Risk for Pelvic Metastasis and Role of Pelvic Lymphadenectomy in Node-Positive Vulvar Cancer-Results from the AGO-VOP.2 QS Vulva Study.

The need for pelvic treatment in patients with node-positive vulvar cancer (VSCC) and the value of pelvic lymphadenectomy (LAE) as a staging procedure to plan adjuvant radiotherapy (RT) is controversial. In this retrospective, multicenter analysis, 306 patients with primary node-positive VSCC treated at 33 gynecologic oncology centers in Germany between 2017 and 2019 were analyzed. All patients received surgical staging of the groins; nodal status was as follows: 23.9% (73/306) pN1a, 23.5% (72/306) pN1b, 20.4% (62/306) pN2a/b, and 31.9% (97/306) pN2c/pN3. A total of 35.6% (109/306) received pelvic LAE; pelvic nodal involvement was observed in 18.5%. None of the patients with nodal status pN1a or pN1b and pelvic LAE showed pelvic nodal involvement. Taking only patients with nodal status ≥pN2a into account, the rate of pelvic involvement was 25%. In total, adjuvant RT was applied in 64.4% (197/306). Only half of the pelvic node-positive (N+) patients received adjuvant RT to the pelvis (50%, 10/20 patients); 41.9% (122/291 patients) experienced recurrent disease or died. In patients with histologically-confirmed pelvic metastases after LAE, distant recurrences were most frequently observed (7/20 recurrences). Conclusions: A relevant risk regarding pelvic nodal involvement was observed from nodal status pN2a and higher. Our data support the omission of pelvic treatment in patients with nodal status pN1a and pN1b.

Peritoneal contamination with ICG-stained cervical secretion as surrogate for potential cervical cancer tumor cell dissemination: A proof-of-principle study for laparoscopic hysterectomy.

INTRODUCTION: Intracorporal colpotomy during radical hysterectomy for cervical cancer is discussed to be a risk factor for peritoneal dissemination of tumor cells. It might lead to increased recurrence rates after laparoscopic radical hysterectomy compared with abdominal hysterectomy, as shown by the recent LACC study. Data on the frequency or mechanisms of peritoneal contamination are missing. We aimed to analyze peritoneal contamination of cervical secretion during intracorporal colpotomy with a novel indocyaningreen (ICG)-based technique. MATERIAL AND METHODS: In this prospective proof-of-principle study, patients undergoing routine laparoscopic or robot-assisted hysterectomy were selected. ICG was specifically applied to the cervical surface and routine surgery was performed. During colpotomy, pictures under white and fluorescence light were taken to evaluate frequency of contamination. RESULTS: By using cervically applied ICG we were able to visualize directly peritoneal contamination with cervical secretion during intracorporal colpotomy. We detected peritoneal contamination in 9/12 (75%) patients undergoing routine laparoscopic hysterectomy. Contamination of laparoscopic instruments occurred in 60% of the patients. When contamination occurred, it was routinely detectable during all steps of colpotomy. There were no adverse effects during surgery. CONCLUSIONS: Peritoneal contamination with cervical secretion frequently occurs during intracorporal colpotomy. This novel technique represents a promising tool for feasible and direct visualization of peritoneal contamination during colpotomy. The technique may be easily implemented in further studies on laparoscopic and abdominal hysterectomy and serve as a quality assessment tool for surgeons and surgical techniques.

Sentinel lymphadenectomy in cervical cancer using near infrared fluorescence from indocyanine green combined with technetium-99m-nanocolloid.

OBJECTIVE: Sentinel diagnostic in cervical cancer is performed using Technetium-99m-nanocolloid as a radioactive marker with or without patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule which emits a light signal in the near infrared band after excitation. Our study aims to evaluate indocyanine green compared to the gold standard Tc-99m-nanocolloid. MATERIALS AND METHODS: We included patients with early cervical cancer up to FIGO stage IIA with clinically node-negative pelvic sites and the indication for nodal staging in this prospective trial. Sentinel diagnostic was carried out using Tc-99m-nanocolloid, indocyanine green and patent blue. We examined each pelvic site for light signals from the near infrared band, for radioactivity and for blue staining. A sentinel lymph node was defined as a Tc-99m-nanocolloid positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested; then sent to histologic examination. RESULTS: Thirty-three patients were included in which we found 211 Tc-99m-nanocolloid-positive sentinel lymph nodes in 66 pelvic sites. Two hundred and seven of these lymph nodes were positive for indocyanine green, too, giving a sensitivity of 98.1% (95%CI 94.9-99.4%) compared to Tc-99m-nanocolloid. One hundred and sixty additional lymph nodes showed indocyanine green fluorescence but no Tc-99m-positivity, so that the sensitivity was 79.6% (95%CI 76.6-82.3%). In one patient, a pelvic site was only identified to be tumor infiltrated due to an ICG-positive, but Tc-99m-negative lymph node. CONCLUSION: Our results show that indocyanine green is a promising approach for pelvic sentinel identification in cervical cancer. ICG has a similar sensitivity as radioactive Tc-99m-nanocolloid and may enhance both patient safety and surgeons' comfort. Lasers Surg. Med. 50:994-1001, 2018. © 2018 Wiley Periodicals, Inc.

