Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial.

PubMed

Han, Gajin; Park, Jae-Woo; Ko, Seok-Jae; Son, Jihee; Seon, Jongki; Kim, Juyeon; Kim, Seulki; Yeo, Inkwon; Ryu, Bongha; Kim, Jinsung

2013-09-03

Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients' quality of life. In traditional Korean medicine, 'Yin-Deficiency' has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve 'Yin-Deficiency', and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that 'Yin-Deficiency' is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and 'Yin-Deficiency'. This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. It will be assessed whether Yukmijihwang-tang can be used as a new herbal treatment for xerostomia in the elderly by

Yukmijihwang-tang for the treatment of xerostomia in the elderly: study protocol for a randomized, double-blind, placebo-controlled, two-center trial

PubMed Central

2013-01-01

Background Xerostomia, a subjective sense of dry mouth, is not generally regarded a disease despite its high prevalence among the elderly, and therefore continues to impair affected patients’ quality of life. In traditional Korean medicine, ‘Yin-Deficiency’ has been implicated in the pathogenesis of xerostomia among the elderly. Yukmijihwang-tang is a famous herbal prescription used to relieve ‘Yin-Deficiency’, and reportedly has antioxidant effects; therefore, it is postulated that Yukmijihwang-tang can be used to treat xerostomia in the elderly. However, to our knowledge, no clinical trial has been conducted on the effects of Yukmijihwang-tang on xerostomia. Thus, we designed a randomized clinical trial to investigate the effects and safety of Yukmijihwang-tang on xerostomia in the elderly. In addition, we will clarify the aforementioned assumption that ‘Yin-Deficiency’ is the major cause of xerostomia in the elderly by identifying a correlation between xerostomia and ‘Yin-Deficiency’. Methods/Design This randomized, double-blind, placebo-controlled trial will be carried out at two centers: Kyung Hee University Korean Medicine Hospital and Kyung Hee University Hospital at Gangdong. We will recruit 96 subjects aged 60-80 years who have experienced xerostomia for 3 months prior to participation. Subjects who present with score >40 on the visual analogue scale for xerostomia and unstimulated salivary flow rate under 0.3mL/min will be included and the randomization will be carried out by an independent statistician by using a random number creation program. The subjects and all researchers except the statistician will be blinded to the group assignment. Yukmijihwang-tang or placebo will be administered to each group for 8 weeks. The primary outcome is change in the scores for the visual analogue scale for xerostomia and the dry mouth symptom questionnaire from 0 to 8 weeks. Discussion It will be assessed whether Yukmijihwang-tang can be used as a

Sham-controlled, randomized, feasibility trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Wu, Caijun; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2013-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients. Quality of life (QOL) is impaired, and available treatments are of little benefit. This trial determined the feasibility of conducting a sham-controlled trial of acupuncture and whether acupuncture could prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A sham controlled, feasibility trial was conducted at Fudan University Shanghai Cancer Center, Shanghai, China among patients with nasopharyngeal carcinoma undergoing radiotherapy. To determine feasibility of a sham procedure, 23 patients were randomized to real acupuncture (N = 11) or to sham acupuncture (N = 12). Patients were treated 3 times/week during their course of radiotherapy. Subjective measures were the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head and Neck Cancer (MDASI-HN). Objective measures were unstimulated whole salivary flow rates (UWSFR) and stimulated salivary flow rates (SSFR). Patients were followed for 1 month after radiotherapy. Results XQ scores for acupuncture were significantly lower than sham controls starting in week 3 and lasted through the 1-month follow-up (all P’s < 0.001 except for week 3, which was 0.006), with clinically significant differences as follows: week 6 – RR 0.28 [95% CI, 0.10, 0.79]; week 11- RR 0.17 [95% CI, 0.03, 1.07]. Similar findings were seen for MDASI-HN scores and MDASI-Intrusion scores. Group differences for UWSFR and SSFR were not found. Conclusions In this small pilot study, true acupuncture given concurrently with radiotherapy significantly reduced xerostomia symptoms and improved QOL when compared with sham acupuncture. Large-scale, multi-center, randomized, placebo-controlled trials are now needed. PMID:22285177

Randomized controlled trial of acupuncture for prevention of radiation-induced xerostomia among patients with nasopharyngeal carcinoma

PubMed Central

Meng, Zhiqiang; Garcia, M. Kay; Hu, Chaosu; Chiang, Joseph; Chambers, Mark; Rosenthal, David I.; Peng, Huiting; Zhang, Ying; Zhao, Qi; Zhao, Genming; Liu, Luming; Spelman, Amy; Palmer, J. Lynn; Wei, Qi; Cohen, Lorenzo

2011-01-01

Background Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients and available treatments are of little benefit. The objective of this trial was to determine if acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy. Methods A randomized, controlled trial among patients with nasopharyngeal carcinoma was conducted comparing acupuncture to standard care. Participants were treated at Fudan University Shanghai Cancer Center, Shanghai, China. Forty patients were randomized to acupuncture treatment and 46 to standard care. Patients were treated 3 times/week on the same days they received radiotherapy. Subjective measures included the Xerostomia Questionnaire (XQ) and MD Anderson Symptom Inventory for Head/Neck (MDASI-HN). Objective measures were unstimulated and stimulated whole salivary flow rates (UWSFR; SSFR). Patients were followed for 6 months after the end of radiotherapy. Results XQ scores for acupuncture were statistically significantly lower than controls starting in week 3 through the 6-months(P=0.003 at week3, all other P’s < 0.0001), with clinically significant differences as follows: week 11- RR 0.63 [95% CI, 0.45, 0.87]; 6 months - RR 0.38 [95% CI, 0.19, 0.76]. Similar findings were seen for MDASI-HN scores. Group differences emerged as early as 3 weeks into treatment for saliva (UWSFR, P = 0.0004), with greater saliva flow in the acupuncture group at week 7 (UWSFR, P < 0.0001; SSFR, P = 0.002) and 11 (UWSFR, P < 0.02; SSFR, P < 0.03) and at 6 months (SSFR, P < 0.003). Conclusions Acupuncture given concurrently with radiotherapy significantly reduced xerostomia and improved QOL. PMID:22072272

Etiology, evaluation, and management of xerostomia.

PubMed

Millsop, Jillian W; Wang, Elizabeth A; Fazel, Nasim

Xerostomia is defined as the complaint of oral dryness. It is a condition that primarily affects older adults and can have a significant negative effect on one's quality of life. Patients with xerostomia often do not have objective signs of hyposalivation. The underlying etiology of xerostomia includes a variety of systemic diseases and local factors. Our aim is to provide a comprehensive review of the differential diagnosis, evaluation, and management of xerostomia. Prompt diagnosis and management can alleviate the clinical manifestations of this debilitating condition. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of xerostomia on the quality of life of adolescents with type 1 diabetes mellitus.

PubMed

Busato, Ivana Maria Saes; Ignácio, Sérgio Aparecido; Brancher, João Armando; Grégio, Ana Maria Trindade; Machado, Maria Angela Naval; Azevedo-Alanis, Luciana Reis

2009-09-01

To evaluate the impact of xerostomia on the quality of life (QOL) of adolescents with type 1 diabetes mellitus (DM1). The sample was comprised of 51 adolescents with DM1. Diabetic status was determined by glycosylated hemoglobin (HbG) and capillary glucose (CG) tests. Poor metabolic control was defined as HbG >8.0% and CG <90 mg/dL or >130 mg/dL. Measurement of salivary flow was performed by means of stimulated saliva collection. Xerostomia was detected by asking a question about the sensation of having "dry mouth," and OHIP-14 was used to measure the impact of xerostomia on QOL. A total of 52.9% of subjects presented with xerostomia and 40.8% with hyposalivation. Significant differences between the subjects with and without xerostomia regarding metabolic control levels were not observed (P > .05). However, OHIP-14 scores were significantly different between the subjects with and without xerostomia (P < .001). Xerostomia is frequent and has a negative impact on QOL of adolescents with DM1.

Systematic literature review: xerostomia in advanced cancer patients.

PubMed

Hanchanale, Sarika; Adkinson, Lucy; Daniel, Sunitha; Fleming, Michelle; Oxberry, Stephen G

2015-03-01

Dry mouth (xerostomia) is one of the commonest symptoms in cancer patients and can adversely affect quality of life. The aim of this review was to determine the effectiveness of pharmacological and non-pharmacological interventions in treating xerostomia in adult advanced cancer patients. The literature search was performed in February 2014 using databases including EMBASE, MEDLINE, CINAHL, BNI and Cochrane library. The search was carried out using standard MeSH terms and was limited to adult population and English language. Studies investigating xerostomia secondary to head and neck cancer treatment and autoimmune disease were excluded. Titles and abstracts were screened and reviewed for eligibility. Only studies involving primary research were included in the analysis. Six studies met the eligibility criteria for review: three randomized controlled trials and three prospective studies. The quality assessment and reporting was performed using PRISMA, Jadad and STROBE. These studies compared acupuncture, pilocarpine, Saliva Orthana and chewing gum with each other or with placebo. All interventions were considered effective in treating xerostomia. However, effectiveness versus placebo could not be demonstrated for Saliva Orthana. Meta-analysis could not be performed due to heterogeneity of the study type and intervention. Limited published data exists reporting the effectiveness of measures in the treatment of xerostomia in cancer patients. Based on primary research of low quality, firm conclusions cannot be drawn. However, pilocarpine, artificial saliva, chewing gum and acupuncture can be tried based on the available data. This highlights the explicit need to improve our evidence base. Properly constructed randomized controlled trials demonstrating effectiveness of pharmacological and non-pharmacological interventions for dry mouth are required.

Xerostomia among older home care clients.

PubMed

Viljakainen, Sari; Nykänen, Irma; Ahonen, Riitta; Komulainen, Kaija; Suominen, Anna Liisa; Hartikainen, Sirpa; Tiihonen, Miia

2016-06-01

The purpose of this study was to examine drug use and other factors associated with xerostomia in home care clients aged 75 years or older. The study sample included 270 home care clients aged ≥75 years living in Eastern and Central Finland. The home care clients underwent in-home interviews carried out by trained home care nurses, nutritionists, dental hygienists and pharmacists. The collected data contained information on sociodemographic factors, health and oral health status, drug use, depressive symptoms (GDS-15), cognitive functioning (MMSE), functional ability (Barthel Index, IADL) and nutrition (MNA). The primary outcome was xerostomia status (never, occasionally or continuously). Among the home care clients, 56% (n = 150) suffered from xerostomia. Persons with continuous xerostomia used more drugs and had more depressive symptoms and a higher number of comorbidities than other home care clients. In multivariate analyses, excessive polypharmacy (OR = 1.83, 95% Cl 1.08-3.10) and depressive symptoms (OR = 1.12, 95% Cl 1.03-1.22) were associated with xerostomia. Xerostomia is a common problem among old home care clients. Excessive polypharmacy, use of particular drug groups and depressive symptoms were associated with xerostomia. The findings support the importance of a multidisciplinary approach in the care of older home care clients. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effectiveness of thyme honey for the management of treatment-induced xerostomia in head and neck cancer patients: A feasibility randomized control trial.

PubMed

Charalambous, Andreas; Lambrinou, Ekaterini; Katodritis, Nicos; Vomvas, Dimitrios; Raftopoulos, Vasilios; Georgiou, Morpho; Paikousis, Lefkios; Charalambous, Melanie

2017-04-01

Radiation-induced xerostomia is one of the most common side effects that head and neck cancer patients experience during and after treatment. Despite the various methods for the prevention and treatment of radiation-induced xerostomia, it remains highly prevalent among patients treated for head and neck cancers negatively influencing their lives. The purpose of this study was to evaluate the effectiveness of thyme honey as a means for managing radiation-induced xerostomia. This was a parallel randomised controlled trial with two equal arms, the experimental arm (thyme honey) and the control arm (saline). 72 head and neck cancer patients receiving radiotherapy or/and chemotherapy or/and surgery were recruited in a specialised cancer centre. Patients in both arms followed the same administration protocol with thyme honey and saline respectively. Identical assessments at baseline, 1 month and 6 months following completion of the intervention were performed in both arms including the National Cancer Institute (NCI) xerostomia scale and the Xerostomia Questionnaire (XQ) additionally to weekly oral clinical assessments. The ClinicalTrials.gov Identifier for this study is NCT01465308. Linear Mixed Models revealed the statistically significant effect of the intervention on xerostomia (F = 8.474 p < 0.001) and overall quality of life (F = 13.158 p < 0.001). Moreover, Generalised Estimating Equations revealed a statistically significant effect on strong and unbearable pain (F = 10.524 p < 0.001) and dysphagia (F = 4.525 p = 0.033). The study has demonstrated the safety and efficacy findings of Thyme honey in head and neck cancer patients for the management of treatment induced xerostomia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Xerostomia and medications among 32-year-olds

PubMed Central

THOMSON, WILLIAM MURRAY; POULTON, RICHIE; BROADBENT, JONATHAN MARK; AL-KUBAISY, SHAIMA

2008-01-01

Objective To describe the prevalence and associations of xerostomia among adults in their early thirties, with particular attention to medication exposure as a putative risk factor. Material and Methods The prevalence and associations of xerostomia were investigated among 32-year-old participants in a long-standing prospective cohort study. Some 950 individuals were assessed at ages 26 and 32 years, with medications being recorded on both occasions. Results The prevalence of xerostomia was 10.0% (with no apparent gender difference), and was significantly higher among those taking antidepressants (odds ratio =4.7), iron supplements (OR =4.1) or narcotic analgesics (OR =2.4). Those taking antidepressants at both ages 26 and 32 years had 22 times the odds of reporting xerostomia. Conclusion Xerostomia may be a problem for a sizeable minority of young adults. PMID:16829502

Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility

PubMed Central

Eidet, Jon R.; Utheim, Tor P.; Ræder, Sten; Lagali, Neil S.; Messelt, Edvard B.; Dartt, Darlene A.

2016-01-01

The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren’s syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as “daily symptoms of dry mouth the last three months” (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients. PMID:27148875

Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum Expressibility.

PubMed

Fostad, Ida G; Eidet, Jon R; Utheim, Tor P; Ræder, Sten; Lagali, Neil S; Messelt, Edvard B; Dartt, Darlene A

2016-01-01

The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren's syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.

A longitudinal study of medication exposure and xerostomia among older people.

PubMed

Murray Thomson, W; Chalmers, Jane M; John Spencer, A; Slade, Gary D; Carter, Knute D

2006-12-01

To describe the incidence of xerostomia among a population of older people over a 6-year period, with particular attention to medications as risk factors. Understanding the natural history of xerostomia requires longitudinal epidemiological research, but only one study has examined changes in xerostomia over time. While medication is a recognised risk factor for dry mouth, the role of particular medication categories continues to be controversial. Older South Australians (aged 60+) underwent an interview and dental examination at baseline, and these assessments were repeated 2, 5 and 11 years afterward. Medication data were collected at baseline, 5 and 11 years. Xerostomia data were collected at 5 and 11 years using the Xerostomia Inventory (XI) and a standard question. Of the 1205 dentate participants assessed at baseline, 669 remained after 5 years, and 246 were assessed at 11 years. Medication prevalence increased over the observation period, such that 94.8% of the cohort were taking at least one medication by 11 years. The prevalence of xerostomia increased from 21.4% to 24.8% between 5 and 11 years (p > 0.05), and the mean XI score increased from 20.0 (SD, 6.7) to 21.5 (SD, 7.9; p < 0.001). Some 14.7% of participants were incident cases of xerostomia, while 11.4% were remitted cases; 10.1% were cases at both 5 and 11 years. After controlling for gender and 'baseline' xerostomia severity (represented by the XI score at 5 years), participants who commenced taking daily aspirin after 5 years had over four times the odds of becoming incident cases, while those who commenced taking a diuretic after 5 years had nearly six times the odds of doing so. While the overall prevalence of xerostomia increased during the observation period, there was considerable instability, with one-quarter of the cohort changing their status. Medication exposure was strongly associated with the incidence of the condition, with recent exposure to diuretics or daily aspirin strongly

Relationship between xerostomia and gingival condition in young adults.

PubMed

Mizutani, S; Ekuni, D; Tomofuji, T; Azuma, T; Kataoka, K; Yamane, M; Iwasaki, Y; Morita, M

2015-02-01

Xerostomia is a subjective symptom of dryness in the mouth. Although a correlation between xerostomia and oral conditions in the elderly has been reported, there are few such studies in the young adults. The aim of this study was to examine the relationship of xerostomia with the gingival condition in university students. A total of 2077 students (1202 male subjects and 875 female subjects), 18-24 years of age, were examined. The disease activity and severity of the gingival condition were assessed as the percentage of teeth with bleeding on probing (%BOP) and the presence of teeth with probing pocket depth of ≥ 4 mm, respectively. Additional information on xerostomia, oral health behaviors, coffee/tea intake and nasal congestion was collected via a questionnaire. Path analysis was used to test pathways from xerostomia to the gingival condition. One-hundred and eighty-three (8.8%) students responded that their mouths frequently or always felt dry. Xerostomia was related to %BOP and dental plaque formation, but was not related to the presence of probing pocket depth ≥ 4 mm. In the structural model, xerostomia was related to dental plaque formation (p < 0.01), and a lower level of dental plaque formation was associated with a lower %BOP. Xerostomia was associated with coffee/tea intake (p < 0.01) and nasal congestion (p < 0.001). Xerostomia was indirectly related to gingival disease activity through the accumulation of dental plaque. Nasal congestion and coffee/tea intake also affected xerostomia. These findings suggest that xerostomia should be considered in screening for gingivitis risk in young adults. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Salivary flow rate and xerostomia in patients with type I and II diabetes mellitus.

PubMed

Hoseini, Amineh; Mirzapour, Ali; Bijani, Ali; Shirzad, Atena

2017-09-01

Diabetes mellitus is one of the most prevalent metabolic diseases, with complications such as decreased salivary flow rate and xerostomia. This study aimed to determine the salivary flow rate and xerostomia in type I and II diabetic patients in comparison with healthy controls. This case-control study was performed on diabetic patients of a private office in Babol, Iran, between May 2015 and October 2016. This study involved two study groups (type I and II diabetes, with 40 in each group) and two control groups (control I and II, with 35 in each group) which were age- and sex-matched with the related study groups. They were all selected through simple sampling. Unstimulated whole saliva was collected through Navazesh method and the salivary flow rate was measured (ml/min). Xerostomia was evaluated via Fox's test. Moreover, the patients' data were recorded including age, sex, disease duration, type of diabetes, fasting blood glucose (FBG) and HbA1C. The obtained data were statistically analyzed by using SPSS version 17. Independent-samples t-test, Chi-square, Pearson correlation and multiple comparison post-hoc tests were employed as appropriated. p<0.05 was considered significant. The mean salivary flow rate in type I diabetics (0.35±0.11 ml/min) was lower than that in control I (0.50±0.07 ml/min) (p=0.01). The same difference was observed between type II diabetics (0.37±0.13 ml/min) and control II groups (0.47±0.11 ml/min) (p=0.01). No significant difference was observed in the salivary flow rate between type I and II diabetics (p=0.345). Furthermore, xerostomia was higher in type I (2.70±2.50, 1.17±1.60) and II (2.65±2.20-1.62±1.50) diabetics compared with the related control groups (p=0.01), (p=0.02). Type I, II diabetic patients revealed lower salivary flow rate and higher xerostomia compared with healthy controls. The salivary flow rate and xerostomia had inverse correlation.

An Evidence-Based Review Literature About Risk Indicators and Management of Unknown-Origin Xerostomia

PubMed Central

Agha-Hosseini, Farzaneh; Moosavi, Mahdieh-Sadat

2013-01-01

This evidence-based article reviews risk indicators and management of unknown-origin xerostomia. Xerostomia and hyposalivation refer to different aspects of dry mouth. Xerostomia is a subjective sensation of dry mouth, whilst hyposalivation is defined as an objective assessment of reduced salivary flow rate. About 30% of the elderly (65 years and older) experience xerostomia and hyposalivation. Structural and functional factors, or both may lead to salivary gland dysfunction. The EBM literature search was conducted by using the medical literature database MEDLINE via PubMed and OvidMedline search engines. Results were limited to English language articles (1965 to present) including clinical trials (CT), randomized controlled trials (RCT), systematic reviews and review articles. Case control or cohort studies were included for the etiology. Neuropathic etiology such as localized oral alteration of thermal sensations, saliva composition change (for example higher levels of K, Cl, Ca, IgA, amylase, calcium, PTH and cortisol), lower levels of estrogen and progesterone, smaller salivary gland size, and illnesses such as lichen planus, are risk indicators for unknown-origin xerostomia. The management is palliative and preventative. Management of symptoms includes drug administration (systemic secretogogues, saliva substitutes and bile secretion-stimulator), night guard, diet and habit modifications. Other managements may be indicated to treat adverse effects. Neuropathic etiology, saliva composition change, smaller salivary gland size, and illnesses such as oral lichen planus can be suggestive causes for unknown-origin xerostomia. However, longitudinal studies will be important to elucidate the causes of unknown-origin xerostomia. PMID:25512755

Close association between oral Candida species and oral mucosal disorders in patients with xerostomia.

PubMed

Shinozaki, S; Moriyama, M; Hayashida, J-N; Tanaka, A; Maehara, T; Ieda, S; Nakamura, S

2012-10-01

Heightened interest in oral health has lead to an increase in patients complaining of xerostomia, which is associated with various oral mucosal disorders. In this study, we investigated the relationship between Candida species and oral mucosal disorders in patients with xerostomia. We evaluated whole salivary flow rate and presence of oral mucosal disorders in 48 patients with xerostomia and 15 healthy controls. The number of Candida species was measured as colony-forming units after propagation on selective medium. Identification of Candida at the species level was carried out by polymerase chain reaction and restriction fragment length polymorphism analysis. We then examined the relationship between Candida species and oral mucosal symptoms. Compared with controls, patients with xerostomia exhibited significantly decreased whole salivary flow rate, increased rate of oral mucosal symptoms, and higher numbers of Candida. Salivary flow rate negatively correlated with the number Candida. Among patients with oral candidiasis, Candida albicans was isolated from the tongue mucosa and Candida glabrata was isolated from the angle of the mouth. These results suggest that particular Candida species are involved in the pathogenesis of oral mucosal disorders in patients with xerostomia. © 2012 John Wiley & Sons A/S.

Prevalence of xerostomia in an adolescent inpatient psychiatric clinic: a preliminary study.

PubMed

Kaur, Manvir; Himadi, Elaine; Chi, Donald L

2016-01-01

Adolescents with psychiatric conditions may be at risk for xerostomia. In this preliminary study, we estimated xerostomia prevalence in adolescents ages 9 to 17 years from an inpatient psychiatric clinic (N = 25) and examined whether: (1) gender and age were associated with xerostomia and (2) xerostomia was associated with self-reported cavities. We used a modified 11-item Xerostomia Index to identify xerostomia (no/yes) and asked if adolescents ever had or currently have cavities (no/yes). The mean age was 14 years (SD = 2.3) and 72% were male. Sixty percent reported xerostomia (SD = 50). There were no significant associations between xerostomia and gender (p = 0.99) or age (p = 0.66), or between xerostomia and past (p = 0.26) or current cavities (p = 0.11). Larger proportions of adolescents with xerostomia reported previous and current cavities. Sixty percent of adolescents from an inpatient psychiatric clinic reported having xerostomia, which may lead to increased caries risk over time. Additional research should examine the prevalence and consequences of xerostomia in high-risk adolescents. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes.

PubMed

Gensheimer, Michael F; Liao, Jay J; Garden, Adam S; Laramore, George E; Parvathaneni, Upendra

2014-11-26

Saliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT). All patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006-2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed. 114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort. cSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients.

Dental patients' self-reports of xerostomia and associated risk factors.

PubMed

Villa, Alessandro; Polimeni, Antonella; Strohmenger, Laura; Cicciù, Domenico; Gherlone, Enrico; Abati, Silvio

2011-07-01

Most studies regarding xerostomia focus on elderly people. Therefore, the authors conducted a study of dental patients 18 years or older to determine the prevalence of self-reported xerostomia and associated risk factors. The authors sent a total of 2,200 questionnaires to four dental clinics to assess patients' self-reported xerostomia. They also collected sociodemographic data and information regarding personal behavior. They used logistic regression models to estimate odds ratios (OR) and 95 percent confidence intervals (CI) to explore the relationship between self-reported xerostomia and risk factors that reasonably might be expected to be associated with self-reported xerostomia. The overall prevalence of xerostomia in participants was 7 percent. Participants with burning-mouth sensations were associated with having higher odds of experiencing dry mouth (OR, 2.1; 95 percent CI, 0.9-5.2). Participants 51 years or older were significantly more likely to report having dry mouth than were younger participants (P < .04). The prevalence of self-reported xerostomia increased with increasing numbers of medications patients reported using. The authors found that medication use and age were highly significant risk factors for dental patients reporting xerostomia. Clinicians should interview their patients carefully regarding their use of medications and provide proper oral health care to improve xerostomia resulting from medication use.

Hyposalivation and xerostomia in dentate older adults

PubMed Central

Wiener, R. Constance; Wu, Bei; Crout, Richard; Wiener, Michael; Plassman, Brenda; Kao, Elizabeth; McNeil, Daniel

2010-01-01

Background Older adults are susceptible to reduced saliva production related to certain medications, radiation and chronic conditions. Many of these people have many physical and oral health problems and limited access to dental care. The use of effective screening tools for xerostomia and hyposalivation would be helpful in identifying those at risk. The authors conducted a study to investigate the association between three measures of oral dryness: hyposalivation (low unstimulated salivary flow), self-reported xerostomia and clinically assessed dry mouth. Methods The authors included a convenience sample of 252 nondemented and dentate West Virginia participants 70 years and older who were part of a larger study on oral health and cognition among older adults. Participants completed a self-reported xerostomia index, provided an unstimulated salivary sample and underwent an oral assessment for the study. Results Twenty-eight (11.1 percent) had hyposalivation, eight of whom reported having xerostomia (sensitivity = 28.6 percent). Of the 43 participants who reported having xerostomia, only eight had hyposalivation (positive predictive value = 18.6 percent). Hyposalivation and self-reported xerostomia were not significantly related. Clinically assessed dry mouth correlated modestly, but significantly, with hyposalivation and self-reported xerostomia. Conclusions Obtaining routine unstimulated salivary flow rates in addition to self-reported information and oral evaluations may increase early detection of oral dryness, which would assist in implementing early interventions to improve patients’ quality of life. Clinical Implications Visually inspecting oral tissues for dryness and asking a patient if his or her mouth is dry are insufficient measures for clinicians to use to determine if the patient has hyposalivation. The authors recommend that clinicians determine the patients’ unstimulated salivary flow rate. PMID:20194383

Natural products for the management of xerostomia: a randomized, double-blinded, placebo-controlled clinical trial.

PubMed

Navarro Morante, Anabel; Wolff, Andy; Bautista Mendoza, Gloria Rocio; López-Jornet, Pia

2017-02-01

The aim of this study was to evaluate the clinical performance of lycopene-enriched virgin olive oil in spray form used to treat patients with drug-induced xerostomia, comparing this with a placebo spray. This double-blind, randomized clinical trial included elderly subjects with drug-induced xerostomia (n = 60). Resting salivary flow was measured using the draining technique. The Xerostomia Inventory (XI) was used to assess symptoms and the Oral Health Impact Profile 14 (OHIP-14) to assess patient quality of life. Evaluations were made before and after 12 weeks of product/placebo application. Sixty patients took part in the study. Symptoms improved among the treatment group (n = 30) after 12 weeks in the following XI domains: 'Rate the difficulty you experience in speaking because of dryness' (P = 0.03); 'Rate how much saliva is in your mouth' (P = 0.03); and 'Rate the dryness of your lips' (P = 0.04). The placebo group (n = 30) underwent improvements in: 'Rate how much saliva is in your mouth' (P = 0.02) and 'Rate the dryness of your mouth' (P = 0.01). A significant improvement (P = 0.001) in oral-related quality of life (OHIP-14) was identified in the treatment group, while no significant differences were observed in the placebo group (P > 0.05). The topical application of lycopene-enriched virgin olive oil and its placebo counterpart improved xerostomia-related symptoms significantly (but not salivary flow rate) in patients with drug-induced xerostomia. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Diagnosis and management of xerostomia and hyposalivation

PubMed Central

Villa, Alessandro; Connell, Christopher L; Abati, Silvio

2015-01-01

Xerostomia, the subjective complaint of dry mouth, and hyposalivation remain a significant burden for many individuals. Diagnosis of xerostomia and salivary gland hypofunction is dependent upon a careful and detailed history and thorough oral examination. There exist many options for treatment and symptom management: salivary stimulants, topical agents, saliva substitutes, and systemic sialogogues. The aim of this review is to investigate the current state of knowledge on management and treatment of patients affected by xerostomia and/or hyposalivation. PMID:25653532

First-in-man mesenchymal stem cells for radiation-induced xerostomia (MESRIX): study protocol for a randomized controlled trial.

PubMed

Grønhøj, Christian; Jensen, David H; Glovinski, Peter V; Jensen, Siri Beier; Bardow, Allan; Oliveri, Roberto S; Specht, Lena; Thomsen, Carsten; Darkner, Sune; Kiss, Katalin; Fischer-Nielsen, Anne; von Buchwald, Christian

2017-03-07

Salivary gland hypofunction and xerostomia are major complications following radiotherapy for head and neck cancer and may lead to debilitating oral disorders and impaired quality of life. Currently, only symptomatic treatment is available. However, mesenchymal stem cell (MSC) therapy has shown promising results in preclinical studies. Objectives are to assess safety and efficacy in a first-in-man trial on adipose-derived MSC therapy (ASC) for radiation-induced xerostomia. This is a single-center, phase I/II, randomized, placebo-controlled, double-blinded clinical trial. A total of 30 patients are randomized in a 1:1 ratio to receive ultrasound-guided, administered ASC or placebo to the submandibular glands. The primary outcome is change in unstimulated whole salivary flow rate. The secondary outcomes are safety, efficacy, change in quality of life, qualitative and quantitative measurements of saliva, as well as submandibular gland size, vascularization, fibrosis, and secretory tissue evaluation based on contrast-induced magnetic resonance imaging (MRI) and core-needle samples. The assessments are performed at baseline (1 month prior to treatment) and 1 and 4 months following investigational intervention. The trial is the first attempt to evaluate the safety and efficacy of adipose-derived MSCs (ASCs) in patients with radiation-induced xerostomia. The results may provide evidence for the effectiveness of ASC in patients with salivary gland hypofunction and xerostomia and deliver valuable information for the design of subsequent trials. EudraCT, Identifier: 2014-004349-29. Registered on 1 April 2015. ClinicalTrials.gov, Identifier: NCT02513238 . First received on 2 July 2015. The trial is prospectively registered.

Salivary flow rate and xerostomia in patients with type I and II diabetes mellitus

PubMed Central

Hoseini, Amineh; Mirzapour, Ali; Bijani, Ali; Shirzad, Atena

2017-01-01

Background Diabetes mellitus is one of the most prevalent metabolic diseases, with complications such as decreased salivary flow rate and xerostomia. Objective This study aimed to determine the salivary flow rate and xerostomia in type I and II diabetic patients in comparison with healthy controls. Methods This case-control study was performed on diabetic patients of a private office in Babol, Iran, between May 2015 and October 2016. This study involved two study groups (type I and II diabetes, with 40 in each group) and two control groups (control I and II, with 35 in each group) which were age- and sex-matched with the related study groups. They were all selected through simple sampling. Unstimulated whole saliva was collected through Navazesh method and the salivary flow rate was measured (ml/min). Xerostomia was evaluated via Fox’s test. Moreover, the patients’ data were recorded including age, sex, disease duration, type of diabetes, fasting blood glucose (FBG) and HbA1C. The obtained data were statistically analyzed by using SPSS version 17. Independent-samples t-test, Chi-square, Pearson correlation and multiple comparison post-hoc tests were employed as appropriated. p<0.05 was considered significant. Results The mean salivary flow rate in type I diabetics (0.35±0.11 ml/min) was lower than that in control I (0.50±0.07 ml/min) (p=0.01). The same difference was observed between type II diabetics (0.37±0.13 ml/min) and control II groups (0.47±0.11 ml/min) (p=0.01). No significant difference was observed in the salivary flow rate between type I and II diabetics (p=0.345). Furthermore, xerostomia was higher in type I (2.70±2.50, 1.17±1.60) and II (2.65±2.20–1.62±1.50) diabetics compared with the related control groups (p=0.01), (p=0.02). Conclusion Type I, II diabetic patients revealed lower salivary flow rate and higher xerostomia compared with healthy controls. The salivary flow rate and xerostomia had inverse correlation. PMID:29038704

Clinical observation of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma: a prospective randomized controlled study of 32 cases

PubMed Central

2014-01-01

Background The aim of this study was to evaluate the clinical efficacy of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Methods Using the randomized controlled clinical research method, 65 patients with nasopharyngeal carcinoma were randomly divided into an experimental group consisting of 32 patients and a control group consisting of 33 patients. The submandibular glands were averted to the submental region in 32 patients with nasopharyngeal carcinoma before they received conventional radiotherapy; a lead block was used to shield the submental region during therapy. Prior to radiotherapy, the function of the submandibular glands was assessed using imaging. Submandibular gland function was measured using 99mTc radionuclide scanning at 60 months after radiotherapy. The data in the questionnaire regarding the degree of xerostomia were investigated and saliva secretion was measured at 3, 6, 12, and 60 months after radiotherapy. In addition, the 5-year survival rate was calculated. Results After follow-up for 3, 6, and 12 months, the incidence of moderate to severe xerostomia was significantly lower in the experimental group than in the control group. The average amount of saliva produced by the experimental and control groups was 1.60 g and 0.68 g, respectively (P < 0.001). After follow-up for 60 months, the uptake and secretion functions of the submandibular glands in the experimental group were found to be significantly higher than in the control group (P < 0.001 and P < 0.001, respectively). The incidence of moderate or severe xerostomia was significantly lower than in the control group (15.4% and 76.9%, respectively; P < 0.001). The 5-year survival rates of the experimental group and the control group were 81.3% and 78.8%, respectively, and there was no significant difference between the two groups (P = 0.806). Conclusions After a 5 year follow-up period involving 32

Clinical observation of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma: a prospective randomized controlled study of 32 cases.

PubMed

Zhang, Xiangmin; Liu, Folin; Lan, Xiaolin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Li, Shaojin

2014-02-21

The aim of this study was to evaluate the clinical efficacy of submandibular gland transfer for the prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Using the randomized controlled clinical research method, 65 patients with nasopharyngeal carcinoma were randomly divided into an experimental group consisting of 32 patients and a control group consisting of 33 patients. The submandibular glands were averted to the submental region in 32 patients with nasopharyngeal carcinoma before they received conventional radiotherapy; a lead block was used to shield the submental region during therapy. Prior to radiotherapy, the function of the submandibular glands was assessed using imaging. Submandibular gland function was measured using 99mTc radionuclide scanning at 60 months after radiotherapy. The data in the questionnaire regarding the degree of xerostomia were investigated and saliva secretion was measured at 3, 6, 12, and 60 months after radiotherapy. In addition, the 5-year survival rate was calculated. After follow-up for 3, 6, and 12 months, the incidence of moderate to severe xerostomia was significantly lower in the experimental group than in the control group. The average amount of saliva produced by the experimental and control groups was 1.60 g and 0.68 g, respectively (P<0.001). After follow-up for 60 months, the uptake and secretion functions of the submandibular glands in the experimental group were found to be significantly higher than in the control group (P<0.001 and P<0.001, respectively). The incidence of moderate or severe xerostomia was significantly lower than in the control group (15.4% and 76.9%, respectively; P<0.001). The 5-year survival rates of the experimental group and the control group were 81.3% and 78.8%, respectively, and there was no significant difference between the two groups (P=0.806). After a 5 year follow-up period involving 32 patients who had their submandibular glands transferred for the prevention of

Xerostomia in the Geriatric Patient: Causes, Oral Manifestations, and Treatment.

