Dietary Methionine Supplementation Exacerbates Gastrointestinal Toxicity in a Mouse Model of Abdominal Irradiation.

BACKGROUND AND PURPOSE: Identification of appropriate dietary strategies for prevention of weight and muscle loss in cancer patients is crucial for successful treatment and prolonged patient survival. High-protein oral nutritional supplements decrease mortality and improve indices of nutritional status in cancer patients; however, high-protein diets are often rich in methionine, and experimental evidence indicates that a methionine-supplemented diet (MSD) exacerbates gastrointestinal toxicity after total body irradiation. Here, we sought to investigate whether MSD can exacerbate gastrointestinal toxicity after local abdominal irradiation, an exposure regimen more relevant to clinical settings. MATERIALS AND METHODS: Male CBA/CaJ mice fed either a methionine-adequate diet or MSD (6.5 mg methionine/kg diet vs 19.5 mg/kg) received localized abdominal X-irradiation (220 kV, 13 mA) using the Small Animal Radiation Research Platform, and tissues were harvested 4, 7, and 10 days after irradiation. RESULTS: MSD exacerbated gastrointestinal toxicity after local abdominal irradiation with 12.5 Gy. This was evident as impaired nutrient absorption was paralleled by reduced body weight recovery. Mechanistically, significant shifts in the gut ecology, evident as decreased microbiome diversity, and substantially increased bacterial species that belong to the genus Bacteroides triggered proinflammatory responses. The latter were evident as increases in circulating neutrophils with corresponding decreases in lymphocytes and associated molecular alterations, exhibited as increases in mRNA levels of proinflammatory genes Icam1, Casp1, Cd14, and Myd88. Altered expression of the tight junction-related proteins Cldn2, Cldn5, and Cldn6 indicated a possible increase in intestinal permeability and bacterial translocation to the liver. CONCLUSIONS: We report that dietary supplementation with methionine exacerbates gastrointestinal syndrome in locally irradiated mice. This study demonstrates the important roles registered dieticians should play in clinical oncology and further underlines the necessity of preclinical and clinical investigations in the role of diet in the success of cancer therapy.

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

PURPOSE: In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. METHODS: We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. RESULTS: The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. CONCLUSIONS: DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.

Complementary and alternative medicine self-care strategies for nausea in patients undergoing abdominal or pelvic irradiation for cancer: A longitudinal observational study of implementation in routine care.

OBJECTIVE: To longitudinally describe practice of Complementary and Alternative Medicine (CAM) self-care strategies for nausea during radiotherapy. METHODS: Two hundred patients daily registered nausea and practice of CAM self-care strategies, beside conventional antiemetic medications, for nausea during abdominal/pelvic irradiation (median five weeks) for gynecological (69%) colorectal (27%) or other tumors (4%). RESULTS: During radiotherapy, 131 (66%) experienced nausea, and 50 (25%) practiced self-care for nausea at least once, for a mean (m) of 15.9days. The six of 50 patients who stayed free from nausea practiced self-care more frequent (m=25.8days) than the 44 patients experiencing nausea (m=14.5) (p=0.013). The CAM self-care strategies were: modifying eating (80% of all self-care practicing patients, 80% of the nauseous patients versus 83% of the patients free from nausea; ns) or drinking habits (38%, 41% vs 17%; ns), taking rests (18%, 20% vs 0%; ns), physical exercising (6%, 2% vs 33%; p=0.035), acupressure (4%, 5% vs 0%; ns) and self-induced vomiting (2%, 2% vs 0%; ns). CONCLUSION: A fourth of patients undergoing emetogenic radiotherapy practiced CAM self-care for nausea, mostly by modifying eating or drinking habits. The CAM self-care practicing patients who did not become nauseous practiced self-care more frequent than the nauseous patients did. To make such self-care evidence based, we need studies evaluating its efficacy.

Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects' abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient's skin.

Preclinical studies of the Chinese Herbal Medicine formulation PHY906 (KD018) as a potential adjunct to radiation therapy.

