Impact of preoperative brachytherapy followed by radical hysterectomy in stage IB2 (FIGO 2018) cervical cancer: An analysis of SENTICOL I-II trials.

INTRODUCTION: The goal of this study was to compare the outcomes of preoperative brachytherapy followed by radical surgery versus radical surgery alone in cervical cancer with tumor between 2 and 4 cm (FIGO 2018 IB2). MATERIAL AND METHODS: SENTICOL I and SENTICOL II were two French prospective multicentric trials evaluating sentinel node biopsy in early-stage cervical cancer between 2005 and 2012. Preoperative brachytherapy (low-dose rate or pulse-dose rate at the dose of 60Gy) could be performed 6 to 8 weeks prior to the radical hysterectomy, at the discretion of each center. SENTICOL I and SENTICOL II cohorts were retrospectively analysed to compare the outcomes of preoperative brachytherapy or upfront surgery in patients with IB2 cervical tumor. RESULTS: A total of 104 patients were included: 55 underwent upfront radical hysterectomy and 49 underwent preoperative brachytherapy followed by radical hysterectomy. Patients with preoperative brachytherapy were more likely to have no residual disease (71.4% vs. 25.5%, p < 0.0001) and to be defined as low risk according to Sedlis criteria (83.3% vs. 51.2%, p < 0.0001). Adjuvant treatments were required less frequently in case of preoperative brachytherapy (14.3% vs. 54.5%, p < 0.0001). Patients with preoperative brachytherapy experienced more postoperative complications grade ≥ 3 (24.5% vs. 9.1%, p = 0.03). Patients with preoperative brachytherapy had better 5-year disease-free survival compared to patients who underwent surgery alone, 93.6% and 74.4% respectively (p = 0.04). CONCLUSION: Although preoperative brachytherapy was significantly associated with more severe postoperative complications, better pathologic features were obtained on surgical specimens and led to a better 5-year disease-free survival in IB2 cervical cancer.

Diagnostic value of frozen section examination of sentinel lymph nodes in early-stage cervical cancer at the time of ultrastaging.

OBJECTIVES: We aimed to assess the diagnostic value of frozen-section pathologic examination (FSE) of sentinel lymph nodes (SLN) in patients with early-stage cervical cancer. METHODS: Two French prospective multicentric database on SLN biopsy for cervical cancer (SENTICOL I and II) were analysed. Patients with IA to IIA1 2018 FIGO stage, who underwent SLN biopsy with both FSE and ultrastaging examination were included. RESULTS AND DISCUSSION: Between 2005 and 2012, 313 patients from 25 centers fulfilled the inclusion criteria. Metastatic involvement of SLN was diagnosed in 52 patients (16.6%). Macrometastases, micrometastases and isolated tumor cells (ITCs) were found in 27, 12 and 13 patients respectively. Among the 928 SLNs analysed, FSE identified 23 SLNs with macrometastases in 20 patients and 5 SLNs with micrometastases in 2 patients whereas no ITCs were identified. Ultrastaging of negative SLNs by FSE found macrometastases, micrometastases and ITCs in additional 7, 11 and 17 SLNs. Ultrastaging increased significantly the rate of patients with positive SLN from 7% to 16.6% (p < 0.0001). The sensitivity and the negative predictive value of FSE were 42.3% and 89.7% respectively or 56.4% and 94.1% if ITCs were excluded. False-negative cases were more frequent with tumor size ≥ 20 mm (OR = 4.46, 95%IC = [1.45-13.66], p = 0.01) and preoperative brachytherapy (OR = 4.47, 95%IC = [1.37-14.63], p = 0.01) and less frequent with patients included in higher volume center (>5 patients/year) (OR = 0.09, 95%IC = [0.02-0.51], p = 0.01). CONCLUSIONS: FSE of SLN had a low sensitivity for detecting micrometastases and ITCs and a high negative predictive value for SLN status. Clinical impact of false-negative cases has to be assessed by further studies.

