Brachytherapy for radiotherapy-resistant head and neck cancer: A review of a single center experience.

OBJECTIVES/HYPOTHESIS: Despite advances in radiotherapy and chemotherapy treatments for head and neck cancers, the local failure rate is high. In most radiotherapy-resistant cases, surgery is performed; however, some cases are considered unresectable. No standard treatment for these situations has been established. In this study, we review our experience with brachytherapy (BT), which has a different biological mechanism than standard radiotherapy. METHODS: All patients received prior radiation to the recurrence area. Median high-dose radiation BT dose was 50 Gy, administered in 5 to 10 Gy fractions twice daily for 5 days. High-dose radiation was given via four to 10 catheters inserted under local anesthesia (3 patients) or general anesthesia with preventive tracheostomy (10 patients). RESULTS: Thirteen patients received BT from 2010 to 2014. Male:female ratio was 1.6:1, and median age was 66 years (range 23-89). Of those 13 patients, 10 patients were diagnosed with squamous cell carcinoma (SCC) of the oral cavity, two patients with SCC of the nasal mucosa, and one patient with eccrine duct carcinoma. Prior radiation dose ranged from 60 to 70 Gy. Local control was achieved in 11 of 13 patients; only 15.3% (2 of 13) had in-field recurrence. Five patients developed local out-of-field recurrence, and two developed distant metastases. Five patients are alive with no evidence of disease. No major toxicities were encountered. Two patients had severe mucositis and recovered within several weeks. CONCLUSION: Brachytherapy for radiotherapy-resistant head and neck cancers is feasible with minor adverse events, which enables good local control. However, many advanced head and neck cancers develop regional or distant metastases; therefore, additional treatment should be suggested. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2246-2251, 2016.

Efficacy of fractional microneedle radiofrequency device in the treatment of primary axillary hyperhidrosis: a pilot study.

BACKGROUND: Fractional microneedle radiofrequency (FMR) devices deliver energy to the deep dermis through insulated microneedles without destroying the epidermis. These FMR devices have been shown to be effective for the treatment of wrinkles, acne scars and large pores. In this study it was postulated that FMR energy could specifically affect the sweat glands, preserving the skin surface even if sweat glands were seated in the deep dermis. OBJECTIVE: To evaluate the efficacy and safety of FMR for primary axillary hyperhidrosis (PAH) treatment and to conduct a histological analysis before and after treatment. METHODS: Twenty patients with PAH had 2 sessions of bipolar FMR treatment at 4-week intervals. Clinical improvement was evaluated using a Hyperhidrosis Disease Severity Scale (HDSS) and photographs were taken using the starch-iodine test at every visit and 2 months after the last treatment. The amount of sweat reduction was indirectly assessed using a Tewameter™. Skin biopsies were obtained from 3 of the enrolled patients before and after treatment. The satisfaction and adverse reactions of the research participants were recorded at every follow-up visit. RESULTS: HDSS scores decreased significantly from a baseline of 3.3 to 1.5 and 1.8 after the first and second months of posttreatment follow-up sessions, respectively (p < 0.001). In response to a subjective assessment at 1 month after the second treatment, 75% of patients (n = 15) had an HDSS score of 1 or 2, and 70% of patients (n = 14) expressed more than 50% improvement in their sweating. The starch-iodine reaction was also remarkably reduced in 95% of patients (n = 19) after FMR treatment. Histological findings showed a decrease in the number and size of both apocrine and eccrine glands 1 month after the final treatment. Side effects were minimal and included mild discomfort, transient swelling and postinflammatory hyperpigmentation. CONCLUSION: FMR treatment was effective for the treatment of PAH without significant adverse reactions due to direct volumetric heating of the lower dermis.

The efficacy of a microwave device for treating axillary hyperhidrosis and osmidrosis in Asians: a preliminary study.

