Efficacy of bath-psoralen and ultraviolet A therapy for mycosis fungoides - retrospective analysis of 62 cases.

Photochemotherapy with psoralen and ultraviolet A (PUVA) is widely used for refractory skin diseases. Bathwater delivery of 8-methoxypsoralen (8-MOPS) with subsequent UVA irradiation (bath-PUVA) or oral administration of 8-MOPS with UVA is used to treat mycosis fungoides. We retrospectively analyzed 62 patients with mycosis fungoides (8 stage IA, 30 stage IB, 5 stage IIB, 18 stage IIIA, and 1 stage IVA2) treated with bath-PUVA at the Dermatology Clinic of Nagoya City University Hospital from November 2004 to December 2013. A complete response was achieved in 37 (59.7%) patients, a partial response was achieved in 16 (25.8%), and stable disease was achieved in 6 (9.7%). Progressive disease was observed in 3 (4.8%) patients. Almost all patients in stage IA/IB achieved a complete response. Of the 5 stage IIB patients, 2 achieved a partial response, 1 achieved stable disease, and 2 had progressive disease. The serum concentrations of soluble interleukin-2 receptor and lactate dehydrogenase decreased significantly following treatment with bath-PUVA (p < 0.001). We examined the risk factors of patients whose stage progressed despite PUVA treatment. A multivariate Cox regression analysis of risk factors associated with stage progression yielded a hazard ratio of 28.5 for stage IIb. Treatment with bath-PUVA is highly effective in the early stages of mycosis fungoides, and partially effective in advanced stages.

Combined serum carcinoembryonic antigen and cytokeratin 19 fragment levels provide a sensitive biomarker for lymph node metastasis in extramammary Paget's disease.

Most cases of extramammary Paget's disease are diagnosed at an early stage. For advanced cases, few effective treatments are available and the prognosis is poor. Therefore, developing sensitive biomarkers for metastatic cases is a critical challenge. Carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA) are two potentially useful biomarkers. In the present retrospective large-scale study, we identified other potential biomarkers of lymph node metastasis. Patients with extramammary Paget's disease who visited our dermatology clinic between April 2004 and March 2019 (n = 138; mean age, 73.4 years; 85 men and 53 women) were enrolled in the study. The patients were divided into three groups according to the presence of regional lymph node metastasis and distant metastasis to evaluate the relationship between metastasis and various tumor markers: serum CEA, carbohydrate antigen (CA)19-9, CA125, CA15-3 and CYFRA. For distal metastasis, each biomarker had high sensitivity and specificity. The sensitivities and specificities for regional lymph node metastasis were as follows: CEA, 50.0% and 88.6%; CA19-9, 50% and 89.5%; CA125, 0% and 98.2%; CA15-3, 0% and 96.0%; and CYFRA, 66.7% and 95.0%, respectively. We also analyzed biomarker combinations. The sensitivity and specificity of the combination of all five biomarkers (CEA, CA19-9, CA125, CA15-3 and CYFRA) were 83.3% and 70.9%, respectively. The sensitivity of the combination of just CEA and CYFRA was also 83.3%. Screening for combinations of these biomarkers will facilitate the detection of early lymph node metastasis in patients with extramammary Paget's disease.

Facial site distribution of basal cell carcinoma in Japanese.

Basal cell carcinoma (BCC) occurs preferentially on the face. We retrospectively analyzed 200 cases of BCC treated at Nagoya City University Hospital from April 2004 to October 2015 and examined regional features based on modified facial aesthetic units. BCC occurred more frequently on the cheek, nasal and orbital areas. There was no significant difference between sides, and age was the only factor affecting tumor size.

Facial distribution of squamous cell carcinoma in Japanese.

