Impact of Perioperative Immunonutrition on Postoperative Outcomes for Patients Undergoing Head and Neck or Gastrointestinal Cancer Surgeries: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To clarify whether perioperative immunonutrition is effective in adult patients with or without malnutrition undergoing elective surgery for head and neck (HAN) or gastrointestinal (GI) cancers. BACKGROUND: It is important to avoid postoperative complications in patients with cancer as they can compromise clinical outcomes. There is no consensus on the efficacy of perioperative immunonutrition in patients with or without malnutrition undergoing HAN or GI cancer surgery. MATERIALS AND METHODS: We searched MEDLINE (PubMed), MEDLINE (OVID), EMBASE, Cochrane Central Register of Controlled Trials, Web of Science Core Selection, and Emcare from 1981 to 2022 using search terms related to immunonutrition and HAN or GI cancer. We included randomized controlled trials. Intervention was defined as immunonutritional therapy including arginine, n-3 omega fatty acids, or glutamine during the perioperative period. The control was defined as standard nutritional therapy. The primary outcomes were total postoperative and infectious complications, defined as events with a Clavien-Dindo classification grade ≥ II that occurred within 30 days after surgery. RESULTS: Of the 4825 patients from 48 included studies, 19 had upper GI cancer, 9 had lower, and 8 had mixed cancer, whereas 12 had HAN cancers. Immunonutrition reduced the total postoperative complications (relative risk ratio: 0.78; 95% CI, 0.66-0.93; certainty of evidence: high) and infectious complications (relative risk ratio: 0.71; 95% CI, 0.61-0.82; certainty of evidence: high) compared with standard nutritional therapy. CONCLUSIONS: Nutritional intervention with perioperative immunonutrition in patients with HAN and GI cancers significantly reduced total postoperative complications and infectious complications.

Low energy availability reduces bone mass and gonadal function in male mice.

INTRODUCTION: In women, the female athlete triad, marked by low energy availability, functional hypothalamic amenorrhea and osteoporosis, is a recognized risk for stress fractures. Stress injuries also occur in men, but by contrast risks and mechanisms underlying them are less characterized. MATERIALS AND METHODS: 5 week-old wild-type male mice were fed ad libitum (ad) or subjected to 60% food restriction (FR) for five weeks. In both groups, some mice were allowed access to an exercise wheel in cages to allow voluntary wheel running (ex) and/or treated with active vitamin D analogues. Mice were sacrificed and analyzed at 10 weeks of age. RESULT: Male FR mice exhibited significantly reduced testicle weight, serum testosterone levels and bone mass. Such bone losses in FR male mice were enhanced by exercise. Histological analysis revealed that both bone-resorbing and -forming activities were significantly reduced in FR or FR plus exercise (FR + ex) mice, mimicking a state of low bone turnover. Significantly reduced bone mass in FR or FR + ex male mice was significantly rescued by treatment with active vitamin D analogues, with significant restoration of osteoblastic activities. Serum levels of insulin-like growth factor I (IGF-I), which is critical for bone remodeling, were significantly lower in FR versus control male mice. CONCLUSIONS: Low energy availability puts men at risk for stress injuries as well, and low energy availability is upstream of gonadal dysfunction and osteoporosis in males. Active vitamin D analogues could serve as therapeutic or preventive options for stress injuries in men.

Prognostic factors for elderly gastric cancer patients who underwent gastrectomy.

