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Abstract: Objective: The objective of this prospective study was to determine the feasibility, safety and performance of a new method for sentinel lymph node (SLN) detection in endometrial cancer (EC) using transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR). Methods: From 2006 to 2011, 74 patients with high-risk EC were included in the study. Twenty-four hours before surgery 148MBq of 99mTc-nanocolloid (8mL) was injected into two spots in the anterior and posterior myometrium using an ultrasound-guided transvaginal puncture. SLN was localized preoperatively by lymphoscintigraphy and intraoperatively with gamma probe. After SLN biopsy the patients underwent a complete laparoscopic pelvic and paraaortic lymphadenectomy. Results: The TUMIR method was successfully achieved in 67/74 patients (90.5%). SLN was identified in 55 women (74.3%). No adverse effects were observed. Pelvic drainage was observed in 87.2% of women and paraaortic SLN was identified in 45.4%, with 12.8% of the patients draining only in this area. The mean number of SLN retrieved was 2.8 per patient (range 1 to 9). Metastatic disease was found in 13 (23.6%) patients. Metastatic involvement of the paraaortic lymph nodes was observed in 4 (30.7%) cases. All were identified by TUMIR. The sensitivity and negative predictive value of SLN detected by TUMIR to detect metastasis were 92.3% (95% CI 22.9–100) and 97.7% (95% CI 82.0–100), respectively. Conclusions: TUMIR is a safe, feasible method to detect SLN in patients with EC, has a good detection rate and provides representative information of the lymphatic drainage of EC. [Copyright &y& Elsevier]

Simple Summary: Some recently published studies in early-stage cervical cancer patients have shown that minimally invasive surgery (MIS), including laparoscopic and robotic approaches, might offer lower survival rates than classic open surgery. We evaluated the oncological results of a series of patients treated by laparoscopically assisted radical vaginal hysterectomy (LARVH), an infrequently used MIS technique. We included 115 patients with early-stage cervical cancer (IA1 with lymphovascular invasion, IA2, IB1, and IIA < 2 cm; International Federation of Gynecology (FIGO), 2008). The 3- and 4.5-year disease-free survival rates were 96.7% and 93.5%, respectively, and the overall survival was 97.8% and 94.8%, respectively. These survival data are comparable with those reported with the open radical hysterectomy but presented the advantages of MIS. LARVH offers excellent disease control in women with early-stage cervical cancer and can be considered as an adequate MIS alternative to open radical hysterectomy. Background: Recent evidence indicates that some minimally invasive surgery approaches, such as laparoscopic and robotic-assisted radical hysterectomy, offer lower survival rates to patients with early-stage cervical cancer than open radical hysterectomy. We evaluated the oncological results of a different minimally invasive surgery approach, that of laparoscopically assisted radical vaginal hysterectomy (LARVH) in this setting. Methods: From January 2001 to December 2018, patients with early-stage cervical cancer were treated by LARVH. Colpotomy and initial closure of the vagina were performed following the Schauta operation, avoiding manipulation of the tumor. Laparoscopic sentinel lymph node (SLN) biopsy was performed in all cases. Women treated between 2001 and 2011 also underwent pelvic lymphadenectomy. Results: There were 115 patients included. Intraoperative complications occurred in nine patients (7.8%). After a median follow-up of 87.8 months (range 1–216), seven women (6%) presented recurrence. Four women died (mortality rate 3.4%). The 3- and 4.5-year disease-free survival rates were 96.7% and 93.5%, respectively, and the overall survival was 97.8% and 94.8%, respectively. Conclusion: LARVH offers excellent disease-free and overall survival in women with early-stage cervical cancer and can be considered as an adequate minimally invasive surgery alternative to open radical hysterectomy. [ABSTRACT FROM AUTHOR]

Abstract: There is an important proportion of reproductive-age patients with early stage cervical cancer, low risk of parametrial or lymph node invasion and 95% overall survival rate at 5 years. Actually, there are two conservative techniques for fertility preservation for which long-term follow-up data consistently show acceptable overall and recurrence-free survival rates: conization and vaginal radical trachelectomy (VRT) (Dargent'' s operation). Conization is optimal for women with stage IA1 disease without lymphvascular space invasion, and Dargent'' s operation is optimal for women with stage IA2 and IB1 disease who have tumors ≤2 cm in diameter. Other criteria are age ≤40 years, a desire to preserve fertility, and negative lymph nodes. In other techniques like conization or simple trachelectomy with lymphadenectomy selection of patients with low -risk factors is essential; no vascular space invasion and stromal invasion ≤1 cm are required. Sentinel node mapping and biopsy are good predictors of node metastasis and could be a good method to select patients for conservative parametrial and cervical surgery. Neoadjuvant chemotherapy could be useful in women with stage IB1 tumors 2 –4 cm in diameter with ≥50% stromal invasion with or without lymphovascular invasion. [Copyright &y& Elsevier]

