The effect of an elemental diet on oral mucositis of esophageal cancer patients treated with DCF chemotherapy: a multi-center prospective feasibility study (EPOC study)

Purpose

Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy.

Methods

We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system.

Results

Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade?≥?2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p?=?0.046).

Conclusions

An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study.

Clinical trial

The date of submission: Dec 08th, 2017.

     

Effects of drug, biobehavioral and exercise therapies on heart rate variability in coronary artery disease: a systematic review

BACKGROUND: Heart rate variability (HRV) is reported as a surrogate index for clinical outcome in trials of secondary prevention strategies for coronary artery disease (CAD), but a standardized guide for interpreting HRV change is not established. DESIGN: We evaluated HRV change in trials with CAD patients who received conventional medications (beta-blockers, calcium channel blockers, angiotensin converting enzyme inhibitors), biobehavioral treatment (psychotropics, biofeedback, relaxation) or exercise training. METHODS: Medline, Pubmed, Psycinfo, the Cochrane database, and Embase were searched until July 2007, without language restriction. We identified 33 randomized controlled trials. Two reviewers independently abstracted all trials using a standardized form. A hierarchy of frequency and time domain HRV indices defined outcome. RESULTS: A random-effects model yielded an overall pooled standardized mean difference (SMD) between treatment and control groups of moderate magnitude across treatment classes, based on a composite of time and frequency domain indices (SMD=0.40, P<0.0001), or only time or frequency indices (SMD=0.37 and 0.43, respectively, both P<0.0001). This change was equivalent to an increase in standard deviation of all normal-to-normal RR intervals of 9.0 ms (95% Confidence Interval, CI, 7.3, 10.7 ms) or a relative increase of 15.9% (95% CI, 13.2, 18.6%). To detect HRV change of this magnitude, a hypothetical trial would require a sample size of 660 patients for conventional medications or 1232 patients for all treatment classes. CONCLUSION: Pharmacologic, biobehavioral and exercise strategies for secondary prevention of CAD significantly increase HRV. This review provides a framework to assist efforts to evaluate the contribution of HRV change to CAD prognosis.     

Can negative cardiac effect of proton pump inhibitor and high-dose H2-blocker have clinical influence on patients with stable angina?

BACKGROUND: Aspirin and anti-platelet drugs are used commonly for patients with coronary heart disease. Proton pump inhibitor (PPI) and high-dose H2-blocker were recommended for preventing NSAIDs-related ulcer. Previously H2-blocker reported to have some negative cardiovascular effects. Additionally, a recent in vitro study showed that PPI reduced cardiac contractility. In this study, we evaluated whether chronic administration of PPI and high-dose H2-blocker affects left ventricular function. METHOD: Fifty-two stable angina patients were enrolled and classified into PPI group ([P]; lansoprazole: 15mg/day, n=28), H2-blocker group ([H]; famotidine: 40mg/day, n=8), and control ([C]; none or mucosal-defense drug, n=16). Eligible patients showed normal cardiac function in initial catheterization without administrated PPI or H2-blocker. They received percutaneous coronary intervention and follow-up catheterization. We compared changes in ejection fraction (EF: %), end diastolic/systolic volume index (EDVI/ESVI: ml/m(2)), and peak positive/negative dp/dt (+/-dp/dt: mmHg/s) in left ventricular angiography series. RESULT: There were no significant differences among three groups regarding patient characteristics, backgrounds of angiographic and intervention, except for fewer smokers in [C]. Other drugs such as beta- and Ca-blocker did not have effects on cardiac function except for aspirin during 255+/-115 days follow-up. Rate of EF changes significantly decreased in [P], and tended to decrease in [H] (C: 3.8+/-9.8%, H: -1.6+/-7.6%, P: -2.1+/-5.9%; p<0.05 for [C] vs. [P]). Those of ESVI changes were significantly greater in [P], and tended to be greater in [H] (C: -4.5+/-16.2%, H: 4.9+/-15.5%, P: 7.3+/-16.2%; p<0.05 for [C] vs. [P]), though, EDVI changes' were similar (C: 2.5+/-8.9%, H: 2.6+/-3.6%, P: 1.6+/-6.1%; p=ns). Rate of +/-dp/dt-changes tended to decrease in [H] (+dp/dt: C: 3.9+/-15.5%, H: -10.0+/-25.2%, P: 0.3+/-19.6%; p=ns, -dp/dt: C: -0.1+/-19.5%, H: -8.5+/-20.4%, P: 5.7+/-27.7%; p=ns). CONCLUSION: In this study, PPI and high-dose H2-blocker have EF-reducing tendency. However, these changes were small and these drugs seemed to exhibit little influence clinically.     

