Pressurized intra-peritoneal aerosol chemotherapy (PIPAC): increased intraperitoneal pressure does not affect distribution patterns but leads to deeper penetration depth of doxorubicin in a sheep model.

BACKGROUND: Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is an innovative treatment against peritoneal carcinomatosis. Doxorubicin is a common intra-venous chemotherapy used for peritoneal carcinomatosis and for PIPAC. This study evaluated the impact of increased PIPAC intraperitoneal pressure on the distribution and cell penetration of doxorubicin in a sheep model. METHODS: Doxorubicin was aerosolized using PIPAC into the peritoneal cavity of 6 ewes (pre-alpes breed): N = 3 with 12 mmHg intraperitoneal pressure ("group 12") and N = 3 with 20 mmHg ("group 20"). Samples from peritoneum (N = 6), ovarian (N = 1), omentum (N = 1) and caecum (N = 1) were collected for each ewe. The number of doxorubicin positive cells was determined using the ratio between doxorubicine fluorescence-positive cell nuclei (DOXO+) over total number of DAPI positive cell nuclei (DAPI+). Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei over the total number of cell nuclei that were stained with DAPI. Penetration depth (µm) was defined as the distance between the luminal surface and the location of the deepest DOXO+ nuclei. RESULTS: DOXO+ nuclei were identified in 87% of samples. All omental samples, directly localized in front of the nebulizer head, had 100% DOXO+ nuclei whereas very few nuclei were DOXO+ for caecum. Distribution patterns were not different between the two groups but penetration depth in ovary and caecum samples was significantly deeper in group 20. CONCLUSIONS: This study showed that applying a higher intra-peritoneal pressure during PIPAC treatment leads to a deeper penetration of doxorubicin in ovarian and caecum but does not affect distribution patterns.

Systematic Nerve Sparing during Surgery for Deep-infiltrating Posterior Endometriosis Improves Immediate Postoperative Urinary Outcomes.

STUDY OBJECTIVE: Evaluate the feasibility and risk-benefit ratio of systematic nerve sparing by complete dissection of the inferior hypogastric nerves and afferent pelvic splanchnic nerves during surgery for deep-infiltrating endometriosis (DIE) on the basis of complication rates and postoperative bladder morbidity. DESIGN: Observational before (2012-2014)-and-after (2015-2017) study based on a prospectively completed database of all patients treated medically or surgically for endometriosis. SETTING: Unicentric study at the Centre Hospitalier Intercommunal de Poissy-St-Germain-en-Laye. PATIENTS: This study included patients undergoing laparoscopic surgery for DIE (pouch of Douglas resection with or without colpectomy or bilateral uterosacral ligament resection), with complete excision of all identifiable endometriotic lesions, with or without an associated digestive procedure, between 2012 and 2017. The exclusion criteria included prior history of surgery for DIE or colorectal DIE excision, unilateral uterosacral ligament resection, and bladder endometriotic lesions. INTERVENTIONS: For the patients in group 1 (2012-2014, n = 56), partial dissection of the pelvic nerves was carried out only if they were macroscopically caught in endometriotic lesions, without dissection of the pelvic splanchnic nerves. The patients in group 2 (2015-2017, n = 65) systematically underwent nerve sparing during DIE surgery, with dissection of the inferior hypogastric nerves and pelvic splanchnic nerves. MEASUREMENTS AND MAIN RESULTS: Both groups were comparable in terms of patient age, parity, body mass index, and previous abdominal surgery. The operating times were similar in both groups (228 ± 105 minutes in group 2 vs 219 ± 71 minutes in group 1), as were intra- and postoperative complication rates. Time to voiding was significantly longer in the patients in group 1 (p <.01), with 7 (12.9%) patients requiring self-catheterization in this group compared with no patients (0%) in group 2. The duration of self-catheterization for the 7 patients in group 1 was 28, 21, 3, 60, 21, 1 (stopped by the patient), and 28 days, respectively. Uroflowmetry on postoperative day 10 was abnormal in 5/25 patients in group 1 compared with 1/33 in group 2 (p = .031). CONCLUSION: Systematic and complete nerve sparing, including pelvic splanchnic nerve dissection, during surgery for posterior DIE improves immediate postoperative urinary outcomes, reducing the need for self-catheterization without increasing operating time or complication rates.

