A case of pelvic squamous cell carcinoma of unknown primary origin that responded well to radiotherapy and nivolumab.

Squamous cell carcinoma of unknown primary origin in the pelvis is rare. We report a case of a 64-year-old woman with a large osteolytic squamous cell carcinoma of unknown primary origin in the pelvis that presented with p16 expression. The patient presented with leg pain and swelling and was admitted to our hospital. Computed tomography scans of the pelvis revealed a large osteolytic tumor. A computed tomography-guided needle biopsy was performed, and pathological examination revealed neoplastic cells with metastatic squamous cell carcinoma presenting with p16 expression. Despite a whole-body examination, tumor origin remained undetected. The patient was treated for this metastatic squamous cell carcinoma of unknown primary using palliative radiotherapy for hip pain and nivolumab. Remarkable reduction in the tumor marker levels and tumor size were obtained after therapy. Finally, partial remission and progression-free survival for more than 7 months were achieved. In conclusion, we experienced a rare case with a large p16-positive squamous cell carcinoma of unknown primary in pelvis, which responded well to radiotherapy and nivolumab.

Evaluation of Pancreatic ß-cell Differentiation Efficiency of Human iPSC Lines for Clinical Use.

BACKGROUND: Transplantation of pancreatic ß-cells generated from human induced pluripotent stem cells (hiPSCs) has great potential as a root treatment for type 1 diabetes. However, their current level of efficiency to differentiate into ß-cells is still not at par for clinical use. Previous research has shown that differentiation efficiency varies among human embryonic stem cells and mouse-induced pluripotent stem cell lines. Therefore, selecting a suitable cell line for efficient induction into desired tissues and organs is crucial. METHOD: In this study, we have evaluated the efficiency of 15 hiPSC lines available for clinical use to differentiate into pancreatic ß-cells. RESULTS: Our investigation has revealed induction efficiency to differ among the hiPSC lines, even when derived from the same donor. Among the hiPSC lines tested, the 16A01 cell line exhibited the highest insulin expression and low glucagon expression, suggesting that this cell line is suitable for differentiation into ß-cells. CONCLUSION: Our study has demonstrated the importance of selecting a suitable hiPSC line for effective differentiation into ß-cells.

SMARCA4-deficient tumors in the adrenal gland and small intestines: A rare case report.

Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are rare undifferentiated thoracic malignancies with poor prognosis. They predominantly affect young men who are heavy smokers. Recently, the category of SMARCA4-deficiency-related malignancy has been expanded to include extra-thoracic sites, such as the paranasal sinuses, gastrointestinal tract, ovary, and uterus. We report a rare case of SMARCA4-deficient tumors in the adrenal gland and small intestines. SMARCA4-deficient tumors should be included in the differential diagnosis when multiple large masses with heterogeneous contrast effect and strong accumulation are seen in cancers of unknown primary on 18F-fluorodeoxyglucose (FDG) positron emission tomography with computed tomography (PET/CT).

SAPHO syndrome with a purely osteolytic form: A case report.

SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare, chronic autoinflammatory disorder that can present with a constellation of cutaneous and osteoarticular symptoms. Osteodestructive lesions are not pathognomonic, whereas hyperostosis and osteitis are the most prominent imaging findings. We report the case of a man with osteolytic changes of the lumbar vertebra and a history of palmoplantar pustulosis. Biopsy revealed no neoplasm, suggesting SAPHO syndrome. Our case demonstrates that knowledge of atypical radiologic findings is necessary for the diagnosis of SAPHO syndrome.

Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells.

Islet transplantation, including pancreatic beta cells, has become an approved treatment for type I diabetes. To date, the number of donors limits the availability of treatment. Induction of pancreatic endocrine cells from pluripotent stem cells including iPSCs in vitro offers promise as a solution, but continues to face problems including high reagent costs and cumbersome differentiation procedures. In a previous study, we developed a low-cost, simplified differentiation method, but its efficiency for inducing pancreatic endocrine cells was not sufficient: induction of endocrine cells is non-uniform, resulting in colonies containing relatively high ratio of non-pancreatic-related cells. Here, we applied cyclin-dependent kinase inhibitors (CDKi) within a specific time window, which improved the efficiency of pancreatic endocrine cell induction. CDKi treatment reduced the prevalence of multi-layered regions and enhanced expression of the endocrine progenitor-related marker genes PDX1 and NGN3 resulting in enhanced production of both INSULIN and GLUCAGON. These findings support a step forward in the field of regenerative medicine of pancreatic endocrine cells.

