[Neutrophil-Lymphocyte Ratio as a Prognostic Indicator in Patients Treated with Nivolumab for Gastric Cancer].

BACKGROUND: Immune checkpoint inhibitors(nivolumab)have been recommended as third-line chemotherapy for advanced gastric cancer(AGC)according to the Guidelines of Gastric Cancer(5th edition). Therefore, they have been used in daily clinical practice. On the other hand, the neutrophil-lymphocyte ratio(NLR)has been reported to be associated with the prognosis of cancer patients. METHODS: Twenty patients treated with nivolumab for AGC between January 2018 and November 2019 were retrospectively examined. RESULTS: Median age of the 20 patients(18 males, 2 females)was 70 years(55- 84 years). Nivolumab was administered as second-, third-, fourth-, and fifth-line therapy in 1, 11, 7, and 1 case, respectively. The best tumor response evaluation was observed in PR 1, SD 7 and PD 10 cases. Median overall survival(OS)was 10 months, and median progression-free survival(PFS)was 3 months. No serious adverse events occurred. Compared to the NLR>2.0 group, OS significantly prolonged(2.2 months vs 21.9 months)and PFS tended to prolong(1.4 months vs 6.2 months)in the NLR≤2.0 group. CONCLUSION: NLR may be an effective prognostic factor in patients with AGC receiving nivolumab treatment.

[A Postoperative Case of Rectal Cancer with Anal Pain Caused by Side Effects of Oxaliplatin].

This case involved a 28-year-old female with rectal cancer in the inner pelvis. Two courses of SOX plus Cmab therapy, and 4 courses of FOLFOX-Cmab therapy were administered as preoperative chemotherapies, which resulted in a reduction in the major lesion. Subsequently, laparoscopic low anterior resection and dissection of the bilateral lymph nodes were performed. After the surgery, adjuvant chemotherapy with FOLFOX was administered. Afterwards, the patient developed severe anal pain and visited us for treatment. The severe anal pain continued even after FOLFOX treatment and increased with defecation. A side effect of oxaliplatin was suspected, and sLV5FU chemotherapy was administered. As a result, the anal pain disappeared. Thus, the pain was considered to be induced by oxaliplatin. While peripheral neuropathy is a widely known side effect of oxaliplatin, this case was considered to be unique because anal pain occurs very rarely with oxaliplatin treatment.

[A case of double cancer of sigmoid colon cancer with lung metastases, peritoneal dissemination and early gastric cancer responding to S-1].

A 73-year-old man was referred to our hospital with complaints of constipation and defecation caused by a sigmoid colon tumor. After examination, he was diagnosed as sigmoid colon cancer with lung metastasis, peritoneal dissemination and early gastric cancer. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative day 20, S-1 (100 mg/body for 4 weeks followed by 2 drug-free weeks) treatment was started. After 13 courses of treatment, gastrointestinal fiberscope revealed that the gastric cancer was remarkably reduced, and after 16 courses, computed tomography revealed that the lung metastasis was remarkably reduced. Although after 12 courses, elevation of bilirubin, the treatment could be possible to continued on a lowered dose of S-1 from 100 mg to 80 mg/body. Twenty-four months after the operation, good control of cancer has been maintained, and the treatment is continuing. S-1 treatment was proved effective for double cancer of the advanced colorectal cancer and the gastric cancer.

A novel gene, RSRC2, inhibits cell proliferation and affects survival in esophageal cancer patients.

In Japan and China, esophageal cancer is common and more than 90% of esophageal cancers are squamous cell carcinoma. Esophageal squamous cell carcinoma (ESCC) shows a poor prognosis, but the mechanism of ESCC and target genes for treatment remains unclear. We searched for genes related to ESCC, and identified a novel gene, FLJ11021, which was designated arginine/serine-rich coiled-coil 2 (RSRC2). We sought to determine the role of RSRC2 in the proliferation of esophageal cell lines and to examine the relationship between RSRC2 and clinicopathologic factors and ESCC prognosis. Expression of RSRC2 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) in 70 primary ESCCs and paired noncancerous esophageal mucosa. To determine the role of RSRC2 in ESCC cell proliferation, we used vector-based transfection and small interfering RNA methods. Our results show that RSRC2mRNA levels in all ESCC cell lines (TE1-15, excluding TE7) were lower than those in a human esophageal squamous epithelial cell line (Het-1A). Cell proliferation of an ESCC cell line was inhibited by overexpression of RSRC2, while reduced expression was accompanied by tumor progression. RSRC2 expression levels were significantly correlated with depth of invasion, lymph node metastasis, lymphatic invasion and vascular invasion. Moreover, ESCC patients with low RSRC2mRNA expression had significantly shorter post-operative survival time than those with high expression. In vitro study revealed that RSRC2 might play a role in cell proliferation. Our study demonstrated that RSRC2 expression may be a novel tumor suppressor of esophageal cancer cell growth and a prognostic factor in ESCC.