Introduction Our objective was to compare the feasibility and safety of surgical procedures to treat gynecological pathologies with intestinal involvement performed by skilled gynecological surgeons and by a multidisciplinary team of gynecologists plus colorectal surgeons. Material and methods We performed a comparative, observational, prospective study at a tertiary referral center. The population included all women undergoing bowel surgery for gynecological pathologies over a 3-year period. Cases were analyzed by the specialty of the main surgeon performing the intestinal procedure. The main outcome measures were surgical procedure characteristics and postoperative outcomes and complications. Results A total of 65 women were included. Surgery was exclusively performed by a subspecialized gynecologist in 30.8% of the women, and undertaken by a multidisciplinary team (colorectal surgeons and gynecologists) in 69.2%. The main demographic and clinical characteristics were comparable in both groups. Main indications for bowel resection in gynecological surgery were advanced ovarian cancer and deep infiltrating endometriosis. In addition to the standard gynecological surgical procedures, a total of 135 intestinal segments were resected, with sigmoid colon the most frequent intestinal segment resected in both groups (53% in the gynecologist group and in 60% in the multidisciplinary group). No significant differences were observed between the two groups in the distribution and frequency of surgical techniques used, rate of complications, mean hospitalization time or frequency of re-intervention. Conclusion Skilled gynecological surgeons appear to be equally good at handling common intestinal problems as a team of gynecologist and colorectal surgeons. [ABSTRACT FROM AUTHOR]

Objectives : Accurate assessment of disease extent is required to select the best primary treatment for advanced epithelial ovarian cancer patients. Estimation of tumour burden is challenging and it is usually performed by means of a surgical procedure. Imaging techniques and tumour markers can help to estimate tumour burden non-invasively. 2-[18F]FDG PET/CT allows the evaluation of the whole-body disease. This study aimed to correlate HE4 and CA125 serum concentrations with tumour burden evaluated by volumetric 2-[18F]FDG PET/CT parameters in advanced high-grade epithelial ovarian cancer. Methods: We included 66 patients who underwent 2-[18F]FDG PET/CT and serum tumour markers determination before primary treatment. Volumes of interest were delimited in every pathological uptake. Whole-body metabolic tumour volume (wb_MTV) and total lesion glycolysis (wb_TLG) were calculated summing up every VOI's MTV value. SUVmax thresholds were set at 40% (MTV40 and TLG40) and 50% (MTV50 and TLG50). In addition, four VOI subgroups were defined: peritoneal carcinomatosis, retroperitoneal nodes, supradiaphragmatic nodes, and distant metastases. MTV and TLG were calculated for each group by adding up the corresponding MTV values. TLG was calculated likewise. Results: wb_MTV and wb_TLG were found to be significantly correlated with serum CA125 and HE4 concentrations. The strongest correlation was observed between HE4 and wb_MTV40 (r = 0.62, p < 0.001). Pearson's correlation coefficients between peritoneal carcinomatosis MTV40 and tumour markers were 0.61 (p < 0.0001) and 0.29 (p = 0.02) for HE4 and CA125 respectively. None of these tumour markers showed a positive correlation with tumour load outside the abdominal cavity assessed by volumetric parameters. Conclusion: HE4 performs better than CA125 to predict metabolic tumour burden in high-grade epithelial ovarian cancer before primary treatment. 2-[18F]FDG PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. These results support the usefulness of HE4 and PET/CT to improve the stratification of these patients in clinical practice. Key Points: • In patients with high-grade advanced ovarian epithelial carcinoma, both CA125 and HE4 correlate to whole-body tumour burden assessed by PET/CT before primary treatment. • HE4 estimates peritoneal disease much better than CA125. • PET/CT volumetric parameters arise as feasible tools for the objective assessment of tumour load and its anatomical distribution. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the accuracy of sentinel lymph node (SLN) mapping with transvaginal ultrasound-guided myometrial injection of radiotracer (TUMIR) to detect lymph node (LN) metastases, in patients with intermediate and high-risk endometrial cancer (EC), focusing on its performance to detect paraaortic involvement. Methods: Prospective study including women with preoperative intermediate or high-risk EC, according to ESMO-ESGO-ESTRO consensus, who underwent SLN mapping using the TUMIR approach. SLNs were preoperatively localized by planar and single photon emission computed tomography/computed tomography images, and intraoperatively by gamma-probe. Immediately after SLN excision, all women underwent systematic pelvic and paraaortic lymphadenectomy by laparoscopy. Results: The study included 102 patients. The intraoperative SLN detection rate was 79.4% (81/102). Pelvic and paraaortic drainage was observed in 92.6% (75/81) and 45.7% (37/81) women, respectively, being exclusively paraaortic in 7.4% (6/81). After systematic lymphadenectomy, LN metastases were identified in 19.6% (20/102) patients, with 45.0% (9/20) showing paraaortic involvement, which was exclusive in 15.0% (3/20). The overall sensitivity and negative predictive value (NPV) of SLNs by the TUMIR approach to detect lymphatic involvement were 87.5% and 97.0%, respectively; and 83.3% and 96.9%, for paraaortic metastases. After applying the MSKCC SLN mapping algorithm, the sensitivity and NPV were 93.8% and 98.5%, respectively. Conclusion: The TUMIR method provides valuable information of endometrial drainage in patients at higher risk of paraaortic LN involvement. The TUMIR approach showed a detection rate of paraaortic SLNs greater than 45% and a high sensitivity and NPV for paraaortic metastases in women with intermediate and high-risk EC. [ABSTRACT FROM AUTHOR]