Fluorodeoxyglucose positron emission tomography (FDG/PET) shows the effect of carbon-ion radiotherapy (CIRT); with pathologic confirmation.

Response evaluation of carbon-ion radiotherapy poses a diagnostic challenge. Due to its functional aspects, fluorodeoxyglucose positron emission tomography (FDG/PET) has a role in the diagnosis of photon radiation therapy. In addition, several studies suggested that FDG/PET may be useful to select the optimal site for performing a diagnostic biopsy. Here, we report a 73-year-old female in which FDG/PET was effective in determining the recurrence of liposarcoma and the therapeutic effect. Based on the results of FDG/PET, we could make a pathologic definitive diagnosis and selectively performing carbon-ion radiotherapy for active tumors.

A simple method of hiPSCs differentiation into insulin-producing cells is improved with vitamin C and RepSox.

Human induced pluripotent stem cells (hiPSCs) are considered a promising source of pancreatic ß-cells for the treatment of diabetes. However, this approach is limited by issues such as low efficiency and high cost. Here, we have developed a new protocol to induce insulin-producing cells. To reduce costs, we decreased the number of reagents and replaced protein reagents with chemical compounds. In this method, we increased induction efficiency with ascorbic acid (vitamin C) and an ALK5 inhibitor, RepSox. In 2D culture, the majority of cells were immature ß-cells with low glucose-stimulated insulin secretion. Transferring to 3D culture immediately after endocrine progenitor cell differentiation, however, improved glucose-stimulated insulin secretion. This simplified method will contribute to realizing transplantation therapy of ß-cells using iPSCs.

A case of bulla formation after treatment for COVID-19 pneumonia.

In December 2019, coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was reported in Wuhan, China. An 82-year-old woman presented to our hospital with high fever (39°C) and chest computed tomography revealed ground-glass opacities in the left lung apex. She was positive for SARS-CoV-2 based on a polymerase chain reaction test, and diagnosed with COVID-19 pneumonia. 6 months after treatment, chest CT showed a large bulla (47 mm × 29 mm) in the left lung apex, although pneumonia had partially resolved. Radiologic follow-up is needed after COVID-19 pneumonia, because patients may develop bullae after treatment.

Quantitative bone scan imaging using BSI and BUV: an approach to evaluate ARONJ early.

OBJECTIVE: The usefulness of bone scan index (BSI), a quantitative metric of the area of uptake in computer-aided diagnosis in bone scintigraphy, has been reported for the diagnosis of anti-resorptive-agent-related osteonecrosis of the jaw (ARONJ). The aim of this study is to validate the diagnostic ability of BSI for the early detection of ARONJ. In addition, the Bone uptake value (BUV), another quantitative index obtained from bone scintigraphy that indicates the degree of radioisotope (RI) accumulation, was used to improve the diagnostic ability for early detection of ARONJ. METHODS: A total of 34 patients (11 with ARONJ, 23 without ARONJ) who were administered anti-resorptive-agents for bone metastasis and had incidentally consulted a dental surgeon within 3 months after regular whole-body bone scintigraphy were retrospectively included in the study. The bone scintigraphy data were subjected to semiquantitative analysis of uptake in the jaw using BONENAVI (FUJIFILM Toyama Chemical, Co. Ltd., Tokyo, Japan; EXINI Diagnostics AB, Lund, Sweden) and BUV software (Technical Society for Quantitative Bone Scintigraphy and Fujifilm Toyama Chemical Co., Ltd. Tokyo, Japan). The ROI was set semi-automatically on mandibular hotspots, and the regional BSI was termed BSIJ. Planar anterior and posterior images were then sent to BUV software, with the ROI set manually as for BSI, and the regional BUV was termed BUVJ. RESULTS: Mean BSIJ values for the ARONJ positive and ARONJ negative groups were 0.17 ± 0.83 and 0.03 ± 0.50%, respectively. Mean BUVJ values for the ARONJ positive and ARONJ negative groups were 0.47 ± 0.17 and 0.19 ± 0.11, respectively. BSIJ × BUVJ values for the ARONJ positive versus ARONJ negative groups were 0.088 ± 0.067 vs. 0.007 ± 0.010. The AUC for BSIJ, BUVJ and BSIJ × BUVJ was 0.949, 0.951 and 0.988, respectively. CONCLUSION: The BSI metric of a CAD system for bone scintigraphy was useful for the early detection of ARONJ. Accuracy was improved with the additional use of BUVJ data. We recommend that SPECT imaging be performed when bone scintigraphy reveals focal or diffuse uptake in the mandible with high BSIJ and BUVJ.

