Mohs micrographic surgery for dermatofibrosarcoma protuberans: comparison of frozen and paraffin techniques.

BACKGROUND: Due to the propensity for local recurrence, Mohs micrographic surgery (MMS) has been suggested for the treatment of dermatofibrosarcoma protuberans (DFSP) and it has shown improved clinical outcomes. Recently, some authors suggested that MMS using paraffin-embedded sections (paraffin MMS) is superior in DFSP treatment compared with the conventional frozen MMS method. However, there have been no studies comparing frozen and paraffin MMS for the treatment of DFSP. OBJECTIVES: To compare the outcomes between DFSP patients who underwent frozen MMS and paraffin MMS. METHODS: Seventy-one DFSP patients treated with frozen MMS (n = 30) or paraffin MMS (n = 41) from 2003 to 2017 at a single institution were retrospectively reviewed. Recurrence rate and recurrence-free survival between frozen and paraffin MMS were assessed. RESULTS: During the mean follow-up duration of 25.4 months, four patients (frozen MMS, n = 1; and paraffin MMS, n = 3) showed recurrence after MMS. Although the local recurrence rate of the frozen MMS group (3.3%) was lower than that of the paraffin MMS group (7.3%), the difference was not statistically significant. In addition, recurrence-free survival was not significantly different between the two groups (P = 0.168). CONCLUSIONS: Frozen MMS, which has the advantages of shorter surgery time and immediate closure, is as effective as paraffin MMS in the treatment of DFSP.

Drug reaction with eosinophilia and systemic symptoms syndrome is not uncommon and shows better clinical outcome than generally recognised.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare disease which can cause severe morbidity and mortality. The aim of this study is to evaluate the clinical manifestation and course of DRESS syndrome. METHODS: We conducted a retrospective analysis of prospectively collected data in 45 patients with DRESS syndrome diagnosed between September 2009 and August 2011. RESULTS: The most common causative drug group was antibiotics (n=13, 28.9%), followed by anticonvulsants (n=12, 26.7%), antituberculosis drugs (n=6, 13.3%), non-steroidal anti-inflammatory drugs (n=4, 8.9%), undetermined agents (n=4, 8.9%), allopurinol (n=3, 6.7%), and others (n=3, 6.7%). The latency period ranged from 2 to 120 days, with a mean of 20.2 ± 24.3 days. The longest latency period was noted for the antituberculosis drug group, at 46.5 ± 29.9 days. Eosinophilia in peripheral blood examination was noted in 35 subjects (77.8%). Atypical lymphocytosis was noted in 16 patients (35.6%), and thrombocytopenia in seven patients (15.6%). Hepatic involvement was noted in 39 (86.7%) study patients, kidney in eight (17.8%), lung in four (8.9%), and central nervous system in one (2.3%). Systemic corticosteroids were administered to 10 patients (22.2%). Forty-three patients (95.6%) showed complete recovery, while two patients had poor outcomes. CONCLUSIONS: DRESS syndrome was not more uncommon than generally recognised. Antibiotics were the most frequently implicated drug group, followed by anticonvulsants. Most patients with this disease showed a better clinical outcome than that which had been generally expected.

Uncertain areas in the diagnosis of allergic bronchopulmonary aspergillosis in patients with asthma.

BACKGROUND AND OBJECTIVE: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in patients with bronchial asthma remains unknown. We evaluated the roles of various laboratory tests in the diagnosis of ABPA, including, skin prick test (SPT) for Aspergillus fumigatus (Af), and serum Af specific IgE and IgG antibody measurement. METHODS: A total of 50 asthma patients with more than 1000cell/µL of peripheral blood eosinophils were prospectively collected between January 2007 and September 2011. Evaluations using SPT for Af, serum total IgE and specific IgE antibody to Af by CAP system, IgG antibody to Af by enzyme immunoassay (EIA) or CAP system were performed according to the essential minimal criteria for the diagnosis of ABPA - asthma, immediate cutaneous reactivity to Af, elevated total IgE, and raised Af specific IgE and IgG. RESULTS: Among 50 patients, three patients (6.0%) were diagnosed as ABPA, of whom each confirmed five items of the essential minimal diagnostic criteria for the diagnosis of ABPA. Six patients (12.0%) showed negative responses to Af in SPT, but positive responses in specific IgE by CAP system. Eight patients (16.0%) showed negative responses to IgG to Af by CAP system, but positive responses by enzyme immunoassay (EIA). CONCLUSIONS: SPT and serum IgE to Af measurement by CAP system should be performed simultaneously. It is reasonable to set up cut-off values in Af specific IgE/IgG by CAP system for the differentiation of ABPA from Af sensitised asthma patients.