Purpose: Sentinel lymph node biopsy (SLNB) can be used for nodal staging in early cervical cancer. For this purpose, the tracers most commonly used are radiotracers based on technetium. For the last decade, indocyanine green (ICG) has been used as a tracer for SLNB in other malignancies with excellent results and, more recently, a combination of ICG and a radiotracer has been shown to have the advantages of both tracers. The aim of this study was to evaluate the role of ICG-Tc-nanocolloid in SLN detection in patients with cervical cancer. Methods: This prospective study included 16 patients with cervical cancer. The hybrid tracer was injected the day (19-21 h) before surgery for planar and SPECT/CT lymphoscintigraphy. Blue dye was administered periorificially in 14 patients. SLNs were removed according to their distribution on lymphoscintigraphy and when radioactive, fluorescent and/or stained with blue dye. Nodal specimens were pathologically analysed for metastases including by immunochemistry. Results: Lymphoscintigraphy and SPECT/CT showed drainage in all patients. A total of 69 SLNs were removed, of which 66 were detected by their radioactivity signal and 67 by their fluorescence signal. Blue dye identified only 35 SLNs in 12 of the 14 patients (85.7%). All patients showed bilateral pelvic drainage. Micrometastases were diagnosed in two patients, and were the only lymphatic nodes involved. Conclusions: SLNB with ICG-Tc-nanocolloid is feasible and safe in patients with early cervical cancer. This hybrid tracer provided bilateral SLN detection in all patients and a higher detection rate than blue dye, so it could become an alternative to the combined technique. [ABSTRACT FROM AUTHOR]

Purpose To analyze vaginal-cuff relapses (VCR) and toxicity of two brachytherapy (BT) schedules in postoperative endometrial carcinoma and to correlate vaginal toxicity with vaginal-surface-EQD2Gy 3 dose (VS-EQD2Gy 3 ). Methods/materials 319 patients (p) I–IIIC-Figo-stage were treated with 2 BT schedules. One schedule included 166p (Group-1) to whom 3 fractions (Fr) of 4–6 Gy per week (w) of BT were administered after external beam radiotherapy (EBI) (125p) and 6Fr/2w of 4–6 Gy in exclusive-BT (41p). The second schedule included 153p (Group-2) with BT administered daily with 2Fr/w of 5–6 Gy after EBI (94p) and 5–6 Gy/4Fr/w in exclusive-BT (59p). Doses were prescribed at 5 mm from the vaginal surface. Toxicity was evaluated using RTOG scores for the rectum and bladder and objective LENT-SOMA scores for the vagina. Statistics Chi-square, Fisher and Student’s- t tests. Results Mean follow-up (months): Group-1: 66.55 (7.73–115.40), Group-2: 41.49 (3.13–87.90). VCR: Group-1: 3p (1.88%); Group-2: 2p (1.3%). No differences were found between the two schedules comparing rectal ( p = 0.170), bladder ( p = 0.125) and vagina ( p = 0.680) late toxicities and comparing vagina EBI + BTp vs. exclusive-BTp ( p = 0.667). Significant differences in VS-EQD2 3Gy were observed considering EBI + BT (Groups 1 + 2) vs. exclusive-BT (Groups 1 + 2) ( p < 0.0001); nevertheless, no association was found between VS-EQD2 3Gy and vaginal complications. Conclusions No differences were found between the two schedules. No association was found between vaginal toxicity and VS-EQD2 3Gy . Consequently, treatment with the least number of fractions is preferable. [ABSTRACT FROM AUTHOR]