Fam46a regulates BMP-dependent pre-placodal ectoderm differentiation in Xenopus.

The pre-placodal ectoderm (PPE) is a specialized ectodermal region which gives rise to the sensory organs and other systems. The PPE is induced from the neural plate border during neurulation, but the molecular mechanism of PPE formation is not fully understood. In this study, we examined the role of a newly identified PPE gene, Fam46a, during embryogenesis. Fam46a contains a nucleoside triphosphate transferase domain, but its function in early development was previously unclear. We show that Fam46a is expressed in the PPE in Xenopus embryos, and Fam46a knockdown induces abnormalities in the eye formation and the body color. At the neurula stage, Fam46a upregulates the expression of PPE genes and inhibits neural crest formation. We also show that Fam46a physically interacts with Smad1/Smad4 and positively regulates BMP signaling. From these results, we conclude that Fam46a is required for PPE formation via the positive regulation of BMP signaling. Our study provides a new mechanism of ectodermal patterning via cell-autonomous regulation of BMP signaling in the PPE.

Swine model of in-stent stenosis in the iliac artery evaluating the serial time course.

The aim of this study was to propose a new animal model evaluating the serial time course of in-stent stenosis by repeated carotid artery catheterization in the same animal. 16 bare-metal stents were implanted in the normal external and internal iliac artery of 8 miniature pigs. Repeated measurements were performed in the same animal every 2 weeks for 12 weeks through carotid artery catheterization. The time course and peak neointimal proliferation were evaluated by intravascular ultrasound. Health of all animals was assessed by clinical and hematological examinations. As a result, 7 times of carotid artery catheterization was performed per pig, but all animals remained healthy without both any complications and hematological inflammatory abnormalities. The time course of neointimal proliferation of each stent was observed from the stage of hyperplasia to partial regression. The peak neointimal proliferation varied from 6 to 12 weeks despite implantation of identical stents using the same deployment method. In conclusion, repeated carotid artery catheterization to the same animal is feasible without animal health deterioration. This model should be useful to evaluate the time course of neointimal proliferation after stent deployment in preclinical study.

Transarterial ethanol ablation for sporadic and non-hemorrhaging angiomyolipoma in the kidney.

PURPOSE: We evaluated the efficacy and side effects of transarterial ethanol ablation in sporadic and non-hemorrhaging angiomyolipomas (AMLs) in the kidney. MATERIAL AND METHODS: A total of 10 patients with solitary and sporadic AMLs underwent selective transarterial absolute ethanol ablation for prophylaxis against hemorrhage. We confirmed the ratio areas of tumor vessel on angiogram, those of infraction on post-ablation computed tomography (CT) and those of tumor reduction in a 3-, 6- and 12-month follow-up CT. RESULTS: Once or twice a single infusion of 1 or 2 ml absolute ethanol achieved in a total occlusion of 22 feeding arteries which consisted of 7 proximal interlobar arteries, 12 distal interlobar arteries and 3 renal capsular arteries. Nontarget occlusion did not occur by ethanol reflux in any cases but occurred causing spasms provoked by repeated inflation and deflation of the balloon in one case. Total occlusion of tumor vessels was observed in 7 patients and 92-95% occlusion in 3. Ethanol ablation produced 1.8-22.5% (mean 8.4+/-6.8%) areas of infarctions but the outcome was not serious in all cases. Mean percentage areas of tumor reduction were 29.4+/-10.6% in a 3-month follow-up, 45.7+/-11.9% in a 6-month and 59.3+/-11.5% in a 12-month follow-up. CONCLUSIONS: Absolute ethanol ablation for sporadic and non-hemorrhaging AML is safe and effective in reducing majority of tumor area in a 1-year follow-up.