Night home enteral nutrition as a novel enforced and physiologically effective nutrition therapy following total gastrectomy for gastric cancer.

Enteral nutrition has been reported to be safe and effective in malnourished patients undergoing upper gastrointestinal surgery. In this study, we devised night home enteral nutrition (N-HEN) as a novel nutritional strategy and evaluated the efficacy in gastric cancer patients following total gastrectomy. Between January 2017 and March 2021, 24 patients were prospectively included in the protocol and supported by N-HEN for three postoperative months through a jejunostomy during the night (Elental:1200 kcal/day), and 22 patients without N-HEN were followed as a control group (CG). Body weight loss, nutritional indicators and tolerance to chemotherapy were evaluated. After 3 and 6 months, patients with N-HEN had significantly less body weight loss than CG (3 months P < 0.0001: N-HEN 4.0% vs. CG 15.2%, 6 months P < 0.0001: N-HEN 7.7% vs. CG 17.7%). Prealbumin was significantly higher in patients with N-HEN than CG after 3 and 6 months (3 months P < 0.0001, 6 months P = 0.0037). Albumin, total protein and hemoglobin, tended to be higher after 3 and 6 months in patients with N-HEN than CG, and total cholesterol after 6 months. Concerning the tolerance to adjuvant chemotherapy in Stage II-III patients, patients with N-HEN significantly had a higher completion rate (P = 0.0420: N-HEN 70% vs. CG 29%) and longer duration (P = 0.0313: N-HEN 458 days vs. CG 261 days) as planned. Continuous monitoring of blood glucose concentration in patients with N-HEN did not show nocturnal hypoglycemia or hyperglycemia. N-HEN could be a novel enforced and physiologically effective nutritional strategy to support potentially malnourished patients following total gastrectomy.

Plasma microRNA profiles: identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer.

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

Influence of magnesium and parathyroid hormone on cisplatin-induced nephrotoxicity in esophageal squamous cell carcinoma.

Magnesium (Mg) supplementation has previously been demonstrated to confer protective effects against nephrotoxicity induced by cisplatin. Parathyroid hormone (PTH) regulates Mg homeostasis. The aim of present study was to determine the protective effects of Mg supplementation against cisplatin-induced nephrotoxicity and its association with PTH levels in patients with esophageal squamous cell carcinoma (ESCC). A total of 55 patients with primary ESCC who received chemotherapy with high-dose cisplatin were examined. Mg was administered intravenously, and serum concentrations of PTH, parathyroid hormone-related protein (PTH-rP), creatinine and Mg were prospectively measured. Of the 55 patients, 37 received Mg supplementation. Post-chemotherapeutic creatinine concentrations were significantly increased in patients without Mg supplementation (P=0.01), with grade 1 and 2 increases of 22.2 and 5.6%, respectively, whereas these increases were suppressed by Mg supplementation (change in creatinine, P=0.21), with grade 1 and 2 increases of 8.1 and 0%, respectively. In addition, PTH and PTH-rP concentrations were high in 8 (14.5%) and 6 (10.9%) of all 55 patients, respectively. Alterations in creatinine concentrations (post-/pre-chemotherapy) due to chemotherapy were higher in patients with high levels of PTH regardless of Mg supplementation (P<0.01). Pre-therapeutic creatinine concentrations did not correlate with the alterations in creatinine concentrations due to chemotherapy. Intravenous Mg supplementation therefore conferred protective effects against cisplatin-induced nephrotoxicity in patients with ESCC. Furthermore, increases in PTH or PTH-rP may have influenced the extent of nephrotoxicity.

Significance of GSTP1 for predicting the prognosis and chemotherapeutic efficacy in esophageal squamous cell carcinoma.

