Oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma involving the cervical lymph nodes of unknown primary origin

Abstract

Background

The purpose of this study was to present our findings on the use of limited-field, oropharynx-directed ipsilateral irradiation for p16-positive squamous cell carcinoma of unknown primary origin.

Methods

Between April 2011 and January 2016, 25 patients with a histological diagnosis of p16-positive squamous cell carcinoma were selectively irradiated to the ipsilateral oropharynx and cervical neck for tumors of unknown primary origin. The dose to the oropharynx ranged from 54-60 Gy (median 60 Gy) in 30-33 fractions. Concurrent cisplatin-based chemotherapy was administered to 8 patients (32%).

Results

The actuarial 2-year estimates of locoregional control, progression-free survival, and overall survival were 91%, 87%, and 92%, respectively. One patient failed in the contralateral neck. There was no grade 3 + toxicity in either the acute or late setting.

Conclusion

Oropharynx-directed, ipsilateral radiation results in disease control that compares favorably with historical controls treated by comprehensive mucosal and bilateral neck radiation.

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American Thyroid Association ultrasound system for the initial assessment of thyroid nodules: Use in stratifying the risk of malignancy of indeterminate lesions

Abstract

Background

The ultrasound risk stratification system of the American Thyroid Association (ATA) is frequently adopted in clinical practice. Here, we evaluated its performance in a series of nodules with indeterminate fine-needle aspiration cytology (FNAC) report.

Methods

Indeterminate thyroid nodules diagnosed at 2 medical centers were retrospectively screened, ultrasound images were reevaluated, and lesions were classified according to the ATA. Single ultrasound parameters were also analyzed.

Results

One hundred seventy-three indeterminate lesions were included with 24.8% of malignancy. The high suspicion class showed a cancer rate (75%) significantly (P < .001) higher than that recorded in the other categories (16.8%). Between ultrasound parameters, halo and microcalcifications were the most sensitive and specific ones. The most accurate receiver operating characteristic (ROC)-derived cutoff of nodule's diameter was >4.1 cm. At multivariate analysis, only the ATA class of high suspicion and size >4.1 cm were significantly associated with cancer (odds ratios [ORs] 19.4 and 5.4, respectively).

Conclusion

The ATA ultrasound system is reliable in the risk stratification of indeterminate thyroid lesions.

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The mechanism of skin lipids influencing skin status

Publication date: Available online 21 November 2017
Source:Journal of Dermatological Science
Author(s): Yan Jia, Yao Gan, Congfen He, Zhou Chen, Cheng Zhou
Skin lipids, compose of sebocyte-, keratinocyte-, and microbe- derived lipids, dramatically influence skin status by different mechanisms. (I) Physical chemistry function: They are "mortar" to establish the physico-chemical barrier function of skin; (II) Biochemistry function: They function as signals in the complex signaling network originating at the epidermal level; (III) Microecology function: Sebocyte- and keratinocyte-derived lipids vary the composition of microbial skin flora, and microorganisms metabolize them to produce lipids as signal starting signaling transduction. Importantly, further research needs lipidiomics, more powerful analytical ability and high-throughput manner, to identify skin lipid components into individual species. The validation of lipid structure and function to research the process that lipid species involved in. Additional, the integration of lipidomics data with other omics strategies can develop the power to study the mechanism of skin lipids influencing skin status.



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Dysregulation of autophagy in melanocytes contributes to hypopigmented macules in tuberous sclerosis complex