Risk factors for failure of bilateral sentinel lymph node mapping in early-stage cervical cancer.

BACKGROUND: The objective of this study was to determine clinical, tumoral and surgical factors associated with successful bilateral sentinel lymph node mapping (SBM) in early-stage cervical cancer. METHODS: We performed an ancillary work on the data of two prospective trials on SLN biopsy for FIGO IA-IIA cervical cancer (SENTICOL I & II). Patients having Sentinel lymph node (SLN) mapping for early-stage cervical cancer were included between 2005 and 2012 from 28 French oncologic centers. SLN was detected by a combined labeling technique (blue and isotopic). RESULTS: 405 patients were included for analysis: SLNs were identified on at least one side of the pelvis in 381 patients (94.1%) and bilaterally in 326 patients (80.5%). The mean age was 45.4 years [22-85 years]. Most patients had IB1 pathologic FIGO 2018 stage (81.3%) and squamous cell carcinoma (71%). Surgeries were mainly performed by minimally invasive approach (368 patients - 90.9%). By multivariate analysis, lower SBM rate was significantly associated with Age ≥70 years (ORa = 0.02, 95%CI = [0.001-0.28], p = 0.004), tumor size larger than 20 mm (ORa = 0.46,95%CI = [0.21-0.99], p = 0.048) and Body-mass index higher than 30 kg/m2 (ORa = 0.28, 95%CI = [0.12-0.65], p = 0.003). SBM rate was significantly higher in high skills centers (>5patients/year) (ORa = 8.05, 95%CI = [2.06-31.50], p = 0.003) and in SENTICOL II (2009-2012) compared to SENTICOL I (2005-2007) (ORa = 2.6, 95%CI = [1.23-5.51], p = 0.01). CONCLUSIONS: In early-stage cervical cancer, bilateral SLN detection rates is lower in patients aged more than 70years, patients with BMI≥30 kg/m2 and larger tumor ≥20 mm whereas stronger experience of SLN biopsy technique improves bilateral SLN detection.

Predictive factors of unexpected lymphatic drainage pathways in early-stage cervical cancer.

OBJECTIVES: The purpose of this study was to describe sentinel lymph nodes (SLN) topography in patients with early-stage cervical cancer and to determine factors associated with atypical lymphatic drainage pathway (LDP). METHODS: We analyzed the data of two prospective multicentric trials on SLN biopsy for cervical cancer (SENTICOL I and II) in women undergoing surgery for early-stage cervical cancer. SLN detection was realized with a combined labeling technique (Patent blue and radioactive tracer). Patients having bilateral SLN detection were included. Univariate and Multivariate analysis were performed by patients and by side to assess clinical and pathologic factors that may predict atypical LDP. RESULTS: Between January 2005 and July 2012, 326 patients with 1104 intraoperative detected SLNs fulfilled the inclusion criteria. The SLNs were mainly located in the interiliac or external iliac area in 83.2%. The other localizations were: 9.2% in the common iliac area, 3.9% in the parametrium, 1.6% in the promontory area, 1.5% in the paraaortic area and 0.5% in other areas. Thirty-five patients (10.7%) had atypical SLN without SLN in typical area on one or both sides. In multivariate analysis, tumor size ≥20 mm appeared as an independent factor of having at least one exclusive atypical LDP (ORa = 3.95 95%CI = [1.60-9.78], p = 0.003). Multiparity decreased significantly the probability of having at least one exclusive atypical LDP (ORa = 0.16 95%CI = [0.07-0.39], p < 0.0001). CONCLUSIONS: Tumor size larger than 20 mm and nulliparity increase the risk of having exclusive atypical LDP in early-stage cervical cancer.

Contribution of Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Women with Early Stage Endometrial Cancer: Results of the SENTI-ENDO Study.

