Reconstruction of the Meatus Urethrae After Oncologic Vulvectomy: Outcome of 42 Vaginal Flap Advancements in 41 Women.

BACKGROUND AND AIM: Resection of the distal part of the urethra is performed in 15% to 55% of women with vulvar cancer to achieve radicality of vulvectomy. Urinary reconstruction in these women may be complicated by urethral stenosis resulting from circular inset of the meatus. We report on our experience with 2 surgical techniques of noncircular inset to prevent such stenosis. METHODS: From January 2005 to January 2020, 42 urethral meatus reconstructions were performed in 41 women after vulvectomy for (pre)malignant skin disorders by a "limited" (n = 17) or "extended" (n = 25) anterior vaginal wall advancement technique, including V-Y insertion of part of the vaginal flap in a posterior longitudinal urethrotomy. Preoperative characteristics, procedural details, and surgical outcomes were reviewed. RESULTS: We observed 1 neomeatal stenosis and 1 case of partial vaginal wall flap necrosis as major complications following the "limited" technique and 1 circumferential neomeatal dehiscence and occlusion as major complication after the "extended" technique. Both the neomeatal stenosis and the dehiscence/occlusion are felt to have been preventable and not caused by a flaw of design of the advancement technique. CONCLUSIONS: We advocate applying these vaginal wall advancement techniques to prevent circular inset of the neomeatus. The "extended" technique offers a solution in cases where the periurethral vulvar defect cannot be closed by transpositioning of labial skin.

Personalising sarcoma care using quantitative multimodality imaging for response assessment.

Over the last decades, technological developments in the field of radiology have resulted in a widespread use of imaging for personalising medicine in oncology, including patients with a sarcoma. New scanner hardware, imaging protocols, image reconstruction algorithms, radiotracers, and contrast media, enabled the assessment of the physical and biological properties of tumours associated with response to treatment. In this context, medical imaging has the potential to select sarcoma patients who do not benefit from (neo-)adjuvant treatment and facilitate treatment adaptation. Due to the biological heterogeneity in sarcomas, the challenge at hand is to acquire a practicable set of imaging features for specific sarcoma subtypes, allowing response assessment. This review provides a comprehensive overview of available clinical data on imaging-based response monitoring in sarcoma patients and future research directions. Eventually, it is expected that imaging-based response monitoring will help to achieve successful modification of (neo)adjuvant treatments and improve clinical care for these patients.

Surgical Complications of Skin-Sparing Mastectomy and Immediate Implant-Based Breast Reconstruction in Women Concurrently Treated With Adjuvant Chemotherapy for Breast Cancer.

BACKGROUND AND AIM: To date, studies on adjuvant chemotherapy as a risk factor for the surgical outcome of combined mastectomy and breast reconstruction were hampered by the inclusion of mixed reconstructive cohorts of both delayed and immediate timing and of both autologous and implant-based techniques. Consequently, there is a paucity of data on the impact of adjuvant chemotherapy on surgical complication rates after combined skin-sparing mastectomy and immediate implant-based breast reconstruction. METHODOLOGY: We compared the postoperative complications that occurred within 16 weeks after this combined procedure in 131 women (139 breasts) treated with adjuvant chemotherapy with those in a control group of 491 women (517 breasts) not receiving any adjuvant therapy within 16 weeks. RESULTS: In line with the clinically indicated selection of women to undergo adjuvant chemotherapy, the interventional group differed significantly from the control group in 7 of the 12 patient- and procedure-related characteristics. The prevalence of minor complications (13.7% and 12.4%, respectively, P = 0.68) and major complications (31.7% and 29.4%, respectively, P = 0.60) did not differ significantly between the interventional group and the controls. The fraction of breasts that needed unscheduled surgery (0.29 and 0.24, respectively, P = 0.20), the fraction of total number of interventions (0.34 and 0.33, respectively, P = 0.24), and the fraction of implants lost (0.72 and 0.67, respectively, P = 0.86) did not differ significantly between both groups. The onset of chemotherapy, furthermore, seemed not to influence the occurrence or severity of complications. CONCLUSIONS: Like other women who have to undergo mastectomy, women who need to undergo adjuvant chemotherapy can potentially benefit from combined skin-sparing mastectomy and immediate implant-based breast reconstruction.

Rembrandt's Aging Face in Plastic Surgical Perspective.

