Search

The development of nonfullerene acceptors (NFAs), represented by ITIC, has contributed to improving the power conversion efficiency (PCE) of organic solar cells (OSCs). Although tuning the electronic structures to reduce the exciton binding energy (E b ) is considered to promote photocharge generation, a rational molecular design for NFAs has not been established. In this study, we designed and developed two ITIC-based NFAs bearing spiro-substituted bithiophene or biphenyl units (named SpiroT-DCI and SpiroF-DCI) to tune the frontier molecular orbital (FMO) distribution of NFAs. While the highest occupied molecular orbitals (HOMOs) of SpiroF-DCI and ITIC are delocalized in the main π-conjugated framework, the HOMO of SpiroT-DCI is distributed on the bithiophene unit. Reflecting this difference, SpiroT-DCI exhibits a smaller E b than either SpiroF-DCI or ITIC, and exhibits greater external quantum efficiency in single-component OSCs. Furthermore, SpiroT-DCI shows improved PCEs for bulk-heterojunction OSCs with a donor of PBDB-T, compared with that of either SpiroT-DCI or ITIC. Time-resolved spectroscopy measurements show that the photo-induced intermolecular charge separation is effective even in pristine SpiroT-DCI films. This study highlights the introduction of spiro-substituted bithiophene units that are effective in tuning the FMOs of ITIC, which is desirable for reducing the E b and improving the PCE in OSCs., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Exciton binding energy (E b ) is understood as the energy required to dissociate an exciton in free-charge carriers, and is known to be an important parameter in determining the performance of organic opto-electronic devices. However, the development of a molecular design to achieve a small level of E b in the solid state continues to lag behind. Here, to investigate the relationship between aggregation and E b , star-shaped π-conjugated compounds DBC-RD and TPE-RD were developed using dibenzo[g,p]chrysene (DBC) and tetraphenylethylene (TPE). Theoretical calculations and physical measurements in solution showed no apparent differences between DBC-RD and TPE-RD, indicating that these molecules possess similar properties on a single-molecule level. By contrast, pristine films incorporating these molecules showed significantly different levels of electron affinity, ionization potential, and optical gap. Also, DBC-RD had a smaller E b value of 0.24 eV compared with that of TPE-RD (0.42 eV). However, these molecules showed similar E b values under dispersed conditions, which suggested that the decreased E b of DBC-RD in pristine film is induced by molecular aggregation. By comparison with TPE-RD, DBC-RD showed superior performances in single-component organic solar cells and organic photocatalysts. These results indicate that a molecular design suitable for aggregation is important to decrease the E b in films., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Cutaneous dermatofibrosarcoma protuberans (DFSP) is a fibrohistiocytic tumor characterized by a high risk of local recurrence but a low risk of metastasis. Wide local excision (WLE) has been an important treatment option, but its clinical outcomes and safety have not been thoroughly evaluated in previous reports. The aim of this study was to determine appropriate surgical margins (deep and lateral) and prognostic factors associated with recurrence-free survival (RFS) of DFSP. A database collected by two dermatology departments in Japan was retrospectively reviewed to identify 116 patients with DFSP who underwent complete resection with WLE between 1994 and 2021. Sixty-one men (53%) and 55 women (47%) were included in our cohort. The primary sites of DFSP were as follows: 11 head and neck (9%); seven face (7%); 12 upper extremities (10%); 20 lower extremities (17%); and 66 trunk (57%). There were 103 cases (89%) of primary DFSP and 13 cases (11%) of recurrent DFSP. Total 10-year RFS was 96.6%. There were significant differences in RFS by tumor size (median size: 3 cm), disease status (primary versus recurrent DFSP), and fibrosarcomatous change (positive versus negative) (all p < 0.05). Two patients (1.7%) with buccal or head lesions had positive deep margins. In all cases, the lateral margin was negative at the postoperative evaluation. Tumor size, disease status, and fibrosarcomatous change are important risk factors for recurrence. Both face and head-neck lesions were more likely to have positive deep margins than other anatomic areas in DFSP. Although this study was limited by its retrospective design, a narrow 2-cm lateral margin is especially considered for low-risk patients., (© 2024 Japanese Dermatological Association.)

