We established a preoperative exercise and nutritional support program for elderly sarcopenic patients with gastric cancer. Twenty-two gastric cancer patients aged 65 years or older with a diagnosis of sarcopenia according to the algorithm proposed by the European Working Group on Sarcopenia in Older People received our preoperative program. The median duration of the program participation was 16 days. Total calorie and protein intakes were significantly higher after the program than before [29.4 ± 6.9 kcal/kg ideal body weight (IBW) vs 27.3 ± 5.6 kcal/kg IBW, p = 0.049, and 1.3 ± 0.4 g/kg IBW vs 1.1 ± 0.3 g/kg IBW, p = 0.0019, respectively]. Handgrip strength significantly increased after the program (21.2 ± 5.2 kg vs 20.0 ± 5.3 kg, p = 0.022). Likewise, gait speed and skeletal muscle mass index increased, although the differences did not reach statistical significance. Four patients became nonsarcopenic after the program. Postoperative complications were observed in three patients (13.6%); however, none of these complications were severe (Clavien-Dindo grade III or lower). A preoperative exercise and nutritional support program has the potential to reduce sarcopenia and improve postoperative outcome in elderly sarcopenic patients with gastric cancer.

Background Malignancy is a secondary cause of sarcopenia, which is associated with impaired cancer treatment outcomes. The aim of this study was to investigate the prevalence of preoperative sarcopenia among elderly gastric cancer patients undergoing gastrectomy and the differences in preoperative dietary intake and postoperative complications between sarcopenic and non-sarcopenic patients. Methods Ninety-nine patients over 65 years of age who underwent gastrectomy for gastric cancer were analyzed. All patients underwent gait and handgrip strength testing, and whole-body skeletal muscle mass was measured using a bioimpedance analysis technique based on the European Working Group on Sarcopenia in Older People (EWGSOP) algorithm for the evaluation of sarcopenia before surgery. Preoperative dietary intake was assessed using a food frequency questionnaire. Results Of these patients, 21 (21.2 %) were diagnosed with sarcopenia. Sarcopenic patients consumed fewer calories and less protein preoperatively (23.9 vs. 27.8 kcal/ kg ideal weight/day and 0.86 vs. 1.04 g/kg ideal weight/-day; P = 0.001 and 0.0005, respectively). Although the overall incidence of postoperative complications was similar in the two groups (57.1 % vs. 35.9 %; P = 0.08), the incidence of severe (Clavien-Dindo grade C IIIa) complications was significantly higher in the sarcopenic group than in the non-sarcopenic group (28.6 % vs. 9.0 %; P = 0.029). In the multivariate analysis, sarcopenia alone was identified as a risk factor for severe postoperative complications (odds ratio, 4.76; 95 % confidence interval, 1.03-24.30; P = 0.046). Conclusions Preoperative sarcopenia as defined by the EWGSOP algorithm is a risk factor for severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy.

Malnutrition, a risk factor for SSI, was prevalent in gastric cancer patients preoperatively. Well-managed preoperative nutritional support decreased the incidence of postoperative SSIs in malnourished patients.

CXCL9, an IFN-γ inducible chemokine, has been reported to play versatile roles in tumor-host interrelationships. However, little is known about its role in intrahepatic cholangiocarcinoma (iCCA). Here, we aimed to elucidate the prognostic and biological implications of CXCL9 in iCCA. Endogenous CXCL9 expression and the number of tumor-infiltrating lymphocytes were immunohistochemically assessed in resection specimens. These data were validated in mice treated by silencing CXCL9 with short hairpin RNA. In addition, the induction of endogenous CXCL9 and the effects of CXCL9 on tumor biological behaviors were evaluated in human cholangiocarcinoma cell lines. Immunohistochemical analyses revealed that high CXCL9 expression was closely correlated with prolonged postoperative survival and a large number of tumor-infiltrating natural killer (NK) cells. In fact, due to the trafficking of total and tumor necrosis factor-related apoptosis-inducing ligand-expressing NK cells into tumors, CXCL9-sufficient cells were less tumorigenic in the liver than CXCL9-deficient cells in mice. Although CXCL9 involvement in tumor growth and invasion abilities differed across cell lines, it did not exacerbate these abilities in CXCL9-expressing cell lines. We showed that CXCL9 was useful as a prognostic marker. Our findings also suggested that CXCL9 upregulation might offer a therapeutic strategy for treating CXCL9-expressing iCCA by augmenting anti-tumor immune surveillance. K E Y W O R D S CXCL9, intrahepatic cholangiocarcinoma, natural killer cell, tumor necrosis factor-related apoptosis-inducing ligand, tumor-infiltrating lymphocyte S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Fukuda Y, Asaoka T, Eguchi H, et al. Endogenous CXCL9 affects prognosis by regulating tumorinfiltrating natural killer cells in intrahepatic cholangiocarcinoma. Cancer Sci. 2020;111:323-333. https ://

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Soluble forms of receptors play distinctive roles in modulating signal-transduction pathways. Soluble CD74 (sCD74) has been identified in sera of inflammatory diseases and implicated in their pathophysiology; however, few relevant data are available in the context of cancer. Here we assessed the composition and production mechanisms, as well as the clinical significance and biological properties, of sCD74 in melanoma. Serum sCD74 levels were significantly elevated in advanced melanoma patients compared with normal healthy donors, and the high ratio of sCD74 to macrophage-migration inhibitory factor (MIF) conferred significant predictive value for prolonged survival in these patients (p = 0.0035). Secretion of sCD74 was observed primarily in melanoma cell lines as well as a THP-1 line of macrophages from monocytes and primary macrophages, especially in response to interferon-γ (IFN-γ). A predominant form that showed clinical relevance was the 25-KDa sCD74, which originated from the 33-KDa isoform of CD74. The release of this sCD74 was regulated by either a disintegrin and metalloproteinase-mediated cell-surface cleavage or cysteine-protease-mediated lysosomal cleavage, depending on cell types. Both recombinant and THP-1 macrophage-released endogenous sCD74 suppressed melanoma cell growth and induced apoptosis under IFN-γ stimulatory conditions via inhibiting the MIF/CD74/AKT-survival pathway. Our findings demonstrate that the interplay between sCD74 and MIF regulates tumor progression and determines patient outcomes in advanced melanoma.

PI was strongly associated with pathological FP, which was independently associated with PDAC. PI shows promise as an imaging predictor for PDAC.

Our data suggested that preoperative sarcopenia, especially a decline in the quality of skeletal muscle, predicted poorer postoperative outcomes in T1D recipients undergoing PTx.