BACKGROUND AND AIM: When the painter Rembrandt van Rijn (1607-1669) died 350 years ago, he left us some 90 self-portraits showing his aging face. Recognizing aging characteristics of the male face is fundamental to the planning of a surgical procedure and a prerequisite when communicating to the male patient. Rembrandt's recordings through the years might offer an optimal aid to train such recognition, provided that they are truthful. In this article, we present an inventory of age-related changes observed in these self-portraits to assess whether they are truthful. METHODS: High-quality photographs of 25 self-portraits that are generally accepted as works by Rembrandt were independently assessed in a standardized fashion for the presence of 25 aging characteristics, by 2 plastic surgeons and a physician-portraitist. RESULTS: The observed proportion of agreement between assessments reached 0.87 (κ = 0.68, indicating good agreement). We found Rembrandt's self-portraits to reflect his facial aging as a chronologically increasing process. Observed characteristics set in as of 1642, the year that he lost his beloved first wife, Saskia. His face appears to have particularly aged from 1652 to 1659, in which period Rembrandt's second great love Hendrickje was summoned because of her living in sin with Rembrandt, and Rembrandt himself faced financial problems. As of 1660, Rembrandt seems to have been less intended to depict his facial aging characteristics. CONCLUSIONS: We conclude that Rembrandt truthfully reflected his ongoing age in the self-portraits, up to 1660. These self-portraits therefore may allow for training the art of observation of such characteristics.

Peptide mimetics of immunoglobulin A (IgA) and FcαRI block IgA-induced human neutrophil activation and migration.

The cross-linking of the IgA Fc receptor (FcαRI) by IgA induces release of the chemoattractant LTB4, thereby recruiting neutrophils in a positive feedback loop. IgA autoantibodies of patients with autoimmune blistering skin diseases therefore induce massive recruitment of neutrophils, resulting in severe tissue damage. To interfere with neutrophil mobilization and reduce disease morbidity, we developed a panel of specific peptides mimicking either IgA or FcαRI sequences. CLIPS technology was used to stabilize three-dimensional structures and to increase peptides' half-life. IgA and FcαRI peptides reduced phagocytosis of IgA-coated beads, as well as IgA-induced ROS production and neutrophil migration in in vitro and ex vivo (human skin) experiments. Since topical application would be the preferential route of administration, Cetomacrogol cream containing an IgA CLIPS peptide was developed. In the presence of a skin permeation enhancer, peptides in this cream were shown to penetrate the skin, while not diffusing systemically. Finally, epitope mapping was used to discover sequences important for binding between IgA and FcαRI. In conclusion, a cream containing IgA or FcαRI peptide mimetics, which block IgA-induced neutrophil activation and migration in the skin may have therapeutic potential for patients with IgA-mediated blistering skin diseases.

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes.

PURPOSE: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients. PATIENTS AND METHODS: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR). RESULTS: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced. CONCLUSION: With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

Repeated Use of Gluteal Fold Flaps for Post-Oncologic Vulvoperineal Reconstruction.

BACKGROUND AND AIM: Because of the associated high recurrence rate, future reconstructive options should be reckoned with during surgical treatment of primary or recurrent (pre)malignant vulvoperineal lesions. One of the claimed advantages of the gluteal fold flap is the possibility of repeated use of the flap in case of recurrence. We present our experience with such reuse of gluteal fold flaps to illustrate this possibility. METHODS: A mean of 27 months after initial use, 10 subcutaneously pedicled or perforator-based V-Y advancement or propeller-rotation flaps were elevated from previously used gluteal fold flaps in 9 women presenting with recurrent vulvoperineal (pre)malignancy. Five of these women had undergone radiotherapy prior to flap reuse. RESULTS: Although short-term complications were observed in 3 women, all flaps survived and healed completely. CONCLUSIONS: We showed the feasibility of successful reuse of subcutaneous pedicled or perforator-based gluteal fold flaps for repeated vulvoperineal reconstruction, both in nonirradiated and irradiated women. This concept of reuse of the gluteal fold flap is useful for recurring (pre)malignant vulvoperineal defects, and reconstructive surgeons and patients may benefit from this potential option.

Clinically node negative breast cancer patients undergoing breast conserving therapy, sentinel lymph node procedure versus follow-up: a Dutch randomized controlled multicentre trial (BOOG 2013-08).

