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Background S‐1 and pemetrexed (PEM) are key treatments for non‐small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S‐1 and PEM is similar. Cross‐resistance between S‐1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S‐1 following PEM‐containing treatment. Methods This retrospective study included patients with advanced (c‐stage III or IV, UICC seventh edition) or recurrent NSCLC who received S‐1 monotherapy following the failure of previous PEM‐containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression‐free survival (PFS), and overall survival (OS). Results A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty‐six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty‐one patients (58.5%) received the standard S‐1 regimen and 18 patients (34.0%) received the modified S‐1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%–10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively. Conclusions Although there were several limitations in this study, the ORR of S‐1 after PEM in patients with nonsquamous (non‐SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S‐1 treatment in PEM‐treated patients who need tumor shrinkage., Predictive factor of S‐1 and PEM is TS expression.Cross‐resistance between S‐1 and PEM is of concern.This study was designed to evaluate the treatment effect of S‐1 following PEM‐containing treatment.ORR of S‐1 after PEM was low.

Pulmonary sarcomatoid carcinoma (SC) is an aggressive subtype of lung cancer that exhibits resistance to cytotoxic chemotherapy. Although programmed cell death 1 (PD‐1) inhibitors have been reported to show antitumor effects in patients with high programmed death‐ligand 1 (PD‐L1) expressing SC, the efficacy of combined therapy with PD‐1 inhibitor plus cytotoxic chemotherapy has not previously been clarified. We herein report a case of SC with low expression of PD‐L1 and few pre‐existing tumor‐infiltrating lymphocytes which showed a remarkable response to pembrolizumab plus cytotoxic chemotherapy as first‐line treatment. Our findings suggest that combined treatment might enhance the immunogenic response, even in immunologically ignored SCs., Pulmonary sarcomatoid carcinoma (SC) is an aggressive subtype of lung cancer that exhibits resistance to cytotoxic chemotherapy and the efficacy of combined therapy with PD‐1 inhibitor plus cytotoxic chemotherapy as first‐line treatment has not previously been clarified. Here we report a case of SC with low expression of PD‐L1 and few pre‐existing tumor‐infiltrating lymphocytes which showed a remarkable response to pembrolizumab plus cytotoxic chemotherapy. Our findings suggest that treatment might enhance the immunogenic response, even in immunologically ignored SCs.

Dabrafenib and trametinib therapy for BRAF V600E‐mutant non‐small cell lung cancer (NSCLC) has demonstrated strong antitumor effects in clinical trials and has been approved for use in clinical practice. However, the efficacy and safety of this combination therapy in elderly patients remain unclear. An 86‐year‐old male patient, who had been diagnosed with lung adenocarcinoma with the BRAF V600E mutation, received dabrafenib and trametinib combination chemotherapy. The tumor shrunk rapidly; however, therapy was discontinued after 40 days because adverse events (hypoalbuminemia, peripheral edema, and pneumonia) developed. Although this targeted combination therapy seemed to cause relatively severe adverse events compared with single‐agent targeted therapy in this “oldest old” elderly patient, the marked tumor shrinkage prolonged the patient's life and helped him to maintain a good general condition. Active targeted therapy may therefore be considered with appropriate drug dose reduction instead of conservative treatment, even if a patient is extremely old., An 86‐year‐old male patient, who had been diagnosed with lung adenocarcinoma with BRAF V600E mutation, received dabrafenib and trametinib combination chemotherapy. The tumor shrunk rapidly; however, therapy was discontinued after 40 days because adverse events (hypoalbuminemia, peripheral edema, and pneumonia) developed. Although this targeted combination therapy seemed to cause relatively severe adverse events compared with single‐agent targeted therapy in this “oldest old” elderly patient, the marked tumor shrinkage prolonged the patient's life and helped him to maintain a good general condition.

