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Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg(-1) body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm(-1) diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg(-1) body weight and an optical dose of 900 J cm(-1) diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose-response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg(-1) and 11 mm using 3 mg kg(-1) photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm(-1) diffuser-length for 30 mg kg(-1) and between 300 and 500 J cm(-1) for 3 mg kg(-1) PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg(-1) photosensitizer was activated with optical doses of 700 J cm(-1) or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 +/- 4.5 days compared to 38.4 +/- 3.8 days and 40.0 +/- 3.6 days for rats treated with 3 mg kg(-1) or 9 mg kg(-1) PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively.

Optical measurements of the cervical transformation zone (sometimes referred to as the transition zone) using elastic-scattering spectroscopy, demonstrate sensitivity to the epithelial cell-type differences. ©2004 Copyright SPIE - The International Society for Optical Engineering.

OBJECTIVE:Our purpose was twofold: to determine the distribution of the endogenous photosensitizer protoporphyrin IX in the uterus and to ascertain the time interval leading to maximal endometrial fluorescence after intrauterine instillation of 5-aminolevulinic acid. STUDY DESIGN:One milliliter of a 400 mg/ml 5-aminolevulinic acid-Hyskon solution was instilled into the uterine cavity of 27 women before hysterectomy. On frozen sections of uterine samples 5-aminolevulinic acid-induced fluorescence was measured with fluorescence microscopy. RESULTS:5-Aminolevulinic acid-induced fluorescence could first be detected in the superficial endometrial glands 75 minutes after drug injection. In the endometrial gland stumps fluorescence intensity peaked 4 to 8 hours after 5-aminolevulinic acid instillation and was > 48 times higher than in the underlying myometrium. CONCLUSIONS:Fluorescence in the endometrial glands suggests that selective photodynamic destruction of the endometrium may be possible 4 to 8 hours after intrauterine 5-aminolevulinic acid instillation.

ObjectiveOur purpose was to determine the optical dose required for irreversible endometrial destruction and prevention of implantation by photodynamic therapy with topical 5-aminolevulinic acid.Study designThree hours after drug application 74 female Sprague-Dawley rats received varying doses of 630 nm of light delivered by an intrauterine cylindric diffusing fiber.ResultsA 64 J/cm2 in situ optical dose resulted in long-term irreversible endometrial destruction; 43 J/cm2 damaged endometrial stroma and myometrium but not glandular epithelium 1 day after photodynamic therapy. At this lower light dose endometrium regenerated to full thickness within 3 weeks; however, implantation sacs were significantly reduced.ConclusionsPhotodynamic destruction of glandular epithelium accompanies irreversible endometrial ablation, whereas isolated stromal damage leads to reproductive impairment only. The optical dose required for endometrial ablation is approximately 1.5-fold higher than for reproductive impairment (functional damage) because of differential cell photosensitivity.

ObjectiveOur purpose was to determine the feasibility of selective photosensitization of vulvar condylomas by use of tropical application of 5-aminolevulinic acid.Study designIn vivo fluorescence was assessed and biopsy specimens of condylomas were taken for fluorescence microscopy in 24 patients at different times after application of 2.5% 5-aminolevulinic acid ointment or 20% 5-aminolevulinic acid cream.ResultsBoth in vivo fluorescence imaging and fluorescence microscopy showed selective fluorescence of condylomas of the labia minora and vestibule only within short time intervals, because fluorescence of poorly keratinized normal epithelium was induced by both 5-aminolevulinic acid formulations. In non-hair-bearing skin, lesional fluorescence remained highly selective. Fluorescence microscopy showed that 90 minutes after drug application peak selectivity in epithelial lesional fluorescence was significantly higher with 2.5% 5-aminolevulinic acid ointment (4.5 +/- 0.9) than it was with 20% cream (2.1 +/- 0.2).ConclusionSelective fluorescence of vulvar condyloma acuminatum can be induced by nonselective topical 5-aminolevulinic acid application. Studies evaluating selective photodynamic destruction of condylomas are justified.

We are involved in the development of photodynamic therapy (PDT) as a minimally invasive method for treating dysfunctional uterine bleeding, one of the primary clinical indications for hysterectomy. In this paper, we analyse light propagation through the uterus in order to specify the requirements for a light delivery system capable of effectively performing endometrial PDT. Our approach involves developing an analytical model based on diffusion theory to predict optical fluence rate distributions when cylindrical and spherical optical applicators are placed in the uterine cavity. We apply the results of our model calculations to estimate the thermal effects of optical irradiation and the effective photodynamic optical dose. Theoretical fluence rate calculations are compared to fluence rate measurements made in fresh, surgically removed human uteri. Our results show that a trifurcated cylindrical optical applicator inserted into the human uterus can provide a light dose that is sufficient to cause photodynamic destruction of the entire endometrium. When the optical power per unit length of each cylindrical applicator is 100 mW cm-1 (at 630 nm), a fluence rate of 40 mW cm-2 is delivered to the boundary layer between the endometrium and the myometrium (a depth of about 4-6 mm). The optical fluence delivered to the boundary layer after 20 min of exposure is 50 J cm-2, a level that is generally accepted to cause tissue damage throughout the endometrium in most patients.

The purpose of this study was to determine the optical dose needed for both lasting endometrial destruction and prevention of implantation by photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) as a photosensitizer. Three hours after topical drug administration 74 female Sprague-Dawley received varying optical doses of 630 nm light delivered by an intrauterine cylindrical light diffusing fiber. Histologic evaluation of the endometrium 1 and 21 days after PDT as well as the number of implantation sacs after mating were assessed. Irreversible endometrial destruction was determined measuring the thickness of the endometrial layer 3 weeks after treatment. An in situ dose of 64 J/cm 2 was required to eradicate endometrial glands and prevent regeneration. In contrast, a 43 J/cm 2 in situ dose visibly damaged the endometrial stroma and myometrium but the endometrial glands survived and the endometrium regenerated to its full thickness within 21 days. However, implantation potential was significantly reduced at these low light levels. Due to differential cell photosensitivity, the optical threshold for lasting endometrial destruction is higher than for functional damage. For lasting endometrial destruction the endometrial glands must be destroyed, whereas for reproductive impairment, damage to the endometrial stroma seems to be sufficient.

