Little is known on the clinical effects of chloride on critically ill patients. We conducted this retrospective, observational study in 488 critically ill patients to investigate the incidence of chloride abnormalities, effects of hypochloremia in acid-base disorders, and association between chloride and clinical outcome. The study involved retrieval of arterial blood gas analyses, biochemical and demographical data from electrical records as well as quantitative acid-base analyses. For statistical analysis, the patients were stratified into three groups according to their chloride level (normal range: 98–106 mEq/L). The distribution of chloride levels was hyperchloremia 16.6%, normochloremia 74.6%, and hypochloremia 8.8%. The hypochloremic group was significantly alkalemic (P < 0.0001) and has significantly higher apparent strong ion difference (SIDa) (P < 0.0001) compared to the two other groups. The hypochloremic group had significantly longer stays in the ICU and hospital (P < 0.0001) with higher mortality (P < 0.0001). However, multiple regression analysis showed that chloride was not an independent factor of poorer outcome. In conclusion, the acid-base characteristics of the hypochloremic patients were alkalemia coexisting with higher SIDa. And although it was not an independent prognostic factor, hypochloremia was related to poorer outcome in critically ill settings.

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Background Soft-tissue sarcomas are rare malignancies that consist of many different histologic subtypes and arise in various locations in the body. In patients with lung metastases from retroperitoneal sarcomas, the long-term outcomes and prognostic factors are unknown. This study is a retrospective review of patients undergoing pulmonary metastasectomy for retroperitoneal sarcoma metastases at one institution, with the purpose of determining prognostic factors and clinical outcomes. Methods This is a single-center, retrospective cohort study of patients undergoing pulmonary metastasectomy for lung metastases from various sarcomas at Okayama University Hospital from January 2006 to December 2018. The Kaplan-Meier method and log-rank test were used for the analyses, and cut-off values of continuous variables were determined by a receiver operating characteristic curve analysis. Results Twenty-four patients underwent the first pulmonary metastasectomy for lung metastases from retroperitoneal sarcoma in our hospital. Leiomyosarcoma was the most common histologic subtype of retroperitoneal sarcoma (79.2%, n = 19). Median overall survival was 49.9 months, and the 3-year and 5-year survival rates after the first pulmonary metastasectomy were 62.5% and 26.4% respectively. In univariate analysis, age ≥56 years, disease-free interval < 15 months, and size of metastasis (≥ 27 mm) were associated with poor survival. Conclusion Pulmonary metastasectomy can be considered as an effective management strategy in retroperitoneal sarcoma patients with lung metastases in appropriately selected cases, just as it is for other sarcomas.

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Background Tumor-produced high molecular weight insulin-like growth factor-II (big insulin-like growth factor-II) is considered to cause non-islet cell tumor hypoglycemia. This paper presents a case of surgically resected retroperitoneal liposarcoma that produced big insulin-like growth factor-II. Case presentation Here, we report the case of a 62-year-old woman who presented with an abdominal mass and hypoglycemia. Non-islet cell tumor hypoglycemia due to retroperitoneal liposarcoma was suspected. After complete resection of the tumor, the patient’s hypoglycemia improved and big insulin-like growth factor-II disappeared in the molecular weight analysis of serum insulin-like growth factor-II by western blotting. The patient had no tumor recurrence or reappearance of hypoglycemia 16 months after the operation without any adjuvant therapy. Conclusions Although insulin-like growth factor-II-producing tumors are generally large and difficult to operate on, surgical resection is currently the most effective and only treatment; thus, it is essential to attempt resection aggressively.

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Background: Cancer-associated fibroblasts (CAFs) are key players in the tumor microenvironment (TME) due to their abundance in most solid tumors and active crosstalk with cancer cells, and promote the initiation of tumor formation, tumor growth, angiogenesis, metastasis, and therapeutic resistance. In this study, we sought to identify effective therapeutic targets in CAFs for non-small cell lung cancer (NSCLC). Experimental Design: We established fibroblast cell lines from the cancerous and non-cancerous parts of surgical lung specimens from patients with NSCLC and evaluated the differences in behaviors towards NSCLC cells using in vitro co-culture models, conditioned medium, and in vivo xenograft mouse models. Next, RNA sequencing analysis was performed to investigate the differentially expressed genes between normal fibroblasts (NFs) and CAFs, and we then verified the biological activity of the identified molecule on NSCLC cells in vitro and in vivo mouse model. Results: Cancer cells showed enhanced cell proliferation, migration, and drug resistance by co-culture with CAFs or CAF-derived conditioned medium. RNA sequencing analysis revealed that CAFs showed higher expressions of POSTN, a matricellular protein, than NFs. Single-cell RNA sequencing data of NSCLC from public database confirmed that POSTN-positive fibroblasts were highly enriched in lung tumor tissues but rarely observed in normal lung tissues, suggesting CAF-specific POSTN expression in lung cancer. Recombinant POSTN increased cell proliferation via NSCLC cells’ ERK pathway activation and induced epithelial-mesenchymal transition (EMT), which improved migration in vitro. In addition, POSTN knockdown in CAFs suppressed these effects, and in vivo experiments demonstrated that the POSTN knockdown improved the sensitivity of EGFR-mutant NSCLC cells for Osimertinib treatment. Conclusion: Our results showed that CAF-derived POSTN is involved in tumor growth, migration, EMT induction, and drug resistance in NSCLC. Targeting CAF-secreted POSTN in TME could be a potential therapeutic strategy for NSCLC. Citation Format: Mao Yoshikawa, Fumiaki Takatsu, Ken Suzawa, Tomohiro Habu, Ohki Masayoshi, Kazuma Iwata, Naoki Matsuda, Yin Min Thu, Kazuhiko Shien, Hiromasa Yamamoto, Shinichi Toyooka. Periostin secreted by cancer-associated fibroblasts promotes cancer progression and drug resistance in non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5845.