Ignacio Zapardiel

Management of recurrent cervical cancer: A review of the literature

OBJECTIVE The aim of this narrative review is to update the current knowledge on the treatment of recurrent cervical cancer based on a literature review. MATERIAL AND METHODS A web based search in Medline and CancerLit databases has been carried out on recurrent cervical cancer management and treatment. All relevant information has been collected and analyzed, prioritizing randomized clinical trials. RESULTS Cervical cancer still represents a significant problem for public health with an annual incidence of about half a million new cases worldwide. Percentages of pelvic recurrences fluctuate from 10% to 74% depending on different risk factors. Accordingly to the literature, it is suggested that chemoradiation treatment (containing cisplatin and/or taxanes) could represent the treatment of choice for locoregional recurrences of cervical cancer after radical surgery. Pelvic exenteration is usually indicated for selected cases of central recurrence of cervical cancer after primary or adjuvant radiation and chemotherapy with bladder and/or rectum infiltration neither extended to the pelvic side walls nor showing any signs of extrapelvic spread of disease. Laterally extended endopelvic resection (LEER) for the treatment of those patients with a locally advanced disease or with a recurrence affecting the pelvic wall has been described. CONCLUSIONS The treatment of recurrences of cervical carcinoma consists of surgery, and of radiation and chemotherapy, or the combination of different modalities taking into consideration the type of primary therapy, the site of recurrence, the disease-free interval, the patient symptoms, performance status, and the degree to which any given treatment might be beneficial.

Class I versus class III radical hysterectomy in stage IB1-IIA cervical cancer. A prospective randomized study

OBJECTIVE The standard treatment for stage IB-IIA cervical cancer over the past three decades has been the Piver-Rutledge type III radical hysterectomy. This surgery implies a high rate of urologic morbidity. The objective was to determine the role of class I radical hysterectomy compared to class III radical hysterectomy in terms of morbidity, overall survival, DFS and patterns of relapse in patients undergoing primary surgery. MATERIALS AND METHODS 125 patients with stage IB1 and IIA cervical cancer ≤ 4 cm were randomized between type I and type III hysterectomy. Clinical, pathologic and follow-up data were prospectively collected. Adjuvant radiotherapy was administered when indicated. Univariate and multivariate analyses were carried out. RESULTS Sixty-two patients were randomized to class I surgery and 63 to class III. No significant differences were observed regarding pathologic findings and adjuvant treatment. Morbidity rates were higher after class III surgery (84% versus 45%). Pelvic recurrences were equal in both groups (8 cases each one). Fifteen-year overall survival rate was 90 and 74% respectively (p = 0.11) and 76 and 80% when cervical size is ≤ 3 cm (p = 0.88). CONCLUSIONS There are no significant differences in terms of both recurrence rate and overall survival among patients with stage IB-IIA cervical cancer undergoing simple extrafascial hysterectomy (class I) or radical hysterectomy (class III). Morbidity is proportional to the extent of radicality. These data confirm the need of tailoring the extent of resection to the characteristics of the cervical neoplasia and open new interesting pathways to upcoming protocols for the conservative management of these tumors.

Conservative treatment of early stage ovarian cancer: Oncological and fertility outcomes

BACKGROUND Ovarian cancer may appear in young women during their reproductive age. As a result of late childbearing nowadays, fertility preservation has become a major issue in young women with gynecological cancer. The aim of this review is to update the current knowledge on conservative treatment and fertility preservation of women affected of early stage epithelial ovarian cancer. MATERIAL AND METHODS A web-based search in Medline and CancerLit databases on conservative treatment for early stage ovarian cancer has been carried out. All relevant information has been collected and analyzed. RESULTS Less than 40% of ovarian cancers are diagnosed at early stages. Conservative treatment may be considered in young patients with a relapse rate that ranges from 9% to 29%, and a 5-year survival ranging from 83% to 100%. Recurrences in the controlateral ovary has been reported to be less than 5%, with most of these patients being alive after savage treatments. Moreover, it has been reported good fertility outcomes after conservative treatment with a successful conception rate that ranges from 60% to 100%, with an abortion rate under 30% in all series reported. CONCLUSIONS Conservative treatment for early epithelial ovarian cancers could be a safe option for women younger than 40 years who wish to preserve their childbearing potential. We need a strict case selection such as FIGO stage I grade 1 and 2, although grade 3 cases could be considered.