Peri- and postoperative management and outcomes of morbidly obese patients (BMI > 40 kg/m2) with gynaecological disease.

INTRODUCTION: For the last two decades, obesity rates have been increasing in both developed and developing countries, with the number of obese women roughly doubling during this period (Stevens et al. in Popul Health Metr 10(1):33, 2012). Obesity represents one of the biggest epidemics of the 21st century. The aim of this retrospective study is to characterise the outcomes of gynaecologic surgeries in cases of extremely obese women with a body mass index (BMI) over 40 kg/m2. METHODS: This study is a retrospective case control study in a single-centre setting. Our clinical database was searched for gynaecological operations performed on morbidly obese patients (BMI > 40 kg/m2) between 2009 and 2014 in the Department of Gynaecology and Obstetrics at Hannover Medical School. We matched these results with random patients of normal body weight who had similar surgical procedures and diseases. RESULTS: We included 97 obese patients in our case group and 99 patients in the control group. We found an association between a strongly elevated BMI and peri- and postoperative morbidity. Both intraoperative and postoperative complications are significantly increased in morbid obesity with a BMI over > 40 kg/m2. We observed intraoperative complications in 55.6% and postoperative complications in 50.5% of patients with extreme obesity. In contrast, the complication rate in the control group with a normal BMI was 11% intraoperatively (p = 0.0001) and 3% postoperatively (p = 0.0001). The data showed that perioperative and postoperative morbidity could be reduced by laparoscopic surgery in many cases, with a significant lower rate of difficulties with closing the wound, a significant shorter duration of surgery and a significant lower rate of infections combined with a significant lower reoperation rate and shorter hospital stay. In gynaecological-oncological diseases, we could demonstrate a reduced radicality during the operative procedure due to extreme obesity. DISCUSSION: Dealing with the growing number of obese patients is essential, because the problems emerging from obesity are manifold for the treating hospitals as well as the general health system. For this high-risk patient group, it is indispensable to obtain a thorough overview of the patient's overall situation preoperatively to ensure good perioperative care and complications management.

Sarcoma Risk in Uterine Surgery in a Tertiary University Hospital in Germany.

OBJECTIVES: There is a risk to incidentally spread uterine malignancies, especially sarcoma, if tissue is morcellated during hysterectomy or myoma enucleation. In the last years, a worldwide discussion has been started about this problem. However, the risk seems to be very small in recent studies. This study aims at further investigating the risk of disseminating uterine malignancy during uterine surgery in a tertiary university hospital in Germany. METHODS: In a retrospective setting, all cases of uterine myometrial surgery (hysterectomies and myomectomies) in our clinic during a period of 10 years were identified using clinical databases. Histology was linked and searched for uterine malignancies. All cases were reviewed for incidental morcellation of malignant tissue. RESULTS: Between 2004 and 2014, we identified 2825 cases of uterine myometrial surgery. Morcellating procedures were used in 20% of the 1402 hysterectomy procedures (280/1402) and in 13.7% of the 1423 fibroid removals (195/1423). We identified 23 uterine mesenchymal malignancies (sarcoma, n = 10; carcinosarcoma, n = 13). In 3 cases, there was no evidence or sign of a malignant disease preoperatively in a procedure with a morcellation (vaginal hysterectomy with morcellation, n = 1; open fibroid enucleation, n = 2). CONCLUSIONS: A small risk (0.35% [1/280]) of accidental morcellation during hysterectomy with morcellation was found in our study. We did not observe an occult case of sarcoma after myomectomy with morcellation (0/195), but we found 2 cases of accidental sarcoma after myomectomy without morcellation. For these reasons, minimally invasive surgery with morcellation should not be excluded a priori. The patient should be well informed about the risks and various options. The advantage of laparoscopic surgery should be balanced against the risk of the unknown spread of malignant tissue.

