Self-Reported Long-Term Autonomic Function After Laparoscopic Total Mesometrial Resection for Early-Stage Cervical Cancer: A Multicentric Study.

OBJECTIVES: This multicentric retrospective study investigates the early and long-term self-reported urinary, bowel, and sexual dysfunctions in early-stage cervical cancer patients who submitted to laparoscopic total mesometrial resection (L-TMMR), total laparoscopic radical hysterectomy, vaginal-assisted laparoscopic radical hysterectomy, and laparoscopic-assisted radical vaginal hysterectomy. METHODS: Cervical cancer patients, FIGO (International Federation of Gynecology and Obstetrics) stage IA2-IB1/IIA1 who submitted to nerve-sparing radical hysterectomy were recruited. Pelvic functions were assessed within 30 days (early outcome) and 12 months after surgery (long-term outcome). RESULTS: Two hundred thirteen subjects receiving nerve-sparing radical hysterectomy were enrolled. Laparoscopic total mesometrial resection was performed in 46 patients (21.6%), total laparoscopic radical hysterectomy in 65 patients (30.5%), vaginal-assisted laparoscopic radical hysterectomy in 54 patients (25.4%), and laparoscopic-assisted radical vaginal hysterectomy in 48 women (22.5%). Operative time was significantly lower in the L-TMMR group (240 minutes; range, 120-670 minutes; P = 0.001). The overall perioperative complication rate was 11.3%, with no statistically significant differences among the 4 groups. Stress incontinence and sensation of bladder incomplete emptying were detected, respectively, in 54 patients (25.6%) and 65 patients (30.7%) with a significantly lower prevalence among those in the L-TMMR group, which resulted, respectively, in 11.1% (P = 0.022) and 13.3% (P = 0.036). The prevalence rates of constipation, sensation of incomplete bowel emptying, and effort during evacuation were significantly higher among those in the L-TMMR group, resulting in, respectively, 37% (P = 0.001), 42.3% (P = 0.012), and 50% (P = 0.039). One hundred forty-nine patients (70%) were sexually active. Fifty-eight women (38.9%) reported low enjoyment, 83 women (55.7%) medium enjoyment, and 8 women (5.4%) reported high enjoyment, without statistically significant differences among the 4 groups. CONCLUSIONS: Laparoscopic total mesometrial resection is associated with improved long-term urinary autonomic functions and worse gastrointestinal autonomic outcome. Further larger prospective trials are needed to evaluate both the oncological and functional outcomes in order to establish the most appropriate surgical approach for early-stage cervical cancer patients.

Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparaoscopic lymphadenectomy.

BACKGROUND AND PURPOSE: The purpose of this work was to evaluate the use of extended-field chemoradiation (EFRT) with concomitant chemotherapy in patients with histologically confirmed para-aortic metastases after laparoscopic para-aortic and pelvic lymphadenectomy (LAE) with regard to oncologic results and treatment-related toxicity. PATIENTS AND METHODS: A total of 44 women with squamous cell carcinoma (82 %) and adenocarcinoma (18 %) of the cervix in FIGO stages IIA (n = 3), IIB (n = 29); IIIB (n = 9), and IVA (n = 3) and histologically proven para-aortic metastases underwent EFRT and chemotherapy. Laparoscopic LAE was performed in 40 patients. Patients underwent chemoradiation with conventional fractionation of 1.8-50.4 Gy to the para-aortic and pelvic region. In addition, MRI-guided brachytherapy was performed to the cervix with 5-6 single doses of 5 Gy for a total dose of 25-30 Gy. RESULTS: The mean number of harvested lymph nodes was 17 in the pelvic as well as para-aortic regions, respectively. Laparoscopic intervention did not delay chemoradiation. Follow-up was 6-76 months (mean 25.1 months). There was no grade 4 or 5 acute radiation toxicity. In all, 8, 4, and 11 % grade 1, 2, and 3 gastrointestinal late toxicities and 7, 11, and 19 % grade 1, 2 and 3 genitourinary late toxicities were recorded. Despite the excellent locoregional (pelvic) control rates of 89.1 and 82.8 % after 2 and 5 years, respectively, the overall survival rates were 68.4 and 54.1 % after 2 and 5 years, respectively. Of the 44 patients, 43 remained tumor free in the para-aortic region. CONCLUSION: In patients with proven para-aortic disease, excellent pelvic and para-aortic control could be achieved by laparoscopic LAE followed by EFRT. More than half of the patients were long-term survivors. The high risk of distant metastases should be addressed by further improving systemic treatment.

Pelvic exenteration for recurrent endometrial adenocarcinoma: a retrospective multi-institutional study about 21 patients.