BACKGROUND: Patients with gastric cancer are aging in Japan. It is not clear which patients and which surgical procedures have survival benefits after gastrectomy. A multivariate analysis was performed. METHODS: The medical records of 166 patients aged ≥ 80 years who underwent gastrectomy without macroscopic residual tumors were retrospectively reviewed. Univariate and multivariate analyses using Cox proportional hazard models were performed to detect prognostic factors for overall survival. RESULTS: In univariate analyses, age (≥ 90 vs. ≥ 80, < 85), performance status (3 vs. 0), American Society of Anesthesiologists physical status (ASA-PS) (3, 4 vs. 1, 2), Onodera's prognostic nutritional index (< 40 vs. ≥ 45), the physiological score of the Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) (≥ 40 vs. ≥ 20, ≤ 29), surgical approach (laparoscopic vs. open), extent of gastrectomy (total, proximal vs. distal), extent of lymphadenectomy (D1 vs. ≥ D2), pathological stage (II-IV vs. I), and residual tumor (R1 vs. R0) were significantly correlated with worse overall survival. Multivariate analysis revealed that ASA-PS [3, 4 vs. 1, 2, hazard ratio (HR) 2.30, 95% confidence interval (CI) 1.24-4.24], extent of gastrectomy (total vs. distal, HR 2.17, 95% CI 1.10-4.31) (proximal vs. distal, HR 4.05, 95% CI 1.45-11.3), extent of lymphadenectomy (D0 vs. ≥ D2, HR 12.4, 95% CI 1.58-97.7), and pathological stage were independent risk factors for mortality. CONCLUSIONS: ASA-PS was a useful predictor for postoperative mortality. Gastrectomy including cardia is best avoided.

Gender bias in sports medicine: an international assessment of sports medicine physicians' perceptions of their interactions with athletes, coaches, athletic trainers and other physicians.

OBJECTIVES: To evaluate the difference between female and male sports medicine physicians regarding disrespectful attitudes and sexual harassment perceived from athletes, coaches, physicians, athletic trainers (ATs) and organisations/administrations. METHODS AND STUDY DESIGN: anonymous survey was distributed to sports medicine physicians practicing in 51 countries. χ2 analysis was used to detect differences between female and male sports medicine physicians and logistic regression analysis was used to determine the independent variables that affect disrespectful attitudes and sexual harassment from sports participants. RESULTS: 1193 sports medicine physicians (31.9% female) participated from 51 countries. The survey revealed that female physicians, compared with male physicians, perceive significantly more disrespect or have their judgement questioned more by the following categories: male and female athletes, male and female coaches, female physicians with more years of experience, male physicians (regardless of years of experience), male and female ATs and organisation/administrations (all p<0.05). The only category where the frequency of disrespect was perceived equally by male and female physicians was during their interactions with female physicians who have the same or lesser years of experience. Female sports medicine physicians noted more sexual harassment than male physicians during interactions with male athletes, coaches, ATs and physicians (all p<0.001). In the logistic regression, gender was a related factor for perceiving disrespect, especially from male coaches (OR=2.01) and physicians with more years of experience (OR=2.18). CONCLUSIONS: Female sports medicine physicians around the world experience disrespectful attitudes, questioning of their judgement and are sexually harassed significantly more often than male counterparts.

Survival analyses of elderly gastric cancer patients with or without surgery.

PURPOSE: Deciding whether or not surgery should be performed for elderly patients is sometimes difficult. This study examined the prognosis of patients ≥ 80 years old with gastric cancer who underwent surgery or not. METHODS: The medical records of 111 patients who underwent surgery (surgery group) and 35 who received best supportive care (BSC group) were retrospectively reviewed, excluding those with clinical stage IVB disease, those with a performance status of 4, and those who underwent endoscopic submucosal dissection. The overall survival was compared between the two groups. RESULTS: The patients in the BSC group were significantly older and had worse performance status scores, worse physiological scores, and lower prognostic nutritional indexes than those in the surgery group. The patients in the surgery group showed a significantly better survival than those in the BSC group (median survival time, 38.9 vs. 11.4 months; p = 0.01) even after propensity score matching. In the subgroups of patients ≥ 90 years old and those with a performance status of 3, no marked difference in the survival between the 2 groups was observed. CONCLUSIONS: Surgery imbued a survival benefit to elderly gastric cancer patients, except for those ≥ 90 years old and those with a performance status of ≥ 3. The surgical indication of patients ≥ 90 years old and those with a performance status of ≥ 3 requires careful deliberation.

Treatment with an active vitamin D analogue blocks hypothalamic dysfunction-induced bone loss in mice.