There is a growing demand for the development of novel solar power systems that can simultaneously solve the problems associated with both energy generation and food supply in agriculture. Green-light wavelength-selective organic solar cells (OSCs), whose transmitted blue and red light can be utilized to promote plant growth were recently reported by our group. However, the influence of wavelength variation on the photosynthetic rate in green-light wavelength-selective OSCs remains unclear. In this study, we report on the design and synthesis of new electron-accepting π-conjugated molecules containing cyclopentene-annelated thiophene with a spiro-substituted 2,7-bis(2-ethylhexyl)fluorene (FT) unit (TT-FT-ID) as a green-light wavelength-selective nonfullerene acceptor along with a reference compound TT-T-ID. Photophysical measurements indicate that the introduction of the FT unit leads to an absorption band with a small full width at half maximum in films, leading to the ability to fine-tune the absorption length. Concerning the optimization of the conditions for the fabrication of the active layers, which are composed of a green-light wavelength-selective donor polymer of poly(3-hexylthiophene) (P3HT) and the new acceptors, Bayesian optimization based on Gaussian process regression was applied to minimize the experimental batches. The green-light wavelength-selective factor ( S G ) and the PCEs in the green-light region (PCE-GR) of the P3HT:TT-FT-ID-based device were determined to be 0.52 and 8.6%, respectively, which are higher values than those of the P3HT:TT-T-ID blend film. The P3HT:TT-FT-ID blend film increased the photosynthetic rate of green pepper compared to that of the P3HT:TT-T-ID blend film. These results indicate that the fine-tuning of the absorbance required for crop growth is an important issue in developing green-light wavelength-selective OSCs for agrivoltaics.

Introduction: Although many studies investigating the mechanical behavior of loop mechanics have focused on loop designs to produce a higher moment-to-force ratio, few studies have clarified the effect of loop position on the force system and resultant tooth movements. This study aimed to simulate orthodontic tooth movements during space closure and to compare the effects of loop position in association with different degrees of gable bend on tooth movements using the finite element method., Methods: Two finite element models of the maxillary dentition were constructed, with the loop placed mesial or distal to the canine. Tooth movements during loop activation were simulated while varying the degree of gable bend., Results: When the loop was placed distal to the canine, the incisor showed uncontrolled tipping even with the gable bend. Placement of the loop mesial to the canine produced controlled tipping or root movement of the incisor, depending on the degree of gable bend., Conclusions: Placement of the closing loop mesial to the canine in combination with the incorporation of a gable bend into the archwire distal to the canine could provide better control of incisor movements, such as controlled tipping or root movement, as compared with placement of a gable bend into the loop located distal to the canine., (Copyright © 2023. Published by Elsevier Inc.)

The efficacy and safety of nivolumab and ipilimumab (N + I) combination therapy for Japanese patients with advanced unresectable melanoma was re-evaluated in clinical practice. One hundred Japanese patients with advanced melanoma were included. The overall response rate was 24%; complete response (CR), 6%; partial response, 18%. The response rates were 33.3% in the systemic therapy-naïve and 15.4% in the prior-treatment groups, and 16.1% for patients who were treated with first-line anti-programmed death 1 antibody monotherapy followed by second-line N + I therapy after progression of the disease. The response rate for cutaneous melanoma was 32.7%, and 47.8% in the naïve group. Response rates for non-acral, acral, and mucosal melanoma were 34.9%, 25%, and 16.7%, respectively. The median progression-free survival (PFS) for all patients was 3.25 months (6.5 and 2.5 months in the naïve and prior-treatment groups, respectively). Median overall survival (OS) was 14.5 months (25.25 and 7.5 months in the naïve and prior-treatment groups, respectively). There were no significant differences in PFS or OS for patients with non-acral, acral, or mucosal melanoma. The 3-year PFS and OS were both 100% in patients who achieved CR with combination therapy. Adverse events occurred in 89% and were grade three or higher in 56% of cases. Although direct comparisons cannot be made due to different patient backgrounds, N + I combination therapy in Japanese patients in clinical practice tended to be inferior when compared to global study and non-Asian patients in clinical practice. The highest response rate was in the cutaneous melanoma therapy-naïve group. The best tumor response was associated with survival outcome, and the PFS and OS were good in cases where CR was obtained. The proportion of grade three and four adverse events was as high as that in the global study., (© 2022 Japanese Dermatological Association.)

