Clinical and dermoscopic findings of benign longitudinal melanonychia due to melanocytic activation differ by skin type and predict likelihood of nail matrix biopsy.

BACKGROUND: Longitudinal melanonychia (LM) is a common dermatologic finding in clinical practice with a broad differential diagnosis. Melanocytic activation is the most common LM etiology. OBJECTIVE: To investigate clinical and dermoscopic differences of benign LM based on Fitzpatrick skin type and in biopsied versus nonbiopsied patients. METHODS: A 10-year retrospective cohort of 248 benign LM cases at Weill Cornell Dermatology was identified and analyzed. RESULTS: Darker-skinned versus lighter-skinned patients had higher band width percentage (P = .0125), had lower band brightness (P < .001), had more band changes (P = .0071), and received more biopsies (P = .032). Biopsied (n = 47) versus nonbiopsied patients (n = 201) had less multidigit band involvement (P = .0008), higher band width percentage (P = .0213), lower band brightness (P = .0003), and more band changes (P < .0001). Darker skin types more often had brown versus gray coloration on dermoscopy (P = .0232). The mean band width percentage for all biopsied patients was 30.81% (range: 5.80%-100%). LIMITATIONS: Single-center retrospective design. Subungual melanoma and other benign LM etiologies were not analyzed. Only 18.95% of patients received a biopsy. CONCLUSION: Darker versus lighter skin types more often present with darker and wider bands, present with brown versus gray coloration on dermoscopy, and receive more biopsies. Multi-institutional studies on LM are needed to determine nail matrix biopsy criteria in different skin types.

The Potential of N-Acetylcysteine for Treatment of Trichotillomania, Excoriation Disorder, Onychophagia, and Onychotillomania: An Updated Literature Review.

BACKGROUND: Trichotillomania (TTM), excoriation disorder, onychophagia, and onychotillomania are categorized as body focused repetitive behavior (BFRB) disorders, causing damage to the skin, hair, and/or nails with clinically significant psychosocial consequences. Currently, there are no standardized treatments for these compulsive, self-induced disorders. Studies on treatment of these disorders using psychotropic drugs (i.e., selective serotonin reuptake inhibitors, tricyclic antidepressants, anticonvulsants) have shown variable efficacy. Recently, there is a growing interest in N-acetylcysteine (NAC) for treating BFRBs. NAC is a glutamate modulator that has shown promise in successfully reducing the compulsive behaviors in BFRB disorders. This article provides an updated review of the literature on the use of NAC in TTM, excoriation disorder, onychophagia, and onychotillomania. METHODS: Relevant articles were searched in the PubMed/MEDLINE database. RESULTS: Twenty-four clinical trials, retrospective cohort studies, and case reports assessing the efficacy of NAC in TTM, excoriation disorder, and onychophagia were included. No studies for onychotillomania were found in our search. CONCLUSIONS: Although NAC has proven successful for treatment of BFRB disorders, data is derived from few clinical trials and case reports assessing small numbers of patients. Larger studies with longer durations are needed to fully establish the efficacy of NAC in these disorders.

Optimal diagnosis and management of common nail disorders.

Nail conditions are not only aesthetic concerns, and nail changes may be a clue to an underlying systemic diseases or infection. Without timely treatment, nail diseases can continue to worsen and significantly impair performance of daily activities and reduce quality of life. Examination of the nails is essential at every medical visit, and may uncover important findings. Brittle nail syndrome, onychomycosis, paronychia, nail psoriasis, longitudinal melanonychia, Beau's lines, onychomadesis and retronychia are common nail disorders seen in clinical practice. These conditions stem from infectious, inflammatory, neoplastic and traumatic aetiologies. Though each nail condition presents with its own distinct characteristics, the clinical findings may overlap between different conditions, resulting in misdiagnosis and treatment delays. Patients can present with nail plate changes (e.g. hyperkeratosis, onycholysis, pitting), discolouration, pain and inflammation. The diagnostic work-up of nail disease should include a detailed history and clinical examination of all 20 nail units. Dermoscopy, diagnostic imaging and histopathologic and mycological analyses may be necessary for diagnosis. Nail findings concerning for malignancy should be promptly referred to a dermatologist for evaluation and biopsy. Nail disease management requires a targeted treatment approach. Treatments include topical and/or systemic medications, discontinuation of offending drugs or surgical intervention, depending on the condition. Patient education on proper nail care and techniques to minimize further damage to the affected nails is also important. This article serves to enhance familiarity of the most common nail disorders seen in clinical practice. It will highlight the key clinical manifestations, systematic approaches to diagnosis and treatment options for each nail condition to improve diagnosis and management of nail diseases, as well as patient outcomes.Key messagesNail disease is not only a cosmetic issue, as nail changes can indicate the presence of a serious underlying systemic disease, infection or malignancy.Nail pain and changes associated with NP are physically and emotionally distressing and may contribute to functional impairment and diminished quality of life.LM is a hallmark sign of subungual melanoma and this finding warrants further investigation to rule out malignancy.

Multiple painful plaques and the Sweet's syndrome.

We present a rare case of Sweet's syndrome. A 39-year-old woman with subjective fevers, polyarthralgia, and malaise presented with worsening painful erythematous plaques on the trunk, arms, and legs. Further examination with biopsy revealed a diagnosis of acute febrile neutrophilic dermatosis, or Sweet's syndrome. Diagnosis by skin biopsy is crucial, and onset requires prompt evaluation for serious associated disorders such as leukemias, inflammatory bowel disease, thyroid disease, sarcoidosis, and infectious etiologies. In general, symptoms and cutaneous manifestations of Sweet syndrome respond rapidly to treatment with systemic corticosteroids or potassium iodide.