Estrogen deficiency can be caused by ovarian dysfunction in females. Mechanisms underlying osteoporosis in this condition have been characterized in animal models, such as ovariectomized mice and rats, although it remains unclear how hypothalamic dysfunction promotes osteoporosis. Here, we show that administration of a gonadotropin-releasing hormone antagonist (GnRHa) significantly decreases uterine weight, a manifestation of hypothalamic dysfunction, and promotes both cortical and trabecular bone loss in female mice in vivo. We also report that osteoclast number significantly increased in mice administered GnRHa, and that the transcription factor hypoxia inducible factor 1 alpha (HIF1α) accumulated in those osteoclasts. We previously reported that treatment of mice with the active vitamin D analogue ED71, also known as eldecalcitol, inhibited HIF1α accumulation in osteoclasts. We show here that in mice, co-administration of ED71 with GnRHa significantly rescued the reduced cortical and trabecular bone mass promoted by GnRHa administration alone. GnRHa-dependent HIF1α accumulation in osteoclasts was also blocked by co-administration of ED71. We conclude that hypothalamic dysfunction promotes HIF1α accumulation in osteoclasts and likely results in reduced bone mass. We conclude that treatment with ED71 could serve as a therapeutic option to counter osteoporotic conditions in humans.

Food restriction reduces cortical bone mass and serum insulin-like growth factor-1 levels and promotes uterine atrophy in mice.

Low energy availability in female athletes often causes hypothalamic amenorrhea and osteoporosis, in turn promoting stress fractures. Mechanisms underlying these conditions remain unclear. Here we show that model mice subjected to food restriction (FR) or FR-plus-voluntary running exercise exhibit significantly reduced bone mineral density, cortical bone parameters and uterine weight than do control mice, and that these parameters worsen in the FR-plus-exercise group. Relative to controls, FR and FR-plus-exercise groups showed significantly lower mineral apposition rate and osteoclast number and significantly reduced serum insulin-like growth factor-1 (IGF1) levels. Outcomes were rescued by ED71 or 1.25(OH)2D3 treatment. Thus, we conclude that administration of active vitamin D analogues represents a possible treatment to prevent these conditions.

Bone parameters of elite athletes with oligomenorrhea and prevalence seeking medical attention: a cross-sectional study.

INTRODUCTION: Since the definition of secondary amenorrhea is cessation of regular menses for more than 3 months, it is likely that athletes with irregular menstrual cycles, including oligomenorrhea, do not consider the condition as serious. However, the consequences of untreated oligomenorrhea have not been investigated in elite track and field athletes. MATERIALS AND METHODS: The cohort consisted of 91 elite-level track and field athletes. Body compositions, including bone parameters and bone turnover markers (BTMs), were measured. RESULTS: Among the 91 participants, 52 were eumenorrheic and 33 were oligomenorrheic. The eumenorrheic athletes had significantly higher bone mineral density (BMD) and bone mineral content (BMC) of the lumbar spine, lower extremities, and whole body than had the oligomenorrheic athletes (p < 0.01). There were no significant differences in BTMs between the two groups, but oligomenorrheic athletes had significantly lower percent body fat. CONCLUSION: More than 40% of the elite-level female track and field athletes in this study reported menstrual disorders with oligomenorrhea as the most common. However, none sought medical attention. As compared to the eumenorrheic athletes, the oligomenorrheic athletes had lower BMC and BMD. Hence, if an athlete is oligomenorrheic, bone parameter measurements are considerably important.

Effective Tools to Predict Depression in Acute and Subacute Phase of Ischemic Stroke.

OBJECTIVE: Despite the high frequency of depression in the first year following stroke, few studies have predicted risk of depression after the acute and subacute stroke periods. The aim of this study was to identify, in the acute and subacute periods, measures that would predict major depression during the first year after stroke. METHODS: Study subjects were inpatients with ischemic stroke aged 20-85 years within 6 weeks of onset. Patients were evaluated at baseline and at 3, 6, 9, and 12 months. Patients were diagnosed with major depression using the Structured Clinical Interview for DSM-IV. The severity of depressive symptoms was measured with the Patient Health Questionnaire-9 (PHQ-9) and the Montgomery-Åsberg Depression Rating Scale (MADRS). RESULTS: Of the 152 potential patients who met inclusion criteria, 49 had follow-up evaluations; one patient with major depression in the acute and subacute periods was excluded from the analysis. Among the remaining 48 patients, the number of those with major depression during the first year of stroke onset was five (10.4%). Patients who developed major depression had significantly more depressive symptoms in the acute and subacute stroke phase as assessed by both the PHQ-9 and MADRS. Patients with PHQ-9 scores ≥9 in the acute and subacute stroke phases were significantly more likely to develop major depression in a chronic phase of stroke. CONCLUSIONS: The self-administered PHQ-9 can identify patients in the acute and subacute stroke periods who are at increased risk for developing major depression during the first year after stroke.