Hysterectomy is the most common major operation performed in the USA with dysfunctional uterine bleeding as one of the major indications. The clinical needs for simple and safe endometrial destruction are essential. Photodynamic therapy (PDT) may offer a simple and cost effective solution for the treatment of dysfunctional uterine bleeding. The dosimetry is discussed for the case of topical application of photosensitizer. This technique might be the method of preference because undesired side effects such as skin photosensitization that is typical for systemically injected photosensitizers, can be avoided. Effective PDT requires a sufficient amount of light delivered to the targeted tissue in a reasonable period of time. A trifurcated optical applicator consisting of three cylindrical diffusing fibers has been constructed, and this applicator can deliver a typical required optical dose of about 50-100 J/cm 2 to the full depth of the endometrium for an exposure time of 10-20 minutes.

BACKGROUND: For patients wishing to preserve fertility conization is regarded as an adequate treatment in cervical cancer stage IA1 without lymphovascular space involvement (LVSI). Reviewing case series with IA1 cervical cancers without LVSI, lymph node metastasis (LNM) is present in 0.5%. MATERIALS AND METHODS: We pr esent a case of a 34-year-old patient treated with conization for squamous cervical cancer invading 1.2 mm without LVSI and horizontal extension of 6 mm (IA1). RESULTS: At a routine postpartum examination after an uneventful pregnancy, a 5-cm pelvic mass was noted at the right pelvic wall. Intraoperative evaluation revealed a LNM which was resected, and postoperative pelvic chemoradiotherapy was performed. The patient remains recurrence-free 84 months after conization and 73 months after resection of the recurrence. CONCLUSIONS: Occurrence of LNM in IA1 cervical cancers is very rare, but if early diagnosed curative treatment is possible. [ABSTRACT FROM AUTHOR]

We investigated whether developing an autoimmune disorder (AID) following a high-grade epithelial ovarian cancer diagnosis improves overall survival. This retrospective study included data from women treated for high-grade serous, endometrioid, or transitional cell ovarian, fallopian tube, or peritoneal cancer FIGO stage III or IV at a Swiss cantonal gynecological cancer center (2008-2023). We used Kaplan-Meier estimates and the Cox proportional hazards model using time-varying covariates for the survival function estimation. In all, 9 of 128 patients developed an AID following a cancer diagnosis. The median time from cancer diagnosis to AID was 2 years (IQR 2-5). These women survived for a median of 3031 days (IQR 1765-3963) versus 972 days (IQR 568-1819) for those who did not develop an AID ( p = 0.001). The median overall survival of nine women with a pre-existing AID was 1093 days (IQR 716-1705), similar to those who never had an AID. The multivariate analyses showed older age ( p = 0.003, HR 1.04, 95% CI 1.013-1.064) was associated with a poorer prognosis, and developing an AID after a cancer diagnosis was associated with longer survival ( p = 0.033, HR 0.113, 95% CI 0.015-0.837). Clinical manifestations of autoimmune disorders following ovarian cancer diagnoses were associated with better overall survival (8 versus 2.7 years), indicating an overactive immune response may improve cancer control.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown., Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node., Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis., Exposure: Omission of ALND after SLNB or TAD., Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed., Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55)., Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown., Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after neoadjuvant chemotherapy (NACT)., Design, Setting, and Participants: This was a prospective, observational, cohort study conducted from August 2018 to June 2022. This was a preplanned study within the phase 3 randomized clinical OPBC-03/TAXIS trial. Included were patients with confirmed cN-positive BC from 44 private, public, and academic breast centers in 6 European countries. After NACT, residual nodal disease was mandatory, and a minimum follow-up of 2 months was required., Exposures: All patients underwent tailored axillary surgery (TAS) followed by ALND or axillary radiotherapy (ART) according to TAXIS randomization. TAS removed suspicious palpable and sentinel nodes, whereas imaging-guidance was optional. Systemic therapy recommendations were at the discretion of the local investigators., Results: A total of 500 patients (median [IQR] age, 57 [48-69] years; 487 female [97.4%]) were included in the study. In the upfront surgery setting, 296 of 335 patients (88.4%) had hormone receptor (HR)-positive and Erb-B2 receptor tyrosine kinase 2 (ERBB2; formerly HER2 or HER2/neu)-negative disease: 145 (49.0%) underwent ART, and 151 (51.0%) underwent ALND. The median (IQR) number of removed positive lymph nodes without ALND was 3 (1-4) nodes compared with 4 (2-9) nodes with ALND. There was no association of ALND with the proportion of patients undergoing adjuvant chemotherapy (81 of 145 [55.9%] vs 91 of 151 [60.3%]; adjusted odds ratio [aOR], 0.72; 95% CI, 0.19-2.67) and type of systemic therapy. Of 151 patients with NACT, 74 (51.0%) underwent ART, and 77 (49.0%) underwent ALND. The ratio of removed to positive nodes was a median (IQR) of 4 (3-7) nodes to 2 (1-3) nodes and 15 (12-19) nodes to 2 (1-5) nodes in the ART and ALND groups, respectively. There was no observed association of ALND with the proportion of patients undergoing postneoadjuvant systemic therapy (57 of 74 [77.0%] vs 55 of 77 [71.4%]; aOR, 0.86; 95% CI, 0.43-1.70), type of postneoadjuvant chemotherapy (eg, capecitabine: 10 of 74 [13.5%] vs 10 of 77 [13.0%]; trastuzumab emtansine-DM1: 9 of 74 [12.2%] vs 11 of 77 [14.3%]), or endocrine therapy (eg, aromatase inhibitors: 41 of 74 [55.4%] vs 36 of 77 [46.8%]; tamoxifen: 8 of 74 [10.8%] vs 6 of 77 [7.8%])., Conclusion: Results of this cohort study suggest that patients without ALND were significantly understaged. However, ALND did not inform systemic therapy recommendations.