BACKGROUND: This study was designed to evaluate detection rate and anatomical location of sentinel lymph node (SLN) at lymphoscintigraphy, to compare short and long lymphoscintigraphy protocols, and to correlate lymphoscintigraphic and surgical mapping of SLN in patients with early-stage endometrial cancer (EC). METHODS: Subanalysis of the prospective multicenter study Senti-endo performed from July 2007 to August 2009. Patients with stage I and II EC received four cervical injections of 0-2 mL of unfiltered technetium sulphur colloid the day before (long protocol) or the morning (short protocol) before surgery. SLN detection used a combined technetium/patent blue labeling technique, and all patients had a systematic bilateral pelvic lymphadenectomy. RESULTS: A total of 133 patients were enrolled in the study and 118 (94.5 %) underwent a lymphoscintigraphy. Of these 118 patients, 44 (37 %) underwent a short protocol and 66 (56 %) a long protocol (data on lymphoscintigraphy were not available in eight patients). Lymphoscintigraphic detection rate was 74.6 % (34 % for short protocol and 60.2 % for long protocol). No difference in the detection rate was observed according to lymphoscintigraphy protocol (p = 0.22), but a higher number of SLN was noted for the long protocol (p = 0.02). Aberrant drainage was noted on lymphoscintigraphy in 30.5 % of the patients. Paraaortic SLNs were exclusively detected using the long protocol. A poor correlation was noted between short (κ test = 0.24) or long lymphoscintigraphy (κ test = 0.3) protocol and SLN surgical mapping. CONCLUSIONS: Our study demonstrates that preoperative lymphoscintigraphy allowed a high SLN detection rate and that long lymphoscintigraphy protocol was associated with a higher detection of aberrant drainage especially in the paraaortic area.

[Current developments in uterine cervical carcinoma prevention and screening]. / Actualités sur le dépistage et la prévention des infections à VPH dans le cadre des cancers du col utérin.

The causality between the HPV infection and the carcinoma of the uterine cervix is demonstrated. The benefits of the prophylactic HPV vaccine are emerging in the general population. This vaccine has no evident general side effect. So it is proposed for young women and young men. The commercialization of a nonavalent vaccine will increase its preventive activity. Already, international societies recommend using the HPV test for cervical carcinoma screening in replacement of the cytology in women more than 30-35 years old. In case of negative test, the interval between screenings can be increase until 5 years. In case of positive test, the cervical cytology is used for the triage, but other tests are under development. Due to the vaccine efficacy, the future modalities and the cost/benefits ratio of the screening should be questioned.

Full labia minora reconstruction with labia sharing flap: a case report.

Full labia minora reconstruction can be necessary due to congenital malformation or genetic syndromes, but more often is required following oncologic excisions, or debridements after vulvar or perineal infections. It is important to note that full labia reconstruction can be needed after genital mutilation, or iatrogenic deformity after previous labia reduction procedure. A 37-year-old female patient, with vulvar necrotizing fasciitis after a marsupialization of the right Bartholin's gland, was referred to the Gynecology and Obstetrics unit. Three surgical debridements were performed, associated with prolonged antibiotic therapy, leading to a total loss of the right labia minora and the clitoris glans, in addition to minimal loss of labia majora. With a two-stage approach on the labia minora, the first procedure allowed to pull the left labia minora as a labia sharing flap, in order to join the remnant scar tissue on the right side, respecting the anterior and posterior leaflets. The second part was performed five weeks later, after autonomization of the new labia minora flap. Once the flap was divided, a perfectly vascularized right neo-labia minora was obtained. The flap healed uneventfully. The patient was asked to complete a questionnaire at six months, which confirmed an excellent aesthetic result with a like with like reconstruction. Eight months later, a final correction was performed to enhance the definitive aesthetic aspect with lipofilling of the right labia majora. Two techniques have been previously published with a two-stage cross-labial transposition flap, one using a top cut leading to a bottom pedicle and another using a bottom cut with an upper pedicle. We proceeded with a one-time edge resection, respecting the full vascular pedicle and transposed the full height of the labia minora. This technique revealed to be extremely effective, guaranteeing a reliable vascularization and decreasing the risk of tearing on the pedicle.