Squamous cell carcinoma (SCC) is a malignant tumor of the skin. SCC is frequently distributed on highly exposed areas such as the face and dorsal surface of the hands because it is closely related to ultraviolet damage. We retrospectively analyzed 106 cases of SCC treated at Nagoya City University Hospital from April 2004 to October 2015 and examined regional features based on modified facial aesthetic units. SCC occurred more frequently on the cheek and forehead on the right side. The site of the tumor (nose and eyelid) was the only factor affecting tumor diameter.

Efficacy of low-dose 5-fluorouracil/cisplatin therapy for invasive extramammary Paget's disease.

Extramammary Paget's disease (EMPD) is one of the cutaneous adenocarcinomas. The effective chemotherapy for advanced EMPD has not been established. This study was designed to evaluate the efficacy of combination 5-fluorouracil (500 mg/body, 7 days/week) and cisplatin (5 mg/body 5 days/week) for invasive EMPD. Seventeen EMPD patients with multiple metastases who visited our dermatology clinic between October 2004 and May 2016 (mean age, 76.9 years; 10 men, seven women) were retrospectively analyzed. Eight EMPD patients underwent low-dose 5-fluorouracil/cisplatin therapy and nine patients chose best supportive care. The average number of treatment cycles was 12.3. All patients had a confirmed response, four (50%) showed a partial response, two (25%) stable disease and two progressive disease. The median times to progression-free and overall survival were 25.0 and 77.4 weeks, respectively. There was no severe (grade 3 and 4) adverse event. Although not significant, the survival of the patients treated with low-dose 5-fluorouracil/cisplatin therapy showed a trend toward improved survival as compared with best supportive care (P = 0.08, log-rank test). This regimen had low risk and relatively high disease control rate, suggesting that this regimen be recommended as one of the treatment options for advanced EMPD.

Dermopathy associated with cetuximab and panitumumab: investigation of the usefulness of moisturizers in its management.

AIMS: Limited data regarding the objective evaluation of skin exsiccation caused by epidermal growth factor receptor (EGFR) inhibitors exist. Objective indices were applied to evaluate the usefulness of a moisturizer against skin exsiccation associated with the use of EGFR inhibitors in cancer patients. PATIENTS AND METHODS: Patients with either colorectal or head and neck cancer treated with either cetuximab or panitumumab were randomly assigned 1:2 to the prophylactic-treatment arm, where participants received prophylactical moisturizer treatment (heparinoid preparation, Hirudoid®), or to the symptomatic-treatment arm, where moisturizer was applied after the onset of cutaneous symptoms. Patients were observed for 6 weeks after the start of the administration of EGFR inhibitor. RESULTS: A total of 15 patients were included and assessed: 6 in the prophylactic treatment group and 9 in the symptomatic treatment group. We evaluated the effect of EGFR inhibitors on the physiologic function of the skin. Administration of EGFR inhibitors resulted in a continued reduction in the moisture content of the horny layer and a decrease in cutaneous sebum levels. Skin observation revealed frequent development of an acneiform rash and significantly higher exsiccation and exfoliation scores. Administration of EGFR inhibitor was associated with a decrease in the horny layer moisture content and lower cutaneous sebum levels in the symptomatic treatment group. In contrast, levels of both the indicators were increased in the prophylactic treatment group. Moreover, the EGFR inhibitor-associated increase in exsiccation and exfoliation scores were minimized in the prophylactic treatment group relative to the symptomatic treatment group. CONCLUSION: Application of a moisturizer is effective against dry skin induced by the administration of an EGFR inhibitor.

Risk factors and treatment responses in patients with vitiligo in Japan--A retrospective large-scale study.