Change in Colonic Motility After Extrinsic Autonomic Denervation in Dogs

Changes in colonic motility were compared indogs undergoing autonomic denervation of the paraaorticand presacral (group A), paraaortic (group B), ormesocolonic region (group C), and sham operation (group D). Five bipolar recording electrodes wereplaced into the seromuscular layer of the colon andrectum. The numbers of continuous electrical responseactivity and contractile electrical complex after an intragastric olive oil injection were smallerin group A than in the other groups (P < 0.05) fromthree weeks through six months after denervation. Thisdifference was significant even in the proximal colon. These data suggest that the pelvic plexus mayplay an important role in colonic motility including theproximal colon. The damage to the plexus did not recoverfor at least six months after denevation. Pelvic plexus injury may thus be one ofpossible explanations for the prolonged change in bowelhabit after anterior resection of the rectum.     

Present status and prospects of living-related liver transplantation

Living-related liver transplantation (LRLT) is a relatively new surgical modality that has developed, in part, to overcome the shortage of available cadaveric livers for transplantation and as a method to provide liver graft implants from living donors for patients end-stage with liver disease in areas where the use of cadaveric livers is not yet practiced or permitted. Since 1988 almost 500 LRLTs have been performed globally. The safety of donors who provide a portion of their liver for grafting is of utmost concern, and only one donor death from this procedure has been reported in the literature. Postoperative survival in recipients depends on their pretransplant physical status, but emergency patients in rapid need of a liver have a poorer survival than elective LRLT patients for whom survival is about 80%. Children and infants are the main recipients of LRLTs, but adult patients particularly in Japan, are increasing in number, and present indications for LRLT surgery include not only cholestatic end-stage liver diseases but also metabolic disorders affecting the liver and emergency LRLTs for fulminant hepatic failure. Many ethical problems relating to the concept of liver transplantation, donor liver source, recipient selection, and reimplantation have yet to be resolved. But we believe that LRLTs and cadaveric liver transplantations are saving lives and that the practice should be continued.     

Triiodothyronine generation from thyroxine in human thyroid: enhanced conversion in Graves' thyroid tissue

Conversion of T4 to T3 was studied in normal, Graves', and neoplastic thyroid tissues obtained at surgery. Homogenates of human thyroid follicular adenoma and carcinomas were incubated with [125I]T4 and dithiothreitol (DTT) at 37 C for 60 min under N2 gas. T3 formation was assessed by measuring [125I]T3 formed, using paper chromatography. In the second series of experiments, the suspensions of the 100,000 X g pellet of normal thyroid tissues adjacent to the tumor and Graves' thyroid tissues were incubated with unlabeled T4 and DTT at 37 C for 60 min under N2 gas. T3 generated was measured by RIA. T3 generation in the thyroid tissue was dependent on incubation time, amount of the tissue used, concentration of DTT, temperature, and pH. Propylthioracil inhibited T3 formation, while methimazole had no effect. A kinetic study with the homogenate of a thyroid adenoma and 100,000 X g pellet suspensions of two normal and three Graves' thyroids gave apparent Km values of 2.7, 4.9, and 4.1 microM for T4, respectively, and Vmax values of 0.8, 3.0, and 10.9 pmol T3/mg protein.min, respectively. Conversion of T4 to T3 was observed in two of three tumor tissues studied and was markedly enhanced in Graves' thyroid tissues (mean +/- SE, 11.9 +/- 2.0 pmol/mg protein.min) compared to that of normal thyroid tissues (3.2 +/- 0.6 pmol/mg protein.min; P less than 0.01). It is concluded that T4 is enzymatically converted to T3 in normal and Graves' thyroids and differentiated thyroid neoplasms. Moreover, enhanced conversion of T4 to T3 was found in Graves' thyroid tissue.     