Bone Metabolism, Bone Mineral Content, and Density in Elite Late Teen Female Sprinters.

With intensive training, bone injuries are a major concern for athletes. To assess bone condition, we often measure bone turnover markers, bone mineral content and density; however, in junior athletes, it is not easy to distinguish changes caused by bone injuries from those caused by growth, because the metabolism is increased in both cases. Moreover, although some studies have examined female endurance athletes, knowledge regarding changes in static and dynamic bone conditions in late teen athletes is limited. In this study, we measured the bone mineral content and density, as well as bone turnover markers, in 40 elite female sprinters in their late teens. Whole body mode dual-energy X-ray absorptiometry was performed to measure bone mineral content and density. Blood samples were collected to determine bone resorption and formation markers at the end of track season in 2016 and during the same period of the following year. Body weight and bone mineral content significantly increased, and tartrate-resistant acid phosphatase type 5b, bone-type alkaline phosphatase, and osteocalcin significantly decreased after a year. Furthermore, the rate of change in bone mineral content was higher in younger athletes, indicating that bone growth approaches completion in the late teen years and that bone metabolism accordingly decreases.

Potential association of metabolic and musculoskeletal disorders with lumbar intervertebral disc degeneration: Cross-sectional study using medical checkup data.

BACKGROUND: The pathogenesis of intervertebral disc (IVD) degeneration is complex and involves the interaction of multiple factors. However, few systemic studies have explored the associations of metabolic disorders and age-related musculoskeletal disorders with the development of IVD degeneration. METHODS: We analyzed clinical data obtained from healthy individuals who had undergone a musculoskeletal checkup. In total, 276 subjects comprising 142 males and 134 females were enrolled. The subjects were divided into two groups based on the degree of IVD degeneration according to Pfirrmann grading: those with grades 1-3, the group with non-degenerative discs; and grades 4 and 5, the group with degenerative discs. The subjects underwent examinations including abdominal circumference, blood pressure, bilateral hand grip strength, abdominal computed tomography, magnetic resonance imaging of the lumbar spine, and dual X-ray absorptiometry. To examine the independent association with IVD degeneration at L3/4, L4/5, and L5/S levels, we constructed a Poisson regression model and estimated relative risks (RRs) and 95% confidence intervals (CIs) of IVD degeneration. RESULTS: Multivariable analysis showed that advanced age was markedly associated with IVD degeneration at all levels and that men had an inverse association with the IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). In addition, metabolic syndrome was significantly associated with IVD degeneration at the L5/S level (RR = 1.4, 95% CI = 1.1-1.8). Meanwhile, sarcopenia showed no significant association with IVD degeneration at any level. Osteoporosis was inversely associated with IVD degeneration, particularly at the L4/5 level (RR = 0.7, 95% CI = 0.6-0.9). CONCLUSIONS: Our data suggest that advanced age, female sex, and metabolic syndrome are associated with IVD degeneration. In addition, osteoporosis showed an inverse association with IVD degeneration. Our data should promote understanding of the etiology of lumbar IVD degeneration.

Factors affecting lower limb muscle strength and cardiopulmonary fitness after allogeneic hematopoietic stem cell transplantation.