Purpose: The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe., Methods: The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the first 500 randomized patients with confirmed nodal disease at the time of surgery. The TAXIS study's pragmatic design allowed both the neoadjuvant and adjuvant setting according to the preferences of the local investigators who were encouraged to register eligible patients consecutively., Results: A total of 500 patients were included at 44 breast centers in six European countries from August 2018 to June 2022, 165 (33%) of whom underwent NST. Median age was 57 years (interquartile range [IQR], 48-69). Most patients were postmenopausal (68.4%) with grade 2 and 3 hormonal receptor-positive and human epidermal growth factor receptor 2-negative breast cancer with a median tumor size of 28 mm (IQR 20-40). The use of NST varied significantly across the countries (p < 0.001). Austria (55.2%) and Switzerland (35.8%) had the highest percentage of patients undergoing NST and Hungary (18.2%) the lowest. The administration of NST increased significantly over the years (OR 1.42; p < 0.001) and more than doubled from 20 to 46.7% between 2018 and 2022., Conclusion: Substantial heterogeneity in the use of NST with HR+/HER2-breast cancer exists in Europe. While stringent guidelines are available for its use in triple-negative and HER2+ breast cancer, there is a need for the development of and adherence to well-defined recommendations for HR+/HER2-breast cancer., (© 2023. The Author(s).)

Aim: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS., Methods: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load., Results: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%., Conclusions: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND., Competing Interests: Declaration of interest statement Outside the submitted work, W.P. Weber received research support from Takeda Pharmaceuticals International paid to the Swiss Group for Clinical Cancer Research (SAKK) and personal honoraria from Genomic Health, Inc., USA. Support for meetings was paid to his institution from Sandoz, Genomic Health, Medtronic, Novartis Oncology, Pfizer and Eli Lilly. Hisham Fansa has no financial interest, and receives royalty payments from Springer-Nature publishers for two textbooks on breast surgery. Florian Fitzal was editor of Oncoplastic Surgery part I and II (SPRINGER), received travel support and scientific support from COMESA (Mentor), NOVARTIS, ROCHE, ASTRA ZENECA, PFIZER, MYRIAD, NANOSTRING, BONDIMED (Polytech, Integra), Lilly, had an advisory role for PFIZER, ASTRA ZENECA, LILLY, ROCHE, and was founder of BREAST ANALYZING TOOL (BAT; breastanalyzing.com). All other authors declare no competing interests relevant to this manuscript., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The emphasis on aesthetic outcomes and quality of life (QoL) has motivated surgeons to develop skin-sparing or nipple-sparing mastectomy (SSM/ NSM) for breast cancer treatment or prevention. During the same operation, a so-called immediate breast reconstruction is performed. The breast can be reconstructed by positioning of a breast implant above (prepectoral) or below (subpectoral) the pectoralis major muscle or by using the patients' own tissue (autologous reconstruction). The optimal positioning of the implant prepectoral or subpectoral is currently not clear. Subpectoral implant-based breast reconstruction (IBBR) is still standard care in many countries, but prepectoral IBBR is increasingly performed. This heterogeneity in breast reconstruction practice is calling for randomised clinical trials (RCTs) to guide treatment decisions., Methods and Analysis: International, pragmatic, multicentre, randomised, superiority trial. The primary objective of this trial is to test whether prepectoral IBBR provides better QoL with respect to long-term (24 months) physical well-being (chest) compared with subpectoral IBBR for patients undergoing SSM or NSM for prevention or treatment of breast cancer. Secondary objectives will compare prepectoral versus subpectoral IBBR in terms of safety, QoL and patient satisfaction, aesthetic outcomes and burden on patients. Total number of patients to be included: 372 (186 per arm)., Ethics and Dissemination: This study will be conducted in compliance with the Declaration of Helsinki. Ethical approval has been obtained for the lead investigator's site by the Ethics Committee 'Ethikkommission Nordwest- und Zentralschweiz' (2020-00256, 26 March 2020). The results of this study will be published in a peer-reviewed medical journal, independent of the results, following the Consolidated Standards of Reporting Trials standards for RCTs and good publication practice. Metadata describing the type, size and content of the datasets will be shared along with the study protocol and case report forms on public repositories adhering to the FAIR (Findability, Accessibility, Interoperability, and Reuse) principles., Trial Registration Number: NCT04293146., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Previous studies using botulinum toxin type A (BT) to treat provoked vestibulodynia (PVD) reported conflicting findings, possibly attributable to singular injections or low doses. We assessed PVD treatment effectiveness with high-dose single injections of BT (50 or 100 units) versus placebo, and then repeat BT 100 U injections over 6 months., Methods: This was a randomized, double-blind, three-arm, placebo-controlled study with 33 PVD patients. BT 50 U (arm A), 100 U (arm B) or saline (arm C) were injected subcutaneously into the dorsal vulvar vestibulum and pain was assessed after 3 months. The investigation proceeded as an unblinded exploratory analysis, in which symptomatic patients received a BT 100 U injection. Symptomatic patients in arm C received a second BT 100 U injection at the 6-month visit. Symptoms were measured at 3-month cycles using: (1) cotton swab-provoked visual analogue scale (VAS), (2) von Frey filaments, and (3) Marinoff dyspareunia scale., Results: The three groups were comparable in terms of demographics and baseline clinical characteristics. Three months after the initial injection, no significant differences in pain were observed among the study arms, yet significant improvements occurred within all groups using the von Frey filaments test. Results from the exploratory analyses showed repeat injections of 100 U BT over 6 months led to significant pain reduction (VAS and von Frey filaments). Fifty-eight percent (7/12) of patients assessable after repeat injections were symptom-free or had ≥ 2 VAS reduction. Adverse events were minor and no serious adverse events occurred during the RCT or exploratory analysis., Conclusions: PVD symptoms after one subcutaneous injection of BT (50 or 100 units) did not significantly differ compared to placebo, yet all three study arms experienced a reduction in pain 3 months after a single injection. Exploratory analyses indicated that repeat high-dose BT injections may significantly reduce pain over 6 months., Trial Registration: This trial was registered with the Swiss Medical Agency (reference number: 2007DR2102) in 2007.