The impact of dermatological toxicities of anti-cancer therapy on the dermatological quality of life of cancer patients.

BACKGROUND: One of the most common side effects of anti-cancer therapies is treatment-induced skin changes, referred to as dermatological toxicities. These dermatological toxicities are noteworthy since they have a negative association with quality of life (QoL). OBJECTIVES: To evaluate the impact of dermatological toxicities on QoL of cancer patients and to identify the relationship between disease-related characteristics and QoL and changes in skin protective behaviours following anti-cancer therapy. METHODS: Cancer patients (n = 80: stage II-IV) in a longitudinal prospective study completed a battery of questionnaires at the time of enrolment and after 3 months of anti-cancer therapy. QoL, skin toxicities, smoking and drinking behaviour, sun-protective and skin care behaviour assessments were performed before and at 3 months after anti-cancer therapy. QoL was measured with the Dermatology Life Quality Index (DLQI). RESULTS: A total of 73 patients completed the study. Among them, 48 patients (65.8%) experienced at least grade 1 skin toxicity at 3 months after anti-cancer therapy. Hair loss, hyperpigmentation and dry skin were the most common dermatological toxicities. The mean baseline DLQI score changed from 1.38 to 3.49 at 3 months after anti-cancer therapy. Domain 1 (symptoms and feelings, 1.38 points) was the most greatly impacted among patients by anti-cancer treatment. Patients who experienced at least grade 1 skin toxicity (P = 0.001, 95% CI: 1.939-4.899), employed (P = 0.042, 95% CI: 0.030-1.476), more highly educated (P = 0.030, 95% CI: 0.161-3.132), and diagnosed with gastric cancer (P = 0.001, 95% CI: 2.141-8.250) or renal cell cancer (P = 0.002, 95% CI: 2.731-11.364) showed significantly higher DLQI scores. Patients showed significant change in skin protective behaviour such as use of body moisturizer (P = 0.021) and change in drinking behaviour (P = 0.006) at 3 months following anti-cancer therapy. CONCLUSION: Dermatological toxicities due to anti-cancer therapy affect the QoL of cancer patients. Therefore, health care professionals should pay attention to the psychological effects of skin problems and educate cancer patients to adapt proactive skin protective behaviours to minimize dermatological toxicities of anti-cancer therapy and maximize QoL.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Topical niacin cream-assisted 595-nm pulsed-dye laser treatment for facial flushing: retrospective analysis of 25 Korean patients.

BACKGROUND: Flushing is defined clinically as a transient reddening of the face and other areas. Due to the transient nature of flushing, a patient may not show signs of flushing during laser treatment. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of 595-nm pulsed-dye laser treatment of flushing or erythema after provocation of flushing by topical niacin cream. METHODS: We retrospectively reviewed a total of 25 Korean patients with facial flushing who were treated with three sessions of 595-nm pulsed-dye laser after the application of topical niacin cream. RESULTS: Follow-up results revealed that 12 of the 25 patients demonstrated marked (51-75%) clinical improvement of baseline facial erythema. Eight patients had moderate (26-50%) improvement and three demonstrated near total (≥ 75%) improvement. Two patients showed minimal to no (0-25%) improvement. We observed that the reactivity to topical niacin cream was markedly reduced in 64% of our patients after 595-nm pulsed-dye laser treatments. Minimal post-therapy facial oedema was noted in most of the patients, which usually resolved spontaneously within 2 days. Pronounced facial swelling was observed in four patients. CONCLUSION: We suggest that 595-nm pulsed-dye laser treatment after provocation of flushing by topical niacin cream may provide a new treatment algorithm for facial flushing in Asians.

Clinical features of drug-induced hypersensitivity syndrome in 38 patients.