Publication date: Available online 11 November 2017
Source:Journal of Dermatological Science
Author(s): Fei Yang, Lingli Yang, Mari Wataya-Kaneda, Junya Hasegawa, Tamotsu Yoshimori, Atsushi Tanemura, Daisuke Tsuruta, Ichiro Katayama
BackgroundTuberous sclerosis complex (TSC) gene mutations lead to constitutive activation of the mammalian target of rapamycin (mTOR) pathway, resulting in a broad range of symptoms. Hypopigmented macules are the earliest sign. Although we have already confirmed that topical rapamycin treatment (an mTOR inhibitor) protects patients with TSC against macular hypopigmentation, the pathogenesis of such lesions remains poorly understood.ObjectiveRecently emerging evidence supports a role for autophagy in skin pigmentation. Herein, we investigated the impact of autophagic dysregulation on TSC-associated hypopigmentation.MethodsSkin samples from 10 patients with TSC, each bearing characteristic hypopigmented macules, and 6 healthy donors were subjected to immunohistochemical and electron microscopic analyses. In addition, TSC2-knockdown (KD) was investigated in human epidermal melanocytes by melanin content examination, real-time PCR, western blotting analyses, and intracellular immunofluorescence staining.ResultsActivation of the mTOR signaling pathway decreased melanocytic pigmentation in hypopigmented macules of patients with TSC and in TSC2-KD melanocytes. In addition, LC3 expression (a marker of autophagy) and autophagosome counts increased, whereas, intracellular accumulation of autophagic degradative substrates (p62 and ubiquitinated proteins) was evident in TSC2-KD melanocytes. Furthermore, depigmentation in TSC2-KD melanocytes was accelerated by inhibiting autophagy (ATG7-KD or bafilomycin A1-pretreatment) and was completely reversed by induction of autophagy via mTOR-dependent (rapamycin) or mTOR-independent (SMER28) exposure. Finally, dysregulation of autophagy, marked by increased LC3 expression and accumulation of ubiquitinated proteins, was also observed in melanocytes of TSC-related hypopigmented macules.ConclusionOur data demonstrate that melanocytes of patients with TSC display autophagic dysregulation, which thereby reduced pigmentation, serving as the basis for the hypomelanotic macules characteristic of TSC.



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Editorial board

Publication date: November 2017
Source:Journal of Dermatological Science, Volume 88, Issue 2





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Cold atmospheric plasma (CAP) activates angiogenesis-related molecules in skin keratinocytes, fibroblasts and endothelial cells and improves wound angiogenesis in an autocrine and paracrine mode

Publication date: Available online 26 November 2017
Source:Journal of Dermatological Science
Author(s): Stephanie Arndt, Petra Unger, Mark Berneburg, Anja-Katrin Bosserhoff, Sigrid Karrer
BackgroundCold atmospheric plasma (CAP) emerged as a novel therapeutic field with applications developed for bacterial sterilization, wound healing and cancer treatment. For clinical implementation it is important to know how CAP works and which molecular changes occur after the CAP treatment. Vascularization is an important step during wound healing, however, the effects of CAP on wound angiogenesis are not well examined so far. Furthermore, it has not been investigated, whether CAP primarily affects endothelial cells directly or via paracrine mechanisms to modulate the vasculature.ObjectiveThis study concentrates on the influence of CAP on angiogenesis-related molecules in human epidermal keratinocytes, dermal fibroblasts and endothelial cells.MethodsCAP was generated by the MicroPlaSter ß® plasma torch system and CAP effects on angiogenesis were determined in vitro and in vivo.ResultsWe observed that CAP significantly induces the expression of Artemin, EGF, EG-VEGF (PK1), Endothelin-1 (ET-1), FGF-2 (FGF basic), IL-8 (CXCL8) and uPA in keratinocytes and Angiogenin (ANG), Endostatin (Col18A1), MCP-1 (CCL2), MMP-9, TIMP-1, uPA and VEGF in fibroblasts. In addition, CAP activates the expression of Angiopoietin-2 (Ang-2), Angiostatin (PLG), Amphiregulin (AR), Endostatin, FGF-2 and angiogenic-involved receptor expression of FGF R1 and VEGF R1 in HUVEC endothelial cells. It was also demonstrated that supernatants collected from CAP activated fibroblasts and keratinocytes elevate tube formation by endothelial cells and FGF-2 appears to be an important pro-angiogenic factor that controls vascularization via paracrine mechanisms. Mouse experiments supplement that CAP promotes angiogenesis during wound healing in vivo.ConclusionsTaken together, these results suggest that CAP modulates angiogenesis-involved factors via autocrine and paracrine mechanisms and may be used to affect angiogenesis during wound healing.



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Sweat mechanisms and dysfunctions in atopic dermatitis

Publication date: Available online 21 November 2017
Source:Journal of Dermatological Science
Author(s): Aleksi J. Hendricks, Alexandra R. Vaughn, Ashley K. Clark, Gil Yosipovitch, Vivian Y. Shi
Skin barrier dysfunction is inherent to atopic dermatitis (AD), causing dryness, irritation, and increased permeability to irritants, allergens and pathogens. Eccrine sweat functions as part of the skin's protective barrier. Variations in sweat responses have been observed in patients with AD, and altered sweat composition and dynamics are under-recognized as important factors in the disease cycle. This review discusses the role that sweat plays in the pathogenesis of AD, examines evidence on abnormal sweat composition, secretion, and neuro-immune responses to sweat in atopic skin, and highlights the value of sweat management.



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