Purpose: Undifferentiated uterine sarcomas (UUS) are rare and aggressive tumor with scarce data on the outcome and best treatment. We aimed to describe the behavior among patients with UUS at our institution. Materials and methods: Thirteen patients with UUS treated in our centre from 1979 to 2010 were analyzed. Statistics: descriptive analysis for frequencies and Kaplan-Meier actuarial method for overall survival (OS). Results: Patients mean age was 66 years. Three had FIGO 2009 stage IA, five IB, two IIB, and three IVB. Ten patients underwent surgery and eight received postoperative radiotherapy. Three patients received adjuvant chemotherapy. The median follow-up was 16 months (2-276 months). Stage I patients developed two local relapses and three distant metastases (DM). DM was also observed in stage II patients and in 61.5 % of the entire series. Fifty percent of patients receiving radiotherapy remain alive without relapse. The median OS was 16 months, being 17 months for stage I and 9 for the remainder. Conclusions: Poor outcome of UUS was associated with a high incidence of DM. Stage I had the best outcome. Radiotherapy seems to have benefited patients, with 100 % of local control and 50 % of long-term survivors. The high incidence of metastasis suggests the need for more accurate initial assessment. [ABSTRACT FROM AUTHOR]

Purpose: To analyse the impact of prognostic factors on specific overall survival (SOS) after postoperative radiotherapy (P-RT) in carcinosarcomas. Methods: We retrospectively analysed 81 patients who received P-RT from 1977 to 2010 after the diagnosis of carcinosarcomas. 2009 FIGO stage: 25-IA, 20-IB, 6-II, 9-IIIA, 11-IIIC. Age, stage, vascular and lymphatic space invasion (VLSI), myometrial invasion, grade, mitotic index, sarcomatous/epithelial components, tumour size and necrosis were considered for the analysis. Statistics: we used the Kaplan-Meier method for survival analysis and the Cox model for risk factor evaluation. Results: The mean follow-up of the series was 78.86 months (range 7-381). The median age was 72 years (range 51-89). 30 out 81 (37 %) patients relapsed and died (22.2 % pelvic and abdominal, 13.5 % exclusive distant metastasis). On univariate and multivariate analysis only stage had a significant impact on SOS. At 5 years, stage I-II had a SOS of 66 % in comparison with stage III with 30 %. Conclusions: Two groups of patients showing different outcome were found after P-RT in uterine carcinosarcomas: stage I-II patients had a life expectancy 2.5-fold longer compared to stage III patients. New therapeutic strategies are warranted in carcinosarcomas considering the high incidence of distant metastasis. [ABSTRACT FROM AUTHOR]

The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to 'general consensus' and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board. [ABSTRACT FROM AUTHOR]

(1) OBJECTIVE: To assess the performance of CA125, HE4, ROMA index and CPH-I index to preoperatively identify epithelial ovarian cancer (EOC) or metastatic cancer in the ovary (MCO). (2) METHODS: single center retrospective study, including women with a diagnosis of adnexal mass. We obtained the AUC, sensitivity, specificity and predictive values were of HE4, CA125, ROMA and CPH-I for the diagnosis of EOC and MCO. Subgroup analysis for women harboring adnexal masses with inconclusive diagnosis of malignancy by ultrasound features and Stage I EOC was performed. (3) RESULTS: 1071 patients were included, 852 (79.6%) presented benign/borderline tumors and 219 (20.4%) presented EOC/MCO. AUC for HE4 was higher than for CA125 (0.91 vs. 0.87). No differences were seen between AUC of ROMA and CPH-I, but they were both higher than HE4 AUC. None of the tumor markers alone achieved a sensitivity of 90%; HE4 was highly specific (93.5%). ROMA showed a sensitivity and specificity of 91.1% and 84.6% respectively, while CPH-I showed a sensitivity of 91.1% with 79.2% specificity. For patients with inconclusive diagnosis of malignancy by ultrasound features and with Stage I EOC, ROMA showed the best diagnostic performance (4) CONCLUSIONS: ROMA and CPH-I perform better than tumor markers alone to identify patients harboring EOC or MCO. They can be helpful to assess the risk of malignancy of adnexal masses, especially in cases where ultrasonographic diagnosis is challenging (stage I EOC, inconclusive diagnosis of malignancy by ultrasound features). [ABSTRACT FROM AUTHOR]

