Homotopy commutativity in symmetric spaces

We extend the former results of Ganea and the two of the authors with Takeda on the homotopy commutativity of the loop spaces of Hermitian symmetric spaces such that the loop spaces of all irreducible symmetric spaces but $\mathbb{C}P^3$ are not homotopy commutative.Comment: 11page

Predictors of Hypotension after Adrenalectomy for Pheochromocytoma

The management of blood pressure is a significant concern for surgeons and anesthesiologists performing adrenalectomy for pheochromocytoma. We evaluated clinical factors in pheochromocytoma patients to identify the predictors of postoperative hypotension. The medical records of patients who underwent adrenalectomy for pheochromocytoma between 2001 and 2017 were retrospectively reviewed and clinical and biochemical data were evaluated. Of 29 patients, 13 patients needed catecholamine support in the perisurgical period while 16 patients did not. There were significant differences in median age, tumor size, and blood pressure drop (maxmin) between the 2 groups (68 vs 53 years old, p=0.045; 50 vs 32 mm diameter, p=0.022; 110 vs 71 mmHg, p=0.015 respectively). In univariate logistic analysis, age > 65.5 years, tumor size > 34.5 mm, urine metanephrine > 0.205 mg/day and urine normetanephrine > 0.665 mg/day were significant predictors of prolonged hypotension requiring postoperative catecholamine support. Tumor size and urine metanephrine and urine normetanephrine levels were correlated with postoperative hypotension. These predictors may help in the safe perioperative management of pheochromocytoma patients treated with adrenalectomy

Insights into gene expression profiles induced by Socs3 depletion in keratinocytes

Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism. At week 10, multiple chemokine and cytokine genes were up-regulated. Functional annotation revealed that the genes differentially expressed in the 2-week-old mice play roles in keratinization, keratinocyte differentiation, and epidermal cell differentiation. By contrast, differentially expressed genes in the 10-week-old animals are involved in acute immune-related functions. A group of activator protein-1–related genes were highly up-regulated in Socs3 cKO mice of both ages. This observation was validated using qRT-PCR by SOCS3-depleted human keratinocyte–derived HaCaT cells. Our results suggest that, in addition to participating in immune-mediated pathways, SOCS3 also plays important roles in skin barrier homeostasis

Insights into gene expression profiles induced by Socs3 depletion in keratinocytes.

Specific deletion of suppressor of cytokine signaling 3 (Socs3) in keratinocytes can cause severe skin inflammation with infiltration of immune cells. The molecular mechanisms and key regulatory pathways involved in these processes remain elusive. To investigate the role of Socs3 in keratinocytes, we generated and analyzed global RNA-Seq profiles from Socs3 conditional knockout (cKO) mice of two different ages (2 and 10 weeks). Over 400 genes were significantly regulated at both time points. Samples from 2-week-old mice exhibited down-regulation of genes involved in keratin-related functions and up-regulation of genes involved in lipid metabolism. At week 10, multiple chemokine and cytokine genes were up-regulated. Functional annotation revealed that the genes differentially expressed in the 2-week-old mice play roles in keratinization, keratinocyte differentiation, and epidermal cell differentiation. By contrast, differentially expressed genes in the 10-week-old animals are involved in acute immune-related functions. A group of activator protein-1-related genes were highly up-regulated in Socs3 cKO mice of both ages. This observation was validated using qRT-PCR by SOCS3-depleted human keratinocyte-derived HaCaT cells. Our results suggest that, in addition to participating in immune-mediated pathways, SOCS3 also plays important roles in skin barrier homeostasis

Intestinal epithelial cell-derived IL-15 determines local maintenance and maturation of intraepithelial lymphocytes in the intestine

