RET fusions in a small subset of advanced colorectal cancers at risk of being neglected

Abstract

Background

Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC).

Patients and methods

In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors. RET rearranged and RET negative mCRCs were retrieved by systematic literature review and by taking advantage of three screening sources: 1) Ignyta's phase 1/1b study on RXDX-105 (NCT01877811); 2) cohorts screened at two Italian and one South Korean Institutions; 3) Foundation Medicine Inc. database. Next generation sequencing data were analyzed for RET rearranged cases.

Results

RET fusions were more frequent in older patients (median age of 66 vs. 60 years, p = 0.052), with ECOG PS 1-2 (90% vs. 50%, p = 0.02), right-sided (55% vs. 32%, P=0.013), previously unresected primary tumors (58% vs. 21%, P<0.001), RAS and BRAF wild-type (100% vs. 40%, p < 0.001) and MSI-high (48% vs. 7%, P<0.001). Notably, 11 (26%) out of 43 patients with right-sided, RAS and BRAF wild-type tumors harbored a RET rearrangement.At a median follow-up of 45.8 months, patients with RET fusion-positive tumors showed a significantly worse OS when compared with RET-negative ones (median OS 14.0 vs. 38.0 months, HR: 4.59; 95% CI, 3.64-32.66; P<0.001). In the multivariable model, RET rearrangements were still associated with shorter OS [HR: 2.97; 95% CI, 1.25-7.07; P=0.014], while primary tumor location, RAS and BRAF mutations and MSI status were not.

Conclusions

Though very rare, RET rearrangements define a new subtype of mCRC that shows poor prognosis with conventional treatments and is therefore worth of a specific management.

Treatment and frequency of follow-up of BCC patients in the Netherlands

Abstract

The incidence of Basal Cell Carcinoma (BCC) rises by 5% per decade in the Netherlands (1), representing an important burden on the health care system and dermatologists' workload (2,3). There is no evidence that intensive follow-up results in better outcomes (burden of disease, cosmetic results) in patients with low risk BCCs (4–6). According to the Dutch BCC guideline, follow-up after treatment is not indicated for patients with a low risk BCC (7), but patients may come for follow-up more frequently for various reasons (4,7,8). Considering the enormous amount of patients, extra follow-up visits represent a substantial workload and healthcare costs. Therefore, we studied follow-up of 482 BCC patients, diagnosed in 2010 from general hospitals (N=291 – random sample from a population-based cancer registry) and academic hospitals (N=191), who had a total of 578 BCC diagnosed in 2010. Information on medical history, tumor characteristics and the treatment and follow-up of all diagnosed BCCs was retrieved from the patient files until April 2015.

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Immunohistochemical identification of nail matrix melanocytes

Abstract

Background

No previous studies have been conducted to determine the normal number of nail matrix melanocytes in Latin American individuals. The objective of this work was to determine the number of melanocytes per linear millimeter present in the nail matrix and the nail bed in samples obtained from Colombian individuals.

Methods

Twenty-six unilateral biopsies were taken from 19 cadavers subjected to clinical and medico-legal autopsies. These biopsy samples were processed with conventional histotechnology and immunohistochemistry (IHC) with anti-HMB-45 and anti-MiTF. Three sets of photographs (HE, HMB-45 and MiTF) were taken of each biopsy sample and independently assessed by three pathologists. Each observer counted the number of melanocytes present in 1 linear mm of the nail matrix or bed.

Results

We found an average of 4.6 melanocytes x linear mm with H & E staining, 9.8 with HMB-45 and 12.4 with MiTF.

Conclusions

The use of IHC significantly increases and facilitates the identification of melanocytes in unilateral biopsies. Our IHC counts exceed the averages found in the literature. This finding warrants new studies to verify whether the Colombian population presents higher numbers of melanocytes in the nail matrix than other populations or whether the observed increase is a result of the use of MiTF.

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A case of subepidermal autoimmune bullous disease with autoantibodies against 200-kDa and 290-kDa antigens

Abstract

Epidermolysis bullosa acquisita (EBA) and anti-p200 pemphigoid are uncommon subepidermal autoimmune bullous diseases caused by autoantibodies against the 200-kDa protein and 290-kDa type VII collagen, respectively. Here we describe a patient with autoantibodies against both 200-kDa and 290-kDa antigens.A 63-year-old-man had itchy tense blisters and edematous erythemas scattered on his trunk, buttocks, extremities and soles (Fig. 1a). There were no ocular or mucosal lesions. Psoriatic skin lesions were not observed. There was no personal or family history of serious diseases.