Accuracy of a nomogram for prediction of lymph-node metastasis detected with conventional histopathology and ultrastaging in endometrial cancer.

BACKGROUND: We developed a nomogram based on five clinical and pathological characteristics to predict lymph-node (LN) metastasis with a high concordance probability in endometrial cancer. Sentinel LN (SLN) biopsy has been suggested as a compromise between systematic lymphadenectomy and no dissection in patients with low-risk endometrial cancer. METHODS: Patients with stage I-II endometrial cancer had pelvic SLN and systematic pelvic-node dissection. All LNs were histopathologically examined, and the SLNs were examined by immunohistochemistry. We compared the accuracy of the nomogram at predicting LN detected with conventional histopathology (macrometastasis) and ultrastaging procedure using SLN (micrometastasis). RESULTS: Thirty-eight of the 187 patients (20%) had pelvic LN metastases, 20 had macrometastases and 18 had micrometastases. For the prediction of macrometastases, the nomogram showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.76, and was well calibrated (average error =2.1%). For the prediction of micro- and macrometastases, the nomogram showed poorer discrimination, with an AUC of 0.67, and was less well calibrated (average error =10.9%). CONCLUSION: Our nomogram is accurate at predicting LN macrometastases but less accurate at predicting micrometastases. Our results suggest that micrometastases are an 'intermediate state' between disease-free LN and macrometastasis.

Accessory and cavitated uterine masses: a case series and review of the literature.

Objectives: The purpose of this study is to report nine patients of young women who underwent a surgical treatment of an accessory and cavitated uterine mass (ACUM) in our hospital between 2014 and 2022 and review all cases described in the literature. Material and methods: The principal outcomes measured are the imaging techniques used to determine the diagnosis, the type of surgery used and the post-operative evolution of symptoms. We also report and analyse the 79 patients found in the literature since 1996 in addition to our 9 patients. Results: Surgical excision is the only long-lasting treatment. Small invasive surgery with laparoscopic access is the gold standard and most widely used (83.0%). Some new therapeutic procedures have been recently described of which ethanol sclerotherapy seems very promising. Post-operatively, 54.5% of patients have a complete relief of symptoms. MRI is the best imaging technique to identify ACUM. Finally, we refine the description of this pathology and give a more precise definition of it. Conclusion: Through our literature review and the analysis of our cases, we want to underline an important diagnostic criterion of this pathology: the fallopian tube on the homolateral side of the ACUM never communicates with the latter. It is a capital element for differential diagnosis.

When obstetrics-gynecology specialists need to call an ophthalmologist urgently: a case report.

BACKGROUND: We report here a case of a healthy 23-year-old female patient who was assessed at the gynecology emergency department for genital ulcers, fever, and blurred vision. After suspicion of herpes simplex virus-2 lesions, the diagnosis of Behçet's disease was made. We report this case with the aim of including Behçet's disease in the differential diagnosis of genital ulcers, and emphasize the emergency of the vision loss that can be irreversible. CASE PRESENTATION: A healthy 23-year-old European female patient was assessed by gynecology in the emergency department for genital lesions associated with fever and blurred vision. At first, these lesions were suspected to be primary herpes simplex virus-2 infection One day later, she experienced decreased visual acuity in both eyes. After 4 days of worsening genital ulcers and persistent blurred vision, the patient was referred to the ophthalmology department. Fundoscopic examination showed retinal hemorrhages that were consistent with the first presentation of Behçet's disease. CONCLUSIONS: This case demonstrates that genital ulcers can be the very initial symptom of this ophthalmologic emergency. The differential diagnosis of genital ulcers is challenging. Behçet's disease should be included, especially when associated with systemic or ocular manifestations, and should be considered an emergency for the gynecologist to prevent long-term vision loss.