PubMed

Ouanounou, Aviv

2016-05-01

Xerostomia, or dry mouth, is common among elderly people and is typically associated with decreased salivary gland function. Causes of xerostomia in the geriatric population have been attributed to the use of medications, chronic disorders, and radiation therapy to the head and neck region. Patients with chronic xerostomia may have multiple oral and dental consequences such as dental caries, periodontal disease, fungal infections, ill-fitting dentures, and taste alterations. Xerostomia can seriously impact quality of life and may alter speech, eating, and swallowing. Current therapeutics for the management of xerostomia are grouped as local and systemic salivary stimulation. This article reviews the main reasons for xerostomia and the complications it causes in the oral cavity. It also discusses the pharmacologic and nonpharmacologic agents used to treat this condition.

Risk factors associated with xerostomia in haemodialysis patients

PubMed Central

López-Pintor, Lucía; Casañas, Elisabeth; de Arriba, Lorenzo; Hernández, Gonzalo

2017-01-01

Background To determine the prevalence of xerostomia and hyposalivation in Haemodialysis (HD) patients, to clarify risk factors, assess patient´s quality of life, and to establish a possible correlation among interdialytic weight gain (IDWG) and xerostomia. Material and Methods This study was performed on a group of 50 HD patients. Data were collected using a questionnaire containing demographic and clinical variables, a visual analogue scale (VAS) for xerostomia, IDWG, and an oral health impact profile questionnaire (OHIP-14). Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. Results A total of 28 HD patients (56%) suffered xerostomia. Dry mouth was associated with hypertension (OR, 5.24; 95% CI, 1.11-24.89) and benzodiazepine consumption (OR, 5.96; 95% CI, 1.05-33.99). The mean xerostomia VAS and OHIP-14 scores were 31.74±14.88 and 24.38±11.98, respectively. No significant correlation was observed between IDWG% and VAS and OHIP total score. Nonetheless, a positive correlation between VAS level of thirst and IDWG% was found (r=0.48 p=0.0001). UWS and SWS means (determined in 30 patients) were 0.16±0.17 and 1.12±0.64, respectively. Decreased values of UWS and SWS were reported in 53.33% and 36.66% of HD patients. Conclusions Xerostomia in HD has a multifactorial aetiology due to accumulative risks as advanced age, systemic disorders, drugs, fluid intake restriction, and salivary parenchymal fibrosis and atrophy. Therefore, it is important to detect possible xerostomia risk factors to treat correctly dry mouth in HD patients and avoid systemic complications. Key words:Haemodialysis patients, xerostomia, salivary flow rate, hyposalivation, interdialytic weight gain, oral health-related quality of life. PMID:28160594

Risk factors associated with xerostomia in haemodialysis patients.

PubMed

López-Pintor, R-M; López-Pintor, L; Casañas, E; de Arriba, L; Hernández, G

2017-03-01

To determine the prevalence of xerostomia and hyposalivation in Haemodialysis (HD) patients, to clarify risk factors, assess patient's quality of life, and to establish a possible correlation among interdialytic weight gain (IDWG) and xerostomia. This study was performed on a group of 50 HD patients. Data were collected using a questionnaire containing demographic and clinical variables, a visual analogue scale (VAS) for xerostomia, IDWG, and an oral health impact profile questionnaire (OHIP-14). Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. A total of 28 HD patients (56%) suffered xerostomia. Dry mouth was associated with hypertension (OR, 5.24; 95% CI, 1.11-24.89) and benzodiazepine consumption (OR, 5.96; 95% CI, 1.05-33.99). The mean xerostomia VAS and OHIP-14 scores were 31.74±14.88 and 24.38±11.98, respectively. No significant correlation was observed between IDWG% and VAS and OHIP total score. Nonetheless, a positive correlation between VAS level of thirst and IDWG% was found (r=0.48 p=0.0001). UWS and SWS means (determined in 30 patients) were 0.16±0.17 and 1.12±0.64, respectively. Decreased values of UWS and SWS were reported in 53.33% and 36.66% of HD patients. Xerostomia in HD has a multifactorial aetiology due to accumulative risks as advanced age, systemic disorders, drugs, fluid intake restriction, and salivary parenchymal fibrosis and atrophy. Therefore, it is important to detect possible xerostomia risk factors to treat correctly dry mouth in HD patients and avoid systemic complications.

Taste function in xerostomia before and after treatment with a saliva substitute containing carboxymethylcellulose.

PubMed

Temmel, Andreas F P; Quint, Christian; Schickinger-Fischer, Bettina; Hummel, Thomas

2005-04-01

The feeling of a dry mouth may affect individual dietary habits, nutritional status, oral hygiene, speech, and gustatory sensitivity. The present study aimed to specifically investigate gustatory function before and after saliva replacement therapy. Whole-mouth gustatory function was assessed in 25 patients suffering from xerostomia (6 male, 19 female; age range 42-82 years) before and after 4 to 6 weeks of saliva replacement therapy using a preparation containing carboxymethylcellulose. The results were compared with those from healthy controls matched for age and sex (6 male, 19 female; age range 42-82 years). Using a whole-mouth test, gustatory function was assessed for sucrose, citric acid, sodium chloride, and caffeine. All subjects detected the four taste qualities at the highest concentration. However, the patients with xerostomia had lower scores in the gustatory test compared with the healthy controls (p < .001). No correlation was found between gustatory scores and the duration or severity of the disorder. Therapy had no effect on measured gustatory function (p = .33); however, saliva replacement led to a significant improvement in other xerostomia-related symptoms (p < .001). This study confirms previous work indicating that xerostomia is accompanied by decreased gustatory sensitivity. Lubricants based on carboxymethylcellulose may have a positive effect on some of the symptoms of xerostomia. However, these "simple" lubricants based on carboxymethylcellulose have little or no effect on whole-mouth gustatory function.

Prevalence of xerostomia in patients attending Shorish dental speciality in Sulaimani city

PubMed Central

2015-01-01

Objectives: The aim of this study was to investigate the prevalence of xerostomia among dental patients and explore the possible risk factors and symptoms associated with this condition. Patient and Methods: The prevalence of xerostomia and its associations were investigated among patients (n=1132) who were visiting the department of oral medicine at shorish dental speciality in sulaimani city. The age range was between 10-79 years. 512 (45.2%) of participants were males and 620 (54.8%) were females. The data collected were age, sex, systemic diseases, medications and habit of smoking. Logistic regression models to estimate odds ratios and 95% confidence intervals were used to investigate the association of xerostomia with age, systemic diseases and medications and Chi Square test was also used to analyze the data. Results: Prevalence of xerostomia was 16.07%. Prevalence of xerostomia was significantly higher among females (19.51%) than males (11.91%) (P=0.001). The most common diseases with the highest prevalence of xerostomia were psychological disorders (57.14%) followed by diabetes mellitus (53.84%), neurological disorders (40%), thyroid disorders (37.5%) and hypertension (36.48%). The most common medication with the highest prevalence of xerostomia was antihistamine (66.66%) followed by psychotherapeutic medications (60%), pain medications (55.88%), endocrinologic agents (51.21%), antidyslipidic agents (50%) and antihypertensive medication (38.98%). Xerostomia was significantly associated with ageing (OR: 1.02, P=0.000), systemic diseases (OR: 2.80, P=0.000) and medications (OR: 5.17, P=0.000). There was a high prevalence of reported symptoms of xerostomia and these symptoms were more prevalent among females, Prevalence of xerostomia was higher in heavy smoker patients (19.48%) than non smoker patients but not significantly (16.14%) (p= 0.44). Conclusions: There was a high prevalence of xerostomia among dental patients; xerostomia was significantly more

[Effects on salivation, xerostomia and halitosis in elders after oral function improvement exercises].

PubMed

Kim, Young Jin; Park, Kyung Min

2012-12-01

The purpose of this study was to investigate effects of Oral Function Improvement Exercises on salivation, xerostomia and halitosis in elderly people. The participants in the study were 48 female community-dwelling elders in D city. The Oral Function Improvement Exercises were given 3 times a week, for a total of 24 times from August to October 2011. Spitting method, Visual Analogue Scale, and halimeter (mBA-21) were used to evaluate the effects of Oral Function Improvement Exercises on salivation, xerostomia, and halitosis. The data were analyzed using χ²-test and t-test with the SPSS program. The experimental group had significantly better salivation, and less xerostomia and halitosis than the control group. The results indicate that Oral Function Improvement Exercises were effective for salivation, xerostomia and halitosis in the elders. Therefore, it was suggested that Oral Function Improvement Exercise are applicable in a community nursing intervention program to improve the quality of life for elders.

Biotechnological advances in neuro-electro-stimulation for the treatment of hyposalivation and xerostomia.

PubMed

Lafaurie, Gloria; Fedele, Stefano; López, Rafael Martín-Granizo; Wolff, Andy; Strietzel, Frank; Porter, Stephen R; Konttinen, Yrjö T

2009-02-01

Treatment of xerostomia is a common clinical challenge in the oral medicine practice. Although some treatments have been used to improve the symptoms of xerostomia, none is completely satisfactory for the patients who suffer of this alteration. In the last years non-pharmacological treatments based on electro-stimulation for the treatment of xerostomia have been developed. This review is aimed at presenting new developments for the treatment of xerostomia, applying neuro-electro-stimulation by miniaturized intra-oral electro-stimulators. These devices increase salivary secretion and improve symptoms of oral dryness. Their effect is obtained by means of stimulation of the lingual nerve, in whose proximity the electrodes of the apparatus are placed. The objective of this mechanism is both to directly stimulate the salivary glands controlled by that nerve and to enhance the salivary reflex. Clinical studies have been carried out that have demonstrated the wetting effect of the method described in this article.

Effectiveness of cevimeline to improve oral health in patients with postradiation xerostomia.

PubMed

Witsell, David L; Stinnett, Sandra; Chambers, Mark S

2012-08-01

We assessed the effectiveness of cevimeline 30 mg 3 times daily in patient-reported oral health (Oral Health Impact Profile [OHIP-49]) and quality of life (QOL) in patients with xerostomia. In our investigator-initiated, multicenter, randomized, double-blind, placebo-controlled study, patients who received >40 Gy of radiation therapy to the head and neck including at least 3 major salivary glands were randomized to cevimeline 30 mg or placebo orally 3 times daily for 6 weeks. Patients had to have grade 1 or 2 xerostomia and be >16 weeks posttreatment. Clinical data were collected and questionnaires administered at baseline and week 6. The primary outcome was change in OHIP-49 total score from baseline to week 6. No statistically significant differences in oral health or QOL were observed. During the 6 weeks of the study, the severity of xerostomia decreased from baseline. Xerostomia is a significant sequela of treatment of head and neck cancer that may improve with time. The role of oral parasympathetic muscarinic secretogogues in alleviating patient symptoms and complaints remains unclear. Copyright © 2012 Wiley Periodicals, Inc.

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

PubMed

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P; Schupak, Karen D; Gelblum, Daphna Y; Wolden, Suzanne L; Rao, Shyam; Lee, Nancy Y

2015-08-01

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; P<0.001), contralateral submandibular gland (45.0 vs. 56.2 Gy; P<0.001), oral cavity (35.9 vs. 45.2 Gy; P<0.001), and contralateral parotid gland (20.0 vs. 24.4 Gy; P<0.001). Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes.

Type 1 diabetes mellitus, xerostomia, and salivary flow rates.

PubMed

Moore, P A; Guggenheimer, J; Etzel, K R; Weyant, R J; Orchard, T

2001-09-01

The Oral Health Science Institute at the University of Pittsburgh has completed a cross-sectional epidemiologic study of 406 subjects with type 1 diabetes and 268 control subjects without diabetes that assessed the associations between oral health and diabetes. This report describes the prevalence of dry-mouth symptoms (xerostomia), the prevalence of hyposalivation in this population, and the possible interrelationships between salivary dysfunction and diabetic complications. The subjects with diabetes were participants in the Pittsburgh Epidemiology of Diabetes Complications study who were enrolled in an oral health substudy. Control subjects were spouses or best friends of participants or persons recruited from the community through advertisements in local newspapers. Assessments of salivary function included self-reported xerostomia measures and quantification of resting and stimulated whole saliva flow rates. Subjects with diabetes reported symptoms of dry mouth more frequently than did control subjects. Salivary flow rates were also impaired in the subjects with diabetes. Regression models of potential predictor variables were created for the 3 self-reported xerostomia measures and 4 salivary flow rate variables. Of the medical diabetic complications studied (ie, retinopathy, peripheral and autonomic neuropathy, nephropathy, and peripheral vascular disease), only neuropathy was found to be associated with xerostomia and decreased salivary flow measures. A report of dry-mouth symptoms was associated with current use of cigarettes, dysgeusia (report of a bad taste), and more frequent snacking behavior. Xerogenic medications and elevated fasting blood glucose concentrations were significantly associated with decreased salivary flow. Resting salivary flow rates less than 0.01 mL/min were associated with a slightly higher prevalence of dental caries. Subjects who reported higher levels of alcohol consumption were less likely to have lower rates of stimulated

Salivary gland transfer to prevent radiation-induced xerostomia: a systematic review and meta-analysis.

PubMed

Sood, Amit J; Fox, Nyssa F; O'Connell, Brendan P; Lovelace, Tiffany L; Nguyen, Shaun A; Sharma, Anand K; Hornig, Joshua D; Day, Terry A

2014-02-01

Salivary gland transfer (SGT) has the potential to prevent radiation-induced xerostomia. We attempt to analyze the efficacy of SGT in prevention of xerostomia and maintenance of salivary flow rates after radiation treatment (XRT). Systematic review and meta-analysis. Primary endpoint was efficacy of SGT in prevention of radiation-induced xerostomia. Secondary endpoint was change from baseline of unstimulated and stimulated salivary flow rates after XRT. Seven articles, accruing data from 12 institutions, met inclusion criteria. In a total of 177 patients at mean follow-up of 22.7months, SGT prevented radiation-induced xerostomia in 82.7% (95% CI, 76.6-87.7%) of patients. Twelve months after XRT, unstimulated and stimulated salivary flow rates rose to 88% and 76% of baseline values, respectively. In comparison to control subjects twelve months after XRT, SGT subjects' unstimulated (75% vs. 11%) and stimulated (86% vs. 8%) salivary flow rates were drastically higher in SGT patients. Salivary gland transfer appears to be highly effective in preventing the incidence of xerostomia in patients receiving definitive head and neck radiation therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

A risk prediction model for xerostomia: a retrospective cohort study.

PubMed

Villa, Alessandro; Nordio, Francesco; Gohel, Anita

2016-12-01

We investigated the prevalence of xerostomia in dental patients and built a xerostomia risk prediction model by incorporating a wide range of risk factors. Socio-demographic data, past medical history, self-reported dry mouth and related symptoms were collected retrospectively from January 2010 to September 2013 for all new dental patients. A logistic regression framework was used to build a risk prediction model for xerostomia. External validation was performed using an independent data set to test the prediction power. A total of 12 682 patients were included in this analysis (54.3%, females). Xerostomia was reported by 12.2% of patients. The proportion of people reporting xerostomia was higher among those who were taking more medications (OR = 1.11, 95% CI = 1.08-1.13) or recreational drug users (OR = 1.4, 95% CI = 1.1-1.9). Rheumatic diseases (OR = 2.17, 95% CI = 1.88-2.51), psychiatric diseases (OR = 2.34, 95% CI = 2.05-2.68), eating disorders (OR = 2.28, 95% CI = 1.55-3.36) and radiotherapy (OR = 2.00, 95% CI = 1.43-2.80) were good predictors of xerostomia. For the test model performance, the ROC-AUC was 0.816 and in the external validation sample, the ROC-AUC was 0.799. The xerostomia risk prediction model had high accuracy and discriminated between high- and low-risk individuals. Clinicians could use this model to identify the classes of medications and systemic diseases associated with xerostomia. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Evaluation of Xerostomia and salivary flow rate in Hashimoto’s Thyroiditis

PubMed Central

Shirzad, Nooshin; Moosavi, Mahdieh-Sadat

2016-01-01

Background One of the most common causes of hypothyroidism is Hashimoto´s Thyroiditis (HT). Early detection of dry mouth is critical in preserving and promoting systemic and oral health. In this study we have assessed, for the first time, salivary function and xerostomia in HT patients who have not been involved with Sjögren´s syndrome. Material and Methods HT was diagnosed in 40 patients based on clinical findings and positive anti-thyroid peroxidase antibodies (anti-TPO). Controls, matched by sex, age and body mass index (BMI), and with no history of thyroid disease, were selected. A questionnaire was used for diagnosis of xerostomia. Saliva samples were taken between 8 a.m. and 9 a.m., and at least 2 hours after the last intake of food or drink. The flow rate was calculated in milliliters per minute. Results Xerostomia was significantly higher in patients with HT. Unstimulated salivary flow rate was significantly lower in the HT group. Stimulated salivary flow rate was lower in HT group, but the difference was not significant. Conclusions The patients with HT experienced xerostomia, and their salivary flow rate was diminished. Spitting the saliva then assessing salivary flow rate based on milliliter per minute is non-invasive, fast, and simple for chair-side diagnosis of dry mouth. Autoimmune diseases can be accompanied by salivary gland dysfunction. This may be due to the effect of cytokines in the autoimmune process or because of thyroid hormone dysfunctions. Key words:Thyroid, salivary gland, xerostomia. PMID:26595829

Xerostomia of Various Etiologies: A Review of the Literature.

PubMed

Tanasiewicz, Marta; Hildebrandt, Tomasz; Obersztyn, Izabela

2016-01-01

This paper presents the etiopathogenesis, symptomatology, evaluation and treatment of mouth dryness. Xerostomia affects 1-29% of the population, mostly women. It is observed in geriatric patients and in individuals using certain medications, those subjected to radiotherapy of the head and neck region or affected with autoimmune conditions. The main signs of xerostomia include the impression of a dry mouth, problems with food ingestion and dryness of the oral mucosa and skin. Evaluation is based on structured interviews (the Fox test) and determinations of unstimulated and stimulated salivary volume. The signs of xerostomia can be attenuated with saliva substitutes, cevimeline or malic acid. Only palliative treatment of this condition is available at present. Untreated xerostomia significantly impairs the quality of life, which can potentially lead to depression.

Xerostomia Among Older Adults With Low Income: Nuisance or Warning?

PubMed

Lee, Young-Shin; Kim, Hee-Gerl; Moreno, Kim

2016-01-01

The purpose of this study was to identify the prevalence of xerostomia and related factors among low-income older adults in South Korea. A cross-sectional, population-based study. Using data from the Home Healthcare Service Project, a population-based interview survey with home healthcare service, a total of 9,840 adults 65 years of age and older were assessed for the presence of xerostomia in association with aspects of health lifestyles, chronic disease, oral conditions, and oral function. Overall, 40% of participants reported experiencing xerostomia. Multivariate regression analysis indicated xerostomia was more likely to be reported by women having symptoms of gingival bleeding/pain, having difficulty swallowing liquid or chewing solid food, and having multiple chronic diseases. Interestingly, older adults who live alone and drink alcohol (two or more times per week) reported fewer problems with xerostomia. Increased focus on the detrimental health consequences of xerostomia would make treatment a higher priority. Improved assessment of at-risk populations, particularly among the elderly, could lead to earlier preventative interventions, lessening the negative impact on quality of life. Health professionals along with the general public need increased knowledge about the detrimental effects of xerostomia on overall health. There is a need for earlier assessment and treatment to facilitate optimal health promotion and disease prevention. © 2015 Sigma Theta Tau International.

Risk factors and symptoms associated with xerostomia: a cross-sectional study.

PubMed

Villa, A; Abati, S

2011-09-01

The aim of this study was to examine the symptoms and risk factors associated with self-reported xerostomia. Data were collected from 601 self-administered questionnaires among dental clinic attendees. Logistic regression models to estimate odds ratios and 95% confidence intervals were used to investigate the association for exposures of interest, such as socio-demographic characteristics, self-reported symptoms, oral hygiene habits and xerostomia. Participants reported having dry mouth in 19.6% of cases. Xerostomia was associated with a significant increase in the odds of having dry lips, throat, eye, skin and nose. Patients with self-reported xerostomia were three times more likely to drink water to swallow food than were patients without xerstomia. Older individuals were significantly more likely to report dry mouth, and the prevalence of xerostomia increased with advancing age. The prevalence of xerostomia in patients taking one or more drugs was significantly higher compared to medication-free patients, and increased with increasing numbers of medications used. Finally, individuals with a nervous or mental disorder, or who wore removable dentures were five times more likely to develop xerostomia than patients without disorder or dentures. Dentists should be familiar with the symptoms of xerostomia and be prepared to take an active role in the diagnosis, management and treatment of the oral complications. © 2011 Australian Dental Association.

Xerostomia: a day and night difference.

PubMed

Dijkema, Tim; Raaijmakers, Cornelis P J; Braam, Pètra M; Roesink, Judith M; Monninkhof, Evelyn M; Terhaard, Chris H J

2012-08-01

To compare patient-reported xerostomia during daytime and during nighttime with objectively measured parotid and submandibular gland function in a cohort of head-and-neck cancer (HNC) patients treated with RT. A cohort of 138 HNC patients underwent objective measurements of parotid (PF) and submandibular (SMF) gland function and completed a xerostomia questionnaire (XQ) before RT, at 6 weeks, 6 months and 1 year after RT. No attempt was made to spare the submandibular gland(s). The XQ contained specific questions concerning the sensation of dry mouth during day- (XD) and nighttime (XN), scored on a 5-point Likert scale. Patients with no or mild (grade 1-3) xerostomia and patients with more severe (grade 4-5) complaints were grouped together. Before RT, no association existed between dry mouth complaints and PF or SMF. At 6 weeks, 6 months and 1 year after RT; 37%, 51% and 36% had grade 4-5 XD and 65%, 64% and 56% had grade 4-5 XN, respectively. Patients with grade 4-5 XD and XN had significantly worse SMF at all time points after RT compared to patients with grade 1-3 XD and XN, while PF was significantly worse only at 6 weeks after RT. In multivariate analyses, SMF was consistently the most important factor related to XN after treatment. PF significantly influenced XD at 6 weeks and 1 year after RT. Differentiating between complaints during day- and nighttime in xerostomia research is necessary. Dry mouth at night is a frequent problem after (parotid-sparing) RT for HNC and is explained by submandibular gland dysfunction. Sparing of the contralateral submandibular gland, in addition to parotid gland sparing, may result in improved patient-reported xerostomia. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

An evaluation of the effect of acupuncture on salivary pH and the Xerostomia Inventory score innasopharyngeal carcinoma patients with chemoradiation-induced xerostomia

NASA Astrophysics Data System (ADS)

Mihardja, H.; Susworo, R.; Srilestari, A.; Umri, H.

2017-08-01

Radiation-induced xerostomia is a distressing side-effect of radiation for nasopharyngeal carcinoma (NPC) treatment, commonly occurring in almost 100% of patients who undergo this procedure. It has been proposed that acupuncture can be used to treat radiation-induced xerostomia. To the best of our knowledge, the current study constitutes the first acupuncture research that has been conducted in Indonesia on xerostomia following chemo-irradiation in NPC patients. Twenty-five patients with xerostomia due tochemo-irradiation for NPC were divided randomly into three groups of auriculopuncture (group A), body acupuncture (group B), and combination acupuncture (group C). The subjects were evaluated according to Xerostomia Inventory scores before and after six and 12 acupuncture treatments. Salivary pH was determined before and after the 12th acupuncture treatment using a saliva check buffer kit. The success rate of acupuncture therapy in group A was 71-100%, 68-89% ingroup B, and 89-100% in group C (p > 0.050). The mean salivary pH increased after therapy from 6.18±0.60 to 6.83±4.48 in group A, from 6.16±0.54 to 6.67±2.26 in group B, and from 6.00±0.40 to 6.60±2.23 in group C (p > 0.050). After the 12th acupuncture therapy session, the mean Xerostomia Inventory score decreased from 35.70±5.14 prior to acupuncture therapy to 22.89±16.15 after it in group A, with corresponding decreases of 34.70±7.77 to 20.89±10.06 in group B, and of 36.70±5.25 to 21.44±8.97 in group C (p > 0.050). Auriculopuncture, body acupuncture, and combination acupuncture had the same effect of increasing salivary pH and decreasing the Xerostomia Inventory score in patients with xerostomia following chemo irradiation for NPC.

Evaluation of Xerostomia and salivary flow rate in Hashimoto's Thyroiditis.

PubMed

Agha-Hosseini, Farzaneh; Shirzad, Nooshin; Moosavi, Mahdieh-Sadat

2016-01-01

One of the most common causes of hypothyroidism is Hashimoto's Thyroiditis (HT). Early detection of dry mouth is critical in preserving and promoting systemic and oral health. In this study we have assessed, for the first time, salivary function and xerostomia in HT patients who have not been involved with Sjögren's syndrome. HT was diagnosed in 40 patients based on clinical findings and positive anti-thyroid peroxidase antibodies (anti-TPO). Controls, matched by sex, age and body mass index (BMI), and with no history of thyroid disease, were selected. A questionnaire was used for diagnosis of xerostomia. Saliva samples were taken between 8 a.m. and 9 a.m., and at least 2 hours after the last intake of food or drink. The flow rate was calculated in milliliters per minute. Xerostomia was significantly higher in patients with HT. Unstimulated salivary flow rate was significantly lower in the HT group. Stimulated salivary flow rate was lower in HT group, but the difference was not significant. The patients with HT experienced xerostomia, and their salivary flow rate was diminished. Spitting the saliva then assessing salivary flow rate based on milliliter per minute is non-invasive, fast, and simple for chair-side diagnosis of dry mouth. Autoimmune diseases can be accompanied by salivary gland dysfunction. This may be due to the effect of cytokines in the autoimmune process or because of thyroid hormone dysfunctions.

Sparing Bilateral Neck Level IB in Oropharyngeal Carcinoma and Xerostomia Outcomes

PubMed Central

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P.; Schupak, Karen D.; Gelblum, Daphna Y.; Wolden, Suzanne L.; Rao, Shyam; Lee, Nancy Y.

2017-01-01

Objectives To assess whether sparing neck level IB in target delineation of node positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising local-regional control (LRC). Methods 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between 5/10 and 12/11. 74% of patients had T1-2 disease, 26% T3-4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) vs. no sparing (the treated cohort). Sparing of contralateral high level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. Results The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 months). No local-regional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P = 0.021) and observer-rated xerostomia scores (P = 0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (SMG; 63.9 Gy vs. 70.5 Gy; P < 0.001), contralateral SMG (45.0 Gy vs. 56.2 Gy; P < 0.001), oral cavity (35.9 Gy vs. 45.2 Gy; P < 0.001), and contralateral parotid gland (20.0 Gy vs. 24.4 Gy; P < 0.001). Conclusions Target delineation sparing of bilateral level IB nodes in N+ OPC reduced mean doses to salivary organs without compromising LRC. Patients with reduced target volumes had better patient-reported xerostomia outcomes. PMID:26208401

Randomized Trial of Vitamin C/E Complex for Prevention of Radiation-Induced Xerostomia in Patients with Head and Neck Cancer.

PubMed

Chung, Man Ki; Kim, Do Hun; Ahn, Yong Chan; Choi, Joon Young; Kim, Eun Hye; Son, Young-Ik

2016-09-01

The present study was conducted to determine the preventive efficacy of vitamin C/E complex supplementation for radiotherapy (RT)-induced xerostomia in patients with head and neck cancer. Prospective, double-blinded, randomized, placebo-controlled study. A single tertiary referral institution. The trial group (n = 25) received antioxidant supplements (100 IU of vitamin E + 500 mg of vitamin C) twice per day during RT, while the control group (n = 20) received an identical placebo. Pre-RT and 1 and 6 months post-RT, patient-reported xerostomia questionnaires, observer-rated xerostomia score, and salivary scintigraphy were serially obtained to compare xerostomia severity between the 2 groups. The trial group showed greater improvements in xerostomia questionnaire and score at 6 months post-RT when compared with those at 1 month post-RT (P = .007 and .008, respectively). In contrast, the control group showed no changes between 1 and 6 months post-RT. By salivary scintigraphy, there was no difference in maximal accumulation or ejection fraction between the 2 groups. However, the trial group maintained significantly better oral indices at the prestimulatory (P = .01) and poststimulatory (P = .009) stages at 1 month post-RT, compared with the control group. At the final follow-up, there was no difference in overall survival and disease-free survival between the 2 groups. Our data suggest that short-term supplementation with an antioxidant vitamin E/C complex exerts a protective effect against RT-induced xerostomia. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Relationship between xerostomia and salivary flow rates in HIV-infected individuals.

PubMed

Nittayananta, Wipawee; Chanowanna, Nilnara; Pruphetkaew, Nannapat; Nauntofte, Birgitte

2013-08-01

The aim of the present study was to determine the relationship between self-reported xerostomia and salivary flow rates among HIV-infected individuals. A cross-sectional study was performed on 173 individuals (81 HIV-infected individuals, mean age: 32 years, and 92 non-HIV controls, mean age: 30 years). Subjective complaints of dry mouth, based on a self-report of xerostomia questions, and dry mouth, based on a visual analogue scale (VAS), were recorded along with measurements of salivary flow rate of both unstimulated and wax-stimulated whole saliva. The relationship between subjective responses to the xerostomia questions, the VAS of dry mouth, and objective measurements of salivary flow rates were analyzed. Responses to the questions--Do you carry water or a saliva substitute? and Have you had taste disturbance?--were significantly different between HIV-infected and non-HIV individuals (P < 0.05). Individuals' responses to questions concerning dry mouth were significantly correlated with a low unstimulated salivary flow rate. A significant correlation between the VAS of dry mouth and salivary flow rates was observed (P = 0.023). Responses to self-reported xerostomia questions reflects low unstimulated salivary flow rates. Thus, questions concerning dry mouth might be useful tools to identify HIV-infected individuals with hyposalivation, especially at a resting stage. © 2013 Wiley Publishing Asia Pty Ltd.

Outcomes and xerostomia after postoperative radiotherapy for oral and oropharyngeal carcinoma.

PubMed

Wang, Zhong-He; Yan, Chao; Zhang, Zhi-Yuan; Zhang, Chen-Ping; Hu, Hai-Sheng; Tu, Wen-Yong; Kirwan, Jessica; Mendenhall, William M

2014-10-01

We compared outcomes and xerostomia grade after postoperative intensity-modulated radiation therapy (IMRT) and conventional radiotherapy (RT) in patients with oral and oropharyngeal carcinoma. Eighty-eight patients with oral cavity (n = 77) and oropharyngeal (n = 11) carcinoma underwent postoperative IMRT (n = 44) or conventional RT (n = 44). Outcomes, failure patterns, volume, doses, salivary gland V30, and xerostomia grade were evaluated. The median follow-up was 53 months (range, 48-58 months). The median interval from surgery to RT was 4 weeks (range, 3-6 weeks). Twenty-one patients (7 and 14 for the IMRT and conventional RT groups, respectively) experienced local-regional failure. For the IMRT group, all 7 local-regional failures occurred in the high-dose target volumes. For the conventional RT group, there were 12 in-field failures, 1 at the margin, and 1 out-of-field. Nine patients experienced distant failure (5 and 4 for the IMRT and conventional RT groups, respectively). The 4-year local-regional control, disease-free survival (DFS), overall survival (OS), and distant-metastasis rates for the IMRT and conventional RT groups were 84.1% versus 68.2% (p = .055), 68.2% versus 52.3% (p = .091), 70.5% versus 56.8% (p = .124), and 11.4% versus 9.1% (p = .927), respectively. Xerostomia grade after RT was lower for IMRT compared to conventional RT (p < .001). Postoperative IMRT for oral and oropharyngeal carcinoma significantly improves mean dose, salivary gland V30, and xerostomia grade when compared to conventional RT. The predominant failure pattern was local. No differences were found in survival outcomes between both groups. There was a marginal difference in local-regional control. © 2014 Wiley Periodicals, Inc.

Chewing gum and a saliva substitute alleviate thirst and xerostomia in patients on haemodialysis.

PubMed

Bots, Casper P; Brand, Henk S; Veerman, Enno C I; Korevaar, Johanna C; Valentijn-Benz, Marianne; Bezemer, Pieter D; Valentijn, Robert M; Vos, Pieter F; Bijlsma, Joost A; ter Wee, Piet M; Van Amerongen, Barbara M; Nieuw Amerongen, Arie V

2005-03-01

Most patients on haemodialysis (HD) have to maintain a fluid-restricted diet to prevent a high interdialytic weight gain (IWG). The prevalence of xerostomia (the feeling of a dry mouth) is higher in HD patients than in controls. Recently, we demonstrated that xerostomia and thirst were positively correlated with IWG in HD patients. Thus, this may play a role as a stimulus for fluid intake between dialysis sessions. The aim of the present study was to investigate the effect of chewing gum or a saliva substitute on xerostomia, thirst and IWG. This study was a randomized two-treatment crossover design with repeated measures. After the use of chewing gum or saliva substitute for 2 weeks, a wash-out period of 2 weeks was introduced and hereafter the other regimen was carried out. Xerostomia and thirst were assessed by validated questionnaires as xerostomia inventory (XI) and dialysis thirst inventory (DTI), at baseline and after each treatment period, as were IWG and salivary flow rates. Sixty-five HD patients (42 men, 54.6+/-14.1 years; 23 women, 54.7+/-16.3 years) participated in this study. Chewing gum decreased XI from 29.9+/-9.5 to 28.1+/-9.1 (P<0.05). Chewing gum as well as a saliva substitute reduced DTI significantly (P<0.05), but no differences occurred for the average IWG or salivary flow rates. The use of chewing gum and, to a lesser extent, a saliva substitute may alleviate thirst and xerostomia in some HD patients.

Parotid gland mean dose as a xerostomia predictor in low-dose domains.

PubMed

Gabryś, Hubert Szymon; Buettner, Florian; Sterzing, Florian; Hauswald, Henrik; Bangert, Mark

2017-09-01

Xerostomia is a common side effect of radiotherapy resulting from excessive irradiation of salivary glands. Typically, xerostomia is modeled by the mean dose-response characteristic of parotid glands and prevented by mean dose constraints to either contralateral or both parotid glands. The aim of this study was to investigate whether normal tissue complication probability (NTCP) models based on the mean radiation dose to parotid glands are suitable for the prediction of xerostomia in a highly conformal low-dose regime of modern intensity-modulated radiotherapy (IMRT) techniques. We present a retrospective analysis of 153 head and neck cancer patients treated with radiotherapy. The Lyman Kutcher Burman (LKB) model was used to evaluate predictive power of the parotid gland mean dose with respect to xerostomia at 6 and 12 months after the treatment. The predictive performance of the model was evaluated by receiver operating characteristic (ROC) curves and precision-recall (PR) curves. Average mean doses to ipsilateral and contralateral parotid glands were 25.4 Gy and 18.7 Gy, respectively. QUANTEC constraints were met in 74% of patients. Mild to severe (G1+) xerostomia prevalence at both 6 and 12 months was 67%. Moderate to severe (G2+) xerostomia prevalence at 6 and 12 months was 20% and 15%, respectively. G1 + xerostomia was predicted reasonably well with area under the ROC curve ranging from 0.69 to 0.76. The LKB model failed to provide reliable G2 + xerostomia predictions at both time points. Reduction of the mean dose to parotid glands below QUANTEC guidelines resulted in low G2 + xerostomia rates. In this dose domain, the mean dose models predicted G1 + xerostomia fairly well, however, failed to recognize patients at risk of G2 + xerostomia. There is a need for the development of more flexible models able to capture complexity of dose response in this dose regime.