Purpose: Primary anorectal melanoma (ARM) accounts for approximately 1.2% of all melanomas and 16.5% of all mucosal melanomas. ARM is associated with the shortest interval to disease progression and the highest rate of metastasis; however, optimal therapeutic strategies for ARM remain controversial. This study aimed to assess the ideal surgical intervention for ARM and to determine the effect of immune checkpoint inhibitors (ICI)., Methods: We included 47 patients with ARM treated at the National Cancer Center Hospital in Japan from 2011 to 2020. We performed a survival analysis for each of these groups: (i) patients with ARM (n = 47); (ii) operable non-stage IV cases at initial presentation (n = 35); and (iii) stage IV cases (n = 32)., Results: The 5-year overall survival (OS) was 53.6%, and the median OS was 78.7 months in patients with ARM. No statistically significant difference in 5-year OS was found between rectal and anal sites (50.9% vs. 56.7%). In the non-stage IV subgroup, the type of surgery (abdominoperineal resection or wide local excision) did not correlate with OS (HR 1.85; 95% CI 0.46-7.5; p = 0.39). In the stage IV subgroup, the 2-year OS of the ICI treatment group was 61.4%, whereas that of the dacarbazine regimen group was 0% (p = 0.048)., Conclusion: Our ARM prognosis was better than that of previous studies. Our findings suggest that the availability of ICI therapy may improve survival in patients with advanced ARM. However, further research is warranted to identify both the clinical and molecular predictors of response to improve patient selection., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Malignant melanoma (MM) is usually resistant to radiotherapy. Brachytherapy may be an option in patients with bleeding or pain, and those in whom surgery is difficult. Brachytherapy has few side effects and can be used in combination with external beam radiotherapy or chemotherapy. We summarize the demographic and clinical characteristics of 15 patients who received brachytherapy for MM at our hospital and describe two of these representative cases. Patient 1 had an approximately 10-mm, dark-red nodule near the external urethral meatus. Excision was not performed to preserve urethral function. A gradual improvement was observed after 48 Gy of remote afterloading system (RALS) brachytherapy and nivolumab therapy. Patient 2 had a 38-mm, black tumor on the vagina. Post-resection, RALS brachytherapy was administered to treat the residual black macule and a lesion quickly disappeared. In all 15 cases, nine patients received radiotherapy for local control and six patients received palliative radiotherapy to reduce symptoms such as bleeding and pain. The irradiation site was the vagina in six patients, lymph node metastasis in five, head and neck in two, skin or subcutaneous metastases in two, and the anus in one. Treatment effect for local control and palliative care was 75% and 83% of patients, respectively. In particular, disappearance of the tumor or disappearance of symptoms was observed in half of the cases of brachytherapy to the vagina. On the other hand, brachytherapy was not very effective for lymph node metastases. Immediately after radiotherapy, eight (53%) patients experienced dermatitis or mucositis. Due to the histological and structural characteristics of mucosal melanoma of the luminal organs, brachytherapy may be an effective therapy. Hence, widespread use of brachytherapy with an appropriate irradiation technique aiming for local control and palliative care in case of unresectable MM should be considered., (© 2022 Japanese Dermatological Association.)

An air-stable λ 3 -phosphinine-containing polycyclic aromatic compound without steric protection was synthesized and its charge transport properties were evaluated, which revealed moderate hole mobility. This research is the first experimental demonstration of the organic electronic applications of low-coordinate phosphorus compounds.

