Vito Chiantera

Fertility outcome after radical vaginal trachelectomy: a prospective study of 212 patients.

Objective For treatment in patients with early-stage cervical cancer, radical vaginal trachelectomy (RVT) as a fertility-preserving surgery can be put on a par with radical hysterectomy as to oncologic safety. Our aim was to investigate the fertility concerns and outcome. Methods Prospective collection of fertility data of patients treated with RVT. The data were collected on personal communication, by telephone, or e-mail correspondence. Descriptive statistical analysis was performed. Results Between March 2005 and April 2010, 212 patients were followed up after RVT. Only 76 patients (35.9%) were seeking parenthood currently. Sixty pregnancies occurred in 50 women. Five patients (8.3%) had first-trimester miscarriage, 3 had second-trimester miscarriage (5.0%), 2 patients decided for pregnancy termination (3.3%), and 1 patient (1.7%) had an ectopic pregnancy. Three women (5.0%) delivered prematurely before 28th weeks of gestation, 15 (25.0%) delivered between 28 and 36 weeks, and 27 women (45.0%) reached full term. Four pregnancies are ongoing. Conclusions Preservation of childbearing function is a great advantage for patients with early-stage cervical cancer. Many patients do not seek parenthood immediately. We see no impairment of fertility and have solid data on pregnancy outcome. Premature labor is the main problem in pregnancy after RVT.

Overexpression of nerve growth factor in peritoneal fluid from women with endometriosis may promote neurite outgrowth in endometriotic lesions

To investigate the role of the nerve growth factor (NGF) in the endometriosis-associated innervation in the development of endometriosis-associated symptoms, 41 peritoneal fluid samples (PF) from patients with surgically and histologically proven endometriosis and 20 PF from patients with other gynecologic conditions were analyzed with Western blot and a novel in vitro model using dorsal root ganglia (DRG) to show neuronal outgrowth; endometrial cells also were analyzed. The results suggest that the PF of endometriosis patients and endometriotic lesions have neurotropic properties, because the Western blot analysis and the cell culture stainings showed NGF expression, and the neurite outgrowth of DRG treated with PF of patients with endometriosis was significantly higher than when treated with PF of patients without endometriosis. Furthermore, blocking NGF with both anti-NGF and K252a leads to a significant decrease in neurite outgrowth.

Clinical recommendation radical trachelectomy for fertility preservation in patients with early-stage cervical cancer.

Abstract Radical trachelectomy (RT) is a fertility-sparing procedure with the aim to provide adequate oncological safety to patients with cervical cancer while preserving their fertility. In the current review, indications, development of the procedure, technical aspects, preoperative and postoperative management, and oncological, fertility, and obstetric outcomes are discussed and studied with respect to whether the procedure is performed abdominally or vaginally. Complications of RT, staging, and more conservative alternatives to RT are discussed as well. A systematic MEDLINE search was performed, which yielded 218 articles, of which 75 were selected for further analysis based on the number of patients and the quality of the study. Strict morphologic criteria should be applied to the candidates to maintain oncological safety. When limited to a tumor less than 2 cm in diameter, the overall recurrence rate after vaginal RT is 3% to 6% and the death rate is 2% to 5%. Data on fertility and obstetric outcome are mostly based on the results of patients who underwent vaginal RT. More data are needed to be able to draw the same conclusions for abdominal RT. Fertility seems not to be decreased, but the risk for premature delivery is 2 to 3 times higher compared to women with an intact cervix. In locally advanced cervical tumors with a diameter larger than 2 cm, neoadjuvant chemotherapy followed by RT may be offered after explaining the experimental nature to the patient. In conclusion, RT is an oncologically safe technique in women with early invasive cancer. The rate of term pregnancies still needs improvement. Fertility-preserving treatment of women with tumors larger than 2 cm in diameter can be done by combining neoadjuvant chemotherapy and trachelectomy; however, experience is still limited.

Imbalance between sympathetic and sensory innervation in peritoneal endometriosis

To investigate possible mechanisms of pain pathophysiology in patients with peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy peritoneum (n=12) were immunostained and analysed with anti-protein gene product 9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve fibres, respectively, to identify the ratio of sympathetic and sensory nerve fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions were analysed and the nerve growth factor (NGF) and interleukin (IL)-1β expression was correlate with the nerve fibre density. Peritoneal fluids from patients with endometriosis (n=40) and without endometriosis (n=20) were used for the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG) and sympathetic ganglia were stained with anti-growth associated protein 43 (anti-GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased sympathetic nerve fibres density in peritoneal lesions compared to healthy peritoneum. Peritoneal fluids of patients with endometriosis compared to patients without endometriosis induced an increased sprouting of sensory neurites from DRG and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this study demonstrates an imbalance between sympathetic and sensory nerve fibres in peritoneal endometriosis, as well as an altered modulation of peritoneal fluids from patients with endometriosis on sympathetic and sensory innervation which might directly be involved in the maintenance of inflammation and pain.