Impact of head and neck cancer adaptive radiotherapy to spare the parotid glands and decrease the risk of xerostomia.

PubMed

Castelli, Joel; Simon, Antoine; Louvel, Guillaume; Henry, Olivier; Chajon, Enrique; Nassef, Mohamed; Haigron, Pascal; Cazoulat, Guillaume; Ospina, Juan David; Jegoux, Franck; Benezery, Karen; de Crevoisier, Renaud

2015-01-09

Large anatomical variations occur during the course of intensity-modulated radiation therapy (IMRT) for locally advanced head and neck cancer (LAHNC). The risks are therefore a parotid glands (PG) overdose and a xerostomia increase. The purposes of the study were to estimate: - the PG overdose and the xerostomia risk increase during a "standard" IMRT (IMRTstd); - the benefits of an adaptive IMRT (ART) with weekly replanning to spare the PGs and limit the risk of xerostomia. Fifteen patients received radical IMRT (70 Gy) for LAHNC. Weekly CTs were used to estimate the dose distributions delivered during the treatment, corresponding either to the initial planning (IMRTstd) or to weekly replanning (ART). PGs dose were recalculated at the fraction, from the weekly CTs. PG cumulated doses were then estimated using deformable image registration. The following PG doses were compared: pre-treatment planned dose, per-treatment IMRTstd and ART. The corresponding estimated risks of xerostomia were also compared. Correlations between anatomical markers and dose differences were searched. Compared to the initial planning, a PG overdose was observed during IMRTstd for 59% of the PGs, with an average increase of 3.7 Gy (10.0 Gy maximum) for the mean dose, and of 8.2% (23.9% maximum) for the risk of xerostomia. Compared to the initial planning, weekly replanning reduced the PG mean dose for all the patients (p<0.05). In the overirradiated PG group, weekly replanning reduced the mean dose by 5.1 Gy (12.2 Gy maximum) and the absolute risk of xerostomia by 11% (p<0.01) (30% maximum). The PG overdose and the dosimetric benefit of replanning increased with the tumor shrinkage and the neck thickness reduction (p<0.001). During the course of LAHNC IMRT, around 60% of the PGs are overdosed of 4 Gy. Weekly replanning decreased the PG mean dose by 5 Gy, and therefore by 11% the xerostomia risk.

Dry mouth: Xerostomia and salivary gland hypofunction.

PubMed

Frydrych, Agnieszka M

2016-07-01

Mouth dryness may present as salivary gland hypofunction (SGH), xerostomia or both. It is considered one of the most underappreciated, underdiagnosed and undermanaged oral health conditions. Despite its common presentation and adverse impact on life quality, it is also generally poorly understood. Increased awareness of the condition is important in addressing these problems. This article discusses SGH and xerostomia, and the associated intra-oral and extra-oral implications. It also summarises currently available management approaches and the evidence behind them. SGH and xerostomia are complex problems. None of the currently available management approaches are entirely satisfactory. Addressing the causative or contributing factors is therefore paramount. While oral health complaints are generally left up to the dental professional to manage, the nature of mouth dryness necessitates increased dialogue between the dental and 
medical professions to ensure optimal patient care.

Assessment of radiation-induced xerostomia: validation of the Italian version of the xerostomia questionnaire in head and neck cancer patients.

PubMed

Pellegrino, Federica; Groff, Elena; Bastiani, Luca; Fattori, Bruno; Sotti, Guido

2015-04-01

Xerostomia is the most common acute and late side effect of radiation treatment for head and neck cancer. Affecting taste perception, chewing, swallowing and speech, xerostomia is also the major cause of decreased quality of life. The aims of this study were to validate the Italian translation of the self-reported eight-item xerostomia questionnaire (XQ) and determine its psychometric properties in patients treated with radiotherapy for head and neck cancer. An observational cross-sectional study was conducted in the Radiotherapy Unit of the Veneto Institute of Oncology - IOV in Padua. The XQ was translated according to international guidelines and filled out by 102 patients. Construct validity was assessed using principal component analysis, internal consistency using Cronbach's α coefficient and test-retest reliability at 1-month interval using the intraclass correlation coefficient (ICC). Criterion-related validity was evaluated to compare the Italian version of XQ with the European Organization for Research and Treatment of Cancer (EORTC) Core Quality-of-Life Questionnaire (QLQ-C30) and its Head and Neck Cancer Module (QLQ-H&N35). Cronbach's α for the Italian version of XQ was strong at α = 0.93, test-retest reliability was also strong (0.79) and factor analysis confirmed that the questionnaire was one-dimensional. Criterion-related validity was excellent with high association with the EORTC QLQ-H&N35 xerostomia and sticky saliva scales. The Italian version of XQ has excellent psychometric properties and can be used to evaluate the impact of emerging radiation delivery techniques aiming at preventing xerostomia.

Xerostomia and medication: a cross-sectional study in long-term geriatric wards.

PubMed

Desoutter, A; Soudain-Pineau, M; Munsch, F; Mauprivez, C; Dufour, T; Coeuriot, J-L

2012-01-01

The purpose of this study was to determine the prevalence of xerostomia in old people living in long-term geriatric wards, and to measure the relationship between xerostomia and etiologic factors such as age and medication (total number of medications, xerogenic medications, anticholinergic medications and medications that induce hypersialorrhea). An observational retrospective, comparative, multicentre epidemiological study. Long-term geriatric wards, in Reims, France. 769 old people living in long-term geriatric wards. Prevalence of xerostomia assessed from age, total number of medications, xerogenic medications, anticholinergic medications and those that induce hypersialorrhea. Multivariable logistic regression was used to calculate Odds Ratios (OR) and their 95% Confidence Intervals (95% CI). Among 769 old people (average age 84.6±8.4 years old), 287 residents suffered from xerostomia (37.3%). Significant predictors of xerostomia were: resident's age OR=1.56, 95% CI (1.30-1.88), p<0.0001 and anticholinergic medications OR=1.35, 95% CI (1.05-1.73), p=0.02. The only protective factor against xerostomia identified was medications that induce hypersialorrhea OR=0.81, 95% CI (0.67-0.98), p=0.03. The total number of medications and xerogenic medications did not play a significant role in xerostomia. Increasing Age and anticholinergic medications induce a dry mouth. Conversely, the total number of medications and xerogenic medications do not influence xerostomia. Medications that induce hypersialorrhea protect against the occurrence of dry mouth.

Effect of low-level laser therapy on radiotherapy-induced hyposalivation and xerostomia: a pilot study.

PubMed

Saleh, Jamil; Figueiredo, Maria Antonia Zancanaro; Cherubini, Karen; Braga-Filho, Aroldo; Salum, Fernanda Gonçalves

2014-10-01

The present pilot study aimed to assess the effect of low-level laser therapy (LLLT) on hyposalivation and xerostomia as a consequence of head and neck radiotherapy. The benefits of LLLT in salivary flow have been shown; however, there are no studies investigating its effects on patients who have already undergone radiotherapy and present hyposalivation and xerostomia as a sequela. Twenty-three patients with a history of head and neck malignancy, who were treated by fractioned teletherapy (dosimetry ranging from 45 to 70 Gy) in the cervicofacial region were selected. They all presented with xerostomia and severe hyposalivation. Patients were randomly distributed into a laser group (n=12) and a control group (n=11). A GaAlAs laser (830 nm, 100 mW, illuminated area 0.028 cm2, 3.57 W/cm2, 20 sec, 2.0 J, 71 J/cm2) was used punctually in the major salivary glands, twice a week for 6 weeks, with a 12 session total. Stimulated and unstimulated salivary flow rate (SFR) were assessed, as well as the xerostomia and quality of life related to oral health (QLROH). The analysis did not show any significant difference between the groups with regards to the SFR and xerostomia, and the QLROH. However, at the end of the treatment, the xerostomia and the QLROH showed significant improvement in both groups compared with assessments performed at baseline, highlighting the importance of advice given to the irradiated patients, and their follow-up. With the parameters used, LLLT was not able to increase SFR or decrease xerostomia. The results may be associated with the late effects of radiotherapy on glandular structure, such as fibrosis and acinar atrophy.

Evaluation of effect of transcutaneous electrical nerve stimulation on salivary flow rate in radiation induced xerostomia patients: a pilot study.

PubMed

Lakshman, Anusha Rangare; Babu, G Subhas; Rao, Suresh

2015-01-01

Xerostomia is a common sequel in patients undergoing irradiation of malignant tumors of the head and neck. Palliative treatments of xerostomia like topical agents such as ice-chips, saliva substitutes, systemic sialogogues like pilocarpine and cevimeline work well for some patients. Electrostimulation was studied in the past and showed moderate promise but never became part of the mainstream therapy for better management of xerostomia patients. The aim of the following study is to evaluate the effectiveness of a transcutaneous electrical nerve stimulation (TENS) unit in stimulating the whole salivary flow rate in radiation induced xerostomia patients. A total of 40 subjects were included in the study. The study group consisted of 30 individuals and was divided into Group S1 (n = 20), which was further subdivided into Group S1A (n = 10) subjects complaining of dry mouth who were undergoing head and neck radiotherapy with TENS stimulation during the commencement of radiotherapy, on the 3 rd , 6 th week and after a month of completion of radiotherapy and Group S1B (n = 10) with TENS stimulation daily during the full course of radiotherapy and Group S2 (n = 10) subjects complaining of dry mouth who had undergone head and neck radiotherapy that ended 1 month prior to their entry into the study. The control group (n = 10) consisted of healthy individuals not complaining of dry mouth and who have not undergone head and neck radiotherapy. Whole saliva was collected without stimulation for 10 min and after electrostimulation with TENS unit for additional 10 min in a graduated test tube. The results were statistically analyzed using Mann-Whitney U-test and Kruskal-Wallis's test. The data analysis revealed that control and S1B group showed increased salivary flow rate after stimulation by TENS therapy compared with the unstimulated salivary flow, whereas in S1A and S2 group it was found to be statistically non-significant. The present study gave us an insight about the

Metabolic imaging biomarkers of postradiotherapy xerostomia.

PubMed

Cannon, Blake; Schwartz, David L; Dong, Lei

2012-08-01

Xerostomia is a major complication of head and neck radiotherapy (RT). Available xerostomia measures remain flawed. [(18)F]fluorodeoxyglucose-labeled positron emission tomography-computed tomography (FDG-PET-CT) is routinely used for staging and response assessment of head and neck cancer. We investigated quantitative measurement of parotid gland FDG uptake as a potential biomarker for post-RT xerostomia. Ninety-eight locally advanced head and neck cancer patients receiving definitive RT underwent baseline and post-RT FDG-PET-CT on a prospective imaging trial. A separate validation cohort of 14 patients underwent identical imaging while prospectively enrolled in a second trial collecting sialometry and patient-reported outcomes. Radiation dose and pre- and post-RT standard uptake values (SUVs) for all voxels contained within parotid gland ROI were deformably registered. Average whole-gland or voxel-by-voxel models incorporating parotid D(Met) (defined as the pretreatment parotid SUV weighted by dose) accurately predicted posttreatment changes in parotid FDG uptake (e.g., fractional parotid SUV). Fractional loss of parotid FDG uptake closely paralleled early parotid toxicity defined by posttreatment salivary output (p < 0.01) and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia scores (p < 0.01). In this pilot series, loss of parotid FDG uptake was strongly associated with acute clinical post-RT parotid toxicity. D(Met) may potentially be used to guide function-sparing treatment planning. Prospective validation of FDG-PET-CT as a convenient, quantifiable imaging biomarker of parotid function is warranted and ongoing. Copyright © 2012 Elsevier Inc. All rights reserved.

Prevalence of xerostomia and the salivary flow rate in diabetic patients.

PubMed

Malicka, Barbara; Kaczmarek, Urszula; Skośkiewicz-Malinowska, Katarzyna

2014-01-01

Diabetes is a metabolic disease characterized by hyperglycemia, which results from relative or absolute insulin deficiency. One of the first oral symptoms of diabetes is xerostomia. The aim of the study was to determine the prevalence of the xerostomia symptoms and salivary flow rate in diabetic patients according to the type of diabetes, the level of metabolic control and the duration of the disease. The study involved 156 adult patients of both sexes including 34 patients with diabetes type 1 (group C1), 59 with diabetes type 2 (group C2), and 63 generally healthy individuals as two control groups, sex- and age-matched to the diabetic group. The patients suffering from both types of diabetes were additionally subdivided according to the level of metabolic control and the duration of the disease. Xerostomia was diagnosed with the use of a specially prepared questionnaire and Fox's test. Moreover, the salivary flow rate of resting mixed saliva was measured. In type 1 diabetics, a significantly lower salivary flow rate in comparison to the age-matched control group (0.38 ± 0.19 mL/min vs. 0.53 ± 0.20 mL/min, p < 0.01) was found. However in type 2 diabetics, a slight lower salivary flow rate was noticed (on average, 20% lower). Dry mouth was far more frequently diagnosed in type 1 diabetics than in the control group. In type 1 diabetics, in comparison to healthy subjects, a significantly lower resting flow rate of saliva and significantly higher prevalence of xerosomia were observed, but in type 2 diabetics, only a trend of such variability was observed.

IMRT for head and neck cancer: reducing xerostomia and dysphagia

PubMed Central

Wang, XiaoShen; Eisbruch, Avraham

2016-01-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose–response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. PMID:27538846

Risk factors, hyposalivation and impact of xerostomia on oral health-related quality of life.

PubMed

Niklander, Sven; Veas, Laura; Barrera, Cristina; Fuentes, Flavio; Chiappini, Giuliana; Marshall, Maureen

2017-01-16

To determine xerostomia-related frequency, factors, salivary flow rates and Oral Health-Related Quality of Life (OHRQoL) of patients attending the Universidad Andrés Bello Dental School Clinic, in the city of Viña del Mar, Chile. The study involved 566 patients assessed with xerostomia, based on a single standardized questionnaire. The severity and impact of xerostomia on OHRQoL was assessed using a visual analogue scale (VAS) and the short version of the Oral Health Impact Profile Questionnaire (OHIP-14sp), respectively. Stimulated and non-stimulated salivary flow rates were obtained from a sample of patients. Xerostomia was reported in 61 patients (10.8%), comprising 50 women (83.3%) and 11 men (16.7%) (p < 0.013). The prevalence was 13% among the women and 6.1% among the men. Gender, age and medication were found to be independent risk factors for the development of xerostomia. Hyposalivation was found in 10 of the 35 patients with xerostomia (28.6%) and in 2 patients without it (p < 0.011). Patients with xerostomia had a reduced OHRQoL, compared with patients without xerostomia, as shown by the total OHIP-14sp score (p < 0.001). Xerostomia was a common, potentially debilitating condition with a major impact on the OHRQoL of a patient population attending a university-based dental clinic. Hyposalivation was present in almost 30% of the patients who complained of xerostomia. It is important that general dentists be aware of this condition, so that they can provide patients with a good diagnosis, treatment and follow-up.

[Long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma].

PubMed

Zhang, Xiangmin; Yu, Lijiang; Wu, Wei; Wu, Xiuhong; Xiao, Fufu; Zeng, Guoxing; Lan, Xiaolin

2013-02-01

To evaluate the long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma. Sixty-five cases of nasopharyngeal carcinoma patients were randomly divided into study group of 32 patients and control group of 33 patents. The submandibular gland was transferred to submental region on 32 cases with nasopharyngeal carcinoma before receiving conventional radiotherapy and a block was used to cover the submental region. Before radiotherapy, two groups of submandibular gland function was detected by imaging of the submandibular gland. At 60 months after radiotherapy, submandibular gland function was detected by 99mTc radionuclide scanning, the questionnaire about the degree of xerostomia was investigated respectively. Five-year survival rate was counted. After following up for 60 months, submandibular gland uptake and secretion function in the study group was significantly higher than that in the control group, there was significant difference between the two groups (P < 0.01) respectively. The incidence of moderate or severe xerostomia in the study group was significantly lower than that in the control group (15.4% vs 76.9%, P < 0.01). Five-year survival rate of the study group and control group was 81.3% and 78.8% respectively, there was no significant difference between the two groups (P > 0.05). The long-term efficacy of submandibular gland transfer for prevention of xerostomia after radiotherapy for nasopharyngeal carcinoma was well. It could improve the quality of life in nasopharyngeal carcinoma patients after radiotherapy, and did not affect the long-term efficacy of nasopharyngeal carcinoma.

Xerostomia, Hyposalivation, and Salivary Flow in Diabetes Patients.

PubMed

López-Pintor, Rosa María; Casañas, Elisabeth; González-Serrano, José; Serrano, Julia; Ramírez, Lucía; de Arriba, Lorenzo; Hernández, Gonzalo

2016-01-01

The presence of xerostomia and hyposalivation is frequent among diabetes mellitus (DM) patients. It is not clear if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. The aims of this systematic review are (1) to compare the prevalence rates of xerostomia, (2) to evaluate the salivary flow rate, and (3) to compare the prevalence rates of hyposalivation in DM versus non-DM population. This systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in biomedical databases from 1970 until January 18th, 2016. All studies showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%-53.5% versus 0-30%. Studies that analyzed the quantity of saliva in DM population in relation to non-DM patients reported higher flow rates in non-DM than in DM patients. The variation flow rate among different studies in each group (DM/CG) is very large. Only one existing study showed higher hyposalivation prevalence in DM than non-DM patients (45% versus 2.5%). In addition, quality assessment showed the low quality of the existing studies. We recommend new studies that use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow collection.

Xerostomia Due to Systemic Disease: A Review of 20 Conditions and Mechanisms

PubMed Central

Mortazavi, H; Baharvand, M; Movahhedian, A; Mohammadi, M; Khodadoustan, A

2014-01-01

Xerostomia is a common complaint of nearly half of the elderly population and about one-fifth of younger adults. It causes several signs and symptoms, and compromise oral functions and health-related quality-of-life. Multiple reasons are proposed to describe the etiology of xerostomia such as local factors, psychogenic factors, and systemic diseases. In order to manage xerostomia effectively, identification of the main causality is mandatory. The aim of this review was to present systemic diseases leading to xerostomia with their mechanisms of action. We used various general search engines and specialized databases such as Google, Google Scholar, Yahoo, PubMed, PubMed Central, MedLine Plus, Medknow, EBSCO, ScienceDirect, Scopus, WebMD, EMBASE, and authorized textbooks to find relevant topics by means of Medical Subject Headings keywords such as “xerostomia,” “hyposalivations,” “mouth dryness,” “disease,” and “systemic.” We appraised 97 English-language articles published over the last 40 years in both medical and dental journals including reviews, meta-analysis, original papers, and case reports. Upon compilation of relevant data, it was concluded that autoimmune diseases most frequently involve salivary glands and cause xerostomia followed by diabetes mellitus, renal failure, and graft-versus-host disease. Moreover, the underlying mechanisms of systemic disease-related xerostomia are: autoimmunity, infiltration of immunocompetent cells, granuloma formation, fibrosis and dehydration, deposition of proteinaceous substances, bacterial infection, and side-effects of medications. PMID:25221694

Salivary flow and xerostomia in patients with type 2 diabetes.

PubMed

Carramolino-Cuéllar, Esther; Lauritano, Dorina; Silvestre, Francisco-Javier; Carinci, Francesco; Lucchese, Alberta; Silvestre-Rangil, Javier

2018-05-01

Saliva is secreted by the major and minor salivary glands. There are a number of physiological factors that can reduce this secretion such as age, sex, body weight, number of teeth present in the mouth or time of day. This decrease may also be caused by the use of certain drugs, radiotherapy for head and neck cancer, chronic rheumatic diseases such as Sjögren's syndrome and other systemic disorders such as diabetes mellitus (DM). Objective of this study was to investigate the effect of type 2 DM on salivary secretion and its relation to the sensation of xerostomia. Forty-seven patients with type 2 DM and 46 healthy individuals, aged 40-80, participated in the study. Samples of saliva were collected, at rest and after stimulation, at baseline and after the administration of a meal. A questionnaire of 10 items was used to define the patients' sensations of xerostomia. For statistical analysis, the Mann-Whitney test was used to assess the difference in salivary flow between the two groups and the relationship between the response to each of the questions and salivary flow levels. The degree of the patients' sensation of xerostomia was analysed by the Fisher test. There was a significant decrease in total saliva levels at rest in patients with type 2 DM compared to the control group. The study group also experienced higher levels of dryness at night and on waking as well as a greater sensation of lingual burning compared to the control group. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Occurrence and impact of xerostomia among dentate adult New Zealanders: findings from a national survey.

PubMed

Benn, A M L; Broadbent, J M; Thomson, W M

2015-09-01

We investigated the prevalence, associations and impact of xerostomia in a nationally representative sample of dentate adult community-dwelling New Zealanders aged 18 years and over. The data were collected from a representative sample of 2209 adults, as part of the 2009 New Zealand Oral Health Survey (NZOHS). Data were collected using face-to-face interviews, dental examinations and the short-form Oral Health Impact Profile (OHIP-14). Data analysis used appropriate weighting for all procedures to account for the complex survey design. The overall prevalence estimate for xerostomia was 13.1% (95% CI 11.7, 14.7), and it was more common among females. Those in the 75+  and 25-34 age groups were more likely (odds ratios of 6.5 and 4.0, respectively) to have xerostomia. After controlling for sociodemographic characteristics and clinical oral disease, the mean OHIP-14 score among xerostomics was 50% higher than among those who did not have the condition. These data indicate that xerostomia is a common condition which can affect quality of life among people of all ages. © 2015 Australian Dental Association.

IMRT for head and neck cancer: reducing xerostomia and dysphagia.

PubMed

Wang, XiaoShen; Eisbruch, Avraham

2016-08-01

Dysphagia and xerostomia are the main sequellae of chemoradiotherapy for head and neck cancer, and the main factors in reducing long-term patient quality of life. IMRT uses advanced technology to focus the high radiation doses on the targets and avoid irradiation of non-involved tissues. The decisions about sparing organs and tissues whose damage causes xerostomia and dysphagia depends on the evidence for dose-response relationships for the organs causing these sequellae. This paper discusses the evidence for the contribution of radiotherapy to xerostomia via damage of the major salivary glands (parotid and submandibular) and minor salivary glands within the oral cavity, and the contribution of radiotherapy-related effect on important swallowing structures causing dysphagia. Recommendations for dose limits to these organs, based on measurements of xerostomia and dysphagia following radiotherapy, are provided here. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis.

PubMed

Mercadante, Valeria; Al Hamad, Arwa; Lodi, Giovanni; Porter, Stephen; Fedele, Stefano

2017-03-01

Salivary gland hypofunction is a common and permanent adverse effect of radiotherapy to the head and neck. Randomised trials of available treatment modalities have produced unclear results and offer little reliable guidance for clinicians to inform evidence-based therapy. We have undertaken this systematic review and meta-analysis to estimate the effectiveness of available interventions for radiotherapy-induced xerostomia and hyposalivation. We searched MEDLINE, Cochrane Central, EMBASE, AMED, and CINAHL database through July 2016 for randomised controlled trials comparing any topical or systemic intervention to active and/or non-active controls for the treatment of radiotherapy-induced xerostomia. The results of clinically and statistically homogenous studies were pooled and meta-analyzed. 1732 patients from twenty studies were included in the systematic review. Interventions included systemic or topical pilocarpine, systemic cevimeline, saliva substitutes/mouthcare systems, hyperthermic humidification, acupuncture, acupuncture-like transcutaneous electrical nerve stimulation, low-level laser therapy and herbal medicine. Results from the meta-analysis, which included six studies, suggest that both cevimeline and pilocarpine can reduce xerostomia symptoms and increase salivary flow compared to placebo, although some aspects of the relevant effect size, duration of the benefit, and clinical meaningfulness remain unclear. With regard to interventions not included in the meta-analysis, we found no evidence, or very weak evidence, that they can reduce xerostomia symptoms or increase salivary flow in this population. Pilocarpine and cevimeline should represent the first line of therapy in head and neck cancer survivors with radiotherapy-induced xerostomia and hyposalivation. The use of other treatment modalities cannot be supported on the basis of current evidence. Copyright © 2017 Elsevier Ltd. All rights reserved.

The impact of xerostomia on oral-health-related quality of life among younger adults

PubMed Central

Thomson, W Murray; Lawrence, Herenia P; Broadbent, Jonathan M; Poulton, Richie

2006-01-01

Background Recent research has suggested that chronic dry mouth affects the day-to-day lives of older people living in institutions. The condition has usually been considered to be a feature of old age, but recent work by our team produced the somewhat surprising finding that 10% of people in their early thirties are affected. This raises the issue of whether dry mouth is a trivial condition or a more substantial threat to quality of life among younger people. The objective of this study was to examine the association between xerostomia and oral-health-related quality of life among young adults while controlling for clinical oral health status and other potential confounding factors. Methods Cross-sectional analysis of data from a longstanding prospective observational study of a Dunedin (New Zealand) birth cohort: clinical dental examinations and questionnaires were used at age 32. The main measures were xerostomia (the subjective feeling of dry mouth, measured with a single question) and oral-health-related quality of life (OHRQoL) measured using the short-form Oral Health Impact Profile (OHIP-14). Results Of the 923 participants (48.9% female), one in ten were categorised as 'xerostomic', with no apparent gender difference. There was a strong association between xerostomia and OHRQoL (across all OHIP-14 domains) which persisted after multivariate analysis to control for clinical characteristics, gender, smoking status and personality characteristics (negative emotionality and positive emotionality). Conclusion Xerostomia is not a trivial condition; it appears to have marked and consistent effects on sufferers' day-to-day lives. PMID:17090332

Understanding of xerostomia and strategies for the development of artificial saliva.

PubMed

Kho, Hong-Seop

2014-01-01

Xerostomia is becoming a major issue in dental and medical clinics with an increase of aged population. Medication is the most common etiology of xerostomia, while the most severe xerostomia generally occurs in patients with a history of head and neck radiotherapy. Xerostomic patients usually suffer from diminished quality of life due to various symptoms and complications. Decreased salivary output is a definite objective sign, but oral mucosal wetness is a more reliable factor for the evaluation of xerostomia. At present there are no effective therapeutic methods for the treatment of xerostomia. Sialogogues may have problematic side effects and their therapeutic effects last only brief duration. Artificial saliva typically does not produce satisfactory results in therapeutic efficacy. Therefore, further research and development of better therapeutic modalities are necessary. The basic concept for the development of ideal and functional artificial saliva is the mimicry of natural human saliva. We need proper candidate molecules and antimicrobial supplements to simulate the rheological and biological properties of human saliva. We also need better understanding of the interactions between the ingredients of artificial saliva themselves and between the ingredients and components of human saliva both in solution and on surface phases. In addition, we need accepted measures to evaluate the efficacy of artificial saliva. In conclusion, for the development of ideal artificial saliva, research based on the understanding of pathophysiology of xerostomia and knowledge about rheological and biological functions of human saliva are necessary.

Effect of Xerostomia on the Functional Capacity of Subjects with Rheumatoid Arthritis.

PubMed

Lins E Silva, Marília; Carvalho, Camila Nunes; Carvalho, Alessandra de Albuquerque Tavares; Leão, Jair Carneiro; Duarte, Angela Luzia Pinto; Gueiros, Luiz Alcino

2016-10-01

To evaluate the intensity of xerostomia and hyposalivation in subjects with rheumatoid arthritis (RA) as well as the effects of these conditions on functional incapacity and disease activity. The study sample comprised 236 individuals of both sexes who had RA. All the individuals were submitted to clinical evaluation and unstimulated sialometry. Functional capacity was determined by using the Health Assessment Questionnaire (HAQ), xerostomia was assessed using the Xerostomia Inventory, and disease activity was evaluated with the 28-joint Disease Activity Score (DAS28). The effect of Sjögren syndrome (SS) was analyzed, and the sample was divided into 2 groups: RA (191 subjects) and RA/SS (45 subjects). The Xerostomia Inventory showed positive and significant correlation with fatigue (r = 0.243; p < 0.0001), number of painful joints (r = 0.218; p = 0.001), HAQ (r = 0.279; p < 0.0001), and DAS28 (r = 0.156; p < 0.0001). On regression analysis, both xerostomia (OR 3.89, 95% CI 1.84-8.23, p < 0.001) and DAS28 (for severe disease activity: OR 13.26, 95% CI 3.15-55.79, p < 0.001) showed influence on functional incapacity. Forty-five individuals (19.1%) presented with secondary SS, and having this diagnosis was not associated with disease activity or functional capacity. Xerostomia demonstrated an adverse effect on quality of life of subjects with RA, being associated with a reduction in functional capacity. In this clinical setting, xerostomia can be monitored as a marker of worse clinical evolution.

Geometric Image Biomarker Changes of the Parotid Gland Are Associated With Late Xerostomia.

PubMed

van Dijk, Lisanne V; Brouwer, Charlotte L; van der Laan, Hans Paul; Burgerhof, Johannes G M; Langendijk, Johannes A; Steenbakkers, Roel J H M; Sijtsema, Nanna M

2017-12-01

To identify a surrogate marker for late xerostomia 12 months after radiation therapy (Xer 12m ), according to information obtained shortly after treatment. Differences in parotid gland (PG) were quantified in image biomarkers (ΔIBMs) before and 6 weeks after radiation therapy in 107 patients. By performing stepwise forward selection, ΔIBMs that were associated with Xer 12m were selected. Subsequently other variables, such as PG dose and acute xerostomia scores, were added to improve the prediction performance. All models were internally validated. Prediction of Xer 12m based on PG surface reduction (ΔPG-surface) was good (area under the receiver operating characteristic curve, 0.82). Parotid gland dose was related to ΔPG-surface (P<.001, R 2  = 0.27). The addition of acute xerostomia scores to the ΔPG-surface improved the prediction of Xer 12m significantly, and vice versa. The final model including ΔPG-surface and acute xerostomia had outstanding performance in predicting Xer 12m early after radiation therapy (area under the receiver operating characteristic curve, 0.90). Parotid gland surface reduction was associated with late xerostomia. The early posttreatment model with ΔPG-surface and acute xerostomia scores can be considered as a surrogate marker for late xerostomia. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Sialendoscopy for Patients with Radioiodine-Induced Sialadenitis and Xerostomia.

PubMed

Bhayani, Mihir K; Acharya, Varun; Kongkiatkamon, Suchada; Farah, Sally; Roberts, Dianna B; Sterba, Jennifer; Chambers, Mark S; Lai, Stephen Y

2015-07-01

We examined outcomes in patients treated for radioactive iodine-induced sialadenitis (RAIS) and xerostomia with sialendoscopy. Data was prospectively collected for all patients undergoing sialendoscopy for RAIS from a single institution. Interventional details and intraoperative findings were recorded. Qualitative data were obtained through patient examination, telephone interviews, and use of a standard quality of life questionnaire, Xerostomia Questionnaire. Quantitative data were obtained from patients who underwent sialometry. Twenty-six patients (24 women and 2 men; median age, 43 years; age range, 19-57 years) underwent interventional sialendoscopy after conservative management of symptoms proved unsuccessful. Sialadenitis was present in 25 patients and xerostomia in 22 patients. Mucus plugging in the duct of the gland was the most common finding (22 patients) followed by stenosis (18 patients), inflammation (eight patients), and erythema (eight patients). Median follow-up time was 23.4±12.1 months. Sixteen patients (64%) reported complete resolution; seven (28%), partial resolution; one (4%), no change in symptoms; and one (4%), regression in RAIS-related symptoms. Patients subjectively noted the following regarding their xerostomia symptoms: seven (31.8%) had complete resolution; 10 (45.5%), partial resolution; four (18.2%), no change; and one (4.5%), regression. Statistical analysis of the available sialometry data revealed a statistically significant difference in saliva production at 6 months following sialendoscopy for unstimulated saliva production (p=0.028). Sialendoscopy is an effective treatment option for the management of RAIS and xerostomia refractory to conservative therapy and medical management. Patients in our cohort report durable improvement in symptoms after intervention.

Xerostomia, Hyposalivation, and Salivary Flow in Diabetes Patients

PubMed Central

Casañas, Elisabeth; Ramírez, Lucía; de Arriba, Lorenzo; Hernández, Gonzalo

2016-01-01

The presence of xerostomia and hyposalivation is frequent among diabetes mellitus (DM) patients. It is not clear if the presence of xerostomia and hyposalivation is greater in DM than non-DM patients. The aims of this systematic review are (1) to compare the prevalence rates of xerostomia, (2) to evaluate the salivary flow rate, and (3) to compare the prevalence rates of hyposalivation in DM versus non-DM population. This systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in biomedical databases from 1970 until January 18th, 2016. All studies showed higher prevalence of xerostomia in DM patients in relation to non-DM population, 12.5%–53.5% versus 0–30%. Studies that analyzed the quantity of saliva in DM population in relation to non-DM patients reported higher flow rates in non-DM than in DM patients. The variation flow rate among different studies in each group (DM/CG) is very large. Only one existing study showed higher hyposalivation prevalence in DM than non-DM patients (45% versus 2.5%). In addition, quality assessment showed the low quality of the existing studies. We recommend new studies that use more precise and current definitions concerning the determination and diagnosis of DM patients and salivary flow collection. PMID:27478847

Analysis of factors influencing the development of xerostomia during intensity-modulated radiotherapy.

PubMed

Randall, Ken; Stevens, Jason; Yepes, Juan Fernando; Randall, Marcus E; Kudrimoti, Mahesh; Feddock, Jonathan; Xi, Jing; Kryscio, Richard J; Miller, Craig S

2013-06-01

Factors influencing xerostomia during intensity-modulated radiation therapy (IMRT) were assessed. A 6-week study of 32 head and neck cancer (HNC) patients was performed. Subjects completed the Xerostomia Inventory (XI) and provided stimulated saliva (SS) at baseline, week 2 and at end of IMRT. Influence of SS flow rate (SSFR), calcium and mucin 5b (MUC5b) concentrations and radiation dose on xerostomia was determined. HNC subjects experienced mean SSFR decline of 36% by visit 2 (N = 27; P = .012) and 57% by visit 3 (N = 20; P = .0004). Concentrations of calcium and MUC5b increased, but not significantly during IMRT (P > .05). Xerostomia correlated most with decreasing salivary flow rate as determined by Spearman correlations (P < .04) and linear mixed models (P < .0001). Although IMRT is sparing to the parotid glands, it has an early effect on SSFR and the constituents in saliva in a manner that is associated with the perception of xerostomia. Copyright © 2013 Elsevier Inc. All rights reserved.

Analysis of Factors Influencing the Development of Xerostomia during Intensity-Modulated Radiotherapy

PubMed Central

Randall, Ken; Stevens, Jason; Yepes, Juan Fernando; Randall, Marcus E.; Kudrimoti, Mahesh; Feddock, Jonathan; Xi, Jing; Kryscio, Richard J.; Miller, Craig S.