Vitiligo is a refractory skin disease. To investigate the risk factors and treatment responses of patients with vitiligo in Japan, we recorded and analyzed the details of 713 vitiligo patients (comorbidity, treatment responses, family history, age, and sex) who visited the dermatology clinic of the Nagoya City University Hospital, Nagoya, Japan between January 2004 and August 2010 (mean age, 35.2 years; 302 men, 411 women) using logistic regression analysis. The results are expressed as odds ratios (OR) with 95% confidence interval (CI). Patients were diagnosed with vitiligo [n = 644; 338 generalized type (47.4%), 170 segmental type (23.8%), and 136 localized type (19.1%)], nevus depigmentosus (n = 53, 7.4%), halo nevus (n = 14, 2.0%), and hypomelanosis of Ito (n = 2, 0.3%). For generalized and localized types, none of the analyzed factors were statistically significant. For the segmental type, antinuclear antibody (OR = 1.005; 95% CI, 1.00-1.01; p < 0.05) and onset age < 14 years were the significant factors in patients between 15 years and 29 years (OR = 0.246; 95% CI, 0.113-0.538; p < 0.001), 30-54 years (OR = 0.0419; 95% CI, 0.0133-0.132; p < 0.001), and >55 years (OR = 0.0171; 95% CI, 0.00333-0.0879; p < 0.001). The treatment response rates for narrow-band UV-B, topical vitamin D3, and punch graft (1 mm minigraft) were, respectively, as follows: (1) generalized type: 46.3%, 21.1%, and 38.9%; (2) segmental type: 20.3%, 29.0%, and 77.3%; and (3) localized type: 29.2%, 54.8%, and 73.3%. We report the comorbidities and efficacy rates of these treatments. The response data for these treatments, in particular, would be of assistance to the previous explanations, because there were only a few reports on the response data for these treatments. The appropriate treatment should be selected depending on the type of vitiligo.

Reconstruction of the external auditory canal using the random flap technique and laser Doppler evaluation.

BACKGROUND: The external auditory canal is one of the most difficult sites to reconstruct after tumor resection. In general, fascia transplantation is used to reconstruct defects of the external auditory canal, but this method is associated with scar formation and prolonged wound healing. Scar tissue might cause stenosis in the external auditory canal and hypoacusis, and wound healing is further delayed by radiation and chemotherapy. OBJECTIVE: To examine the safety of a random flap for reconstruction of an external auditory canal based on blood flow evaluation using a laser Doppler system. METHODS: Ten healthy volunteers were enrolled in this study to compare blood flow in the face, back, and behind the ear using a laser Doppler system. Two cases of external auditory canal reconstruction are presented. RESULTS: Blood flow behind the ear was abundant compared with that in the back. Blood flow in the face was higher than that behind the ear or on the back. CONCLUSION: Blood flow in the random flap was easily evaluated using the laser Doppler method. Based on our findings, we propose the random flap to reconstruct the external auditory canal after tumor resection.

Highly frequent and enhanced injection site reaction induced by peripheral venous injection of fosaprepitant in anthracycline-treated patients.

BACKGROUND: Fosaprepitant-associated injection site reaction (ISR) has been reported in patients treated with cisplatin, an irritant drug. We conducted this retrospective study to clarify the incidence and symptoms of fosaprepitant-associated ISR in patients treated with anthracycline. PATIENTS AND METHODS: Fifty six patients receiving 159 injections administering doxorubicin/cyclophosphamide (AC), fluorouracil/epirubicin/cyclophosphamide (FEC), or rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-)CHOP regimen through a peripheral vein at ambulatory treatment centers reviewed for this study from patients' medical records. Incidence of ISR was compared between 24 patients with fosaprepitant injection (fosaprepitant group) and 32 patients without fosaprepitant (control group). Frequency and symptoms of ISR per injection were also compared between 61 injections with fosaprepitant and 98 injections without fosaprepitant. RESULTS: Both the ISR incidence rate per patient and per injection were significantly higher in the fosaprepitant group than in the control group (67% vs. 16%; P=0.0002, 34% vs. 8.2%; P<0.0001, respectively). By multivariate analysis, fosaprepitant injection was found to be a significant independent variable correlated with ISR risk. Symptoms observed in 61 injections of fosaprepitant were pain (n=14, 23%), erythema (n=10, 16%), swelling (n=6, 10%), and delayed drip infusion (n=6, 10%). After the observation period, no ISR occurred when the administration route was changed to central venous injection or oral aprepitant was administered despite the continuation of chemotherapy. CONCLUSION: ISR occurred more frequently and severely when fosaprepitant was injected through the peripheral vein in patients treated with anthracyclines compared to those without fosaprepitant.