BACKGROUND: Studies showed that axillary lymph node dissection can be safely omitted in presence of positive sentinel lymph node(s) in breast cancer patients treated with breast conserving therapy. Since the outcome of the sentinel lymph node biopsy has no clinical consequence, the value of the procedure itself is being questioned. The aim of the BOOG 2013-08 trial is to investigate whether the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients treated with breast conserving therapy. METHODS: The BOOG 2013-08 is a Dutch prospective non-inferiority randomized multicentre trial. Women with pathologically confirmed clinically node negative T1-2 invasive breast cancer undergoing breast conserving therapy will be randomized for sentinel lymph node biopsy versus no sentinel lymph node biopsy. Endpoints include regional recurrence after 5 (primary endpoint) and 10 years of follow-up, distant-disease free and overall survival, quality of life, morbidity and cost-effectiveness. Previous data indicate a 5-year regional recurrence free survival rate of 99% for the control arm and 96% for the study arm. In combination with a non-inferiority limit of 5% and probability of 0.8, this result in a sample size of 1.644 patients including a lost to follow-up rate of 10%. Primary and secondary endpoints will be reported after 5 and 10 years of follow-up. DISCUSSION: If the sentinel lymph node biopsy can be safely omitted in clinically node negative breast cancer patients undergoing breast conserving therapy, this study will cost-effectively lead to a decreased axillary morbidity rate and thereby improved quality of life with non-inferior regional control, distant-disease free survival and overall survival. TRIAL REGISTRATION: The BOOG 2013-08 study is registered in ClinicalTrials.gov since October 20, 2014, Identifier: NCT02271828. https://clinicaltrials.gov/ct2/show/NCT02271828.

Prevalence and risk factors for extended-spectrum ß-lactamase or AmpC-producing Escherichia coli in organic dairy herds in the Netherlands.

Extended-spectrum ß-lactamase and AmpC-producing Escherichia coli (ESBL/AmpC) are an emerging problem and are hypothesized to be associated with antimicrobial use (AMU), and more specifically with the use of third- and fourth-generation cephalosporins. Whether ESBL/AmpC also occur in organic dairy herds, which have restricted AMU, is not known. Additionally, it is unknown whether, in addition to restricted AMU, other factors in organic herd management are associated with ESBL/AmpC herd status. The aim of this study was to estimate the prevalence of ESBL/AmpC in organic dairy herds in the Netherlands. Subsequently, the relationships between the ESBL/AmpC herd status and AMU and between ESBL/AmpC herd status and farmers' management were assessed in organic dairy herds. For this study, 90 randomly selected, officially registered organic dairy herds were included. The ESBL/AmpC herd status was determined based on the bacteriological culture result of a slurry sample. The sensitivity of testing slurry samples for ESBL/AmpC herd status is less than 100% for detecting herds with a low ESBL/AmpC prevalence. For that reason, herds that tested positive for ESBL/AmpC in slurry were defined as positive and herds with negative slurry samples were defined as unsuspected. A comprehensive questionnaire on management practices was conducted and records on specified antimicrobials that were provided to these herds by the veterinary service providers were obtained. From the data on antimicrobial supplies by the veterinarian, the animal daily defined dose of antimicrobials per farm per year (DDDAF) was calculated. Descriptive statistics were used to describe the relation between the ESBL/AmpC herd status and DDDAF. Multivariable logistic regression models were used to evaluate management factors associated with the ESBL/AmpC herd status. We found ESBL/AmpC in 12 of the 90 (13%; 95% confidence interval=7-22%) slurry samples from organic dairy herds. The median DDDAF in organic dairy herds was 0.5, which was not significantly different between ESBL/AmpC-positive and unsuspected dairy herds. No association could be found between the use of different types of antimicrobials, such as third- and fourth-generation cephalosporins, and ESBL/AmpC herd status. Factors that were associated with higher odds of being ESBL/AmpC-positive were pig farms located within a 2-km radius of the barn, applying parental treatment for clinical mastitis, and providing milk replacer to the female calves after colostrum intake. The prevalence of ESBL/AmpC in organic dairy herds appeared lower than the prevalence in previous studies conducted in conventional dairy herds. Apparently, ESBL/AmpC are also present in herds with low AMU; this indicates that other factors than AMU are also associated with ESBL/AmpC herd status.

The occurrence of maedi-visna virus in Lebanon.