2013-01-01

OBJECTIVES Factors influencing xerostomia during intensity-modulated radiation therapy (IMRT) were assessed. METHODS A 6-week study of 32 head and neck cancer (HNC) patients was performed. Subjects completed the Xerostomia Inventory (XI) and provided stimulated saliva (SS) at baseline, week two and at end of IMRT. Influence of SS flow rate (SSFR), calcium and mucin 5b (MUC5b) concentrations and radiation dose on xerostomia was determined. RESULTS HNC subjects experienced mean SSFR decline of 36% by visit two (N=27; p=0.012) and 57% by visit three (N=20; p=0.0004), Concentrations of calcium and MUC5b increased, but not significantly during IMRT (p>0.05). Xerostomia correlated most with decreasing salivary flow rate as determined by Spearman correlations (p<0.04) and linear mixed models (p<0.0001). CONCLUSIONS Although IMRT is sparing to the parotid glands, it has an early effect on SSFR and the constituents in saliva in a manner that is associated with the perception of xerostomia. PMID:23523462

The efficacy of cevimeline hydrochloride in the treatment of xerostomia in Sjögren's syndrome in southern Chinese patients: a randomised double-blind, placebo-controlled crossover study.

PubMed

Leung, K C M; McMillan, A S; Wong, M C M; Leung, W K; Mok, M Y; Lau, C S

2008-04-01

Cevimeline hydrochloride, a specific agonist of the M3 muscarinic receptor, is beneficial in the treatment of symptoms of xerostomia and xerophthalmia associated with Sjögren's syndrome (SS). Cevimeline has not been evaluated in southern Chinese patients. Furthermore, the effects of cevimeline on health-related quality of life and oral health status are not known. In this randomised, double-blind, placebo-controlled crossover study, patients received cevimeline 30 mg or matched placebo three times per day over 10 weeks followed by a 4-week washout period before treatment crossover. Participants self-completed the following questionnaires: Xerostomia Inventory (XI), the General Oral Health Assessment Index (GOHAI), the Ocular Surface Disease Index (OSDI) and the Medical Outcomes Short Form (SF-36). Clinical assessments included sialometry, examination of the oral cavity for the degree of xerostomia and dental complications of xerostomia. Fifty patients (22 primary SS and 28 secondary SS) were enrolled in the trial. Forty-four patients completed the study. There was a significant improvement in the XI and GOHAI scores as well as the objective rating of xerostomic signs of the oral cavity after treatment with cevimeline. However, there was no improvement in salivary flow rates and dry eye symptoms. SS patients had lower SF-36 scores, but these did not improve after treatment with cevimeline.

Trismus, xerostomia and nutrition status in nasopharyngeal carcinoma survivors treated with radiation.

PubMed

Chen, Y-J; Chen, S-C; Wang, C-P; Fang, Y-Y; Lee, Y-H; Lou, P-J; Ko, J-Y; Chiang, C-C; Lai, Y-H

2016-05-01

The aims of the study were to: (1) examine levels of trismus, xerostomia and nutritional status; (2) compare levels of trismus, xerostomia and nutritional status in patients with nasopharyngeal carcinoma (NPC) receiving different types of radiation modalities; and (3) identify factors related to NPC survivors' risk status for malnutrition and existing malnutrition. A cross-sectional study with consecutive sampling was conducted. NPC survivors were recruited from otolaryngology/oncology outpatient clinics in a medical centre in Northern Taiwan. Study measures included (1) Mandibular Function Impairment Questionnaire, (2) Xerostomia Questionnaire, (3) Mini Nutrition Assessment, (4) Hospital Anxiety and Depression Scale - Depression subscale, and (5) Symptom Severity Scale. A total of 110 subjects were recruited. Those receiving intensity-modulated radiation therapy had less trismus and xerostomia than patients receiving two-dimensional radiation therapy. Patients with female gender, advanced stage, completion of treatments within 1 year, higher levels of depression, more severe trismus and higher symptom severity tended to have malnutrition or were at risk of malnutrition. Trismus and xerostomia are long-term problems in some NPC survivors and may contribute to malnutrition. To better manage a patient's trismus and xerostomia and to enhance nutritional status, clinicians should develop a patient-specific care programme based on careful assessment and targeted measures to improve oral function and insure adequate nutritional intake. © 2014 John Wiley & Sons Ltd.

Relationship of hyposalivation and xerostomia in Mexican elderly with socioeconomic, sociodemographic and dental factors

PubMed Central

Islas-Granillo, Horacio; Borges-Yáñez, Aida; Fernández-Barrera, Miguel Ángel; Ávila-Burgos, Leticia; Patiño-Marín, Nuria; Márquez-Corona, María de Lourdes; Mendoza-Rodríguez, Martha; Medina-Solís, Carlo Eduardo

2017-01-01

We determined the prevalence of hyposalivation and xerostomia in older Mexicans (≥60 years), and its relationship with diverse factors. A cross-sectional study was realized in elderly subjects from Pachuca, Mexico. Chewing-stimulated saliva was collected under standardized conditions and salivary flow was measured; subjects were considered to have hyposalivation if their stimulated salivary flow was less than 0.7 mL per minute. Xerostomia was evaluated by asking subjects ‘Does your mouth feel dry?’. Hyposalivation was present in 59.7%, and xerostomia in 25.2% of subjects. 16.5% of subjects had both conditions. Xerostomia was present in 27.7% of subjects with hyposalivation and 21.4% of subjects without hyposalivation, but the difference was not significant (p > 0.05). Thus, 68.3% of older Mexicans had xerostomia and/or hyposalivation. Factors associated with hyposalivation were: using fewer devices in oral hygiene, lacking social benefits for retirement/pension, living in a public retirement home, brushing teeth less than twice a day and lacking teeth without dentures. None of the factors included in this study were associated with xerostomia. We concluded that several variables studied were associated with hyposalivation, but none for xerostomia. Additional research should examine the amount of hyposalivation and factors associated with hyposalivation especially in elderly with increased risk for hyposalivation. PMID:28094800

A Clinical Evaluation Denture Adhesives Used by Patients With Xerostomia

PubMed Central

Bogucki, Zdzislaw A.; Napadlek, Piotr; Dabrowa, Tomasz

2015-01-01

Abstract The purpose of study was to analyze the participants’ opinions concerning the effectiveness of 6 denture adhesives (DA). The study group included 60 participants. Criteria for selecting the patients were as follows: reduced retention and stabilization of maxillary complete dentures and xerostomia. These features were evaluated on basis of clinical examination and standard sialometry tests (u-SFR). Retention of maxillary dentures was scored by modified Kapur index before application of DA. All participants were divided randomly into 6 groups regarding the use of the 6 DA during a 6-month period. After this time, participants completed an HRQL questionnaire. DA noticeably improved retention and stabilization of maxillary complete dentures. DA in the glue form had the best retention effectiveness in participants with xerostomia. These materials are difficult to clean from the denture base. The data are presented in tables and figures. The results of the study collected positive influence of adhesives on retention of dentures in xerostomia patients. The cleaning dentures and denture bearing tissues was difficult. DA help in the use of prostheses, but it is also necessary for the treatment of the causes and symptoms of xerostomia. PMID:25700320

A clinical evaluation denture adhesives used by patients with xerostomia.

PubMed

Bogucki, Zdzislaw A; Napadlek, Piotr; Dabrowa, Tomasz

2015-02-01

The purpose of study was to analyze the participants' opinions concerning the effectiveness of 6 denture adhesives (DA). The study group included 60 participants. Criteria for selecting the patients were as follows: reduced retention and stabilization of maxillary complete dentures and xerostomia. These features were evaluated on basis of clinical examination and standard sialometry tests (u-SFR). Retention of maxillary dentures was scored by modified Kapur index before application of DA. All participants were divided randomly into 6 groups regarding the use of the 6 DA during a 6-month period. After this time, participants completed an HRQL questionnaire. DA noticeably improved retention and stabilization of maxillary complete dentures. DA in the glue form had the best retention effectiveness in participants with xerostomia. These materials are difficult to clean from the denture base. The data are presented in tables and figures. The results of the study collected positive influence of adhesives on retention of dentures in xerostomia patients. The cleaning dentures and denture bearing tissues was difficult. DA help in the use of prostheses, but it is also necessary for the treatment of the causes and symptoms of xerostomia.

Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with 225Ac-PSMA-617: Swimmer-Plot Analysis Suggests Efficacy Regarding Duration of Tumor Control.

PubMed

Kratochwil, Clemens; Bruchertseifer, Frank; Rathke, Hendrik; Hohenfellner, Markus; Giesel, Frederik L; Haberkorn, Uwe; Morgenstern, Alfred

2018-05-01

The aim of this evaluation was to identify the first indicators of efficacy for 225 Ac-labeled prostate-specific membrane antigen (PSMA)-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with three 100 kBq/kg cycles of 225 Ac-PSMA-617 at 2-mo intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 wk. PSMA PET/CT or PSMA SPECT/CT were used for baseline staging and imaging follow-up at month 6. Follow-up included the duration of PSA response and radiologic progression-free survival at month 6. Patient histories were reviewed for the duration of previous treatment lines, and a swimmer plot was used to intraindividually compare the duration of tumor control by PSMA therapy versus prior treatment modalities. Results: Thirty-one of 40 patients were treated per protocol. Five patients discontinued treatment because of nonresponse, and 4 because of xerostomia. Of the 38 patients surviving at least 8 wk, 24 (63%) had a PSA decline of more than 50%, and 33 (87%) had a PSA response of any degree. The median duration of tumor control under 225 Ac-PSMA-617 last-line therapy was 9.0 mo; 5 patients had an enduring response of more than 2 y. Because all patients had advanced disease, this result compares favorably with the tumor control rates associated with earlier-phase disease; the most common preceding first-, second-, third-, and fourth-line therapies were abiraterone (median duration 10.0 mo), docetaxel (6.5 mo), enzalutamide (6.5 mo), and cabazitaxel (6.0 mo), respectively. Conclusion: A positive response for surrogate parameters demonstrates remarkable antitumor activity for 225 Ac-PSMA-617. Swimmer-plot analysis indicates a promising duration of tumor control, especially considering the unfavorable prognostic profile of the selected advanced-stage patients. Xerostomia was the main reason patients discontinued therapy or refused

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer.

PubMed

Eisbruch, A; Kim, H M; Terrell, J E; Marsh, L H; Dawson, L A; Ship, J A

2001-07-01

To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ("oral cavity") were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be independently associated with the

Radiotherapy induced xerostomia: mechanisms, diagnostics, prevention and treatment--evidence based up to 2013.

PubMed

Kałużny, Jarosław; Wierzbicka, Małgorzata; Nogala, Hanna; Milecki, Piotr; Kopeć, Tomasz

2014-01-01

Definition and prevalence of xerostomia were shortly presented. Radiosensitivity of the salivary glands, mechanism, diagnostics, and possible prediction methods of the intensity of xerostomia in the pre-radiotherapy period are widely discussed. Prevention of xerostomia: salivary gland sparing radiotherapy, cytoprotective agents, preservation by stimulation with cholinergic muscarinic agonists, surgical transfer of submandibular glands according to ASCO Management Guidelines and Quality of Life Recommendations were cited. Oral Care Study Group (2010) therapeutic approaches for relieving xerostomia are referred. Current therapies, restricted to symptom relief such as oral hygiene with fluoride agents, antimicrobials to prevent dental caries, saliva substitutes to relieve symptoms, and sialogenic agents to stimulate saliva were also discussed. Copyright © 2013 Polish Otorhinolaryngology - Head and Neck Surgery Society. Published by Elsevier Urban & Partner Sp. z.o.o. All rights reserved.

Impact of Radiation-Induced Xerostomia on Quality of Life After Primary Radiotherapy Among Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jellema, Anke Petra; Department of Radiation Oncology, VU University Medical Center, Amsterdam; Slotman, Ben J.

2007-11-01

Purpose: To investigate the impact of xerostomia on overall quality of life (QoL) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy. Methods and Materials: A total of 288 patients with Stage I-IV disease without distant metastases were included. Late xerostomia according to the Radiation Therapy Oncology Group (RTOG-xerostomia) and QoL (European Organization for Research and Treatment of Cancer QLC-C30) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy. Results: A significant association was found between RTOG-xerostomia and overall QoL outcome (effect size [ES] 0.07, p < 0.001).more » A significant relationship with global QoL, all functioning scales, and fatigue and insomnia was observed. A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age. In terms of gender, RTOG-xerostomia had a larger impact on overall QoL outcome in women (ES 0.13 for women vs. 0.07 for men). Furthermore, in women ES on individual scales were larger, and a marked worsening was observed with increasing RTOG-xerostomia. No different ES according to age was seen (ES 0.10 for 18-65 years vs. 0.08 for >65 years). An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months. With elapsing time, a worsening was found for these individual scales with increasing RTOG-xerostomia. Conclusions: The results of this prospective study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade {>=}2 RTOG-xerostomia decreases with time, its impact on QoL increases. This finding emphasizes the importance of prevention of xerostomia.« less

Influence of xerostomia on oral health-related quality of life in the elderly: a 5-year longitudinal study.

PubMed

Enoki, Kaori; Matsuda, Ken-Ich; Ikebe, Kazunori; Murai, Shunsuke; Yoshida, Minoru; Maeda, Yoshinobu; Thomson, William Murray

2014-06-01

Xerostomia and tooth loss are major oral health problems in the elderly. The aim of this longitudinal study was to characterize the influence of xerostomia on oral health-related quality of life (OHRQoL) among elderly Japanese people. A total of 99 community-dwelling, independently living individuals aged 60 years and older were interviewed and underwent dental examination at baseline and at a 5-year follow-up. The Oral Health Impact Profile-14 and the Xerostomia Inventory were used to assess OHRQoL and xerostomia severity, respectively. Participants whose xerostomia worsened over the 5-year period had a significantly poorer follow-up OHRQoL. Linear regression models showed that tooth loss and worsening xerostomia were significant predictors of poorer follow-up OHRQoL. Tooth loss and worsening xerostomia result in poorer OHRQoL among older Japanese people. Copyright © 2014 Elsevier Inc. All rights reserved.

Xerostomia in patients treated for oropharyngeal carcinoma: comparing linear accelerator-based intensity-modulated radiation therapy with helical tomotherapy.

PubMed

Fortin, Israël; Fortin, Bernard; Lambert, Louise; Clavel, Sébastien; Alizadeh, Moein; Filion, Edith J; Soulières, Denis; Bélair, Manon; Guertin, Louis; Nguyen-Tan, Phuc Felix

2014-09-01

In comparison to sliding-window intensity-modulated radiation therapy (sw-IMRT), we hypothesized that helical tomotherapy (HT) would achieve similar locoregional control and, at the same time, decrease the parotid gland dose, thus leading to a xerostomia reduction. The association between radiation techniques, mean parotid dose, and xerostomia incidence, was reviewed in 119 patients with advanced oropharyngeal carcinoma treated with concurrent chemoradiation using sw-IMRT (n = 59) or HT (n = 60). Ipsilateral and contralateral parotid mean doses were significantly lower for patients treated with HT versus sw-IMRT: 24 Gy versus 32 Gy ipsilaterally and 20 Gy versus 25 Gy contralaterally. The incidence of grade ≥2 xerostomia was significantly lower in the HT group than in the sw-IMRT group: 12% versus 78% at 6 months, 3% versus 51% at 12 months, and 0% versus 25% at 24 months. Total parotid mean dose <25 Gy was strongly associated to a lower incidence of grade ≥2 xerostomia at 6, 12, and 24 months. This retrospective series suggests that using HT can better spare the parotid glands while respecting quantitative analysis of normal tissue effects in the clinic (QUANTEC)'s criteria. Copyright © 2013 Wiley Periodicals, Inc.

Efficacy of a new oral lubricant solution in the management of psychotropic drug-induced xerostomia: a randomized controlled trial.

PubMed

Mouly, Stéphane J; Orler, Jean-Baptiste; Tillet, Yves; Coudert, Anne-Claude; Oberli, Frantz; Preshaw, Phillip; Bergmann, Jean-François

2007-10-01

Xerostomia is a subjective sensation of mouth dryness often occurring as an unwanted effect of psychotropic drugs. The clinical efficacy and acceptability of a new oxygenated glycerol triester (OGT) oral spray (1 or 2 sprays up to 4 times daily) in the treatment of xerostomia was compared with those of a commercially available artificial saliva substitute (ASS [Saliveze]) in a 2-week, open-labeled, randomized, parallel-group study. Clinical assessment of xerostomia included evaluation of mouth dryness by means of a 10-cm-long visual analog scale, objective blinded assessment of the oral tissue condition by a dental hygienist by means of a 4-point ordinal scale, and subjective patient-based assessment of dry mouth symptoms by means of dichotomous responses to a questionnaire. [Day 14 - baseline] patient-based mouth dryness score was the primary end point. Seventy-four patients (41 women and 33 men, 44 +/- 15 years) undergoing long-term psychotropic drug treatment were consecutively enrolled. At day 14, OGT resulted in better efficacy than ASS in mouth dryness score (mean difference, 1.2 +/- 0.4; P = 0.006), speech difficulties (mean difference, 1.2 +/- 0.4; P = 0.005), taste (mean difference, 1.1 +/- 0.4; P = 0.02), and overall mouth condition (mean difference, 1.4 +/- 0.9; P = 0.005). Taste of OGT was better than that of ASS (mean difference, 1.4 +/- 0.6; P = 0.04), as was OGT acceptability (mean difference, 1.4 +/- 0.9; P = 0.005). Oxygenated glycerol triester lubricant oral spray was superior to a commercially available ASS in improving xerostomia and overall condition of the oral tissue.

Xerostomia after radiotherapy and its effect on quality of life in head and neck cancer patients.

PubMed

Kakoei, Shahla; Haghdoost, Ali-Akbar; Rad, Maryam; Mohammadalizadeh, Sakineh; Pourdamghan, Nasim; Nakhaei, Mahdieh; Bahador, Maryam

2012-04-01

Xerostomia is one of the one complications following radiotherapy that can affect quality of life (QoL). This study aims to assess the severity of xerostomia in patients with head and neck cancers after radiotherapy and its effect on QoL. In this longitudinal prospective study, the severity of xerostomia and related QoL were was assessed in 63 head and neck cancer patients who referred to the Radiotherapy Ward. Patients completed a xerostomia questionnaire (XQ) at the beginning, and 2, 4, and 6 weeks after treatment over a period of 6 months. Additionally, unstimulated saliva was collected using the spitting method at all 4 visits. QoL significantly worsened with increased time (P = 0.0001); meanwhile, the severity of xerostomia increased significantly (P = 0.0001). However, there was no significant change in the amount of saliva at these 4 time points (P = 0.23). Regression analysis showed that with each milliliter decrease in saliva secretion, the QoL score decreased 2.25%. With one score increase in xerostomia, from the QoL mean score there was a 1.65% decrease. The decrease in saliva and xerostomia that resulted from radiotherapy plays an important role in worsening QoL among patients who undergo radiotherapy for head and neck cancers. Although the amount of saliva has a significant association with QoL, the xerostomia score which shows subjects' general feeling also independently impacts QoL. In future studies, we recommend patient assessments for periods longer than 6 months.

Review of the Pharmacological Properties and Clinical Usefulness of Muscarinic Agonists for Xerostomia in Patients with Sjögren's Syndrome.

PubMed

Yasuda, Hiroshi; Niki, Hiroshi

2002-01-01

The anti-xerostomia effects of muscarinic agonists (cholinomimetics) are reviewed. Cevimeline (cevimeline monohydrochloride hemihydrate) is a novel muscarinic agonist that stimulates salivary secretion in animals and humans both with normal salivary gland function and with impaired salivary secretion (xerostomia or oral dryness) as effectively as pilocarpine. Other classic and nonselective muscarinic agonists, such as arecoline, carbachol, muscarine and oxotremorine, as well as acetylcholine, failed to exhibit a sufficient salivation effect even at sublethal doses in animals.Oral administration of cevimeline 30mg to humans induces a moderate and lasting increase in salivary flow, and the effect is maintained for at least 4 to 6 hours, longer than with pilocarpine. Mean increases in salivary flow rates after cevimeline treatment were 2-fold higher than after placebo, and no evidence of tolerance of the pharmacological effect has been observed during prolonged administration for up to 12 months.The clinical efficacy of cevimeline in relieving symptoms of xerostomia, including oral dryness and difficulties in chewing, swallowing and speaking, has been demonstrated by placebo-controlled, double-blind, randomised clinical trials in the USA and Japan. In these studies, cevimeline 30mg three times daily increased salivary flow and improved the symptoms of xerostomia in a significantly higher percentage of patients compared with placebo. Some patients receiving cevimeline therapy for xerostomia experienced adverse events such as sweating, gastrointestinal symptoms (nausea, diarrhoea, abdominal pain and vomiting), dizziness and rigors; these effects were related to muscarinic activity and were generally mild and tolerable in comparison with those of pilocarpine.These findings suggest that muscarinic M3 agonists are suitable for the treatment of xerostomia. Cevimeline in particular has a long-lasting salivation effect with fewer adverse events than pilocarpine, and so is

Study on the clinical significance and related factors of thirst and xerostomia in maintenance hemodialysis patients.

PubMed

Fan, Wei-Feng; Zhang, Qi; Luo, Li-Hong; Niu, Jian-Ying; Gu, Yong

2013-01-01

To analyse the clinical significance and related factors of thirst and xerostomia and to find methods to alleviate thirst and xerostomia in maintenance hemodialysis (MHD) patients. Forty-two MHD patients were included for observational study and eleven patients were enrolled for crossover trial. Thirst was assessed by 100-mm visual analog scales (VAS) and dialysis thirst inventory (DTI). Meanwhile, xerostomia was assessed by VAS and xerostomia inventory (XI). Depression, kidney disease quality of life (KDQOL), salivary flow rates and inter dialytic weight gain (IDWG) were measured. Data were analyzed by ANOVA and correlation coefficient was used to assess the correlations between continuous variables. The results of crossover trial were investigated by two-sample T-tests. Strong positive correlations among DTI, VAS thirst score, XI and VAS xerostomia score were found (P=0.000). Daily IDWG was positively correlated with VAS thirst score (r=0.315, P=0.042) and DTI(r=0.391, P=0.010). UWS (unstimulated whole saliva) was negatively correlated with VAS xerostomia score (r=-0.308, P=0.048). Residual urine output was negatively correlated with DTI (r=-0.402, P=0.008), VAS xerostomia score (r=-0.461, P=0.002) and XI (r=-0.403, P=0.008). In the crossover trial, DTI, XI, IDWG2d, IDWG3d, VAS thirst and xerostomia score were significantly reduced by the use of chewing gum (P=0.000, 0.001, 0.009, 0.017, 0.038, 0.001). The VAS thirst score, DTI and IDWG3d were significantly reduced by receiveing straw (P=0.016, 0.003, 0.049). Thirst and xerostomia might affect the quality of life in MHD patients. Both chewing gum and straw could decrease thirst and IDWG. © 2013 S. Karger AG, Basel.

Impact of xerostomia on oral health and quality of life among adults infected with HIV-1.

PubMed

Jeganathan, Sarangapany; Carey, Helen; Purnomo, Julianita

2012-01-01

The study investigated the impact of xerostomia on oral health and quality of life (QoL) among patients infected with human immunodeficiency virus (HIV) who were attending for routine HIV monitoring in Australia. This cross-sectional, self-administered questionnaire survey and oral screening (OS) included 100 subjects who were HIV positive. The OS was conducted by a dentist blinded to the subject's survey responses. Xerostomia was determined by asking the subjects a single question. Subjects with xerostomia were found to have increased caries activity and poorer QoL, especially in the psychological dimensions of the oral health impact profile. Age and duration of HIV infection were associated with xerostomia. Early diagnosis of xerostomia and intervention with preventive dental care would potentially reduce caries and improve QoL among patients infected with HIV-1. Ongoing chronic inflammation of salivary glands despite the beneficial effects of antiretroviral therapy may play a role in the etiology of xerostomia in patients infected with HIV and requires further study. © 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Significance and Implications of Patient-reported Xerostomia in Sjögren's Syndrome: Findings From the National Institutes of Health Cohort.

PubMed

Billings, Monisha; Dye, Bruce A; Iafolla, Timothy; Baer, Alan N; Grisius, Margaret; Alevizos, Ilias

2016-10-01

Xerostomia is a chief complaint of patients with Sjögren's syndrome (SS). However, newer proposals for SS classification remove xerostomia and hyposalivation from the criteria list. Given these developments and the importance of patient-centered research outcomes, we sought to evaluate the utility of patient-reported xerostomia with implications for classification criteria, and clinical trials targeting SS treatment modalities. A nested case-control study was designed within The National Institute of Dental and Craniofacial Research/National Institutes of Health (NIDCR/NIH) SS Cohort - one of the largest SS cohorts in the US. Clinical characteristics of those with and without xerostomia in SS and other salivary gland dysfunctions were compared. Several analytical methods were employed, including multivariable logistic regression modeling. The NIDCR/NIH Sjögren's Syndrome Clinic has an open cohort with ongoing enrollment since 1984. This open cohort comprised of 2046 participants by August 27, 2015. Baseline data of 701 SS, 355 Sicca, and 247 ISS participants within the source cohort were analyzed. Xerostomia was highest among SS participants (87.4%, 95% CI: 84.8%-89.8%) compared to Sicca (72.4%, 95% CI: 67.4%-77.0%, p<0.001) and ISS groups (38.1%, 95% CI: 32.0%-44.4%, p<0.001). Those with xerostomia were more likely to have SS than Sicca/ISS (OR=4.98, 95% CI: 3.78-6.56). The ability of xerostomia to screen for SS among those with salivary gland dysfunction was higher than screening for Sicca/ISS. Screening diagnostics of xerostomia were of greater utility compared to hyposalivation. After adjusting for confounding in multivariable modeling, SS participants with xerostomia were more likely to be White (Black/African Americans (OR: 0.40, 95% CI: 0.23-0.68, p-value=0.001) and Asians (OR: 0.49, 95% CI: 0.25-0.96, p-value=0.038) were less likely to have xerostomia compared to Whites), have dry eye symptoms for >3months (OR: 5.80, 95% CI: 3.62-9.28, p-value <0.001), a

Prevalence and impact of xerostomia on the quality of life of people living with HIV/AIDS from Brazil.

PubMed

Busato, Ivana Maria Saes; Thomaz, Mariana; Toda, Alexandre Issamu; Alanis, Danilo Gustavo Pulita; França, Beatriz Helena Sottile; de Lima, Antônio Adilson Soares; Azevedo-Alanis, Luciana Reis

2013-01-01

To evaluate the impact of xerostomia on the quality of life (QOL) of people living with HIV/AIDS (PLWHA) from Brazil. A cross-sectional study was performed on 195 PLWHA. Xerostomia was detected by asking a question about the sensation of having "dry mouth," and Oral Health Impact Profile 14 (OHIP-14) was used to measure the impact of xerostomia on QOL. Time of diagnosis of HIV/AIDS was assessed. A total of 78 (40.0%) subjects presented with xerostomia. Xerostomia was associated with female gender, low amount of saliva perceived (p ≤ .01), difficulty in swallowing food (p ≤ .05), and showed to have a negative impact on QOL as measured by OHIP-14 (p ≤ .01). Xerostomia was frequent and showed to have a negative impact on the QOL of PLWHA. ©2012 Special Care Dentistry Association and Wiley Periodicals, Inc.

Xerostomia in geriatric patients: a burgeoning global concern.

PubMed

Anil, Sukumaran; Vellappally, Sajith; Hashem, Mohamed; Preethanath, Reghunathan S; Patil, Shankargouda; Samaranayake, Lakshman P

2016-02-01

Saliva plays a key role in maintaining oral homeostasis, function, and health. The prevalence of xerostomia and its consequences are rising due to the increasing aging population, the effects of some systemic diseases, medical management, and commonly-prescribed medications that reduce saliva production. When salivary function is diminished, patients are at a greater risk of developing caries, discomfort in wearing dentures, and opportunistic diseases, such as candidiasis. The psychosocial aspects of xerostomia can range from a mild effect on self-rated oral health to frustration, embarrassment, unhappiness, or substantial disruptions in quality of life. This article reviews the clinical features, diagnosis, and prevalence of dry mouth, as well as its treatment strategies. © 2014 Wiley Publishing Asia Pty Ltd.

Auricular Acupressure Helps Alleviate Xerostomia in Maintenance Hemodialysis Patients: A Pilot Study.

PubMed

Yang, Guowen; Lin, Shaoqin; Wu, Yuchi; Zhang, Shangpeng; Wu, Xiuqing; Liu, Xusheng; Zou, Chuan; Lin, Qizhan

2017-04-01

Xerostomia is one of the most common complaints in maintenance hemodialysis (MHD) patients. This problem contributes to excess fluid intake and results in poor survival outcome. Based on Traditional Chinese Medicine (TCM) theory and literature studies, the authors have been practicing auricular acupressure therapy (AAT) to help patients with xerostomia. This pilot study was conducted to demonstrate the potential of AAT for xerostomia in MHD patients. Eligible subjects who agreed to participate in this study were recruited and provided with AAT for 4 weeks. The Summated Xerostomia Inventory (SXI), as well as measurement of inter-dialytic weight gain (IDWG), daily inter-dialytic weight gain (daily IDWG), percentage of inter-dialytic weight gain (IDWG%), blood pressure, and biochemical parameters, were completed at baseline and after a 4-week intervention. A total of 26 eligible participants were recruited. Of them, 10 men and 16 women (M age  = 52.92 ± 11.80 years; dialysis vintage 81.86 ± 46.05 months) completed the study. After the 4-week AAT intervention, the SXI scores were significantly decreased compared with baseline (from 10.08 ± 2.26 to 9.04 ± 2.14; p < 0.05). However, the IDWG, daily IDWG, IDWG%, blood pressure, and biochemical parameters did not change significantly after the intervention. This study provides preliminary evidence that AAT may be effective in reducing xerostomia intensity for MHD patients.

Reducing Xerostomia After Chemo-IMRT for Head and Neck Cancer: Beyond Sparing the Parotid Glands

PubMed Central

Little, Michael; Schipper, Matthew; Feng, Felix Y.; Vineberg, Karen; Cornwall, Craig; Murdoch-Kinch, Carol-Anne; Eisbruch, Avraham

2011-01-01

Purpose To assess whether in addition to sparing parotid glands (PGs), xerostomia after chemo-IMRT of head and neck cancer is affected by reducing doses to other salivary glands. Methods Prospective study: 78 patients with stages III/IV oropharynx/nasopharynx cancers received chemo-IMRT aiming to spare the parts outside the targets of bilateral PGs, oral cavity (OC) containing the minor salivary glands, and contralateral submandibular gland (SMG) (when contralateral level I was not a target). Pretherapy and periodically through 24 months, validated patient-reported xerostomia questionnaires (XQ) scores and observer-graded xerostomia were recorded, and stimulated and unstimulated saliva measured selectively from each of the PGs and SMGs. Mean OC doses served as surrogates of minor salivary glands dysfunction. Regression models assessed XQ and observer-graded xerostomia predictors. Results Statistically significant predictors of the XQ score in univariate analysis included OC, PG, and SMG mean doses, as well as baseline XQ score, time since RT, and both stimulated and unstimulated PG saliva flow rates. Similar factors were statistically significant predictors of observer-graded xerostomia. OC, PG and SMG mean doses were moderately inter-correlated (r=0.47–0.55). In multivariate analyses, after adjusting for PG and SMG doses, OC mean dose (p < 0.0001), time from RT (p < 0.0001), and stimulated PG saliva (p < 0.0025) were significant predictors for XQ scores, and OC mean dose and time for observer-graded xerostomia. While scatter plots showed no thresholds, OC mean doses <40 Gy and contralateral SMG mean <50 Gy were each associated with low patient-reported and observer-rated xerostomia at almost all post-therapy time points. Conclusion PG, SMG and OC mean doses were significant predictors of both patient-reported and observer-rated xerostomia after chemo-IMRT, with OC doses remaining significant after adjusting for PG and SMG doses. These results support efforts to

[Cappuccino coffee treatment of xerostomia in patients taking tricyclic antidepressants: preliminary report].

PubMed

Chodorowski, Zygmunt

2002-01-01

10 patients underwent a trial treatment with Cappuccino coffee. All of them (8 university lecturers and 2 clerks) aged from 60 to 69 (average 63) years old, used tricyclic antidepressant because of insomnia as a monosymptomatic type of depression or insomnia as a dominant symptom in the course of depression. One, evening dose of doxepine was from 150 to 250 (average 225) mg, causing xerostomia next day usually between 9-15 o'clock. The five-minute--chewing of 15.0 g of Cappuccino coffee increased the amount of saliva, decreased xerostomia and improved the ability of speech. Beneficial effect of coffee lasted from 0.5 to 4 (average about 2) hours. To the best of our knowledge there are no publications dealing with the positive effect of coffee in xerostomia.

Self-reported prevalence and severity of xerostomia and its related conditions in individuals attending hospital for general health examinations.

PubMed

Lee, E; Lee, Y-H; Kim, W; Kho, H-S

2014-04-01

The aim of this study was to investigate the prevalence, severity, and relationships between xerostomia and its related symptoms in individuals who attended hospital for general health examinations. Participants included 883 men and 618 women aged between 30 and 60 years. History of symptoms during the previous 6 months, current symptoms, and severity of current symptoms were evaluated using a questionnaire that included questions about xerostomia, burning mouth, taste disturbance, and oral malodor. The prevalence of xerostomia and its related symptoms was 60.2%; the prevalence of oral malodor was 52.3%, xerostomia 33.0%, burning mouth 13.6%, and taste disturbance 12.5%. Men in their 30s and women in their 60s showed significantly higher prevalence and greater severity of xerostomia, burning mouth, and taste disturbance compared with their counterparts. The prevalence of xerostomia, burning mouth, and taste disturbance, and the severity of xerostomia increased significantly with age in women. The prevalence and severity of these four symptoms were significantly related and the association was the highest between burning mouth and taste disturbance. In conclusion, xerostomia and its related symptoms were highly prevalent at all ages. The prevalence and severity of these symptoms were closely related. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

A relationship between salivary flow rates and Candida counts in patients with xerostomia.

PubMed

Nadig, Suchetha Devendrappa; Ashwathappa, Deepak Timmasandra; Manjunath, Muniraju; Krishna, Sowmya; Annaji, Araleri Gopalkrishna; Shivaprakash, Praveen Kunigal

2017-01-01

Most of the adult population is colonized by Candida in their oral cavity. The process of colonization depends on several factors, including the interaction between Candida and salivary proteins. Therefore, salivary gland hypofunction may alter the oral microbiota and increase the risk for opportunistic infections, such as candidiasis. Hence, it is necessary to evaluate the relationship between salivary flow rates (SFRs) and Candida colony counts in the saliva of patients with xerostomia. This study aims to determine and evaluate the relationship between SFRs and Candida colony forming units (CFUs) in patients with xerostomia. This study was a descriptive study. The study participants were taken from the patients attending outpatient department in a private dental college. Fifty patients, who reported xerostomia in a questionnaire of the symptoms of xerostomia, were selected. Chewing stimulated whole saliva samples were collected from them and their SFRs were assessed. Saliva samples were inoculated in the Sabouraud dextrose agar culture media for 24-48 h, and Candida CFUs were counted. Chi-squared test was used to analyze the data. There was a significant inverse relationship between salivary flow and candida CFUs count when patients with high colony counts were analyzed (cutoff point of 400 or greater CFU/mL). Females had less SFR than males. Most of the patients who had hyposalivation were taking medication for the underlying systemic diseases. Candida albicans was the most frequent species. There was a significantly negative correlation between SFRs and Candida CFUs in the patients with xerostomia.

The standardization of acupuncture treatment for radiation-induced xerostomia: A literature review.