Sentinel Lymphadenectomy in Vulvar Cancer Using Near-Infrared Fluorescence From Indocyanine Green Compared With Technetium 99m Nanocolloid.

OBJECTIVE: Nowadays, sentinel diagnostic is performed using technetium 99m (Tc) nanocolloid as a radioactive marker and sometimes patent blue. In the last years, indocyanine green has been evaluated for sentinel diagnostic in different tumor entities. Indocyanine green is a fluorescent molecule that emits a light signal in the near-infrared band after excitation. Our study aimed to evaluate indocyanine green compared with the criterion-standard Tc-nanocolloid. METHODS: We included patients with primary, unifocal vulvar cancer of less than 4 cm with clinically node-negative groins in this prospective trial. Sentinel diagnostic was carried out using Tc-nanocolloid, indocyanine green, and patent blue. We examined each groin for light signals from the near-infrared band, for radioactivity, and for blue staining. A sentinel lymph node was defined as a Tc-nanocolloid-positive lymph node. All sentinel lymph nodes and all additional blue or fluorescent lymph nodes were excised and tested and then sent for histologic examination. RESULTS: In all, 27 patients were included in whom we found 91 sentinel lymph nodes in 52 groins. All these lymph nodes were positive for indocyanine green, also giving a sensitivity of 100% (95% confidence interval [CI], 96.0%-100%) compared with Tc-nanocolloid. Eight additional lymph nodes showed indocyanine green fluorescence but no Tc positivity, so that the positive predictive value was 91.9% (95% confidence interval, 84.6%-96.5%). In 1 patient, a false-negative sentinel missed by all 3 modalities was found. CONCLUSIONS: Our results show that indocyanine green is a promising approach for inguinal sentinel identification in vulvar cancer with a similar sensitivity as radioactive Tc-nanocolloid and worth to be evaluated in further studies.

Association between intraabdominal pressure during gynaecologic laparoscopy and postoperative pain.

PURPOSE: Laparoscopy is nowadays a well-established surgical method and plays a main role in an ever-increasing range of indications in gynaecology. High-quality studies of surgical techniques are necessary to improve the quality of patient care. The present study aims at evaluating postoperative pain after gynaecological laparoscopy depending on the intraoperative CO2 pressure. METHODS: In a prospective, monocentric, randomized single-blind study at the Department of Gynaecology and Obstetrics at the Hannover Medical School, we include patients scheduled for different laparoscopic procedures. Randomization of the intraoperative CO2 pressure was carried out in six groups. Pain was assessed the day after surgery by the blinded nurse using a visual analogue scale. RESULTS: 550 patients were included in the period from May 2013 to January 2016. The analysis of the per protocol population PPP (n = 360) showed no statistically significant difference between the six intervention groups with regard to mean postoperative pain perception. In direct comparison between two groups, an intraoperative CO2 pressure of 15 mmHg was associated with a significant higher pain score than a pressure of 12 mmHg. The difference was 7.46 mm on a 10 cm VAS. CONCLUSIONS: The results of our study indicate that a CO2 pressure of 12 versus 15 mmHg can be advantageous. However, the clinical relevance remains unclear due to the low difference in pain. The additional benefit of an even lower pressure of 10 or 8 mmHg cannot be reliably assessed; we found signs of poor visibility conditions in these low pressure groups.

Application of sentinel lymph node dissection in gynecological cancers: results of a survey among German hospitals.

PURPOSE: Evaluating the application of the sentinel lymph node dissection (SLND) in gynecological cancers among German hospitals. METHODS: Between March and June 2016 an online questionnaire on SLND in gynecologic cancers was sent by email to all German gynecologic cancer centers, all university hospitals and general hospitals for which an email address was available. The survey contained 61 questions regarding the SLND in vulvar, cervical, endometrial and ovarian cancer. RESULTS: In total, 63 clinics, including 13 (20.6%) university hospitals, 28 (44.4%) hospitals offering maximum care and 22 (34.9%) general hospitals, responded to the questionnaire. Most clinics (46/63, 73%) performed SLND in vulvar cancer with a median amount of 7.8 (range 1-43) SLND per year. 56.5% of the clinics included patients according to the German national guidelines and performed ultrastaging of negative SLN. Furthermore, 18/63 (28.5%) of the responding clinics applied SLND in cervical cancer including 7 (77.8%) centers which conducted isolated SLND without radical pelvic lymph node dissection (LND). Preoperative imaging with planar lymphoscintigraphy (LSG) was applied in 12/18 (66.7%) of the clinics. SLND in endometrial cancer was reported by 4/63 (6.4%) hospitals. Three of them (75%) regularly performed a subsequent radical pelvic LND. One clinic (1.5%) reported SLND in ovarian cancer in combination with radical LND. CONCLUSION: Especially in vulvar and cervical cancer, isolated SLND appears to be partially implemented in the routine surgical treatment. However, this survey illustrates a wide heterogeneity regarding inclusion criteria and application of the SLND approach.