Maedi-visna (MV) is a chronic viral disease prevalent in adult sheep that is caused by a virus belonging to the small ruminant lentivirus group (SRLV). This disease is considered to affect the international trade of sheep and is classified in the World Organisation for Animal Health (OIE) list of notifiable animal diseases. Although maedi-visna virus (MVV) has been detected in many countries, no study on its occurrence has been carried out in Lebanon. For this purpose, a serological survey of infection with MVV was conducted in seven of the eight Lebanese governorates using a competitive enzyme-linked immunosorbent assay (ELISA). A total of 184 individual blood samples from sheep of the local breed 'Awassi', originating from 16 farms distributed throughout the seven Lebanese governorates, were collected and analysed. Among the 184 tested sheep, 131 sheep from the16 farms visited were MVV positive. This presents a prevalence of 71% MVV-positive animals and 100% MVV-positive farms. The results indicate the need for further systematic investigations into the between-herd and within-herd prevalence of MV in Lebanon.

Le maedi-visna (MV) est une maladie virale chronique causée par un virus appartenant au groupe des lentivirus des petits ruminants (SRLV) et affectant les moutons adultes. La maladie a une incidence sur les échanges internationaux d'ovins et figure sur la liste des maladies à déclaration obligatoire de l'Organisation mondiale de la santé animale (OIE). La présence du virus maedi-visna est attestée dans de nombreux pays mais jusqu'à présent aucune étude ne lui avait été consacrée au Liban. Pour y remédier, une enquête sérologique recourant à une épreuve immuno-enzymatique (ELISA) par compétition a été conduite dans sept des huit gouvernorats du Liban afin de déterminer la prévalence de l'infection par le virus maedi-visna. Au total, 184 échantillons sanguins prélevés sur des moutons de race locale (Awassi) originaires de 16 élevages répartis dans les sept gouvernorats ont été analysés. Des résultats positifs ont été obtenus sur 131 des 184 prélèvements ; tous les élevages étaient représentés. La prévalence est donc de 71 % à l'échelle des individus et de 100 % à l'échelle des élevages. Il ressort de ces résultats que la prévalence à l'intérieur des élevages ainsi que celle entre élevages devraient faire l'objet d'enquêtes systématiques plus poussées au Liban.

El maedi-visna (MV) es una enfermedad viral crónica prevalente en ovejas adultas, cuyo agente etiológico es un virus del grupo de los lentivirus de los pequeños rumiantes. Figura en la lista de enfermedades de declaración obligatoria de la Organización Mundial de Sanidad Animal (OIE) porque se considera que afecta al comercio internacional de ovejas. Aunque el virus maedi-visna (VMV) ha sido detectado en muchos países, nunca antes se había estudiado su presencia en el Líbano. Para ello se llevó a cabo un estudio serológico de la infección por el virus en siete de los ocho distritos administrativos del país mediante un ensayo inmunoenzimático (ELISA) de competición. Se extrajeron y analizaron un total de 184 muestras sanguíneas de ovejas de la raza autóctona «awassi¼ procedentes de 16 explotaciones repartidas en los siete distritos libaneses. De esas 184 muestras, dieron resultado positivo para el VMV 131, correspondientes a ovejas de las 16 explotaciones visitadas. Ello supone una prevalencia del 71% de animales positivos al virus y del 100% de explotaciones positivas. Los resultados ponen de manifiesto la necesidad de investigar más sistemáticamente la prevalencia del maedi-visna entre los rebaños y dentro de los rebaños del Líbano.

A Prospective Assessment of Surgical Risk Factors in 114 Gluteal Fold Flap Reconstructions After Oncological Vulvoperineal Resection.

BACKGROUND AND AIM: To date, clinically relevant selection criteria have not been established for the use of the gluteal fold flap after oncological vulvoperineal resection. We prospectively assessed the surgical risk factors of this reconstructive technique in a large series. METHODOLOGY: From April of 2000 through December of 2015, 114 gluteal fold flaps were used for vulvoperineal reconstruction after excision of (pre)malignant skin disorders in 75 women. The possible influence of 10 patient-related and 6 procedure-related risk factors on flap-related postoperative complications was statistically analyzed. RESULTS: We observed a major complication in 13 flaps (11%) and a minor complication in 19 flaps (17%). Previous radiotherapy (P = 0.01) was associated with significantly more complications, and a rotation flap design rather than VY advancement (P = 0.02) was associated with major complications. Recurrent disease, multifocal tumor localization, incomplete removal of tumor, and bilateral flap procedure were found to be clinically relevant risk factors, but not significantly so. The same applied to recurrence of disease during postoperative follow-up. CONCLUSIONS: We identified surgical risk factors for gluteal fold flap use after oncological vulvoperineal resection. These observations may potentially allow for more favorable future surgical outcomes by adaption of selection of patients or procedure.

Andreas Vesalius' 500th Anniversary: First Description of the Mammary Suspensory Ligaments.