A case of cutaneous malignant fibrous histiocytoma with multiple organ metastases.

Malignant fibrous histiocytoma is a soft tissue sarcoma that most commonly occurs in the extremities and rarely metastasizes cutaneously. A 79-year-old male patient consulted a dermatologist 11 months after recognizing an intractable ulcer on the right mandible. Punch biopsy revealed eosinophilic tumor cells in the dermal area and proliferation of rich spindle cells. Malignant fibrous histiocytoma or atypical fibroxanthoma was suspected and he was referred to our hospital. Red plaque tumors on the right mandible and right temple were 30 mm and 15 mm in size, respectively. The right mandible lesion was ulcerated. Immunohistochemically, the lesions were positive for CD10, CD74 and alpha-smooth muscle actin. Radiological analysis revealed multiple organ metastases, including bone, liver, lung and skin on the right temple. The patient was diagnosed with malignant fibrous histiocytoma, stage IV and died 8 weeks after the first visit due to respiratory failure. Cutaneous malignant fibrous histiocytoma has a poor prognosis resulting in death.

A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion.

We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography-computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV) plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam) chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma.

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium-99m ((99m)Tc)-tin colloid, (99m)Tc-phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. (99m)Tc-tin colloid, (99m)Tc-phytate, PBV and indocyanine green are useful tracers for SN mapping.

A multilayered polyurethane foam technique for skin graft immobilization.

BACKGROUND: Several techniques are applicable for skin graft immobilization. Although the sponge dressing is a popular technique, pressure failure near the center of the graft is a weakness of the technique that can result in engraftment failure. OBJECTIVE: To evaluate the efficacy of a new skin graft immobilization technique using multilayered polyurethane foam in vivo and in vitro. METHODS AND MATERIALS: Twenty-six patients underwent a full-thickness skin graft. Multiple layers of a hydrocellular polyurethane foam dressing were used for skin graft immobilization. In addition, we created an in vitro skin graft model that allowed us to estimate immobilization pressure at the center and edges of skin grafts of various sizes. RESULTS: Overall mean graft survival was 88.9%. In the head and neck region (19 patients), mean graft survival was 93.6%. Based on the in vitro outcomes, this technique supplies effective pressure (<30 mmHg) to the center region of the skin graft. CONCLUSIONS: This multilayered polyurethane foam dressing is simple, safe, and effective for skin graft immobilization.

Efficacy of 1-mm minigrafts in treating vitiligo depends on patient age, disease site and vitiligo subtype.

Vitiligo vulgaris is a refractory skin disease. Treatment modalities include topical steroids, phototherapy, suction blister roof grafts and cellular grafting techniques. Adverse effects may occur, however, and some cases remain unresponsive to treatment. To evaluate the efficacy of small (1-mm) punch minigraft therapy in relation to patient age, disease site, disease duration and vitiligo subtype. We used a recently developed disposable 1.0-mm punch apparatus to perform minigraft therapy in 20 patients with either generalized (n = 4), segmental (n = 9) or limited (n = 7) vitiligo, and evaluated the area and rate of repigmentation in relation to patient age, disease site, disease duration and vitiligo subtype. The area of repigmentation was significantly greater in patients with segmental vitiligo (n = 9) than in those with generalized vitiligo (n = 4). Repigmentation covered a broader area and occurred more quickly in patients under 15 years of age than in those over 20 years of age (n = 9). Disease duration did not affect the repigmentation rate. The results of the present study suggest that 1-mm minigrafts are effective for treating patients with vitiligo. Better results occurred in patients under 15 years of age, patients with facial grafts, and patients with segmental and limited subtypes.

