Milena Sansone

Update on urodynamic bladder dysfunctions after radical hysterectomy for cervical cancer

INTRODUCTION Bladder dysfunctions are a common sequela after radical hysterectomy (RH, former type III sec Piver) ranging from 8 to 80%. This discrepancy, probably, reflects the different bladder function evaluation methods utilized in literature. MATERIAL AND METHODS We searched English-language medical reports published from 1952 to 2010, on MEDLINE. Inclusion criteria were: (1) studies of urological dysfunctions in patients with cervical cancer, treated with type III sec Piver (C2 sec Querleu) radical hysterectomy; (2) use of urodynamic measurement. RESULTS The overall incidence of urodynamic bladder dysfunctions is 72%. Follow-up >12 months studies report a high incidence of overactive detrusor low compliance (34%). Eight out of 19 studies show a decrease of the maximal urethral closure pressure (MUCP). DISCUSSION AND CONCLUSIONS Follow-up timing seems to be the major factor influencing the wide range of incidence of bladder dysfunction. Urodynamic data could help physicians to formulate appropriate evaluation and treatment for patients having urge incontinence (UI) after RH.

Quality of Life and Sexual Function after Type c2/Type III Radical Hysterectomy for Locally Advanced Cervical Cancer: A Prospective Study

INTRODUCTION The introduction of screening programs have made cervical cancer detectable at earlier stages and in younger patients. Nevertheless, only a few studies have examined the QoL and sexual function in disease-free cervical cancer survivors. AIM The objective of this study is to evaluate the sexual function in a cervical cancer patients group treated with neoadjuvant chemotherapy (NACT) plus type C2/type III radical hysterectomy (RH). METHODS We have enrolled in the oncologic group (OG) sexually active patients affected by cervical cancer (stage IB2 to IIIB) treated with NACT followed by RH. MAIN OUTCOME MEASURES Included subjects were interviewed with the European Organization for Research and Treatment of Cancer (EORTC) QLQ-CX24 Questionnaire. Two consecutive assessments were recorded: at the first evaluation postoperatively (T1) and at the 12-month follow-up visit (T2). Results were compared with a benign gynecological disease group (BG) and with a healthy control group (HG). RESULTS A total of 33 patients for OG, 37 for BG, and 35 women for HG were recruited. After surgery, sexual activity has been resumed by 76% of the OG patients and 83.7% of the BG patients (P = not significant). Cancer survivors had clinically worse problems with symptom experience, body image, and sexual/vaginal functioning than controls (P < 0.05). OG patients also reported more severe lymphedema, peripheral neuropathy, menopausal symptoms, and sexual worry. For sexual activity, the score difference between cancer survivors and women with benign gynecological disease is not statically significant. Concerning sexual enjoyment assessment, our study shows comparable results for OG and BG. CONCLUSION Nevertheless, the worsening of symptom experience, body image, and sexual/vaginal functioning, OG patients have same sexual activity and sexual enjoyment data compared with those of BG patients. Thus, NACT followed by RH could be a valid therapeutic strategy to treat and improve well-being especially in young cervical cancer patients.

Post radical hysterectomy urinary incontinence: A prospective study of transurethral bulking agents injection

OBJECTIVE(S) The aim of the present study is to prospectively investigate the efficacy and complications of macroplastique transurethral implantation in cervical cancer patients affected by stress urinary incontinence (SUI) after radical hysterectomy (RH). METHODS Patients affected by de novo SUI post type 3 RH were considered for eligibility in this study. Preoperative and postoperative assessment included a standardized urogynecological history, urogynecological and neurological physical examination, evaluation of severity of SUI symptoms, a 3-day voiding diary, urine culture and urodynamic assessment. All patients underwent transurethral implantation using Macroplastique Implantation System (MIS). Patient follow-up was performed 6 and 12 months after surgery. RESULTS A total of 24 consecutive patients were enrolled. At the 12 month follow up SUI cure rate was 42% (10 of 24 patients), the improvement rate was 42% (10 of 24) and the failure rate was 16% (4 of 24). The overall success rate was 84% (10 patients cured and 10 improved). No intraoperative or postoperative early complications were found. The 4 patients in whom treatment was not a success had preoperative urethral hypermobility. Subjective patient perception of SUI symptom severity showed significant improvement (mean severity of urinary loss perception 6.6+/-1.8 vs 2.3+/-3.3, p<0.05). The frequency of incontinence on the 3-day voiding diary was significantly reduced at the follow up (14.5+/-5.8 vs 4.3+/-7.9 episodes per 3 days, p<0.05). CONCLUSION(S) Bulking agents urethral injection could be a valid option having no surgical complications. This therapeutic strategy is able to treat SUI and improve well being of cervical cancer patients after radical surgery.

