Sentinel lymph node biopsy in Japan

Similar to the practice in Western countries, intra-operative lymphatic mapping and selected lymphadenectomy (SLNB) have been validated and are widely performed for the staging of melanoma in Japan. Recent studies have shown that approximately 90% (73/81) of university hospitals and several cancer hospitals routinely perform SLNB, and half of all melanoma patients receive this examination. SLNB is performed according to a variation of the standard procedure described by Morton and Cochran. The most frequently used tracers are Tc-99m-tin colloid or Tc-99m-phytate for scintigraphy and patent blue violet or indigo carmine as a blue dye. Some institutions use indocyanine green, which is fluorescent and can be used to visualize sentinel lymph node(s) (SLNs) under an infrared camera. The recent detection rate of SLNs has increased to more than 95% with the method using blue dye, lymphoscintigraphy, and a handheld gamma probe. In a multicenter study, the rates of metastasis in SLN were as follows: pTis, 0% (0/36); pT1, 10.7% (6/56); pT2, 21.0% (13/63); pT3, 34.0% (35/103); and pT4, 62.4% (63/101). The metastasis rate was also significantly related to ulceration of the primary tumor. Here, we discuss data from Japanese patients and the present status of SLNB in Japan.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 14(6):490-496 (2009)journal articl

Key point in dermoscopic differentiation between early nail apparatus melanoma and benign longitudinal melanonychia

Longitudinal melanonychia presents in various conditions including neoplastic and reactive disorders. It is much more frequently seen in non-Caucasians than Caucasians. While most cases of nail apparatus melanoma start as longitudinal melanonychia, melanocytic nevi of the nail apparatus also typically accompany longitudinal melanonychia. Identifying the suspicious longitudinal melanonychia is therefore an important task for dermatologists. Dermoscopy provides useful information for making this decision. The most suspicious dermoscopic feature of early nail apparatus melanoma is irregular lines on a brown background. Evaluation of the irregularity may be rather subjective, but through experience, dermatologists can improve their diagnostic skills of longitudinal melanonychia, including benign conditions showing regular lines. Other important dermoscopic features of early nail apparatus melanoma are micro-Hutchinson's sign, a wide pigmented band, and triangular pigmentation on the nail plate. Although there is as yet no solid evidence concerning the frequency of dermoscopic follow up, we recommend checking the suspicious longitudinal melanonychia every 6 months. Moreover, patients with longitudinal melanonychia should be asked to return to the clinic quickly if the lesion shows obvious changes. Diagnosis of amelanotic or hypomelanotic melanoma affecting the nail apparatus is also challenging, but melanoma should be highly suspected if remnants of melanin granules are detected dermoscopically.ArticleJOURNAL OF DERMATOLOGY. 38(1):45-52 (2011)journal articl

High-frequency 30-MHz sonography in preoperative assessment of tumor thickness of primary melanoma: usefulness in determination of surgical margin and indication for sentinel lymph node biopsy

The original publication is available at www.springerlink.comHigh-frequency sonographic imaging has been used for the preoperative evaluation of primary malignant melanoma. In the present study, to identify the usefulness of 30-MHz sonography for determination of the surgical margin and indication for sentinel lymph node biopsy, the correlation between sonometric and histometric tumor thickness was investigated. A total of 74 primary melanomas, in patients seen at the dermatology clinic, Shinshu University Hospital, from 1998 to 2006, were evaluated using high-frequency sonographic equipment with two probes (15 MHz and 30 MHz), and tumor thickness was measured using electronic calipers before surgical treatment. All the primary lesions were surgically excised and Breslow's tumor thickness was measured histologically. In 68 melanomas, excluding 2 lesions of melanoma in situ and 4 lesions with poor sonographic images, sonographic and histologic thickness showed good correlation (r = 0.887). Particularly, in 26 melanomas affecting the soles of the feet, sonographic and histologic thickness showed excellent correlation (r = 0.945). Regarding the T categorization, in which T1-T4 are divided at 1, 2, and 4 mm in thickness, the categories determined with sonometry corresponded very well to those determined with histometry. The correspondence was particularly excellent in thinner primary lesions with thickness around 1 mm. We excised almost all these primary melanomas with surgical margins based on the sonometric thickness. In 22 patients with sonometric thickness more than 1 mm, sentinel lymph node biopsy and/or radical lymphadenectomy was performed. High-frequency sonography (30-MHz) is very useful in the preoperative prediction of tumor thickness, particularly in thinner primary lesions, which allows us to determine surgical margins and indication for sentinel lymph node biopsy.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 14(5):426-430 (2009)journal articl

