Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

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.

Association of Axillary Dissection With Systemic Therapy in Patients With Clinically Node-Positive Breast Cancer.

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.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

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.

Prepectoral versus subpectoral implant-based breast reconstruction after skin-sparing mastectomy or nipple-sparing mastectomy (OPBC-02/ PREPEC): a pragmatic, multicentre, randomised, superiority trial.

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.

Predictors of a Successful Bipolar Radiofrequency Endometrial Ablation.

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.

Subcutaneous botulinum toxin type A injections for provoked vestibulodynia: a randomized placebo-controlled trial and exploratory subanalysis.

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.

Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy.

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.

Role of intrinsic sphincter deficiency with and without urethral hypomobility on the outcome of tape insertion.

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.

Sensory Hyperinnervation Distinguishes Bladder Pain Syndrome/Interstitial Cystitis from Overactive Bladder Syndrome.

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), p75NTR (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 p75NTR 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 p75NTR 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.

Risk factors for emergency caesarean section in planned vaginal breech delivery.

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.

Neutrophil expression of ICAM1, CXCR1, and VEGFR1 in patients with breast cancer before and after adjuvant chemotherapy.

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.

Bone marrow micrometastases do not impact disease-free and overall survival in early stage sentinel lymph node-negative breast cancer patients.

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.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia.

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.

[The incidence of human papilloma virus associated vulvar cancer in younger women is increasing and wide local excision with sentinel lymph node biopsie has become standard]. / Vulvakarzinom.

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.

Expression pattern of class I histone deacetylases in vulvar intraepithelial neoplasia and vulvar cancer: a tissue microarray study.

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.

IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity.

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.

Accuracy of frozen section of sentinel lymph nodes: a prospective analysis of 659 breast cancer patients of the Swiss multicenter study.

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

Outcome of treated anogenital intraepithelial neoplasia among human immunodeficiency virus-infected women.

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.

Curative treatment of a pelvic side wall recurrence after conization for microinvasive cervical cancer stage IA1: a case report and review of the literature.

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.