Challenges and advances in cervix cancer treatment in elder women.

With population ageing, cancer treatments in elder patients is becoming a true public health care issue. There is an authentic dilemma between patient's frailty, residual life expectancy and the toll that take anticancer treatments. Since elder patients are almost always excluded from clinical trials, it is hard to get robust scientific data on the tolerability of oncologic treatments and to set in place recommendations. Cervix cancer is traditionally diagnosed in younger women but it has a 2nd incidence peak between 60 and 70 years old. Cervix cancer in elder patients is a subject to many questions in terms of screening and is a therapeutic challenge. This article reviews literature data on these different aspects, from screening to surgery, from radiotherapy to brachytherapy, from chemotherapy to supportive care, from immunotherapy to geriatric assessment. We tried to show how modern therapeutic innovations may benefit elder patients. Expected benefits in terms of efficacy and toxicity may overcome the long-lasting tendency to undertreatment in elder patients and improve their quality of life after cancer treatment. In 2020, there seems to be less and less reasons justifying that elder women with cervix cancer may not receive the appropriate treatment.

Predictive factors of severe perioperative morbidity of radical hysterectomy with lymphadenectomy in early-stage cervical cancer: A French prospective multicentric cohort of 248 patients.

OBJECTIVE: The purpose of this study was to assess the postoperative morbidity after radical hysterectomy (RH) for early-stage cervical cancer and to determine risk factors of severe perioperative morbidity. METHODS: Data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II) were analysed. Patients having a radical hysterectomy were included between 2005 and 2012 from 25 French oncologic centers. Postoperative complications were prospectively recorded in a pre-specified analysis. RESULTS: 248 patients met the inclusion criteria. The median age was 44.5 years [25-85]. 88.7% of patients had a stage IB1 disease. There were 71.4% epidermoid carcinomas and 25% adenocarcinomas. 125 patients (50.4%) had a laparoscopic-assisted vaginal RH, 88 patients (35.5%) had a total laparoscopic RH, 26 patients (10.5%) had an open RH and 9 patients (3.6%) had a robotic-assisted RH. Sixteen patients (6.4%) had intraoperative complications. On a multivariate analysis, intraoperative complications were significantly associated with BMI >30 kg/m2. The urinary, lymphovascular and neurologic complications rates were respectively 34.3%, 20.6% and 19.8%. 31 patients (12.5%) had severe postoperative complications (Clavien-Dindo ≥ 3 or CTCAE ≥ 3). On multivariate analysis, severe postoperative complications were associated with parametrial involvement, preoperative brachytherapy and inclusion in low surgical skills center. CONCLUSIONS: This study based on prospective data showed that RH has low severe postoperative complications. The main complications were urinary infections and lower limb lymphedema. Patients with early-stage cervical cancer should be referred to expert center to ensure best surgical outcomes.

Clomiphene citrate effect on testosterone level and semen parameters in 18 infertile men with low testosterone level and normal/low gonadotropines level.

OBJECTIVE: To determine the effect of a 3-month course of clomiphene citrate (CC) on plasma testosterone (T) level and on semen parameters in 18 infertile men with low T level and normal or low gonadotropines level. STUDY DESIGN: A retrospective study was conducted by reviewing the medical records of men referred to a university fertility medicine unit for infertility management between January 2010 and March 2015. Men treated with CC for at least 3 months were included if they presented with: RESULTS: 18 patients met the inclusion criteria. CC was prescribed for 3 months at the dose of 50 mg every 48 h. Plasma T level was assessed at baseline and after 1 month of CC administration. Semen parameters were assessed at baseline and after 3 months of CC administration. The median pre-treatment T level was 9.1 nmol/l; after 1 month of CC treatment the median post-treatment T level increased to 20.2 nmol/l (p = <0.001). Median baseline sperm concentration was 7 millions/ml with a median progressive motility of 18%. After 3 months of CC, the median post-treatment sperm concentration was 17.5 millions/ml (p = 0.024) and the median post-treatment progressive sperm motility was 18% (p = 0.40). Three natural pregnancies occurred during the treatment period. CONCLUSION: CC is an effective and inexpensive treatment to increase plasma T level in infertile men with low T level and normal or low gonadotropines level. Our study suggests that CC could increase sperm concentration even in oligospermic infertile men, without, however, a significant effect on progressive sperm motility. More powered randomized controlled trials are needed to definitively assess CC effect on sperm parameters and on natural pregnancy rates.