Platinum and anthracycline therapy for advanced cutaneous squamous cell carcinoma

Because metastatic cutaneous squamous cell carcinoma (CSCC) is rare, standard chemotherapy has not been fully established. In Japan, combination platinum and anthracycline chemotherapy has been used for elderly patients with advanced CSCC because of its low toxicity. However, the clinical benefit of this therapy has not been fully examined. We retrospectively examined the response rate of combination platinum and anthracycline chemotherapy for metastatic CSCC. Eight patients received combination chemotherapy for metastatic lesions; there were lymph node lesions in 6 patients and skin and lung lesions in one patient each. The combination regimens were as follows: cisplatin (CDDP) (60-90 mg/m(2)/day, day 1) and adriamycin (ADM) (20-40 mg/m(2)/day, day 1 or 2) was administered in 5 patients; CDDP (10-15 mg/m(2)/day, days 1-5) and epirubicin (epi-ADM) (10-15 mg/m(2)/day, days 1-5) was administered in 2 patients; and carboplatin (CBDCA) (200-400 mg/m(2)/day, day 1) and ADM (20-40 mg/m(2)/day, day 1 or 2) was administered in one patient. The responses were as follows: complete response in 2 patients (CDDP + ADM for lung metastasis, CDDP + epi-ADM for lymph node metastasis), partial response in 1 (CDDP + ADM for lymph node metastasis), stable disease in 2, and progressive disease in 3. A durable response was observed in 2 patients showing complete responses (58 and 112 months). The clinical effect of the combination of platinum and anthracycline for metastatic CSCC was limited despite the findings of two patients showing durable complete responses.ArticleINTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY. 18(3):506-509 (2013)journal articl

Clinical effects of stereotactic radiation surgery in patients with metastatic melanoma

We examined the effectiveness of stereotactic radiation surgery (SRS) in 14 patients with brain metastasis in our hospital. The age of the patients ranged 45-85 years old (mean, 65). Brain metastasis was detected by neurological symptoms in seven patients and by regular imaging examination in the remaining patients. The number of metastatic lesions in the brain before SRS ranged 1-11 (median, 2). The treatment number of SRS was 1-4 times (median, 2). Six of 14 patients had neurological symptoms before SRS. Overall survival (OS) after SRS was 1.721.2 months (median, 8.2). The progression-free survival (PFS) after SRS was 0.9-10.5 months (median, 2.2). The result of univariate analysis showed that the application of two or more courses of SRS was significantly related to OS (P = 0.005). Single metastatic lesion (P = 0.051) and no extracranial lesion (P = 0.055) showed a slight tendency to be related to disease-free survival (DFS). Neither lactate dehydrogenase nor neurological symptoms were significantly related to OS or DFS. Although OS and DFS after SRS were not very long, the treatment of brain metastases has the potential to prevent neurological events. Repeating SRS may be accepted as a local therapy in the multimodal approach including new molecular targeting drugs for metastatic melanoma.ArticleJOURNAL OF DERMATOLOGY. 40(8):626-628 (2013)journal articl

A Case of Mycobacterial Skin Disease Caused by Mycobacterium peregrinum, and a Review of Cutaneous Infection

An 83-year-old Japanese man presented with a 2-month history of symptomatic nodules on the left hand. He was not in an immunocompromised condition and reported no causal events. A biopsy specimen demonstrated granulomatous tissue with mixed cell infiltration consisting of neutrophils, histiocytes, lymphocytes, and multinuclear giant cells. No bacillus was detected by PAS, acid-fast stain, immunofluorescent stain or polymerase chain reaction analysis. The isolate was found to be a rapidly growing mycobacterium after 4 weeks of incubation at 25°C on an Ogawa egg slant. Mycobacterium peregrinum was isolated by DNA-DNA hybridization analysis, 16S rRNA gene sequence, and by its production of 3-day arylsulfatase. The patient received 200 mg oral minocycline for 28 weeks. The lesion disappeared after 10 weeks of this treatment

