Erlotinib-related skin toxicities: treatment strategies in patients with metastatic non-small cell lung cancer.

Skin toxicities are the most common side effects associated with the epidermal growth factor receptor inhibitor erlotinib, occurring in most patients receiving the drug. Clinical trials evaluating erlotinib for the treatment of non-small cell lung cancer have reported a range of skin disorders, the most common being acneiform rash, xeroderma (dry skin), pruritus, and paronychia. Although in the majority of cases these effects are mild and transient, they can have a considerable impact on a patient's quality of life and, if particularly severe and persistent, may necessitate treatment interruption or cessation and compromise treatment outcome. This coupled with recent evidence to suggest a positive correlation between the incidence and severity of rash and clinical outcome among erlotinib-treated patients with advanced or metastatic non-small cell lung cancer highlights the importance of adequately managing epidermal growth factor receptor inhibitor--related skin disorders. Clear treatment strategies are therefore necessary to ensure the prevention and optimal management of erlotinib-related skin toxicities thereby enabling patients to continue erlotinib treatment. In this review we present a practical approach for the treatment of erlotinib-related cutaneous side effects in Japanese patients with advanced non-small cell lung cancer providing details of specific treatment interventions, according to symptom severity, for each of the common skin disorders. In addition, the importance of preventive skin care measures--namely maintaining cleanliness, moisturization, and protection from external stimuli--in preventing the development of serious skin disorders is discussed and guidelines for the practice of proper skin care are presented.

Clinical and histopathological characteristics and survival analysis of 4594 Japanese patients with melanoma.

BACKGROUND: The incidence of melanoma among those of an Asian ethnicity is lower than in Caucasians; few large-scale Asian studies that include follow-up data have been reported. OBJECTIVES: To investigate the clinical characteristics of Japanese patients with melanoma and to evaluate the prognostic factors. METHODS: Detailed patient information was collected from the database of Japanese Melanoma Study Group of the Japanese Skin Cancer Society. The American Joint Committee on Cancer seventh Edition system was used for TNM classification. The Kaplan-Meier method and Cox proportional hazards model were used to estimate the impact of clinical and histological parameters on disease-specific survival in patients with invasive melanoma. RESULTS: In total, 4594 patients were included in this analysis. The most common clinical type was acral lentiginous melanoma (40.4%) followed by superficial spreading melanoma (20.5%), nodular melanoma (10.0%), mucosal melanoma (9.5%), and lentigo maligna melanoma (8.1%). The 5-year disease-specific survival for each stage was as follows: IA = 98.0%, IB = 93.9%, IIA = 94.8%, IIB = 82.4%, IIC = 71.8%, IIIA = 75.0%, IIIB = 61.3%, IIIC = 41.7%, and IV = 17.7%. Although multivariate analysis showed that clinical classifications were not associated with survival across all stages, acral type was an independent poor prognostic factor in stage IIIA. CONCLUSIONS: Our study revealed the characteristics of melanoma in the Japanese population. The 5-year disease-specific survival of each stage showed a similar trend to that of Caucasians. While clinical classification was not associated with survival in any stages, acral type was associated with poor survival in stage IIIA. Our result might indicate the aggressiveness of acral type in certain populations.

Classification of 3097 patients from the Japanese melanoma study database using the American joint committee on cancer eighth edition cancer staging system.

BACKGROUND: The American Joint Committee on Cancer (AJCC) 8th Edition Cancer Staging System was implemented in 2018; however, it has not been validated in an Asian melanoma population. OBJECTIVE: The purpose of this study was to validate the new system using a cohort of Japanese melanoma patients. METHODS: The AJCC 7th and 8th Editions were used for TNM classification of patients in a database established by the Japanese Melanoma Study Group. Patient data with sufficient information to be applicable to the AJCC 8th staging were selected. The Kaplan-Meier method was used to estimate disease-specific survival and relapse-free survival. RESULTS: In total, data for 3097 patients were analyzed. The 5-year disease-specific survival according to the 7th and 8th Edition staging system were as follows: IA = 98.5%/97.9%; IB = 95.4%/96.2%; IIA = 94.2%/94.1%; IIB = 84.6%/84.4%; IIC = 72.2%/72.2%; IIIA = 76.2%/87.5%; IIIB = 60.7%/72.6%; IIIC = 42.0%/55.3% and IIID = none/26.0%. The 5-year relapse-free survival according to the 7th and 8th Edition staging was as follows: IA = 94.5%/92.7%; IB = 85.4%/85.3%; IIA = 80.1%/79.4%; IIB = 71.4%/70.6%; IIC = 56.8%/55.7%; IIIA = 56.8%/69.4%; IIIB = 42.6%/56.8%; IIIC = 20.0%/33.3% and IIID = none/6.5%. CONCLUSION: The results show that new staging system could efficiently classify our Japanese melanoma cohort. Although there was no difference in Stage I and II disease between the 7th and 8th Edition systems, we should be careful in managing Stage III disease since the survival curves of the 8th Edition staging were completely different from the 7th Edition. Moreover, our results indicate that adjuvant therapies for Stage IIB and IIC should be developed, since the relapse-free survival for these stages were equivalent to Stage IIIA and IIIB, respectively.

Prolonged growth of infantile hemangioma after pulsed dye laser and oral propranolol treatment.