Sensitization of immune cells following hexylaminolevulinate photodynamic therapy of cervical intraepithelial neoplasia.

BACKGROUND: Effects of photodynamic therapy (PDT) were tested with respect to immune cell stimulation in cervical intraepithelial neoplasia (CIN). METHODS: A patient with CIN received hexaminolevulinate (HAL) and subsequent PDT. These data were compared to a placebo PDT patient and a healthy HPV16-vaccinated donor. Isolation of peripheral blood mononuclear cells (PBMC) was performed before PDT and at 4 different time points after PDT. The proliferation of these PBMC was tested by [3H]thymidine incorporation following stimulation with control or HPV16-L1 peptides. Potential effects on the CD4+ and CD8+ cell subsets were analysed. RESULTS: The data revealed an unchanged or decreased proliferation of HPV16-L1 peptide-stimulated PBMC as compared to placebo patient. HPV16-L1 peptide incubation of PBMC from the HAL patient demonstrated significant proliferative capacity after PDT. The CD4+ and CD8+ T cell populations in placebo patient were slightly increased after HPV16-L1 peptide administration at each time point. Mixed results were obtained for CD4+ cells as compared to controls and nearly unchanged amounts of CD8+ cells were detectable following HPV16-L1 peptide exposure of PBMC from the HAL/PDT-treated patient. CONCLUSIONS: These findings suggest a T cell reaction from CIN patients during repeated HAL/PDT treatment. However, further immune cell populations might be involved during PDT.

Groin Recurrences in Node Negative Vulvar Cancer Patients After Sole Sentinel Lymph Node Dissection.

OBJECTIVE: This study aimed to evaluate the recurrence rates after sole sentinel dissection in vulvar cancer and describe characteristics of groin recurrences. METHODS: All vulvar cancer cases between 2008 and 2014 were reviewed. Inclusion criteria were restricted to lymph node-negative patients, sole sentinel lymph node dissection (SLND), and tumor diameter less than 4 cm. In all patients, Tc-99m nanocolloid was used for preoperative SLN imaging. Regularly, planar lymphoscintigraphy and single-photon emission computed tomography with computed tomography were performed. Ultrastaging was routinely conducted on all negative lymph nodes. RESULTS: Of 140 vulvar cancer cases, 30 node-negative patients underwent sole SLND and met inclusion criteria. Keratinizing squamous cell carcinoma was determined in final histology in 20/30 (66.7%) patients and the mainly diagnosed tumor stage was pT1b (21/30, 70%). Three perioperative complications occurred. On average, 4.6 (1-9) SLNs were dissected per patient and 2.5 (1-6) per each groin, respectively. During a median follow-up of 43.5 (4-75) months, 5/30 (16.7%; 95% confidence interval, 7.3%-33.6%) local recurrences occurred. In addition, 2/30 (6.6%; 95% confidence interval, 1.9%-21.3%) groin recurrences were identified within a period of 12 months after the primary surgery. Both patients had large (>2 cm) midline tumors. Despite surgical as well as adjuvant treatment of the recurrent disease, both patients with groin recurrences died. CONCLUSIONS: Sentinel lymph node dissection is a safe and feasible alternative in early vulvar cancer. But false-negative sentinel carry a high risk of mostly fatal groin recurrences. Especially, midline tumors larger than 2 cm have to be treated with caution, because they are mostly found in cases with groin recurrences after sole SLND.

Late radiation side effects, cosmetic outcomes and pain in breast cancer patients after breast-conserving surgery and three-dimensional conformal radiotherapy : Risk-modifying factors.