[Precancerous cervical lesions during pregnancy: diagnostic and treatment]. / Diagnostic et prise en charge des lésions précancéreuses du col utérin pendant la grossesse.

The rate of CIN discovered during pregnancy is around 1%. Pregnancy should be a period for the checking of pap-smear. So a pap-smear should be performed if the last one is more than two years old. If the pap-smear is less than two years old, a copy of its result should be obtained. The cervical cytology is valid during pregnancy, and usually pregnancy induced an opening of the junction zone that helps to have a good evaluation of the cervix. When atypical cells are found in the pap-smear performed during pregnancy, the management should include a colposcopy and biopsies, whatever the severity of the abnormal cells (ASC-US, ASC-H, AGC, LBG, LHG, invasive carcinoma). The biopsy should be guided by the colposcopy. Biopsy is required for an optimal diagnosis. The management of the pregnant patient should be based on the results of cytology, and colposcopy and biopsies. Currently there is no indication for HPV-typing during pregnancy. If an invasive tumor is excluded after cytology, and colposcopy and biopsy, no treatment is performed during pregnancy, and the treatment is postponed after delivery following a complete cervical reevaluation. If an invasion cannot be excluded with the biopsy; a diagnostic conization completed with a cerclage should be performed. This procedure should be exceptionally performed. During pregnancy, CIN lesions are usually stable or regress; progression of CIN is rare. When managing an abnormal pap-smear during pregnancy, a microinvasive cervical cancer may be found on a biopsy or conization specimen. Staging of these lesions requires always a conization and eventually a pelvic MRI. Microinvasive cervical cancers can be only followed until the end of the pregnancy.

[Left extraperitoneal laparoscopic para-aortic lymphadenectomy: morbidity and learning curve of the technique]. / Lymphadénectomie lombo-aortique caelioscopique par voie extrapéritonéale gauche: morbidité et apprentissage de la technique.

OBJECTIVE: Description of the morbidity and the learning curve of the left extraperitoneal laparoscopic paraaortic lymphadenectomy in patients with gynecologic cancers. PATIENTS AND METHODS: Retrospective study of patients treated with the left extraperitoneal laparoscopic paraaortic lymphadenectomy between August 1999 and January 2005. Duration of surgery, per and post-operative complications, duration of the hospital stay, number of retrieved nodes, and pathologic results were studied. A comparative analysis of the results was performed between trained and training surgeons. RESULTS: Eighty-one patients were planned for the left extraperitoneal laparoscopic paraaortic lymphadenectomy. The major indication (90% of cases) was advanced cervical carcinomas (stage IB2 and more). The median number of retrieved nodes was 14, with a mean operative time of 109 minutes. The median hospital stay was 3 days. Two major complications related to the surgical technique were observed: a laceration of the inferior vena cava and an acute abdominal syndrome. Seven lymphocysts (8.6%) were observed (with associated symptoms in 2 cases). Trained surgeons to the technique displayed higher success rate of this surgical technique and higher number of retrieved lymph nodes. DISCUSSION AND CONCLUSIONS: The left extraperitoneal laparoscopic paraaortic lymphadenectomy allows the accurate staging and management of patients with gynecologic cancers and mainly women affected by advanced cervical carcinoma. The surgical technique is safe and reproducible when performed by trained surgeons.