Invasive cervical cancer during pregnancy: laparoscopic nodal evaluation before oncologic treatment delay.

INTRODUCTION Cervical cancer is the most frequently encountered malignancy during pregnancy. Presence of nodal metastasis is the most important negative prognostic factor and its assessment represents a crucial parameter to decide if pregnancy can safely continue. We describe the results of 18 pregnant patients with cervical cancer who had their nodal status proved by means of laparoscopy. MATERIAL AND METHODS Eighteen patients with cervical cancer who underwent laparoscopic pelvic lymphadenectomy during pregnancy at Charité-University Berlin and Friedrich-Schiller-University Jena between 1999 and 2010 were analyzed retrospectively. RESULTS The mean age at diagnosis was 32 years (26-40) and gestational age between 6 and 23 weeks of pregnancy. The following FIGO stages of cervical cancer were treated: 1a1 for two women, 1a2 for one woman, 1b1 for thirteen women, 1b2 for one woman and 2a for one woman. The histological type was squamous carcinoma in nine cases and adenocarcinoma also in nine cases. All laparoscopic procedures were successfully completed; there was no surgery-associated mortality, morbidity, or conversion to laparotomy. Additionally, there were no complications for either mother or child related to the general anesthesia. The mean number of lymph nodes removed was 17 (6-46). Definitive cancer treatment was delayed for fourteen out of eighteen patients until delivery with an average delay interval of 17 (9-28) weeks. Lymph nodes were positive in 16% of the cases (3/18) and these patients received immediate cancer treatment. One patient decided to interrupt the gestation before delivery despite negative lymph nodes. Fourteen patients reached fetal maturity and gave birth to healthy babies by caesarean section. All patients are alive without evidence of disease at a mean follow-up time of 38 (5-128) months. CONCLUSION Laparoscopic pelvic lymphadenectomy during pregnancy is feasible and safe. Results suggest that in patients with cervical cancer complicated by pregnancy a planned delay of oncologic treatment can be a safe option after tumor metastasis to lymph nodes has been histopathologically ruled out.

Laparoscopic lymph node dissection should be performed before fertility preserving treatment of patients with cervical cancer

OBJECTIVE The aim of this study is to assess our results of treatment of women with stage I cervical cancer>2 cm in diameter seeking fertility preservation. Treatment consisted of Laparoscopic Pelvic and Paraaortic Lymphadenectomy (LPPLND), and when no nodal metastasis was detected, neoadjuvant chemotherapy (NACT) followed by radical vaginal trachelectomy (RVT). Patients with positive lymph nodes underwent primary chemoradiation. METHODS A cohort of women younger than 40 years of age with stage I disease>2 cm who underwent LPPLND and either NACT and RVT or chemoradiation. Oncological outcome was evaluated prospectively. RESULTS Eighteen women were eligible for this study. Twelve (67%) women were diagnosed with metastasis in one or more pelvic and/or paraaortic lymph nodes, and thus received primary chemoradiation. After a mean follow-up of 25.5 months, three out of these 12 women (25%) developed a recurrence. Six women (33%) underwent NACT and RVT. Three patients experienced complete response to NACT and three patients showed more than 50% tumor size reduction. After a mean follow-up of 30.6 months all six women are free of recurrence. One patient delivered a healthy infant. CONCLUSIONS Staging LPPLND allows separating patients in high or low recurrence risk groups. NACT and RVT seem to be safe for women with completely staged stage I cervical cancer>2 cm in diameter, whereas even after primary chemoradiation, patients with positive lymph nodes experienced recurrence. Therefore, selection of patients with stage I cervical carcinoma>2 cm, eligible for fertility preservation should include histopathologic evaluation of lymph node status before any further treatment.

Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of a concept

OBJECTIVE To develop an updated laparoscopy-based model to predict incomplete cytoreduction (RT>0) in advanced epithelial ovarian cancer (AEOC), after the introduction of upper abdominal surgery (UAS). PATIENTS AND METHODS The presence of omental cake, peritoneal extensive carcinomatosis, diaphragmatic confluent carcinomatosis, bowel infiltration, stomach and/or spleen and/or lesser omentum infiltration, and superficial liver metastases was evaluated by staging laparoscopy (S-LPS) in a consecutive series of 234 women with newly diagnosed AEOC, receiving laparotomic PDS after S-LPS. Parameters showing a specificity≥75%, PPV≥50%, and NPV≥50% received 1 point score, with an additional one point in the presence of an accuracy of ≥60% in predicting incomplete cytoreduction. The overall discriminating performance of the LPS-PI was finally estimated by ROC curve analysis. RESULTS No-gross residual disease at PDS was achieved in 135 cases (57.5%). Among them, UAS was required in 72 cases (53.3%) for a total of 112 procedures, and around 25% of these patients received bowel resection, excluding recto-sigmoid resection. We observed a very high overall agreement between S-LPS and laparotomic findings, which ranged from 74.7% for omental cake to 94.8% for stomach infiltration. At a LPS-PIV≥10 the chance of achieving complete PDS was 0, and the risk of unnecessary laparotomy was 33.2%. Discriminating performance of LPS-PI was very high (AUC=0.885). CONCLUSIONS S-LPS is confirmed as an accurate tool in the prediction of complete PDS in women with AEOC. The updated LPS-PI showed improved discriminating performance, with a lower rate of inappropriate laparotomic explorations at the established cut-off value of 10.