OBJECTIVE: Abdominal and pelvic radiotherapy is limited by the radiosensitivity of the small and large intestine. PHY906 (KD018), a state-of-the-art, well defined adaptation of a traditional Chinese medicine, decreased intestinal injury from chemotherapy in preclinical studies and is in clinical trials with chemotherapy. This project assessed whether PHY906 would also reduce intestinal injury from abdominal irradiation in mice. MATERIALS AND METHODS: BALB/c mice received whole-abdomen irradiation (2 Gy/day) ± PHY906 by oral gavage twice daily for 4 days. Intestinal injury was assayed by physiological observations and histological studies. Effects of PHY906 on EMT6 mouse mammary tumors were assayed in tumor growth studies. RESULTS: PHY906 decreased toxicity from fractionated abdominal irradiation. Radiation alone produced marked blunting and loss of villi, crypt hyperplasia and irregular crypt morphology, which were reduced by PHY906. The radiation-induced reduction in viable crypt numbers was also mitigated by PHY906. PHY906 did not alter radiation-induced weight loss, but resulted in more rapid recovery. PHY906 did not alter tumor growth, local invasion or metastatic spread and did not protect tumors from growth delays produced by single-dose or fractionated irradiation. CONCLUSION: In this mouse model, PHY906 (KD018) decreased the toxicity of abdominal irradiation without protecting tumors and thereby increased the therapeutic ratio.

An in vivo histopathological comparison of single and double pulsed modes of a fractionated CO(2) laser.

INTRODUCTION: Studies examining the histopathological changes that occur in human skin following fractional laser treatment have been performed mainly in animals or abdominal tissue prior to abdominoplasty. This study looks at the effect of double pulse fractional CO(2) laser compared to single pulse treatments to assess differences in tissue injury in the face and abdomen. METHODS: Twelve healthy subjects randomized into two groups, had two 1 cm(2) areas (infraumbilical and forehead) treated with the fractional CO(2) laser (Deep Fx, Lumenis). Settings used were 15 mJ double pulse, and 30 mJ single pulse, 300 Hz, 10% density and compared to the historic control of 15 patients treated at 15 mJ single pulse [Bailey et al. (2011), Lasers Surg Med 43: 99-107]. Treated sites were biopsied and analyzed with H&E and TUNEL staining to measure width and depth of the microthermal zones (MTZ) of ablation. RESULTS: When comparing 15 mJ double pulse to single pulse there were significant differences both in depth (abdominal skin, P = 0.002 and facial skin, P = 0.001) and width (facial skin, P = 0.0002) of MTZ. When comparing double pulsing at 15 mJ with single pulsing at 30 mJ there were significant differences between MTZ depths in the abdomen (P < 0.01) but not in either the MTZ depth (P = 0.69) or the width in the face (P = 0.502). DISCUSSION: This study demonstrates the differences between histopathological laser injury patterns in the face compared to the abdomen when single pulsing is used. It also demonstrates that double pulsing at 15 mJ is statistically similar to single pulsing at 30 mJ in the face. We think this could have ramifications for clinical practice where by double pulsing at lower energies may result in better clinical outcomes than increasing energies or using multiple passes at single pulse. Clinical studies needs to be performed to investigate this further.

Hyperbaric oxygen therapy and delayed radiation injuries (soft tissue and bony necrosis): 2012 update.

Informal surveys at CME meetings have shown that approximately one-third of patients in the United States receive hyperbaric oxygen (HBO2) for delayed radiation injury. More than 600,000 patients receive radiation for malignancy in our country annually, and about one-half will be long-term survivors. Serious radiation complications occur in 5-10% of survivors. A large population of patients is therefore at risk for radiation injury. HBO2 has been applied to treat patients with radiation injury since the mid-1970s. Published results are consistently positive, but the level of evidence for individual publications is usually not high level, consisting mostly of case series and case reports. Only a rare randomized controlled trial has been accomplished. Radiation injury is one of the UHMS "approved" indications, and third-party payors will usually reimburse for this application. This updated review summarizes the publications available reporting results in treating radiation-injured patients. Mechanisms of HBO2 in radiation injury are discussed briefly. Outcome is reported on a mostly anatomic basis though due to the nature of the injury a positive outcome at one anatomic site is supportive of HBO2 at other sites. The potential benefit of prophylactic HBO2 before frank damage is also discussed in high-risk patients. The concerns of HBO2 enhancing growth of or precipitating recurrence of malignancy is discussed and largely refuted.