BACKGROUND: The clinical features of drug-induced hypersensitivity syndrome (DIHS) or drug rash with eosinophilia and systemic symptoms (DRESS) syndrome are complicated, and the incidence of this condition is very low. OBJECTIVE: To evaluate the clinical course of DIHS/DRESS and identify effective treatment options. METHODS: This study was a retrospective analysis of prospectively collected clinical data in 38 consecutive patients with DIHS/DRESS diagnosed between March 2004 and January 2009. We investigated the clinical features, response to treatment, and outcome of 38 patients. RESULTS: The study patients consisted of 18 men (47.4%) and 20 women (52.6%). The most common causative drugs were anticonvulsants (47.4%) and antibiotics (18.4%), followed by nonsteroidal anti-inflammatory drugs (NSAIDs) (13.2%), allopurinol (5.3%), and undetermined agents (15.8%). The latency period ranged from 3 to 105 days, with a mean (SD) of 25.2 (21.5) days. Systemic corticosteroids were administered to 16 patients (42.1%). Twenty-two (57.9%) patients were treated with topical corticosteroids and antihistamines (no systemic corticosteroids). Complete recovery was noted in 36 patients (94.8%). Two of the patients treated with systemic corticosteroids had a poor outcome: one died due to an opportunistic infection secondary to long-term systemic corticosteroid treatment; the other showed progressive deterioration of liver damage, although the final outcome is not known. CONCLUSION: The drugs associated with DIHS/DRESS were variable and most frequently included anticonvulsants, beta-lactam antibiotics, and NSAIDs. The syndrome was more common than generally recognized. Additional studies are needed to evaluate the clinical indications for systemic corticosteroids in patients with DIHS/DRESS.

Mohs' micrographic surgery for dermatofibrosarcoma protuberans.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare soft-tissue tumour with a high local recurrence rate. Recent reports indicate more favourable cure rates with Mohs' micrographic surgery (MMS). AIM: To investigate the beneficial use of MMS for DFSP in a single institution in Korea. METHODS: A retrospective review was performed of pertinent demographic data, tumour data, treatment characteristics and follow-up data of 11 patients between 1997 and 2007. A review of literature for treatment methods and recurrence rates of DFSP was also performed. RESULTS: In total, 11 patients (7 female, 4 male; mean age 26.9 years, range 3-36) with DFSP were identified and analysed. A mean number of 1.8 MMS layers were required to clear the tumour. All tumours were excised and reconstructed by the surgeon. There were no identifiable recurrences in the follow-up period of an average of 26 months. CONCLUSIONS: Treatment of primary and recurrent DFSP by MMS results in a low recurrence rate with possible benefits of smaller defects compared with wide local excision. This study provides further support for MMS as the treatment of choice for DFSP.

Treatment of infraorbital dark circles by autologous fat transplantation: a pilot study.

BACKGROUND: Infraorbital dark circles are a cosmetic concern for a large number of individuals. However, the exact definition and precise cause has not been elucidated clearly. In our experience infraorbital dark circles due to thin and translucent lower eyelid skin overlying the orbicularis oculi muscle can be treated successfully with autologous fat transplantation. OBJECTIVES: This study was conducted to clarify the nature of dark circles under the eyes and determine the efficacy of autologous fat transplantation. PATIENTS AND METHODS: Ten patients with dark circles due to increased vascularity and translucency of the skin were included. They received at least one autologous fat transplantation and follow-up evaluations were conducted at least 3 months after the last treatment. RESULTS: An average of 1.6 autologous fat transplantations were done in both infraorbital areas. Patients showed an average of 78% improvement (average grading scale: 2.6 out of 4). Most of the patients showed improvement in the infraorbital darkening and contour of the lower eyelids. CONCLUSIONS: Autologous fat transplantation is an effective method for the treatment of infraorbital dark circles due to thin and translucent lower eyelid skin overlying the orbicularis oculi muscle.

Acute generalized exanthematous pustulosis as a manifestation of carbamazepine hypersensitivity syndrome.

Anticonvulsant hypersensitivity syndrome (AHS) is a multisystemic disorder involving cutaneous changes and typical blood abnormalities that can be triggered by aromatic anticonvulsant drugs.The syndrome is commonly associated with a macular or papular rash or erythroderma. Acute generalized exanthematous pustulosis is a very rare cutaneous manifestation of AHS. A 41-year-old man was referred to our hospital for evaluation of a 3-day history of fever, leukocytosis, and generalized skin eruption. The patient had been taking carbamazepine for 1 month to treat hand tremor following surgery for intracerebral hemorrhage. Physical examination revealed facial edema and a large number of variable-sized pustules covering the body. Initial laboratory testing showed peripheral blood eosinophilia and abnormal liver function.A biopsy of pustular lesions revealed intraepidermal pustules, with perivascular lymphocytic infiltration. The skin lesions and laboratory results improved after withdrawal of carbamazepine and treatment with oral corticosteroids.

Syndecan-1 expression in gallbladder cancer and its prognostic significance.