Prognosis impact of posttreatment pelvic MRI in patients treated for stage IB2-IIB cervical cancer with chemoradiation therapy.

OBJECTIVES: To evaluate the performances of systematic posttreatment pelvic magnetic resonance imaging (PPMRI) in predicting prognosis of patients treated with chemoradiation therapy (CRT) for locally advanced cervical cancer (LACC). MATERIALS AND METHODS: Multi-institutional data from 216 patients presenting FIGO IB2-IIB cervical cancer for which PPMRI was performed following CRT were retrospectively reviewed. Incomplete response was defined as the identification of persistent lesion on PPMRI. Primary endpoints were patients' 5-year recurrence free (RFS) and overall (OS) survivals. Secondary endpoint was the identification of residual histologic disease on hysterectomy specimens when completion surgery was performed. RESULTS: PPMRI identified an incomplete response in 102 (47.2%) cases. A 70% or more reduction in tumor size on PPMRI was identified as the best predictive cut-off for recurrence (37.7% sensitivity and 78.7% specificity) and death (50% sensitivity and 77.9% specificity) with significant impact on those risks (HRa: 0.42; 95%CI: 0.23-0.77 and HRa: 0.18; 95%CI: 0.06-0.50, respectively). Completion hysterectomy was performed in 117 (54.4%) cases, with histologic residual disease in 55 (47.4%). PPMRI demonstrated 74.5% sensitivity and 50.8% specificity in predicting residual disease. Although survival of patients with complete response at PPMRI was not impacted by completion hysterectomy, it significantly increased 5-year RFS and OS of those with incomplete response: 38.7% vs. 65.3% (p < 0.001) and 63% vs. 82.9% (p = 0.038), respectively. CONCLUSION: A 70% or more reduction of in tumor size on PPMRI following CRT in patients with LACC is predictive of RFS and OS. PPMRI could help triaging patients who could benefit from completion hysterectomy.

Prognostic value of posttreatment FEDG-PET imaging following combined chemoradiation therapy in locally advanced cervical cancer.

OBJECTIVES: To evaluate the performances of posttreatment FEDG-PET to predict the prognosis of patients treated with concurrent chemoradiotherapy (CT/RT) for locally advanced cervical cancer. MATERIALS AND METHODS: The medical records of 131 patients treated in 9 French academic institutions for IB2-IIB cervical cancer and for which a posttherapy FEDG-PET was performed were reviewed. All patients received CT/RT, possibly completed with vaginal brachytherapy (VBT) and completion surgery. Posttreatment FEDG-PET was performed within 3 months after completion of CT/RT or VBT. Incomplete metabolic response (IMR) was defined as the persistence of FEDG uptake. RESULTS: An IMR was identified in 44 (33.6 %) cases. IMR was associated with higher risk of recurrence (aHR = 2.8; 95 %CI: 1.3-5.7; p = 0.006) and death (aHR = 4.5 ;95 %CI: 1.4-13.8; p = 0.009). Completion surgery was performed in 61 (46.9 %) patients with histologic cervical residual disease identified in 31 (50.8 %). FEDG-PET sensitivity and specificity in predicting cervical residual disease following CT/RT was 48.4 % (95 %CI: 30.8-66) and 80 % (95 %CI: 65.7-94.3), respectively. CONCLUSIONS: In patients treated with CT/RT for locally advanced cervical cancer, despite limited performances to predict cervical residual disease, posttreatment FEDG-PET is predictive of patients' prognosis and long-term outcome.

Three-Dimensional Modelization of the Female Human Inferior Hypogastric Plexus: Implications for Nerve-Sparing Radical Hysterectomy.