From Conventional Radiotracer Tc-99 m with Blue Dye to Indocyanine Green Fluorescence: A Comparison of Methods Towards Optimization of Sentinel Lymph Node Mapping in Early Stage Cervical Cancer for a Laparoscopic Approach

AbstractBackground The credibility of sentinel lymph node (SLN) mapping is becoming increasingly more established in cervical cancer. We aimed to assess the sensitivity of SLN biopsy in terms of detection rate and bilateral mapping in women with cervical cancer by comparing technetium-99 radiocolloid (Tc-99m) and blue dye (BD) versus fluorescence mapping with indocyanine green (ICG).MethodsData of patients with cervical cancer stage 1A2 to 1B1 from 5 European institutions were retrospectively reviewed. All centers used a laparoscopic approach with the same intracervical dye injection. Detection rate and bilateral mapping of ICG were compared, respectively, with results obtained by standard Tc-99m with BD.ResultsOverall, 76 (53 %) of 144 of women underwent preoperative SLN mapping with radiotracer and intraoperative BD, whereas 68 of (47 %) 144 patients underwent mapping using intraoperative ICG. The detection rate of SLN mapping was 96 % and 100 % for Tc-99m with BD and ICG, respectively. Bilateral mapping was achieved in 98.5 % for ICG and 76.3 % for Tc-99m with BD; this difference was statistically significant (p < 0.0001).ConclusionsThe fluorescence SLN mapping with ICG achieved a significantly higher detection rate and bilateral mapping compared to standard radiocolloid and BD technique in women with early stage cervical cancer. Nodal staging with an intracervical injection of ICG is accurate, safe, and reproducible in patients with cervical cancer. Before replacing lymphadenectomy completely, the additional value of fluorescence SLN mapping on both perioperative morbidity and survival should be explored and confirmed by ongoing controlled trials.

Renal Angiomyolipoma during Pregnancy: Review of the Literature

The incidence of renal angiomyolipoma (RA) is 0.3% in the general population, and even more infrequent during pregnancy. Pregnancy can increase the risk of rupture, although the causal mechanism is still not clearly defined. We completed a Medline literature search for articles on RA and pregnancy and its complications. We identified 16 articles (all case reports), but selected only 13 because of unavailable data in the 3 other articles. We report the case of a 30-year-old primiparous woman who presented at the emergency ward with a non-reassuring pattern at fetal monitoring; an urgent cesarean section was decided and carried out. After surgery, a wide retroperitoneal hematoma was observed caused by the rupture of an RA. Conservative management by means of arterial embolism was done and the patient was discharged on postoperative day 10. RAs seem to have a higher risk of rupture during pregnancy, but they should be managed conservatively when hemodynamically possible. Individualization of each case is necessary in order to achieve the best outcome for both the mother and fetus.

Rectosigmoid resection at the time of primary cytoreduction for advanced ovarian cancer. A multi-center analysis of surgical and oncological outcomes

OBJECTIVE The aim of the study was to determine the impact of rectosigmoid resection, at the time of primary cytoreductive surgery, on morbidity and survival of patients with advanced ovarian cancer. METHODS We performed a retrospective medical chart review of patients who underwent rectosigmoid resection for ovarian, tubal and peritoneal cancers between 1998 and 2008 at the IEO in Milan and JHMI in Baltimore. Perioperative and follow-up data were collected. RESULTS A total of 238 patients were identified; 180 (75%) had stages IIC-IIIC and 58 (25%) had stage IV. Complete cytoreduction was achieved in 41% of the cases. Stapled coloproctostomy was performed in 98% while hand sewn in only 2%; a protective ileostomy and colostomy were necessary (constructed) in 2 (0.8%) and 5 (2%) cases respectively. The complications associated to rectosigmoid resection were anastomotic leakage in 7 (3%) patients and pelvic abscess in 9 (3.7%). Fifty percent of patients recurred during the study period, but only 5% of them showed a relapse at the level of the pelvis whereas 8% presented with abdominal recurrence associated with pelvic disease as well. The median overall survival time among patients with complete cytoreduction was 72 months compared with 42 months among the rest of patients (p=0.002). CONCLUSIONS Rectosigmoid colectomy may significantly contribute to achieve a complete primary cytoreduction for advanced stage ovarian, tubal and peritoneal cancers. Pelvic complete debulking accomplished by rectosigmoid resection could be associated with a lower rate of pelvic recurrence as well.

Hemodynamic changes during pregnancy and postpartum: a prospective study using thoracic electrical bioimpedance.