RNASEN regulates cell proliferation and affects survival in esophageal cancer patients.

PURPOSE: MicroRNAs (miRNA) are small noncoding RNAs thought to be involved in physiologic and developmental processes by negatively regulating the expression of target genes. Little is known about the role of miRNAs in normal and cancer cells. It is possible that deregulation of miRNA may contribute to the oncogenesis of some cancers. We studied the expression level of the miRNA processing enzyme (DICER1, DGCR8, and RNASEN) in esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: The expression levels of DICER1, DGCR8, and RNASEN mRNA in 73 ESCC tissues were compared with that in corresponding normal esophageal epithelium by Taqman real-time reverse-transcription PCR. We also examined RNASEN protein expression in 27 cell lines. The role of RNASEN in cell proliferation in ESCC cells was assessed by small interfering RNA. Paraffin sections of ESCC patients were immunohistochemically investigated. RESULTS: We found that RNASEN expression levels were enhanced in a fraction of esophageal cancers. Multivariate Cox regression analysis showed that the prognostic effect of RNASEN (P = 0.0036) seems to be independent of disease stage (P = 0.0060). Knockdown of RNASEN in esophageal cancer cell lines resulted in a 46% to 85% reduction in cell number. In an immunohistochemical study, the intensity of RNASEN expression was often increased in the tumor compared with that in normal epithelium. CONCLUSIONS: The relationship between the RNASEN expression and the prognosis of the ESCC patients warrants a further study on the role of miRNA and tumor progression.

Expression of ACP6 is an independent prognostic factor for poor survival in patients with esophageal squamous cell carcinoma.

ACP6 (acid phosphatase 6, lysophosphatidic) is a lysophosphatidic acid (LPA)-specific phosphatase that hydrolyzes LPA to monoacylglycerol and is involved in lipid metabolism in the mitochondria. Its role in oncogenesis and cancer progression has not been studied. In this study, we examined the expression of ACP6 mRNA and evaluated its clinical significance in esophageal squamous cell carcinoma (ESCC). Expression of ACP6 mRNA was quantified by real-time reverse transcription polymerase chain reaction using the LightCycler in 70 esophageal ESCC specimens and their paired normal esophageal mucosa. The data were analyzed with reference to clinicopathological factors. ACP6 mRNA expression in esophageal cancer tissue was significantly lower than that in corresponding normal esophageal mucosa (P=0.0301). Among the esophageal cancer tissues, ACP6 mRNA expression significantly correlated with local tumor invasion (T factor, P=0.0461) and lymph node metastasis (P=0.0128). Furthermore, low ACP6 mRNA expression was associated with a significantly shorter survival time compared with high expression (log-rank test, P=0.0358). In multivariate analysis, ACP6 mRNA expression emerged as a significant independent factor (P=0.0148). Impaired ACP6 expression may lead to more aggressive invasion of ESCC, and ACP6 mRNA expression level could be an independent prognostic factor for patients with ESCC.

Expression and prognostic roles of PABPC1 in esophageal cancer: correlation with tumor progression and postoperative survival.

The prognosis of patients with esophageal cancer remains poor. TNM classification is not sufficient to predict their prognosis, and novel predictive markers of the prognosis of esophageal cancer patients are therefore needed. Poly A binding protein, cytoplasmic 1 (PABPC1) plays a role in post-transcriptional control of mRNA and may be involved in tumorigenesis. PABPC1 expression has not been studied in esophageal cancer. Expression of PABPC1 was quantified by real-time reverse transcription polymerase chain reaction (RT-PCR) using LightCycler in 41 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We examined the correlation between PABPC1 expression and the clinicopathological factors and prognosis of ESCC patients. Reduced expression of PABPC1 was accompanied by locally invasive tumors (t-factor, p=0.0145) and more advanced tumors (pathologic stage, p=0.0264). Moreover, ESCC patients with low PABPC1 mRNA expression had a significantly shorter postoperative survival time than those with high expression (median survival, 3.1 vs. 6.5 months, p=0.002). In esophageal cancer, reduced expression of PABPC1 was correlated with local tumor progression and poor prognosis after surgery.