Effects of an elemental diet, Elental®, may differ between healthy oral cells and oral cancer cells.

The effectiveness of an elemental diet (ED), Elental®, against radiotherapy­ or chemoradiotherapy­induced oral mucositis was previously reported. However, the administration of additional nutrition or an ED in patients with oral cancer may also provide extra nutrition for cancer cells, which could result in cancer development. At present, it remains unclear whether the beneficial effects of an ED are likely to surpass its potential harmful effects on oral cancer treatment. In the present study, we aimed to clarify whether Elental® has different effects on a healthy human oral keratinocyte (HOK) cell line compared with its effects on oral squamous cell carcinoma (OSCC) cell lines (HSC2, HSC3, HSC4). The efficacy of Elental® was compared in relation to the growth and migration ability of HOK and OSCC cell lines using MTT assay and migration assay, respectively. In addition, whole transcriptome analysis and network analysis were performed to determine the difference in the mechanism of action of Elental® between HOK and HSC2 cells. In addition, Elental® promoted growth and migration ability of­malnourished and 5­fluorouracil (5­FU)­treated damaged HOK cells cultured in low nutrition medium (0% growth supplement). However, Elental® did not affect the growth ability of 5­FU­treated damaged HSC2 cell line in low nutrition medium (0 or 1% fetal bovine serum (FBS), as well as the growth ability of HSC3 and HSC4 cell lines in medium containing 0% FBS. Elental® pre­treatment also enhanced the apoptosis­inducing effect of anticancer agents against OSCC cells. In addition, whole transcriptome analysis and Ingenuity Pathways Analysis (IPA) data suggested that Elental® may help in the proliferation and survival of HOK through the induction of ERK. Moreover, Elental® added stress to HSC2 cells through the induction of the endoplasmic reticulum stress response marker, BiP and GRP 94. The results showed that Elental® may add stress to HSC2 cells and provide growth stimulation to HOK. These findings suggest that the effects of Elental® on healthy oral cells and oral cancer cells may differ.

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.

The Efficacy of an Oral Elemental Diet in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Objective Conditioning regimens for hematopoietic stem cell transplantation (HSCT) are well known to cause severe gastrointestinal toxicities that often disturb the oral intake of the patients followed by poor nutrition and life-threatening infection. An oral elemental diet (ED) is an easily consumed and assimilated form of liquid nutrients mainly composed of amino acids. It alleviates the digestive loading from the intestine and is mainly used for enteral nutritional support in patients with Crohn's disease. We herein report, for the first time, the efficacy of ED for patients undergoing HSCT. Methods We evaluated the efficacy of ED in a prospective cohort study. The primary endpoint for this study was the hospitalization period. The secondary endpoint was the occurrence of oral mucositis, nausea, diarrhea and fever. Patients A total of 73 patients were consecutively enrolled between March 2011 and March 2013. Twenty-three patients underwent autologous HSCT and 50 patients underwent allogeneic HSCT. The first 21 patients did not receive ED (non-ED group; NEG) while in the successive 52 patients (ED group; EG), oral ED was started before conditioning and was continued until 28 days after transplantation. Results The patient characteristics were similar between the two groups. The mean duration of ED administration for EG was 28.7 days (range, 3-37 days), and the mean total-dose of ED administration was 1904 g (range, 240-2,960 g). The median hospitalization period was significantly shorter in EG compared to NEG, (34 days vs. 50 days; p=0.007). Grade 3-4 oral mucositis occurred less in EG than NEG (25% vs. 48%; p=0.06). Conclusion Oral ED may promote an early mucosal recovery and thereby shorten the duration of hospitalization.

Efficacy of elemental diet on prevention for chemoradiotherapy-induced oral mucositis in patients with oral squamous cell carcinoma.

PURPOSE: Oral mucositis induced by radiation or chemoradiation can compromise the quality of life of oral squamous cell carcinoma (OSCC) patients. The present study was designed to evaluate the preventive effects of elemental diet (ED), Elental®, on radiotherapy- or chemoradiotherapy-induced mucositis in OSCC patients. PATIENTS AND METHODS: Seventy-four patients who underwent radiation (60-70 Gy) with/without chemotherapy [S-1, cisplatin (CDDP), CDDP plus S-1] were enrolled in this retrospective study; 37 had received Elental® during treatment (Elental® group) and 37 had not (control group). Factors related to alleviation of oral mucositis were identified by multivariate logistic regression analysis. Rates of completion of chemoradiation treatments were compared between Elental® and control groups according to the treatment regimen. The comparison of the nutritional status between groups was also performed. RESULTS: Multivariate analysis indicated that the administration of Elental® and no combined chemotherapy (radiation alone) were significant factors associated with the degree of oral mucositis, i.e., most of the patients who consumed Elental® suffered from a lower degree of mucositis compared to the control group. Elental® was associated with a significantly improved rate of completion of chemoradiation (no interruption). There was no significant difference between Elental® group and control group in terms of mean change of body weight or total protein and albumin levels in blood serum before and after (chemo)radiation. CONCLUSIONS: The present study indicates that Elental® is effective for ameliorating oral mucositis induced by (chemo)radiation in OSCC patients. Elental® was also associated with improved completion rates of (chemo)radiotherapy.