PubMed

Li, Ling-Xin; Tian, Guang; He, Jing

2016-07-01

To assess the relative standardization of acupuncture protocols for radiation-induced xerostomia. A literature search was carried out up to November 10, 2012 in the databases PubMed/MEDLINE, EMBASE and China National Knowledge Infrastruction with the terms: radiation-induced xerostomia, acupuncture, acupuncture treatment, and acupuncture therapy. Five ancient Chinese classic acupuncture works were also reviewed with the keywords "dry mouth, thirst, dry tongue, dry eyes and dry lips" to search the effective acupuncture points for dry mouth-associated symptoms in ancient China. Twenty-two full-text articles relevant to acupuncture treatment for radiation-induced xerostomia were included and a total of 48 acupuncture points were searched in the 5 ancient Chinese classic acupuncture works, in which the most commonly used points were Chengjiang (CV24), Shuigou (GV 26), Duiduan (GV 27), Jinjin (EX-HN 12), and Yuye (EX-HN 13) on head and neck, Sanjian (LI 3), Shangyang (LI 1), Shaoshang (LU 11), Shaoze (SI 1), Xialian (LI 8) on hand, Fuliu (KI 7), Dazhong (KI 4), Zuqiaoyin (GB 44), Taichong (LR 3), Zhaohai (KI 6) on foot, Burong (ST 19), Zhangmen (LR 13), Tiantu (CV 22), Qimen (LR 14) on abdomen, Feishu (BL 13), Danshu (BL 19), Xiaochaogshu (BL 27), Ganshu (BL 18) on back, Shenmen (TF 4), Shen (CO10, Kidney), Yidan (CO11, Pancreas) and Pi (CO13, Spleen) on ear. There were considerable heterogeneities in the current acupuncture treatment protocols for radiation-induced xerostomia. Based on the results of the review and the personal perspectives, the authors provide a recommendation for manual acupuncture protocols in treating radiationinduced xerostomia patients with head and neck cancer.

Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life

PubMed Central

van Rij, CM; Oughlane-Heemsbergen, WD; Ackerstaff, AH; Lamers, EA; Balm, AJM; Rasch, CRN

2008-01-01

Background and purpose To assess the impact of intensity modulated radiotherapy (IMRT) versus conventional radiation on late xerostomia and Quality of Life aspects in head and neck cancer patients. Patients and nethods Questionnaires on xerostomia in rest and during meals were sent to all patients treated between January 1999 and December 2003 with a T1-4, N0-2 M0 head and neck cancer, with parotid gland sparing IMRT or conventional bilateral neck irradiation to a dose of at least 60 Gy, who were progression free and had no disseminated disease (n = 192). Overall response was 85% (n = 163); 97% in the IMRT group (n = 75) and 77% in the control group (n = 88) the median follow-up was 2.6 years. The prevalence of complaints was compared between the two groups, correcting for all relevant factors at multivariate ordinal regression analysis. Results Patients treated with IMRT reported significantly less difficulty transporting and swallowing their food and needed less water for a dry mouth during day, night and meals. They also experienced fewer problems with speech and eating in public. Laryngeal cancer patients in general had fewer complaints than oropharynx cancer patients but both groups benefited from IMRT. Within the IMRT group the xerostomia scores were better for those patients with a mean parotid dose to the "spared" parotid below 26 Gy. Conclusion Parotid gland sparing IMRT for head and neck cancer patients improves xerostomia related quality of life compared to conventional radiation both in rest and during meals. Laryngeal cancer patients had fewer complaints but benefited equally compared to oropharyngeal cancer patients from IMRT. PMID:19068126

Salivary flow and xerostomia in older patients with type 2 diabetes mellitus.

PubMed

Lima, Danilo Lopes Ferreira; Carneiro, Sandro Dias Rocha Mendes; Barbosa, Fladia Taciana de Sousa; Saintrain, Maria Vieira de Lima; Moizan, Jean André Hervé; Doucet, Jean

2017-01-01

To assess salivary flow in older patients with type 2 diabetes mellitus (DM2) and its association with xerostomia. Cross-sectional clinical study conducted with older patients diagnosed with type 2 diabetes for at least one year receiving treatment at the Integrated Center for Diabetes and Hypertension of Ceará (CIHD) in the city of Fortaleza, Ceará, Northeastern Brazil. Oral clinical examination was carried out to assess the decayed, missing and filled teeth index (DMFT). Perception of the presence of xerostomia/dry mouth was assessed using the Visual Analogue Scale. Stimulated salivary flow was measured and samples were obtained using an extra-soft silicone device. 120 older patients with diabetes (60 insulin-dependent and 60 non-insulin-dependent) aged 65-91 years, with a mean age of 72.26 ± 6.53 years, were assessed. Of these, 111 (92.5%) presented a decrease in salivary flow while 59 (49.2%) reported moderate to severe xerostomia/dry mouth. The DMFT Index presented a mean of 27.53 ± 4.86 teeth. Reduced salivary flow was found in the group assessed in the present research; however, this finding is not in accordance with the perception of xerostomia/dry mouth reported by the patients.

Salivary flow and xerostomia in older patients with type 2 diabetes mellitus

PubMed Central

Lima, Danilo Lopes Ferreira; Carneiro, Sandro Dias Rocha Mendes; Barbosa, Fladia Taciana de Sousa; Moizan, Jean André Hervé; Doucet, Jean

2017-01-01

Objectives To assess salivary flow in older patients with type 2 diabetes mellitus (DM2) and its association with xerostomia. Methods Cross-sectional clinical study conducted with older patients diagnosed with type 2 diabetes for at least one year receiving treatment at the Integrated Center for Diabetes and Hypertension of Ceará (CIHD) in the city of Fortaleza, Ceará, Northeastern Brazil. Oral clinical examination was carried out to assess the decayed, missing and filled teeth index (DMFT). Perception of the presence of xerostomia/dry mouth was assessed using the Visual Analogue Scale. Stimulated salivary flow was measured and samples were obtained using an extra-soft silicone device. Results 120 older patients with diabetes (60 insulin-dependent and 60 non-insulin-dependent) aged 65–91 years, with a mean age of 72.26 ± 6.53 years, were assessed. Of these, 111 (92.5%) presented a decrease in salivary flow while 59 (49.2%) reported moderate to severe xerostomia/dry mouth. The DMFT Index presented a mean of 27.53 ± 4.86 teeth. Conclusions Reduced salivary flow was found in the group assessed in the present research; however, this finding is not in accordance with the perception of xerostomia/dry mouth reported by the patients. PMID:28767676

Association of Xerostomia and Ultrasonographic Features of the Major Salivary Glands After Radioactive Iodine Ablation for Papillary Thyroid Carcinoma.

PubMed

Soo Roh, Sang; Wook Kim, Dong; Jin Baek, Hye

2016-11-01

The objective of this study is to evaluate the association between xerostomia and sonographic features of the major salivary glands after patients undergo radioactive iodine ablation (RIA) for papillary thyroid carcinoma (PTC). The study included 256 consecutive patients who underwent total thyroidectomy, RIA, and neck ultrasound examinations. Changes in the ultrasound features of the parotid and submandibular glands after RIA were evaluated retrospectively by a single radiologist, on the basis of direct comparison of sonograms obtained before and after RIA. Clinical data, including the presence of xerostomia, were investigated retrospectively by the same radiologist via a review of the electronic medical records. For 111 of the 256 patients (43.4%), ultrasound examination revealed changes in the major salivary glands after RIA. The presence of xerostomia was undetermined in 85 of the 256 patients. Among the remaining 171 patients, the frequency of xerostomia was 36.8% (63/171). When patients with xerostomia were compared with those without xerostomia, no statistically significant differences in patient sex and age, the dose of RIA received, or the number of RIA sessions were noted (p > 0.05). Considering the changes in the ultrasound features of the major salivary glands after RIA, no statistically significant association was found between xerostomia and the number of involved major salivary glands or the presence of an involved submandibular gland (p > 0.05). In this study, ultrasound was unhelpful for evaluating xerostomia after RIA in patients with PTC.

A relationship between salivary flow rates and Candida counts in patients with xerostomia

PubMed Central

Nadig, Suchetha Devendrappa; Ashwathappa, Deepak Timmasandra; Manjunath, Muniraju; Krishna, Sowmya; Annaji, Araleri Gopalkrishna; Shivaprakash, Praveen Kunigal

2017-01-01

Context: Most of the adult population is colonized by Candida in their oral cavity. The process of colonization depends on several factors, including the interaction between Candida and salivary proteins. Therefore, salivary gland hypofunction may alter the oral microbiota and increase the risk for opportunistic infections, such as candidiasis. Hence, it is necessary to evaluate the relationship between salivary flow rates (SFRs) and Candida colony counts in the saliva of patients with xerostomia. Aims: This study aims to determine and evaluate the relationship between SFRs and Candida colony forming units (CFUs) in patients with xerostomia. Settings and Design: This study was a descriptive study. Subjects and Methods: The study participants were taken from the patients attending outpatient department in a private dental college. Fifty patients, who reported xerostomia in a questionnaire of the symptoms of xerostomia, were selected. Chewing stimulated whole saliva samples were collected from them and their SFRs were assessed. Saliva samples were inoculated in the Sabouraud dextrose agar culture media for 24–48 h, and Candida CFUs were counted. Statistical Analysis Used: Chi-squared test was used to analyze the data. Results: There was a significant inverse relationship between salivary flow and candida CFUs count when patients with high colony counts were analyzed (cutoff point of 400 or greater CFU/mL). Females had less SFR than males. Most of the patients who had hyposalivation were taking medication for the underlying systemic diseases. Candida albicans was the most frequent species. Conclusions: There was a significantly negative correlation between SFRs and Candida CFUs in the patients with xerostomia. PMID:28932047

The QUANTEC criteria for parotid gland dose and their efficacy to prevent moderate to severe patient-rated xerostomia.

PubMed

Beetz, Ivo; Steenbakkers, Roel J H M; Chouvalova, Olga; Leemans, Charles R; Doornaert, Patricia; van der Laan, Bernard F A M; Christianen, Miranda E M C; Vissink, Arjan; Bijl, Henk P; van Luijk, Peter; Langendijk, Johannes A

2014-05-01

Recently, the Quantitative Analysis of Normal Tissue Effect in the Clinic (QUANTEC) Group defined dose-volume constraints for the parotid glands to avoid severe xerostomia. The aim of this study was to determine if application of these QUANTEC criteria also protected against moderate-to-severe patient-rated xerostomia. The study population consisted of 307 head and neck cancer patients treated with primary (chemo)radiotherapy, either with 3D-CRT (56%) or with IMRT (44%). All patients participated in a standard follow-up program in which radiation-induced toxicity and quality of life were prospectively assessed. Patients who met the QUANTEC criteria were classified as low risk and otherwise as high risk. In total, 41% of the patients (treated with 3D-CRT and IMRT) were classified as low risk patients. In the group treated with 3D-CRT and IMRT, it was possible to meet the QUANTEC criteria in 47% and 32% of the patients, respectively. Sparing the parotid glands with IMRT was considerably more difficult in patients with lymph node metastases and in patients with nasopharyngeal and oropharyngeal tumours. Low risk patients reported significantly less moderate-to-severe xerostomia than high risk patients. However, the predicted risk of elderly patients and patients with pre-existing minor patient-rated xerostomia at baseline was > 20%, even when the QUANTEC criteria were met. Significantly lower rates of radiation-induced patient-rated xerostomia were found among low risk patients treated according to the QUANTEC criteria, but these criteria do not completely protect against xerostomia. Particularly in elderly patients and patients already suffering from minor xerostomia at baseline, the QUANTEC criteria do not sufficiently protect against persistent, moderate-to-severe patient-rated xerostomia.

Hermeneutic phenomenological interpretations of patients with head and neck neoplasm experiences living with radiation-induced xerostomia: the price to pay?

PubMed

Charalambous, Andreas

2014-10-01

Patients with head and neck neoplasms often experience a number of persistent treatment related symptoms including xerostomia. The impact of xerostomia can be profound and wearing on the patients, hence negatively influencing their quality of life. The purpose of this study was to explore the in-depth experiences of the patients living with radiation-induced xerostomia. This was a hermeneutic phenomenological study inspired by the Philosophy of Paul Ricoeur. Research data were retrieved with individual narratives from 15 patients diagnosed with head and neck neoplasm that underwent radiotherapy. Interpretation proceeded through three phases: naïve reading, structural analysis and comprehensive understanding. Five themes consisting of ten sub-themes emerged from the narratives reflecting on the patients' lived experiences. The themes were "suffering of the body", "suffering of the person's world", "being helpless against xerostomia", "suffering of the mind" and "being alone". The comprehensive understanding disclosed new possibilities for being-in-the world in relation to living with xerostomia. The precedent consideration of xerostomia mainly as a physical side-effect of radiotherapy was outweighed by the social and psychological effects revealed by this study. These xerostomia's effects are inflicted on the patients with an obvious reflection on their perceived quality of life. The findings call upon a shift towards acknowledging the severity of xerostomia and the need to care for these patients holistically. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of the efficacy of a topical sialogogue spray containing malic acid 1% in elderly people with xerostomia: a double-blind, randomized clinical trial.

PubMed

Gómez-Moreno, Gerardo; Cabrera-Ayala, Maribel; Aguilar-Salvatierra, Antonio; Guardia, Javier; Ramírez-Fernández, María Piedad; González-Jaranay, Maximino; Calvo-Guirado, José Luis

2014-12-01

The aim of this study was to evaluate the clinical efficacy of a topical sialogogue spray containing 1% malic acid for elderly people affected by xerostomia. This research took the form of a double-blind, randomized clinical trial. Forty-one individuals (mean age: 78.7 years) with xerostomia were divided into two groups: for the first 'intervention group' (21 subjects) a topical sialogogue spray (1% malic acid) was applied, while for the second 'control group' (20 subjects), a placebo spray was applied; for both groups, the sprays were applied on demand during 2 weeks. The Xerostomia Inventory (XI) was used to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after spray application, were measured. XI scores decreased significantly (clinically meaningful) from 36.4 ± 7.3 points to 29.1 ± 7.1 (p < 0.05) with an XI difference of 7.2 ± 6.1, after the combination among 1% malic acid with xylitol and fluoride application. After 2 weeks of 1% malic acid application, unstimulated and stimulated salivary flows rates increased significantly (p < 0.05). A topical sialogogue spray containing 1% malic acid improved xerostomia in an elderly population and increased unstimulated and stimulated salivary flows rates. © 2013 The Gerodontology Society and John Wiley & Sons A/S.

Prevalence of Drug-Induced Xerostomia in Older Adults with Cognitive Impairment or Dementia: An Observational Study.

PubMed

Gil-Montoya, José Antonio; Barrios, Rocío; Sánchez-Lara, Inés; Carnero-Pardo, Cristobal; Fornieles-Rubio, Francisco; Montes, Juan; Gonzalez-Moles, Miguel Angel; Bravo, Manuel

2016-08-01

Older adults, especially those with cognitive impairment or dementia, frequently consume drugs with potential xerostomic effects that impair their quality of life and oral health. The objective of this study was to determine the prevalence and analyze the possible pharmacological etiology of xerostomia in older people with or without cognitive impairment. Individuals with cognitive impairment were recruited from patients diagnosed using standardized criteria in two neurology departments in Southern Spain. A comparison group was recruited from healthcare centers in the same city after ruling out cognitive impairment. Data on oral health, xerostomia, and drug consumption were recorded in both groups. Dry mouth was evaluated using a 1-item questionnaire and recording clinical signs of oral dryness. All drugs consumed by the participants were recorded, including memantine, anticholinesterases, antipsychotics, antidepressants, and anxiolytics. The final sample comprised 200 individuals with mild cognitive impairment or dementia and 156 without. Xerostomia was present in 70.5 % of participants with cognitive impairment versus 36.5 % of those without, regardless of the drug consumed. Memantine consumption was the only variable significantly related to xerostomia in the multivariate model (OR 3.1; 95 % CI 1.1-8.7), and this relationship persisted after adjusting for possible confounders and forcing the inclusion of drugs with xerostomic potential. More than 70 % of participants diagnosed with cognitive impairment or dementia had xerostomia. Anticholinesterases and memantine were both associated with the presence of xerostomia. In the case of memantine, this association was independent of the consumption of the other drugs considered.

Impact of clinical status and salivary conditions on xerostomia and oral health-related quality of life of adolescents with type 1 diabetes mellitus.

PubMed

Busato, Ivana Maria Saes; Ignácio, Sérgio Aparecido; Brancher, João Armando; Moysés, Simone Tetu; Azevedo-Alanis, Luciana Reis

2012-02-01

To investigate the influence of clinical status and salivary conditions on the presence of xerostomia on adolescents with and without type 1 diabetes mellitus (DM1), and further to investigate the influence of clinical status, salivary conditions and xerostomia on oral health-related quality of life (OHQoL) of those with DM1. A cross-sectional study was performed on 102 adolescents, 51 with DM1 and 51 nondiabetics. Xerostomia was detected by asking a question about the sensation of having 'dry mouth', and Oral Health Impact Profile-14 was used to measure the impact of xerostomia on OHQoL. The clinical status was assessed by using decayed, missing or filled and Community Periodontal indices, and by evaluating oral manifestations; and the following salivary conditions were evaluated: stimulated salivary flow, pH, buffer capacity, total protein, amylase, urea, calcium, and glucose salivary concentrations. Multiple logistic regression analysis was used to evaluate the influence of clinical status and salivary conditions on xerostomia and the impact of xerostomia on the OHQoL of adolescents with DM1. Clinical status and salivary conditions was shown to have no influence on the presence of xerostomia. Bivariate (P = 0.00) and logistic regression (P = 0.01) analysis showed a significant association between DM1 and xerostomia. Logistic regression analysis showed association between xerostomia (P = 0.00) and OHQoL, and caries experience (P = 0.03) and OHQoL. DM1 showed to be predictive of a high prevalence of xerostomia in adolescents. Caries experience and xerostomia showed to have a negative impact on the OHQoL of adolescents with DM1. © 2011 John Wiley & Sons A/S.

Clinical Management of Salivary Gland Hypofunction and Xerostomia in Head-and-Neck Cancer Patients: Successes and Barriers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vissink, Arjan; Mitchell, James B.; Baum, Bruce J.

The most significant long-term complication of radiotherapy in the head-and-neck region is hyposalivation and its related complaints, particularily xerostomia. This review addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy.

Clinical management of salivary gland hypofunction and xerostomia in head and neck cancer patients: successes and barriers*

PubMed Central

Vissink, Arjan; Mitchell, James B; Baum, Bruce J; Limesand, Kirsten H; Jensen, Siri Beier; Fox, Philip C; Elting, Linda S; Langendijk, Johannes A; Coppes, Robert P; Reyland, Mary E

2010-01-01

The most significant long-term complication of radiotherapy in the head and neck region is hyposalivation and its related complaints, particularily xerostomia. This paper addresses the pathophysiology underlying irradiation damage to salivary gland tissue, the consequences of radiation injury, and issues contributing to the clinical management of salivary gland hypofunction and xerostomia. These include ways to: (1) prevent or minimize radiation injury of salivary gland tissue, (2) manage radiation-induced hyposalivation and xerostomia, and (3) restore the function of salivary gland tissue damaged by radiotherapy. PMID:20970030

Prevalence and factors associated with xerostomia and hyposalivation among community-dwelling older people in Japan.

PubMed

Ohara, Yuki; Hirano, Hirohiko; Yoshida, Hideyo; Obuchi, Shuichi; Ihara, Kazushige; Fujiwara, Yoshinori; Mataki, Shiro

2016-03-01

This study investigated the prevalence and factors associated with xerostomia and hyposalivation among community-dwelling older people. Xerostomia and hyposalivation are common symptoms in the older population. This study included with 894 community-dwelling, Japanese older people (355 men, 539 women; age 65-84 years) who participated in a comprehensive geriatric health examination, which included questionnaires and interviews regarding medical history, medications, Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC), depressive condition. The Zung Self-Rating Depression Scale (SDS) was used to evaluate depression. Resting salivary flow rate was evaluated by the modified cotton roll method. In this study, 34.8% of the participants (mean age, 73.5 ± 5.0 years) complained about xerostomia, while the prevalence of hyposalivation was 11.5%. Multiple regression analysis revealed hypnotics use [odds ratio (OR) = 1.71, 95% confidence interval (CI) = 1.13-2.61], SDS (OR = 1.05, CI = 1.04-1.07) and TMIG-IC total points (OR = 0.87, CI = 0.76-0.99) to be significantly associated with xerostomia. In contrast, female gender (OR = 2.59, CI = 1.55-4.31) and the use of agents affecting digestive organs (OR = 1.78, CI = 1.11-2.86) were associated with hyposalivation. Our findings showed that the prevalence of xerostomia and hyposalivation were approximately 1 in 3 and 1 in 10 respectively. The factors associated with psychological factors and high-level functional competence, while hyposalivation was associated with medications and gender, as well as systemic and/or metabolic differences. It is important to consider these multidimensional factors associated with xerostomia and hyposalivation. © 2013 John Wiley & Sons A/S and The Gerodontology Society. Published by John Wiley & Sons Ltd.

Texture analysis as a predictor of radiation-induced xerostomia in head and neck patients undergoing IMRT.

PubMed

Nardone, Valerio; Tini, Paolo; Nioche, Christophe; Mazzei, Maria Antonietta; Carfagno, Tommaso; Battaglia, Giuseppe; Pastina, Pierpaolo; Grassi, Roberta; Sebaste, Lucio; Pirtoli, Luigi

2018-06-01

Image texture analysis (TA) is a heterogeneity quantifying approach that cannot be appreciated by the naked eye, and early evidence suggests that TA has great potential in the field of oncology. The aim of this study is to evaluate parotid gland texture analysis (TA) combined with formal dosimetry as a factor for predicting severe late xerostomia in patients undergoing radiation therapy for head and neck cancers. We performed a retrospective analysis of patients treated at our Radiation Oncology Unit between January 2010 and December 2015, and selected the patients whose normal dose constraints for the parotid gland (mean dose < 26 Gy for the bilateral gland) could not be satisfied due to the presence of positive nodes close to the parotid glands. The parotid gland that showed the higher V30 was contoured on CT simulation and analysed with LifeX Software©. TA parameters included features of grey-level co-occurrence matrix (GLCM), neighbourhood grey-level dependence matrix (NGLDM), grey-level run length matrix (GLRLM), grey-level zone length matrix (GLZLM), sphericity, and indices from the grey-level histogram. We performed a univariate and multivariate analysis between all the texture parameters, the volume of the gland, the normal dose parameters (V30 and Mean Dose), and the development of severe chronic xerostomia. Seventy-eight patients were included and 25 (31%) developed chronic xerostomia. The TA parameters correlated with severe chronic xerostomia included V30 (OR 5.63), Dmean (OR 5.71), Kurtosis (OR 0.78), GLCM Correlation (OR 1.34), and RLNU (OR 2.12). The multivariate logistic regression showed a significant correlation between V30 (0.001), GLCM correlation (p: 0.026), RLNU (p: 0.011), and chronic xerostomia (p < 0.001, R2:0.664). Xerostomia represents an important cause of morbidity for head and neck cancer survivors after radiation therapy, and in certain cases normal dose constraints cannot be satisfied. Our results seem promising as texture

Effectiveness of malic acid 1% in patients with xerostomia induced by antihypertensive drugs

PubMed Central

Guardia, Javier; Aguilar-Salvatierra, Antonio; Cabrera-Ayala, Maribel; Maté-Sánchez de-Val, José E.; Calvo-Guirado, José L.

2013-01-01

Objectives: Assessing the clinical effectiveness of a topical sialogogue on spray (malic acid, 1%) in the treatment of xerostomia induced by antihypertensive drugs. Study Design: This research has been carried out through a randomized double-blind clinical trial. 45 patients suffering from hypertensive drugs-induced xerostomia were divided into 2 groups: the first group (25 patients) received a topical sialogogue on spray (malic acid, 1%) whereas the second group (20 patients) received a placebo. Both of them were administered on demand for 2 weeks. Dry Mouth Questionnaire (DMQ) was used in order to evaluate xerostomia levels before and after product/placebo application. Unstimulated and stimulated salivary flows rates, before and after application, were measured. All the statistical analyses were performed by using SPSS software v17.0. Different DMQ scores at the earliest and final stage of the trial were analysed by using Mann-Whitney U test, whereas Student’s T-test was used to analyse salivary flows. Critical p-value was established at p<0.05. Results: DMQ scores increased significantly (clinical recovery) from 1.21 to 3.36 points (p<0.05) after malic acid (1%) application whereas DMQ scores increased from 1.18 to 1.34 points (p>0.05) after placebo application. After two weeks of treatment with malic acid, unstimulated salivary flow increased from 0.17 to 0.242 mL/min whereas the stimulated one increased from 0.66 to 0.92 mL/min (p<0.05). After placebo application unstimulated flow ranged from 0.152 to 0.146 mL/min and stimulated flow increased from 0.67 to 0.70 mL/min (p>0.05). Conclusions: Malic acid 1% spray improved antihypertensive-induced xerostomia and stimulated the production of saliva. Key words:Xerostomia, hyposialia, malic acid, antihypertensive drugs. PMID:22926481

Parotid gland shrinkage during IMRT predicts the time to Xerostomia resolution.

PubMed

Sanguineti, Giuseppe; Ricchetti, Francesco; Wu, Binbin; McNutt, Todd; Fiorino, Claudio

2015-01-17

To assess the impact of mid-treatment parotid gland shrinkage on long term xerostomia during IMRT for oropharyngeal SCC. All patients treated with IMRT at a single Institution from November 2007 to June 2010 and undergoing weekly CT scans were selected. Parotid glands were contoured retrospectively on the mid treatment CT scan. For each parotid gland, the percent change relative to the planning volume was calculated and combined as weighted average. Patients were considered to be xerostomic if developed GR2+ dry mouth according to CTCAE v3.0. Predictors of the time to xerostomia resolution or downgrade to 1 were investigated at both uni- and multivariate analysis. 85 patients were selected. With a median follow up of 35.8 months (range: 2.4-62.6 months), the actuarial rate of xerostomia is 26.2% (SD: 5.3%) and 15.9% (SD: 5.3%) at 2 and 3 yrs, respectively. At multivariate analysis, mid-treatment shrink along with weighted average mean parotid dose at planning and body mass index are independent predictors of the time to xerostomia resolution. Patients were pooled in 4 groups based on median values of both mid-treatment shrink (cut-off: 19.6%) and mean WA parotid pl-D (cut-off: 35.7 Gy). Patients with a higher than median parotid dose at planning and who showed poor shrinkage at mid treatment are the ones with the outcome significantly worse (3-yr rate of xerostomia ≈ 50%) than the other three subgroups (3-yr rate of xerostomia ≈ 10%). For a given planned dose, patients whose parotids significantly shrink during IMRT are less likely to be long-term supplemental fluids dependent.

Relationship between salivary flow rates and Candida counts in subjects with xerostomia.

PubMed

Torres, Sandra R; Peixoto, Camila Bernardo; Caldas, Daniele Manhães; Silva, Eline Barboza; Akiti, Tiyomi; Nucci, Márcio; de Uzeda, Milton

2002-02-01

This study evaluated the relationship between salivary flow and Candida colony counts in the saliva of patients with xerostomia. Sialometry and Candida colony-forming unit (CFU) counts were taken from 112 subjects who reported xerostomia in a questionnaire. Chewing-stimulated whole saliva was collected and streaked in Candida plates and counted in 72 hours. Species identification was accomplished under standard methods. There was a significant inverse relationship between salivary flow and Candida CFU counts (P =.007) when subjects with high colony counts were analyzed (cutoff point of 400 or greater CFU/mL). In addition, the median sialometry of men was significantly greater than that of women (P =.003), even after controlling for confounding variables like underlying disease and medications. Sjögren's syndrome was associated with low salivary flow rate (P =.007). There was no relationship between the median Candida CFU counts and gender or age. There was a high frequency (28%) of mixed colonization. Candida albicans was the most frequent species, followed by C parapsilosis, C tropicalis, and C krusei. In subjects with high Candida CFU counts there was an inverse relationship between salivary flow and Candida CFU counts.

XRCC3 polymorphisms are associated with the risk of developing radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with intensity modulation radiated therapy.

PubMed

Zou, Yan; Song, Tao; Yu, Wei; Zhao, Ruping; Wang, Yong; Xie, Ruifei; Chen, Tian; Wu, Bo; Wu, Shixiu

2014-03-01

The incidence of radiation-induced late xerostomia varies greatly in nasopharyngeal carcinoma patients treated with radiotherapy. The single-nucleotide polymorphisms in genes involved in DNA repair and fibroblast proliferation may be correlated with such variability. The purpose of this paper was to evaluate the association between the risk of developing radiation-induced late xerostomia and four genetic polymorphisms: TGFβ1 C-509T, TGFβ1 T869C, XRCC3 722C>T and ATM 5557G>A in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. The severity of late xerostomia was assessed using a patient self-reported validated xerostomia questionnaire. Polymerase chain reaction-ligation detection reaction methods were performed to determine individual genetic polymorphism. The development of radiation-induced xerostomia associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for equivalent uniform dose. A total of 43 (41.7%) patients experienced radiation-induced late xerostomia. Univariate Cox proportional hazard analyses showed a higher risk of late xerostomia for patients with XRCC3 722 TT/CT alleles. In multivariate analysis adjusted for clinical and dosimetric factors, XRCC3 722C>T polymorphisms remained a significant factor for higher risk of late xerostomia. To our knowledge, this is the first study that demonstrated an association between genetic polymorphisms and the risk of radiation-induced late xerostomia in nasopharyngeal carcinoma patients treated with Intensity Modulation Radiated Therapy. Our findings suggest that the polymorphisms in XRCC3 are significantly associated with the risk of developing radiation-induced late xerostomia.

[Dynamic observation on the short-term change of xerostomia after intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma].

PubMed

Li, Yanjie; Zhao, Changqing

2015-01-01

To dynamically analyze the change of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy by DW MRI. Twenty-three nasopharyngeal carcinoma patients confirmed by pathology were enrolled. Male/Female: 19/4. The age was from 37 to 69 years. The patients were divided into two groups: G1, Dmean<26 Gy, G2, Dmean ≥ 26 Gy. All patients underwent salivary glands examination by DW MRI before IMRT, at the end of IMRT, 6 months and 12 months after IMRT, at the same time the ADC value of salivary glands were calculated. According to the RTOG/EORTC salivary gland injury grading standard and referring the subjective index, the degree of xerostomia was assessed. SPSS 13.0 and SAS 8.2 software were used to analyze the data. At the end of IMRT, the change tendency of ADC in parotid and submandibular glands value was different in patients with different degree of xerostomia (F = 11.52, P < 0.01). At the end of IMRT, a significant difference for degree of xerostomia could be found in patients within different irradiation dose groups (Z = -3.622, P < 0.01). Clinical stage, treatment mode and age had no significant effect on the degree of xerostomia for patients at the end of IMRT (Z value was -0.791, -0.949, 2.488, all P > 0.05). A significant difference of xerostomia degree in patients was found at the various follow-up time after IMRT (χ(2) = 19.59, P < 0.01). There is good correlation between the function of salivary gland and subjective rating of xerostomia in patients with nasopharyngeal carcinoma after radiotherapy. The degrees of salivary gland function and dry mouth in patients with nasopharyngeal carcinoma damage evaluate with illuminated dose increases. The function of salivary gland gradually restored and the degree of dry mouth gradually reduce with the extension of time after radiotherapy.

Impact of xerostomia on dysphagia after chemotherapy-intensity-modulated radiotherapy for oropharyngeal cancer: Prospective longitudinal study.

PubMed

Vainshtein, Jeffrey M; Samuels, Stuart; Tao, Yebin; Lyden, Teresa; Haxer, Marc; Spector, Matthew; Schipper, Matthew; Eisbruch, Avraham

2016-04-01

The purpose of this study was to assess how xerostomia affects dysphagia. Prospective longitudinal studies of 93 patients with oropharyngeal cancer treated with definitive chemotherapy-intensity-modulated radiotherapy (IMRT). Observer-rated dysphagia (ORD), patient-reported dysphagia (PRD), and patient-reported xerostomia (PRX) assessment of the swallowing mechanics by videofluoroscopy (videofluoroscopy score), and salivary flow rates, were prospectively assessed from pretherapy through 2 years. ORD grades ≥2 were rare and therefore not modeled. Of patients with no/mild videofluoroscopy abnormalities, a substantial proportion had PRD that peaked 3 months posttherapy and subsequently improved. Through 2 years, highly significant correlations were observed between PRX and PRD scores for all patients, including those with no/mild videofluoroscopy abnormalities. Both PRX and videofluoroscopy scores were highly significantly associated with PRD. On multivariate analysis, PRX score was a stronger predictor of PRD than the videofluoroscopy score. Xerostomia contributes significantly to PRD. Efforts to further decrease xerostomia, in addition to sparing parotid glands, may translate into improvements in PRD. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1605-E1612, 2016. © 2015 Wiley Periodicals, Inc.

Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy

PubMed Central

Sasportas, Laura S.; Hosford, Andrew T.; Sodini, Maria A.; Waters, Dale J.; Zambricki, Elizabeth A.; Barral, Joëlle K.; Graves, Edward E.; Brinton, Todd J.; Yock, Paul G.; Le, Quynh-Thu; Sirjani, Davud

2014-01-01

Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%–85% of the patients. Not only does xerostomia significantly impair patients’ quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape. PMID:23643579

Relationship among perceived stress, xerostomia, and salivary flow rate in patients visiting a saliva clinic.

PubMed

Bulthuis, Marjolein S; Jan Jager, Derk H; Brand, Henk S

2018-03-09

This aimed to assess the potential role of chronic stress in saliva secretion, xerostomia, and oral health in a population attending a saliva clinic. Data of 114 patients who met the inclusion criteria and completed all questionnaires were analyzed in this study. Participants completed several validated questionnaires, including the Perceived Stress Scale, the Oral Health Impact Profile (OHIP-14), Xerostomia Inventory (XI), and Bother xerostomia Index (BI). Subsequently, the unstimulated, chewing-stimulated, and citric acid-stimulated saliva secretion rates were determined gravimetrically. Data were evaluated using Spearman's correlation analysis and the Mann-Whitney U test. A significant correlation was observed between perceived stress and XI score (r = 0.312, p = 0.001), as well as between perceived stress and BI score (r = 0.334, p = 0.001). Stress levels also were significantly associated with OHIP-14 scores (r = 0.420, p < 0.001), but an association between experienced stress and salivary flow rate could not be established. In this population, perceived chronic stress seems to be related to several aspects of dry mouth, including the perception of dry mouth, suffering from dry mouth, and the impact on quality of life. These effects were independent of the use of psychotropic medication. No actual reduction in salivary flow was found. Further studies to explore the causal linkage of stress with xerostomia seem warranted. Perceived chronic stress seems to be related with several aspects of dry mouth. This finding might be relevant in future prevention and treatment of xerostomia.

Can sparing of the superficial contralateral parotid lobe reduce xerostomia following radiotherapy for head and neck cancer?