Abstract: Objective: Recent evidence has confirmed two independent pathways in the development of vaginal squamous cell carcinoma (VaSCC): one related to and the other independent of human papillomavirus (HPV). The aim of our study was to evaluate whether HPV status has prognostic significance in this neoplasm. Methods: All confirmed primary VaSCCs diagnosed and treated from 1995 to 2009 in two institutions were retrospectively evaluated (n=57). HPV infection was detected by PCR using SPF-10 primers and typed with the INNO-LIPA HPV assay and p16INK4a expression by immunohistochemistry. Disease-free and overall survival (DFS and OS) were analyzed by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 70.2% patients. HPV16 was the most prevalent genotype (67.5% of cases). p16INK4a was positive in 97.5% HPV-positive and 17.6% HPV-negative tumors (p<.001). FIGO stage was associated with DFS (p=.042) and OS (p=.008). HPV-positive tumors showed better DFS (p=.042) and OS (p=.035) than HPV-negative tumors. Multivariate analysis confirmed better DFS and OS of HPV-positive patients independent of age and stage. This reduced risk of progression and mortality in HPV-positive patients was limited to women with FIGO stages I and II tumors (HR=0.26; 95% CI 0.10–0.69; p=0.006). Conclusions: HPV-positive early stage (FIGO I and II) VaSCCs have a better prognosis than early HPV-negative tumors. HPV detection and/or p16INK4a immunostaining can be easily implemented in routine pathology and should be considered as valuable prognostic biomarkers in the study of patients with VaSCC. [Copyright &y& Elsevier]

Purpose: To evaluate the results of high-dose-rate brachytherapy (HDRBT) using a schedule of three or four fractions per week, when possible, in 89 patients on local control and toxicity in postoperative treatment of endometrial carcinoma. The effect of the overall HDRBT treatment time (OTT) on toxicity was also evaluated. Patients and Methods: Fédération Internationale de Gynécologie Obstétrique Stage: 24 IB, 45 IC, 4 IIA, 6 IIB, 4 IIIA, 2 IIIB, and 4 IIIC. Radiotherapy: Group 1—67 of 89 patients received external beam irradiation (EBI; 44–50 Gy) plus HDRBT (3 fractions of 4–6 Gy); Group 2—22 of 89 patients received HDRBT alone (6 fractions of 4–5 Gy). OTT: Group 1—HDRBT was completed in a median of 5 days in 32 patients and in >5 days in 35; Group 2—HDRBT was completed in <15 days in 11 patients and in ≥16 days in 11. Toxicity was evaluated using Radiation Therapy Oncology Group scores and the bioequivalent dose (BED) study was performed in vaginal mucosa surface. Statistics included Student''s t test, chi-square test, and receiving operator curves. Results: With a mean follow-up of 31 months (range, 6–70), 1 of 89 patients had vaginal relapse. Early toxicity appeared in 8 of 89 (9%) patients and was resolved. Late toxicity appeared in 13/89 (14%): vaginal nine Grade 1, three Grade 2, one Grade 4; bladder two Grade 2; rectal three Grade 1, one Grade 2. No differences were found in relation to OTT in Groups 1 and 2. Mean BED was 88.48 Gy in Group 1 and 165.28 Gy in Group 2. Cases with Grade 2 late vaginal toxicity received >75 Gy after EBI and >165 Gy in Group 2. Conclusions: Three fractions of 4–5 Gy in 3–5 days after EBI or 6 fractions in <15 days in patients receiving HDRBT alone was a safe treatment in relation to toxicity and local control. Vaginal surface BED less than 75 Gy after EBI and less than 160 Gy in HDRBT alone may be safe to avoid G2 toxicity. [Copyright &y& Elsevier]