The effect of imaging modality (magnetic resonance imaging vs. computed tomography) and patient position (supine vs. prone) on target and organ at risk doses in partial breast irradiation.

INTRODUCTION: Conventionally computed tomography (CT) has been used to delineate target volumes in radiotherapy; however, magnetic resonance imaging (MRI) is being continually integrated into clinical practice; therefore, the investigation into targets derived from MRI is warranted. The purpose of this study was to evaluate the impact of imaging modality (MRI vs. CT) and patient positioning (supine vs. prone) on planning target volumes (PTVs) and organs at risk (OARs) for partial breast irradiation (PBI). METHODS: A retrospective data set, of 35 patients, was accessed where each patient had undergone MRI and CT imaging for tangential whole breast radiotherapy in both the supine and prone position. PTVs were defined from seroma cavity (SC) volumes delineated on each respective image, resulting in 4 PTVs per patient. PBI plans were generated with 6MV external beam radiotherapy (EBRT) using the TROG 06.02 protocol guidelines. A prescription of 38.5Gy in 10 fractions was used for all cases. The impact analysis of imaging modality and patient positioning included dose to PTVs, and OARs based on agreed criteria. Statistical analysis was conducted though Mann-Whitey U, Fisher's exact and chi-squared testing (P < 0.005). RESULTS: Twenty-four patients were eligible for imaging analysis. However, positioning analysis could only be investigated on 19 of these data sets. No statistically significant difference was found in OAR doses based on imaging modality. Supine patient position resulted in lower contralateral breast dose (0.10Gy ± 0.35 vs. 0.33Gy ± 0.78, p = 0.011). Prone positioning resulted in a lower dose to ipsilateral lung volumes (10.85Gy ± 11.37 vs. 3.41Gy ± 3.93, P = <0.001). CONCLUSIONS: PBI plans with PTVs derived from MRI exhibited no clinically significant differences when compared to plans created from CT in relation to plan compliance and OAR dose. Patient position requires careful consideration regardless of imaging modality chosen. Although there was no proven superiority of MRI derived target volumes, it indicates that MRI could be considered for PBI target delineation.

Pediatric phase I trials in oncology: an analysis of study conduct efficiency.

PURPOSE: To determine the efficacy and safety of pediatric phase I oncology trials in the era of dose-intensive chemotherapy and to analyze how efficiently these trials are conducted. METHODS: Phase I pediatric oncology trials published from 1990 to 2004 and their corresponding adult phase I trials were reviewed. Dose escalation schemes using fixed 30% dose increments were studied to theoretically determine whether trials could be completed utilizing fewer patients and dose levels. RESULTS: Sixty-nine pediatric phase I oncology trials enrolling 1,973 patients were identified. The pediatric maximum-tolerated dose (MTD) was strongly correlated with the adult MTD (r = 0.97). For three-fourths of the trials, the pediatric and adult MTD differed by no more than 30%, and for more than 85% of the trials, the pediatric MTD was less than or equal to 1.6 times the adult MTD. The median number of dose levels studied was four (range, two to 13). The overall objective response rate was 9.6%, the likelihood of experiencing a dose-limiting toxicity was 24%, and toxic death rate was 0.5%. CONCLUSION: Despite the strong correlation between the adult and pediatric MTDs, more than four dose levels were studied in 40% of trials. There appeared to be little value in exploring dose levels greater than 1.6 times the adult MTD. Limiting pediatric phase I trials to a maximum of four doses levels would significantly shorten the timeline for study conduct without compromising safety.

Adherens junctions and tight junctions are regulated via different pathways by progastrin in epithelial cells.

Adhesion between neighbouring epithelial cells is a crucial and tightly controlled process. In the gastrointestinal tract, the integrity of cell-cell contacts is essential for the regulation of electrolyte absorption and for the prevention of tumour metastasis. We recently showed that migration of the gastric epithelial cell line IMGE-5 is stimulated by the nonamidated form of the hormone gastrin(17). Here, we examine the effect on cell-cell adhesion of the prohormone progastrin, the concentration of which is increased in the plasma of patients with colorectal carcinoma. Progastrin induced the dissociation of both tight junction (TJ) and adherens junction (AJ) complexes in IMGE-5 cells. In progastrin-secreting DLD-1 human colorectal carcinoma cells, expression of an antisense gastrin construct restored membrane localisation of zonula occludens-1 (ZO-1), occludin, beta-catenin and E-cadherin. This restoration was reversed by treatment with exogenous progastrin. Endogenous or exogenous progastrin also increased the paracellular flux of mannitol, and induced cell migration of several gastrointestinal cell lines. In addition, progastrin enhanced Src tyrosine kinase activity and induced a spatial delocalisation of protein kinase C alpha. Using dominant-negative mutants and pharmacological inhibitors, we showed that the stimulation of Src kinase activity was essential for the regulation of TJs. By contrast, the dissociation of AJs involved phosphatidylinositol 3-kinase, partly through the formation of a complex with protein kinase C alpha. We conclude that separate pathways mediate the disruption of AJs and TJs by progastrin. Either pathway may contribute to the co-carcinogenic role of this prohormone in colorectal carcinoma.