Introduction The study's objectives were to determine the success rate following radiofrequency endometrial ablation to treat abnormal menstrual bleeding and to assess risk factors for failure of the method. Materials and Methods 195 women who were treated with bipolar radiofrequency endometrial ablation between 01/2009 and 06/2016 were included in this prospective cohort study. Postoperative data from 187 women were collected at a median of 17.5 months (IQR 4.5-34.9; 1-82). Multivariate analyses of risk factors were performed. Success was defined as amenorrhoea or spotting. Results Patient characteristics were as follows: mean age 44 years (SD ± 5), median parity 2 (IQR 2-3), median hysterometer 8.7 cm (SD ± 1.1), and median BMI 23.5 kg/m 2 (IQR 21-27). 30 patients (19.5%) had intramural masses that could be measured with ultrasound. Postoperative success rate was 86.1%. 10 patients (5%) had a hysterectomy postoperatively - 6 for heavy bleeding, 3 due to prolapse, and 1 due to dysmenorrhoea. Multivariate analyses showed the presence of intramural masses in women < 45 years was a significant risk factor for therapeutic failure (p = 0.033; 95% CI 1.08-12.57), with an increased risk of hysterectomy (OR 7.9, 95% CI 1.2-52.7, p = 0.033). Conclusion Bipolar radio frequency endometrial ablation was highly successful in the absence of an intramural mass (88%). Even smaller intramural fibroids (DD: adenomyomas of a median of 15 mm) reduce the success rate (76%), which is why preoperative ultrasound is recommended. In the presence of intramural masses, the risk of a hysterectomy for women < 45 years increases eightfold.

Purpose: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion., Methods: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology., Results: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference., Conclusions: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.

Background: Several studies and a meta-analysis showed that fibrin sealant patches reduced lymphatic drainage after various lymphadenectomy procedures. Our goal was to investigate the impact of these patches on drainage after axillary dissection for breast cancer., Methods: In a phase III superiority trial, we randomized patients undergoing breast-conserving surgery at 14 Swiss sites to receive versus not receive three large TachoSil ® patches in the dissected axilla. Axillary drains were inserted in all patients. Patients and investigators assessing outcomes were blinded to group assignment. The primary endpoint was total volume of drainage., Results: Between March 2015 and December 2016, 142 patients were randomized (72 with TachoSil ® and 70 without). Mean total volume of drainage in the control group was 703 ml [95% confidence interval (CI) 512-895 ml]. Application of TachoSil ® did not significantly reduce the total volume of axillary drainage [mean difference (MD) -110 ml, 95% CI -316 to 94, p = 0.30]. A total of eight secondary endpoints related to drainage, morbidity, and quality of life were not improved by use of TachoSil ® . The mean total cost per patient did not differ significantly between the groups [34,253 Swiss Francs (95% CI 32,625-35,880) with TachoSil ® and 33,365 Swiss Francs (95% CI 31,771-34,961) without, p = 0.584]. In the TachoSil ® group, length of stay was longer (MD 1 day, 95% CI 0.3-1.7, p = 0.009), and improvement of pain was faster, although the latter difference was not significant [2 days (95% CI 1-4) vs. 5.5 days (95% CI 2-11); p = 0.2]., Conclusions: TachoSil ® reduced drainage after axillary dissection for breast cancer neither significantly nor relevantly.

Aims: Intrinsic sphincter deficiency (ISD) is a known risk factor for therapy failure after tension-free vaginal tape (TVT) insertion. The purpose of this study was to investigate if the severity of ISD alone or other factors such as urethral mobility and tape localization influence outcomes., Methods: One hundred and nine women with urodynamically determined ISD, a TVT insertion, and a 6-month follow-up visit were included. Urethral length, mobility, and tape localization were evaluated by pelvic floor sonography. Patients were classified into three urethral mobility groups (hypomobile, normomobile, hypermobile). Surgical outcome was assessed by a combination of objective and subjective criteria., Results: Therapeutic success rate after TVT insertion was 81.6%. The severity of ISD did not associate with therapy failure. But urethral mobility (P < 0.0001), relative tape position (P = 0.0003), and tape-urethra distance (P < 0.0001) differed between cured and not cured patient groups. Patients with a relative tape position toward 1/2 of urethral length had a higher cure rate. Significantly different cure rates (P = 0.0003) were found for hypomobile (67%), normomobile (76%), and hypermobile (100%) urethras. For ISD patients with a hypomobile urethra, highest cure rates were obtained for tape-urethra distances between 2.5 and 3.5 mm., Conclusions: The reduced cure rate for ISD patients was due to the subgroup with a hypomobile urethra. A prospective study is needed to confirm that slightly shorter tape-urethra distances and a relative tape position more toward the mid-urethra will lead to better outcomes for this patient group., (© 2017 Wiley Periodicals, Inc.)