Sexual Function after Modified Radical Hysterectomy (Piver II/Type B) vs. Classic Radical Hysterectomy (Piver III/Type C2) for Early Stage Cervical Cancer. A Prospective Study

INTRODUCTION When cervical cancer is detected at an early stage (International Federation of Gynecology and Obstetrics [FIGO] IA2-IB1), it can be successfully treated by radical surgery alone. Considering that most patients are young and sexually active at the moment of diagnosis and the long life expectancy of survivors after the treatment, quality of life (QoL) and sexual function are important issues for cancer survivors and caregivers. However, only a few studies have examined the QoL and sexual function in disease-free cervical cancer survivors, and there are no studies in the literature comparing prospectively sexual function after different types of radical hysterectomy. AIM To compare sexual function in two groups of early stage cervical cancer survivors treated by radical surgery alone, undergoing two different types of radical hysterectomy. METHODS Patients treated by radical hysterectomy with systematic lymphadenectomy for early stage cervical cancer (FIGO IA2-IB1) have been enrolled and divided in two groups with regard to type of radical hysterectomy performed; S1: modified radical hysterectomy (Piver II/Type B), S2: classic radical hysterectomy (Piver III/ Type C2). MAIN OUTCOME MEASURE Twenty-four months after surgery we assessed the sexual function using the European Organization for Research and Treatment of Cancer Cervix Cancer Module Questionnaire, which is a validated system for the assessment of disease- and treatment-specific issues that affect the QoL and sexual functioning of women who are treated for cervical cancer. RESULTS Of the 31 patients enrolled in the S1 group and 46 in the S2 group, 23 and 33 patients have been included, respectively. We observed significant differences between the two groups in terms of symptom experience, sexual/vaginal functioning, sexual activity, and sexual enjoyment. There was not any significant difference regarding lymphedema, peripheral neuropathy, and sexual worry. CONCLUSION Survivors of early stage cervical cancer treated by modified radical hysterectomy (Piver II/ Type B) have a better sexual function than those operated by classic radical hysterectomy (Piver III/ Type C2).

Laparoscopic fertility-sparing staging in unexpected early stage ovarian malignancies

OBJECTIVE To assess feasibility and safety of fertility-sparing laparoscopic staging in women affected by unexpected ovarian cancer desiring to preserve their fertility. DESIGN Prospective study. SETTING University clinic. PATIENT(S) Twenty-seven patients already operated on elsewhere for a presumably benign ovarian cyst. INTERVENTION(S) Laparoscopic fertility-sparing staging operations. MAIN OUTCOME MEASURE(S) Perioperative and survival data, reproductive outcome. RESULT(S) Histologic findings after first surgery: 12 low malignant potential neoplasms, 11 invasive epithelial ovarian carcinomas,1 sex-cord stromal, and 3 germ cell neoplasms. Fertility-sparing staging consisted of exploration of the peritoneal cavity, peritoneal washing cytology, multiple peritoneal biopsies, omolateral adnexectomy (except in borderline tumors), omentectomy, omolateral or bilateral pelvic and aortic lymph node sampling (except in borderline tumors, well differentiated, mucinous, and granulosa cell (GC) neoplasms), endometrial biopsy, appendectomy in mucinous type. Overall, seven patients (26%) were upstaged. Six patients received adjuvant platinum-based chemotherapy. Two term pregnancies occurred. After a median follow-up of 20 months all patients are alive; one patient has FIGO stage Ic clear cell carcinoma, which recurred 8 months after surgery. CONCLUSION(S) Laparoscopic fertility-sparing staging in early ovarian malignancies is feasible and safe in selected and counseled patients and should be performed in experienced gynecological oncology centers trained in endoscopic procedures.