OBJECTIVE: The aim of our study was to evaluate morbidity, mortality, and long-term survival of patients who underwent pelvic exenteration (PE) with curative intent for recurrence of endometrial adenocarcinoma during a single decade. METHODS: We defined a cohort of 21 patients who met our inclusion criteria, referred to 4 cooperating gynecologic oncology settings in Germany and Italy between 2000 and 2011. Data regarding surgery, histology, and oncologic outcomes were collected and statistically evaluated. Survival was determined from the day of exenteration until the last follow-up or death. RESULTS: The median age was 66 years. A total of 42.9% of the patients had major complications, and a complete resection was achieved in 85.7% of the patients. A total of 71.4% of the patients had negative nodes. No patient died intraoperatively. The perioperative mortality, calculated within 30 days from PE, was 4.8%. The overall 5-year survival rate, evaluated using the Kaplan-Meier method, was 40%. For the subgroup with complete resection and negative lymph nodes, overall survival reached 60%. CONCLUSIONS: Despite a high complication rate, PE for solitary pelvic recurrence of endometrial cancer yields a high rate of long-term survival.

Laparoscopic pelvic lymphadenectomy in 32 pregnant patients with cervical cancer: rationale, description of the technique, and outcome.

OBJECTIVE: Individualized treatment of pregnant patients with cervical cancer is mandatory; hence, information on nodal status is pivotal to allow a waiting strategy in early-stage disease.We aimed to verify the oncological safety and surgical reproducibility of a standardized laparoscopic pelvic lymphadenectomy in pregnant patients with cervical cancer. METHODS: We standardized laparoscopic pelvic lymphadenectomy during the first and second term of gestation in 32 patients with cervical cancer since 1999. According to gestational week (GW) of less than 16 GWs or more than 16 GWs, 2 different techniques were used. RESULTS: The International Federation of Gynecology and Obstetrics stages were IA in 10 patients, IB1 in 17 patients, IB2 in 4 patients, and IIA in 1 patient. Mean (SD) GW was 17.5 (5.1) weeks. Mean (SD) operative time was 105.4 (29) minutes. Mean (SD) blood loss was 5.3 (10.2) mL. There were no conversion to laparotomy and no intraoperative complications. A median number of 14 pelvic lymph nodes (range, 8-57) were harvested. Median hospital stay was 6 days. Median follow-up is 42.5 months (range, 17-164). Four patients had lymph node metastases. Five patients interrupted their pregnancy. Fourteen patients were given neoadjuvant platin-based systemic therapy. All patients are alive and disease free. All children born through cesarean delivery at a mean (SD) 34 (1.9) GWs are well and show normal clinical neurological development. CONCLUSIONS: To the best of our knowledge, this is the largest series so far reported on laparoscopic pelvic lymphadenectomy during pregnancy. This procedure is safe and associated with good oncological and obstetrical outcomes.

Survival after curative pelvic exenteration for primary or recurrent cervical cancer: a retrospective multicentric study of 167 patients.

OBJECTIVE: Evaluate the survival of patients who underwent pelvic exenteration (PE) with curative intent for primary persistent or recurrent cervical cancer. METHODS: We retrospectively investigated 167 consecutive patients, referred to the gynecological oncology units of 4 centers in Germany or Italy, who underwent PE. Data regarding surgery, histology, and oncologic outcomes were collected and statistically evaluated. Survival was determined from the day of exenteration until last follow-up or death. RESULTS: The median age was 51 years. Twenty-seven patients (16.2%) underwent PE owing to advanced primary tumors (group A), 34 patients (20.4%) underwent PE owing to persistent cancer after chemotherapy or chemoradiation (group B), and 106 patients (63.4%) underwent PE owing to recurrence (group C). The prevalent histologic type was squamous cell cancer. A complete tumor resection (R0), was achieved in 121 patients (72.5%). Forty-nine patients (29.3%) had pelvic lymph node metastases and 44 patients (26.3%) had pelvic sidewall involvement. Overall survival at the end of the study was 40.7%. The cumulative 5-year overall survival for the entire cohort was 38%. Resection margins, pelvic lymph node state, and sidewall involvement were independent prognostic factors in multivariate analysis. CONCLUSION: Pelvic exenteration is a valid therapeutic option for patients with locally advanced primary persistent or recurrent cervical cancer, with a long-term survival in 40% of the patients.

Morbidity after pelvic exenteration for gynecological malignancies: a retrospective multicentric study of 230 patients.