[Vaginal vault suspension by posterior transobturator sling]. / Suspension du fond du vagin par bandelette transobturatrice postérieure.

OBJECTIVE: A study on the feasibility and safety of a new surgical procedure of vaginal vault suspension using a polypropylene mesh placed in the uterovaginal septum by a posterior transobturator approach. PATIENTS AND METHODS: Longitudinal study from March 2002 to January 2006 of patients treated by this new surgical procedure. Postoperative visits, including an interview and a physical examination were made at two, six and 12 months and annually thereafter. The minimal required follow-up time was 12 months up to January 2007. RESULTS: Seventy-eight patients were included. Three cases of intraoperative bleeding occurred. In these cases no transfusion was required and no complications were observed later on. The mean hospital stay was five days (range 3-9). The mean follow-up time was 20.36 months (range 12-48). Six recurrences were observed in the medial compartment (8%) and two anterior recurrences (2%). There was no recurrence in the posterior compartment. New-onset moderate dyspareunia was noted in 13% of the cases and a severe in two cases. No erosion occurred. DISCUSSION AND CONCLUSION: The analysis of our experience shows that vaginal vault suspension by posterior transobturator approach is a safe and simple procedure, and demonstrates its median efficacy. Further, this study should confirm these results over the long-term follow-up.

[How do I prevent caesarean wound infections in obese patients in 2017?] / Comment je préviens les infections de paroi après césarienne chez des patientes obèses en 2017 ?

Obesity is an important risk factor of cesarean section and is associated with an increased risk of wound complications such as infections. This review focuses on the available strategies to limit complications in this population. Choice of antiseptic solution, appropriate dose and type of antibiotic prophylaxy, suture closure of subcutaneous fat, suture skin closure and closed incision negative pressure wound therapy may reduce the risk of wound infections associated with cesarean section in obese patients. Vaginal desinfection, plastic adhesive draps, high-concentration supplemental perioperative oxygen, use of a barrier retractor, wound drainage and type of skin incision are discussed in this review. Clinical trials of good quality are needed to improve our clinical practice.

Pressurized IntraPeritoneal Aerosol Chemotherapy - Practical aspects.

INTRODUCTION: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) has been introduced as novel treatment for peritoneal carcinomatosis. Only proper patient selection, stringent safety protocol and careful surgery allow for a secure procedure. We hereby report the essentials for safe implementation. METHODS: All consecutive procedures within 20 months after PIPAC implementation were analyzed with regards to practical and surgical aspects. Special emphasis was laid on modifications of technique and safety measures during the implementation process with systematic use of a dedicated checklist. Further, surgical difficulty was documented by use of a visual analogue scale (VAS). RESULTS: 127 PIPAC procedures were performed in 58 patients from January 2015 until October 2016. 81% of patients had at least one previous laparotomy. Median operation time was 91 min (87-103) for the first 20 cases, 93 min (IQR 88-107) for PIPAC21-50, and 103 min (IQR 91-121) for the following 77 procedures. Primary and secondary non-access occurred in 3 patients (2%), all of them having prior hyperthermic intraperitoneal chemotherapy (HIPEC). Using open Hasson technique, one single bowel lesion occurred, which was the only intraoperative complication. One 5 mm and another 10/12 mm trocar were used in 88% of procedures while additional trocars were needed in 12%. No leak of cytostatics was observed and no procedure needed to be stopped. VAS for overall difficulty of the procedure was 3 ± 2.4, and 3 ± 2.9 and 3 ± 2.5, respectively, for abdominal access and intraoperative staging. CONCLUSIONS: With standardized surgical approach and dedicated safety checklist, PIPAC can be safely introduced in clinical routine with minimal learning curve.