BACKGROUND AND PURPOSE: The purpose of this work was to identify parameters influencing the risk of late radiation side effects, fair or poor cosmetic outcomes (COs) and pain in breast cancer patients after breast-conserving therapy (BCT) and three-dimensional conformal radiotherapy (3D-CRT). PATIENTS AND METHODS: Between 2006 and 2013, 159 patients were treated at the Hannover Medical School. Physician-rated toxicity according to the LENT-SOMA criteria, CO and pain were assessed by multivariate analysis. RESULTS: LENT-SOMA grade 1-4 toxicity was observed as follows: fibrosis 10.7 %, telangiectasia 1.2 %, arm oedema 8.8 % and breast oedema 5.0 %. In addition, 15.1 % of patients reported moderate or severe breast pain, and 21.4 % complained about moderate or severe pain in the arm or shoulder. In multivariate analysis, axillary clearing (AC) was significantly associated with lymphoedema of the arm [odds ratio (OR) 4.37, p = 0.011, 95 % confidence interval (CI) 1.4-13.58]. Breast oedema was also highly associated with AC (OR 10.59, p = 0.004, 95 % CI 2.1-53.36), a ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C (OR 5.34, p = 0.029, 95 % CI 1.2-24.12). A ptosis grade 2/3 or pseudoptosis and a bra size ≥ cup C were the parameters significantly associated with an unfavourable CO (OR 3.19, p = 0.019, 95 % CI 1.2-8.4). Concerning chronic breast pain, we found a trend related to the prescribed radiation dose including boost (OR 1.077, p = 0.060, 95 % CI 0.997-1.164). Chronic shoulder or arm pain was statistically significantly associated with lymphoedema of the arm (OR 3.9, p = 0.027, 95 % CI 1.17-13.5). CONCLUSION: Chronic arm and breast oedema were significantly influenced by the extent of surgery (AC). Ptotic and large breasts were significantly associated with unfavourable COs and chronic breast oedema. Late toxicities exclusive breast pain were not associated with radiotherapy parameters.

Clinical presentation, treatment and outcome of vaginal intraepithelial neoplasia.

PURPOSE: To characterize the clinical presentation and outcome of patients with vaginal intraepithelial neoplasia (VAIN). METHODS: Medical records of 65 women with VAIN treated between 2005 and 2012 at the colposcopy clinic of a German university hospital were retrospectively evaluated for VAIN grade, HPV status, VAIN localization, treatment method and relapse rate. Follow-up data were available for 53 patients (82 %). RESULTS: Mean age was 61 years (range 32-89 years). Most lesions (55 %) were found in the upper vaginal third; 42 % were multifocal. Multifocal VAIN was more frequently HPV positive than single lesions (p = 0.059). Of all women with known HPV status, 83 % were high-risk (HR) HPV positive and 32 % had a simultaneous CIN earlier or at the same time as the VAIN, mostly CIN 3 (66 %). Two-thirds had a hysterectomy in the past, often because of high-grade CIN. Most cases of VAIN were treated with CO2 laser vaporization. A relapse of the disease could be confirmed for 57 %. HR-HPV positive VAIN was significantly more likely to relapse than HR-HPV negative VAIN (p = 0.005). There were three cases of vaginal cancer with surrounding VAIN 3 or vaginal cancer diagnosed after primary treatment of VAIN 3 and one case of vaginal cancer during follow-up 22 months after the first laser vaporization. All of these cases were HR-HPV positive. CONCLUSIONS: VAIN has a high relapse rate and a high progression rate to invasive cancer especially if HR-HPV positive. Therefore, adequate follow-up examinations are mandatory.

Dermoglandular rotation flaps for breast-conserving therapy: aesthetic results, patient satisfaction, and morbidity in comparison to standard segmentectomy.

We compared a dermoglandular rotation flap (DGR) in the upper inner, lower inner, and upper outer quadrant regarding similar aesthetic results, patient satisfaction, and comfort after breast-conserving therapy with standard segmentectomy (SE). Between 2003 and 2011, 69 patients were treated with breast-conserving surgery using DGR for cancers with high tumor-to-breast volume ratios or skin resection in the three above mentioned quadrants; 161 patients with tumors in the same quadrants were treated with SE. The outcome of the procedures was assessed at least 7 months after completed radiation therapy using a patient and breast surgeon questionnaire and the BCCT.core software. Symmetry, visibility of the scars, the position of the nipple-areola complex, and the appearance of the treated breast were each assessed on a scale from 1 to 4 by an expert panel and by the patients. Univariate and multivariate analysis were used to evaluate the relationship between patient-, tumor-, and treatment-dependent factors and patient satisfaction. 94.2% of the patients with rotation flaps and 83.5% of the patients with lumpectomy were very satisfied with the cosmetic appearance of their breast. Younger patient age was significantly associated with a lower degree of satisfaction. DGR provides good cosmetic results compared with SE and shows high patient satisfaction despite longer scarring and higher median resection volume.