PURPOSE: The aim of this study is to clarify the factors affecting physical function after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: We retrospectively analyzed 88 patients (median age, 44.5 years) who received allogeneic HSCT. Leg extension torque and peak oxygen consumption (VO2) were evaluated before and after HSCT. Patient factors (age, sex, underlying diseases, hemoglobin, serum albumin, and Karnofsky performance status score before transplant) and transplant factors (conditioning regimen, days to neutrophil engraftment, grades of acute graft-versus-host disease [GVHD], infections, and the interval between pre- and post-evaluation) were collected via chart review, and were used for correlational and comparison analyses in order to identify the variables associated with reduced post-HSCT leg extension torque and peak VO2. Stepwise multiple regression analyses for post-HSCT leg extension torque and post-HSCT peak VO2 were performed using age, sex, and the related variables with a p value < 0.2 in the correlational and comparison analyses. RESULTS: Leg extension torque and peak VO2 were significantly reduced after HSCT (p < 0.001). Pre-HSCT leg extension torque, grades of acute GVHD, age, and the interval between pre- and post-evaluation were identified as significant factors associated with reduced post-HSCT leg extension torque. However, none of these factors were significantly associated with reduced post-HSCT peak VO2, and only its pre-transplant value was identified as a significant factor. CONCLUSIONS: These findings suggest that improvements in muscle strength and cardiopulmonary fitness before HSCT are crucial for maintaining post-treatment physical function, especially in elderly individuals with acute GVHD requiring a long-term stay in a protective environment.

Intrathecal betamethasone for cancer pain: A study of its analgesic efficacy and safety.

BACKGROUND: A preliminary study has shown effective cancer pain relief by intrathecal betamethasone (ITB). However, further evidence is needed to support this new approach. METHODS: Cancer patients with opioid-resistant pain received lumbar intrathecal administration of betamethasone 2 or 3 mg once a week for 28 days. Immediate and short-term analgesia (using a percentage pain reduction scale and a numerical rating scale, NRS) and long-term analgesia (using NRS) were assessed. Patients were classified into two groups according to the most painful site of metastasis: vertebral column and/or surrounding nerve plexus metastases (group A) and other metastases distal from the vertebral column (group B). RESULTS: A total of 104 patients received ITB. Pain relief was observed not only in the lower half but also in the upper half of the body. The proportion of group A patients who experienced immediate analgesia was 81% (47/58), which was significantly greater than that of group B (P < 0.001). A decrease in NRS scores 1 day after ITB administration was observed in significantly more patients in group A than in group B (P < 0.001). Long-term analgesia was also recorded in a greater proportion of patients in group A than in group B in the 7-day (59%, 38/64 vs 6%, 2/33) and 28-day periods (71%, 40/56 vs 31%, 8/26) (P < 0.001). No adverse effects related to neurotoxicity were recorded. CONCLUSION: Intrathecal injection of betamethasone produced analgesia for opioid-resistant cancer pain, and may be a potent therapeutic option for intolerable pain from vertebral column and/or surrounding nerve plexus metastases.

Safety and efficacy from a 6-week double-blind study and a 52-week open-label extension of aripiprazole in adolescents with schizophrenia in Japan.

AIM: The purpose of this study was to evaluate the safety and efficacy of aripiprazole in adolescents with schizophrenia (SCZ) in Japan. METHODS: In a 6-week, randomized, double-blind, dose-comparison study, adolescents (aged 13-17 years) with SCZ were randomized to receive aripiprazole 2, 6-12, or 24-30 mg/day. Patients who completed the 6-week study participated in a 52-week, flexible-dose, open-label extension (OLE) study of aripiprazole (initial dose: 2 mg/day, maintenance dose: 6-24 mg/day, maximum dose: 30 mg/day). RESULTS: In the 6-week study, the percentage of patients completing treatment was: 77.1% (27/35) for 2 mg/day; 80.0% (24/30) for 6-12 mg/day; and 85.4% (35/41) for 24-30 mg/day. The least squares mean change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to endpoint (primary efficacy endpoint, last observation carried forward) was -19.6 for 2 mg/day, -16.5 for 6-12 mg/day, and - 21.6 for 24-30 mg/day. The most common (≥20% patients in any group) treatment-emergent adverse events (TEAE) were nausea, akathisia, insomnia, and somnolence. Most TEAE were mild or moderate in severity. There were no deaths. In the OLE, 60.3% (41/68) of patients completed treatment, and the PANSS total score decreased by -7.9 from OLE baseline to week 52. The most common (≥20% patients) TEAE were nasopharyngitis and somnolence. Most TEAE were mild or moderate in severity. There were no deaths. CONCLUSION: These study results suggest that aripiprazole would be safe and well tolerated in both short- and long-term treatment for adolescents with SCZ in Japan.

