels constitute a biomarker for risk stratification among patients with NSCLC.

Fertility and borderline ovarian tumor: a systematic review of conservative management, risk of recurrence and alternative options

BACKGROUND The aim of this systematic review was to evaluate the fertility outcome after borderline ovarian tumor (BOT) management and the results of conservative management, risk of recurrence and alternative options. METHODS The search strategy was based on relevant terms concerning BOT using Medline and the Central Cochrane Library. Both early and advanced stages of serous and mucinous BOT were included, but not rare entities such as endometrioid, Brenner or clear-cell BOT because of their low incidence. We considered all articles-case reports, original studies, meta-analyses and reviews-in English and French. RESULTS Overall, 230 articles were screened of which 120 were retained for review. Most pregnancies were spontaneous but some data were obtained from studies analyzing the contribution of assisted reproductive technology (ART). However, not all studies differentiated spontaneous pregnancy from those obtained after fertility treatment including ovulation induction, intrauterine insemination and IVF. Conservative management of early stage BOT resulted in a pooled estimate for spontaneous pregnancy rate of 54% with a low risk of lethal recurrence (pooled estimate: 0.5%). In patients with advanced stage BOT, the spontaneous pregnancy rates was lower (34% in the single series reporting pregnancy rate in this context) and the risk of lethal recurrence increased (pooled estimate: 2%). CONCLUSIONS This systematic review underlines that fertility subsequent to treatment of BOT depends mainly on histology and initial staging to distinguish early from advanced stages. In patients with advanced stage BOT, several alternative options to conservative management are available to allow patients to conceive without compromising their prognosis.

Outcomes after conservative treatment of advanced-stage serous borderline tumors of the ovary

BACKGROUND The aim of this study was to assess the outcomes of the largest series of patients treated conservatively for a stage II or III serous borderline ovarian tumor. MATERIALS AND METHODS From 1969 to 2006, 41 patients were treated conservatively for an advanced-stage serous borderline ovarian tumor. Patient outcomes were reviewed. RESULTS Twenty patients had undergone a unilateral salpingo-oophorectomy, 18 a unilateral cystectomy and two bilateral cystectomy (unknown for one patient). Three patients had invasive implants. The median duration of follow-up was 57 months (range 4-235). The recurrence rate was high (56%), but overall survival remained excellent (100% at 5 years, 92% at 10 years). One death had occurred due to an invasive ovarian recurrence. Eighteen pregnancies (nine spontaneous) were observed in 14 patients. CONCLUSIONS This study demonstrates that spontaneous pregnancies can be achieved after conservative treatment of advanced-stage borderline ovarian tumors (with noninvasive implants) but the recurrence rate is high. Nevertheless, this high rate has no impact on survival. Conservative surgery can be proposed to patients with a borderline tumor of the ovary and noninvasive peritoneal implants. Should infertility persist following treatment of the borderline tumor, an in vitro fertilization procedure can be cautiously proposed.

Immediate Reconstruction After Neoadjuvant Chemotherapy: Effect on Adjuvant Treatment Starting and Survival

BackgroundFor patients treated with initial surgery, the safety of immediate breast reconstruction after mastectomy has been demonstrated. Some concerns exist after neoadjuvant chemotherapy because this sequence is proposed for patients with large tumors and for whom adjuvant therapies are considered cornerstones of treatment. In this study, we sought to determine whether reconstruction after neoadjuvant chemotherapy and mastectomy for large operable breast cancer affects the interval between surgery and adjuvant treatment and affects survival.MethodsA single-institution retrospective analysis was performed by using the database of the Institut Gustave-Roussy.ResultsForty-eight patients who had undergone mastectomy and immediate reconstruction (implant, 60%) followed by adjuvant chemotherapy were identified. They were compared with 181 patients who underwent mastectomy without reconstruction and with 32 patients who underwent mastectomy followed by delayed reconstruction (implant, 19%). No difference was found concerning the interval between surgery and adjuvant chemotherapy: 26 vs. 23 days for patients with immediate breast reconstruction and for patients treated with modified radical mastectomy followed or not by delayed reconstruction, respectively (P = .11). No difference was found concerning the onset of radiotherapy: 87 vs. 81 days (P = .22). Survival was not different in patients treated with immediate reconstruction compared with those with mastectomy alone.ConclusionsImmediate breast reconstruction does not delay the starting of adjuvant therapy and has no significant effect on local relapse–free or distant disease–free survival. Additional data are needed concerning the use of flap for this indication.

Analysis of Morbidity and Clinical Implications of Laparoscopic Para-Aortic Lymphadenectomy in a Continuous Series of 98 Patients with Advanced-Stage Cervical Cancer and Negative PET–CT Imaging in the Para-Aortic Area

BACKGROUND Laparoscopic para-aortic lymphadenectomy (PAL) is being used increasingly to stage patients with locally advanced cervical cancer (LACC) and to define radiation field limits before chemoradiation therapy (CRT). This study aimed to define clinical implications, review complications, and determine whether surgical complications delayed the start of CRT. METHODS We retrospectively reviewed a continuous series of patients with LACC, with no positive para-aortic (PA) nodes on positron emission tomography-computed tomography (PET-CT) and who had undergone a primary laparoscopic PAL. RESULTS From November 2007 to June 2010, 98 patients with LACC underwent pretherapeutic PAL. Two patients did not undergo PAL: extensive carcinomatosis was discovered in one case and a technical problem arose in the other. No perioperative complications occurred. Seven patients had a lymphocyst requiring an imaging-guided (or laparoscopic) puncture. Eight patients (8.4%, which corresponds to the false-negative PET-CT rate) had metastatic disease within PA lymph nodes. In cases of suspicious pelvic nodes on PET-CT, the risk for PA nodal disease was greater (24.0% versus 2.9%). When patients with and without surgical morbidity were compared, the median delay to the start of treatment was not significantly different (15 days; range, 3-49 days versus 18 days; range, 3-42 days). CONCLUSIONS The morbidity of laparoscopic PAL was limited and the completion of treatment was not delayed when complications occurred. Nevertheless, if PET-CT of the pelvic area is negative, the interest in staging PAL could be discussed because the risk for PA nodal disease is very low.