Abstract: Background: Two independent pathways in the development of vulvar squamous cell carcinoma (VSCC) have been described, one related to and the other independent of high-risk human papillomavirus (HR-HPV). The aim of our study was to evaluate whether the HPV status has a prognostic significance or can predict response to radiotherapy. Methods: All VSCC diagnosed from 1995 to 2009 were retrospectively evaluated (n =98). HPV infection was detected by amplification of HPV DNA by PCR using SPF-10 primers and typed by the INNO-LIPA HPV research assay. p16INK4a expression was determined by immunohistochemistry. Disease-free and overall survival (DFS and OS) were estimated by Kaplan–Meier analysis with the log-rank test and a multivariate Cox proportional hazard''s model. Results: HR-HPV DNA was detected in 19.4% of patients. HPV16 was the most prevalent genotype (73.7% of cases). p16INK4a stained 100% HPV-positive and 1.3% HPV-negative tumors (p <.001). No differences were found between HPV-positive and -negative tumors in terms of either DFS (39.8% vs. 49.8% at 5years; p =.831), or OS (67.2% vs. 71.4% at 5years; p =.791). No differences in survival were observed between HPV-positive and -negative patients requiring radiotherapy (hazard ratio [HR] 1.04, 95% confidence interval [CI] .45 to 2.41). FIGO stages III–IV (p =.002), lymph node metastasis (p =.030), size≥20mm (p =.023), invasion depth (p =.020) and ulceration (p =.032) were associated with increased mortality but in multivariated only lymph node metastasis retained the association (HR 13.28, 95% CI 1.19 to 148.61). Conclusions: HPV-positive and -negative VSCCs have a similar prognosis. Radiotherapy does not increase survival in HPV-positive women. [Copyright &y& Elsevier]

Fuste V, del Pino M, Perez A, Garcia A, Torne A, Pahisa J & Ordi J (2010) Histopathology 907-916 To determine the role of human papillomavirus (HPV) in the pathogenesis of primary squamous cell carcinoma of the vagina (SCCVa), and to evaluate its clinicopathological significance. All cases of SCCVa diagnosed over a 15-year period from two hospitals in Barcelona, Spain ( n = 32) were retrieved. Patients with a history of carcinoma of the cervix diagnosed <5 years before were excluded. HPV was detected and typed by polymerase chain reaction (PCR) using SPF10 primers. Immunohistochemistry was performed for p16 and p53. HPV was detected in 25 cases (78.1%). HPV16 was the most prevalent type. Patients with HPV-positive tumours were associated frequently with a history of carcinoma or intraepithelial neoplasia of the cervix or vulva diagnosed more than 5 years before (56% versus 0%; P = 0.01). HPV-positive tumours were more frequently of non-keratinizing, basaloid or warty type than HPV-negative neoplasms (84% versus 14.3%; P < 0.001), and showed diffuse positive immunoreactivity for p16 (96%, versus 14.3%; P < 0.001). The sensitivity and specificity of p16 to identify HPV-positive tumours were 96% and 85.7%, respectively. A high number of SCCVs are related to HPV infection and may be identified by immunohistochemistry for p16. HPV-positive tumours tend to affect women with history of cervical neoplasia. [ABSTRACT FROM AUTHOR]

The aim of this study was to validate a nomogram and a scoring system to predict non-sentinel lymph node status in breast cancer patients with sentinel lymph node (SLN) involvement. A total of 516 breast cancer patients underwent sentinel lymph node biopsy at our institution from January 2001 to August 2006. A prospective database was used to identify breast cancer patients with a positive SLN biopsy examination who underwent a completion axillary lymph node dissection. A total of 114 patients were identified. The Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and an axilla scoring system from Paris (Hôpital Tenon) were used to predict the probability of having non-SLN involvement. One hundred fourteen patients were included in the study. The areas under the receiver operating characteristics (ROC) curves were 0.671 (95% CI: 0.552–0.790) for the MSKCC nomogram and 0.703 (95% CI: 0.596–0.811) for the Tenon score. The univariate analysis shows that size of SLN metastases, the number of positive and negative SLN and the proportion of positive SLN were statistically significant. On multivariate logistic regression analysis, the size of SLN metastases and the proportion of positive SLN were statistically significant. The two scoring systems are similar according to their area under ROC curves, but should be improved to be valid and determinant to the general population. Meanwhile, the use of scoring systems could be applied in an individual manner in some patients. [ABSTRACT FROM AUTHOR]