Objective. To describe hemodynamic changes in normal pregnancy and postpartum by means of thoracic electrical bioimpedance (TEB). Methods. Eighteen healthy pregnant women were included in the study. Eight different hemodynamic variables were measured by thoracic electrical bioimpedance, from 12th week of gestation until 6th month of postpartum period. Data along pregnancy and postpartum were analyzed with SAS statistical software to compare the different values, so normality curves are reported. Results. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and peripheral vascular resistances (PVRs) seem to significantly decrease until 24th week of gestation, and then they seem to increase until delivery, recovering normal values gradually during postpartum period. End-diastolic volume (EDV), systolic volume (SV), cardiac output (CO), and ejection fraction (EF) seem to decrease until 48 h after delivery; statistical significance was found. Conclusions. Thoracic electrical bioimpedance may be the most appropriate and accurate technique to measure normal hemodynamic changes during pregnancy and postpartum.

A novel diagnostic index combining HE4, CA125 and age may improve triage of women with suspected ovarian cancer — An international multicenter study in women with an ovarian mass

AIM To develop and validate a biomarker-based index to optimize referral and diagnosis of patients with suspected ovarian cancer. Furthermore, to compare this new index with the Risk of Malignancy Index (RMI) and Risk of Ovarian Malignancy Algorithm (ROMA). PATIENTS AND METHODS A training study, consisting of patients with benign ovarian disease (n=809) and ovarian cancer (n=246), was used to develop the Copenhagen Index (CPH-I) utilizing the variables serum HE4, serum CA125 and patient age. Eight international studies provided the validation population; comprising 1060 patients with benign ovarian masses and 550 patients with ovarian cancer. RESULTS Overall, 2665 patients were included. CPH-I was highly significant in discriminating benign from malignant ovarian disease. At the defined cut-off of 0.070 for CPH-I the sensitivity and specificity were 95.0% and 78.4% respectively in the training cohort and 82.0% and 88.4% in the validation cohort. Comparison of CPH-I, ROMA and RMI demonstrated area-under-curve (AUC) at 0.960, 0.954 and 0.959 respectively in the training study and 0.951, 0.953 and 0.935 respectively in the validation study. Using a sensitivity of 95.0%, the specificities for CPH-I, ROMA and RMI in the training cohort were 78.4%, 71.7% and 81.5% respectively, and in the validation cohort 67.3%, 70.7% and 69.5% respectively. CONCLUSION All three indices perform well at the clinically relevant sensitivity of 95%, but CPH-I, unlike RMI and ROMA, is independent of ultrasound and menopausal status, and may provide a simple index to optimize referral of women with suspected ovarian cancer.

Prognostic factors associated with local recurrence in squamous cell carcinoma of the vulva

Objective To analyze the prognostic factors related to the recurrence rate of vulvar cancer. Methods Retrospective study of 87 patients diagnosed of vulvar squamous cell carcinoma diagnosed at a tertiary hospital in Madrid between January 2000 and December 2010. Results The pathological mean tumor size was 35.1±22.8 mm, with stromal invasion of 7.7±6.6 mm. The mean free margin after surgery was 16.8±10.5 mm. Among all patients, 31 (35.6%) presented local recurrence (mean time 10 months; range, 1 to 114 months) and 7 (8%) had distant metastases (mean time, 5 months; range, 1 to 114 months). We found significant differences in the mean tumor size between patients who presented a relapse and those who did not (37.6±21.3 mm vs. 28.9±12.1 mm; p=0.05). Patients with free margins equal or less than 8 mm presented a relapse rate of 52.6% vs. 43.5% of those with free margin greater than 8 mm (p=0.50). However, with a cut-off of 15 mm, we observed a local recurrence rate of 55.6% vs. 34.5%, respectively (p=0.09). When the stromal invasion cut-off was >4 mm, local recurrence rate increased up to 52.9% compared to 37.5% when the stromal invasion was ≤4 mm (p=0.20). Conclusion Tumor size, pathologic margin distance and stromal invasion seem to be the most important predictors of local vulvar recurrence. We consider the cut-off of 35 mm of tumor size, 15 mm tumor-free surgical margin and stromal invasion >4 mm, high risk predictors of local recurrence rate.

The need for accredited training in gynaecological oncology: a report from the European Network of Young Gynaecological Oncologists (ENYGO)

BACKGROUND Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbachs-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbachs alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.