Acyl/free carnitine ratio is a risk factor for hepatic steatosis after pancreatoduodenectomy and total pancreatectomy.

OBJECTIVES: Hepatic steatosis, one of the most frequent long-term complications of pancreatectomy, influences not only hepatic function but also survival rate. However, its risk factors and pathogenesis have not been established. The purpose of this study was to clarify the risk factors for hepatic steatosis after pancreatectomy. METHODS: In this retrospective study of 21 patients who had undergone pancreatectomy (19 cases of pancreatoduodenectomy and 2 cases of total pancreatectomy), serum carnitine concentrations, fractions of carnitine, and hepatic attenuation on computed tomography images were analyzed with the aim of identifying risk factors for hepatic steatosis. RESULTS: Thirteen (61.9%) of the 21 patients were diagnosed as having hypocarnitinemia after pancreatectomy. Average hepatic attenuation was as low as 42.2HU (±21.3 SD). A high ratio of acyl/free carnitine was associated with less pronounced hepatic attenuation according to both univariate (P < 0.001) and multivariate (P = 0.020) regression analyses. CONCLUSIONS: The serum carnitine concentrations were low after pancreatectomy in some patients. The statistical analyses suggest that a high ratio of acyl/free carnitine is an independent risk factor for hepatic steatosis after pancreatectomy.

Prognosis Prediction for Postoperative Esophageal Cancer Patients Using Onodera's Prognostic Nutritional Index.

PURPOSE: Preoperative nutritional status may impact surgical outcome and prognosis. We evaluated the predictive value of Onodera's prognostic nutritional index (O's-PNI) of surgical outcome following esophagectomy in esophageal cancer patients. PATIENTS AND METHODS: In total, 144 patients undergoing esophagectomy for esophageal cancer from April 2010 to May 2015 were evaluated, retrospectively. Eighty-four patients were enrolled in this study. O's-PNIs were calculated before surgery, discharge, and 1, 2, and 6 mo after discharge. The relationship between O's-PNI and occurrence of complications as classified by the Clavien-Dindo (C-D) classification, length of hospital stay, and survival time was investigated. RESULTS: The mean O's-PNI for patients with complications of more than Grade 2 by the C-D classification was 37.4, which was significantly lower than that for Grades 0 or 1 (40.5, P = 0.0094). A negative correlation was obtained between O's-PNI and hospital stay length (P = 0.0006), whereas a positive correlation was obtained for O's-PNI at 6 mo postsurgery and overall survival (P = 0.0171, P = 0.0201). CONCLUSION: O's-PNI may represent a useful indicator of the occurrence of complications and length of hospital stay, and may influence overall survival at 6 mo postsurgery. Nutritional management during the perioperative period could therefore contribute to satisfactory outcomes following esophagectomy in esophageal cancer patients.

A minimal impact of long-term S-flurbiprofen plaster application on kidney function in osteoarthritis patients.

BACKGROUND: The number of kidney injury due to nonsteroidal anti-inflammatory drugs (NSAIDs) is the largest among drug-induced kidney diseases. Newly developed NSAID plaster containing S-flurbiprofen (SFP) shows innovative percutaneous absorption. However, systemic exposure to SFP following the repeated application of 80 mg/day was estimated as comparable to that of oral 120 mg/day flurbiprofen and prolonged use of topical NSAIDs is common in clinical practice. Thus, we report the safety focusing on the kidney function after long-term application of SFP plaster (SFPP). METHODS: A total of 201 osteoarthritis patients (mean age; 66.3, 151 females, mean estimated glomerular filtration rate; 74.6 mL/min/1.73 mm2) were applied 40 or 80 mg SFPP for 52 weeks, and kidney function was examined by blood urea nitrogen (BUN), serum creatinine (SCr), eGFR, and urinalysis. RESULTS: 161 (80.1%) patients completed 52-week application. In both groups of 40 and 80 mg, small but statistically significant increases were observed in BUN (mean 1.91 and 1.89 mg/dL, p < 0.05) and SCr (mean 0.019 and 0.022 mg/dL, p < 0.05). Although abnormal changes in laboratory test for renal function were observed in seven patients, all the changes were small and subclinical. Acute kidney injury was observed in two patients. Meanwhile, the investigators denied the relevance of SFPP according to the clinical course. CONCLUSION: Toward the end of 52-week application, a statistically significant increase in SCr was observed in both 40 and 80 mg, but increment was small and subclinical. Attention should be paid to kidney function when applying SFPP to patients with multiple risk factors.