Background: Single-agent amrubicin chemotherapy is a key regimen, especially for small cell lung cancer (SCLC), however, it can cause severe myelosuppression. Purpose: The purpose of this study was to determine the real-world incidence of febrile neutropenia (FN) among patients treated with single-agent amrubicin chemotherapy for thoracic malignancies. Patients and methods: The medical records of consecutive patients with thoracic malignancies, including SCLC and non-small cell lung cancer (NSCLC), who were treated with single-agent amrubicin chemotherapy in cycle 1 between January 2010 and March 2020, were retrospectively analyzed. Results: One hundred and fifty-six patients from four institutions were enrolled. Their characteristics were as follows: median age (range): 68 (32–86), male/female: 126/30, performance status (0/1/2): 9/108/39, SCLC/NSCLC/others: 111/30/15, and prior treatment (0/1/2/3-): 1/96/31/28. One hundred and thirty-four (86%) and 97 (62%) patients experienced grade 3/4 and grade 4 neutropenia, respectively. One hundred and twelve patients (72%) required therapeutic G-CSF treatment, and 47 (30%) developed FN. Prophylactic PEG-G-CSF was not used in cycle 1 in any case. The median overall survival of the patients with FN was significantly shorter than that of the patients without FN (7.2 vs. 10.0 months, p = 0.025). Conclusions: The real-world incidence rate of FN among patients with thoracic malignancies that were treated with single-agent amrubicin chemotherapy was 30%. It is suggested that prophylactic G-CSF should be administered during the practical use of single-agent amrubicin chemotherapy for patients who have already received chemotherapy.

Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients.

Pulmonary pleomorphic carcinoma has been shown to respond remarkably to PD-1 inhibitors; however, the biomarkers for this therapy have not been fully proven. We report a case of pulmonary pleomorphic carcinoma with overexpressed PD-L1, in which a complete response to nivolumab was sustained for >14 months. Immunohistochemical analysis revealed few PD-1+ immune cells and regulatory T cells in the tumor, in addition to predominant infiltration of CD8+ cells and macrophages. Our findings suggest that the presence of a small number of PD-1+ immune cells and regulatory T cells should be investigated as candidate therapeutic biomarkers.

Promising outcomes of salvage chemotherapy after nivolumab therapy have been reported; however, little is known about the detailed clinical and immunologic features in lung cancer patients in whom nivolumab is unsuccessful. We report two cases of nivolumab-refractory lung cancer, in which chemotherapy resulted in rapid regression of the lung cancer. Upon initial diagnosis, the biopsy specimens showed PD-ligand 1 (PD-L1)-expressing cancer cells, accompanied by tumor-infiltrating lymphocytes with a favorable CD8/CD4 ratio. Immunosuppressive regulatory T cells and cells positive for TIM-3 were also observed. Physicians should take caution in treating lung cancer patients after progression on nivolumab. Further studies with a large cohort are warranted to identify the patients that may benefit from salvage chemotherapy.

We report a case of immunoglobulin G4-related disease (IgG4-RD) which presented with prurigo on the trunk and extremities. A 66-year-old man had a 2-month history of itchy erythematous papules on his trunk and extremities. Bilateral eyelid swelling and enlargement of the submandibular and parotid glands were also observed. Computed tomography revealed pleural thickening and diffuse pancreatic enlargement. Serum levels of IgG4 were markedly increased. A biopsy specimen obtained from an erythematous papule showed a perivascular inflammatory infiltrate of lymphocytes with eosinophils in the dermis, whereas a parotid gland biopsy revealed an infiltrate of abundant IgG4-positive plasma cells. Treatment with prednisolone resulted in improvement of the skin and other lesions along with a decrease in IgG4 serum levels. A flow cytometric assay revealed that percentages of interleukin (IL)-4- and IL-13-producing CD4(+) T cells were markedly higher in the circulation of the IgG4-RD patient than in that of healthy subjects. Moreover, those populations dramatically decreased after treatment. Thus, prurigo may be a skin manifestation of IgG4-RD and T-helper 2 cells may contribute to the pathogenesis.

Primary mediastinal large B-cell lymphoma (PMLBCL) is one of the subtypes of diffuse large B-cell lymphoma. We experienced a rare case of PMLBCL that exhibited endobronchial involvement. A 33-year-old Japanese female with the chief complaints of epigastralgia, back pain, and nausea visited a primary care hospital. Computed tomography of the chest and abdomen demonstrated a bulky mass in the left anterior mediastinum, multiple pulmonary nodules, axillary lymph node swelling, and a pancreatic tumor. Fiberoptic bronchoscopy showed a white-tinged irregularly shaped endobronchial tumor accompanied by capillary vessel dilation in the left upper lobar bronchus. Taken together, these findings resulted in a diagnosis of PMLBCL., Internal Medicine, 55(21), pp.3147-3150; 2016

The circulating tumor DNA (ctDNA) assay has recently been approved for the selection of EGFR-tyrosine kinase inhibitors as first-line treatment in lung cancer. However, it remains to be determined whether this assay can detect all complex EGFR mutations within a single tumor. We report a case of an elderly woman with stage IV lung adenocarcinoma, in which EGFR mutation assays detected L858R and pretreatment T790M from a tissue biopsy. In contrast, the circulating tumor DNA assay detected L858R, but not pretreatment T790M in the plasma, regardless of the fact that similar amounts of each mutation were present in the biopsy specimen. Treatment with afatinib was not effective, but subsequent treatment with osimertinib remarkably regressed the tumor. Our findings indicate that physicians should accurately evaluate EGFR-tyrosine kinase inhibitor-insensitive mutations using tissue samples in the first-line setting, even when L858R and exon 19 deletions are detected in the plasma.