A microwave-based device has been developed to treat axillary hyperhidrosis by selectively heating the interface between the skin and underlying fat in the axilla. This study was conducted to evaluate the efficacy and safety of microwave-based devices for axillary hyperhidrosis and osmidrosis in Asians. Eleven patients (8 females and 3 males, age range 20-52 years, mean age 37.6 years) with axillary hyperhidrosis or osmidrosis were enrolled, treated with the microwave-based device, and followed up for 7 months. Procedure efficacy, patient satisfaction, and treatment safety were assessed. The clinical records were reviewed and the patients were interviewed individually at follow-up visits or via telephone. Evaluation of sweating showed at least a 2-point drop or greater in hyperhidrosis disease severity scale (HDSS) in 83.3% subjects (10/12 axillae) as measured at the 7-month follow-up. Of 16 axillae with osmidrosis, 93.8% (15/16 axillae) showed good to excellent results. Histologic findings also showed destruction of eccrine and apocrine glands that were replaced with fibrosis. Regarding safety, altered sensation of arms developed in one case that resolved after 3 months. This novel microwave-based treatment appears to be effective and well tolerated for the treatment of axillary hyperhidrosis and osmidrosis in Asians.

Siringometaplasia escamosa ecrina / Eccrine squamous syringometaplasia

Introducción: la siringometaplasia escamosa ecrina (SEE) podría diferenciar algunas erupciones en pacientes tratados con quimioterapia. Material y métodos: se realizó un estudio clínicopatológico de 59 biopsias procedentes de 46 pacientes codificadas como SEE entre junio 1986 y marzo 1998. Treinta pacientes (43 biopsias) habían recibido quimioterapia y 16 pacientes (16 biopsias) no. Resultados: la SEE relacionada con la quimioterapia se caracterizó por una erupción maculopapulosa o placas que afectaban las axilas y/o ingles y/o región palmoplantar en el 82,7% de los casos. Esta distribución correlacionó con el acondicionamiento pretrasplante y las drogas ciclofosfamida y busulfán. La SEE no relacionada con quimioterapia se observó en lesiones erosivas, ulceradas o cicatrices recientes en el 87,5% de los casos, que afectaron estas áreas sólo en el 6,3%. Histológicamente la SEE no asociada a quimioterapia era focal y tenía una relación morfológica directa con una patología previa local en el 93,8% de los casos y la SEE asociada a quimioterapia se acompañaba de una dermatitis de interfase vacuolar en la mayoría de los casos. Conclusiones: Los casos de SEE no relacionada a quimioterapia y los casos de SEE relacionada a quimioterapia tienen características clínicas y histológicas que permiten individualizarlas (AU)

Recall phenomenon with the unusual presence of eccrine squamous syringometaplasia.

The recall phenomenon is an inflammatory reaction limited to a previously X-irradiated field when the patient is treated months or years later with certain drugs. Only a few cases have been reported in dermatological journals. We report a patient with lymphoma who was treated with low-dose abdominal irradiation and high-dose irradiation to the knees and who, 2 months later, when chemotherapy was started, developed a pronounced inflammatory reaction limited to the areas treated with high-dose irradiation. A skin biopsy specimen showed features of radiation damage, marked epidermal changes and extensive eccrine squamous syringometaplasia. This case of the recall phenomenon is of interest because we have found that there is apparently a radiation dose threshold for this event, and because this is the first report of its association with eccrine squamous syringometaplasia.

Radiation response of murine eccrine sweat glands.

Following irradiation of the left-hind feet of mice, we measured the ability of the eccrine glands to secrete sweat following stimulation by pilocarpine. Silicone elastomer impression moulds of the foot pads gave repeatable, detailed localization of sweat ducts by retaining the impression of each emerging sweat droplet. Loss of gland function occurred rapidly following irradiation (within 2 weeks) and the rate of loss was dose-dependent, being over three times greater following a dose of 13.0 Gy than after 6.8 Gy. There was a dose-dependent nadir of function at around 8 weeks, followed by a gradual recovery that was complete by about 30 weeks after irradiation, leaving a dose-dependent residual functional deficit. Eccrine sweat glands are very radiosensitive organs compared with the epidermis. A single dose of 13 Gy resulted in complete loss of eccrine gland function at 8 weeks whilst about 23 Gy would be required to elicit transient moist desquamation, in oxygen-breathing mice. Substantial sparing was seen when two doses were split by intervals of up to 24 h.

Time evolution of the number of functional murine eccrine sweat glands after irradiation: a quantitative analysis of experimental data using a model of proliferative and functional organization.