Advanced malignant melanoma (MM) is treated with immune checkpoint inhibitor (ICI) therapy, which often results in several immune-related adverse events. Fulminant type 1 diabetes mellitus (T1DM) is a rare, rapidly progressive, life-threatening disease. Here, we summarize 8 cases of MM with ICI-induced T1DM and describe one case that developed fulminant T1DM due to nivolumab therapy. We retrospectively reviewed patients treated with ICI from 2014 to 2021 at our hospital. The clinical features and risk factors of ICI-induced T1DM were discussed. ICIs were administered to 426 MM patients at our hospital. Among these, nivolumab was administered in 5 cases, pembrolizumab in 1 case, and the combination of nivolumab and ipilimumab in 2 cases. The frequency of ICI-associated T1DM was 1.88%. The mean glycated hemoglobin level at T1DM onset was 8.0 ± 1.0%. Of the patients, 75% were diagnosed with fulminant T1DM, 62.5% developed diabetic ketoacidosis, and 25% had glutamic acid decarboxylase (GAD) antibodies (an early predictive marker for T1DM). The mean interval between the first ICI administration and T1DM development was 201 ± 187 days. The mean duration of resumption was 13 ± 7 days. We should monitor for T1DM development following treatment with ICIs. ICI can be continued to be used to treat MM if insulin therapy successfully controls T1DM. A 67-year-old patient who received adjuvant nivolumab therapy developed fulminant T1DM and thyrotoxicosis 57 days later and tested positive for GAD antibodies. Subsequently, he developed hypophysitis and an isolated adrenocorticotropin deficiency. He continued receiving nivolumab along with self-injected insulin without developing recurrence., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The objectives of this study were to simulate long-term orthodontic tooth movement in en-masse retraction using the finite element method and investigate the effects of power arms on tooth movements when using a lingual appliance in comparison with a labial appliance., Methods: A 3-dimensional finite element model of the maxillary dentition was constructed with 0.018-in brackets and 0.016 × 0.022-in stainless steel archwire. An en-masse retraction was performed by applying retraction force at various lengths of the power arm (4, 6, 8, and 10 mm) to the second molar tube, and long-term tooth movements with the lingual and labial appliances were analyzed using the finite element method., Results: Although lingual crown tipping of the incisor was more marked with the lingual appliance than with the labial appliance in the early phase of space closure, only a slight difference was evident after space closure. Although the power arm was effective for achieving better-controlled tooth movement and reducing vertical and transverse bowing effects, bodily movement of the incisor could not be achieved, and bowing effects could not be eliminated., Conclusions: To provide better torque control of the incisor or prevent a vertical bowing effect, the incorporation of extra torque into brackets of incisors was recommended, and the use of power arms for the lingual appliance. To prevent a transverse bowing effect, incorporation of the antibowing bend or application of retraction force from both buccal and lingual sides or temporary skeletal anchorage devices was recommended., (Copyright © 2022 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Background: In most cutaneous melanomas of the distal extremity, sentinel lymph nodes (SLNs) are identified in the axillary or inguinal basin; however, they may be occasionally found in the epitrochlear or popliteal basins. The incidence and patterns of lymphatic drainage to the epitrochlear or popliteal SLNs are unclear., Methods: To clarify the incidence and clinical characteristics of melanoma draining to these ectopic SLNs, we performed a retrospective study of the patients with distal extremity melanoma who underwent SLN biopsy at the National Cancer Center Hospital between April 2010 and December 2017., Results: We identified 27 patients with melanoma of the distal upper extremity and 113 patients with melanoma of the distal lower extremity. All patients with distal upper and lower extremity melanomas had SLNs in the axillary and inguinal basins. Epitrochlear SLNs were found in 14.8% (4/27) of the patients with upper extremity melanoma, and the frequency increased by 36.4% (4/11) when the primary melanoma was located in the basilic vein area (P = 0.00188). Popliteal SLNs were found in 21.2% (24/113) of the patients with lower extremity melanoma, and the frequency increased by 37.9% (22/58) when the primary melanoma was located in the lesser saphenous vein area (P < 0.0001)., Conclusion: The incidence of SLNs identified in the epitrochlear or popliteal basin is not uncommon, and physicians need to be aware of these ectopic SLNs, especially when the primary melanoma is located in the basilic vein or lesser saphenous vein areas accordingly., (© 2022 the International Society of Dermatology.)

Background: Completion lymph node dissection (CLND) has long been the standard treatment for stage III melanomas identified as metastasis on the sentinel node (SN-positive). Two major changes occurred in 2017 and 2018, the change in the CLND criteria for SN-positive patients and the approval of several adjuvant therapies could revolutionize such management approach. However, their effects have not been fully investigated on the real-world outcomes of stage III melanoma patients. Therefore, we investigated the impact of these changes on the prognosis of Japanese stage III melanoma patients., Methods: Totally, 119 stage III, SN-positive melanoma patients were included. They were categorized into those diagnosed as SN-positive between January 2015 and June 2017 (pre-June 2017 group) and between July 2017 and December 2019 (post-July 2017 group). Recurrence-free survival (RFS), overall survival, and prognostic factors were analyzed., Results: The frequency of patients who received CLND was significantly higher in the pre-June 2017 group (p = 0.001), and those who received adjuvant therapy were significantly higher in the post-July 2017 group (p < 0.001). The 2-year RFS was 50.1% and 68.5% in the pre-June and post-July 2017 groups, respectively (p = 0.049). Cox proportional hazards model analysis for RFS showed that adjuvant therapies reduce the risk of recurrence (hazard ratio 0.37; 95% confidence interval 0.14-0.99; p = 0.047)., Conclusion: Changes in the CLND criteria in SN-positive patients and the approval of adjuvant therapies for stage III melanomas have significantly impacted Japanese melanoma medicine. Adjuvant therapy tended to prolong patient's RFS while omitting immediate CLND had no significant negative influence on it., (© 2021. Japan Society of Clinical Oncology.)