Background Previous reports suggested that development of an immune-related adverse event (irAE), including thyroid disorder (TD), is associated with better outcomes of immune checkpoint inhibitor (ICI) therapy. Though TD has been reported most frequently as an irAE, it has not been well analyzed compared to life-threatening adverse events such as interstitial lung disease or colitis. Methods We conducted a chart-based retrospective analysis of patients (Pts) with advanced or recurrent non-small cell lung cancer (NSCLC), who are treated with monotherapy using nivolumab, pembrolizumab, or atezolizumab between January 2016 and June 2019 in two facilities in Japan. TD emerging after the first treatment with an ICI was considered as an irAE. Tumor response was evaluated with Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) on ICIs were evaluated with Kaplan-Meier method. The correlations between time to onset of TD and PFS or OS were analyzed with Spearman's rank correlation coefficient. Results In total, 164 consecutive Pts were enrolled. The median age was 68 (range: 34-84) years, and 40 (24.4%) were women. TD of any grade occurred in 26 Pts (15.8%); 11/15/0/0/0 cases were classified as Grade 1/2/3/4/5, respectively, according to Common Terminology Criteria for Adverse Events version 5.0. Onset of TD ranged from 6 to 455 (median: 77.5) days after the first treatment with an ICI. Objective response rates in Pts with and without TD were 28.0% and 18.1%; disease control rates were 68.0% and 50.7%, respectively. Median PFS and OS were significantly longer in Pts with TD (PFS: 226 vs 100 days, p = 0.029; OS: not reached vs 434 days, p = 0.050, log-rank test). Among TD Pts, however, a positive correlation between time to onset of TD and PFS was identified (p = 0.0015). Significantly shorter PFS was observed in Pts with earlier TD onset, especially within 30 days, compared to Pts with later TD onset (median PFS: 72.5 vs 329 days, p = 0.00096, log-rank test). Conclusions Development of TD caused by ICIs was associated with longer PFS. Nevertheless, the prognosis of Pts with early onset of TD was poor. This study suggested that physicians should consider the onset of TD in Pts using ICIs. Legal entity responsible for the study Hiroyuki Yamaguchi. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

This paper presents a study on multi-modal human emotional state detection while riding a powered wheelchair (PMV; Personal Mobility Vehicle) in an indoor labyrinth-like environment. The study reports findings on the habituation of human stress response during self-driving. In addition, the effects of "loss of controllability", change in the role of the driver to a passenger, are investigated via an autonomous driving modality. The multi-modal emotional state detector sensing framework consists of four sensing devices: electroencephalograph (EEG), heart inter-beat interval (IBI), galvanic skin response (GSR) and stressor level lever (in the case of autonomous riding). Physiological emotional state measurement characteristics are organized by time-scale, in terms of capturing slower changes (long-term) and quicker changes from moment-to-moment. Experimental results with fifteen participants regarding subjective emotional state reports and commercial software measurements validated the proposed emotional state detector. Short-term GSR and heart signal characterizations captured moment-to-moment emotional state during autonomous riding (Spearman correlation; ρ = 0.6, p < 0.001). Short-term GSR and EEG characterizations reliably captured moment-to-moment emotional state during self-driving (Classification accuracy; 69.7). Finally, long-term GSR and heart characterizations were confirmed to reliably capture slow changes during autonomous riding and also of emotional state during participant resting state. The purpose of this study and the exploration of various algorithms and sensors in a structured framework is to provide a comprehensive background for multi-modal emotional state prediction experiments and/or applications. Additional discussion regarding the feasibility and utility of the possibilities of these concepts are given.

Diastereoselective conjugate addition of 1-enoyl-5-substituted hydantoins with allyltrimethylsilane in the presence of Ti(IV) chloride proceeded to give the corresponding allyl adducts in high yield and high diastereoselectivity. In order to determine the absolute configuration on the β-position of the acyl group, the hydantoin was removed by hydrolysis of the allyl adducts with a base to give the corresponding carboxylic acid. It was found that the absolute configuration was S on the basis of specific rotation.