Sir Astley Paston Cooper has, to date, been acknowledged to be the first to describe the suspensory ligaments of the breast, or Cooper's ligaments, in 1840. We found these ligaments to be recorded in the first edition of 'De Humani Corporis Fabrica Libri Septem' by Andreas Vesalius, published in 1543. To commemorate Vesalius' 500th birthday, we quote and discuss this earlier record. Vesalius' record of the nature and function of the fleshy membrane between mammary gland and pectoral muscle, the hard fat intervening the mammary glands, and the fibers running from the fleshy membrane to the skin are a clear representation of posterior layer of the superficial fascial system, the fibro-adipose stroma surrounding and linking the mammary glandular elements, and the suspensory ligaments as we know them. Vesalius recorded the anatomy and function of the latter structures nearly 300 years before Sir Astley Paston Cooper did.

Prevalence and risk factors for extended-spectrum ß-lactamase- and AmpC-producing Escherichia coli in dairy farms.

A cross-sectional study was conducted to evaluate the prevalence of extended-spectrum ß-lactamase (ESBL)- and plasmid-mediated AmpC-producing Escherichia coli and associated risk factors in dairy herds. One hundred dairy herds were randomly selected and sampled to study the presence of ESBL- and AmpC-producing E. coli in slurry samples. The sensitivity of testing slurry samples for ESBL/AmpC herd status is less than 100%, especially for detecting herds with a low ESBL/AmpC prevalence. Therefore, whereas herds that tested positive for ESBL/AmpC-producing E. coli in slurry were defined as positive herds, herds with negative slurry samples were defined as unsuspected. Isolates of ESBL- and AmpC-producing E. coli were further characterized by detection and typing of their ESBL/AmpC gene. At the initial sampling, a comprehensive questionnaire was conducted at the participating farms. The farmers were asked questions about management practices potentially associated with the ESBL/AMPC herd status. Also, data on antimicrobial purchases during 2011 were acquired to evaluate whether the animal-defined daily dose of antimicrobials per year at farm level was associated with the ESBL/AmpC herd status. Multivariable logistic regression models were used to determine the association between management practices and the ESBL/AmpC herd status. Six months after the initial slurry sampling, 10 positive herds and 10 herds that had an unsuspected ESBL/AmpC herd status during the first visit were resampled. At each farm, slurry samples and feces from 24 individual cows were collected to evaluate within herd dynamics. During the first sampling, ESBL/AmpC-producing E. coli were isolated from the slurry samples collected at 41% of the herds. In total, 37 isolates were further characterized, revealing 7 different ESBL genes (blaCTX-M-1, -2, -14, -15, -32, -55 and blaTEM-52), 1 plasmid-encoded AmpC gene (blaCMY-2), and 1 chromosomally encoded ampC gene (ampC type 3). The total animal-defined daily dose of antimicrobials per year at farm level was not significantly different between ESBL/AmpC-positive and unsuspected dairy herds. The use of third- and fourth-generation cephalosporins, however, was found to be associated with ESBL/AmpC status, with higher use of these antimicrobials resulting in a significant higher odds to be ESBL/AmpC-positive. Management factors that were associated with a higher odds of being ESBL/AmpC-positive were treatment of all cases of clinical mastitis with antimicrobials, a higher proportion of calves treated with antimicrobials, not applying teat sealants in all cows at dry off, and the use of a floor scraper. This last association, however, was considered a methodological effect rather than a true risk factor. On 5 of the 10 initially positive farms, no ESBL/AmpC-producing E. coli were cultured from the slurry or any of the individual cow samples collected during the second sampling. In 4 of the initially unsuspected farms, slurry or individual cow samples tested positive during the second sampling. In conclusion, ESBL/AmpC could frequently be cultured from slurry samples collected from Dutch dairy farms and the ESBL/AmpC genes carried by the isolates were consistent with those reported earlier. The use of third- and fourth-generation cephalosporins appeared to be associated the ESBL/AmpC herd status.

Andreas Vesalius' 500th Anniversary: Initiation of the Superficial Facial System and Superficial Musculoaponeurotic System Concepts.