[Central action of orexins on sympathetic outflow and cardiovascular function with a focus on the paraventricular nucleus of the hypothalamus].

Orexins were initially reported as regulators of food intake. More recent reports suggest that they might play roles in the multiple functions of neuronal systems, causing medical conditions such as narcolepsy, a sleep disorder. Orexins and their receptors (OX1R and OX2R) are distributed in the neural tissue and brain regions involved in the autonomic and neuroendocrine control. Within the hypothalamus, orexin fibers and orexin receptors, especially OX2R, are found extensively in the paraventricular nucleus (PVN) of the hypothalamus. The PVN is an integrative center of the autonomic nervous system and the neuroendocrine system. Thus, orexins may play a role in the regulation of cardiovascular and autonomic nervous systems. This article provides a summary of our studies, in which we used direct recording of renal sympathetic nerve and PVN neuronal activities in conscious freely-moving rats and the in vitro whole cell patch-clamp technique to examine the direct effect of orexins on PVN neurons using a hypothalamic slice. Functional studies demonstrated that intracerebroventricularly (i.c.v.) administered orexins evoke increases in blood pressure, heart rate, and sympathetic nerve activity and depolarize both the magno- and parvo-cellular neurons through the activation of non-selective cation channels. The present studies suggest that PVN plays a role as one of the efferent pathways of orexin-induced activation of the sympathetic outflow.

First episodes of behavioral symptoms in Alzheimer's disease patients at age 90 and over, and early-onset Alzheimer's disease: comparison with senile dementia of Alzheimer's type.

We evaluated dementia symptoms to clarify the character of dementia with Alzheimer's disease (AD) observed in the oldest old patients and that of dementia with early-onset AD. Subjects were consecutive AD inpatients admitted for the first time at age of 90 years and over because of behavioral symptoms (demented nonagenarian group: D90G; n=18) and those with 24 consecutive inpatients with AD with early-onset (EOG). The Gottfries, Brane and Steen's scale and the Dementia Behavior Disturbance scale were used to evaluate the symptoms and troublesome behaviors. The scores of these scales in D90G and in EOG were compared with those of 26 sex distribution-, severity of dementia-, and disease duration-matched inpatients with AD with late-onset (LOG). Compared with LOG, wakefulness was more impaired and waking up at night was more frequent in D90G, while memory, orientation and inappropriate behaviors were more severe in EOG. These results suggest that the clinical features of dementia in EOG were quantitatively different from those of LOG. In contrast, the clinical feature of dementia of D90G were sleep-wake pattern disturbance and were qualitatively different from those of LOG.

Central stresscopin modulates cardiovascular function through the adrenal medulla in conscious rats.

Stresscopin (SCP or urocortin III), a member of the corticotropin-releasing factor (CRF) neuropeptide family, is a high-affinity ligand for the type 2 CRF receptor (CRF(2)). When administered peripherally, SCP suppresses food intake, delays gastric emptying and decreases heat-induced edema. Central administration of CRF produces marked hypertension and increased plasma catecholamine. However, the effects of SCP on the cardiovascular system are unknown. Thus, the present study compared the effects of intracerebroventricular (i.c.v.) administration of CRF and SCP on cardiovascular function. Central administration of SCP (0.05 or 0.5 nmol) elicited transient increases in mean arterial blood pressure (MABP) and heart rate (HR), and the higher dose of SCP (0.5 nmol) resulted in increased plasma epinephrine. In contrast, central administration of CRF provoked long-lasting increases in MABP, HR and plasma catecholamine levels (norepinephrine and epinephrine). Intravenously administered CRF and SCP (0.5 nmol) did not elicit significant changes in MABP and HR. Therefore, these data suggest that centrally administered SCP modulates cardiovascular function, likely through the sympatho-adrenal-medullary (SAM) system.