[Effects of heat therapy using a far infrared rays heating element for dysmenorrhea in high school girls].

PURPOSE: The purpose of this study was designed to identify the effects of heat therapy on dysmenorrhea, heat being provided using a far infrared rays heating element. METHODS: The research design for the study was a non-equivalent control group quasi-experimental design. Participants were 22 students for the experimental group, and 26 students for the control group. Data were analyzed using SAS WIN 9.1 program. RESULTS: The experimental group had significantly lower mean scores for menstrual pain, dysmenorrhea, and blood pressure than those in the control group. However, no significant differences were found between two groups for pulse, respiration, and temperature. CONCLUSION: These findings show that thermotherapy was effective for reduction of menstrual pain, dysmenorrhea, and B/P. Therefore, this therapy could be used as a nursing intervention for students with dysmenorrhea.

Whole abdominal field versus standard field radiotherapy plus concomitant and adjuvant chemotherapy for patients with locally advanced gastric cancer.

PURPOSE: To compare standard radiotherapy field (SRTF) with whole abdomen irradiation (WAI), used in conjunction with adjuvant chemotherapy following curative surgery in patients with gastric cancer. METHODS AND MATERIAL: Ninety patients were included in the study and divided into two treatment arms. In the first treatment arm, SRTF, including 45 Gy radiation to the primary tumor and regional lymph nodes, was performed in 45 patients. In the second treatment arm, a total of 45.2 Gy RT was delivered; 20 Gy to the whole abdomen followed by 25.2 Gy RT to the tumor and regional lymph nodes, in 45 patients. An intravenous bolus dose of 250 mg/m(2)/week 5-fluorouracil (5-FU) was administered concomitantly with RT in both treatment arms. Patients who completed concomitant chemoradiotherapy, received adjuvant treatment, including 4 cycles of 5-FU (425 mg/m(2)) and folinic acid (20 mg/m(2)) in 4 week intervals. RESULTS: Median age was 56 years (range: 22-81), 89% of the patients (n = 80) had serosal involvement, 78% (n = 70) were node positive. The rate of hematological (40% vs. 16%, p = 0.010) and gastrointestinal toxicities (80% vs. 53%, p = 0.010) were higher, and performance loss (60% vs. 29%, p = 0.003) was greater in the second treatment arm. Number of patients who experienced Grade 3 and Grade 4 gastrointestinal toxicities (especially diarrhea) were higher in the second treatment arm (4% vs. 16%, p = 0.049). The median follow-up was 19 months (range: 7-96). The median 5-year survival was 29% and 17%, locoregional control was 30% and 25%, and disease-free survival was 27% and 16% in the first and second treatment arms, respectively. There was no significant difference between the treatment groups in terms of survival, locoregional control and disease-free survival rates (p > 0.05). CONCLUSION: Whole abdomen irradiation was not found to be superior to standard field radiotherapy used in conjunction with adjuvant chemotherapy in gastric cancer.

Effects of Heat Therapy Using a Far Infrared Rays Heating Element for Dysmenorrhea in High School Girls

PURPOSE: The purpose of this study was designed to identify the effects of heat therapy on dysmenorrhea, heat being provided using a far infrared rays heating element. METHODS: The research design for the study was a non-equivalent control group quasi-experimental design. Participants were 22 students for the experimental group, and 26 students for the control group. Data were analyzed using SAS WIN 9.1 program. RESULTS: The experimental group had significantly lower mean scores for menstrual pain, dysmenorrhea, and blood pressure than those in the control group. However, no significant differences were found between two groups for pulse, respiration, and temperature. CONCLUSION: These findings show that thermotherapy was effective for reduction of menstrual pain, dysmenorrhea, and B/P. Therefore, this therapy could be used as a nursing intervention for students with dysmenorrhea.

Prevention and mitigation of acute death of mice after abdominal irradiation by the antioxidant N-acetyl-cysteine (NAC).