Introduction: Although many attempts have been made to study the mechanical behavior of closing loops, most have been limited to analyses of the magnitude of forces and moments acting on the end of the closing loop. The objectives of this study were to simulate orthodontic tooth movement during the activation of a newly designed closing loop combined with a gable bend and to investigate the optimal loop activation condition to achieve the desired tooth movement., Methods: We constructed a 3-dimensional model of maxillary dentition reproducing the state wherein a looped archwire combined with a gable bend was engaged in brackets and tubes. Orthodontic tooth movements were simulated for both anterior and posterior teeth while varying the degree of gable bend using the finite element method., Results: The incorporation of a 5° gable bend into the newly designed closing loop produced lingual crown tipping for the central incisor and bodily movement for the first molar. The incorporation of 10° and 15° gable bends produced bodily movement and root movement, respectively, for the central incisor and distal tipping for the first molar., Conclusions: Torque control of the anterior teeth and anchorage control of the posterior teeth can be carried out effectively and simply by reducing by half the thickness of a teardrop loop with a height of 10 mm and a 0.019 × 0.025-in cross-section, to a distance of 3 mm from its apex, and by incorporating various degrees of gable bend into the loop corresponding to the treatment plan., (Copyright © 2021. Published by Elsevier Inc.)

In recent years, advances in artificial intelligence (AI) technology have led to the rapid clinical implementation of devices with AI technology in the medical field. More than 60 AI-equipped medical devices have already been approved by the Food and Drug Administration (FDA) in the United States, and the active introduction of AI technology is considered to be an inevitable trend in the future of medicine. In the field of oncology, clinical applications of medical devices using AI technology are already underway, mainly in radiology, and AI technology is expected to be positioned as an important core technology. In particular, "precision medicine," a medical treatment that selects the most appropriate treatment for each patient based on a vast amount of medical data such as genome information, has become a worldwide trend; AI technology is expected to be utilized in the process of extracting truly useful information from a large amount of medical data and applying it to diagnosis and treatment. In this review, we would like to introduce the history of AI technology and the current state of medical AI, especially in the oncology field, as well as discuss the possibilities and challenges of AI technology in the medical field.

The efficacy and safety of nivolumab + ipilimumab combination therapy were retrospectively examined in Japanese patients with unresectable advanced melanoma in clinical practice. Fifty-seven patients with advanced melanoma received the nivolumab + ipilimumab combination therapy. The primary site was cutaneous, mucosal, uveal and unknown in 35, 16, two and four patients, respectively. The overall response rate was 26.3%, with complete response observed in two (3.5%) patients, partial response in 13 (22.8%), stable disease in 12 (21.1%) and progressive disease in 30 (52.6%). The response rate in the treatment-naive and prior systemic therapy group was 40.7% and 13.3%, respectively. For those treated with a single immune checkpoint inhibitor followed by the nivolumab + ipilimumab combination therapy as second-line therapy after disease progression, the response rate was 18.8%. Median progression-free survival (PFS) and overall survival (OS) in all patients was 3.3 and 14 months, respectively. Median PFS in the treatment-naive and prior systemic therapy groups was 13 and 2 months, respectively. Median OS was unreached in the treatment-naive group and was 6.3 months in prior systemic therapy groups. There was no significant difference in PFS and OS for non-acral, acral and mucosal melanoma. Adverse events occurred in 86% of patients; 56.1% were grade 3 or worse. The response rate in an actual clinical setting, including the prior systemic therapy group, was lower than that in the global study and the Japanese phase II study. However, in the treatment-naive group, the rate was equivalent to that in the Japanese phase II study. PFS and OS in the treatment-naive group were comparable with those in the global study and Japanese phase II study, suggesting that the treatment was effective. The proportion of grade 3 and 4 immune-related adverse events was as high as that in the global study and Japanese phase II study., (© 2020 Japanese Dermatological Association.)