Because of their relevance for liposuction and rhytidectomies, respectively, the superficial fascial system (SFS) and superficial musculoaponeurotic system (SMAS) have been thoroughly studied over the past decennia. Although it is well known that the SMAS concept was introduced by Tessier in 1974, it remains unknown who first properly described the stratum membranosum of the SFS. In light of the 500th birthday of Andreas Vesalius (1515-1564), we searched his 1543 masterwork De Humani Corporis Fabrica Libri Septem and related work for references to these structures. We found ample reference to both structures as the membrana carnosa (or fleshy membrane) in his works and concluded that Vesalius recognized the extension, nature, and functions of the stratum membranosum of the SFS, as well as its more musculous differentiation as the SMAS in the head and neck area, and the dartos in the perineogenital area. In doing so, Vesalius recorded most details of the SFS and SMAS concepts avant la lettre.

Guidelines for time-to-event end point definitions in breast cancer trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: Using surrogate end points for overall survival, such as disease-free survival, is increasingly common in randomized controlled trials. However, the definitions of several of these time-to-event (TTE) end points are imprecisely which limits interpretation and cross-trial comparisons. The estimation of treatment effects may be directly affected by the definitions of end points. The DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for randomized cancer clinical trials (RCTs) in breast cancer. PATIENTS AND METHODS: A literature review was carried out to identify TTE end points (primary or secondary) reported in publications of randomized trials or guidelines. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points based on a validated consensus method that formalize the degree of agreement among experts. RESULTS: Recommended guidelines for the definitions of TTE end points commonly used in RCTs for breast cancer are provided for non-metastatic and metastatic settings. CONCLUSION: The use of standardized definitions should facilitate comparisons of trial results and improve the quality of trial design and reporting. These guidelines could be of particular interest to those involved in the design, conducting, reporting, or assessment of RCT.

The value of completion axillary treatment in sentinel node positive breast cancer patients undergoing a mastectomy: a Dutch randomized controlled multicentre trial (BOOG 2013-07).

BACKGROUND: Trials failed to demonstrate additional value of completion axillary lymph node dissection in case of limited sentinel lymph node metastases in breast cancer patients undergoing breast conserving therapy. It has been suggested that the low regional recurrence rates in these trials might partially be ascribed to accidental irradiation of part of the axilla by whole breast radiation therapy, which precludes extrapolation of results to mastectomy patients. The aim of the randomized controlled BOOG 2013-07 trial is therefore to investigate whether completion axillary treatment can be safely omitted in sentinel lymph node positive breast cancer patients treated with mastectomy. DESIGN: This study is designed as a non-inferiority randomized controlled multicentre trial. Women aged 18 years or older diagnosed with unilateral invasive clinically T1-2 N0 breast cancer who are treated with mastectomy, and who have a maximum of three axillary sentinel lymph nodes containing micro- and/or macrometastases, will be randomized for completion axillary treatment versus no completion axillary treatment. Completion axillary treatment can consist of completion axillary lymph node dissection or axillary radiation therapy. Primary endpoint is regional recurrence rate at 5 years. Based on a 5-year regional recurrence free survival rate of 98 % among controls and 96 % for study subjects, the sample size amounts 439 per arm (including 10 % lost to follow-up), to be able to reject the null hypothesis that the rate for study and control subjects is inferior by at least 5 % with a probability of 0.8. Results will be reported after 5 and 10 years of follow-up. DISCUSSION: We hypothesize that completion axillary treatment can be safely omitted in sentinel node positive breast cancer patients undergoing mastectomy. If confirmed, this study will significantly decrease the number of breast cancer patients receiving extensive treatment of the axilla, thereby diminishing the risk of morbidity and improving quality of life, while maintaining excellent regional control and without affecting survival. TRIAL REGISTRATION: The BOOG 2013-07 study is registered in the register of ClinicalTrials.gov since April 10, 2014, Identifier: NCT02112682 .

Malignant differential diagnosis in children referred for infantile hemangioma.

BACKGROUND AND AIM: Early age malignant tumors can mimic benign infantile hemangioma (IH). The purpose of this study was to determine the percentage of patients referred with a diagnosis of IH that were misdiagnosed, including that of those who in fact had malignant lesions and to assess how the misdiagnosis was reached. METHODS: From April 2003 through December 2009, all records of children, referred with a diagnosis of IH, were studied to determine the definitive diagnosis. Characteristics of the children with malignant diagnoses and of their diagnostic process were retrospectively analyzed. RESULTS: The referral diagnosis "hemangioma" was recorded in 423 children and confirmed in 89%. Thirty-nine children were rediagnosed with a vascular malformation (7%) or other benign anomalies (2%). The 7 (2%) remaining children were diagnosed with a malignancy. CONCLUSIONS: In cases where the diagnosis of IH is equivocal, biopsy has to be performed in a specialized center to prevent delay.