Glutathione S-transferases (GSTs) have been reported to be activated in several types of cancers, including esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate whether GSTP1 protein expression is a useful predictor of the clinical outcome or drug resistance in ESCC. Immunohistochemistry was conducted with 75 ESCC resected specimens using a monoclonal antibody against GSTP1. The patients were divided into two groups according to the degree of GSTP1 staining, and the relationship between the GSTP1 level and the clinicopathological features was examined. Seventy-five patients were divided into low (grade 1, n=36) and high (grade 2, n=39) GSTP1 expression groups. The overall survival was significantly worse in the grade 2 patients than in the grade 1 patients (5­year survival rate, 78.5 vs. 51.2%; p=0.027). Cox proportional hazard analysis revealed that macroscopic type 3 or 4 disease (p=0.001), lymph node metastasis (p=0.010), and high GSTP1 expression (p=0.029) were independent predictors of a poor prognosis. With regard to the subgroup analysis among the 31 patients undergoing adjuvant chemotherapy, the grade 2 patients had a worse prognosis than did the grade 1 patients (5­year survival rate, 45.0 vs. 81.8%; p=0.081). This tendency was not observed in the subgroup without adjuvant chemotherapy (5­year survival rate, 51.7 vs. 59.9%; p=0.979). In conclusion, the GSTP1 expression is a good predictor of prognosis, and it may be closely related to the chemotherapeutic efficacy of 5-FU plus cisplatin in ESCC patients.

Case involving long-term survival after esophageal cancer with liver and lung metastases treated by multidisciplinary therapy: report of a case.

A 57-year-old male with lower esophageal cancer underwent subtotal esophagectomy with lymphadenectomy. The histopathological diagnosis was poorly differentiated squamous cell carcinoma, pT2N1M0 pStageIIB. After one course of postoperative adjuvant chemotherapy involving low-dose CDDP/5FU, a PET-CT scan obtained 12 months after surgery revealed a solitary liver metastasis in the S2 area. The patient then underwent five courses of docetaxel chemotherapy (80 mg/body, tri-weekly), and a partial response was observed. We also performed radiofrequency ablation (RFA), after which a complete response was observed. Twenty months after surgery, we detected local liver recurrence in the same position and performed additional RFA. Twenty-four months after surgery, a solitary lung metastasis was detected in the left S2 area and the patient was administered five additional courses of docetaxel therapy. Subsequently, PET-CT revealed growth of lung and liver tumors without recurrence in other areas. Twenty-nine months after surgery, we partially excised metastatic liver and lung tumors, and no subsequent recurrence has since been detected. The prognoses of patients who suffer from esophageal cancer organ recurrence are known to be extremely poor, and optimal therapeutic strategies for treating these patients have not been established. This long-term survival case suggests that multidisciplinary therapy for the treatment of liver and lung recurrence after esophagectomy is effective.

[A long-term survival case in advanced mucinous cystadenocarcinoma of the appendix using cytoreductive surgery and S-1/CDDP chemotherapy].

Prognosis of patients with advanced mucinous cystadenocarcinoma of the appendix (AMCA) is extremely poor. However, there has been no established treatment strategy. We preliminary report here a successfully treated case with AMCA using intensive cytoreductive surgery and chemotherapy. A 61-year-old woman had a right lower abdominal pain and was diagnosed as acute appendicitis. At surgery, about 5 cm tumor with mucosal fluid was detected at the distal part of the appendix. The tumor was invading the ileum and bladder. We performed appendectomy with tumor, partial resection of the small intestine and debridement of mucosal fluid. Histopathology revealed AMCA invading the ileum and bladder. After non curative surgery, we started S-1 plus cisplatin chemotherapy, which S-1 was given orally, twice daily for 3 consecutive weeks, and cisplatin was given intravenously on day 1, 8 and 15 followed by a 3-week rest period. After 6 courses starting with chemotherapy, a complete response was obtained. We followed by S-1 until two years after the initial surgery. At 36 months after the initial surgery, CT scan demonstrated a peritoneal recurrence. Then, she underwent intensive peritonectomy with intraperitoneal hyperthermic chemotherapy. Currently, she had no apparent recurrence for 59 months after initial surgery.