Purpose: To identify risk factors for emergency caesarean section in women attempting a vaginal breech delivery at term., Methods: Data from 1092 breech deliveries performed between 1998 and 2013 at a Swiss cantonal hospital were extracted from an electronic database. Of the 866 women with a singleton, full term pregnancy, 464 planned a vaginal breech delivery. Fifty-seven percent (265/464) were successful in delivering vaginally. Multivariate regression analyses of risk factors were performed, and neonatal and maternal complications were compared., Results: Risk factors for failed vaginal delivery were peridural anaesthesia (OR 2.05; 95 % CI 1.09-3.84; p = 0.025), nulliparity (OR 2.82; 95 % CI 1.87-4.25; p < 0.001), high birth weight (OR 1.17; 95 % CI 1.04-1.30; p = 0.006) and induction of labour (OR 1.56; 95 % CI 1.003-2.44; p = 0.048). Maternal age, height and weight; gestational age; or newborn length and head circumference were not associated with an unplanned caesarean section. The rate of successful vaginal delivery in the low risk sub-group (multiparous women without induction of labour) was 58-83 %, depending on birth weight category. The likelihood of success for the high risk sub-group (nulliparous women with induction of labour) fell below a third at neonatal birth weights >3250 g. Complication rates were low in the cohort., Conclusions: Use of peridural anaesthesia, nulliparity, high birth weight and induction of labour were risk factors for unsuccessful vaginal breech delivery requiring an unplanned caesarean section. Awareness of these risk factors is useful when counselling women who are considering a vaginal breech delivery.

Purpose: Pain is the key symptom that distinguishes bladder pain syndrome/interstitial cystitis from overactive bladder syndrome but overlap occurs. To find a discriminating marker for these bladder diseases we examined sensory hyperinnervation and neurotrophin receptor expression in bladder biopsies as well as nerve growth factor levels in urine., Materials and Methods: Bladder biopsies from patients with bladder pain syndrome/interstitial cystitis, including 12 with and 19 without Hunner lesions, 13 with overactive bladder syndrome and 12 healthy controls, were analyzed by immunohistochemistry with antibodies to the nerve cell marker PGP9.5 (neuron-specific protein gene product 9.5), p75 NTR (p75 neurotrophin receptor), the B-lymphocyte marker CD20 and mast cell tryptase. Urinary nerve growth factor was quantified by enzyme-linked immunosorbent assay., Results: Subepithelial sensory hyperinnervation on PGP9.5 staining had 97% sensitivity and 76% specificity, increased lymphocytic infiltration had 90% sensitivity and 80% specificity, and urothelial defects had 97% sensitivity and 76% specificity to distinguish bladder pain syndrome/interstitial cystitis with and without Hunner lesions from overactive bladder syndrome and healthy controls. Increased sensory innervation was associated with submucosal mast cell localization. Staining of p75 NTR in basal urothelial cells was indicative of bladder pain syndrome/interstitial cystitis. Urinary nerve growth factor levels were below the detection level and did not differentiate bladder diseases from healthy controls., Conclusions: Sensory hyperinnervation and basal urothelial p75 NTR staining together with assessment of inflammatory lymphocytes and urothelial integrity allow for the differentiation of bladder pain syndrome/interstitial cystitis and overactive bladder syndrome even in the absence of Hunner lesions. Furthermore, these histopathological criteria enable the identification of early disease stages or oligosymptomatic/asymptomatic cases and may permit timely treatment to prevent disease progress., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Scalp cooling has been used since the 1970s to prevent chemotherapy-induced alopecia, one of the most common and psychologically troubling side effects of chemotherapy. Currently available scalp cooling systems demonstrate varying results in terms of effectiveness and tolerability., Methods: For the present prospective study, 55 women receiving neoadjuvant, adjuvant, or palliative chemotherapy were enrolled. The aim was to assess the effectiveness of a sensor-controlled scalp cooling system (DigniCap: Sysmex Europe GmbH, Norderstedt, Germany) to prevent chemotherapy-induced alopecia in breast or gynecologic cancer patients receiving 1 of 7 regimens. Clinical assessments, satisfaction questionnaires, and alopecia evaluations [World Health Organization (who) grading for toxicity] were completed at baseline, at each cycle, and at completion of chemotherapy., Results: Of the 55 patients, 78% underwent scalp cooling until completion of chemotherapy. In multivariate analysis, younger women and those receiving paclitaxel weekly or paclitaxel-carboplatin experienced less alopecia. The compound successful outcome ("no head covering" plus "who grade 0/1") was observed in all patients 50 years of age and younger receiving 4 cycles of docetaxel-cyclophosphamide or 6 cycles of paclitaxel-carboplatin. Conversely, alopecia was experienced by all women receiving triplet polychemotherapy (6 cycles of docetaxel-doxorubicin-cyclophosphamide). For women receiving sequential polychemotherapy regimens (3 cycles of fluorouracil-epirubicin-cyclophosphamide followed by 3 cycles of docetaxel or 4 cycles of doxorubicin-cyclophosphamide followed by 4 cycles of docetaxel), the subgroup 50 years of age and younger experienced a 43% success rate compared with a 10% rate for the subgroup pf older women receiving the same regimens., Conclusions: The ability of scalp cooling to prevent chemotherapy-induced alopecia varies with the chemotherapy regimen and the age of the patient. Use of a compound endpoint with subjective and objective measures provides insightful and practical information when counselling patients.