Influence of nerve growth factor in endometriosis-associated symptoms.

To investigate the role of the nerve growth factor (NGF) in the development of dysmenorrhea/pelvic pain in patients with endometriosis, we performed a prospective, clinical, blind study. Peritoneal fluids (PFs) were obtained from patients with histologically proven endometriosis. Patients with endometriosis were divided into 7 different groups depending on their preoperative pain score and symptomatology: patients with no pain, patients with minimal pain (dysmenorrhea, pelvic pain, or both), and patients with severe pain (dysmenorrhea, pelvic pain, or both) and were used for the neuronal growth assay with cultured chicken dorsal root ganglia (DRG) and for Western blot analyses. Dorsal root ganglia were stained with anti-calcitonin gene-related peptide (CGRP) and anti-growth-associated protein 43 (GAP 43). Peritoneal fluids from patients with endometriosis induce neurite outgrowth. There was no significant difference in the outgrowth between the 7 pain groups. Western blot analyses showed a moderate NGF expression in the PFs from patients with endometriosis, without significant differences in the 7 pain groups. The present study suggests that the neurotrophic properties of endometriotic tissues are endometriosis- and not pain-associated.

Laparoscopic staging of apparent early stage ovarian cancer: results of a large, retrospective, multi-institutional series.

OBJECTIVE The aim of this study is to analyze the safety, adequacy, perioperative and survival figures in a large series of laparoscopic staging of patients with apparent early stage ovarian malignancies (ESOM). PATIENTS AND METHODS Retrospective data from seven gynecologic oncology service databases were searched for ESOM patients undergoing immediate laparoscopic staging or delayed laparoscopic staging after an incidental diagnosis of ESOM. Between May 2000 and February 2014, 300 patients were selected: 150 had been submitted to immediate laparoscopic staging (Group 1), while 150 had undergone delayed laparoscopic staging (Group 2) of ESOM. All surgical, pathologic, and oncologic outcome data were analyzed in each group and a comparison between the two was carried out. RESULTS Longer operative time, higher blood loss, more frequently spillage/rupture of ovarian capsule and conversion to laparotomy occurred in Group 1. No significant differences of post-operative complications were observed between the two groups. Histological data revealed more frequently serous tumors (0.06), Grade 3 (p=0.0007) and final up-staging (p=0.001) in Group 1. Recurrence and death of disease were documented in 25 (8.3%), and 10 patients (3.3%%), respectively. The 3-year disease free survival (DFS) and overall survival (OS) rates were 85.1%, and 93.6%, respectively in the whole series. There was no difference between Group 1 and Group 2 in terms of DFS (p value=0.39) and OS (p value=0.27). CONCLUSION In this very large multi-institutional study, it appears that patients with apparent ESOM can safely undergo laparoscopic surgical management.

Evidence of neurotrophic events due to peritoneal endometriotic lesions

To investigate the neurotrophic properties of endometriosis, as well as the involvement of neurotrophic factors in the development of chronic pelvic pain in patients with endometriosis, we performed a prospective clinical study. The presence of neurotrophins was investigated in the peritoneal fluid (PF) of patients with peritoneal endometriotic lesions or adenomyosis, as well as from women with non-endometriotic adhesions and from women without endometriosis/adenomyosis/adhesions. The PF from patients with peritoneal endometriotic lesions was divided in three groups: asymptomatic endometriosis, minimal pain and severe pain. PF from patients with adenomyosis or with non-endometriotic adhesions and the control group were divided in patients without pain and with pain. Neurotrophin expression in PF was analyzed using Elisa and the neuronal growth assay with cultured chicken sensory ganglia (dorsal-root-ganglia, DRG) and sympathetic ganglia. PF from women with peritoneal endometriotic lesions overexpress nerve growth factor (NGF) and neurotrophin-3 (NT-3), but not brain derived neurotrophic factor (BDNF), whereas the PF of women with adenomyosis or adhesions seems to express normal amounts of these factors. Neurotrophin expression did not differ among the pain groups. Furthermore, the PF from patients with peritoneal endometriotic lesions induced a strong sensory and a marginal sympathetic neurite outgrowth, while the PF from women with adenomyosis and non-endometriotic adhesions induced an outgrowth similar to the control group. The induced neurite outgrowth could only be inhibited in DRG incubated with peritoneal endometriotic lesions. Interestingly, the outgrowth of sympathetic ganglia was inhibited in all studied groups. The present study suggests that only peritoneal endometriotic lesions lead to an increased release of NGF and NT-3 into the PF and that NGF modulates the nerve fiber growth in endometriosis.