Laparoscopic hysterectomy after concurrent radiochemotherapy in locally advanced cervical cancer compared to laparotomy: A multi institutional prospective pilot study of cost, surgical outcome and quality of life.

OBJECTIVE: Laparoscopy allows hysterectomies after chemoradiation to be performed without opening the abdominal wall. We measured the costs and quality of life for locally advanced cervical cancer patients operated on via laparoscopy compared to laparotomy. STUDY DESIGN: We conducted an observational prospective multicenter study on locally advanced cervical cancer patients undergoing an extrafascial hysterectomy after concurrent chemoradiotherapy (CRT). We assessed the costs from the medical visit before surgery up to the first month after surgery from the providers' perspective and measured the quality of life using the EORTC QLQ-C30 and QLQ-CX24 up to six months. RESULTS: Sixty two patients (39 laparoscopy and 23 laparotomy) from December 2008 to November 2011 were included. There was no difference in operative time, or intraoperative and post-operative complication rates between the two groups. Intraoperative transfusion and abdominal drain were significantly lower in the laparoscopy group (respectively, p = 0.04 and p < 0.01), as well as the duration of hospital stay (7.3 d vs. 5.7 d, p < 0.001). All patients who underwent laparoscopic hysterectomy were discharged to home, whereas 4 laparotomy patients used convalescence homes (p = 0.01). Mean costs at one month were €10,991 for laparotomy and €11,267 for laparoscopy (p = 0.76). Sexual activity is better for the laparoscopy group at six months (p = 0.01). CONCLUSION: Laparoscopy for an extrafascial hysterectomy after CRT in locally advanced cervical cancer patients brought better quality of life with similar costs compared to laparotomy, and should therefore be the first choice for surgeons.

Epidermal growth factor receptor expression in cervical intraepithelial neoplasia and its modulation during an alpha-difluoromethylornithine chemoprevention trial.

Chemoprevention trials designed to prevent progression to invasive cervical cancer will benefit from the identification of biomarkers that assess the risk of developing tumors, predict likelihood of response to treatment, and measure biological response to intervention. The purpose of this study was to examine expression of epidermal growth factor receptor (EGFR) as a marker for progression of cervical intraepithelial neoplasia (CIN) and as a surrogate end point biomarker in a chemoprevention trial with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase. To evaluate quantitative and spatial changes in EGFR expression during cervical tumorigenesis, paraffin sections from 42 archival cervical cone biopsies, each containing multiple stages of CIN, were immunohistochemically stained for EGFR, and the level and spatial expression of EGFR were quantitated by image analysis. In the progression from normal epithelium to CIN 1 to CIN 2 to CIN 3 to invasive cancer, EGFR expression showed two types of changes. Normal control epithelium showed EGFR expression predominantly confined to the basal layer, while histologically normal epithelium in specimens containing CIN showed relatively increased EGFR expression in the basal layer and the extension of EGFR expression away from the basal layer. The total EGFR relative staining intensity (RSI) of epithelium increased with the degree of CIN, predominantly due to a progressive expansion of EGFR-expressing cells away from the basal layer rather than an increase in the level of EGFR expression per cell. To determine whether EGFR expression would be modulated by a 1-month chemopreventive intervention with DFMO, pretreatment and posttreatment cervical biopsy specimens from 25 patients (22 evaluable) were examined for EGFR expression. Although the overall levels of EGFR expression were not modulated in either histological responders or nonresponders, responders showed a prominent down-regulation of EGFR expression away from the basal layer after DFMO treatment. Interestingly, pretreatment EGFR expression levels predicted for DFMO response [i.e., eight responses (72.7%) for 11 cases with RSI levels below 0.35 versus one response (9.1%) for 11 cases with RSI levels above 0.35 (P < 0.01)]. These results suggest that CIN progression is associated with a spatial dysregulation of EGFR expression that can be reversed by DFMO treatment, especially in patients whose pretreatment CIN 3 lesions exhibit relatively low EGFR expression.