OBJECTIVE: Our study purpose was to evaluate morbidity and postoperative mortality in patients who underwent pelvic exenteration (PE) for primary or recurrent gynecological malignancies. METHODS: We identified 230 patients who underwent PE, referred to the gynecological oncology units of 4 institutions: Charitè University in Berlin, Friedrich-Schiller University in Jena, S. Orsola-Malpighi University in Bologna, and Catholic University in Rome and in Campobasso. RESULTS: The median age was 55 years. The tumor site was the cervix in 177 patients, the endometrium in 28 patients, the vulva in 16 patients, and the vagina in 9 patients. Sixty-eight anterior, 31 posterior, and 131 total PEs were performed in 116 women together with hysterectomy. A total of 82.6% of the patients required blood transfusion. The mean operative time was 446 (95-970) minutes, and the median hospitalization was 24 (7-210) days. We noted a major complication rate of 21.3% (n = 49). We registered 7 perioperative deaths (3%) calculated within 30 days. The operation was performed within clear margins in 166 patients (72.2%). The overall mortality rate depending on tumor site at the end of the study was 75% for vulvar cancer, 57.6% for cervical cancer, 55.6% for vaginal cancer, and 53.6% for endometrial cancer. CONCLUSIONS: Although an important effort for surgeons and for patients, PE remains a therapeutic option with an acceptable complication rate and postoperative mortality. A strict selection of patients is mandatory to reach adequate surgical and oncologic outcomes.

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.

Neuroimmunomodulatory alterations in non-lesional peritoneum close to peritoneal endometriosis.

OBJECTIVES: An imbalance in the ratio of sensory to sympathetic nerve fibre (NF) density in peritoneal endometriotic lesions (pEL) has recently been demonstrated and leads to the assumption that this preponderance of the sensory pro-inflammatory milieu is a major cause of pain in endometriosis. Therefore, the density of sensory and sympathetic NFs was determined in distal unaffected peritoneum of endometriosis patients to be able to detect possible alterations in unaffected peritoneum. METHODS: In serial pEL sections (n = 40), lesional and matching unaffected peritoneum as well as healthy peritoneum (HP) from patients without endometriosis (n = 15) were immunohistochemically analysed to identify protein gene product 9.5-, substance P- and tyrosine hydroxylase-positive NFs (intact, sensory and sympathetic NFs, respectively). In addition, the amount of immune cell infiltrates and the expression of nerve growth factor (NGF) and interleukin (IL)-1ß in nerves of peritoneal endometriotic specimens were compared to those in the HP. RESULTS: The overall NF density in the non-lesional, unaffected peritoneum of endometriosis patients is significantly reduced in comparison to both HP and pEL, while sensory NFs remain the same; the sympathetic NF density is significantly decreased compared to HP, but is still higher than the density close to the pEL. Immune cell infiltrates as well as NGF and IL-1ß expression in nerves is significantly elevated in distal unaffected peritoneum in comparison to HP. CONCLUSION: The altered NF density in the non-lesional, unaffected peritoneum of endometriosis patients suggests new aspects in the understanding of the development of endometriosis and pain management in endometriosis.

Evaluation of the VITOM in digital high-definition video exocolposcopy.

OBJECTIVE: : Our aim was to present our initial clinical experience using a novel exoscopically based colposcopy system (VITOM) for the evaluation of cervical, vulvar, and vaginal diseases. MATERIALS AND METHODS: : Women referred to the Charite Cervix Center, Charite University, Berlin, Germany, were included. Patients with abnormal Pap smear results, vulvar lesions, or a biopsy report of neoplasia of the lower genital tract were included into the study. The VITOM was used for colposcopic evaluation and directed biopsies. Colposcopic findings were reported according to the criteria of the Committee on Nomenclature of the International Federation of Cervical Pathology and Colposcopy. Histologic diagnosis was described as normal, low-grade lesion, high-grade lesion (including cervical intraepithelial neoplasia 2,3, vulvar intraepithelial neoplasia 2,3, vaginal intraepithelial neoplasia 2,3), or cancer. RESULTS: : We recruited 76 patients (54 with cervical, 4 with vaginal, and 18 with vulvar disease) to the prospective study. Four patients were pregnant. Of patients with cervical disease, 29% had a history of previous conization and 3.7% had a history of trachelectomy. The sensitivity, specificity, negative predictive value, and positive predictive value of the VITOM for cervical intraepithelial neoplasia 2, 3 were 90%, 77%, 90% and 77%, respectively. Concordance of exocolposcopic impressions and histologic results was higher in high-grade lesions (K = 0.68, 95% CI = 0.32-0.87, p < .001) than in low-grade lesions (K = 0.41, 95% CI = 0.1-0.41, p < .05). CONCLUSIONS: : Exocolposcopy with the VITOM is accurate and shows good correlation to histologic findings in high-grade disease of the lower genital tract. The potential advantages include patient and trainee involvement in examination, decision making, and documentation.