Background: Distinct populations of neutrophils have been identified based on the expression of intercellular adhesion molecule 1 (ICAM1, CD54) and chemokine receptor 1 (CXCR1, interleukin 8 receptor α)., Aim: We analyzed the expression of vascular endothelial growth factor receptor 1 (VEGFR1), a physiological negative regulator of angiogenesis, on distinct populations of neutrophils from the blood of patients before and after adjuvant chemotherapy for breast cancer., Materials and Methods: Neutrophil populations were distinguished as reverse transmigrated (ICAM1(high)/CXCR1(low)), naïve (ICAM1(low)/CXCR1(high)), or tissue-resident neutrophils (ICAM1(low)/CXCR1(low)), and their VEGFR1 expression quantified., Results: Reverse transmigrated ICAM1(high)/CXCR1(low) neutrophilic granulocytes decreased significantly after chemotherapy and these were also the cells with highest mean fluorescence intensity for VEGFR1., Conclusion: Chemotherapy mainly reduces the number of reverse transmigrated long-lived ICAM1(high)/CXCR1(low) VEGFR1-expressing neutrophils. The decrease of antiangiogenic VEGFR1 may have a potential impact on tumour angiogenesis in patients undergoing adjuvant chemotherapy., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The presence of lymph node metastases is the most important prognostic factor in early stage breast cancer. Whether bone marrow micrometastases (BMM) impact the prognosis in sentinel lymph node (SLN)-negative breast cancer patients remains a matter of debate. Therefore, the objective of this study was to assess the impact of BMM on 5-year disease-free and overall survival among those patients., Methods: We analyzed 410 patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, cN0) who were prospectively enrolled into the Swiss Multicenter Sentinel Lymph Node Study in Breast Cancer between January 2000 and December 2003. All patients underwent bone marrow aspiration followed by SLN biopsy. All SLN were stained with hematoxylin and eosin and immunohistochemistry (Lu-5, CK-22). Cancer cells in the bone marrow were identified after staining with monoclonal antibodies A45-B/B3 against CK-8, -18, and -19., Results: Negative SLN were found in 67.6% (277 of 410) of the enrolled patients. Of those, BMM status was negative in 75.8% (210 of 277) and positive in 24.2% (67 of 277) patients. Median follow-up was 61 (range 11-96) months. Five-year disease-free survival was 93.6% (95% confidence interval [CI] 89.1-96.0) in BMM-negative and 92.2% (95% CI 82.5-96.2) in BMM-positive patients (p = 0.50). Five-year overall survival was 92.7% (95% CI 87.9-95.8) for the BMM-negative and 92.5% (95% CI 83.4-96.2) for the BMM-positive group (p = 0.85)., Conclusions: This is one of the first prospective studies to examine 5-year disease-free and overall survivals in SLN-negative patients in correlation to their BMM status. Although BMM are identified in one of four SLN-negative patients, they do not impact disease-free and overall survival.

Objective: The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease., Methods: Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs)., Results: Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality., Conclusion: Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Background: Epigenetic regulation is an important mechanism leading to cancer initiation and promotion. Histone acetylation by histone deacetylases (HDACs) represents an important part of it. The development of HDAC inhibitors has identified the utility of HDACs as a therapeutic target. Little is known about the epigenetic regulation of vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell cancer (VSCC). In this study, the expression of class I HDACs (HDAC 1, 2 and 3) was compared in a series of VIN and VSCC tissues., Methods: A tissue micro array (TMA) with specimens from 106 patients with high-grade VIN and 59 patients with vulvar cancer was constructed. The expression of HDACs 1, 2 and 3 were analyzed with immunohistochemistry (IHC). The nuclear expression pattern was evaluated in terms of intensity and percentage of stained nuclei and was compared between vulvar preinvasive lesions and vulvar cancer., Results: HDAC 2 expression was significantly higher in VIN than in VSCC (p < 0.001, Fisher's test). Also, 88.7% (n = 94/106) of VIN samples and only 54.5% (n = 31/57) of VSCC samples were scored at the maximum level. Conversely, HDAC 3 expression was significantly higher in VSCC (93%, 53/57) compared to VIN (73.6%, 78/106, p = 0.003), whereas only a small difference in the expression of HDAC 1 was found between these two entities of vulvar neoplasia., Conclusions: These results suggest that epigenetic regulation plays a considerable role in the transformation of VIN to invasive vulvar neoplasia.

Purpose of Review: Sentinel lymph node (SLN) dissections have been shown to be sensitive for the evaluation of nodal basins for metastatic disease and are associated with decreased short-term and long-term morbidity when compared with complete lymph node dissection. There has been increasing interest in the use of SLN technology in gynecologic cancers. This review assesses the current evidence-based literature for the use of SLN dissections in gynecologic malignancies., Recent Findings: Recent literature continues to support the safety and feasibility of SLN biopsy for early stage vulvar cancer with negative predictive value approaching 100 % and low false negative rates. Alternatively, for endometrial cancer most studies have reported low false-negative rates, with variable sensitivities and have reported low detection rates of the sentinel node. Studies examining the utility of SLN biopsy in early-stage cervical cancer remain promising with detection rates, sensitivities, and false-negative rates greater than 90 % for stage 1B1 tumors., Summary: SLN dissections have been shown to be effective and safe in certain, select vulvar cancer patients and can be considered an alternative surgical approach for these patients. For endometrial and cervical cancer, SLN dissection continues to have encouraging results and however needs further investigation.

Purpose: The insulin-like growth factor (IGF) signaling system is involved in breast cancer initiation and progression. The prognostic relevance of tumor expression patterns of IGFI-related proteins remains poorly understood. This study associates the expression of selected IGF proteins with breast tumor and patient characteristics., Experimental Design: IGFI, IGFI receptor, IGF-binding protein (IGFBP)2, and IGFBP3 expression was measured in 855 primary breast carcinomas by immunohistochemistry using tissue microarrays. We investigated the association of tumor and nodal stage, grade, hormone receptor status, HER2 gene amplification, menopausal status, body mass index, and survival with IGF protein expression., Results: In contrast to IGFI, the expression of IGFI receptor, IGFBP2, and IGFBP3 was associated with estrogen receptor status. In addition, IGFBP3 was positively correlated with body mass index and premenopausal status. Importantly, IGFBP2 was an independent and positive predictor of overall survival (hazard ratio, 0.48; 95% confidence interval, 0.24-0.95; P = 0.04). There was a weak suggestion for IGFBP2 and overweight to modify each other's effect on survival., Conclusions: According to these results, which need confirmation in larger patient series, the prognostic relevance of IGFBP2 and IGFBP3 protein expressions in breast cancer may depend on the hormonal context and body weight.