BACKGROUND/AIMS: This study aims to describe the autonomic nervous network of the female pelvis with a 3D model and to provide a safe plane of dissection during radical hysterectomy for cervical cancer. METHODS: Pelvises of 3 human female fetuses were studied by using the computer-assisted anatomic dissection. RESULTS: The superior hypogastric plexus (SHP) was located at the level of the aortic bifurcation in front of the sacral promontory and divided inferiorly and laterally into 2 hypogastric nerves (HN). HN ran postero-medially to the ureter and in the lateral part of the uterosacral ligament until the superior angle of the inferior hypogastric plexus (IHP). IHP extended from the anterolateral face of the rectum, laterally to the cervix and attempted to the base of the bladder. Vesical efferences merged from the crossing point of the ureter and the uterine artery and ran through the posterior layer of the vesico-uterine ligament. CONCLUSIONS: The SHP could be injured during paraaortic lymphadenectomy. Following the ureter and resecting the medial fibrous part of the uterosacral ligament may spare the HN. No dissection should be performed under the crossing point of the ureter and the uterine artery.

A pre-operative predictive score to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer.

OBJECTIVE: Postoperative residual tumor is the major prognostic factor in ovarian cancer. The feasibility of complete cytoreductive surgery is assessed by laparoscopy. Our goal was to develop a predictive score prior to laparoscopy to evaluate the feasibility of complete cytoreductive surgery in patients with epithelial ovarian cancer. METHODS: We developed a score to predict incomplete cytoreductive surgery by performing multiple logistic regressions after bootstrap procedures on data from a retrospective cohort of 247 patients with advanced ovarian cancer. This score was validated on a different population of 45 patients with ovarian cancer. RESULTS: Four criteria were independently associated with incomplete cytoreduction, confirmed by surgery: BMI ≥ 30 kg/m2 (adjusted odds ratio [aOR], 3.07; 95% confidence interval [95% CI], 1.0-9.6), CA125 > 100 IU/L (aOR, 3.99; 95% CI, 1.6-10.1), diaphragmatic and/or omental carcinomatosis by CT-Scan (aOR, 5.82; 95% CI, 2.6-13.1), and positive parenchymal metastases by PET/CT (aOR, 3.59; 95% CI, 1.0-12.8). The 100-point score was based on these criteria. The area-under-the-curve of the score was 0.79 (95% CI, 0.73-0.86). In the validation group, no patient ranked in the high-risk group of incomplete cytoreductive surgery had a complete upfront cytoreductive surgery (95% CI 0-16). Three of 29 patients for whom primary complete cytoreduction was not possible were classified in the group at low risk of incomplete cytoreductive surgery (12%; 95% CI 4-27). CONCLUSION: This pre-operative score may be useful for distinguishing which patients may have complete cytoreductive surgery from those who will receive neoadjuvant chemotherapy, while avoiding unnecessary laparoscopy.

[External multicentric validation of two scores predicting the risk of relapse in patients with borderline ovarian tumors: The nomogram of Bendifallah and the score of Ouldamer]. / Validation externe de 2 scores prédictifs de récidive de tumeurs mucineuses et séreuses borderline de l'ovaire : le nomogramme de Bendifallah et le score d'Ouldamer.

BACKGROUND: Borderline ovarian tumors are rare and can occur in young women. For these patients, a fertility sparing surgery should be discussed. Two predicting borderline ovarian tumor relapse risk models were developed in 2014 (Nomogram of Bendifallah) and 2017 (Score of Ouldamer). This study aimed to valid in an external population, these two scores using a multi-institutional BOT database. METHODS: In this bicentric and retrospective study, all consecutive patients comprising the variable nomogram documented treated between January 2006 and December 2012 for BOT in centre hospitalier de Poissy-Saint-Germain and hôpital René-Huguenin were included. A ROC model was established for each predicting scores. RESULTS: Sixty-five patients were included in the study. Twelve patients showed a recurrence (19%), three of them experienced an infiltrative cancer (5%). The median time of recurrence was 25 months (range: 8-115). The concordance index for the Nomogram of Bendifallah and the Score of Ouldamer were 0.88 (IC 95% [0.78-0.98]) and 0.87 (IC 95% [0.77-0.96]) respectively. CONCLUSION: This study from an independent population valids the Bendifallah nomogram and Ouldamer score for clinical use in predicting borderline ovarian recurrence.