Synergistic Effect of Eicosapentaenoic Acid on Antiproliferative Action of Anticancer Drugs in a Cancer Cell Line Model.

BACKGROUND/AIMS: It has been found experimentally and clinically that eicosapentaenoic acid (EPA) exerts an anticancer effect and that it has a minimal adverse event profile relative to other anticancer drugs. Any synergy between EPA and other anticancer drugs could be of therapeutic relevance, especially in elderly or high-risk patients. Therefore, we investigated the synergism between anticancer drugs and EPA experimentally. METHODS: EPA was coadministered in vitro with various anticancer drugs (paclitaxel, docetaxel, 5-fluorouracil and cis-diamminedichloridoplatinum[II]) to TE-1 cells, which were derived from human esophageal cancer tumors. Cell proliferation was measured by the water soluble tetrazolium-1 method. RESULT: Sub-threshold concentrations of EPA, which alone produced no anticancer effect, caused a synergistic suppressive effect on TE-1 cell proliferation when combined with other anticancer agents. CONCLUSION: Coadministration of EPA with other anticancer drugs may represent a new therapeutic paradigm offering a reduced side effect profile.

Repeated Combined Chemotherapy with Cisplatin Lowers Carnitine Levels in Gastric Cancer Patients.

BACKGROUND/AIMS: Carnitine plays an important role in the metabolism of fatty acids. It has also been reported that the administration of anticancer drugs may lead to reductions in serum carnitine levels due to decreased activity of organic cation transporter novel 2, which plays a role in the reabsorption of carnitine in the tubules of the kidney. We therefore studied the change in carnitine levels when chemotherapy was administered repeatedly to patients with gastric cancer. METHODS: Ten patients with upper gastrointestinal cancer were enrolled in this study between December 2014 and August 2015. All patients were administered chemotherapy consisting of TS-1 and cisplatin every 3 weeks: 3 received it as adjuvant therapy post resection, the remaining 7 received it as treatment for unresectable tumors. Before the start of each chemotherapy cycle, serum was collected. RESULTS: The mean total carnitine level was 54.5 ± 13.7 µmol/L prior to commencing chemotherapy; it was 46.7 ± 13.5 and 41.4 ± 14.8 µmol/L at the second and third cycles respectively. The total carnitine level was decreased in a statistically significant manner (p = 0.0039). The serum level of total protein and cholinesterase was also decreased significantly (p = 0.0218 and p = 0.0418). CONCLUSION: Carnitine levels decreased during repeated chemotherapy in patients with gastric cancer, and they are associated with the nutritional status.

Prognostic factors for gastrectomy in elderly patients with gastric cancer.

BACKGROUND: The aim of the present study was to investigate the age-specific prognostic factors in patients who underwent gastrectomy for gastric cancer. METHODS: The medical records of 366 patients with gastric cancer who underwent surgical resection at our hospital between January 2007 and December 2014 were retrospectively reviewed. Of the 366 patients, 117 were aged 75 years or older and 249 were aged 74 years or younger. All factors that were identified as significant using univariate analysis were included in the multivariate analysis. RESULTS: The median follow-up duration was 52.9 months (range, 1.0-117.5 months). We found that in patients aged 75 years or older, postoperative complications and the extent of cancer were independent prognostic factors of overall survival and disease-free survival. In contrast, in patients aged 74 years or younger, only the lymph node status and postoperative chemotherapy were independent prognostic factors for overall survival and disease-free survival, respectively. CONCLUSIONS: Pathological outcomes and postoperative complications are important prognostic factors for survival in patients aged 75 years or older with gastric cancer, whereas pathological outcomes and postoperative chemotherapy are important prognostic factors for survival in patients aged 74 years or younger. Because the prevention of postoperative complications may contribute to improvements in the prognosis of elderly patients with gastric cancer, we suggest that it is necessary to consider limited surgery instead of radical surgery, depending on the patient's general condition and co-morbidities.