Gastrointestinal (GI) injury is a major cause of acute death after total-body exposure to large doses of ionizing radiation, but the cellular and molecular explanations for GI death remain dubious. To address this issue, we developed a murine abdominal irradiation model. Mice were irradiated with a single dose of X rays to the abdomen, treated with daily s.c. injection of N-acetyl-l-cysteine (NAC) or vehicle for 7 days starting either 4 h before or 2 h after irradiation, and monitored for up to 30 days. Separately, mice from each group were assayed 6 days after irradiation for bone marrow reactive oxygen species (ROS), ex vivo colony formation of bone marrow stromal cells, and histological changes in the duodenum. Irradiation of the abdomen caused dose-dependent weight loss and mortality. Radiation-induced acute death was preceded not only by a massive loss of duodenal villi but also, surprisingly, abscopal suppression of stromal cells and elevation of ROS in the nonirradiated bone marrow. NAC diminished these radiation-induced changes and improved 10- and 30-day survival rates to >50% compared with <5% in vehicle-treated controls. Our data establish a central role for abscopal stimulation of bone marrow ROS in acute death in mice after abdominal irradiation.

Berberine inhibits acute radiation intestinal syndrome in human with abdomen radiotherapy.

Radiation-induced acute intestinal symptoms (RIAISs) are the most relevant complication of abdominal or pelvic radiation. Considering the negative impact of RIAIS on patients' daily activities, the preventive effects of berberine on RIAIS in patients were investigated. Thirty-six patients with seminoma or lymphomas were randomized to receive berberine oral (n = 18) or not (n = 18). Forty-two patients with cervical cancer were randomized to a trial group (n = 21) and control group (n = 21). Radiotherapy used a parallel opposed anterior and posterior. 300-mg berberine was administered orally three times daily in trial groups. Eight patients with RIAIS were treated with 300-mg berberine three times daily from the third to the fifth week. Toxicities, such as fatigue, anorexia/nausea, etc., were graded weekly according to CTC version 2.0. Patients with abdominal/pelvic radiation in the control group showed grade 1 fatigue, anorexia/nausea, colitis, vomiting, proctitis, weight loss, diarrhea and grade 2 anorexia/nausea, fatigue. Only grade 1 colitis, anorexia/nausea, and fatigue were seen in patients of abdominal radiation treated with berberine. Grade 1 fatigue, colitis, anorexia/nausea, and proctitis occurred in patients of pelvic radiotherapy treated with berberine. Pretreatment with berberine significantly decreased the incidence and severity of RIAIS in patients with abdominal/pelvic radiotherapy when compared with the patients of the control group (P < 0.05). RIAIS were reduced in patients with abdominal radiotherapy/pelvic radiation after receiving berberine treatment. Berberine significantly reduced the incidence and severity of RIAIS and postponed the occurrence of RIAIS in patients with abdominal or whole pelvic radiation.

Treatment of striae distensae with a TriPollar radiofrequency device: a pilot study.

BACKGROUND: Striae distensae are a frequent skin condition for which treatment remains a challenge. OBJECTIVES: To determine the efficacy and safety of a TriPollar radiofrequency (RF) device for the treatment of striae in skin phototypes IV-V. METHODS: Seventeen females with striae received six weekly treatments with a TriPollar RF device. The participants were evaluated using standardized photographs and a UVA-light video camera at baseline, and at 1 and 6 weeks after the final treatment. Side effects of treatment were recorded at every session. RESULTS: At 1 week after the final treatment, 38.2% and 11.8% of the subjects were assessed to have 25-50% and 51-75% improvement of their striae, respectively. Compared with the 1-week follow-up, at the 6-week follow-up a higher percentage of the subjects were rated to have improvement of their striae. There were no significant differences in the striae surface smoothness at the 1- (p = 0.907) and 6-week (p = 0.057) follow-ups, compared with that of baseline. Twelve percent (2/17), 23% (4/17), and 65% (11/17) of the study subjects rated their satisfaction of the overall improvement as slightly satisfied, satisfied, and very satisfied, respectively. No adverse effect was reported. CONCLUSION: TriPollar RF appears to be a promising alternative for the treatment of striae distensae.

Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.

Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.

Phase I-II pilot of whole abdominal radiation and concomitant 5-FU as an adjuvant in colon cancer: a Southwest Oncology Group Study.

Thirty-eight patients with Stage B2, C1 or C2 colon cancer (Astler-Coller Modification of Dukes) received 3000 rads whole abdominal radiation and concomitant intermittent bolus 5-FU as part of a phase I-II adjuvant trial. Patients whose tumor penetrated the serosa (B2 or C2) in addition received a 1600 rad boost to the tumor bed. 5-FU was administered only during radiation. It was given at a dose of 300 mg/m2 days 1-5 and 28-32 in 21 patients (Group A) and day 1-3 and 28-31 in 17 patients (Group B). Median follow-up time for Group A is 44 months. Group A patients have a disease-free survival of 66% and overall survival of 73% at 44 months. The 16 C2 patients in Group A have a disease-free survival of 54% and overall survival of 65% at 44 months. There was a 26% incidence of moderate to severe acute toxicity in Group A but no long term bowel, liver, or hematologic toxicity. One patient developed acute myelogenous leukemia 2 years after treatment. Group B patients had only a 6% incidence of moderate to severe toxicity, but had a disease-free survival of 60% and overall survival of 100% at median follow-up of 23 months. Group B Stage C2 patients had a disease-free survival of 53% and overall survival of 100% at this same follow-up period. Disease-free and overall survival in Group A Stage C2 patients is superior to that in several published trials. Given the manageable toxicity, adjuvant whole abdominal radiation with concomitant 5-FU and tumor bed boost should be tested in a randomized fashion for possible therapeutic benefits.

Effects of Nd:YAG laser photoradiation on intra-abdominal tissues: a histological study of tissue damage versus power density applied.

Liver, spleen, and pancreas were subjected to laser photoradiation of 50- to 100-Watt power levels. Samples were evaluated by light microscopy at 0 hours and 7, 14, and 21 days. Four zones of cellular damage were visible in liver and pancreas: coagulum, cavitation, acidophilia, and transition. Only the first three zones were clearly visible in the spleen. Mean lateral tissue penetration was 3.1 mm in liver, 3.3 mm in spleen, and 1.0 mm in pancreas. No significant increase in lateral penetration occurred with increasing power. Normal healing was observed in liver and spleen. Pancreatitis was found in all samples at 7 days postoperatively. At power levels of 80 W or less, recovery was observed. Above 80 W, pancreatic pseudocysts and necrosis led to death of the animals.

Adjuvant therapy for Dukes C adenocarcinoma of colon.

Forty-two patients with adenocarcinoma of the colon, who received surgery between 1975 and 1978 and were to found to have pericolonic fat infiltration and lymph node metastases, were analyzed for disease free period and overall survival. Twenty-one patients had received post-operative X ray therapy, and post-X ray therapy intravenous 5-Fluorouracil adjuvant therapy. Twenty-one patients, matched by age, sex, ethnic origin and site of disease were untreated. The 5 year survival rate for the treated group was 65% compared with 36% for the control group (P greater than 0.2). At 5 years 55% of the treated group were disease free but only 12% of the control group remained disease free (P = 0.04). The significance of this work needs to be established by a randomized and prospectively controlled clinical trial.

Nutritional and clinical aspects of parenteral nutrition in pigs irradiated on the abdomen with supralethal doses.

Nutritional balances of nitrogen and minerals (sodium potassium, calcium, phosphorus) were established in 10 pigs of 40 kg receiving a continuous parenteral nutrition supplying a daily amount of 1500 ml containing 1500 kcal and 2.2-5.4 g of protein, and in addition, 2 liters of water per day. The balances were recorded for 5 days in the animals used as controls and for 9 days in those irridated with 1000 rd in the median plane. This dose represents the inferior limit for appearence of the gastrointestinal syndrome in this species. The irradiated subjects seemed to be able to use a relatively high supply of energy and protein. Water and nitrogen balances were easy to obtain with respect to sodium, potassium and calcium, whereas the deficiency in phosphorus was difficult to compensate for through the intravenous route only.