Infantile hemangiomas are the most common tumor of childhood and undergo rapid growth during early infancy followed by gradual involution. After involution, residual lesions sometimes remain. Oral propranolol usually induces earlier involution and redness reduction of infantile hemangiomas. However, the optimal treatment duration is unknown and infantile hemangiomas sometimes recur after cessation of treatment. We report three Japanese patients with recurrent infantile hemangiomas on their cheek. These patients were a 1-month-old female baby with a superficial infantile hemangioma, a 3-month-old female baby with a mixed infantile hemangioma and a 4-month-old male baby with a mixed infantile hemangioma. Two of them also received pulsed dye laser treatment. They did not reach complete or nearly complete resolution of infantile hemangiomas at week 25. These patients experienced regrowth of their infantile hemangioma after 20 months of age and took propranolol after the age of 24 months. There were no severe adverse effects. Propranolol may not only be therapeutic but also prophylactic. Patients with infantile hemangiomas who have taken oral propranolol should be followed up at least 6 months after cessation of treatment, especially infantile hemangiomas on the cheek, and those with partial response to propranolol may require close attention in prolonged growth.

Evaluation of the treatment of port-wine stains with the 595-nm long pulsed dye laser: a large prospective study in adult Japanese patients.

BACKGROUND: Treatments of port-wine stains with conventional pulsed dye laser yield inconsistent results. OBJECTIVE: We evaluated the efficacy and safety of the longer pulse duration 595-nm dye laser. METHODS: Sixty-six adult Japanese patients were enrolled in this prospective study. The laser treatment with a cooling device was repeated 4 times at 8-week intervals with a consistent setting of 10-ms pulse duration and an energy fluence of 12 J/cm2, using 7-mm spot size. RESULTS: Improvement of port-wine stains was observed after multiple treatments, and 67% of the patients achieved either good or excellent response after the fourth treatment. Transient purpura, edema, or both were noted immediately after each treatment (76%-79% and 58%-67%, respectively). Hyperpigmentation (8%-17%) and hypopigmentation (6%-14%) were also mild and their occurrence did not increase by repeating treatments. LIMITATIONS: Eighty five percent of the patients were classified as having Fitzpatrick skin type IV. CONCLUSION: Our study indicated that the 595-nm dye laser with 10-ms pulse duration may be effective and well tolerated in the treatment of port-wine stains in adult Asians.

Mycosis fungoides in a hemodialysis patient with intractable pruritus.

A 69-year-old Japanese man developed pruritus 3 years after beginning hemodialysis. Although eczema was not apparent at first, erythematous patches and plaques developed gradually on the affected skin. Secondary hyperparathyroidism was considered to be a main cause of this patient's pruritus, but skin lesions worsened even after parathyroidectomy had markedly decreased parathyroid hormone concentrations. Two months later, he developed an antibiotic-refractory fever of unknown origin and cervical, axillary, and inguinal lymphadenopathy. Elevations of soluble interleukin-2 receptor with 7410 U/mL and IgE with 24 600 U/mL in serum were noted, as was eosinophilia. The skin showed multiple slightly scaly patches and infiltrative plaques, which were reddish brown and distributed widely over the body surface except for the scalp and face. Mycosis fungoides, a cutaneous T-cell lymphoma, was diagnosed from biopsy specimens findings in skin and lymph node. Mycosis fungoides has not been documented as a cause of pruritus in hemodialysis patients. However, if skin lesions steadily worsen in hemodialysis patients, malignant diseases such as mycosis fungoides should be considered.

Effects of non-amputative wide local excision on the local control and prognosis of in situ and invasive subungual melanoma.

Subungual melanomas (SUM) are rare, and amputation is often required. Non-amputative wide local excision (WLE) of the nail unit with the periosteum of the distal phalanx, followed by skin graft, has been accepted for in situ or SUM of 0.5 mm or less thickness. However, previous reports have included a limited number of cases, and not all more than 0.5-mm thick SUM exhibit invasion or attachment to the distal phalanx. The aim of the present study was to investigate the local recurrence and prognosis for in situ, minimally invasive and invasive SUM that were treated using WLE. We retrospectively reviewed 50 patients with in situ (n = 48) or minimally invasive SUM (n = 2) (in situ or minimally invasive group) and 12 patients with more than 0.5-mm thick invasive SUM (invasive group) who were treated using WLE. All patients survived the follow-up period (24-207 months), although four patients with in situ SUM experienced local recurrence at the lateral margin and re-excision was required. In the invasive group, no patients experienced local recurrence, although one patient (8.3%) developed nodal metastasis at 86 months and regional lymph node dissection was required. WLE may provide acceptable local control for in situ and intermediate thickness SUM, without compromising the vital prognosis. However, a larger randomized prospective study with long-term follow up is required to evaluate adequately the risks associated with a non-amputative WLE for in situ and invasive SUM.

Vesicles as initial skin manifestation of disseminated fusariosis after non-myeloablative stem cell transplantation.

A 52-year-old man underwent non-myeloablative stem cell transplantation from his HLA identical sister for the treatment of mantle cell lymphoma. On day 0, he developed a high-grade fever, watery diarrhea and vesicles scattered on the skin. Well experienced dermatologists diagnosed these lesions as VZV reactivation. High dose antiviral agents were ineffective, and Fusarium solani was cultured from his stool and sputum. Systemic fusariosis progressed rapidly and he died of multiorgan failure on day 18. It is sometimes difficult to differentiate between viral and fungal blisters based on macroscopic examinations. We recommend early histopathological examination of the skin, when HSCT recipients develop vesicles.