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Patch Testing in Gastrointestinal Diseases – A Systematic Review of the Patch Test (PT) and Atopy Patch Test (APT)

Abstract

Food allergy is common and the prevalence is increasing. The pathogenesis of food allergy has been extensively reviewed. Immunologic and clinical tolerance to food requires production of regulatory T cells that are food-antigen specific. Loss of tolerance to food can lead to IgE-mediated reactions and non-IgE-mediated reactions.

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Contact hypersensitivity in rosacea – a report on 143 cases

Abstract

Rosacea is a chronic skin disease characterized by inflammatory processes affecting mainly the center of the face. The pathophysiology is complex, environmental factors seem to play an important role in the exacerbation and worsening of the lesions. The barrier-dysfunction theory in atopic dermatitis has been well described in the literature.

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Reply to: Kubiak K. And al. Endosymbiosis and its significance in dermatology

Abstract

We would like to begin by congratulating Kubiak K et al on their work[1], which has the potential to contribute to review the question of endosymbiosis and its significance.We would like to add some new data, notes and comments. Some data regarding viral endosymbiosis other than those discussed by the authors, showed the transmission of a Gemycircularvirus - Sclerotinia sclerotiorum hypovirulence-associated DNA1- like virus (SsHADV-1–LV)- via insect vectors - Lycoriella ingenua.

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The iris signal: blue periphery, tan collaret and freckles pattern – strong indicators for epidermal skin cancer in South-Eastern Europe

Abstract

Background

Eye and skin share the embryological origin. Both are established risk factors in epidermal skin cancer. There are few reports using iris colour classification scales, most of them analyse colour in general or are too complex to use in daily practice.

Objectives

To investigate which iris colour pattern is associated with epidermal skin cancer in a S-E European Caucasian population.

Methods

A case control study was conducted on 480 patients: 229 skin cancers patients and 251 controls (dermatological patients free of skin cancers), admitted in two medical clinics of Dermatology in Bucharest, between October 2011 and May 2014. High resolution iris photos were taken for each patient. Three parameters of the iris were analysed individually and in association for each patient: periphery, collaret and freckles.

Results

The most frequent iris colour pattern associated with epidermal skin cancer was blue periphery with light brown collaret and freckles present. In terms of individual parameters, the strongest indicators for skin cancer patients were blue periphery and blue collaret.

Conclusions

The results of this study sustain the hypothesis that blue periphery with light brown collaret and freckles iris pattern is a reliable phenotypic marker for epidermal skin cancer. The results of this study differ from previous reports in which skin cancer risk was associated with a homogenous blue iris. We account these differences to the characteristics of the recruited patients (S-E European, skin type II and III). The assessment of iris colour patterns is an easy and inexpensive detection tool in skin cancer risk assessment.

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5 alpha-reductase inhibitor treatment for frontal fibrosing alopecia: An evidence-based treatment update

Abstract

Background

Treatment for frontal fibrosing alopecia (FFA) is challenging and its treatment regimen often mirrors other lymphocytic-predominant cicatricial alopecia. 5 alpha-reductase inhibitor (5ARI) has been reported with some treatment success in severe cases of FFA.

Objective

To carry out evidence-based analysis of articles published on treatment efficacy and safety of 5 alpha-reductase inhibitor for the treatment of FFA.

Methods

Articles published on the use of 5ARI to treat FFA between 2005 to 2017 were reviewed, analysed and graded according to the American College of Physicians outcome study grading system.

Results

There were two studies with moderate-level of evidence that described the efficacy of 5ARI for treatment of FFA. 5ARI was commonly used as adjunctive therapy with positive results in recalcitrant disease. Mild to moderate hair regrowth was reported in one grade 2 and three lower grade (one grade 3 and two grade 4) studies. There is limited evidence on the safety aspects of this medication in most studies that were analysed.

Limitations

Database studies might not fully account for confounders and is subjected to variations in methodology and data collection.

Conclusion

This review demonstrated that FFA patients treated with 5ARI could achieve either disease stability or reduction in the rate of progression in selected cases. A well designed randomised, double-blind, controlled study would strengthen the role of 5ARI as part of treatment armamentarium for FFA.

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(Meth)acrylate allergy: frequently missed?

Mutilating male genital Crohn's without gastrointestinal involvement

Abstract

A 58 year old gentleman developed multiple fissures and discharging sinuses in the groin and perineum. Skin biopsies showed non-caseating granulomas suggestive of Crohn's disease. The patient had no gastrointestinal symptoms and a radio-labelled white cell scan demonstrated no bowel involvement.