PubMed

Nevens, Daan; Nuyts, Sandra

2017-12-01

The purpose of this study is to see whether sparing the superficial contralateral parotid lobe can help limiting xerostomia following radiotherapy for head and neck cancer. 88 patients that were included in two prospective randomized studies were analysed in the current study. Using the dosimetry of both the parotid glands, we divided our patients in four groups. Group 1 includes patients where we were able to reduce the radiation dose below the threshold in order to spare both the ipsilateral and contralateral parotid glands, Group 2 consists of patients where only the contralateral parotid gland could be spared. Group 3 consists of patients where only the contralateral superficial parotid lobe could be spared, while in Group 4 not even the contralateral superficial lobe could be spared. When we compared Group 1 and Group 2, we did not observe a significant difference between both groups in terms of xerostomia scores at 6 or 12 months. When we compared these groups with Group 3, we observed significant differences with more xerostomia in Group 3 where only the contralateral superficial lobe was spared. A significant difference was also observed between Group 3 and Group 4 with more xerostomia in Group 4. Sparing of just one superficial parotid lobe results in less xerostomia when compared to not sparing any lobe of both parotid glands. Advances in knowledge: When sparing of the whole contralateral parotid gland is not possible, delineating both the superficial parotid glands and trying to spare at least one of them can mean a way forward in limiting xerostomia in head and neck cancer patients treated with radiotherapy.

[Xerostomia and its impact on oral health-related quality of life].

PubMed

Herrmann, Gianna; Müller, Karolina; Behr, Michael; Hahnel, Sebastian

2017-02-01

Dry mouth is a frequently occurrence in elderly people and causes numerous clinical and social problems. To investigate the quality of life in geriatric patients living in nursing homes depending on the subjective sensation of dry mouth and associated oral parameters. A total of 62 male and female elderly patients living in 7 cooperating nursing homes were interviewed employing questionnaires with regard to their oral health-related quality of life (GOHAI) and their subjective perception of dry mouth (sXI-D). Dental status, drinking habits and current medication were documented. The mean GOHAI score was 53.6 and the mean sXI-D score was 7.9. Oral health-related quality of life was significantly influenced by the subjective sensation of dry mouth (p < 0.001), whereas no significant impact of the number of residual teeth or implants or the character of prosthetic restorations could be identified. Xerostomia was significantly influenced by the number of medications consumed (p = 0.039). Xerostomia has a significant impact on the oral health-related quality of life of elderly people living in nursing homes. Thus, dental treatment should focus on the alleviation of xerostomia to improve the oral health-related quality of life in the elderly population.

Submandibular gland transfer for the prevention of postradiation xerostomia in patients with head and neck cancer: a systematic review and meta-analysis.

PubMed

Wu, Fanglong; Weng, Shengxin; Li, Chunjie; Sun, Jun; Li, Longjiang; Gao, Qinghong

2015-01-01

Submandibular gland transfer has been widely used to prevent postradiation xerostomia in head-and-neck cancers. However, there are still some controversies. Six databases were searched, data extraction was performed and the risk of bias was assessed by 2 reviewers independently. The meta-analysis was performed using Review Manager, version 5.2. A total of 7 trials (12 articles) and 369 participants were included. The present clinical evidence suggests that submandibular gland transfer might be highly effective to prevent postradiation xerostomia in head-and-neck cancers without serious adverse events. However, more randomized controlled trials are still needed to confirm this conclusion. © 2015 S. Karger AG, Basel.

Effectiveness of an oral health educational program on community-dwelling older people with xerostomia.

PubMed

Ohara, Yuki; Yoshida, Naomi; Kono, Yoko; Hirano, Hirohiko; Yoshida, Hideyo; Mataki, Shiro; Sugimoto, Kumiko

2015-04-01

The purpose of the present study was to evaluate the changes in oral health and function through an oral health educational program for the independent older people with xerostomia. Community-dwelling older people with xerostomia aged over 65 years who participated in a preliminary comprehensive health survey in 2011 were recruited for the educational program. A total of 47 participants were randomly assigned into two groups, the intervention group (n = 26) and the control group (n = 21). The intervention group attended a 90-min oral health education program every 2 weeks for 3 months. The program consisted of oral hygiene instruction, facial and tongue muscle exercise, and salivary gland massage. The control group was provided only general information about oral health. The assessments of oral function, such as oral diadochokinesis of articulation, swallowing, taste threshold and salivary flow rate, were carried out before and after 3 months with or without intervention. A total of 38 participants (21 of intervention group and 17 of control group) completed the study protocol. In the intervention group, resting salivation significantly improved after the program. The second and third cumulated Repetitive Saliva Swallowing Test times significantly improved in the intervention group. The threshold for bitterness significantly lowered in the intervention group, whereas the sour threshold significantly heightened in the control group after 3 months (P < 0.05). The present study suggests that the educational program targeting oral function improvement is effective among the independent older population. © 2014 Japan Geriatrics Society.

Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia

PubMed Central

May, A.J.; Chatzeli, L.; Proctor, G.B.; Tucker, A.S.

2017-01-01

Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia. PMID:26321752

Salivary Gland Dysplasia in Fgf10 Heterozygous Mice: A New Mouse Model of Xerostomia.

PubMed

May, A J; Chatzeli, L; Proctor, G B; Tucker, A S

2015-01-01

Xerostomia, or chronic dry mouth, is a common syndrome caused by a lack of saliva that can lead to severe eating difficulties, dental caries and oral candida infections. The prevalence of xerostomia increases with age and affects approximately 30% of people aged 65 or older. Given the large numbers of sufferers, and the potential increase in incidence given our aging population, it is important to understand the complex mechanisms that drive hyposalivation and the consequences for the dentition and oral mucosa. From this study we propose the Fgf10 +/- mouse as a model to investigate xerostomia. By following embryonic salivary gland development, in vivo and in vitro, we show that a reduction in Fgf10 causes a delay in branching of salivary glands. This leads to hypoplasia of the glands, a phenotype that is not rescued postnatally or by adulthood in both male and female Fgf10 +/- mice. Histological analysis of the glands showed no obvious defect in cellular differentiation or acini/ductal arrangements, however there was a significant reduction in their size and weight. Analysis of saliva secretion showed that hypoplasia of the glands led to a significant reduction in saliva production in Fgf10 +/- adults, giving rise to a reduced saliva pellicle in the oral cavity of these mice. Mature mice were shown to drink more and in many cases had severe tooth wear. The Fgf10 +/- mouse is therefore a useful model to explore the causes and effects of xerostomia.

The management of xerostomia in patients on haemodialysis: comparison of artificial saliva and chewing gum.

PubMed

Bots, Casper P; Brand, Henk S; Veerman, Enno C I; Valentijn-Benz, Marianne; Van Amerongen, Barbara M; Nieuw Amerongen, Arie V; Valentijn, Robert M; Vos, Pieter F; Bijlsma, Joost A; Bezemer, Pieter D; ter Wee, Piet M

2005-04-01

Many patients on haemodialysis (HD) therapy suffer from a dry mouth and xerostomia. This can be relieved by mechanical and gustatory stimulation or palliative care. The aim of this crossover study was to investigate the effect and preferences of a sugar-free chewing gum (Freedent White) and a xanthan gum-based artificial saliva (Xialine) in the management of xerostomia in chronic HD patients. Sixty-five HD patients participated in a 6-week crossover trial. The artificial saliva was rated significantly lower than the chewing gum for effectiveness, taste and a global assessment. No preference differences were found for gender and age, although older subjects rated the artificial saliva with a higher mark. Thirty-nine subjects (60%) preferred chewing gum, 15% (n=10) preferred the artificial saliva. Therefore, both chewing gum and artificial saliva could play an important role in the palliative care of xerostomia in HD patients.

Management of xerostomia and salivary gland hypofunction.

PubMed

Ram, Saravanan; Kumar, Satish; Navazesh, Mahvash

2011-09-01

Xerostomia and salivary gland hypofunction are conditions that have been associated with increased prevalence of caries, periodontitis, and candidiasis. Oral health care providers must be aware of the etiologies and clinical manifestations of salivary gland hypofunction in order to identify patients with this condition and to prevent its potential complications. The various modalities available to manage this condition range from frequent sips of water to the intake of systemic medications like pilocarpine or cevimeline.

Effect of radiation-induced xerostomia on the human oral microflora. Report no. 12 (final), 1 Jul 1971-30 Jun 1976

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dreizen, S.; Brown, L.R.

1976-06-30

The caries-conducive impact of xerostomia was studied in 42 irradiated cancer patients. The radiation-induced xerostomia was paralleled by changes in the physical, microbial, biochemical, immunologic and dietary parameters of cariogenicity that collectively comprised an overwhelming caries challenge. Microbiologically, significant xerostomia-related increases in Strep. mutans, lactobacilli, staphylococci, yeasts and catalase-positive diphtheroids were accompanied by decreases in Strep. sanguis, bacteroides and fusobacteria in each of the 5 microenvironments tested. The scanty xerostomic saliva contained greater amounts of Na(+), Cl(-), Ca(++), Mg(++), Prot(-), lysozyme, IgA and IgG and considerably less HCO3(-). The increased concentrations of caries protective electrolytes and immunoproteins were negated bymore » huge reductions in total daily saliva output. The xerostomia created caries challenge was almost completely neutralized by a preventive program of daily topical NaF applications and strict oral hygiene. (GRA)« less

The effect of xerostomia and hyposalivation on the quality of life of patients with type II diabetes mellitus

PubMed Central

Molania, Tahereh; Alimohammadi, Mona; Akha, Ozra; Mousavi, Jaber; Razvini, Ramin; Salehi, Maedeh

2017-01-01

were not statistically meaningful. Conclusion Hyposalivation possibility increases in diabetic patients with low metabolic control which can cause more severe side effects in relation to oral health. Xerostomia in diabetic patients has negative effects on oral health related quality of life. Diabetic control and patients’ oral problem improvement is effective in their quality of life promotion. PMID:29403624

The effect of xerostomia and hyposalivation on the quality of life of patients with type II diabetes mellitus.

PubMed

Molania, Tahereh; Alimohammadi, Mona; Akha, Ozra; Mousavi, Jaber; Razvini, Ramin; Salehi, Maedeh

2017-11-01

. Hyposalivation possibility increases in diabetic patients with low metabolic control which can cause more severe side effects in relation to oral health. Xerostomia in diabetic patients has negative effects on oral health related quality of life. Diabetic control and patients' oral problem improvement is effective in their quality of life promotion.

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer

PubMed Central

Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O

2016-01-01

Background and Purpose To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Material and Methods Objective xerostomia was assessed in 121 patients (nCohort1=55; nCohort2=66) treated to 70Gy@2Gy in 2006–2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves. Results The observed xerostomia rate was 38%/47% (3 months) and 19%/23% (11–12 months) in Cohort1/Cohort2. Risk of xerostomia at 3 months increased for higher Dmeancontra and Dmeanipsi (Cohort1: 0.17•Dmeancontra+0.11•Dmeanipsi−8.13; AUC=0.90±0.05; p=0.0002±0.002; pHL=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; pHL=0.27). The identified minimum Dmeancontra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra=12/19 Gy; Dmeancontra, Dmeanipsi=16, 25/20, 26 Gy). Conclusions Increased Dmeancontra and Dmeanipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontra to below 20 Gy, while keeping Dmeanipsi to around 25 Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. PMID:27890427

Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer.

PubMed

Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O

2017-02-01

To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose-response curves. The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi (Cohort1: 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p=0.0002±0.002; p HL =0.22±0.23; Cohort2: AUC=0.81; p<0.0001; p HL =0.27). The identified minimum Dmean contra thresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmean contra =12/19Gy; Dmean contra , Dmean ipsi =16, 25/20, 26Gy). Increased Dmean contra and Dmean ipsi explain short-term xerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cevimeline for the treatment of xerostomia in patients with Sjögren syndrome: a randomized trial.

PubMed

Fife, Rose S; Chase, Walter F; Dore, Robin K; Wiesenhutter, Craig W; Lockhart, Peter B; Tindall, Elizabeth; Suen, James Y

2002-06-10

Cevimeline hydrochloride is a cholinergic agent with muscarinic agonist activity prominently affecting the M1 and M3 receptors prevalent in exocrine glands. We evaluated the safety and efficacy of cevimeline in the treatment of xerostomia in patients with Sjögren syndrome. Seventy-five patients with Sjögren syndrome and associated salivary gland dysfunction were enrolled in a double-blind, randomized, placebo-controlled trial at 8 university- and office-based outpatient clinical facilities in the United States. Eligible study participants were randomized to receive 30 mg of cevimeline 3 times daily, 60 mg of cevimeline 3 times daily, or placebo for 6 weeks. Subjective responses were determined using global patient evaluation and visual analog scales. Salivary flow was measured objectively. Sixty-one participants completed the study. Patients in both cevimeline groups had significant improvements in dry mouth, as indicated by symptoms, salivary flow, and use of artificial saliva, compared with the placebo group. The drug was generally well tolerated, with expected adverse events resulting from the drug's muscarinic agonist action. Fourteen patients withdrew from the study because of adverse events, the most frequent being nausea. Therapy with cevimeline, 30 mg 3 times daily, seems to be well tolerated and to provide substantive relief of xerostomia symptoms. Although both dosages of cevimeline provided symptomatic improvement, 60 mg 3 times daily was associated with an increase in the occurrence of adverse events, particularly gastrointestinal tract disorders. Use of 30 mg of cevimeline provides a new option for the treatment of xerostomia in Sjögren syndrome.

Treatment of xerostomia and hyposalivation in the elderly: A systematic review

PubMed Central

Gil-Montoya, José-Antonio; Silvestre, Francisco-Javier; Barrios, Rocío

2016-01-01

Background Therapeutic strategies for xerostomia, regardless of etiology, have so far not had definitive or clearly effective results. Objectives. To systematically revise the latest scientific evidence available regarding the treatment of dry mouth, regardless of the cause of the problem. Material and Methods The literature search was conducted in March 2015, using the Medline and Embase databases. The “Clinical Trial”, from 2006 to March 2015, was carried out in English and only on human cases. The draft of the systematic review and assessment of the methodological quality of the trials was carried out following the criteria of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and the “Oxford Quality Scale”. Results Finally, a total of 26 trials were identified that met the previously defined selection and quality criteria; 14 related to drug treatments for dry mouth, 10 with non-pharmacological treatment and 2 with alternative treatments. Conclusions Pilocarpine continues to be the best performing sialogogue drug for subjects with xerostomia due to radiation on head and neck cancer or diseases such as Sjogren’s Syndrome. For patients with dry mouth caused solely by medication, there are some positive indications from the use of malic acid, along with other elements that counteract the harmful effect on dental enamel. In general, lubrication of oral mucous membrane reduces the symptoms, although the effects are short-lived. Key words:Systematic review, xerostomia, clinical trial, hyposalivation. PMID:27031061

Xerostomia and salivary hypofunction in vulnerable elders: prevalence and etiology.

PubMed

Liu, Bing; Dion, Michael R; Jurasic, M Marianne; Gibson, Gretchen; Jones, Judith A

2012-07-01

The goal of this article is to review existing research on the prevalence and etiology of dry mouth in the vulnerable elders and identify knowledge gaps. Vulnerable elders (VE) are persons aged >65 years who have any or all of the following: limited mobility, limited resources, or complex health status. A systematic search was conducted of PubMed sources from 1989 to May 2010. Evidence was evaluated on the prevalence and etiology of xerostomia and salivary gland hypofunction (SGH) in VE. The search identified 1,422 publications. The inclusion/exclusion criteria yielded 348 articles, 80 of which are cited herein. Research has showed a high prevalence of xerostomia and SGH in VE. Common etiologies include medications, poor general health, female gender, and age. Gaps still exist in the evaluation of dry mouth in VE. Nonetheless, oral dryness will remain an important health issue as life expectancy increases. Copyright © 2012 Elsevier Inc. All rights reserved.

Xerostomia induced by radiotherapy: an overview of the physiopathology, clinical evidence, and management of the oral damage

PubMed Central

Pinna, Roberto; Campus, Guglielmo; Cumbo, Enzo; Mura, Ida; Milia, Egle

2015-01-01

Background The irradiation of head and neck cancer (HNC) often causes damage to the salivary glands. The resulting salivary gland hypofunction and xerostomia seriously reduce the patient’s quality of life. Purpose To analyze the literature of actual management strategies for radiation-induced hypofunction and xerostomia in HNC patients. Methods MEDLINE/PubMed and the Cochrane Library databases were electronically evaluated for articles published from January 1, 1970, to June 30, 2013. Two reviewers independently screened and included papers according to the predefined selection criteria. Results Sixty-one articles met the inclusion criteria. The systematic review of the literature suggests that the most suitable methods for managing the clinical and pathophysiological consequences of HNC radiotherapy might be the pharmacological approach, for example, through the use of cholinergic agonists when residual secretory capacity is still present, and the use of salivary substitutes. In addition, a modified diet and the patient’s motivation to enhance oral hygiene can lead to a significant improvement. Conclusion Radiation-induced xerostomia could be considered a multifactorial disease. It could depend on the type of cancer treatment and the cumulative radiation dose to the gland tissue. A preventive approach and the correct treatment of the particular radiotherapeutic patient can help to improve the condition of xerostomia. PMID:25691810

Buccal drug delivery technologies for patient-centred treatment of radiation-induced xerostomia (dry mouth).

PubMed

Malallah, Osamah S; Garcia, Cristina M Aller; Proctor, Gordon B; Forbes, Ben; Royall, Paul G

2018-04-25

Radiotherapy is a life-saving treatment for head and neck cancers, but almost 100% of patients develop dry mouth (xerostomia) because of radiation-induced damage to their salivary glands. Patients with xerostomia suffer symptoms that severely affect their health as well as physical, social and emotional aspects of their life. The current management of xerostomia is the application of saliva substitutes or systemic delivery of saliva-stimulating cholinergic agents, including pilocarpine, cevimeline or bethanechol tablets. It is almost impossible for substitutes to replicate all the functional and sensory facets of natural saliva. Salivary stimulants are a better treatment option than saliva substitutes as the former induce the secretion of natural saliva from undamaged glands; typically, these are the minor salivary glands. However, patients taking cholinergic agents systemically experience pharmacology-related side effects including sweating, excessive lacrimation and gastrointestinal tract distresses. Local delivery direct to the buccal mucosa has the potential to provide rapid onset of drug action, i.e. activation of minor salivary glands within the buccal mucosa, while sparing systemic drug exposure and off-target effects. This critical review of the technologies for the local delivery of saliva-stimulating agents includes oral disintegrating tablets (ODTs), oral disintegrating films, medicated chewing gums and implantable drug delivery devices. Our analysis makes a strong case for the development of ODTs for the buccal delivery of cholinergic agents: these must be patient-friendly delivery platforms with variable loading capacities that release the drug rapidly in fluid volumes typical of residual saliva in xerostomia (0.05-0.1 mL). Copyright © 2018 Elsevier B.V. All rights reserved.

Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes

PubMed Central

Saiki, Julie P.; Cao, Hongbin; Van Wassenhove, Lauren D.; Viswanathan, Vignesh; Bloomstein, Joshua; Nambiar, Dhanya K.; Mattingly, Aaron J.; Jiang, Dadi; Chen, Che-Hong; Simmons, Amanda L.; Park, Hyun Shin; von Eyben, Rie; Kool, Eric T.; Sirjani, Davud; Knox, Sarah M.; Le, Quynh Thu; Mochly-Rosen, Daria

2018-01-01

Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1−/− adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy. PMID:29794221

Liposomal treatment of xerostomia, odor, and taste abnormalities in patients with head and neck cancer.

PubMed

Heiser, Clemens; Hofauer, Benedikt; Scherer, Elias; Schukraft, Johannes; Knopf, Andreas

2016-04-01

Smell and taste disorders, sicca symptoms, can be detected in patients with head and neck cancer. The purpose of this study was to assess the utility of local liposomal application in the treatment of patients with head and neck cancers. Ninety-eight patients with head and neck cancer were included in this study. The groups were defined as: group 1 = only surgery; group 2 = surgery + adjuvant radiochemotherapy; and group 3 = primarily radiochemotherapy. All patients had finished cancer treatment and received liposomal sprays for the nose and mouth for 2 months (LipoNasal, LipoSaliva; Optima Pharmaceutical GmbH, Germany) and suffered from taste and smell disorders. We performed tests with "Sniffin' Sticks," "Taste Strips," and a xerostomia questionnaire before and after treatment. After application of liposomes, patients demonstrated a statistically significant increase in smell and taste, and reduced xerostomia. Our results demonstrate that using nonpharmaceutical liposomal sprays improve smell, taste, and symptoms of xerostomia in patients with head and neck cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1232-E1237, 2016. © 2015 Wiley Periodicals, Inc.

Managing xerostomia and salivary gland hypofunction: executive summary of a report from the American Dental Association Council on Scientific Affairs.

PubMed

Plemons, Jacqueline M; Al-Hashimi, Ibtisam; Marek, Cindy L

2014-08-01

Xerostomia, also known as "dry mouth," is a common but frequently overlooked condition that is typically associated with salivary gland hypofunction, which is the objective measurement of reduced salivary flow. Patients with dry mouth exhibit symptoms of variable severity that are commonly attributed to medication use, chronic disease and medical treatment, such as radiotherapy to the head and neck region. Chronic xerostomia significantly increases the risk of experiencing dental caries, demineralization, tooth sensitivity, candidiasis and other oral diseases that may affect quality of life negatively. This article presents a multidisciplinary approach to the clinical management of xerostomia, consistent with the findings of published systematic reviews on this key clinical issue. Initial evaluation of patients with dry mouth should include a detailed health history to facilitate early detection and identify underlying causes. Comprehensive evaluation, diagnostic testing and periodic assessment of salivary flow, followed by corrective actions, may help prevent significant oral disease. A systematic approach to xerostomia management can facilitate interdisciplinary patient care, including collaboration with physicians regarding systemic conditions and medication use. Comprehensive management of xerostomia and hyposalivation should emphasize patient education and lifestyle modifications. It also should focus on various palliative and preventive measures, including pharmacological treatment with salivary stimulants, topical fluoride interventions and the use of sugar-free chewing gum to relieve dry-mouth symptoms and improve the patient's quality of life.

Translation and validation of a Spanish version of the xerostomia inventory.

PubMed

Serrano, Carlos; Fariña, María P; Pérez, Cristhian; Fernández, Marcos; Forman, Katherine; Carrasco, Mauricio

2016-12-01

The aim of this study was to validate a Spanish cross-cultural adaptation of the xerostomia inventory (XI). The original English version of XI was translated into Spanish, cross-culturally adapted and field tested. The Spanish version of XI (XI-Sp) was tested with a sample of 41 patients with xerostomia. The reliability of the XI-Sp was determined through internal consistency and test-retest methods. The construct validity of XI-Sp was determined by means of correlation between XI-Sp scores and salivary flow measurements. Overall XI-Sp scores were 40.8 (SD = 10) for the first application and 40.2 (SD = 9.5) for the second. Cronbach's alpha value for the XI-Sp was 0.89 and 0.87, respectively, while interitem correlation averages were r = 0.44 and r = 0.39 for each application. Interitem correlation and corrected total was r c ≥0.30. The test-retest intraclass correlation coefficient value for the XI-Sp score was 0.59 and 0.91. Convergent validity for construct validity correlation with salivary flow showed a medium effect size (r 2  = 0.10) for the first application but did not make a statistically significant prediction for the second (r 2  = 0.7). This study provides evidence concerning the reliability of the XI-Sp, showing that it may be a useful tool for Spanish-speaking xerostomia patients for both clinical and epidemiologic research. © 2015 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Diagnostic accuracy of ultrasonic histogram features to evaluate radiation toxicity of the parotid glands: a clinical study of xerostomia following head-and-neck cancer radiotherapy.

PubMed

Yang, Xiaofeng; Tridandapani, Srini; Beitler, Jonathan J; Yu, David S; Chen, Zhengjia; Kim, Sungjin; Bruner, Deborah W; Curran, Walter J; Liu, Tian

2014-10-01

To investigate the diagnostic accuracy of ultrasound histogram features in the quantitative assessment of radiation-induced parotid gland injury and to identify potential imaging biomarkers for radiation-induced xerostomia (dry mouth)-the most common and debilitating side effect after head-and-neck radiotherapy (RT). Thirty-four patients, who have developed xerostomia after RT for head-and-neck cancer, were enrolled. Radiation-induced xerostomia was defined by the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer morbidity scale. Ultrasound scans were performed on each patient's parotids bilaterally. The 34 patients were stratified into the acute-toxicity groups (16 patients, ≤ 3 months after treatment) and the late-toxicity group (18 patients, > 3 months after treatment). A separate control group of 13 healthy volunteers underwent similar ultrasound scans of their parotid glands. Six sonographic features were derived from the echo-intensity histograms to assess acute and late toxicity of the parotid glands. The quantitative assessments were compared to a radiologist's clinical evaluations. The diagnostic accuracy of these ultrasonic histogram features was evaluated with the receiver operating characteristic (ROC) curve. With an area under the ROC curve greater than 0.90, several histogram features demonstrated excellent diagnostic accuracy for evaluation of acute and late toxicity of parotid glands. Significant differences (P < .05) in all six sonographic features were demonstrated between the control, acute-toxicity, and late-toxicity groups. However, subjective radiologic evaluation cannot distinguish between acute and late toxicity of parotid glands. We demonstrated that ultrasound histogram features could be used to measure acute and late toxicity of the parotid glands after head-and-neck cancer RT, which may be developed into a low-cost imaging method for xerostomia monitoring and assessment. Copyright © 2014 AUR

Xerostomia is associated with old age and poor appetite in patients on chronic hemodialysis.

PubMed

Bossola, Maurizio; Di Stasio, Enrico; Giungi, Stefania; Vulpio, Carlo; Papa, Valerio; Rosa, Fausto; Tortorelli, Antonio; Tazza, Luigi

2013-11-01

The objective of this study was to assess variables associated with xerostomia in patients on chronic hemodialysis (HD). This was a cross-sectional study of 75 HD patients at an outpatient HD service. Demographic, clinical (renal disease, HD regimen/duration, Charlson comorbidity index, activities of daily living, instrumental activities of daily living [IADL], body mass index), and laboratory (hemoglobin, albumin, interleukin-6 [IL-6], and parathyroid hormone) parameters were recorded. We assessed the appetite through the Hemodialysis Study Appetite questionnaire and xerostomia through the Xerostomia Inventory (XI). A single question ("How often does your mouth feel dry?"; never = Class 1, almost never = Class 2, occasionally = Class 3, often = Class 4, very often = Class 5) was also included in the study questionnaire. The main outcome measure was factors correlated with XI. The median XI score was 18 (min-max = 11-33). Forty patients had an XI score of 18 or less (Group 1) and between 18 and 35 (Group 2). In Group 2, age, Charlson comorbidity index score, and number of patients with poor/very poor appetite were significantly higher. At the univariate analysis, the score of the XI was significantly associated with age, appetite, IADL, Charlson comorbidity index, and serum IL-6 levels. Multiple linear regression analysis showed that the XI was independently associated with age and appetite. Thirty-one patients were in Class 1 to 2, 23 were in Class 3, and 21 were in Class 4 to 5. In Classes 4 to 5, age and the number of patients with poor/very poor appetite were higher (P = .012 and .09, respectively). Xerostomia is associated with old age and poor appetite in patients on chronic HD. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

The role of stem cells in the prevention and treatment of radiation-induced xerostomia in patients with head and neck cancer.

PubMed

Nevens, Daan; Nuyts, Sandra

2016-06-01

Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation-induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation-induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow-derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-induced Xerostomia in Head-and-Neck Cancer (RTOG 0244)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jha, Naresh, E-mail: naresh.jha@albertahealthservices.ca; Harris, Jonathan; Seikaly, Hadi

Purpose: We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials: Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were 'not per protocol,'more » then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of {<=}51% was acceptable. Results: Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was 'per protocol' or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions: The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.« less

A phase II study of submandibular gland transfer prior to radiation for prevention of radiation-induced xerostomia in head-and-neck cancer (RTOG 0244).

PubMed

Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R; McEwan, A J B; Robbins, K Thomas; Grecula, John; Sharma, Anand K; Ang, K Kian

2012-10-01

We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤ 51% was acceptable. Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia. Copyright © 2012 Elsevier Inc. All rights reserved.

Validity and reliability of the Greek version of the xerostomia questionnaire in head and neck cancer patients.

PubMed

Memtsa, Pinelopi Theopisti; Tolia, Maria; Tzitzikas, Ioannis; Bizakis, Ioannis; Pistevou-Gombaki, Kyriaki; Charalambidou, Martha; Iliopoulou, Chrysoula; Kyrgias, George

2017-03-01

Xerostomia after radiation therapy for head and neck (H&N) cancer has serious effects on patients' quality of life. The purpose of this study was to validate the Greek version of the self-reported eight-item xerostomia questionnaire (XQ) in patients treated with radiotherapy for H&N cancer. The XQ was translated into Greek and administered to 100 XQ patients. An exploratory factor analysis was performed. Reliability measures were calculated. Several types of validity were evaluated. The observer-rated scoring system was also used. The mean XQ value was 41.92 (SD 22.71). Factor analysis revealed the unidimensional nature of the questionnaire. High reliability measures (ICC, Cronbach's α, Pearson coefficients) were obtained. Patients differed statistically significantly in terms of XQ score, depending on the RTOG/EORTC classification. The Greek version of XQ is valid and reliable. Its score is well related to observer's findings and it can be used to evaluate the impact of radiation therapy on the subjective feeling of xerostomia.

Xerostomia after Radiotherapy for Oral and Oropharyngeal Cancer: Increasing Salivary Flow with Tasteless Sugar-free Chewing Gum.

PubMed

Kaae, Julie Killerup; Stenfeldt, Lone; Eriksen, Jesper Grau

2016-01-01

Radiation-induced xerostomia is a frequent late side effect after treatment for oral and oropharyngeal cancers. This may induce swallowing difficulties, compromised oral well-being, reduced nutrition intake, or speech deficiencies. Consequently, quality of life is often impaired for these patients. The purpose of this study was to investigate the possibility to mechanically stimulate residual saliva function by using tasteless and sugar-free chewing gum. It was hypothesized that tasteless and sugar-free chewing gum could immediately increase salivary flow and potentially improve oral well-being when used on a regular basis. From October to December 2014, 31 consecutive patients treated with primary radiotherapy (RT) and concomitant cisplatin (in locally advanced cases) for oral or oropharyngeal cancer consented to participate. All patients had finalized RT 2-8 months prior to participation and suffered from xerostomia. Samples of unstimulated and chewing gum-stimulated saliva were obtained at the entry into the study (Visit 1). For 2 weeks, patients used chewing gum on a regular basis whereupon saliva measurements were repeated to verify the changes (Visit 2). An abbreviated EORTC H&N35 questionnaire was completed for both visits. A small control group consisting of young and healthy individuals also tested the chewing gum. Twenty patients completed the study and an increase in saliva flow was observed for 14 patients. Before and after intervention with chewing gum, an increase in mean saliva output was seen between unstimulated and stimulated saliva for both Visit 1 and 2 (p = 0.008 and p = 0.05, respectively). No change in saliva output was seen in the control group. The chewing gum was able to stimulate saliva output that was seen at the beginning and at the end of the intervention. No improvement in baseline saliva was seen. Relevant changes in subjective measures of xerostomia were seen after 2 weeks of chewing the gum.

Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter.

PubMed

Okamoto, A; Miyachi, H; Tanaka, K; Chikazu, D; Miyaoka, H

2016-12-01

Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non-psychotropic medications. Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjögren's syndrome I, were excluded. A total of 127 patients were enrolled. Mean oral moisture was 27·81 ± 2·27% (normal, ≥30·0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia. © 2016 John Wiley & Sons Ltd.

Sedative load and salivary secretion and xerostomia in community-dwelling older people.

PubMed

Tiisanoja, Antti; Syrjälä, Anna-Maija; Komulainen, Kaija; Hartikainen, Sirpa; Taipale, Heidi; Knuuttila, Matti; Ylöstalo, Pekka

2016-06-01

The aim was to investigate how sedative load and the total number of drugs used are related to hyposalivation and xerostomia among 75-year-old or older dentate, non-smoking, community-dwelling people. The study population consisted of 152 older people from the Oral Health GeMS study. The data were collected by interviews and clinical examinations during 2004-2005. Sedative load, which measures the cumulative effect of taking multiple drugs with sedative properties, was calculated using the Sedative Load Model. The results showed that participants with a sedative load of either 1-2 or ≥3 had an increased likelihood of having low stimulated salivary flow (<0.7 ml/min; OR: 2.4; CI: 0.6-8.6 and OR: 11; CI: 2.2-59; respectively) and low unstimulated salivary flow (<0.1 ml/min; OR: 2.7, CI: 1.0-7.4 and OR: 4.5, CI: 1.0-20, respectively) compared with participants without a sedative load. Participants with a sedative load ≥3 had an increased likelihood of having xerostomia (OR: 2.5, CI: 0.5-12) compared with participants without a sedative load. The results showed that the association between the total number of drugs and hyposalivation was weaker than the association between sedative load and hyposalivation. Sedative load is strongly related to hyposalivation and to a lesser extent with xerostomia. The adverse effects of drugs on saliva secretion are specifically related to drugs with sedative properties. © 2014 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Xerostomia, salivary characteristics and gland volumes following intensity-modulated radiotherapy for nasopharyngeal carcinoma: a two-year follow up.

PubMed

Sim, Cpc; Soong, Y L; Pang, Epp; Lim, C; Walker, G D; Manton, D J; Reynolds, E C; Wee, Jts

2018-06-01

To evaluate changes in xerostomia status, salivary characteristics and gland volumes 2 years following radiotherapy in nasopharyngeal carcinoma patients. Xerostomia scores, salivary flow rates, pH and buffering capacity were measured at pre-radiotherapy, mid-radiotherapy, 2 weeks, 3 months and 2 years post-radiotherapy. Salivary gland volumes and their correlation with radiation dose were also assessed. Mean radiation dose to oral cavity, parotid and submandibular glands (SMG) was 44.5, 65.0 and 38.6 Gy respectively. Parotid and SMG volumes decreased 33% at 3 months post-radiotherapy; volumes at 2 years post-radiotherapy were 84% and 51% of pre-radiotherapy levels, respectively. Correlations were observed between parotid gland volume per cent reduction and its radiation dose and between resting salivary flow rate reduction and post-radiotherapy/pre-radiotherapy SMG volume ratio. Salivary flow rates and resting saliva pH remained significantly low at 2 years post-radiotherapy (both flow rates, P = 0.001; resting saliva pH, P = 0.005). Similarly, xerostomia scores remained significantly higher compared with pre-radiotherapy levels. Submandibular gland volumetric shrinkage persisted 2 years after radiotherapy. Xerostomia scores remained significantly higher, and salivary flow rates and resting saliva pH remained significantly lower, suggesting that study participants were still at risk for hyposalivation-related oral diseases. © 2018 Australian Dental Association.

A Phase II Study of Submandibular Gland Transfer Prior to Radiation for Prevention of Radiation-Induced Xerostomia in Head and Neck Cancer (Rtog 0244)s

PubMed Central

Jha, Naresh; Harris, Jonathan; Seikaly, Hadi; Jacobs, John R.; McEwan, AJB.; Thomas Robbins, K.; Grecula, John; Sharma, Anand K.; Ang, K. Kian

2012-01-01

Purpose We report the results of a phase II study to determine reproducibility of surgical technique of submandibular salivary gland transfer (SGT) for prevention of radiation (XRT) induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials Eligible patients had surgery for primary, neck dissection, and SGT followed by XRT during which the transferred salivary gland was shielded. IMRT, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by two and radiation by one reviewer. If 13 or more (out of 43) were “not per protocol”, then technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, Grade 2 or higher and a rate of ≤ 51% was acceptable. Results 44 of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was “per protocol” or with acceptable variation in 34 patients (77.3%) and XRT in 79.5%. 9 patients (20.9%) developed grade II acute xerostomia; 2 had grade 0 -1 xerostomia (4.7%) but started on amifostine/pilocarpine. These 11 patients (25.6%) were considered failures for the xerostomia endpoint. 13 patients have died; median follow-up for 31 surviving patients is 2.9 years. Two-year overall and disease-free survival rates are 76.4% and 71.7%, respectively. Conclusions the technique of submandibular salivary gland transfer procedure is reproducible in a multicenter setting. Seventy-four percent of patients had prevention of XRT induced acute xerostomia. PMID:22541957

Salivary hypofunction and xerostomia: diagnosis and treatment.