Abstract: Objective. : To evaluate whether high-risk human papillomavirus (HR-HPV) detection and viral load prior to treatment and status of cone margins can predict residual/recurrent disease as well as the ability of current diagnostic tools to identify residual/recurrent disease during follow-up of high-grade cervical intraepithelial neoplasia (CIN) treated by conization using loop electrosurgical procedure (LEEP). Methods. : Two hundred and three women (mean age 38.6 ± 9.7; range 22–83) with CIN2–3 treated by LEEP conization and confirmed in the surgical specimen, attending follow-up visits were included. Age, HR-HPV detection and viral load determined by HybridCapture 2, and cone margins were evaluated as possible predictors of residual/recurrent disease. Value of single and repeated cytology as well as HR-HPV detection and viral load during follow-up were analyzed as screening tools of recurrence. Results. : Residual/recurrent disease was demonstrated by colposcopy guided biopsy in 36 patients (17.7%). High HR-HPV load (>1000 RLU) prior to LEEP and positive cone margins were significantly associated with higher risk of recurrence (31.8% vs. 9.4%, P = 0.005; and 36.4% vs. 11.9%, P < 0.001 respectively). HR-HPV detection at 6–12 m after LEEP showed higher sensitivity than a single or repeated cytology (97.2% vs. 83.3% and 94.4% respectively) although it showed less specificity (81.4% vs. 92.2% and 82.6%). The combination of HR-HPV detection and the first cytology during follow-up detected all patients with residual/recurrent disease (sensitivity 100%, negative predictive value 100%) with an acceptable specificity (76.6%). Conclusion. : The inclusion of HR-HPV testing with cytology in follow-up of patients treated for CIN2–3 would allow for fewer post-treatment visits and avoid unnecessary cytologies. High HR-HPV load prior to LEEP or positive margins should be considered as risk factors for developing residual/recurrent disease. [Copyright &y& Elsevier]

Purpose: Despite the widespread use of sentinel lymph node (SLN) biopsy in breast cancer patients, some controversy exists about the correct management of extra-axillary nodes, especially those located in the internal mammary chain. The aim of this study was to evaluate the incidence of SLNs in this region, calculate the lymphoscintigraphic and surgical detection rates and evaluate the clinical impact on staging and therapeutic decisions. Methods: The study involved 383 consecutive women diagnosed with early breast cancer with T1 or T2 tumours. Eight patients had a bilateral tumour, which brought the total to 391 lesions. Lymphoscintigraphy was performed on the day before surgery by injection of 99mTc-labelled nanocolloid. The injection site was subdermal (68 patients), peritumoural (107 patients) or intratumoural (216 patients). During surgery a gamma probe was used to guide the surgeon and the SLNs were removed. SLNs were analysed by a conventional pathological study and processed for H&E examination and immunohistochemistry. Results: Lymphoscintigraphy detected at least one SLN in 369 out of the 391 procedures (94.4%). SLNs were found in the axillary chain in 367 cases and in the internal mammary chain in 55. In two of these 55 cases (3.6%), the SLN was the only one detected. There was no drainage to the internal mammary chain in any case of subdermal injection but such drainage was found in 15.9% of cases with peritumoural injection and 17.6% of those with intratumoural injection. Compared with tumours located in the outer quadrants, a higher percentage of tumours located in the inner quadrants showed drainage to the internal mammary chain (p«0.001). A total of 42 SLNs in the internal mammary chain could be removed in 32 patients without appreciable morbidity. In 20 cases both axillary and internal mammary SLNs were negative, in four both were positive, and in five axillary SLNs were positive and internal mammary SLNs were negative. More interestingly, in the remaining patient with both axillary and internal mammary SLNs, the axillary SLN was negative while malignant cells were found in the internal mammary region. In the evaluation of the clinical impact of internal mammary SLN biopsy, we found that staging was modified from pN1a to pN1c in four patients and, more importantly, from pN0 to pN0(i+) in one patient. The change in stage led to a modification of the postoperative treatment plan with respect to radiotherapy and systemic therapy. Conclusion: Evaluation of the SLNs in the internal mammary chain provides more accurate staging of breast cancer patients. If internal mammary sampling is not performed, patients can be understaged. This technique can offer a better indication of those patients who will benefit from selective treatment options like radiotherapy to this region or systemic therapy. [ABSTRACT FROM AUTHOR]