Feasibility and safety of type C2 total extraperitoneal abdominal radical hysterectomy (TEARH) for locally advanced cervical cancer

INTRODUCTION Radical hysterectomy represents the gold standard treatment in patients with early-stage cervical cancer and a valid choice of treatment, after neoadjuvant chemotherapy (NACT), in locally advanced tumors. Laparotomy is still considered the standard approach for radical hysterectomy; however, the extraperitoneal route has been described as a valid alternative for pelvic lymphadenectomy, with shorter operative time, shorter ileus and reduced postoperative pain and hospitalization. We designed the first prospective study to evaluate the technique of total extraperitoneal radical hysterectomy for surgical treatment of locally advanced cervical cancer after platinum-based NACT, in terms of feasibility and safety. METHODS Consecutive patients affected by locally advanced cervical carcinoma were considered for eligibility in this observational study. After a primary complete evaluation, all patients were submitted to platinum-based NACT. Inclusion criteria were: stage IB2-IIIB cervical carcinoma already submitted to neoadjuvant chemotherapy with a complete or partial response after three cycles of chemotherapy, WHO performance status≤1, adequate renal, hepatic and cardiac function, BMI<40, age≤75 years, no concurrent or previous malignant disease, no previous radiation therapy, and signed informed consent. Patients included in the study were submitted to type C2 extraperitoneal radical hysterectomy. RESULTS From January 2006 to October 2008, 46 patients were enrolled and compared with a control group selected from the historical database. The mean operative time in the extraperitoneal radical hysterectomy group was 195 min (range: 120-240) versus 235 min (range: 215-310) in the intraperitoneal radical hysterectomy group (P<0.05). Median postoperative ileus was 32 h (range: 24-36) versus 67 h (range: 42-78) (P<0.05). VAS (Visual Analogue Scale) score at 24 and 48 h was 8 (range: 6-8) versus 8 (range: 6-9) (P=NS) and 3.5 (range: 2-7) versus six (range: 5-9) (P<0.05) respectively. No differences in terms of intraoperative and postoperative complications were recorded. CONCLUSIONS Total extraperitoneal radical hysterectomy in locally advanced cervical cancer is feasible and safe. If compared with intraperitoneal abdominal radical hysterectomy, no significant differences in terms of surgical data or complications were found. Extraperitoneal radical hysterectomy seems to compare favorably to the intraperitoneal approach in terms of operative time, postoperative ileus, and VAS score at 48 h.

Long-term lower urinary tract dysfunction after radical hysterectomy in patients with early postoperative voiding dysfunction

Dear Editor, In a recent interesting study, Manchana et al. [1] compare long-term lower urinary tract dysfunction after radical hysterectomy (RH) in patients with or without early postoperative voiding dysfunction. In this study, between 1997 and 2006, 314 early stage cervical cancer patients underwent type III RH; of them, 15 patients (group A) had early postoperative voiding dysfunction and 15 patients (group B) had no early postoperative voiding dysfunction, while 25 patients before surgery (group C) were the control group. They reported that, at least 2 years after surgery, voiding dysfunction was significantly increased. In detail, this dysfunction was higher in group A than group B. On the other hand, no significant change of urethral pressure profile was demonstrated in patients with urodynamic stress incontinence. In this respect, we would like to give our contribution to the argument as follows. In our opinion the follow-up timing is the major factor influencing urinary symptoms and urodynamic diagnosis after RH. In fact many theories have been reported in the literature in attempts to elucidate the pathophysiology of surgical damage of RH. Haferkamp et al. demonstrated that the plasticity reorganization that occurs in the nervous system in response to peripheral injury has different evolutions during time with: (a) short-term changes that included widespread degeneration of intrinsic axons and muscle cells and (b) long-term changes that included a reversal of degeneration with restitution of cholinergic axon terminals, increases in adrenergic and copeptidergic axons, and muscle cell regeneration [2]. On the other hand, voiding dysfunction is significantly less frequent when assessed 1 year after surgery. A 12-month interval was considered sufficiently long for the adequate recovery and stabilization of bladder function [3]. Thus follow-up timing is fundamental in detecting bladder dysfunction after RH because urologic symptoms could change over time after RH. In this study, Manchana et al. reported that urodynamic tests were performed at a long time after radical hysterectomy (median post-treatment interval: 2–11 years). Thus, their results could be influenced by a wide and variable evaluation timing. Another parameter that should be very interesting to know is the maximal urethral closure pressure (MUCP) and the difference among groups. In fact, in our previous series, we found that a main parameter with respect to postoperative bladder function was MUCP. We found a significant decrease in MUCP after RH and some patients show a severe urinary incontinence with low MUCP (<20 CM/H2O) few years after RH [2]. In conclusion, to avoid misinterpretation and in order to draw definitive conclusions, future prospective trials including large series with standardized follow-up will be necessary. M. Sansone (*) : P. B. Panici Department of Obstetrics and Gynecology, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy e-mail: milenasansone@gmail.com