Efficacy and safety of hexaminolevulinate photodynamic therapy in patients with low-grade cervical intraepithelial neoplasia.

OBJECTIVE: Non-surgical therapies are needed to reduce the rate of progression of low-grade cervical intraepithelial neoplasia (CIN 1) to high grade CIN (CIN 2/3). The aim of this study was to assess the efficacy and safety of hexaminolevulinate (HAL) photodynamic therapy (PDT) in the treatment of patients with CIN 1. STUDY DESIGN: This phase IIa prospective double-blind study randomized patients with CIN 1 into three groups: HAL vaginal suppository, placebo vaginal suppository or follow-up only. Patients in the first two groups received HAL or placebo suppositories 5 hours before illumination with 50 J/cm(2) red coherent light (633 nm) using a special light catheter. All patients had a follow up including colposcopy, cytology and human papilloma virus (HPV) testing 3 and 6 months and additional biopsy 6 months after PDT. The main outcome measure was efficacy, defined as complete histologic remission 6 months after PDT. Secondary outcomes were histologic remission 3 months and HPV eradication 6 months after first PDT. RESULTS: Seventy patients were randomized: 47 to HAL, 12 to placebo, 11 to follow up only. After 6 months CIN lesions had cleared in 57% of patients in the HAL-PDT group compared to 25% in the combined control group (per protocol population, P = 0.04). Twenty-six patients (37%) reported 44 adverse events (AEs), of which 40 were mild or moderate. Nineteen treatment-related AEs were reported by 15 patients (32%) in the HAL PDT group, one in the placebo PDT group (8%), and none in the follow-up group. The most common adverse events were local discomfort including mild pain/cramping (11) and leucorrhoea (2). CONCLUSION: HAL PDT shows a favorable efficacy and safety profile and represents a promising alternative to observation and surgical procedures in patients with CIN 1.

Detection of E6-AP as a potential therapeutic target in cervical specimen of HPV-infected women.

PURPOSE: Silencing of HPV oncogenes or their human host client proteins using topically applied small interfering RNA (siRNA) may be an attractive nonsurgical strategy for CIN treatment. An exploratory clinical investigation was designed to evaluate E6-AP mRNA expression levels in different stages of cervical intraepithelial neoplasia and during the menstrual cycle. METHODS: In 38 premenopausal women aged 18-45 years referred to colposcopy clinic, analysis of serum hormones, cervical smears for cytology and HPV DNA, cervical biopsy, p16 immunohistochemistry and E6-AP mRNA expression levels in cervical smears and biopsies were performed. The intra-subject variability in E6-AP mRNA expression of vaginal smears was assessed and compared to cervical biopsy specimens. RESULTS: RNA of sufficient quantity and quality was available for E6-AP expression analysis from 97 % of the collected cervical smears and from 56 % of the collected biopsy samples. The normalized RNA levels from cervical smears were approximately tenfold higher compared to biopsies. There was little influence by the phase of the menstrual cycle or by CIN stage. Real-time PCR showed that the expression level of E6-AP is in a range (<28 C t) that would allow for detection of at least 100-fold modulation by a therapeutic agent (based on an assay LOD of C t = 36). CONCLUSIONS: Our findings suggest a potential therapeutic approach using E6-AP siRNA as a specific molecular target in cervical intraepithelial neoplasia.

Diagnostic performance and inter-observer concordance in lesion detection with the automated breast volume scanner (ABVS).