Objective. The aim was to determine the feasibility of surgical identification and pathological ultrastaging of sentinel nodes (SNs) in vulvar carcinoma and to evaluate whether SN negativity rules out the possibility of metastasis in other nodes and can therefore avoid conventional lymphadenectomy.Material and methods. In 26 patients with vulvar squamous cell carcinoma the SNs were detected using both peritumoral injection of 99mTc and blue dye (isosulfan or methylene) before the surgical procedure. Dissection of the SNs was followed by standard lymphadenectomy and vulvar exeresis. For pathological ultrastaging at least eight histological sections of every node separated 400 μm were evaluated using hematoxylin & eosin and immunostaining against cytokeratin.Results. We identified the SNs in 25/26 patients (96%). In 19 patients (76%) the SN was unilateral and in 6 (24%) it was bilateral. A total of 46 SNs were isolated. Metastatic carcinoma was identified in 9 SNs from 8 patients (30.8%). Thirty-eight percent (3 of 8) patients with metastatic SNs presented micrometastasis detected only in ultrastaging. Seven (3.3%) of 239 nonsentinel nodes (non-SNs) showed metastasis. No metastatic implant was detected in non-SNs when SNs were negative in patients without clinical suspicious adenopathy (100% negative predictive value).Conclusion. Inguinofemoral lymph nodes can be confidently avoided when sentinel node metastases are excluded by histological ultrastaging. This may reduce the surgical morbidity of conventional inguinofemoral lymphadenectomy, without worsening vulvar cancer prognosis. [Copyright &y& Elsevier]

Background: Sarcomatous neoplasms of the uterine corpus are still a challenge in terms of obtaining prognostic factors and the most optimum complementary treatment to surgery. The most important prognostic factor is stage; relapses usually appear during the first 2 years, and most patients die within the first 3 years. We have performed a multivariate study of prognostic factors, stratifying patients by stage, to determine their impact on overall survival, disease-free survival, local relapse-free survival, and distant metastasis-free survival. Special emphasis has been given to vascular and lymphatic space invasion (VLSI).Methods: Sixty patients diagnosed with uterine neoplasms with a main sarcomatous component were treated at Hospital Clı´nic i Universitari of Barcelona between January 1975 and June 1999. Pathologic type: 32 carcinosarcomas, 14 leiomyosarcomas, 9 adenosarcomas, and 5 endometrial stromal sarcomas. Treatment: 58/60 surgery, 35/60 postoperative radiotherapy, 2/60 exclusive chemotherapy, and 3/60 complementary chemotherapy. FIGO stages: 43 Stage I, 4 Stage II, 11 Stage III, and 2 Stage IV. Variables analyzed: age, stage, vascular and lymphatic space invasion, myometrial invasion, mitotic index, tumor size, unicentricity/multicentricity, necrosis, and radiotherapy. Statistics: the S and Cox proportional risk models. The partial effect of each risk factor was calculated by hazard ratio (HR) with a confidence interval of 95%.Results: Early stages: Multivariate analysis showed that tumor size larger than 8 cm and VLSI had an impact on overall survival (HR = 4.01 and HR = 24.45, respectively). VLSI was present in 23% of the cases. Myometrial invasion greater than 50% had an impact on disease-free survival and local relapse-free survival (HR was 9.75 and 3.20, respectively). VLSI had an impact on distant metastasis-free survival (HR = 2.92). Advanced stages: VLSI was present in 89% of the cases. Only leiomyosarcoma type made the overall survival worse (HR = 10.54).Conclusions: Vascular and lymphatic space invasion was a relevant prognostic factor in our series, with an impact on overall survival and distant metastasis-free survival in early stages. In advanced stages, VLSI had no impact on survival, but was present in 89% of cases. Myometrial invasion >50% had an impact on local relapse. Advanced stages had a more aggressive behavior, and there was a higher incidence of poor prognostic factors in these stages. Nevertheless, prospective studies are still needed on prognostic factors and on the best treatment option. [Copyright &y& Elsevier]

Abstract: The recent development of two highly effective vaccines against persistent infection by the 2 most important types of human papillomavirus (HPV) (16 and 18) and against high grade premalignant lesions (CIN2+) has opened a new scenario for the primary prevention of cervical cancer. The optimum target population for vaccination should be individually defined taking the following into account: 1) the efficacy of the vaccine, 2) the epidemiological context and 3) the vaccination programs available in each country. To achieve the maximum preventive benefits, the vaccine should be administered before the initiation of sexual relations. So, the HPV vaccine should be integrated in the school vaccination programs of adolescents together with other vaccines. The vaccination of sexually active women may considerably increase the speed with which results in the fight against this disease will be achieved. Developed countries will probably consider the vaccination of these women, although vaccination strategies and the efforts to reach this population will be conditioned by the resources of each country and by the estimations of the cost-efficacy relationship in each situation. Women with a previous history of premalignant cervical disease or with an abnormal screening test should not be excluded from the potential benefits which the vaccine may provide. There is no contraindication for the administration of the vaccine in immunosupressed women. However, it is still unknown under what specific circumstances of immunosuppression the immunogenicity of the vaccine may be affected and there are currently ongoing studies for an answer to this question. [Copyright &y& Elsevier]