Preventive effects of amino-acid-rich elemental diet Elental® on chemotherapy-induced oral mucositis in patients with colorectal cancer: a prospective pilot study.

PURPOSE: The prospective pilot study was designed to evaluate the preventive effects of amino-acid-rich elemental diet (ED), Elental(®), on chemotherapy-induced oral mucositis in patients with colorectal cancer. The factors influencing its efficacy are also investigated. METHODS: A total of 22 eligible patients with colorectal cancer experiencing grade 1-3 oral mucositis during treatment with fluorouracil-based chemotherapy entered the current study. Their average age was 67 years. There were 10 male and 12 female. The PS was 0 in the majority of patients. Patients received two courses of the same chemotherapy regimen and Elental(®) concurrently after recovery to grade 0 or 1 oral mucositis. RESULTS: FOLFOX6 + bevacizumab in 8 patients, FOLFIRI + bevacizumab in 8 patients, FOLFIRI + panitumumab in 1 patient, FOLFIRI in 1 patient, XELOX + bevacizumab in 2 patients, and S-1 + cetuximab in 2 patients were used as first-line (16 cases) or as second-line (6 cases) chemotherapy. Dose reduction of 5-fluorouracil (5-FU) or oral fluoropyrimidine was performed in the 2 patients achieving grade 3 oral mucositis and in the 3 patients achieving grade 2 oral mucositis. The maximum grade of oral mucositis decreased in 18 of the 22 patients during the first treatment course with Elental(®) (p = 0.0002) and in 20 of the 22 patients in the second course (p < 0.0001). Multivariate analyses found that the dose reduction in 5-FU or oral fluoropyrimidine, ED intake, and the prior administration of ED were each a significant factor for the preventive efficacy on oral mucositis. CONCLUSION: The amino-acid-rich elemental diet Elental(®) may be useful as a countermeasure for 5-FU-based chemotherapy-induced oral mucositis in patients with colorectal cancer.

Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study.

PURPOSE: We investigated the effect of glutamine (Gln) and an elemental diet (ED) on chemotherapy-induced oral mucositis in esophageal cancer patients. METHODS: Thirty patients were randomized to the control group (no treatment: n = 10), Gln group (oral intake of 8910 mg Gln/day: n = 10), or Gln plus ED group (total oral intake of 8862 mg Gln/day, including the Gln in ED: n = 10). Oral administration of Gln and ED began 1 week before chemotherapy and continued during treatment. Oral mucositis was evaluated during 2 cycles of chemotherapy using Common Terminology Criteria for Adverse Events v3.0. RESULTS: The incidence of grade ≥2 oral mucositis was 60 % in the control group, 70 % in the Gln group, and 10 % in the Gln plus ED group. Gln plus ED showed a significant preventive effect on the development and severity of oral mucositis. By multivariate analysis, Gln plus ED and cancer stage were independent factors affecting chemotherapy-induced oral mucositis. The percentage of change in body weight and diamine oxidase activity from before chemotherapy was higher in the Gln plus ED group than in the control group. CONCLUSIONS: Oral administration of Gln plus ED may prevent chemotherapy-induced oral mucositis in esophageal cancer patients.

Nutritional, microbiological, and therapeutic factors related to mucositis in head and neck cancer patients: a cohort study / Factores nutricionales, microbiológicos y terapéuticos relacionados con el desarrollo de mucositis en pacientes con cáncer de cabeza y cuello: un estudio de cohorte

Purpose: the objective was to demonstrate if treatment modality, nutritional status and oropharyngeal flora contribute to the development of mucositis in radiotherapy-treated head and neck cancer. Methods: single-cohort study of patients with head and neck cancer (H&N) in which radiotherapy was indicated. Nutritional status was evaluated using SGA, BMI, and FFMI. A buccal smear was performed before radiotherapy for cultivation of bacteria and yeasts. Mucositis was evaluated using the WHO grades. Relative risk (RR) and its 95% CI were calculated. Results: the study included 35 patients, 74.3% males, 63.8 (9.9) years of age, and 34.3% malnourished. The diagnoses included larynx (40.0%), oral (25.7%), and pharynx cancer (11.4%). Treatment comprised 66.0 Gy of radiation, chemotherapy (60.0%), and surgery (57.1%). Bacteria were found in 28.6%, including Staphylococcus aureus (8.6%) and Escherichia coli (8.6%). Yeasts (Candida spp.) were found in 35.3%. Mucositis was more frequent in patients with definitive radiotherapy [100% vs. 65%, p = 0.01; RR = 1.54 (CI95% 1.12 to 2.12)]. Neither SGA nor BMI or FFMI were related to the development or severity of mucositis. Positive cultures for bacteria before radiotherapy were related to severe mucositis [44.4% vs. 12%, p = 0.039; RR = 4.17 (CI95% 1.22 to 14.24)], but there was no relationship with the presence of yeasts. Previous surgery was not associated with the appearance of the studied strains of bacteria. Conclusion: bacterial colonization of the oropharynx prior to radiotherapy may be a factor for severe mucositis in H&N patients (AU)