Pemphigus vulgaris as an immune-related adverse event in recurrent metastatic esophageal squamous cell carcinoma treated with ipilimumab plus nivolumab: a case report and literature review

Ipilimumab plus nivolumab therapy is approved for patients with unresectable advanced esophageal squamous cell carcinoma (ESCC). Although a combination of immune checkpoint inhibitors (ICIs), compared to conventional chemotherapy, can improve overall survival in patients with advanced ESCC, this increases the incidence of immune-related adverse events (irAEs). Here, we describe an ESCC case that developed pemphigus vulgaris (PV), an extremely rare cutaneous irAE, during ipilimumab plus nivolumab treatment. The patient achieved a partial response to treatment. The PV was successfully managed after the cessation of ipilimumab and the use of a topical steroid. We should thus re-treat ESCC with nivolumab monotherapy. In the era of ICIs as standard cancer therapeutics, diagnostic criteria for blistering diseases need to be established to properly manage patients with cutaneous irAEs

Efficacy and safety of nivolumab in Japanese patients with previously untreated advanced melanoma: A phase II study

Treating advanced or recurrent melanoma remains a challenge. Cancer cells canevade the immune system by blocking T-cell activation through overexpressionof the inhibitory receptor programmed death 1 (PD-1) ligands. The PD-1 inhibitornivolumab blocks the inhibitory signal in T cells, thus overcoming the immuneresistance of cancer cells. Nivolumab has shown promising anticancer activity invarious cancers. We carried out a single-arm, open-label, multicenter, phase IIstudy to investigate the efficacy and safety of nivolumab in previously untreatedJapanese patients with advanced melanoma. Twenty-four patients with stage III/IV or recurrent melanoma were enrolled and received i.v. nivolumab 3 mg/kgevery 2 weeks until disease progression or unacceptable toxicity. The primaryendpoint was overall response rate evaluated by an independent radiologyreview committee. The independent radiology review committee-assessed overallresponse rate was 34.8% (90% confidence interval, 20.8–51.9), and the overallsurvival rate at 18 months was 56.5% (90% confidence interval, 38.0–71.4). Treatment-related adverse events (AEs) of grade 3 or 4 only occurred in three patients(12.5%). Two patients discontinued nivolumab because of AEs, but all AEs wereconsidered manageable by early diagnosis and appropriate treatment. Subgroupanalyses showed that nivolumab was clinically beneficial and tolerable regardlessof BRAF genotype, and that patients with treatment-related select AEs and withvitiligo showed tendency for better survival. In conclusion, nivolumab showedfavorable efficacy and safety profiles in Japanese patients with advanced orrecurrent melanoma, with or without BRAF mutations. (Trial registration no.JapicCTI-142533.

Long‐term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma

The immune checkpoint inhibitor nivolumab inhibits the programmed death 1 receptor and suppresses the immune resistance of cancer cells. This is a long-term follow up of a single-arm, open-label, multicenter, phase II study of nivolumab in untreated Japanese patients with stage III/IV or recurrent melanoma. In addition, a post-hoc subgroup analysis stratified by melanoma types was performed. Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), best overall response, the disease control rate and change in tumor diameter. Safety was assessed by recording treatment-related adverse events (TRAE), including select immune-related adverse events. Of the 24 patients initially included in the primary phase II study, 10 survived for over 3 years (41.7%). The ORR was 34.8% (90% confidence interval [CI]: 20.8, 51.9) for all patients. When analyzing by melanoma type, the ORR was 66.7% (90% CI: 34.7, 88.3) for superficial spreading, 33.3% (90% CI: 11.7, 65.3) for mucosal, and 28.6% (90% CI: 10.0, 59.1) for acral lentiginous tumors. The median OS was 32.9 months, the 3-year OS rate was 43.5%, and the 3-year PFS rate was 17.2%. A long-term response was observed in all the tumor types. The most common TRAE included skin toxicity (45.8%) and endocrine disorders (29.2%). This study demonstrated the long-term efficacy and tolerability of nivolumab in patients with advanced or recurrent melanoma, irrespective of melanoma type