70歳, 女性。神経線維腫症1型の既往はない。10年来の左大腿部に多発した皮下腫瘤を切除し, 神経線維腫の診断で経過観察されていた。1年半後, 左鼠径部に自覚症状を伴わない3cm大の皮下腫瘤が出現。生検標本の組織像では皮下に巨大な腫瘍として認められ, 個々の腫瘍細胞は異型性の強い大小さまざまな核を持っており, 細胞密度も高かった。また免疫組織化学染色では, S-100蛋白とビメンチンが腫瘍細胞に陽性であった。組織学的に悪性末梢神経鞘腫 (malignant peripheral nerve sheath tumor, 以下MPNSTと略す) と診断した。拡大切除術およびリンパ節郭清を施行したところ, 摘出したリンパ節に転移を認めた。追加治療として, 局所に合計63Gyの4MeVのX線照射を行った。術後1年の時点で再発・転移は認めていない。MPNSTのリンパ行性転移は極めて稀であり, また, 自験例が神経線維腫症5型である可能性を考えた。

Pseudohypoparathyroidism (PHP) type Ia is characterized by hypocalcemia due to PTH resistance and by features of Albright's hereditary osteodystrophy, including short stature, obesity, subcutaneous calcification and brachydactyly. A wide variety of clinical and biochemical manifestations have been reported. We report two cases of PHP type Ia in duozygotic twins with different phenotypes. The proband was a 10-yr-old girl. She showed subcutaneous ossification, shortening of the metacarpal bone, short stature, obesity and round face. She had normocalcemia (8.9 mg/dl), high-normal phosphate (5.0 mg/dl) and increased levels of serum intact PTH (152 pg/ml) and TSH (9.17 μIU/ml) levels. Her twin younger brother had atypical Albright's hereditary osteodystrophy with only mild obesity and subcutaneous calcifications, but he showed a low level of serum calcium (7.0 mg/dl) and high levels of serum phosphate (7.6 mg/dl), intact PTH (377 pg/ml) and TSH (6.9 μIU/ml). We diagnosed them as having PHP type Ia on the basis of clinical and biochemical findings, Ellsworth-Howard test and family history. There is considerable variability in clinical and biochemical features of PHP type Ia even among affected duozygotic twins. The differences of intrauterine environment and growth history cannot account for the variable phenotypes of PHP type Ia. Even if a patient shows no AHO features, examination of all family members should be undertaken.

We report a case of malignant peripheral nerve sheath tumor (MPNST) of the nape. A 52-year-old woman suffering from neurofibromatosis type I since her childhood noticed a tumor on the nape six years ago. The tumor gradually became enlarged and elevated. On her visit to our hospital on July 25th, 2002, physical examination revealed an elastic soft, 15×13×6cm sized tumor on the left side of her nape. The tumor grew rapidly and ruptured with bleeding on August 23rd. Immediate excision of the tumor was performed. Histologically, the tumor mainly consisted of spindle cells showing palisading arrangement.A part of the specimen showed nuclear atypia and mitoses. Immunohistochemically, the spindle cells were positive for S-100 protein and NSE. The tumor was diagnosed as MPNST. Multiple lung and liver metastases developed and the patient died of respiratory failure caused by lung metastases in 5 months after her first visit to our institution. [Skin Cancer (Japan) 2004; 19: 229-232]

(Case 1) A 62-year-old man suffered from psoriasis for several decades and was treated with ultraviolet A. He noticed a tumor on the right side of his scrotum 10 months ago. A biopsy specimen of the tumor led us to the diagnosis of squamous cell carcinoma (SCC) . Wide excision and right inguinal lymph node dissection were performed. Inspite of the treatment, paraaortic lymph node and lung metastases developed 18 months later. Combination chemotherapy (carboplatin, 5-FU, and peplomycin) could not inhibit the tumor progression and he died 3 years after the first visit.(Case 2) A 42-year-old man presented with a tumor on the left side of his scrotum. He had worked at an ironworks and used machine oil. After wide excision and left inguinal lymph node dissection, he was treated with 3 courses of peplomycin chemotherapy. The tumor recurred locally 4 years later and was surgically removed again. He has been tumor-free for more than 6 years.(Case 3) A 77-year-old man, who also worked at an ironworks before, had a tumor on the left side of his scrotum and had it resected at another hospital 4 years ago. Local recurrence occurred and was widely excised. He has been tumor-free for more than 4 years.During the past 11 years, we experience 251 cases of SCC in our institutions. Among them, 3 cases developed on the scrotum. It is often indicated that SCC occurs on the scrotum soaked with machine oil or exposed to ultraviolet rays. [Skin Cancer (Japan) 2004; 19: 181-185]

Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging in the regional lymph nodes of patients with malignant melanoma. Popliteal lymph nodes have been rarely identified as SLNs in patients with melanoma at or distal to the knee. However, its significance has not been well established. We reported a case of a patient with melanoma on the heel, who had positive SLN metastases in both popliteal and groin lymph nodes. In addition, experience with the past cases metastasized to popliteal lymph nodes in our hospitals were reviewed. Among 76 patients with melanoma of the distal lower limb, five (6.6%) developed popliteal lymph node metastases in its clinical course. The primary tumor sites in four of five patients were located on the heel, especially on the lateral or proximal aspects. Although elective lymphadenectomy of popliteal node seems to be unnecessary considering the low incidence of metastasis, once the popliteal node is identified as SLN on lymphoscintigraphy, biopsy procedureshould be performed. [Skin Cancer (Japan) 2003; 18: 298-302]

To develop a more efficient transdermal delivery system, it is very important to regulate the intradermal disposition of drugs after topical application. We tried to elucidate the factors determining the intradermal disposition kinetics, especially drug penetration from the viable skin to the muscular layer, mainly based on the six-compartment model, including the contralateral skin and muscle for ten model drugs with different physicochemical characteristics. In vivo transdermal absorption study was performed for six model drugs using the stripped-skin rats. The fitting analyses by the six-compartment model gave the theoretical curves describing the observed data very well and the reasonable pharmacokinetic parameters, showing the pharmacokinetic model should be useful for the estimation of the intradermal disposition kinetics of drugs applied topically again. The simulation study using the pharmacokinetic parameters obtained above could show the relative contribution of the direct penetration and the distribution from the systemic circulation to the muscular distribution of drugs. The largest contribution of direct penetration was observed for antipyrine (90.8%) and the smallest was for felbinac (43.3%). Among the pharmacokinetic parameters obtained above, the clearance from the viable skin to the muscle (CL(vs-m)) was found to be significantly correlated with the unbound fraction of drugs in the viable skin (fu(vs)). Although the clearance from the viable skin to the plasma (CL(vs-p)) also tended to increase as fu(vs) increased, the ratio of CL(vs-m) to CL(vs-p) was significantly correlated with fu(vs), meaning that the larger amount of unbound drug in the viable skin significantly contributes to the direct penetration into the muscle more than to the systemic absorption. On the other hand, k(direct) values obtained in in vitro penetration study-the penetration rate constant of drugs from the viable skin to the muscular layer-were found to be correlated with CL(vs-m) values for seven model drugs. Therefore, adding the in vitro experiments for the other three model drugs, the multiple linear regression analysis of k(direct) was performed for ten model drugs in terms of fu(vs), logarithm of the partition coefficient (Log P) and molecular weight. The results clearly showed the largest and significant contribution of fu(vs) to the direct penetration of drugs from the viable skin to the muscular layer, indicating that a drug with the higher value of fu(vs) in the viable skin can penetrate more into the muscular layer.