Objetivo: el objetivo fue demostrar si la modalidad de tratamiento, el estado nutricional y la flora orofaríngea contribuyen al desarrollo de mucositis en pacientes con cáncer de cabeza y cuello tratados con radioterapia. Métodos: estudio de cohorte de pacientes con cáncer de cabeza y cuello (CyC) tratados con radioterapia. El estado nutricional se evaluó utilizando VGS, IMC e IMM. Se realizó un frotis bucal antes de la radioterapia para el cultivo de bacterias y levaduras. Se evaluó la mucositis usando los criterios de la OMS. Se calcularon el riesgo relativo (RR) y su IC del 95%. Resultados: el estudio incluyó a 35 pacientes, 74,3% hombres, 63,8 (9,9) años de edad, y 34,3% desnutridos. Los tumores estaban localizados en laringe (40,0%), boca (25,7%) y faringe (11,4%). El tratamiento consistió en 66,0 Gy de radiación, quimioterapia (60,0%) y cirugía (57,1%). Se encontraron bacterias en 28,6%, incluyendo Staphylococcus aureus (8,6%) y Escherichia coli (8,6%). Se encontró Candida spp. en el 35,3%. La mucositis fue más frecuente en los pacientes con radioterapia radical [100% vs. 65%, p = 0,01; RR = 1,54 (IC95% 1,12 a 2,12)]. Ni VGS, IMC ni IMM se relacionaron con el desarrollo o la gravedad de la mucositis. Los cultivos positivos para bacterias antes de la radioterapia se relacionaron con mucositis severa [44,4% vs. 12%, p = 0,039; RR = 4,17 (IC95% 1,22 a 14,24)], pero no hubo ninguna relación con la presencia de levaduras. La cirugía no se asoció con la aparición de las cepas estudiadas de bacterias. Conclusión: la colonización bacteriana de la orofaringe antes de la radioterapia puede ser un factor para la mucositis graves en pacientes con cáncer CyC (AU)

Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

Relationship of protein and calorie intake to the severity of oral mucositis in patients with head and neck cancer receiving radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the relationship of calorie and protein intake to the severity of oral mucositis in patients with head and neck cancer receiving radiation therapy. METHODS: Patients with head and neck cancer undergoing ≥60 Gy of radiation were eligible. Weekly data were collected for oral mucositis grade and protein and calorie intake. Proportional odds models examined the association of oral mucositis severity with nutritional predictors. RESULTS: During a 24-month period, 40 evaluable patients met criteria for inclusion. In a multivariate backward selection model, the sole significant nutritional predictor of reduced oral mucositis severity was meeting the protein goal for the current week (p = .01; adjusted odds ratio [OR], 2.30). CONCLUSION: Patients who met protein-related goals during radiotherapy for head and neck cancer had less severe oral mucositis. Nutritional counseling during radiotherapy, with emphasis on protein goals, may reduce oral mucositis severity.

The role of allergy in oral mucosal diseases.

We retrospectively assessed the prevalence of positive results to cutaneous patch testing, and the relevance of exclusion of identified allergens in the disease process, in 1252 patients with oral mucosal diseases presenting to the Department of Oral Medicine in Glasgow Dental Hospital and School and referred to the Contact Dermatitis Investigation Unit in Glasgow Royal Infirmary. The prevalence of patch-test positivity in each disease cohort was compared with that in 100 control volunteers. Patients with oral mucosal diseases were significantly more likely to have demonstrable hypersensitivity to food additives, especially benzoic acid, and perfumes and flavourings, especially cinnamaldehyde, than controls, and avoidance therapy caused improvement in the majority. Patch testing and the resultant avoidance therapy are useful adjuncts in the management of oral mucosal diseases.

Some findings in patients with uraemic stomatitis.

Uraemic stomatitis may occur in patients with advanced renal failure. Thirteen patients with severe oral lesions due to their uraemic state are discussed. The stomatitis became manifest after a few days of severe renal failure (blood urea level was at least 20 mnol./1) and persisted for 2-3 weeks even when the urea concentration had decreased.