Recent studies have demonstrated the usefulness of convolutional neural networks (CNNs) to classify images of melanoma, with accuracies comparable to those achieved by dermatologists. However, the performance of a CNN trained with only clinical images of a pigmented skin lesion in a clinical image classification task, in competition with dermatologists, has not been reported to date. In this study, we extracted 5846 clinical images of pigmented skin lesions from 3551 patients. Pigmented skin lesions included malignant tumors (malignant melanoma and basal cell carcinoma) and benign tumors (nevus, seborrhoeic keratosis, senile lentigo, and hematoma/hemangioma). We created the test dataset by randomly selecting 666 patients out of them and picking one image per patient, and created the training dataset by giving bounding-box annotations to the rest of the images (4732 images, 2885 patients). Subsequently, we trained a faster, region-based CNN (FRCNN) with the training dataset and checked the performance of the model on the test dataset. In addition, ten board-certified dermatologists (BCDs) and ten dermatologic trainees (TRNs) took the same tests, and we compared their diagnostic accuracy with FRCNN. For six-class classification, the accuracy of FRCNN was 86.2%, and that of the BCDs and TRNs was 79.5% ( p = 0.0081) and 75.1% ( p < 0.00001), respectively. For two-class classification (benign or malignant), the accuracy, sensitivity, and specificity were 91.5%, 83.3%, and 94.5% by FRCNN; 86.6%, 86.3%, and 86.6% by BCD; and 85.3%, 83.5%, and 85.9% by TRN, respectively. False positive rates and positive predictive values were 5.5% and 84.7% by FRCNN, 13.4% and 70.5% by BCD, and 14.1% and 68.5% by TRN, respectively. We compared the classification performance of FRCNN with 20 dermatologists. As a result, the classification accuracy of FRCNN was better than that of the dermatologists. In the future, we plan to implement this system in society and have it used by the general public, in order to improve the prognosis of skin cancer.

Treatment for patients with unresectable melanoma has been dramatically changed by the use of immunocheckpoint inhibitors (ICI). In this study, we reviewed patients with unresectable stage III/IV melanoma, who were treated with nivolumab between July 2014 and March 2017 at the Department of Dermatologic Oncology, National Cancer Center Hospital, Tokyo, and retrospectively recorded cutaneous adverse events (cAE), development of vitiligo, clinical characteristics and clinical responses. We identified 128 patients, 61 (47.7%) of whom showed cAE, including 30 (23.4%) with development or exacerbation of vitiligo. The prognosis of patients with melanoma treated with ICI correlated with cAE, including development of vitiligo. Patients with cAE showed better objective responses (41.0% vs 6.0%, P < 0.001), progression-free survival (PFS) (377 vs 61 days, P < 0.001) and overall survival (OS) (763 vs 209 days, P < 0.001) than did patients without cAE. Patients who developed vitiligo showed better objective responses (53.3% vs 29.0% vs 6.0%, P < 0.001), PFS (median, not reached vs 317 vs 65 days, P < 0.001) and OS (not reached vs 689 vs 209 days, P < 0.001) than did patients with other cAE and patients without cAE. Landmark analysis showed development of vitiligo starting 20 weeks after starting nivolumab correlated with better OS. In multivariate analysis, OS correlated with performance status, number of metastasized organs, cAE other than vitiligo and development of vitiligo. Despite the fact that the correlation between other cAE and OS was less than that of vitiligo, cAE may be a simple marker of favorable prognosis., (© 2020 Japanese Dermatological Association.)

Extramammary Paget's disease (EMPD) often invades the dermis and metastasizes to the lymph nodes. Patients with EMPD associated with lymph node metastases have poor prognosis; to date, effective treatment has not yet been established. Lymph node dissection, aiming to control the local disease, is a standard form of management for EMPD patients with lymph node metastases (LNM). We investigated the clinical and pathological features, treatment strategies and prognostic factors of patients with metastatic EMPD who underwent lymph node dissection. We retrospectively evaluated 38 cases of extramammary Paget's disease with lymph node metastasis over 10 years. All patients underwent wide resection of the primary lesion and lymph node dissection. Univariate analysis revealed the number of metastatic nodes and lymphadenopathy as prognostic factors. In multivariate analysis, the number of metastatic lymph nodes retained statistical significance (hazard ratio, 35.3; 95% confidence interval, 3.23-387.0; P = 0.003). The 5-year survival rate was 100% and 19.1% in patients with two or less LNM and with three or more LNM, respectively. In patients with three or more LNM, the 5-year survival rate after adjuvant radiation therapy was better than that after surgery alone (75% vs 0%). In conclusion, patients with two or less LNM can be expected to have long-term survival with lymph node dissection only, while patients with three or more LNM may require adjuvant radiation therapy to improve prognosis. These results suggest that lymph node dissection may be a strategy to treat EMPD with regional LNM., (© 2020 Japanese Dermatological Association.)