BACKGROUND: Automated whole breast ultrasound scanners of the latest generation have reached a level of comfortable application and high quality volume acquisition. Nevertheless, there is a lack of data concerning this technology. We investigated the diagnostic performance and inter-observer concordance of the Automated Breast Volume Scanner (ABVS) ACUSON S2000™ and questioned its implications in breast cancer diagnostics. METHODS: We collected 100 volume data sets and created a database containing 52 scans with no detectable lesions in conventional ultrasound (BI-RADS®-US 1), 30 scans with benign lesions (BI-RADS®-US 2) and 18 scans with breast cancer (BI-RADS®-US 5).Two independent examiners evaluated the ABVS data on a separate workstation without any prior knowledge of the patients' histories. RESULTS: The inter-rater reliability reached fair agreement (κ=0.36; 95% confidence interval (CI): 0.19-0.53). With respect to the true category, the conditional inter-rater validity coefficient was κ=0.18 (95% CI: 0.00-0.26) for the benign cases and κ=0.80 (95% CI: 0.61-1.00) for the malignant cases.Combining the assessments of examiner 1 and examiner 2, the diagnostic accuracy (AC), sensitivity (SE) and specificity (SP) for the experimental ABVS were AC = 79.0% (95% CI: 67.3-86.1), SE = 83.3% (95% CI: 57.7-95.6) and SP = 78.1% (% CI: 67.3-86.1), respectively.However, after the ABVS examination, there were a high number of requests for second-look ultrasounds in up to 48.8% of the healthy women due to assumed suspicious findings in the volume data.In an exploratory analysis, we estimated that an ABVS examination in addition to mammography alone could detect a relevant number of previously occult breast cancers (about 1 cancer in 300 screened and otherwise healthy women). CONCLUSIONS: The ABVS is a reliable imaging method for the evaluation of the breast with high sensitivity and a fair inter-observer concordance. However, we have to overcome the problem of the high number of false-positive results. Therefore, further prospective studies in larger collectives are necessary to define standard procedures in image acquisition and interpretation. Nevertheless, we consider the ABVS as being suitable for integration into breast diagnostics as a beneficial and reliable imaging method.

Is there a place for sentinel technique in treatment of vaginal cancer?: feasibility, clinical experience, and results.

OBJECTIVE: To evaluate the clinical feasibility of sentinel lymph node (SLN) technique and the role of single-photon emission computed tomography with CT (SPECT/CT) compared to lymphoscintigraphy for detection of SLN in vaginal cancer. METHODS: The study was performed in a prospective, unicentric setting. Patients with vaginal carcinoma were scheduled for surgery and SLN labeling by peritumoral injection of 10-MBq technetium Tc 99m nanocolloid and patent blue. After 30 minutes, lymphoscintigraphy and SPECT/CT were carried out. We evaluated the number of SLNs in lymphoscintigraphy, SPECT/CT, and intraoperative histology of SLN and non-SLN as well as the impact of these results to therapeutic approach. RESULTS: Between January 2009 and December 2012, the SLN technique was used for 7 of 11 patients treated due to vaginal cancer. Detection rate was 100% (7/7). Lymphoscintigraphy and SPECT/CT showed at least one SLN in each patient. Lymphoscintigraphy detected 2.6 SLNs (range, 2-4 SLNs) per patient compared to 4.3 SLNs (range, 2-8 SLNs) in SPECT/CT (P = 0.053). Sentinel lymph nodes were detected in all patients during surgery with a mean number of 4.3 (range, 1-5). Pelvic SLNs were detected in all 6 patients with infiltration of middle or proximal vaginal third (100%). If the distal vaginal third was additional (3/7 patients) or exclusively (1/7 patients) infiltrated, the inguinal SLN detection rate was 33% and 100%, respectively. All patients with nodal metastases had at least one SLN positive for tumor. There were no false negatives. In 2 (29%) of 7 patients, treatment approach was modified owing to affected SLN. CONCLUSION: The SLN technique was favorably used in vaginal cancer in this series. It assists in identifying an inguinal and/or pelvic lymphatic drainage. When performed accurately (technetium Tc 99m nanocolloid, lymphoscintigraphy and/or SPECT/CT, blue dye), this technique predicts regional nodal status. This allows tumor stage-adjusted therapy. Single photon emission computed tomography/CT improves preoperative planning and facilitates detection, thus enhancing the clinical value of the SLN technique and improving the oncologic safety of surgery.

Evaluation of a multiplex real time PCR assay for the detection of human papillomavirus infections on self-collected cervicovaginal lavage samples.