The function of eccrine sweat glands in the beta-pad of the mouse foot after irradiation was followed over time. Graded doses of X-rays were given to the foot, either as single doses or in two equal fractions separated by a 24-h interval. A quantitative, non-invasive, functional assay was used allowing repeated evaluation of the animals. Sweat gland function was assessed once a week for the first 6 weeks, and at 8, 10, 14, 18, 28, 38 and 45 weeks after irradiation. The beta-pad of the unirradiated foot was used as a control. The function dropped to a nadir within 8-10 weeks after irradiation, whereafter it gradually recovered, reaching a stable level 20-25 weeks after irradiation. These data were analyzed using a mathematical model of proliferative and functional organization of the sweat pore. The model provides a description of the time evolution of pore function, and its basic features were as follows. The functional subunit is a single sweat pore, which will be assayed as functional provided that it contains a number of functional cells above a critical threshold. The functional cells are capable of self renewal (a so-called 'flexible' tissue), and the proportion of proliferating cells is subject to homeostatic control. Irradiation is assumed to transfer a certain fraction of the cells into a state with a limited probability of successful division. This fraction is assumed to have a linear-quadratic dependence on dose. The values of all free model parameters were optimized by a maximum-likelihood fit to the experimental data. With optimized parameter values, the initial decrease, nadir, and long-term level of tissue function estimated from the model were in close agreement with the experimental observations for all the 28 dose groups. Some of the estimated model parameters are: growth fraction 4.2 +/- 0.2%; cell cycle time, 0.95 +/- 0.04 days; number of functional cells in a single pore in the unirradiated animal, 9.9 +/- 0.5; and alpha/beta ratio, 4.3 Gy (95% confidence interval 3.1-5.0 Gy). It is concluded that the present model, despite its relative mathematical simplicity, provides a close description of the postirradiation kinetics of functional cells in the mouse sweat gland.

[Metastasizing eccrine porocarcinoma]. / Metastasierendes ekkrines Porokarzinom.

We report on an 84-year-old female patient who presented with abundant firm skin nodules and massive lymphoedema restricted to the left leg. Metastasizing eccrine porocarcinoma was diagnosed by the unusual circumscribed pattern of the cutaneous metastases and the histological detection of intraepidermal and intradermal PAS-positive tumour cells. This diagnosis was established by the histopathological reexamination of a small skin tumour on the left ankle, which had been misinterpreted as actinic keratosis 5 years before. The initiated local radiation therapy with fast neurons and cobalt-60 resulted in partial regression of the cutaneous metastases and lymphoedema, but was not able to hamper the fatal outcome directly resulting from tumour cachexia.

A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin.

Following stimulation with pilocarpine, the secretion from eccrine sweat glands produces characteristic imprints in hardening silicone polymers applied to the skin. This permits an accurate determination of the numerical density of functional eccrine glands in irradiated skin which can be compared to non-irradiated skin. A description of this inexpensive, noninvasive, and quantitative technique is presented as well as preliminary results determined in six normal subjects and 28 irradiated patients. Eleven patients, with atrophy and telangiectasia after radiotherapy to the skin to a high dose, were found to have no functional eccrine glands by this technique. A range of results from normal numbers of eccrine glands through partial and, rarely, complete loss was observed in patients given lower doses and in whom the skin was visually normal. When the irradiated side outside the boost area in 16 breast cancer patients who received postoperative radiotherapy was compared to an equivalent area on the untreated, contralateral side, 11 showed a greater than 50% reduction in the density of functional eccrine glands. The method appears to be a sensitive, quantitative assay for a permanent change in skin and so ought to facilitate meaningful comparison of different regimens of radiotherapy. Further studies are required to determine the dose-response relationship, latency and progression of the observed changes.

Electron beam therapy. Its effect on eccrine gland function in mycosis fungoides patients.

An observed clinical side effect of total skin surface electron beam therapy is the patient's inability to perspire. An evaluation of eccrine sweat gland function was performed, utilizing acetylcholine chloride and a silicone impression material. The patient's inability to sweat after therapy, and recovery within a three- to six-month period after therapy was demonstrated. This phenomenon should be appreciated by both the physician and the patient prior to electron beam therapy in order to avoid the potential complications of this condition.