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Melanoma is a major malignant cutaneous neoplasm with a high mortality rate. In recent years, the treatment of melanoma has developed dramatically with the invention of new therapeutic agents, including immune checkpoint inhibitors and molecular‐targeted agents. These agents are available as adjuvant therapies for postoperative patients with stage IIB, IIC, and III melanomas. Furthermore, neoadjuvant therapy has been studied in several global clinical trials and has demonstrated promising and favorable clinical efficacy, mainly in patients with palpable regional lymph nodes. A recent large phase III clinical trial investigating early lymph node dissection for sentinel lymph node metastases demonstrated no survival benefits. Based on these data, surgery should be reconsidered as an appropriate treatment modality for melanoma. The need for invasive surgical procedures will be reduced with the invention of effective adjuvant and neoadjuvant therapies and novel clinical trial data on regional lymph node dissection. However, surgery still plays an important role in treating early‐stage melanoma, accurately determining the disease stage, and effective palliative treatment for advanced melanoma. In this article, we focus on surgery for primary tumors, regional lymph nodes, and metastatic sites in an era of remarkably revolutionary drug treatments for melanoma. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma is usually treated with surgery; however, locoregionally advanced cutaneous squamous cell carcinoma can be difficult to resect. Although recent guidelines from Western countries recommend using anti–programmed cell death protein 1 (PD‐1) antibodies, including cemiplimab and pembrolizumab, there are no approved anti–PD‐1 antibodies for locoregional cutaneous squamous cell carcinoma in Asian countries. S‐1 is an oral drug with a low incidence of severe toxicity that can be used for head and neck cancers, including head and neck locoregional cutaneous squamous cell carcinoma, in Japan. We retrospectively evaluated patients with head and neck locoregional cutaneous squamous cell carcinoma treated with S‐1 at two Japanese institutions (2008–2022). The initial dosage was determined by the body surface area (<1.25 m2: 80 mg/day, 1.25–1.5 m2: 100 mg/day, ≥1.5 m2: 120 mg/day) for 28 consecutive days. The outcome measures were objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Fourteen patients were included. The ORR was 78%, and the complete response (CR) rate was 64.3%. The median PFS and OS were not reached (NR) (95% confidence interval [CI], 5.9 months–NR) and NR (95% CI, 13.8 months–NR), respectively. The 12‐month PFS and OS rates were 51% and 85%, respectively. Six of the nine patients who achieved CR showed no recurrence during the follow‐up period (median follow‐up, 24.7 months). After CR, three patients experienced recurrence. Among these, two resumed S‐1 treatment and subsequently underwent salvage surgery, resulting in a sustained absence of recurrence. One patient developed lung metastasis and died, although S‐1 therapy was resumed. Only one patient (7.1%) developed grade 3 anemia. S‐1 showed favorable efficacy and low toxicity in patients with head and neck locoregionally advanced cutaneous squamous cell carcinoma. S‐1 may be a good alternative to the anti–PD‐1 antibody for treating head and neck locoregionally advanced squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment. We herein investigated whether the addition of adipose tissue–derived stem cells (ADSCs) to GHNF affected the outcome. A silicone spacer sandwiched between two GHNFs with (AG group) or without (GHNF group) ADSCs, or a silicone spacer alone (Silicone group) was implanted into the subcutaneous space of healthy mice at 6 weeks before transplantation, then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Intraportal transplantation (IPO group) was also performed to compare the transplant efficiency. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, and inflammatory mediators were evaluated. The results in the subcutaneous transplantation were compared using the Silicone group as a control. The results of the IPO group were also compared with those of the AG group. The AG group showed significantly better blood glucose changes than the Silicone and the IPO groups. The cure rate of AG group (72.7%) was the highest among the groups (GHNF; 40.0%, IPO; 40.0%, Silicone; 0%). The number of vWF-positive vessels in the subcutaneous space of the AG group was significantly higher than that in other groups before transplantation (P < 0.01). Lectin angiography also showed that the same results (P < 0.05). According to the results of the ADSCs tracing, ADSCs did not exist at the transplant site (6 weeks after implantation). The positive rates for laminin and collagen III constructed around the transplanted islets did not differ among groups. Inflammatory mediators were higher in the Silicone group, followed by the AG and GHNF groups. Pretreatment using bioabsorbable scaffolds combined with ADSCs enhanced neovascularization in subcutaneous space, and subcutaneous islet transplantation using GHNF with ADSCs was superior to intraportal islet transplantation. [ABSTRACT FROM AUTHOR]

Although subcutaneous islet transplantation has many advantages, the subcutaneous space is poor in vessels and transplant efficiency is still low in animal models, except in mice. Subcutaneous islet transplantation using a two-step approach has been proposed, in which a favorable cavity is first prepared using various materials, followed by islet transplantation into the preformed cavity. We previously reported the efficacy of pretreatment using gelatin hydrogel nonwoven fabric (GHNF), and the length of the pretreatment period influenced the results in a mouse model. We investigated whether the preimplantation of GHNF could improve the subcutaneous islet transplantation outcomes in a rat model. GHNF sheets sandwiching a silicone spacer (GHNF group) and silicone spacers without GHNF sheets (control group) were implanted into the subcutaneous space of recipients three weeks before islet transplantation, and diabetes was induced seven days before islet transplantation. Syngeneic islets were transplanted into the space where the silicone spacer was removed. Blood glucose levels, glucose tolerance, immunohistochemistry, and neovascularization were evaluated. The GHNF group showed significantly better blood glucose changes than the control group (p < 0.01). The cure rate was significantly higher in the GHNF group (p < 0.05). The number of vWF-positive vessels was significantly higher in the GHNF group (p < 0.01), and lectin angiography showed the same tendency (p < 0.05). The expression of laminin and collagen III around the transplanted islets was also higher in the GHNF group (p < 0.01). GHNF pretreatment was effective in a rat model, and the main mechanisms might be neovascularization and compensation of the extracellular matrices. [ABSTRACT FROM AUTHOR]