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma. This condition is difficult to diagnose because of its large size and expansive nature and may be diagnosed as a malignant tumor. There are various treatments such as surgery and oral retinoids; however, limited studies have verified their effectiveness. Here, we report a case of KCM on the anterior chest of a 50-year-old woman and evaluate the efficacy of oral retinoids. In this case, oral retinoids were highly effective for KCM treatment. A total of 55 cases of KCM, including 54 previously reported cases, were reviewed, and their clinical characteristics and treatment were examined. In this report, 14 of 16 patients were effectively treated with oral retinoids, resulting in a treatment rate of 87.5%. Furthermore, even low-to-medium doses were sufficient for treatment and prevention. KCM can be misdiagnosed as a malignant disease based on its clinical features. Due to its large size and expansive nature, a wide excision may be performed; however, because oral retinoids have a very high response rate, an accurate diagnosis will help avoid an unnecessary wide excision., (© 2020 Wiley Periodicals LLC.)

We evaluated the efficacy of nivolumab in patients with metastatic uveal melanoma previously untreated with ipilimumab. We performed a retrospective study at the National Cancer Center Hospital in Tokyo, Japan, where nivolumab was approved 1 year earlier than ipilimumab. Clinical efficacy outcomes were determined by assessing best overall response according to the Response Evaluation Criteria in Solid Tumors (version 1.1), progression-free survival and overall survival. Fourteen patients were analyzed; none had received any prior systemic therapies although eight had undergone transarterial chemoembolization. The median follow-up period was 15 months. The objective response and disease control rates were 7.1% and 42.9%, respectively (one partial response and five stable diseases). The median progression-free survival and overall survival were 10 (range, 4-105) and 60 (range, 5-105) weeks, respectively. Liver metastases in three patients were all programmed cell death-1 ligand negative. Lower lactate dehydrogenase, development of vitiligo, and a neutrophil-to-lymphocyte ratio less than 5 at week 6 were associated with favorable progression-free survival and overall survival; of these, only a neutrophil-to-lymphocyte ratio less than 5 at week 6 was statistically significant. Even with the use of nivolumab before ipilimumab, metastatic uveal melanoma appears to remain refractory to nivolumab monotherapy. However, because one patient in our cohort achieved an objective response, and the median overall survival exceeded 1 year, treatment strategies that incorporate anti-PD1 antibody should be further investigated. Whether a neutrophil-to-lymphocyte ratio less than 5 at week 6 is a favorable early on-treatment marker should be validated in larger cohorts.

To achieve a complete closed-shell quinoidal state, bis(dicyanomethylene)-substituted quinoidal terthiophenes bearing benzene annelation at all thiophene rings were synthesized using a retro-Diels-Alder reaction as the key step. The unique structures and properties originating from the full benzene annelation were revealed by X-ray analysis as well as property measurements. Organic solar cells based on the combination of a donor polymer with a quinoidal terthiophene as an acceptor showed a power conversion efficiency of 1.39%.

Background: The combination of PD-1 inhibitors and cytotoxic drugs is reported to enhance anti-tumor activity in non-small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor-infiltrating immune cells., Methods: The medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression-free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab., Results: Eight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4-90.6%; P = 0.004) and median progression-free survival to six months (95% CI 4.6-7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD-L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm 2 of PD-1 + immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm 2 . Responders had fewer PD-1 + immune cells than non-responders (percentage P = 0.028; density P = 0.034)., Conclusion: Salvage chemotherapy following nivolumab improved anti-tumor activity regardless of tumor PD-L1 status, but nivolumab following chemotherapy did not. The presence of few PD-1 + tumor-infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re-sensitizes the tumor immune microenvironment to chemotherapy., (© 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objective Mamushi (Gloydius blomhoffii) snakebite is the most common type of snake injury in Japan and is also seen in China and Korea. Although the components of Mamushi venom have been investigated, epidemiological and clinical descriptions still remain limited in the English literature. The aim of this study was to review the clinical features and management of patients with injuries related to Mamushi snakebites. Methods We conducted a retrospective examination of 114 Mamushi snakebite cases encountered at a general hospital in Japan from January 2004 to November 2016. Data were collected from the medical records. Results We found that Mamushi snakebites commonly occurred during summer and the daytime, with elderly men typically being affected. The symptom grade at initial consultation was significantly worse in the walk-in group than in the ambulance admission group, probably due to treatment delay. The number of fangs that pierced the skin was not related to the severity of the symptoms. The group treated with a tourniquet more frequently exhibited exacerbation of symptoms than those that received other treatments (p<0.001). Conclusion The delay between patients being bitten and arriving at hospital as well as the number of fangs that pierced the skin did not affect the duration of hospitalization; however, proximal tourniquation should be avoided in such cases, as significant exacerbation of local symptoms was observed when this procedure was applied.