AIM: To determine whether the immunohistochemical detection of syndecan-1 could provide useful information as a novel therapeutic or prognostic factor in primary gallbladder (GB) cancer. MATERIALS AND METHODS: Forty-three GB cancer tissues were evaluated by immunohistochemistry for syndecan-1 expression. The relationship between syndecan-1 expression and clinicopathological characteristics, and the univariate survival analysis for the influence of the syndecan-1 expression on the overall survival were analysed. RESULTS: Epithelial syndecan-1 immunoreactivity was observed in 25 (58.1%) of the 43 GB cancer cases. The tumors with a positive syndecan-1 expression more frequently showed lymph node metastasis (p = 0.037). Although there was no statistically significant association, the tumors with a positive syndecan-1 expression tended to show a deeper invasion depth (p = 0.087) and more frequent lymphovascular invasion (p = 0.064). The Kaplan-Meier survival curves demonstrated that patients with positive syndecan-1 expression had a significantly shorter survival time than those patients with negative syndecan-1 expression (p = 0.05). CONCLUSIONS: A subset of GB cancers revealed an epithelial overexpression of syndecan-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, epithelial syndecan-1 expression may be a predictor for a poor prognosis in patients with GB cancer.

Increase in activity and level of pp60c-src in progressive stages of human colorectal cancer.

Activation of the tyrosine kinase of the c-src gene product, pp60c-src, has been shown to occur in nearly every primary colorectal carcinoma, and is found as early as in polyps of high malignant potential. However, no studies have addressed potential pp60c-src changes which occur during progression. To examine this question, we have studied kinase activity and protein levels in 7 colonic polyps, 19 primary lesions, and 19 liver metastases relative to normal colonic mucosa. Significant increases in tyrosine kinase activity were seen as early as in colonic polyps of high malignant potential. Further increases were observed in activity and level in primary tumors. However, the greatest increases in activity and protein levels were observed in liver metastases. Additionally, six metastatic lesions were obtained in which synchronous primary tumor was resected. In each of these liver metastases, pp60c-src activity and level were significantly increased relative to the corresponding primary tumor, as well as to normal colonic mucosa. Our results demonstrate that progression of colon primary tumors to liver metastases correlates with increased pp60c-src kinase activity and protein level.

Preoperative and postoperative combination chemotherapy for potentially resectable gastric carcinoma.

BACKGROUND: Median survival of patients with local-regional gastric carcinoma is 10 months. Resection of the primary tumor and regional lymph nodes, with tumor-free margins (curative resection), has been the most effective treatment for local-regional gastric carcinoma. However, median survival of patients with curative resection of gastric carcinoma is 24 months, and the 5-year survival rate is about 20%. A single institution pilot study has established the feasibility of administering two courses of chemotherapy preoperatively and three courses postoperatively. In another study, a 15% pathologically documented complete response (pathologic complete response) has been reported in unresectable gastric carcinoma treated with etoposide, doxorubicin, and cisplatin. PURPOSE: Our purpose was to increase the curative resection rate in potentially resectable gastric carcinoma and to delay or eliminate micrometastases and thus improve survival. We also evaluated clinical and pathologic response to chemotherapy. METHODS: Forty-eight previously untreated patients with potentially resectable gastric carcinoma received a chemotherapy regimen (EAP) consisting of etoposide (120 mg/m2 intravenously over a 2-hour period on days 4, 5, and 6), doxorubicin (20 mg/m2 as a 10-minute intravenous infusion on days 1 and 7), and cisplatin (40 mg/m2 as a 1-hour intravenous infusion on days 2 and 8). Patients received three courses of chemotherapy before resection, and responding patients received two courses postoperatively. Clinical and pathologic response rates, toxicity, patterns of treatment failure, and survival times were assessed. RESULTS: A median of three courses (range, 1-5) of preoperative therapy was administered; six (12%) of the 48 patients had clinical complete response, and nine (19%) had partial response. Forty-one (85%) underwent surgery; 37 (90%) of these 41 (77% of the 48 patients) had a curative resection. There were no pathologic complete responses. Median survival for all patients is 15.5 months (range, 2-29+ months). Therapy was discontinued because of the toxic effects in one patient before surgery and in six patients after surgery. Doses were reduced in 37 patients (77%), mainly because of hematologic toxicity. Nineteen (40%) were hospitalized because of toxic effects, including 15 patients who developed fever with neutropenia. Grade 3 or 4 nausea and vomiting occurred in 15 patients and grade 3 or 4 diarrhea in seven patients. One death was directly related to chemotherapy. CONCLUSIONS: These data support that administration of preoperative and postoperative chemotherapy for local-regional gastric carcinoma is feasible in a multi-institutional setting. Our findings demonstrate that this EAP regimen is modestly active but is associated with substantial toxicity. IMPLICATIONS: Use of preoperative chemotherapy in resectable gastric carcinoma merits further evaluation, but more effective drug regimens will be required before a controlled trial is initiated.