Reexcision for positive margins in breast cancer: A predictive score of residual disease.

BACKGROUND: Guidelines recommend re-excision if resection margins are positive in lumpectomy for breast cancer. However, residual disease (RD) is not always found. The aim of our study was to develop a score to predict RD in re-excision specimens. MATERIALS AND METHODS: We carried out a multicenter, retrospective study with two population groups. The 'modeling' group was composed of 148 patients treated in the Centre Hospitalier Poissy-St-Germain or the Georges Pompidou European Hospital and the 'validation' group was composed of 67 patients treated in Curie Institute. The score was built with a logistic regression model. RESULTS: Factors independently associated with RD were: a cumulative length of all positive margins>5 mm, invasion by ductal carcinoma in situ only, a pathological tumor size>30 mm and a pathological tumor size<30 mm with a discrepancy of >50% between pathological and radiological tumor size. The 7-point score allowed the classification of patients into three risk groups for RD: low (16% of patients experienced RD), moderate (65%) and high (100%). The areas under the ROC curve of the score and the logistic model were 0.72(95%CI:0.68-0.75,p = 0.60). The proportion of RD in each group of the validation population (25%, 48%, and 100% in the low, moderate and high group, respectively) confirmed the accuracy of the score in an independent population. CONCLUSIONS: This score enables the identification of patients at high risk of RD but it cannot provide guidance for the decision to undertake re-excision surgery in the low-risk group. Further studies are needed to test the score in extensive datasets and better identify low-risk patients.

Robotic extraperitoneal paraaortic lymphadenectomy in gynecological cancers: feasibility, safety, and short-term outcomes of isolated and combined procedures.

OBJECTIVE: The aim of our study was to report the technique, the feasibility, and perioperative results of robotic extraperitoneal paraaortic lymphadenectomy in gynecological cancers performed for isolated or combined procedures. METHODS: This is a retrospective study of 24 consecutive patients undergoing robotic extraperitoneal paraaortic lymphadenectomy using the Da Vinci Surgical system (Intuitive Inc, Sunnyvale, CA) (cervical cancer, n = 15; high-risk endometrial cancer, n = 8; and ovarian cancer, n = 2, including 1 synchronous tumor). Extraperitoneal paraaortic lymphadenectomy was performed using the surgical technique previously described by laparoscopy. RESULTS: Of the 24 included patients, 12 patients had isolated robotic extraperitoneal paraaortic lymphadenectomy, whereas the others underwent the following associated procedures: total hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and omentectomy (n = 7); pelvic transperitoneal lymphadenectomy (n = 3), laparotomic Bricker procedure (n = 1), and colpectomy (n = 1). The median age of patients was 55 (42-64) years, and body mass index was 24.1 kg/m (20.9-26.1). The operation was completed in all patients except three with associated procedures. Perioperative difficulties were encountered in 9 patients (gas leakage, n = 7; adhesions, n = 2; and dissection difficulties, n = 1). The number of removed paraaortic lymph nodes was 18 (14-25). The operating times were 180 (150-210) minutes for isolated extraperitoneal paraaortic lymphadenectomy and 240 (180-300) minutes in case of associated procedures. There were 2 intraoperative (pneumothorax and renal artery injury) and 5 postoperative (3 grades 1-2 and 2 grade 3) complications. CONCLUSIONS: If robotic-assisted extraperitoneal paraaortic lymphadenectomy seems feasible in case of isolated procedure, further studies are required to prove its benefit compared with conventional laparoscopy.