Effects of arotinolol on exercise capacity and humoral factors during exercise in normal subjects

Summary A placebo-controlled, double-blind crossover study was undertaken in 10 normal subjects to examine the effects of arotinolol (10 mg bid), a nonselective beta blocker with alpha-blocking activity, on exercise capacity and hormone levels during exercise after a 2-week treatment period. Maximal oxygen uptake (VO₂ max) and blood lactic acid concentration (LA) were measured during progressive exercise testing. An exercise intensity equivalent to 4 mmol/l of LA was used for the constant workload exercise test. Humoral factors were measured after 20 minutes of constant workload exercise. The administration of arotinolol significantly decreased systolic blood pressure and heart rate at rest and during exercise, but diastolic blood pressure did not change. No significant difference was found between arotinolol and placebo with regard to VO₂ max and maximal workload. Plasma renin activity (PRA), aldosterone (PAC), and norepinephrine (NE) levels at rest and during exercise did not differ between the two treatments. In contrast, plasma epinephrine (EN) levels at rest and during exercise were significantly greater with arotinolol. Atrial natriuretic peptide (ANP) at rest did not differ between the two treatments. However, exercise caused a significant increase in ANP after arotinolol treatment. These findings suggest that arotinolol decreases blood pressure and heart rate without affecting exercise capacity.     

Health benefits associated with exercise habituation in older Japanese men

BACKGROUND AND AIMS: The purpose of this study was to compare the effects of exercise habituation (3-32 years, mean 13.2 years) on physical vitality among five different groups. METHODS: One hundred and two independent, community-dwelling elderly Japanese men, aged 64.6 +/- 6.6 years, were recruited as subjects. The vital age test battery consisted of various coronary heart disease risk factors and physical fitness elements. RESULTS: The results of analysis of variance revealed that vital age as an index of physical vitality was youngest in joggers (47.9 yr, N=18), intermediate in trekkers (55.8 yr, N=20) and walkers (59.1 yr, N=18), and oldest (69.6 yr, N=20) in patients with ischemic heart disease (IHD). The difference between chronological age and vital age was approximately 15 years (p<0.05) in joggers, and 8 years (p<0.05) in trekkers and walkers. The vital age of sedentary persons (N=26) was only 1.9 years (NS) younger than their chronological age, which was similar to the difference (vital age of 64.1 +/- 8.5 yr vs chronological age of 65.7 +/- 5.4 yr) previously observed in similarly aged exercising IHD patients. CONCLUSIONS: These results indicate that exercise habituation significantly affects the overall health status of most individuals, irrespective of mode of exercise. Among the three modes of exercise, jogging may be most beneficial. Furthermore, regularly exercising coronary patients may have physical vitality similar to that of sedentary men.     

Effect of H. pylori on COX-2 expression in gastric remnant after distal gastrectomy

BACKGROUND/AIMS: Helicobacter pylori infection is known to induce gastritis, oxidative stress, and cyclooxygenase (COX)-2 expression in the gastric mucosa. However, the effect of H. pylori infection on remnant gastritis has not been studied. We investigated whether the severity of remnant gastritis and COX-2 expression were affected by H. pylori infection after distal gastrectomy. METHODOLOGY: The study included 97 patients with gastric cancer who underwent curative distal gastrectomy with lymphadenectomy in our department between May 1999 and April 2001. All patients underwent endoscopic examination 2 weeks before and 12 weeks after surgery. The presence of H. pylori infection was determined by urease activity, hematoxylin-eosin staining, and immunochemical staining. Histologic remnant gastritis was graded based on the degree of neutrophil infiltration using the updated Sydney System. COX-2 expression was estimated immunohistochemically. RESULTS: Both the degree of neutrophil infiltration and the level of COX-2 expression were significantly higher in patients with than without H. pylori (p<0.05). There was a significant correlation between the degree of neutrophil infiltration and the degree of COX-2 expression (p<0.001). CONCLUSIONS: H. pylori eradication may become a treatment for preventing both remnant gastritis as well as remnant gastric carcinoma after distal gastrectomy.