Long-term cervical cancer survivors suffer from pelvic floor symptoms

In a recent interesting study, Hazewinkel et al. [1] evaluate the prevalence of and experienced distress from pelvic floor symptoms in cervical cancer survivors (CCS) using validated pelvic-floor-related questionnaires. The authors matched CCS, treated between 1997 and 2007, to a random female population sample aged 20 to 70 years. One hundred and forty-six CCS underwent radical hysterectomy and pelvic lymph node dissection (RH and LND), 49 underwent surgery and adjuvant radiotherapy (SART), and 47 underwent primary radiotherapy (PRT). They conclude that patients treated with PRT report the most adverse effects on pelvic floor function. In this respect, we would like to give our contribution to the argument as follows. In our opinion the unbalanced distribution of the FIGO stage and tumor diameter could represent and important confounding factor of the results. In fact 64% of patients included in the PRT groupwas affected by locally advanced (IIB-IVA) cervical cancer instead of 1 and 2% for RH and SART groups respectively. We think that patients affected by IVA cervical cancer may have both rectal and vesical symptoms directly related to the tumor invasion. Moreover we think that the use of standardized follow-up is one of the major factor influencing urinary symptoms after cervical cancer treatment. In the present study the median follow up was 6 years ranging from 1 to 11 years. Haferkamp et al. demonstrated that the plasticity reorganization, that occurs in the nervous system in response to peripheral injury, has different evolutions during time with: (a) short-term changes that included widespread degeneration of intrinsic axons and muscle cells and (b) long-term changes that included a reversal of degeneration with restitution of cholinergic axon terminals, increases in adrenergic and copeptidergic axons, and muscle cell regeneration [2]. Moreover it is well known that the risk of radiotherapy complications increase during follow up [3]. Thus follow-up timing is fundamental in detecting pelvic floor dysfunction after cervical cancer treatment because urologic symptoms could change over time. Another parameter that should be very interesting to know is the length of vaginal tissue resection among surgical groups. In fact in our previous study we found that the most damaging step with respect to bladder function was vaginal tissue resection. In particular we found that the length of vagina removed, that is strictly related to the tumor volume, was significantly longer among patients who had vesical dysfunction compared with patients who had normal diagnoses [4]. We think that the present and the future trial will be fundamental in order to understand the real impact of the different treatment modality on pelvic floor dysfunction in order to better counsel cervical cancer patients to the most appropriate approach. Conflict of interest statement The authors declare that no potential conflict of interest exists.

Where should bulking agents for female urodynamic stress incontinence be injected

Dear Editor, In a recent interesting study, by Kuhn A. et al., 30 women reporting stress urinary incontinence (SUI) were randomly allocated to either transurethral collagen injection midurethrally or to the bladder neck [1]. They reported a continence rate of 66.6% in the midurethral group and of 60% for the bladder neck group, respectively. They conclude that both procedures improve patients’ satisfaction almost equally with a small advantage for midurethral injections. In this view, we would like to give our contribution to the argument as follows.

Three-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients

Objective: To evaluate the clinical benefit of a 3-day topotecan schedule in heavily pretreated recurrent ovarian cancer patients scheduled for palliative treatment. Methods: Eligibility criteria were 2 or more prior chemotherapy regimens, Eastern Cooperative Oncology Group performance status of 2 or less; adequate organ function, assessable disease by serum CA-125 measurement before each cycle; and 1 or more cycle of topotecan (1.5 mg/m2 per day) on 3 consecutive days of a 28-day treatment cycle. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria version 3. Tumor response, stable disease, and progression were evaluated on the basis of CA-125 levels. Results: A total of 68 patients were considered eligible for the study. Median age was 58 years (range, 40-77 years), and the median number of prior chemotherapy regimens was 2 (range, 2-6). A total of 272 cycles of topotecan were administered, with a median of 4 cycles per patient (range, 1-8). No treatment delays or dose reduction was recorded. Major toxicities were grade 3/4 (18%) neutropenia, neutropenic fever (6%), grade 4 thrombocytopenia (3%), requirements for blood (5%), and platelet transfusions (3%). Thirty-five (54%) of the 64 evaluable patients showed a clinical benefit. Of these, 11 patients (17%) had a partial response, and 24 (37%) had stable disease with a median time to progression of 7.5 months (range, 6-10 months) and 4 months (range, 2-6 months), respectively. Conclusion: More than half of heavily pretreated ovarian cancer patients may benefit from 3-day topotecan.