Self-collection of cervical samples for human papillomavirus (HPV) testing can help to raise the participation rate in cervical cancer screening among non-responders. This study was conducted to compare the analytical and clinical performance of the Abbott RealTime High-Risk HPV Test (RealTime) with the Hybrid Capture 2 assay (HC2) on self-collected cervicovaginal lavage samples. One hundred samples from women referred for colposcopy (reference smears and biopsies in case of abnormalities) were included. Fifty-seven women had a normal cytology, 27 had low grade and 16 had high grade squamous intraepithelial lesions. Fourteen of 49 biopsies (28.6%) were benign, 14 (28.6%) cervical intraepithelial neoplasia 1, 11 (22.4%) cervical intraepithelial neoplasia 2, 8 (16.3%) cervical intraepithelial neoplasia 3 and 2 (4.1%) invasive cancer. The agreement between RealTime and HC2 in the self-collected and in the reference samples was 85% (κ=0.665) and 83% (κ=0.620), respectively. The agreement between self-sampling and the reference smears was higher with RealTime (93%; κ=0.849) than with HC2 (89%; κ=0.741). In the self-collected samples, the sensitivity and specificity for cervical intraepithelial neoplasia 2 or worse of RealTime/HC2 were 81.0%/66.7% (p=0.25) and 53.6%/57.1%, respectively. The sensitivity for cervical intraepithelial neoplasia 3 or worse of RealTime and HC2 were 80.0% and 70.0% (p=1.0). The specificity for cervical intraepithelial neoplasia 3 or worse was 43.6% (RealTime) and 51.3% (HC2). This study shows that RealTime can be used for HR-HPV testing of self-collected lavage samples in a referral population with at least equal quality and performance as HC2.

Ultrasound real-time elastography can predict malignancy in BI-RADS®-US 3 lesions.

BACKGROUND: Lesions of the breast that are classified BI-RADS®-US 3 by ultrasound are probably benign and observation is recommended, although malignancy may occasionally occur. In our study, we focus exclusively on BI-RADS®-US 3 lesions and hypothesize that sonoelastography as an adjunct to conventional ultrasound can identify a high-risk-group and a low-risk-group within these patients. METHODS: A group of 177 breast lesions that were classified BI-RADS®-US 3 were additionally examined with real-time sonoelastography. Elastograms were evaluated according to the Tsukuba Elasticity Score. Pretest and posttest probability of disease (POD), sensitivity (SE), specificity (SP), positive (PPV) and negative predictive values (NPV) and likelihood-ratios (LR) were calculated. Furthermore, we analyzed the false-negative and false-positive cases and performed a model calculation to determine how elastography could affect the proceedings in population screening. RESULTS: In our collection of BI-RADS®-US 3 cases there were 169 benign and eight malignant lesions. The pretest POD was 4.5% (95% confidence interval (CI): 2.1-9.0). In patients with a suspicious elastogram (high-risk group), the posttest POD was significantly higher (13.2%, p = 0.041) and the positive LR was 3.2 (95% CI: 1.7-5.9). With a benign elastogram (low-risk group), the posttest POD decreased to 2.2%. SE, SP, PPV and NPV for sonoelastography in BI-RADS®-US 3 lesions were 62.5% (95% CI: 25.9-89.8), 80.5% (95% CI: 73.5-86.0), 13.2% (95% CI: 5.0-28.9) and 97.8% (95% CI: 93.3-99.4), respectively. CONCLUSIONS: Sonoelastography yields additional diagnostic information in the evaluation of BI-RADS®-US 3 lesions of the breast. The examiner can identify a low-risk group that can be vigilantly observed and a high-risk group that should receive immediate biopsy due to an elevated breast cancer risk.

Chest wall resection and reconstruction for locally advanced primary breast cancer.

OBJECTIVE: We sought to evaluate clinical and oncologic outcomes of selected patients with locally advanced breast cancer undergoing full thickness chest wall resection (FTCWR) and reconstruction in a multidisciplinary setting. PATIENTS AND METHODS: Between 2008 and 2010, five women underwent FTCWR followed by chest wall repair for locally advanced primary breast cancer. In all cases, chest wall repair was performed with a Peri-Guard Repair Patch (Synovis, St. Paul, MN, USA). At follow-up (7-12 months) quality of life, respiratory function and oncologic status were assessed. RESULTS: Successful chest wall resection and repair were achieved in all patients. Plastic reconstruction of post-mastectomy tissue defects was necessary in one case. One patient was treated by breast conserving therapy. Chest ultrasound imaging confirmed absence of adhesions, haematoma or seroma and normal expansion and respiratory movement of the underlying lung in all patients. On follow-up all patients reported good quality of life. CONCLUSION: Multidisciplinary surgical approaches to chest wall resection and reconstruction in selected patients with locally advanced primary breast cancer are feasible, safe, associated with short operation time and hospital stay and negligible morbidity.