PubMed

Atkinson, Jane C; Grisius, Margaret; Massey, Ward

2005-04-01

Salivary gland hypofunction and complaints of xerostomia are common in elderly patients, irrespective of their living situation. Medication use is frequently related to dry mouth symptoms and reductions in salivary flow rates. Patients with reduced salivary flow are at increased risk for caries, oral fungal infections, swallowing problems, and diminished or altered taste. Oral health care providers should institute aggressive preventive measures and recommend palliative care for patients with significant reduction in salivary gland function. The systemic agents pilocarpine and cevimeline may help selected patients. Selective use of fluoride-releasing restorative materials and conservative treatment plans are recommended for this patient group.

Role of minor salivary glands in developing patient-rated xerostomia and sticky saliva during day and night.

PubMed

Beetz, Ivo; Schilstra, Cornelis; Visink, Arjan; van der Schaaf, Arjen; Bijl, Henk P; van der Laan, Bernard F A M; Steenbakkers, Roel J H M; Langendijk, Johannes A

2013-11-01

The purpose of this prospective study was to investigate the relationship between xerostomia during the day (XERday) and night (XERnight) and sticky saliva during the day (STICday) and night (STICnight) and dose distributions in different major and minor salivary glands among head and neck cancer (HNC) patients treated with primary radiotherapy (RT) or chemoradiation (CHRT). The study population was composed of 201 consecutive HNC patients treated with intensity modulated radiotherapy (IMRT) or 3-dimensional conformal radiotherapy (3D-CRT). All patients were included in a standard follow up programme in which acute and late side effects and quality of life (QoL) were prospectively assessed, prior to, during and after treatment. The primary endpoints were XERday, XERnight, STICday, STICnight as assessed by the Groningen Radiotherapy Induced Xerostomia questionnaire (GRIX) six months after completion of treatment. Organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, buccal mucosa and lips. Patients with moderate-to-severe xerostomia or moderate-to-severe sticky saliva, respectively, at baseline were excluded. In order to determine which salivary glands were most important, a multivariate logistic regression analysis with an extended bootstrapping technique was used. In total, 29% and 19% of the cases suffered from XERday and XERnight, respectively. The multivariate analysis showed that baseline xerostomia and the mean parotid gland dose were the most important predictors for XERday and XERnight. At 6months after (CH)RT, 10% and 12% of the cases reported STICday and STICnight respectively. We were not able to identify prognostic factors related to dose distributions with regard to STICday. The mean submandibular gland dose was associated with STICnight. Baseline xerostomia and sticky saliva scores on the GRIX were associated

Products based on olive oil, betaine, and xylitol in the post-radiotherapy xerostomia.

PubMed

Martín, Margarita; Marín, Alicia; López, Mario; Liñán, Olga; Alvarenga, Felipe; Büchser, David; Cerezo, Laura

2017-01-01

The objective of this study was determining if the use of products based in olive oil, betaine and xylitol are efficacious to decrease the impact of the dry mouth in the quality of life of the patients with xerostomia due to radiotherapy treatment. Following therapeutic irradiation of the head and neck, patients with profound xerostomia have complaints associated with oral dryness, speech, and taste. There is no strong evidence that any topical therapy is effective for relieving the symptom of dry mouth. 40 patients who had been treated with radiotherapy for head and neck carcinoma and reported symptoms of dry mouth were included in the study. A xerostomia-related quality of life questionnaire, visual analogue scale questionnaire for subjective assessment of salivary dysfunction and salivary flow were reported before and 15 days after the use of topical products based on olive oil, betaina and xylitol. The four primary quality of life areas demonstrated significantly greater improvement after the use of topical products and all eight VAS items had favourable changes. The reduction of symptoms was statistically significant in 7 of the 8 items. After the use of the products, there were improvements in salivary flow in 45%. The use of products based on olive oil, betaine and xylitol, shaped like collutory, toothpaste, gel and spray significantly improved most symptoms and the quality of life limitations produced by dry mouth in patients treated with radiotherapy.

Treatment planning constraints to avoid xerostomia in head and neck radiotherapy: an independent test of QUANTEC criteria using a prospectively collected dataset

PubMed Central

Moiseenko, Vitali; Wu, Jonn; Hovan, Allan; Saleh, Ziad; Apte, Aditya; Deasy, Joseph O.; Harrow, Stephen; Rabuka, Carman; Muggli, Adam; Thompson, Anna

2011-01-01

Purpose The severe reduction of salivary function (xerostomia) is a common complication following radiation therapy for head and neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group (1) and by Ortholan et al. (2). We perform a validation test of these guidelines against a prospectively collected dataset and compared to a previously published dataset. Method and Materials Whole-mouth stimulated salivary flow data from 66 head and neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12 month follow-up. Previously published data from a second institution (WUSTL) were used for comparison. A logistic model was used to describe the incidence of grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value, NPV) was computed for both the QUANTEC constraints and Ortholan et al. (2) recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. Results Both data sets showed a rate of xerostomia < 20 % when the mean dose to the least-irradiated parotid gland is kept below 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D50=32.4 Gy and and γ=0.97. NPVs for QUANTEC guideline were 94% (BCCA data), 90% (WUSTL data). For Ortholan et al. (2) guideline NPVs were 85% (BCCA), and 86% (WUSTL). Conclusion This confirms that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy. PMID:21640505

Early changes of parotid density and volume predict modifications at the end of therapy and intensity of acute xerostomia.

PubMed

Belli, Maria Luisa; Scalco, Elisa; Sanguineti, Giuseppe; Fiorino, Claudio; Broggi, Sara; Dinapoli, Nicola; Ricchetti, Francesco; Valentini, Vincenzo; Rizzo, Giovanna; Cattaneo, Giovanni Mauro

2014-10-01

To quantitatively assess the predictive power of early variations of parotid gland volume and density on final changes at the end of therapy and, possibly, on acute xerostomia during IMRT for head-neck cancer. Data of 92 parotids (46 patients) were available. Kinetics of the changes during treatment were described by the daily rate of density (rΔρ) and volume (rΔvol) variation based on weekly diagnostic kVCT images. Correlation between early and final changes was investigated as well as the correlation with prospective toxicity data (CTCAEv3.0) collected weekly during treatment for 24/46 patients. A higher rΔρ was observed during the first compared to last week of treatment (-0,50 vs -0,05HU, p-value = 0.0001). Based on early variations, a good estimation of the final changes may be obtained (Δρ: AUC = 0.82, p = 0.0001; Δvol: AUC = 0.77, p = 0.0001). Both early rΔρ and rΔvol predict a higher "mean" acute xerostomia score (≥ median value, 1.57; p-value = 0.01). Median early density rate changes for patients with mean xerostomia score ≥ / < 1.57 were -0.98 vs -0.22 HU/day respectively (p = 0.05). Early density and volume variations accurately predict final changes of parotid glands. A higher longitudinally assessed score of acute xerostomia is well predicted by higher rΔρ and rΔvol in the first two weeks of treatment: best cut-off values were -0.50 HU/day and -380 mm(3)/day for rΔρ and rΔvol respectively. Further studies are necessary to definitively assess the potential of early density/volume changes in identifying more sensitive patients at higher risk of experiencing xerostomia.

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy

PubMed Central

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Ting, Hui-Min; Chang, Liyun; Lee, Hsiao-Yi; Wan Leung, Stephen; Huang, Chih-Jen; Chao, Pei-Ju

2015-01-01

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration. PMID:26289304

Patient- and therapy-related factors associated with the incidence of xerostomia in nasopharyngeal carcinoma patients receiving parotid-sparing helical tomotherapy.

PubMed

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Ting, Hui-Min; Chang, Liyun; Lee, Hsiao-Yi; Wan Leung, Stephen; Huang, Chih-Jen; Chao, Pei-Ju

2015-08-20

We investigated the incidence of moderate to severe patient-reported xerostomia among nasopharyngeal carcinoma (NPC) patients treated with helical tomotherapy (HT) and identified patient- and therapy-related factors associated with acute and chronic xerostomia toxicity. The least absolute shrinkage and selection operator (LASSO) normal tissue complication probability (NTCP) models were developed using quality-of-life questionnaire datasets from 67 patients with NPC. For acute toxicity, the dosimetric factors of the mean doses to the ipsilateral submandibular gland (Dis) and the contralateral submandibular gland (Dcs) were selected as the first two significant predictors. For chronic toxicity, four predictive factors were selected: age, mean dose to the oral cavity (Doc), education, and T stage. The substantial sparing data can be used to avoid xerostomia toxicity. We suggest that the tolerance values corresponded to a 20% incidence of complications (TD20) for Dis = 39.0 Gy, Dcs = 38.4 Gy, and Doc = 32.5 Gy, respectively, when mean doses to the parotid glands met the QUANTEC 25 Gy sparing guidelines. To avoid patient-reported xerostomia toxicity, the mean doses to the parotid gland, submandibular gland, and oral cavity have to meet the sparing tolerance, although there is also a need to take inherent patient characteristics into consideration.

SU-F-J-218: Predicting Radiation-Induced Xerostomia by Dosimetrically Accounting for Daily Setup Uncertainty During Head and Neck IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, S; Quon, H; McNutt, T

2016-06-15

Purpose: To determine if the accumulated parotid dosimetry using planning CT to daily CBCT deformation and dose re-calculation can predict for radiation-induced xerostomia. Methods: To track and dosimetrically account for the effects of anatomical changes on the parotid glands, we propagated physicians’ contours from planning CT to daily CBCT using a deformable registration with iterative CBCT intensity correction. A surface mesh for each OAR was created with the deformation applied to the mesh to obtain the deformed parotid volumes. Daily dose was computed on the deformed CT and accumulated to the last fraction. For both the accumulated and the plannedmore » parotid dosimetry, we tested the prediction power of different dosimetric parameters including D90, D50, D10, mean, standard deviation, min/max dose to the combined parotids and patient age to severe xerostomia (NCI-CTCAE grade≥2 at 6 mo follow-up). We also tested the dosimetry to parotid sub-volumes. Three classification algorithms, random tree, support vector machine, and logistic regression were tested to predict severe xerostomia using a leave-one-out validation approach. Results: We tested our prediction model on 35 HN IMRT cases. Parameters from the accumulated dosimetry model demonstrated an 89% accuracy for predicting severe xerostomia. Compared to the planning dosimetry, the accumulated dose consistently demonstrated higher prediction power with all three classification algorithms, including 11%, 5% and 30% higher accuracy, sensitivity and specificity, respectively. Geometric division of the combined parotid glands into superior-inferior regions demonstrated ∼5% increased accuracy than the whole volume. The most influential ranked features include age, mean accumulated dose of the submandibular glands and the accumulated D90 of the superior parotid glands. Conclusion: We demonstrated that the accumulated parotid dosimetry using CT-CBCT registration and dose re-calculation more accurately

Candidate chromosome 1 disease susceptibility genes for Sjogren’s syndrome xerostomia are narrowed by novel NOD.B10 congenic mice

PubMed Central

Mongini, Patricia K. A.; Kramer, Jill M.; Ishikawa, Tomo-o; Herschman, Harvey; Esposito, Donna

2014-01-01

Sjogren’s syndrome (SS) is characterized by salivary gland leukocytic infiltrates and impaired salivation (xerostomia). Cox-2 (Ptgs2) is located on chromosome 1 within the span of the Aec2 region. In an attempt to demonstrate that COX-2 drives antibody-dependent hyposalivation, NOD.B10 congenic mice bearing a Cox-2flox gene were generated. A congenic line with non-NOD alleles in Cox-2-flanking genes failed manifest xerostomia. Further backcrossing yielded disease-susceptible NOD.B10 Cox-2flox lines; fine genetic mapping determined that critical Aec2 genes lie within a 1.56 to 2.17 Mb span of DNA downstream of Cox-2. Bioinformatics analysis revealed that susceptible and non-susceptible lines exhibit non-synonymous coding SNPs in 8 protein-encoding genes of this region, thereby better delineating candidate Aec2 alleles needed for SS xerostomia. PMID:24685748

Treatment planning constraints to avoid xerostomia in head-and-neck radiotherapy: an independent test of QUANTEC criteria using a prospectively collected dataset.

PubMed

Moiseenko, Vitali; Wu, Jonn; Hovan, Allan; Saleh, Ziad; Apte, Aditya; Deasy, Joseph O; Harrow, Stephen; Rabuka, Carman; Muggli, Adam; Thompson, Anna

2012-03-01

The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50 patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D(50) = 32.4 Gy and and γ = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment Planning Constraints to Avoid Xerostomia in Head-and-Neck Radiotherapy: An Independent Test of QUANTEC Criteria Using a Prospectively Collected Dataset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moiseenko, Vitali, E-mail: vmoiseenko@bccancer.bc.ca; Wu, Jonn; Hovan, Allan

2012-03-01

Purpose: The severe reduction of salivary function (xerostomia) is a common complication after radiation therapy for head-and-neck cancer. Consequently, guidelines to ensure adequate function based on parotid gland tolerance dose-volume parameters have been suggested by the QUANTEC group and by Ortholan et al. We perform a validation test of these guidelines against a prospectively collected dataset and compared with a previously published dataset. Methods and Materials: Whole-mouth stimulated salivary flow data from 66 head-and-neck cancer patients treated with radiotherapy at the British Columbia Cancer Agency (BCCA) were measured, and treatment planning data were abstracted. Flow measurements were collected from 50more » patients at 3 months, and 60 patients at 12-month follow-up. Previously published data from a second institution, Washington University in St. Louis (WUSTL), were used for comparison. A logistic model was used to describe the incidence of Grade 4 xerostomia as a function of the mean dose of the spared parotid gland. The rate of correctly predicting the lack of xerostomia (negative predictive value [NPV]) was computed for both the QUANTEC constraints and Ortholan et al. recommendation to constrain the total volume of both glands receiving more than 40 Gy to less than 33%. Results: Both datasets showed a rate of xerostomia of less than 20% when the mean dose to the least-irradiated parotid gland is kept to less than 20 Gy. Logistic model parameters for the incidence of xerostomia at 12 months after therapy, based on the least-irradiated gland, were D{sub 50} = 32.4 Gy and and {gamma} = 0.97. NPVs for QUANTEC guideline were 94% (BCCA data), and 90% (WUSTL data). For Ortholan et al. guideline NPVs were 85% (BCCA) and 86% (WUSTL). Conclusion: These data confirm that the QUANTEC guideline effectively avoids xerostomia, and this is somewhat more effective than constraints on the volume receiving more than 40 Gy.« less

Analysis of in situ proliferative activity in oral gingival epithelium in patients with xerostomia.

PubMed

Celenligil-Nazliel, Haviye; Palali, Ali; Ayhan, Ayşe; Ruacan, Sevket

2003-02-01

Sjögren's syndrome is an autoimmune disease characterized by xerostomia and keratoconjunctivitis sicca. The relationship between xero-stomia and proliferative activity in human gingival epithelium is not known. Proliferating cell nuclear antigen (PCNA) is a nuclear protein associated with the cell cycle. Nuclear PCNA immunoreactivity is found in the proliferative compartment of normal tissues. The aims of this study were to evaluate PCNA expression in oral gingival epithelium of healthy and inflamed gingiva obtained from patients with Sjögren's syndrome, and to compare the results to age- and gender-matched subjects with normal salivary function. Eighteen Sjögren's syndrome patients and 28 controls (14 with chronic periodontitis and 14 with no clinical evidence of periodontal disease) were included in the study. Biopsies were obtained from both inflamed and healthy gingiva. The expression of PCNA was evaluated in formalin-fixed, paraffin-embedded gingival samples using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. PCNA expression was observed both in the basal and suprabasal layers, and was found to be more prominent in the suprabasal layers. Proliferative index (PI) in inflamed gingiva was significantly lower in the Sjögren's syndrome group. However, no significant difference was observed between the study and control groups with respect to PI in healthy gingiva. In both groups, PI was found to be increased due to inflammation. Our data indicate that proliferative activity is observed in the suprabasal layers and, less frequently, in the basal layer. Inflammation caused increased proliferative activity. However, this positive effect of inflammation on epithelial cell proliferation decreased significantly with a lack of saliva. Therefore, it appears that saliva-derived biological mediators may also contribute to increased proliferative activity observed during inflammation.

A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI.

PubMed

Wolff, Andy; Joshi, Revan Kumar; Ekström, Jörgen; Aframian, Doron; Pedersen, Anne Marie Lynge; Proctor, Gordon; Narayana, Nagamani; Villa, Alessandro; Sia, Ying Wai; Aliko, Ardita; McGowan, Richard; Kerr, Alexander Ross; Jensen, Siri Beier; Vissink, Arjan; Dawes, Colin

2017-03-01

Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the above-mentioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.

Two-stage autotransplantation of human submandibular gland: a novel approach to treat postradiogenic xerostomia.

PubMed

Hagen, Rudolf; Scheich, Matthias; Kleinsasser, Norbert; Burghartz, Marc

2016-08-01

Xerostomia is a persistent side effect of radiotherapy (RT), which severely reduces the quality of life of the patients affected. Besides drug treatment and new irradiation strategies, surgical procedures aim for tissue protection of the submandibular gland. Using a new surgical approach, the submandibular gland was autotransplanted in 6 patients to the patient's forearm for the period of RT and reimplanted into the floor of the mouth 2-3 months after completion of RT. Saxon's test was performed during different time points to evaluate patient's saliva production. Furthermore patients had to answer EORTC QLQ-HN35 questionnaire and visual analog scale. Following this two-stage autotransplantation, xerostomia in the patients was markedly reduced due to improved saliva production of the reimplanted gland. Whether this promising novel approach is a reliable treatment option for RT patients in general should be evaluated in further studies.

Prevalence of xerostomia and hyposalivation and their association with quality of life in elderly patients in dependence on dental status and prosthetic rehabilitation: a pilot study.

PubMed

Hahnel, Sebastian; Schwarz, Simone; Zeman, Florian; Schäfer, Lina; Behr, Michael

2014-06-01

The aims of this pilot study were to investigate the prevalence of xerostomia and hyposalivation and their impact on quality of life in a cohort of elderly patients including dental status and the character of potential prosthetic restorations as independent variables. Patients aged 60 years or older without any objective or subjective need for prosthodontic treatment taking part in a regular recall programme were included in the trial. Quality of life was assessed using the German version of the GOHAI; prevalence and severity of xerostomia was investigated using the shortened version of the Xerostomia Inventory (XI). Stimulated salivary flow rate was determined using a sialometric approach. Dental status and the character of prosthetic restorations (no/fixed restorations and removable but tooth-supported dentures vs. gum-supported dentures) were assessed in a clinical examination by experienced dentists specialized in prosthodontic treatment. A total of 68 patients were included in the trial; a prevalence of xerostomia of 16% and a prevalence of hyposalivation of 31% were identified. The quality of life in the study cohort decreased significantly as a function of xerostomia severity but not salivary flow; moreover, a significant impact of the number of teeth/implants in the upper jaw and the presence of gum-supported dentures in both jaws on GOHAI scores could be identified. Within the limitations of a pilot study, the results support the assumption that the quality of life in elderly patients is particularly related to their subjective perception of xerostomia. A decline in salivary flow, the dental status and the character of prosthetic restorations appear to play a subordinate role for the quality of life in elderly patients. The quality of life in elderly patients may be severely diminished due to an increased subjective perception of dry mouth. Dental treatment should focus on alleviating xerostomia, whereas the impact of dental status and prosthetic

ARIX: a randomised trial of acupuncture v oral care sessions in patients with chronic xerostomia following treatment of head and neck cancer.

PubMed

Simcock, R; Fallowfield, L; Monson, K; Solis-Trapala, I; Parlour, L; Langridge, C; Jenkins, V

2013-03-01

Radiation treatment of head and neck cancer can cause chronic xerostomia which impairs patients' quality of life. The study reported here examined the efficacy of acupuncture in alleviating xerostomia symptoms especially dry mouth. A total of 145 patients with chronic radiation-induced xerostomia >18 months after treatments were recruited from seven UK cancer centres. The study employed a randomised crossover design with participants receiving two group sessions of oral care education and eight of acupuncture using standardised methods. Patient-reported outcome (PROs) measures were completed at baseline and weeks 5, 9, 13, 17, and 21. The primary outcome was improvement in dry mouth. saliva measurements were also carried out. Acupuncture compared with oral care, produced significant reductions in patient reports of severe dry mouth (OR = 2.01, P = 0.031) sticky saliva (OR = 1.67, P = 0.048), needing to sip fluids to swallow food (OR = 2.08, P = 0.011) and in waking up at night to drink (OR = 1.71, P = 0.013). There were no significant changes in either stimulated or unstimulated saliva measurements over time. Eight sessions of weekly group acupuncture compared with group oral care education provide significantly better relief of symptoms in patients suffering from chronic radiation-induced xerostomia.

Xerostomia and Salivary Gland Hypofunction in Patients with Oral Lichen Planus Before and After Treatment with Topical Corticosteroids.

PubMed

Al-Janaby, Hala; El-Sakka, Haytham; Masood, Manal; Ashani W Mendis, Walimuni; M Slack-Smith, Linda; Parsons, Richard; M Frydrych, Agnieszka

2017-01-01

Oral lichen planus and mouth dryness are common pathoses, yet not entirely understood. These two conditions may be associated, with a few studies investigating the relationship between mouth dryness and oral lichen planus providing conflicting results. None of the studies have explored the specific impact of disease treatment on mouth dryness. The purpose of this observational before and after comparison study was to examine the effect of treatment of oral lichen planus with topical corticosteroids on mouth dryness. Nineteen subjects with oral lichen planus were evaluated for the severity of xerostomia using a xerostomia inventory and a visual analogue scale. Stimulated and unstimulated whole salivary flow rates, unstimulated salivary pH and buffering capacity were also measured. All subjects were evaluated before and after treatment with topical corticosteroids. All subjects reported xerostomia before treatment with topical corticosteroids, with 79% reporting a significant improvement ( P = 0.03) after treatment. Topical corticosteroid treatment was not associated with statistically significant differences in stimulated or unstimulated salivary flow rates, unstimulated salivary pH or buffering capacity. The results of this study suggest that treatment of oral lichen planus with topical corticosteroids may decrease the severity of dry mouth symptoms.

Translation and Validation of a Korean Version of the Xerostomia Inventory in Patients with Primary Sjögren's Syndrome.

PubMed

Lee, Jennifer; Koh, Jung Hee; Kwok, Seung-Ki; Park, Sung-Hwan

2016-05-01

This study was conducted to generate and validate a cross-culturally adapted Korean version of the xerostomia inventory (XI), an 11-item questionnaire designed to measure the severity of xerostomia. The original English version of the XI was translated into Korean according to the guidelines for cross-cultural adaptation of health-related quality-of-life measures. Among a prospective cohort of primary Sjögren's syndrome (pSS) in Korea, 194 patients were analyzed. Internal consistency was evaluated by using Cronbach's alpha, and test-retest reliability was obtained by using an intraclass correlation coefficient (ICC) analysis. Construct validity was investigated by performing a correlation analysis between XI total score and salivary flow rate (SFR). Cronbach's alpha for internal consistency was 0.868, and the ICC for test-retest reliability ranged from 0.48 to 0.827, with a median value of 0.72. Moderate negative correlations between XI score and stimulated SFR, unstimulated SFR, and differential (stimulated minus unstimulated) SFR were observed (Spearman's rho, ρ = -0.515, -0.447, and -0.482, respectively; P < 0.001). The correlation analysis between the visual analogue scale (VAS) score of overall dryness and SFR indicated a smaller ρ value (-0.235 [P = 0.006], -0.243 [P = 0.002], and -0.252 [P = 0.003], respectively), which supports that XI more accurately reflects the degree of xerostomia in the pSS patients. In conclusion, the Korean version of the XI is a reliable tool to estimate the severity of xerostomia in patients with pSS.

Regional Control of Tumor Growth

PubMed Central

Zaslavsky, Alexander; Chen, Catherine; Grillo, Jenny; Baek, Kwan-Hyuck; Holmgren, Lars; Yoon, Sam S.; Folkman, Judah; Ryeom, Sandra

2010-01-01

Tumors implanted near the scapulae have been shown to grow four-times faster than the same tumors implanted at the iliac crest. While there were marked differences in the vascularization of tumors from these two different sites, the mechanism controlling regional angiogenesis was not identified. Here we demonstrate site-specific growth of intraperitoneal tumor implants in the mouse abdomen. Our data indicate that the angiogenic response of the host differs significantly between the upper and lower sites in the mouse abdomen and reveals that the expansion of tumor mass is restricted at sites with low angiogenic responses such as the bowel mesentery in the lower abdomen. We show that in this model, this suppression of angiogenesis is due to an expression gradient of thrombospondin-1, a potent endogenous angiogenesis inhibitor. Mice with a targeted deletion of thrombospondin-1 no longer demonstrate regional restriction of tumor growth. The physiological relevance of these findings may be seen in patients with peritoneal carcinomatosis, whereby tumors spread within the peritoneal cavity and show differential growth in the upper and lower abdomen. We hypothesize that the difference in tumor growth in these patients may be due to a gradient of thrombospondin-1 expression in stroma. Finally, our studies suggest that upregulation of thrombospondin-1 in tumor cells is one method to suppress the growth of tumors in the upper abdomen. PMID:20736295

Placebo-controlled clinical trial of use of 10% hydrogen peroxide whitening strips for medication-induced xerostomia.

PubMed

Papas, Athena S; Kugel, Gerard; Singh, Mabi; Barker, Matthew L; Gerlach, Robert W

2009-01-01

A randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the effectiveness and safety of peroxide-containing strip-based tooth whitening among subjects with medication-induced hyposalivation. Eligibility for this tooth whitening study was limited to dentate adults taking xerogenic medications with an unstimulated salivary flow < or = 0.2 ml/min. After giving informed consent, 42 subjects were randomized using a 2:1 ratio to 10% hydrogen peroxide whitening strips (Crest Whitestrips Premium) or placebo strips without peroxide. Strips were used for 30 min twice daily for a 14-day period. Usage was unsupervised, and only the maxillary arch was treated. On days 8 and 15, efficacy was assessed from standard digital images of the anterior dentition and quantified using the Cielab color system, while safety was assessed from interviews and clinical examinations. At day 8, the peroxide group experienced significant (p < 0.001) color improvement relative to baseline and placebo. Adjusted means +/- standard errors for yellowness reduction were -1.65 +/- 0.115 units for the peroxide group and -0.32 +/- 0.170 units for the placebo group. For the increase in lightness, adjusted means +/- standard errors on day 8 were 1.53 +/- 0.130 units for the peroxide group and 0.37 +/- 0.191 units for the controls. Continued strip use through day 15 yielded incremental color improvement for the peroxide group. Mild and transient tooth sensitivity represented the most common adverse events. No subject discontinued treatment due to a product-related adverse event. Twice daily use of 10% hydrogen peroxide whitening strips by adults with medication-induced xerostomia was well tolerated, with significant tooth color improvement evident within 7 days. Copyright 2009 S. Karger AG, Basel.

Assessment of the use of sialogogues in the clinical management of patients with xerostomia.

PubMed

Chainani-Wu, Nita; Gorsky, Meir; Mayer, Priscilla; Bostrom, Alan; Epstein, Joel B; Silverman, Sol

2006-01-01

This study was conducted to assess the clinical efficacy and adverse effects of pilocarpine, bethanechol and cevimeline in patients with xerostomia. In this open-label crossover assessment in 20 patients with xerostomia, a one- to two-week course of each medication with a one-week washout period was prescribed. Side effects, symptoms, whole stimulated and unstimulated saliva were measured. Each sialogogue was found to increase saliva and decrease symptoms. A mixed-effects analysis showed a greater increase in stimulated saliva on bethanechol compared to pilocarpine (0.106, p = 0.0272). Increased sweating was the most common side effect, experienced more frequently with pilocarpine as compared to bethanechol (p = 0.0588) or cevimeline (p = 0.0143). A carryover effect beyond the washout period was seen. Effects on saliva and side effects vary between sialogogues, suggesting a benefit of trials with different sialogogues to determine individual patient preference. The observed carryover effect suggests that intermittent treatment may be an alternative to continuous treatment with sialogogues.

Quantitative analysis of normal tissue effects in the clinic (QUANTEC) guideline validation using quality of life questionnaire datasets for parotid gland constraints to avoid causing xerostomia during head-and-neck radiotherapy.

PubMed

Lee, Tsair-Fwu; Fang, Fu-Min

2013-03-01

To perform a validation test of the quantitative analysis of normal tissue effects in the clinic (QUANTEC) guidelines against quality of life (QoL) questionnaire datasets collected prospectively from patients with head and neck (HN) cancers, including HN squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC). QoL questionnaire datasets from 95 patients with NPC and 142 with HNSCC were analyzed separately. The European Organization for Research and Treatment of Cancer H&N35 QoL questionnaire was used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate to severe xerostomia 3 and 12 months after the completion of RT, and excluded patients with grade 3(+) xerostomia at the baseline. The Lyman-Kutcher-Burman normal tissue complication probability (NTCP) model was used to describe the incidence of xerostomia. Negative predictive values (NPVs) were used to determine the rate of correctly predicting the lack of complications. NTCP fitted parameters were TD₅₀=37.8 Gy (CI: 29.1-46.9 Gy), m=0.59 (CI: 0.48-0.80) and TD50=43.9 Gy (CI: 33.2-52.8 Gy), m=0.48 (CI: 0.37-0.76) at the 3-month and 12-month time points, respectively. For QUANTEC validation, HN and HNSCC data validation gave similar results at 3 months; at mean doses to the spared parotid of ≤20 and ≤25 Gy, the QoL dataset showed approximately 22% and 28% rates of xerostomia, respectively. At 12 months, the rates of xerostomia were approximately 13% and 19%, respectively. For NPC cases, the dataset showed approximately 0% and 33% (∼67% NPV) rates of xerostomia at 3 months. At 12 months, both rates of xerostomia were approximately 0% (∼100% NPV), which differed significantly from the results for the HNSCC cohort. The QoL datasets validated the QUANTEC guidelines and suggested that the modified QUANTEC 20/20-Gy spared-gland guideline is suitable for clinical use in HNSCC cohorts to effectively avoid xerostomia, and the QUANTEC 25-Gy guideline is

Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

PubMed

Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

2003-07-01

The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being

Xerostomia Quality of Life Scale (XeQoLS) questionnaire: validation of Italian version in head and neck cancer patients.

PubMed

Lastrucci, Luciana; Bertocci, Silvia; Bini, Vittorio; Borghesi, Simona; De Majo, Roberta; Rampini, Andrea; Gennari, Pietro Giovanni; Pernici, Paola

2018-01-01

To translate the Xerostomia Quality-of-Life Scale (XeQoLS) into Italian language (XeQoLS-IT). Xerostomia is the most relevant acute and late toxicity in patients with head and neck cancer treated with radiotherapy (RT). Patient-reported outcome (PRO) instruments are subjective report on patient perception of health status. The XeQoLS consists of 15 items and measures the impact of salivary gland dysfunction and xerostomia on the four major domains of oral health-related QoL. The XeQoLS-IT was created through a linguistic validation multi-step process: forward translation (TF), backward translation (TB) and administration of the questionnaire to 35 Italian patients with head and neck cancer. Translation was independently carried out by two radiation oncologists who were Italian native speakers. The two versions were compared and adapted to obtain a reconciled version, version 1 (V1). V1 was translated back into English by an Italian pro skilled in teaching English. After review of discrepancies and choice of the most appropriate wording for clarity and similarity to the original, version 2 (V2) was reached by consensus. To evaluate version 2, patients completed the XeQoLS-IT questionnaire and also underwent a cognitive debriefing. The questionnaire was considered simple by the patients. The clarity of the instructions and the easiness to answer questions had a mean value of 4.5 (± 0.71) on a scale from 1 to 5. A valid multi-step process led to the creation of the final version of the XeQoLS-IT, a suitable instrument for the perception of xerostomia in patients treated with RT.

Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's syndrome in a vegetarian with stomatitis, glossodynia, xerostomia, and elevated antinuclear antibodies: Case report
.

PubMed

Cuny, Clemens; Vaerst, Barbara; Gabrielpillai, Jennis; Tahtali, Aykut; Balster, Sven; Lissner, Reinhard; Woodcock, Barry G

2018-01-01

Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin^®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
.

Management of cancer therapy-induced oral mucositis pain and xerostomia with extra- and intra oral laser irradiation

NASA Astrophysics Data System (ADS)

Libik, T. V.; Gileva, O. S.; Danilov, K. V.; Grigorev, S. S.; Pozdnyakova, A. A.

2017-09-01

This study evaluated the efficacy of combined (intra- and extraoral) low-level laser therapy (LLLT) and conventional pharmacological modalities in prevention and treatment of oral mucositis (OM) and associated pain and xerostomia in patients with head and neck cancer (HNC) undergoing concurrent chemoradiotherapy (CRT). A prospective comparative randomized study was conducted with 21 patients with head and neck cancer subjected to CRT. Eleven patients received extra- and intraoral LLLT daily from the 1st day until the end of CRT-course before each session during 5 consecutive days, and the other 10 patients received conventional preventive and treatment procedures based on the use of benzidamine 0.15% solution also throughout the duration of CRT, including weekends. OM was measured using an oral toxicity scale (OTS), oral pain was measured using the color-numeric visual analogue scale (VAS), unstimulated salivary flow rate measured by the spitting technique (ml/min), dry mouth symptoms were self-estimated by patients using The Xerostomia Inventory (XI). The LLLT group showed lower mean OTS and VAS scores, lower level of reduction of salivary flow rate during the course of CRT. In both groups, no interruption of CRT was needed. The prophylactic use of both treatments proposed in this study seems to reduce the incidence of severe OM lesions. However, the LLLT was more effective in delaying the appearance of severe OM, oral pain and xerostomia.

The role of parotid gland irradiation in the development of severe hyposalivation (xerostomia) after intensity-modulated radiation therapy for head and neck cancer: Temporal patterns, risk factors, and testing the QUANTEC guidelines.

PubMed

Owosho, Adepitan A; Thor, Maria; Oh, Jung Hun; Riaz, Nadeem; Tsai, C Jillian; Rosenberg, Haley; Varthis, Spyridon; Yom, Sae Hee K; Huryn, Joseph M; Lee, Nancy Y; Deasy, Joseph O; Estilo, Cherry L

2017-04-01

The aims of this study were to investigate temporal patterns and potential risk factors for severe hyposalivation (xerostomia) after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and to test the two QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines. Sixty-three patients treated at the Memorial Sloan Kettering Cancer Center between 2006 and 2015, who had a minimum of three stimulated whole mouth saliva flow measurements (WMSFM) at a median follow-up time of 11 (range: 3-24) months were included. Xerostomia was defined as WMSFM ≤25% compared to relative pre-radiotherapy. Patients were stratified into three follow-up groups: 1: <6 months; 2: 6-11 months; and 3: 12-24 months. Potential risk factors were investigated (Mann-Whitney U test), and relative risks (RRs) assessed for the two QUANTEC guidelines. The incidence of xerostomia was 27%, 14% and 17% at follow-up time points 1, 2 and 3, respectively. At <6 months, the mean dose to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) was higher among patients with xerostomia (Dmean contra : 25 Gy vs. 15 Gy; Dmean ipsi : 44 Gy vs. 25 Gy). Patients with xerostomia had higher pre-RT WMSFM (3.5 g vs. 2.4 g), and had been treated more frequently with additional chemotherapy (93% vs. 63%; all 4 variables: p < 0.05). At 6-11 months, Dmean contra among patients with xerostomia was higher compared to patients without (26 Gy vs. 20 Gy). The RR as specified by the one- and two-gland QUANTEC guideline was 2.3 and 1.4 for patients with <6 months follow-up time, and 2.0 and 1.2 for patients with longer follow-up (6-11 + 6-24 months). Xerostomia following IMRT peaks within six months post-radiotherapy and fades with time. Limiting the mean dose to both parotid glands (ipsilateral <25 Gy, contralateral <25 Gy) and reducing the use of chemotherapy will likely decrease the rate of xerostomia. Both QUANTEC guidelines are effective in

Xerostomia health-related quality of life: NRG oncology RTOG 0537.