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Long-Term Optimization of Outcomes With Flexible Adalimumab Dosing in Patients With Moderate to Severe Plaque Psoriasis

Abstract

Background

The recently updated dosing recommendation for adalimumab for moderate to severe plaque psoriasis states that patients with inadequate response to adalimumab every other week (EOW) after 16 weeks may benefit from an increase in dosing frequency to 40 mg every week (EW).

Objective

To determine the long-term efficacy of adalimumab in patients with psoriasis with flexibility to escalate and de-escalate between EOW and EW dosing.

Methods

Data from an open-label study in patients with psoriasis who had received adalimumab in phase 2/3 studies and their extensions were included. Patients initially received 40 mg adalimumab EOW for 24 weeks. From weeks 24 to 252, patients whose Psoriasis Area and Severity Index response was <50% (PASI 50) could be dose-escalated to 40 mg EW and were re-evaluated at 6 and 12 weeks and then every 12 weeks thereafter. Patients who dose-escalated and achieved a PASI 75 response were de-escalated to EOW and could re-escalate to EW if response fell below PASI 50 again; no further de-escalation was allowed. Changes in PASI scores were reported at the last visit before dose escalation or de-escalation.

Results

By week 24, 64.1% of patients in the overall population (n=1256) achieved ≥PASI 75 response, 40.3% ≥PASI 90 response, and 21.7% PASI 100 response. Patients who had a <PASI 50 during weeks 24 to 252 (349/1256, 27.8%) were dose-escalated to EW; 182 (52.1%) remained on EW dosing and 167 (47.9%) achieved a PASI 75 response and were de-escalated to EOW; 83 patients were later re-escalated to EW dosing owing to a <PASI 50 response. Dose escalation was not associated with additional safety concerns.

Conclusion

Optimizing therapy by temporarily increasing the dosing of adalimumab to EW in patients with psoriasis and an inadequate response to adalimumab 40 mg EOW permitted the achievement and long-term maintenance of clinical improvement.

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Erythromelalgia: improvement in pain with transcranial magnetic stimulation

Clinical evaluation of simultaneously applied monopolar radiofrequency and targeted pressure energy as a new method for noninvasive treatment of cellulite in postpubertal women

Summary

Introduction

This study investigates noninvasive cellulite treatments based on simultaneous application of monopolar radiofrequency (RF) and targeted pressure energy to evaluate efficacy and safety and to see whether simultaneous application has any benefits in noninvasive cellulite treatments.

Methods

Thirty women with cellulite (fibrous/adipose/aqueous types) received 4 gluteofemoral treatments (~24 minutes; ~1000 cm²) using a simultaneous application of RF and targeted pressure energy. Clinical improvement was assessed using a pentile grading scale and satisfaction questionnaires. Hip/thigh circumference was measured. Ultrasonography and thermography observed changes in dermal/subcutaneous tissue composition and in gluteofemoral thermal profile. Evaluation at 3 months posttreatment was compared against the baseline.

Results

The clinical improvement averaged 2.17 ± 0.95 (54% improvement). Cellulite was reduced in 93% of cases, while 73% of patients showed good/very good/excellent improvement, with most significant improvement seen in patients with moderately severe cellulite. Hips and thigh circumference decreased on average by 2.31 cm and 2.13 cm, respectively (P < .001). Patient satisfaction was very high, averaging 4.47 ± 0.57 points (1-5 scale). Ultrasonography revealed smoothing and thickening (+0.28 ± 0.15 mm) of the dermis and an average reduction of 1.96 ± 1.60 mm in fat thickness (P < .05). Subjects with significant cellulite reduction had a more homogenous thermal profile at follow-up as a result of therapy-induced diminution of topographic skin defects. No adverse events were recorded.

Conclusion

The application is effective and safe for treating cellulite. The level of clinical improvement after 4 sessions is comparable to results reported after 6-20 sessions in studies on stand-alone RF/laser/targeted pressure energy devices. The technology is promising and deserves further attention and research.

Blunt cannula subcision is more effective than Nokor needle subcision for acne scars treatment

Summary

Background and aim

A comprehensive study comparing two different modalities, Nokor needle subcision (NNS) and blunt cannula subcision (BCS), for treatment of acne scars, has not been reported previously. The aim was to compare the effectiveness of these two methods based on patient's and doctor's satisfaction measures, in addition to the late complications 3 months postsubcision.

Method of intervention

Patients had 18-65 years old, with acne scars on both malar sides. They were treated at one malar side with NNS and with BCS at another side. They were monitored during the first week, at one and 3 months postintervention. Patient's and two dermatologist's satisfactions were compared during 3 months, for each modality and between modalities.