Objective: To assess the accuracy of sentinel lymph node (SLN) frozen section in a prospective multicenter study of early-stage breast cancer patients., Summary Background Data: The decision to perform an immediate completion axillary node dissection (ALND) is based on results of SLN frozen section. However, SLN frozen sections are not routinely performed in all centers. Moreover, the accuracy of SLN frozen section remains a matter of great debate., Methods: Prospective multicenter trial analyzing 659 early stage breast cancer patients (pT1 and pT2

Objective: To determine characteristics and clinical course of high-grade anogenital intraepithelial neoplasia (AIN) in human immunodeficiency virus (HIV)-infected women., Study Design: HIV-positive women with biopsy-proven high-grade (II and III) vulvar (VIN), vaginal (VAIN) or perianal intraepithelial neoplasia (PAIN) were identified in the electronic databases of 2 colposcopy clinics., Results: A total of 31 patients were identified from 1992 to 2007, of which 30 had a mean follow-up of 47.7 months (SD = 46.0; range, 2.6-166.2). Of the patients, 77.4% had VIN, 12.9% VAIN and 9.7% PAIN at first diagnosis. Age at diagnosis of IN was 36.2 years (SD +/- 5.2; range, 23.5-47.0). Ninety percent of patients received antiretroviral therapy at first diagnosis of IN; 65% (13 of 20) of patients with a follow-up of > 2 years required a second treatment, and 2 developed invasive vulvar cancer (10%)., Conclusion: AIN among HIV-positive women shows a high relapse rate despite treatment modality used and a substantial invasive potential.

NY-BR-1 is a recently identified differentiation antigen of the mammary gland. To use NY-BR-1 for T-cell-based immunotherapy, analysis of its co-expression with HLA class I antigens is required. In the present tissue microarray study, primary breast cancers (n = 1,444), recurrences (n = 88), lymph node (n = 525) and distant metastases (n = 91) were studied for NY-BR-1 expression using a novel monoclonal antibody. NY-BR-1 expression was compared with prognosis, estrogen receptor, HER2-status, EGFR and HLA class I antigen expression. NY-BR-1 was more frequently expressed in grade 1 (82%) than in grade 2 (69%) and grade 3 (46%) carcinomas (P < 0.0001). Moreover, NY-BR-1 expression correlated directly with estrogen receptor expression (P < 0.0001) and inversely correlated with HER2-status and EGFR expression (P < 0.0001 for both). Considering high expression level of co-expression, 198/1,321 (15%) primary breast carcinomas and 4/65 (6%) distant metastases expressed NY-BR-1 and HLA class I, suggesting that active immunotherapy can be applied to about 10% of breast cancer patients. Survival analysis showed an association of NY-BR-1 expression with better patient outcome (P = 0.015). No difference between NY-BR-1 expression of primary tumors and metastases could be found, indicating that the presence of NY-BR-1 in metastases can be deduced from their corresponding primary. Forty-three paired biopsies taken from patients before and after chemotherapy suggest that NY-BR-1 expression is not influenced by preceding chemotherapy (kappa = 0.89, P < 0.0001). In summary, the co-expression of NY-BR-1 with HLA class I antigens and its expression in metastases without modification by chemotherapy suggest that NY-BR-1 targeted immunotherapy represents a viable strategy in addition to other targeted cancer drug therapies of breast cancer.

Background: Routine adjuvant administration of trastuzumab (T) has been implemented in most centers, but its economic impact has not yet been well examined., Methods: A Markov model was constructed based on clinical data of the Herceptin Adjuvant (HERA) and the Finland Herceptin (FinHer) trials. Costs from the perspective of a Swiss health care provider were calculated based on resource use., Results: On the basis of HERA data, our model yielded an overall survival rate of 71.8% for the T group versus 62.8% for the control group [risk ratio (RR) = 0.87) after 10 years and 62.9% versus 52.7% (RR = 0.84) after 15 years. Cost-effectiveness resulted in 40505 Euros (EUR) per life years gained (LYG) after 10 years and 19673 EUR per LYG after 15 years. For the FinHer regimen, overall survival after 10 and 15 years resulted in 81.8% versus 66.1% (RR = 0.81) and 73.6% versus 57.0% (RR = 0.77). Costs of 8497 EUR per patient could be saved after 10 years and 9256 EUR after 15 years compared with the control group., Conclusion: In a long-term perspective, adjuvant T based on the HERA regimen can be considered cost-effective. The regimen used in the FinHer trial is even cost saving, but estimations are based on a single small trial.

Background: The sentinel lymph node (SLN) status has proven to accurately reflect the remaining axillary lymph nodes and represents the most important prognostic factor. It is unknown whether an association exists between the SLN status and the presence of bone marrow (BM) micrometastases. The objective of the present investigation was to evaluate whether or not such an association exists., Methods: In the present investigation 410 patients with early stage breast cancer (pT1 and pT2

Objective: To assess the morbidity after sentinel lymph node (SLN) biopsy compared with SLN and completion level I and II axillary lymph node dissection (ALND) in a prospective multicenter study., Summary Background Data: ALND after breast cancer surgery is associated with considerable morbidity. We hypothesized: 1) that the morbidity in patients undergoing SLN biopsy only is significantly lower compared with those after SLN and completion ALND level I and II; and 2) that SLN biopsy can be performed with similar intermediate term morbidity in academic and nonacademic centers., Methods: Patients with early stage breast cancer (pT1 and pT2

Endometrial cancer is a heterogeneous tumour with two types which can be distinguished clinically, histologically and pathogenetically:the classical endometrioid cancer (type 1) with a good prognosis and the aggressive histological type 2 with a poor prognosis and early metastatic spread. The most active cytotoxic drugs in advanced or metastatic endometrial cancer are the anthracyclines, the platinum salts and the taxanes. In most studies, combination chemotherapy is superior to monotherapy in terms of response rates. In the last few years there is growing evidence that chemotherapy can prolong overall survival in metastatic endometrial cancer and that adjuvant chemotherapy can reduce recurrence rates in high-risk situations.

Sentinel lymph node biopsy is a widely accepted new surgical procedure in the treatment of early breast cancer. However, not only numerous details of the technique, but also limitations of the method, such as maximal tumor size, multifocal disease, accuracy following neoadjuvant chemotherapy and appropriateness in ductal carcinoma in situ are being debated. Recent multicenter studies could establish the lower morbidity of sentinel lymph node biopsy compared to axillary clearance as well as the false-negative rate which lies between 7 and 9.7%. In unifocal T1 disease with clinically negative axillary lymph nodes, the method is considered to be standard of care. Evidence is growing that it may also be appropriate in larger and multifocal tumors while the method is unreliable after neoadjuvant chemotherapy.