Rituximab treatment may cause or exacerbate Kaposi's sarcoma (KS) in patients with human immunodeficiency virus (HIV)-associated multicentric Castleman's disease. Despite the widespread use of rituximab, rituximab-induced KS has not yet been reported in HIV-negative patients with diffuse large B cell lymphoma (DLBCL). We herein report a case of KS that developed after undergoing rituximab-containing chemotherapy in an HIV-negative patient with DLBCL. An 84-year-old man who received rituximab-containing chemotherapy for the treatment of DLBCL developed severe infection, and subsequently KS. Our observations indicate that serious infections under rituximab treatment may trigger KS. KS should therefore be considered when skin tumors appear in lymphoma patients receiving rituximab-containing chemotherapy.

OVOL1 is an important transcription factor for epidermal keratinization, which suppresses proliferation and switches on the differentiation of keratinocytes. A recent genome-wide association study has revealed that OVOL1 is one of the genes associated with susceptibility to atopic dermatitis. Although it is known to be expressed in murine skin and hair follicles, no investigations have focused on its localization in human skin. In the present study, we thus immunolocalized the expression of OVOL1 in normal and diseased human skin. In normal human skin, OVOL1 was preferentially expressed in the suprabasal layer of the epidermis, inner root sheath of hair, mature sebocytes and the ductal portion of the eccrine glands. Compared to this, no remarkable change in the expression of OVOL1 was observed among inflammatory skin diseases. The expression of OVOL1 was evident in eccrine poroma and hidradenoma. Moreover, it was overexpressed in Bowen's disease and sebaceous adenoma, in sharp contrast to its downregulation in their more malignant counterparts, squamous cell carcinoma and sebaceous carcinoma. OVOL1 may play an important role in human skin morphogenesis and tumorigenesis.

Electron-donor function of methanofullerenes (MFs) in bulk heterojunction systems is demonstrated by the combination of MFs with the electron-transporting π-system that has a much higher electron affinity than MFs.

The synthesis of three-dimensional compounds containing perylene bis(dicarboximide) for application as acceptor materials in organic photovoltaics is reported. Physicochemical measurements as well as device evaluations revealed that the characteristic properties of these materials are derived from their three-dimensional structure.

An HPLC method using fluorescence detection for the quantitation of curcuminoids, such as curcumin (C), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) in turmeric products is described. This method involves a simple ultrasonic extraction with methanol as a pretreatment of turmeric products. The separation of curcuminoids and 2,5-xylenol (internal standard) was achieved within 30 min on a Cadenza CD-C(18) column (250 x 4.6 mm; i.d., 3 microm) with a mixture of acetate buffer and CH(3)CN. The calibration curves of standard curcuminoids showed good linearities of more than 0.993 of the correlation coefficient. The instrumental detection limits for C, DMC and BDMC (signal-to-noise ratio = 3) were 1.5, 0.9 and 0.09 ng mL(-1), respectively. The relative standard deviations of intra-and inter-day assays by curcuminoids spiked to turmeric powder were less than 6.1%. The proposed method was successfully applied to determine curcuminoids in commercial turmeric products, such as turmeric powders, a tablet, a dressing, a beverage, tea, and crude drugs.

The combination of 1 KE/day of OK-432 (everyday) and 10 mg/day of Carboquone (once a week) had been administered for three weeks to 18 cases of the patients with unresectable lung cancer. The response rate was 50% in the patients whose diameters of tumors could be measured. These results might be provided by the fact that the large dose administration of Carboquone became possible with simultaneous administration of OK-432, which might have an activating effect of bone marrow function; consequently, original properties of alkylating agent could be utilized in this therapy. Leukopenia, (leukocyte counts: less than 3,000) was observed in 10 out of 18 cases (55.6%) at one week after administration of the drugs, and in all but one case leukopenia was recovered after 4 weeks of the administration. No other severe side effects were observed.