Background: Synovial sarcoma (SS) is representative sarcoma types, which is account for 6% of sarcomas. Although the gold-standard of treatment is surgery, SS is often diagnosed in an advanced clinical stage. Chemotherapy is the primary treatment modality. Amrubicin (AMR), an anthracycline agent, is converted in the body to amrubicinol (AMRol) by reduction of the 13-position ketone, which has a higher antitumor activity than the parentmolecule. In this study, we evaluate the effectiveness in vitro and in vivo. Materials and Methods: Cell lines and reagent. The SS cell lines, SW982, HSSYII and SS1. Cell viability assay. WST-1 mixture was used. Cell-cycle analysis. To evaluate the cell cycle, FITC BrdU Kit Flow Kit was used. HSSY-II, SW982 were treated with AMRol for 4 hours and analyzed by flow cytometry using BD FACSVerseTM. Animal experiments. Severe Combined Immuno-Deficiency mice were used. SS cells were injected subcutaneously or into right intrathoracic space. These mice were assigned randomly to AMR group and normal saline group (NS). Micro-computed tomography (μCT). The R-mCT system was used to measure the diameter of tumor in intrathoracic space. Statistical analysis: All of the results are expressed as meanSEM. The Kaplan-Meier method was used to estimate survival. Treatment groups were compared using a two-sided log-rank test. Results: Cell viability assay. AMR was highly metabolized into AMRol in tumor tissue and AMRol was more toxic than AMR. AMRol was used to in vitro assay. AMRol was equivalent to, or even more toxic than DXR in this experiments. Cell-cycle analysis. After AMRol treatment, more cells were found in S-phase compared with no treatment control. Subcutaneous SS model. AMR showed cytostatic effect compared with normal saline (NS) in each of HSSYII and SW982. Intrathoracic space SS model. SS-1 was established from primary pleural SS patient. In preliminary experiments, location of tumor was confirmed on μCT. Tumor growth was suppressed in AMR group compared with in NS group and AMR showed cytostatic effect. In survival analysis, it was shown that AMR group was tend to survive longer than NS group. Discussion: It was shown that AMR is effective for SS in vitro and in vivo. Our results suggest an alternative treatment of SS patients, including primary pleural SS. The effectiveness and safety should be addressed in future studies. Citation Format: Shinnosuke Takemoto, Hiroshi Gyotoku, Hiroaki Senjuu, Takayuki Suyama, Noritaka Honda, Kosuke Mizoguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Yoichi Nakamura, Minoru Fukuda, Hiroshi Mukae. Amrubicin is effective for synovial sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4133. doi:10.1158/1538-7445.AM2017-4133

We reported a case of squamous cell carcinoma (SCC) of the nail bed, with very rapid multiple metastases in various organs. A 65-year-old man had a hyperkeratotic tumor which had been around the nail bed of his right 5th toe for two months. A digital X-ray film of the toe showed the disappearance of the digital phalanx. A biopsy specimen of the tumor led us to diagnose as poorly differentiated SCC. Amputation of the toe at the level of metatarsal bone and therapeutic dissection of the right ilio-inguinal and popliteal lymphnodes were performed. Additionaly the patient was followed by radiation therapy. Histologically, the tumor invaded the bone underneath, and two metastatic lymphnodes were detected on his right groin.In spite of irradiation on his right foot toe and groin, many in-transit metastases appeared on his right leg and thigh three months later. Several times of resection and two courses of combination chemotherapy (cisplatin, 5-FU and peplomycin) could not inhibit the tumor progression. Bone and lung metastases occurred and he died seven months after the first visit.Although the prognosis of subungual SCCs is thought to be relatively favorable, some cases may take a miserable course.

We report a case of an 85-year-old man with a doughnut-shaped basal cell carcinoma around the base of the penis invading the cavernosum urethra. In cases in which curative resection is planned, the penis is resected, cystostomy is performed, and postoperative self-management is required. In line with the patient's wishes and the fact that he was an elderly person living alone without family support, we decided to perform penis-conserving surgery. Relapse occurred once, for which additional resection was conducted. Two years after the resection, there was no evidence of tumor recurrence. The therapeutic plan for elderly patients should be modified after considering the patient's social background, wishes, activity and life expectancy.

In the title compound, C5H11N5S2, the mol­ecule adopts a zwitterionic structure. No H atoms are bonded to the di­thio­carboxy S atoms nor to the N atom at the 3-position (N3), but the two imino groups in the biguanide moiety are converted to amino groups. The mol­ecule consists of two planar moieties sharing atom N3; the dihedral angle between them is 58.0 (1)°.

Fabry disease is an X-linked recessive inborn metabolic disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (EC 3.2.1.22). The causative mutations are diverse, include both large rearrangements and single-base substitutions, and are dispersed throughout the 7 exons of the alpha-galactosidase A gene (GLA). Mutation hotspots for Fabry disease do not exist. We examined 62 Fabry patients in Japan and found 24 GLA mutations, including 11 novel ones. A potential treatment reported for Fabry disease is active site specific chaperone (ASSC) therapy using 1-deoxygalactonojirimycin (DGJ), an inhibitor of alpha-galactosidase A, at subinhibitory concentrations. We transfected COS-7 cells with the 24 mutant GLAs and analyzed the alpha-galactosidase A activities. We then treated the transfected COS-7 cells with DGJ and analyzed its effect on the mutant enzyme activities. The activity of 11 missense mutants increased significantly with DGJ. Although ASSC therapy is useful only for misfolding mutants and therefore not applicable to all cases, it may be useful for treating many Japanese patients with Fabry disease.