Virtually all cases of cervical cancer are caused by one of the 18 oncogenic types of human papillomavirus (HPV). It is estimated that 80% of all women will be infected by HPV in a lifetime, and the prevalence of HPV is highest among young, sexually active women and declines with increasing age. The risk of developing high-grade squamous intraepithelial lesions depends on the actual HPV type,the duration of infection, and the viral load. Due to the high prevalence of HPV infection, HPV testing in young women is of little value. The high negative predictive value of this test, combined with nor-mal Papanicolaou smear results, almost ensures that the patient is or will be free of a cancer precursor at the time of testing or in the immediate future. Hence, HPV testing combined with cytology is a reasonable approach in elderly women in order to increase the screening interval to 3-5 years. HPV testing is established for triage of borderline cytology findings of atypical squamous cells of undetermined significance if colposcopy is not performed immediately and if HPV-negative women are rescheduled within 12 months. HPV testing 6 months after cone biopsy allows increasing the follow-up interval due to its high negative predictive value. In atypical glandular lesions not otherwise specified, HPV testing may identify patients requiring immediate treatment. In immunocompromised patients with borderline cytology due to persistent HPV infection, HPV test-ing identifies patients with a low risk of cancer precursors not requiring treatment.

Axillary lymph node dissection (ALND) is the standard of care for nodal staging of patients with invasive breast cancer. Due to significant somatic and psychological side effects, replacement of ALND with less invasive techniques is desirable. The goal of this study was to evaluate the clinical usefulness of axillary lymph node (ALN) staging by means of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in breast cancer patients qualifying for sentinel lymph node biopsy (SLNB). FDG-PET was performed within 1 week before surgery in 24 clinically node-negative breast cancer patients with tumors smaller than 3 cm. Sentinel lymph nodes (SLNs) were identified by preoperative lymphoscintigraphy following peritumoral technetium 99m-labeled colloid albumin injection, and by intraoperative gamma detector and blue dye localization. Following SLNB, a standard ALND was performed. Serial sectioning and immunohistochemistry of the SLN as well as standard histologic examination of the non-SLN was performed. FDG-PET detected all primary breast cancers. Staging of ALNs by PET was accurate in 15 of 24 patients (62.5%), whereas PET staging was false negative in 8 of 10 node-positive patients and false-positive in 1 patient. The sensitivity, specificity, positive predictive value, and negative predictive value of FDG-PET for nodal status was 20%, 93%, 67%, and 62%, respectively. The mean diameter of false-negative ALN metastases was 7.5 mm (range 1-15 mm). Lymph node staging using FDG-PET is not accurate enough in clinically node-negative patients with breast cancer qualifying for SLNB and should not be used for this purpose.

Background and Objectives: To evaluate feasibility and functional effects of photodynamic endometrial ablation (PEA) in patients., Study Design/patients and Methods: A total of 15 PEAs has been performed in 11 patients using topically applied 5-aminolevulinic acid (ALA) solutions and a balloon-light diffuser (160 J/cm(2), 635 nm). Uterine bleeding intensity has been determined on a daily basis 3 months prior to and up to 6 months after endometrial ablation using an analogous scale scoring from 1 (spotting) to 6 U (severe bleeding). Statistical analysis by unpaired Student's t-test., Results: The mean number of bleeding units per cycle (n = 44) was 35.7 prior to PEA. The decrease in bleeding units was significant for the months 1-3 (24.4 U per cycle; P = 0.03), but not for the months 4-6 (25.9 U; P = 0.11) following PEA., Conclusions: PEA is feasible and provides a significant short-term reduction of uterine bleeding., (Copyright 2004 Wiley-Liss, Inc.)

Introduction: For routine staging of patients with primary breast cancer, clinical practice guidelines of many medical societies recommend chest X-ray, liver ultrasound and bone scan. With respect to expanding health care costs and patients' psychological distress it has been supposed, that there might be a group of breast cancer patients, who do not need these imaging studies., Methods: Four hundred and eighty-eight consecutive patients with primary breast cancer who had primary surgery at our institution and complete work-up for distant metastases including chest X-ray, liver ultrasound, and bone scan were studied., Results: We found distant metastases at the time of primary diagnosis in 19 patients (3.9%). Bone metastases were found in 2.7%, liver metastases in 1.0%, and pulmonary metastases in 0.4%. However, in breast tumors smaller than 1 cm, no metastatic lesions were found, whereas 18.2% of the patients with pT4 tumors had metastases. In 2.4% of screening imaging studies, metastases were ruled out by additional imaging., Conclusion: Based on our data and a review of the literature, we suggest that chest X-ray, liver ultrasound and bone scan can be omitted in the staging of asymptomatic patients with pT1a or pT1b disease.

The aim of this study was to compare MRI of the breast with (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET) in patients with suspected local or regional breast cancer recurrence or suspected contralateral breast cancer. Thirty-two patients (mean age 57.2 years, age range 32-76 years) with suspected loco-regional recurrence ( n=19), chest wall recurrence ( n=5), and suspected secondary tumor of the contralateral breast ( n=8) underwent MRI of the breast and FDG PET of the whole body and breast region. Cytology/histology ( n=17) or a clinical follow-up examination ( n=15) with additional imaging served as the standard of reference. A McNemar test was performed to compare PET and MRI, and kappa was determined to quantify agreement of both methods. Sensitivity was 79 and 100%, specificity was 94 and 72%, and accuracy was 88 and 84% for MRI and PET, respectively. Additional metastases outside the field of view of MRI were found in PET in 5 patients. In this study both imaging methods had comparable accuracy. The detection of distant metastases with whole-body PET imaging can influence patient management.