Results

From 34 patients, 29.4%, 55.9%, and 14.7% had mild, moderate, and severe acne scars, respectively. Ecchymosis, nodule formation post-NNS, and edema after BCS were the complications. Patients were satisfied with BCS during 3-month monitoring (P = .021), but not with NNS (P = .353). Physician-1 was satisfied from the outcome of both BCS and NNS procedures (P = .044 and .006, respectively). However, physician-2 was only satisfied with NNS at the month 3 than the month 1 (P = .002). All patients and physicians were significantly more satisfied with BCS than NNS (P = .000). Anyway, at the month 3, physician-2 had no significant different points of view about applied methods (P = .25).

Discussion

Considering the complications and satisfaction rates, BCS was more efficient than NNS for acne scar treatment. Then, we suggest BCS as a good replacement for NNS.

Antiaging and antioxidant effects of topical autophagy activator: A randomized, placebo-controlled, double-blinded study

Summary

Background

Recently, potential roles of autophagy in skin homeostasis received many interests. But, little has been reported for the potential antiaging effects of autophagy activator.

Objective

With the newly synthesized autophagy activator, heptasodium hexacarboxymethyl dipeptide-12 (Aquatide™) in vitro and clinical efficacy of the topical autophagy activator as an antiaging cosmeceutical ingredient was evaluated.

Methods

Antioxidant effect of Aquatide™ was evaluated by radical scavenging assay. In vitro effect was assessed by measuring the cytotoxicity of hydrogen peroxide in cultured normal human epidermal keratinocytes. Clinical evaluation was performed by a randomized, placebo-controlled, double-blinded study. Antioxidant efficacy was observed by measuring the carbonylated proteins in stratum corneum (SC) by fluorescein-5-thiosemicarbazide (FTZ) staining.

Results

Radical scavenging effects of Aquatide were observed with the ABTS assay, and significant reduction in hydrogen peroxide-induced cytotoxicity was observed in Aquatide™-treated cells. Autophagy inhibitor treatment abrogated cytoprotective effects of Aquatide™. In a clinical study, statistically significant increase in skin elasticity was observed after 4 and 8 weeks. Quantitative analysis of carbonylated proteins in SC also showed significant reduction in Aquatide™-treated group, which is consistent with the in vitro data.

Conclusion

These results suggest that autophagy plays important roles in antioxidant system and aging process in skin, and topical autophagy activators can be potential cosmeceutical ingredients for skin antiaging.

Interleukin-31 and interleukin-31 receptor–new therapeutic targets for atopic dermatitis

Abstract

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions caused by skin barrier dysfunction and T helper (Th)2 cell–mediated immunity. Interleukin (IL)-31 is a potent pruritogenic cytokine primarily produced by Th2 cells. Both IL-31 transgenic mice and wild-type mice treated with IL-31 exhibit AD-like skin lesions and scratching behaviour. IL-31 receptor α-chain (IL-31RA) are also expressed in peripheral nerves and epidermal keratinocytes, and the roles of IL-31 on pruritus and skin barrier have been investigated. Recently, an anti–IL-31 receptor antibody was shown to significantly improve pruritus in AD patients. This review focuses on IL-31 and IL-31RA in AD.

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Pyriform Aperture Stenosis Repair in Infants

Congenital nasal pyriform aperture stenosis is a rare developmental anomaly, which is considered a variant of holoprosencephaly. It is characterized by a pyriform aperture width of 11mm or less on maxillofacial computed tomography, and is frequently associated with a solitary median maxillary central incisor. It presents with cyclical cyanosis, feeding difficulty, and respiratory distress. Conservative management includes nasal decongestant, saline and steroid drops, or a McGovern nipple. When conservative management fails, surgical intervention is indicated.

Pediatric Sinus Surgery for Chronic Rhinosinusitis

Pediatric chronic rhinosinusitis (CRS) is a common health problem. Pathophysiology is complicated which leads to different treatment options and approaches. Medical treatment with antibiotics and topical nasal sprays is first line treatment. Surgical intervention includes adenoidectomy and endoscopic sinus surgery (ESS). ESS has proven to be an effective and safe option when everything else fails. In this article, we review the indications, our surgical approach and techniques, and the safety considerations in pediatric ESS.

Columellar Reconstruction in Children

Defects of the nasal complex can cause significant functional and psychosocial impairment. Nasal reconstruction aims to restore the normal trilaminar structure of the nose, which includes the internal lining, cartilaginous framework, and soft tissue envelope. Among the nasal subunits, the columella is especially challenging to reconstruct due to its unique contour and composite nature. Multiple techniques have been described, each carrying distinct advantages and disadvantages; however, the optimal procedure for an isolated defect of the columella remains elusive.