Health insurance or subsidy has universal advantage for management of hospital malnutrition unrelated to GDP.

BACKGROUND AND OBJECTIVES: Protein-energy and micronutrient malnutrition are global public health problems which, when not prevented and severe, require medical management by clinicians with nutrition expertise, preferably as a collectively skilled team, especially when disease-related. This study aimed to investigate barriers and facilitators of clinical nutrition services (CNS), especially the use of oral, enteral (EN) and parenteral (PN) nutrition in institutional and home settings. METHODS AND STUDY DESIGN: An international survey was performed between January and December 2014 in twenty-six countries from all continents. Electronic questionnaires were distributed to 28 representatives of clinical nutrition (PEN) societies, 27 of whom responded. The questionnaire comprised questions regarding a country's economy, reimbursement for CNS, education about and the use of EN and PN. RESULTS: The prevalence of malnutrition was not related to gross domestic product (GDP) at purchasing power parity (PPP) per capita (p=0.186). EN and PN were used in all countries surveyed (100%), but to different extents. Reimbursement of neither EN nor PN use depended on GDP, but was associated with increased use of EN and PN in hospitals (p=0.035), although not evident for home or chronic care facilities. The size of GDP did not affect the use of EN (p=0.256), but it mattered for PN (p=0.019). CONCLUSIONS: A worldwide survey by nutrition support societies did not find a link between national economic performance and the implementation of medical nutrition services. Reimbursement for CNS, available through health insurance systems, is a factor in effective nutrition management.

Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients.

BACKGROUND: Chemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC. PATIENTS AND METHODS: HLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor-II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60 Gy) with concurrent cisplatin (40 mg/m²) and 5-fluorouracil (400 mg/m²). Peptide vaccines mixed with incomplete Freund's adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT. RESULTS: Vaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years. CONCLUSIONS: A combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC. TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00632333.

Double-blind, placebo-controlled, randomized phase II study of TJ-14 (hangeshashinto) for gastric cancer chemotherapy-induced oral mucositis.

BACKGROUND: Hangeshashinto (TJ-14, a Kampo medicine), which reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, alleviates chemotherapy-induced oral mucositis (COM). We conducted a randomized comparative trial to investigate whether TJ-14 prevents and controls COM in patients with gastric cancer. METHODS: We randomly assigned patients with gastric cancer who developed moderate-to-severe oral mucositis (CTCAE v4.0 grade ≧1) during any cycle of chemotherapy to receive either TJ-14 or a placebo as a double-blind trial. The patients received a placebo or TJ-14 for 2-6 weeks according to the chemotherapy regimen from the beginning of the next course of chemotherapy. The primary end point was the incidence of grade ≧2 oral mucositis in the protocol treatment course, and the secondary end points were the time to disappearance of oral mucositis and the incidence of adverse events. RESULTS: Following the key opening of the blinding protocol, we analyzed 91 eligible patients (TJ-14: 45, placebo: 46) using a "per protocol set" analysis. The incidence of ≧grade 2 COM was 40.0 % in the TJ-14 group and 41.3 % in the placebo group (p = 0.588). The median duration of ≧grade 2 COM was 14 days in the TJ-14 group and 16 days in the placebo group (p = 0.894). Meanwhile, the median duration of any grade of COM was 9 days in the TJ-14 group and 17 days in the placebo group among the patients who developed grade 1 symptoms during the screening cycle [hazard ratio 0.60; 95 % CI (0.23-1.59), p = 0.290]. CONCLUSIONS: Although TJ-14 treatment did not reduce the incidence of ≥2 COM in the patients who developed mucositis during chemotherapy for gastric cancer, a trend was observed in which TJ-14 reduced the risk of COM in the patients who developed grade 1 COM during the screening cycle. Further, phase III studies with a larger sample size are needed to clarify the protective effects of TJ-14 for COM.

A Phase III trial to evaluate the effect of perioperative nutrition enriched with eicosapentaenoic acid on body weight loss after total gastrectomy for T2-T4a gastric cancer.

This randomized Phase III trial will evaluate whether perioperative nutrition enriched with eicosapentaenoic acid can prevent body weight loss after total gastrectomy for gastric cancer. The patients who enroll in this study will be randomly assigned to Group A: no supplementation with oral nutrients (standard diet) or Group B: standard diet with eicosapentaenoic acid-enriched supplementation for 7 days before surgery and for 21 days after surgery. For both groups, patients will undergo total gastrectomy with Roux-en Y reconstruction. The extent of dissection will principally follow the third edition of the Gastric Cancer Treatment Guideline published by the Japanese Gastric Cancer Association. When patients are diagnosed with pathological Stage II or III disease, adjuvant chemotherapy with S-1 will be initiated within 6 weeks after surgery and administered for 1 year. The primary endpoint will be the body weight loss at 1 and 3 months after surgery (double primary endpoints). The secondary endpoints will be the relative performance of the supplement, loss of lean body mass at 1 and 3 months after surgery, the lowest serum albumin level, quality of life, the incidence of surgical morbidity and mortality, and the incidence of surgical site infection.