Interleukin-15 (IL-15) is a cytokine critical for maintenance of intestinal intraepithelial lymphocytes (IELs), especially CD8αα+ IELs (CD8αα IELs). In the intestine, IL-15 is produced by intestinal epithelial cells (IECs), blood vascular endothelial cells (BECs) and hematopoietic cells. However, the precise role of intestinal IL-15 on IELs is still unknown. To address the question, we generated two kinds of IL-15 conditional knockout (IL-15cKO) mice: villin-Cre (Vil-Cre) and Tie2-Cre IL-15cKO mice. IEC-derived IL-15 was specifically deleted in Vil-Cre IL-15cKO mice, whereas IL-15 produced by BECs and hematopoietic cells is deleted in Tie2-Cre IL-15cKO mice. The cell number and frequency of CD8αα IELs and NK IELs were significantly reduced in Vil-Cre IL-15cKO mice. By contrast, CD8αα IELs were unchanged in Tie2-Cre IL-15cKO mice, indicating that IL-15 produced by BECs and hematopoietic cells is dispensable for CD8αα IELs. Expression of an anti-apoptotic factor, Bcl-2, was decreased, whereas Fas expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. Forced expression of Bcl-2 by a Bcl-2 transgene partially restored CD8αα IELs in Vil-Cre IL-15cKO mice, suggesting that some IL-15 signal other than Bcl-2 is required for maintenance of CD8αα IELs. Furthermore, granzyme B production was reduced, whereas PD-1 expression was increased in CD8αα IELs of Vil-Cre IL-15cKO mice. These results collectively suggested that IEC-derived IL-15 is essential for homeostasis of IELs by promoting their survival and functional maturation

Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma

[Background] The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy. [Methods] We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019. [Results] We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed “PLR-CYFRA,” is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665–0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRALow (< 237.6, n = 21) and PLR-CYFRAHigh (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRALow was significantly higher in patients with a better pathological response (P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival (P = 0.014), recurrence-free survival (P = 0.014), and overall survival (P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy (P = 0.002). [Conclusion] Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma

Feasibility of Laparoscopic Radical Cystectomy in Elderly Patients: A Comparative Analysis of Clinical Outcomes in a Single Institution

Laparoscopic radical cystectomy (LRC) is a standard surgical treatment for muscle-invasive bladder cancer and high-risk non-muscle-invasive bladder cancer. LRC is a less invasive modality than conventional open surgery. Therefore, even elderly patients with invasive bladder cancer may be candidates for LRC. In this study, a comparative analysis of perioperative/oncological outcomes between elderly patients and younger patients who underwent LRC was performed to assess the feasibility of LRC in elderly patients. Sixty-eight consecutive patients who underwent LRC between October 2013 and March 2018 were enrolled and stratified into those younger than 75 years (n=37) and those ≥ 75 years old (n=31). The median follow-up period was 28.2 months. The preoperative and operative parameters and complications were similar in both groups. The 2-year overall survival (OS) was 64.4% in the younger vs. 76.4% in the elderly group (p=0.053), cancer-specific survival (CSS) was 79.3% vs. 81.7% (p=0.187), and recurrence-free survival (RFS) was 58.2% vs. 75.7% (p=0.174), respectively. No significant differences were observed in OS, CSS, or RFS between the groups. No significant differences were found between the groups with respect to peri-surgical/oncological outcomes. We conclude that LRC is feasible in elderly patients

Less Invasive Surgery for Remnant Stomach Cancer After Esophago-proximal Gastrectomy with ICG-guided Blood Flow Evaluation : A Case Report

The standard procedure for remnant gastric cancer after esophago-proximal gastrectomy is total resection of the remnant stomach considering blood supply. However, sometimes surgery may be too invasive due to severe adhesion in the thoracic and mediastinal cavity. The blood supply to the remnant stomach depends on the right gastroepiploic artery and the right gastric artery. Therefore, preservation of the proximal region of the remnant stomach is thought to be anatomically impossible. We report a case of remnant gastric cancer that developed more than 12 years after lower thoracic esophagectomy plus proximal gastrectomy for Siewert Type I squamous cell carcinoma. We used intra-operative indocyanine green (ICG) venous-injection to evaluate blood flow and distal gastrectomy of the remnant stomach was performed by preserving the proximal stomach in the thoracic cavity through an abdominal approach. There were no complications of the remnant stomach or the anastomosis to the jejunum after surgery. In this case, we focused on the blood supply by collateral circulation through the anastomotic line from the remnant esophagus. After confirming blood supply with intra-operative evaluation using ICG fluorescence, less-invasive distal gastrectomy was successfully performed. As the intra-operative ICGbased evaluation for blood supply is a simple and safe method, it might be useful for determining the resection margin of various organs and be effective for the introduction of less invasive surgery. Here, we report a case and a review of the literature