Vitamin C supplementation in patients receiving peripheral parenteral nutrition after gastrointestinal surgery.

OBJECTIVE: We investigated an adequate vitamin C dose during peripheral parenteral nutrition therapy in patients after gastrointestinal surgery by measuring blood concentrations and urine excretions of vitamin C. We also sought to identify the effects of vitamin C on the oxidative status. METHODS: In a randomized trial, 2 d after undergoing gastrointestinal surgery, 16 patients started to receive a 5-d continuous intravenous infusion of vitamin C, either 100 or 500 mg/d. Blood concentrations of vitamin C and inflammatory and immunologic parameters were measured preoperatively, the day after surgery, and 3 and 5 d after starting administration of vitamin C (day 3 and day 5). Also, excretions of vitamin C and oxidative stress markers in 24-h, cumulative urine samples, collected and stored under light protection at 0°C, were measured on day 3 and day 5. RESULTS: Mean blood vitamin C concentration decreased markedly after surgery. The concentration returned to normal on day 3 and on day 5 in the 500-mg group and only on day 5 in the 100-mg group. Concentrations differed significantly between the groups on day 3 and on day 5 (P < 0.001 for both days). Urinary vitamin C excretion was above normal on both days in the 500-mg group, but it never reached normal in the 100-mg group (P < 0.001 for both days). Urinary excretion of 8-isoprostane, a marker of oxidative stress, was significantly lower in the 500-mg than in the 100-mg group on day 3 (P = 0.002). CONCLUSION: Vitamin C dose of 500 mg/d, not 100 mg/d, is adequate for patients undergoing gastrointestinal surgery and receiving peripheral parenteral nutrition therapy. Vitamin C may decrease postsurgical oxidative stress.

Vitamin C requirement in surgical patients.

PURPOSE OF REVIEW: To summarize recent findings on vitamin C status and assess the requirement and optimal dose of supplementation in surgical patients. RECENT FINDINGS: Blood vitamin C concentration falls after uncomplicated surgery and further decreases in surgical intensive care unit patients. The decline may be owing to increased demand caused by increased oxidative stress. To normalize plasma vitamin C concentration, much higher doses than the recommended daily allowance or doses recommended in parenteral nutrition guidelines are needed in these patients. In uncomplicated surgical patients, more than 500 mg/day of vitamin C may be required, with much higher doses in surgical intensive care unit patients. In uncomplicated gastrointestinal surgery, continuous parenteral administration of 500 mg/day of vitamin C reduced postoperative oxidative stress as manifested by reduced urinary excretion of isoprostane. In some studies, postoperative atrial fibrillation was prevented after cardiac surgery by perioperative vitamin C supplementation. In critically ill patients, some prospective randomized controlled trials support parenteral supplementation of high doses of vitamin C, E and trace elements. SUMMARY: Vitamin C requirement is increased in surgical patients, and the potential advantage of supplementation is to increase the plasma and tissue levels of vitamin C and thereby reduce oxidative stress. Although some clinical benefits of high-dose vitamin C supplementation have been shown in the critically ill, the optimal dose for supplementation and the clinical benefits remain to be investigated in surgical patients.

[Perioperative nosocomial infection preventive measures].

For the prevention of perioperative nosocomial infection, 1) topical mupirocin treatment, 2) tight perioperative glycemic control and 3) immunonutrition are described. A large, prospective, randomized trial showed that the nasal application of mupirocin may effectively reduce postoperative Staphylococcus aureus nosocomial infection in the subgroup of patients who had S. aureus in their nares. Tight glycemic control after surgery, especially in the early period after operation, may also be effective in decreasing postoperative infection. In septic ICU patients, strict glycemic control even reduces ICU and hospital mortality rates. Several specific nutritional substrates such as arginine, omega-3 fatty acids, glutamine, and RNA have been shown to modulate host immune function. Some enteral formulas enriched with such immunonutrients have been commercially available in the USA and in Europe and are now available in Japan. Recent meta-analyses of randomized, controlled trials have shown that the administration of these formulas to elective surgical patients results in a significant reduction in the risk of developing infectious complications by approximately 50% and shortens the overall hospital stay.