PubMed

Wyatt, Gwen; Pugh, Stephanie L; Wong, Raimond K W; Sagar, Stephen; Singh, Anurag K; Koyfman, Shlomo A; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Francis S; Sultanem, Khalil; Hodson, Ian; Krempl, Greg A; Lukaszczyk, Barbara; Yeh, Alexander M; Berk, Lawrence

2016-09-01

The purpose of this secondary analysis was to determine change in overall health-related quality of life (HRQOL) based on patient data obtained from NRG Oncology RTOG 0537 as measured by the RTOG-modified University of Washington Head and Neck Symptom Score (RM-UWHNSS). A multi-site prospective randomized clinical trial design stratified 137 patients with post-radiation therapy xerostomia according to prior pilocarpine (PC) treatment and time after radiation therapy and/or chemotherapy and randomized patients into two groups. Patients were assigned to acupuncture or PC. Twenty-four sessions of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) were administered over 12 weeks, or oral PC (5 mg) three times daily over the same 12 weeks. The RM-UWHNSS was administered at baseline and at 4, 6, 9, and 15 months after the date of randomization. There were no between-arm differences in change scores on the RM-UWHNSS in the individual items, total score, or factor scores. For statistical modeling, race and time were significant for all outcomes (total and factor scores), while treatment arm was not significant. The ALTENS arm showed greater yet nonsignificant improvement in outcomes compared to the PC arm. Although no significant treatment differences were seen in this trial, patients receiving ALTENS consistently had lower scores, indicating better function, as compared to those receiving PC. Radiation-induced xerostomia improved over time for all patients.

General health influences episodes of xerostomia: a prospective population-based study.

PubMed

da Silva, Luciana; Kupek, Emil; Peres, Karen G

2017-04-01

The aim of this study was to investigate the associated factors of changes in symptoms of xerostomia (SOX) in adults aged 20-59. A prospective population-based study was conducted in 2009 (n = 1720) and 2012 (n = 1222) in the urban area of Florianópolis, SC, Brazil. Information on SOX was collected in both years together with age, family income, years of schooling, smoking habit, alcohol consumption, changes in the body mass index (BMI; kg/m²), medicine use, self-reported diagnosis of chronic diseases, change in hypertension status and in the use and need for dentures, and number of remaining teeth. Associated factors with changes in SOX were investigated using multinomial logistic regression, considering those who had never reported this symptom as the reference. Prevalence of regular SOX was equal to 3.8% (95% CI: 2.9-5.1) and irregular (one period only) equal to 12.2% (95% CI: 10.2-14.5). Age, smoking habit, medicine use, self-reported diagnosis of depression, and weight gain increased the probability of regular SOX, whereas highest schooling level was associated with lower probability of this symptom. General and psychosocial health influenced the number of episodes of xerostomia symptoms, calling for multidisciplinary actions to prevent common risk behaviors for oral and general diseases. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Evaluation of the efficacy of two mouthrinses formulated for the relief of xerostomia of diverse origin in adult subjects.

PubMed

Morales-Bozo, Irene; Rojas, Gonzalo; Ortega-Pinto, Ana; Espinoza, Iris; Soto, Lilian; Plaza, Anita; Lozano, Carla; Urzúa, Blanca

2012-06-01

To evaluate the efficacy of two new mouthrinses in the reduction of xerostomía-associated symptomatology. Xerostomia is a common chronic health condition that affects a great number of adults and significantly deteriorates quality of life, such that treatment is necessary. Sixty-seven adult subjects of both sexes presenting xerostomia of diverse origin were selected. Mouthrinses were tested using a double-blind, randomized, cross-over clinical trial with an intervining wash out period. The 100% of subjects presented sensation of dry mouth, and 86% stated sensation of thick saliva. Burning tongue sensation, need to drink liquids to swallow and the sensation of swallowing difficulty were recorded in more than 50% of the patients. The most frequent pathologies in the sample were depression, arthritis, and arterial hypertension. Results of the clinical tests showed that mouthrinse 1 relieves sensation of dry mouth, need to drink liquids, and swallowing difficulty. In contrast, mouthrinse 2 relieves only latter two symptoms. Both rinses were more effective in relieving xerostomía-associated symptomatology in patients taking 3 or more medicines simultaneously. Both mouthrinses were effective in relieving various xerostomia symptoms, could be distributed at a low cost, thereby improving the quality of life of population affected. © 2012 The Gerodontology Society and John Wiley & Sons A/S.

Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

PubMed Central

Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

2011-01-01

Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

PubMed

Guckenberger, Matthias; Klement, Rainer J; Allgäuer, Michael; Andratschke, Nicolaus; Blanck, Oliver; Boda-Heggemann, Judit; Dieckmann, Karin; Duma, Marciana; Ernst, Iris; Ganswindt, Ute; Hass, Peter; Henkenberens, Christoph; Holy, Richard; Imhoff, Detlef; Kahl, Henning K; Krempien, Robert; Lohaus, Fabian; Nestle, Ursula; Nevinny-Stickel, Meinhard; Petersen, Cordula; Semrau, Sabine; Streblow, Jan; Wendt, Thomas G; Wittig, Andrea; Flentje, Michael; Sterzing, Florian

2016-03-01

To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

LASSO NTCP predictors for the incidence of xerostomia in patients with head and neck squamous cell carcinoma and nasopharyngeal carcinoma

PubMed Central

Lee, Tsair-Fwu; Liou, Ming-Hsiang; Huang, Yu-Jie; Chao, Pei-Ju; Ting, Hui-Min; Lee, Hsiao-Yi

2014-01-01

To predict the incidence of moderate-to-severe patient-reported xerostomia among head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT). Multivariable normal tissue complication probability (NTCP) models were developed by using quality of life questionnaire datasets from 152 patients with HNSCC and 84 patients with NPC. The primary endpoint was defined as moderate-to-severe xerostomia after IMRT. The numbers of predictive factors for a multivariable logistic regression model were determined using the least absolute shrinkage and selection operator (LASSO) with bootstrapping technique. Four predictive models were achieved by LASSO with the smallest number of factors while preserving predictive value with higher AUC performance. For all models, the dosimetric factors for the mean dose given to the contralateral and ipsilateral parotid gland were selected as the most significant predictors. Followed by the different clinical and socio-economic factors being selected, namely age, financial status, T stage, and education for different models were chosen. The predicted incidence of xerostomia for HNSCC and NPC patients can be improved by using multivariable logistic regression models with LASSO technique. The predictive model developed in HNSCC cannot be generalized to NPC cohort treated with IMRT without validation and vice versa. PMID:25163814

Dosimetric Predictors of Patient-Reported Xerostomia and Dysphagia With Deintensified Chemoradiation Therapy for HPV-Associated Oropharyngeal Squamous Cell Carcinoma.

PubMed

Chera, Bhishamjit S; Fried, David; Price, Alex; Amdur, Robert J; Mendenhall, William; Lu, Chiray; Das, Shiva; Sheets, Nathan; Marks, Lawrence; Mavroidis, Panayiotis

2017-08-01

To estimate the association between different dose-volume metrics of the salivary glands and pharyngeal constrictors with patient reported severity of xerostomia/dysphagia in the setting of deintensified chemoradiation therapy (CRT). Forty-five patients were treated on a phase 2 study assessing the efficacy of deintensified CRT for favorable-risk, HPV-associated oropharyngeal squamous cell carcinoma. Patients received 60 Gy intensity modulated radiation therapy with concurrent weekly cisplatin (30 mg/m 2 ), and reported the severity of their xerostomia/dysphagia (before and after treatment) using the patient-reported outcome version of the Common Terminology Criteria for Adverse Events (CTCAE) (PRO-CTCAE). Individual patient dosimetric data of the contralateral parotid and submandibular glands and pharyngeal constrictors were correlated with changes in PRO-CTCAE severity. A change in severity (from baseline) of ≥2 was considered clinically meaningful. Associations between dose-volume metrics and patient outcomes were assessed with receiver operating characteristic (ROC) curve and logistic regression model. Six months after CRT, patients reporting <2 change in xerostomia severity (n=14) had an average D mean = 22 ± 9 Gy to the sum of the contralateral glands (parotid + submandibular) compared with the patients reporting ≥2 change (n=21), who had an average D mean = 34 ± 8 Gy. V15 to V55 for the combined contralateral glands showed the strongest association with xerostomia (area under the curve [AUC] = 0.83-0.86). Based on the regression analysis, a 20% risk of toxicity was associated with V15 = 48%, V25 = 30%, and D mean =21 Gy. Six months after CRT, patients reporting <2 change in dysphagia severity (n=26) had an average V55 = 76 ± 13 (%) to the superior pharyngeal constrictor compared with the patients reporting ≥2 change in severity (n=9), who had average V55 = 89 ± 13 (%). V55to V60 had the strongest association with dysphagia (AUC = 0

Development of NTCP models for head and neck cancer patients treated with three-dimensional conformal radiotherapy for xerostomia and sticky saliva: the role of dosimetric and clinical factors.

PubMed

Beetz, Ivo; Schilstra, Cornelis; Burlage, Fred R; Koken, Phil W; Doornaert, Patricia; Bijl, Henk P; Chouvalova, Olga; Leemans, C René; de Bock, Geertruida H; Christianen, Miranda E M C; van der Laan, Bernard F A M; Vissink, Arjan; Steenbakkers, Roel J H M; Langendijk, Johannes A

2012-10-01

The purpose of this multicentre prospective study was to investigate the significance of the radiation dose in the major and minor salivary glands, and other pre-treatment and treatment factors, with regard to the development of patient-rated xerostomia and sticky saliva among head and neck cancer (HNC) patients treated with primary (chemo-) radiotherapy ((CH)RT). The study population was composed of 167 consecutive HNC patients treated with three-dimensional conformal (3D-CRT) (CH) RT. The primary endpoint was moderate to severe xerostomia (XER6m) as assessed by the EORTC QLQ-H&N35 at 6 months after completing (CH)RT. The secondary endpoint was moderate to severe sticky saliva at 6 months (STIC6m). All organs at risk (OARs) potentially involved in salivary function were delineated on planning-CT, including the parotid, submandibular and sublingual glands and the minor glands in the soft palate, cheeks and lips. Patients with moderate to severe xerostomia or sticky saliva at baseline were excluded. The optimum number of variables for a multivariate logistic regression model was determined using a bootstrapping method. The multivariate analysis showed the mean parotid dose, age and baseline xerostomia (none versus a bit) to be the most important predictors for XER6m. The risk of developing xerostomia increased with age and was higher when minor baseline xerostomia was present in comparison with patients without any xerostomia complaints at baseline. Model performance was good with an area under the curve (AUC) of 0.82. For STIC6m, the mean submandibular dose, age, the mean sublingual dose and baseline sticky saliva (none versus a bit) were most predictive for sticky saliva. The risk of developing STIC6m increased with age and was higher when minor baseline sticky saliva was present in comparison with patients without any sticky saliva complaints at baseline. Model performance was good with an AUC of 0.84. Dose distributions in the minor salivary glands in patients

Management of Hyposalivation and Xerostomia: Criteria for Treatment Strategies.

PubMed

Epstein, Joel B; Beier Jensen, Siri

2015-09-01

Saliva management in patients with hyposalivation is potentially complex. Future development of oral care products and treatment strategies requires attention to the biology of saliva and the best means of providing a continuum of relief for people with xerostomia--the sensation of dry mouth--and hyposalivation--documented reduction in saliva flow. Improvement in patient care requires that clinicians be aware of approaches to management, desirable qualities of methods and products, and that they seek the development of products that support the functions of saliva and promote comfort and health. In this brief review of the epidemiology of hyposalivation, the biology and functions of saliva are presented in order to guide clinical decision-making to address the needs of patients with dry mouth.

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Raimond K.W., E-mail: wongrai@hhsc.ca; Deshmukh, Snehal; Wyatt, Gwen

Purpose and Objectives: This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Methods and Materials: Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reductionmore » in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. Results: One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were −0.53 and −0.27 (P=.45) and −0.6 and −0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. Conclusions: The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint—the change in radiation-induced xerostomia symptom burden at 9 MFR—was not significantly different between the ALTENS and PC groups. There was

Acupuncture-Like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Radiation-Induced Xerostomia: Results of RTOG 0537 Phase 3 Study.

PubMed

Wong, Raimond K W; Deshmukh, Snehal; Wyatt, Gwen; Sagar, Stephen; Singh, Anurag K; Sultanem, Khalil; Nguyen-Tân, Phuc F; Yom, Sue S; Cardinale, Joseph; Yao, Min; Hodson, Ian; Matthiesen, Chance L; Suh, John; Thakrar, Harish; Pugh, Stephanie L; Berk, Lawrence

2015-06-01

This report presents the analysis of the RTOG 0537 multicenter randomized study that compared acupuncture-like transcutaneous stimulation (ALTENS) with pilocarpine (PC) for relieving radiation-induced xerostomia. Eligible patients were randomized to twice-weekly 20-minute ALTENS sessions for 24 sessions during 12 weeks or PC (5 mg 3 times daily for 12 weeks). The primary endpoint was the change in the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS) scores from baseline to 9 months from randomization (MFR). Secondary endpoints included basal and citric acid primed whole salivary production (WSP), ratios of positive responders (defined as patients with ≥20% reduction in overall radiation-induced xerostomia symptom burden), and the presence of adverse events based on the Common Terminology Criteria for Adverse Events version 3. An intention-to-treat analysis was conducted. One hundred forty-eight patients were randomized. Only 96 patients completed the required XeQOLS and were evaluable at 9 MFR (representing merely 68.6% statistical power). Seventy-six patients were evaluable at 15 MFR. The median change in the overall XeQOLS in ALTENS and PC groups at 9 and 15 MFR were -0.53 and -0.27 (P=.45) and -0.6 and -0.47 (P=.21). The corresponding percentages of positive responders were 81% and 72% (P=.34) and 83% and 63% (P=.04). Changes in WSP were not significantly different between the groups. Grade 3 or less adverse events, mostly consisting of grade 1, developed in 20.8% of patients in the ALTENS group and in 61.6% of the PC group. The observed effect size was smaller than hypothesized, and statistical power was limited because only 96 of the recruited 148 patients were evaluable. The primary endpoint-the change in radiation-induced xerostomia symptom burden at 9 MFR-was not significantly different between the ALTENS and PC groups. There was significantly less toxicity in patients receiving ALTENS. Copyright © 2015 Elsevier Inc. All

Efficacy and safety of pilocarpine for radiation-induced xerostomia in patients with head and neck cancer: A systematic review and meta-analysis.

PubMed

Cheng, Cai-Qi; Xu, Hao; Liu, Ling; Wang, Rui-Nan; Liu, Yu-Ting; Li, Jing; Zhou, Xi-Kun

2016-04-01

Pilocarpine has been used widely in the treatment of dry mouth and glaucoma. In this review, the authors assessed the efficacy and safety of pilocarpine for patients with head and neck cancer who have radiation-induced xerostomia. The authors conducted a systematic search including meta-analyses and randomized controlled trials in the following databases: MEDLINE, Embase, Cochrane Library, and Science Citation Index Expanded. The primary outcome was the severity of xerostomia (measured using visual analog scale [VAS] scores). Adverse events were other outcomes of interest. The authors performed meta-analyses where appropriate. The authors used the Cochrane Collaboration's tool for assessing risk of bias to assess the quality of the study. The authors identified 6 studies (including 752 patients in total). The results of a meta-analysis of 3 articles showed that pilocarpine was associated with a 12-point increase in VAS score (mean difference, 12.00; 95% confidence interval [CI], 1.93-22.08; P = .02) and higher rates of adverse events compared with placebo in terms of sweating (odds ratio [OR], 3.71; 95% CI, 2.34-5.86; P < .00001). There were no differences in rhinitis (OR, 1.21; 95% CI, 0.68-2.16; P = .52) and nausea (OR, 1.44; 95% CI, 0.83-2.49; P = .19). On the basis of the best available evidence, the results of this meta-analysis provide evidence that pilocarpine offers statistically significant clinical benefits for the symptomatic treatment of radiation-induced xerostomia in patients with head and neck cancer. However, the authors of this systematic review found the best available evidence in the meta-analysis in 3 studies, 1 of which showed no effect. The authors of this systematic review suggest that these patients take 5 milligrams of pilocarpine 3 times daily, and that there is need for further study. Copyright © 2016 American Dental Association. Published by Elsevier Inc. All rights reserved.

Salivary gland function 5 years after radioactive iodine ablation in patients with differentiated thyroid cancer: direct comparison of pre- and postablation scintigraphies and their relation to xerostomia symptoms.

PubMed

Jeong, Shin Young; Kim, Hae Won; Lee, Sang-Woo; Ahn, Byeong-Cheol; Lee, Jaetae

2013-05-01

Chronic sialadenitis is one of the most frequent chronic complications after radioactive iodine (RAI) therapy for thyroid cancer. To evaluate the long-term effects of RAI ablation on salivary gland function, we investigated scintigraphic changes in salivary glands by direct comparison of two salivary gland scintigraphies (SGSs) taken before and at 5 years after an RAI ablation. SGS was performed just before RAI ablation (pre-SGS) and ∼5 years after RAI ablation (F/U SGS) in 213 subjects who underwent thyroidectomy for thyroid cancer. The uptake score (U score) was graded, and the ejection fraction (EF) was quantified for the parotid and submandibular glands at pre-SGS and F/U SGS. Changes in salivary gland function were graded as mild, moderate, or severe according to the differences in U score and EF between the two SGSs. Xerostomia was assessed and compared with the SGS findings. Worsening of the U score was observed in 182 of 852 salivary glands (total: 21.3%; mild: 4.2%, moderate: 7.4%, severe: 9.7%), and 47.4% of the patients had a worsening U score for at least one of four salivary glands. A decrease in EF was observed in 173 of 852 salivary glands (total: 20.3%; mild: 5.4%, moderate: 6.8%, severe: 8.1%), and 43.7% of the patients experienced a decrease in the EF of at least one of the four salivary glands. Bilateral parotid gland dysfunction was the most commonly observed condition. Thirty-five (16.4%) patients complained of xerostomia at 5 years after RAI ablation. Scintigraphic changes in salivary gland function and xerostomia were more common in patients receiving 5.55 GBq, compared with 3.7 GBq. Xerostomia was more common in patients with submandibular gland dysfunction than those with parotid gland dysfunction (68.8% vs. 33.3%, p<0.05). The number of dysfunctional salivary glands was correlated with xerostomia (p<0.01). About 20% of the salivary glands were dysfunctional on SGS 5 years after a single RAI ablation, especially in patients who

Synergistic Effects of Hemoglobin and Tumor Perfusion on Tumor Control and Survival in Cervical Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayr, Nina A.; Center for Advanced Radiation Technology and Therapy; Wang, Jian Z.

2009-08-01

Purpose: The tumor oxygenation status is likely influenced by two major factors: local tumor blood supply (tumor perfusion) and its systemic oxygen carrier, hemoglobin (Hgb). Each has been independently shown to affect the radiotherapy (RT) outcome in cervical cancer. This study assessed the effect of local tumor perfusion, systemic Hgb levels, and their combination on the treatment outcome in cervical cancer. Methods and Materials: A total of 88 patients with cervical cancer, Stage IB2-IVA, who were treated with RT/chemotherapy, underwent serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) before RT, at 20-22 Gy, and at 45-50 Gy. The DCE-MRI perfusion parameters,more » mean and lowest 10th percentile of the signal intensity distribution in the tumor pixels, and the Hgb levels, including pre-RT, nadir, and mean Hgb (average of weekly Hgb during RT), were correlated with local control and disease-specific survival. The median follow-up was 4.6 years. Results: Local recurrence predominated in the group with both a low mean Hgb (<11.2 g/dL) and low perfusion (lowest 10th percentile of signal intensity <2.0 at 20-22 Gy), with a 5-year local control rate of 60% vs. 90% for all other groups (p = .001) and a disease-specific survival rate of 41% vs. 72% (p = .008), respectively. In the group with both high mean Hgb and high perfusion, the 5-year local control rate and disease-specific survival rate was 100% and 78%, respectively. Conclusion: These results suggest that the compounded effects of Hgb level and tumor perfusion during RT influence the radioresponsiveness and survival in cervical cancer patients. The outcome was worst when both were impaired. The management of Hgb may be particularly important in patients with low tumor perfusion.« less

Modified schirmer test--a screening tool for xerostomia among subjects on antidepressants.

PubMed

Kumar, Nerella Narendra; Panchaksharappa, Mamatha Gowda; Annigeri, Rajeshwari G

2014-08-01

The aim of the present study is to assess salivary flow rate in the subjects who were on antidepressant medications and its comparison with healthy controls and assessment of unstimulated salivary flow rate by modified Schirmer test (MST) and volumetric method (spitting method) for evaluation of xerostomia and whether any correlation exists between two methods. Thirty subjects who were on antidepressants were divided into two groups: tricyclic antidepressants (TCA) and selective sertonin reuptake inhibitors (SSRI) of 15 each, compared with 30 age and gender matched controls. Unstimulated salivary flow rate was measured by both MST and spitting method. The unstimulated salivary flow rate measured by MST at the end of 3rd minute was 13.7 ± 10.08, 19.86 ± 8.95 and 31.0 ± 5.4 mm and by spitting method was 0.12 ± 0.07, 0.19 ± 0.10 and 0.30 ± 0.75 ml/min in TCA, SSRI and controls respectively (p<0.001). The Pearson correlation coefficient of r=0.85 shows excellent correlation between the two screening tests. Sensitivity and Specificity of MST was 90.9% and 31.5%. Salivary flow rate was less in antidepressant subjects when compared to the healthy controls. Results of the present study showed an excellent correlation excellent correlation between the two screening tests which suggests that MST can be routinely used as chair-side screening tool to evaluate hyposalivation which is time saving, patient friendly and specific of salivary secretions. Copyright © 2014 Elsevier Ltd. All rights reserved.

A double-blind, randomized, placebo-controlled study of cevimeline in Sjögren's syndrome patients with xerostomia and keratoconjunctivitis sicca.

PubMed

Petrone, Dianne; Condemi, John J; Fife, Rose; Gluck, Oscar; Cohen, Stanley; Dalgin, Paul

2002-03-01

To evaluate the safety and efficacy of 2 dosages of cevimeline for the treatment of xerostomia and keratoconjunctivitis sicca in patients with Sjögren's syndrome. A 12-week double-blind, randomized, placebo-controlled study was performed. Patients were randomly assigned to receive either placebo, 15 mg of cevimeline 3 times daily, or 30 mg of cevimeline 3 times daily. Patients were evaluated at baseline and throughout the study for their global assessment of dryness (mouth, eyes, overall) as well as their subjective assessment of the specific symptoms of dry mouth and dry eyes. Total saliva and tear flow also were measured. Patients taking 30 mg of cevimeline 3 times daily had statistically significant improvements in their subjective global assessment of dry eyes (P = 0.0453), dry mouth (P = 0.0004), and increased salivary flow (P = 0.007). Patients receiving the 30-mg dosage also showed greater objective improvement (increased salivary and lacrimal flow rates, as measured by Schirmer's test) than did patients receiving placebo. Frequently reported adverse events included headache, increased sweating, abdominal pain, and nausea. Treatment with cevimeline at a dosage of 30 mg 3 times daily resulted in substantive improvement by increasing the rate of saliva and tear flow in patients with Sjögren's syndrome, as well as improving subjective symptoms of dry mouth, dry eyes, and overall dryness. The 15-mg dosage relieved some symptoms, and both dosages were well tolerated.

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments

PubMed Central

2012-01-01

Background With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman–Kutcher–Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Methods Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson’s chi-squared test, Nagelkerke’s R2, the area under the receiver operating characteristic curve, and the Hosmer–Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson’s chi-squared test was used to test the goodness of fit and association. Results Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose–response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Conclusions Our study shows the agreement between the NTCP

Normal tissue complication probability model parameter estimation for xerostomia in head and neck cancer patients based on scintigraphy and quality of life assessments.

PubMed

Lee, Tsair-Fwu; Chao, Pei-Ju; Wang, Hung-Yu; Hsu, Hsuan-Chih; Chang, PaoShu; Chen, Wen-Cheng

2012-12-04

With advances in modern radiotherapy (RT), many patients with head and neck (HN) cancer can be effectively cured. However, xerostomia is a common complication in patients after RT for HN cancer. The purpose of this study was to use the Lyman-Kutcher-Burman (LKB) model to derive parameters for the normal tissue complication probability (NTCP) for xerostomia based on scintigraphy assessments and quality of life (QoL) questionnaires. We performed validation tests of the Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines against prospectively collected QoL and salivary scintigraphic data. Thirty-one patients with HN cancer were enrolled. Salivary excretion factors (SEFs) measured by scintigraphy and QoL data from self-reported questionnaires were used for NTCP modeling to describe the incidence of grade 3+ xerostomia. The NTCP parameters estimated from the QoL and SEF datasets were compared. Model performance was assessed using Pearson's chi-squared test, Nagelkerke's R2, the area under the receiver operating characteristic curve, and the Hosmer-Lemeshow test. The negative predictive value (NPV) was checked for the rate of correctly predicting the lack of incidence. Pearson's chi-squared test was used to test the goodness of fit and association. Using the LKB NTCP model and assuming n=1, the dose for uniform irradiation of the whole or partial volume of the parotid gland that results in 50% probability of a complication (TD50) and the slope of the dose-response curve (m) were determined from the QoL and SEF datasets, respectively. The NTCP-fitted parameters for local disease were TD50=43.6 Gy and m=0.18 with the SEF data, and TD50=44.1 Gy and m=0.11 with the QoL data. The rate of grade 3+ xerostomia for treatment plans meeting the QUANTEC guidelines was specifically predicted, with a NPV of 100%, using either the QoL or SEF dataset. Our study shows the agreement between the NTCP parameter modeling based on SEF and QoL data, which gave a

Expression of NF-κB p50 in Tumor Stroma Limits the Control of Tumors by Radiation Therapy

PubMed Central

Crittenden, Marka R.; Cottam, Benjamin; Savage, Talicia; Nguyen, Cynthia; Newell, Pippa; Gough, Michael J.

2012-01-01

Radiation therapy aims to kill cancer cells with a minimum of normal tissue toxicity. Dying cancer cells have been proposed to be a source of tumor antigens and may release endogenous immune adjuvants into the tumor environment. For these reasons, radiation therapy may be an effective modality to initiate new anti-tumor adaptive immune responses that can target residual disease and distant metastases. However, tumors engender an environment dominated by M2 differentiated tumor macrophages that support tumor invasion, metastases and escape from immune control. In this study, we demonstrate that following radiation therapy of tumors in mice, there is an influx of tumor macrophages that ultimately polarize towards immune suppression. We demonstrate using in vitro models that this polarization is mediated by transcriptional regulation by NFκB p50, and that in mice lacking NFκB p50, radiation therapy is more effective. We propose that despite the opportunity for increased antigen-specific adaptive immune responses, the intrinsic processes of repair following radiation therapy may limit the ability to control residual disease. PMID:22761754

Using Multivariate Regression Model with Least Absolute Shrinkage and Selection Operator (LASSO) to Predict the Incidence of Xerostomia after Intensity-Modulated Radiotherapy for Head and Neck Cancer

PubMed Central

Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan

2014-01-01

Purpose The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Methods and Materials Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3+ xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R2, chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Results Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R2 was satisfactory and corresponded well with the expected values. Conclusions

Using multivariate regression model with least absolute shrinkage and selection operator (LASSO) to predict the incidence of Xerostomia after intensity-modulated radiotherapy for head and neck cancer.

PubMed

Lee, Tsair-Fwu; Chao, Pei-Ju; Ting, Hui-Min; Chang, Liyun; Huang, Yu-Jie; Wu, Jia-Ming; Wang, Hung-Yu; Horng, Mong-Fong; Chang, Chun-Ming; Lan, Jen-Hong; Huang, Ya-Yu; Fang, Fu-Min; Leung, Stephen Wan

2014-01-01

The aim of this study was to develop a multivariate logistic regression model with least absolute shrinkage and selection operator (LASSO) to make valid predictions about the incidence of moderate-to-severe patient-rated xerostomia among head and neck cancer (HNC) patients treated with IMRT. Quality of life questionnaire datasets from 206 patients with HNC were analyzed. The European Organization for Research and Treatment of Cancer QLQ-H&N35 and QLQ-C30 questionnaires were used as the endpoint evaluation. The primary endpoint (grade 3(+) xerostomia) was defined as moderate-to-severe xerostomia at 3 (XER3m) and 12 months (XER12m) after the completion of IMRT. Normal tissue complication probability (NTCP) models were developed. The optimal and suboptimal numbers of prognostic factors for a multivariate logistic regression model were determined using the LASSO with bootstrapping technique. Statistical analysis was performed using the scaled Brier score, Nagelkerke R(2), chi-squared test, Omnibus, Hosmer-Lemeshow test, and the AUC. Eight prognostic factors were selected by LASSO for the 3-month time point: Dmean-c, Dmean-i, age, financial status, T stage, AJCC stage, smoking, and education. Nine prognostic factors were selected for the 12-month time point: Dmean-i, education, Dmean-c, smoking, T stage, baseline xerostomia, alcohol abuse, family history, and node classification. In the selection of the suboptimal number of prognostic factors by LASSO, three suboptimal prognostic factors were fine-tuned by Hosmer-Lemeshow test and AUC, i.e., Dmean-c, Dmean-i, and age for the 3-month time point. Five suboptimal prognostic factors were also selected for the 12-month time point, i.e., Dmean-i, education, Dmean-c, smoking, and T stage. The overall performance for both time points of the NTCP model in terms of scaled Brier score, Omnibus, and Nagelkerke R(2) was satisfactory and corresponded well with the expected values. Multivariate NTCP models with LASSO can be used to

A systematic review of the effects of acupuncture on xerostomia and hyposalivation.

PubMed

Assy, Zainab; Brand, Henk S

2018-02-13

Saliva is fundamental to our oral health and our well-being. Many factors can impair saliva secretion, such as adverse effects of prescribed medication, auto-immune diseases (for example Sjögren's syndrome) and radiotherapy for head and neck cancers. Several studies have suggested a positive effect of acupuncture on oral dryness. Pubmed and Web of Science were electronically searched. Reference lists of the included studies and relevant reviews were manually searched. Studies that met the inclusion criteria were systematically evaluated. Two reviewers assessed each of the included studies to confirm eligibility and assessing the risk of bias. Ten randomized controlled trials investigating the effect of acupuncture were included. Five trials compared acupuncture to sham/placebo acupuncture. Four trials compared acupuncture to oral hygiene/usual care. Only one clinical trial used oral care sessions as control group. For all the included studies, the quality for all the main outcomes has been assessed as low. Although some publications suggest a positive effect of acupuncture on either salivary flow rate or subjective dry mouth feeling, the studies are inconclusive about the potential effects of acupuncture. Insufficient evidence is available to conclude whether acupuncture is an evidence-based treatment option for xerostomia/hyposalivation. Further well-designed, larger, double blinded trials are required to determine the potential benefit of acupuncture. Sample size calculations should be performed before before initiating these studies.

A longitudinal analysis of salivary flow in control subjects and older adults with type 2 diabetes.

PubMed

Chávez, E M; Borrell, L N; Taylor, G W; Ship, J A

2001-02-01

Many diabetics complain of xerostomia, a condition that can affect oral health, nutritional status, and diet selection. This study's purposes were (1) to investigate the effect on salivary flow of type 2 diabetes and change in glycemic control in a group of older adults over time and (2) to compare flow rates with subjective complaints of xerostomia. A total of 39 older adults, 24 with type 2 diabetes and 15 who were nondiabetic (controls), aged 54-90 years, participated in a 1-year follow-up study. Diabetic status was determined by means of glycosylated hemoglobin (HbA1c) levels and 2-hour glucose tolerance tests. Poor glycemic control was defined as HbA1c > 9%. Unstimulated whole, unstimulated parotid, and stimulated parotid saliva flow rates were measured for all subjects by a single examiner at baseline and 1 year later. Each subject completed a standardized xerostomia questionnaire at every visit. Age, sex, and duration of diabetes did not adversely affect salivary flow rates. Subjects with poorly controlled diabetes had significantly lower stimulated parotid saliva flow rates at both visits. There were no significant changes in flow rates over time on the basis of diabetic status or glycemic control. Subjects with diabetes reported significantly more complaints of thirst but not of xerostomia at 1 year. These results suggest that older adults with poorly controlled diabetes may have impaired salivary flow in comparison with subjects with better controlled diabetes and nondiabetic subjects, yet they may not have concomitant xerostomic complaints. There were no significant changes in salivary flow rates or glycemic control over the 1-year period.

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma

PubMed Central

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-01-01

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased (P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease (P = 0.022), and SD, 75th and 90th percentiles continued to increase (P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADCmean, ADCmin, kurtosis, and 25th, 50th, 75th, 90th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADCmax could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 (P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy. PMID:29050274

Apparent diffusion coefficient histogram analysis can evaluate radiation-induced parotid damage and predict late xerostomia degree in nasopharyngeal carcinoma.

PubMed

Zhou, Nan; Guo, Tingting; Zheng, Huanhuan; Pan, Xia; Chu, Chen; Dou, Xin; Li, Ming; Liu, Song; Zhu, Lijing; Liu, Baorui; Chen, Weibo; He, Jian; Yan, Jing; Zhou, Zhengyang; Yang, Xiaofeng

2017-09-19

We investigated apparent diffusion coefficient (ADC) histogram analysis to evaluate radiation-induced parotid damage and predict xerostomia degrees in nasopharyngeal carcinoma (NPC) patients receiving radiotherapy. The imaging of bilateral parotid glands in NPC patients was conducted 2 weeks before radiotherapy (time point 1), one month after radiotherapy (time point 2), and four months after radiotherapy (time point 3). From time point 1 to 2, parotid volume, skewness, and kurtosis decreased ( P < 0.001, = 0.001, and < 0.001, respectively), but all other ADC histogram parameters increased (all P < 0.001, except P = 0.006 for standard deviation [SD]). From time point 2 to 3, parotid volume continued to decrease ( P = 0.022), and SD, 75 th and 90 th percentiles continued to increase ( P = 0.024, 0.010, and 0.006, respectively). Early change rates of parotid ADC mean , ADC min , kurtosis, and 25 th , 50 th , 75 th , 90 th percentiles (from time point 1 to 2) correlated with late parotid atrophy rate (from time point 1 to 3) (all P < 0.05). Multiple linear regression analysis revealed correlations among parotid volume, time point, and ADC histogram parameters. Early mean change rates for bilateral parotid SD and ADC max could predict late xerostomia degrees at seven months after radiotherapy (three months after time point 3) with AUC of 0.781 and 0.818 ( P = 0.014, 0.005, respectively). ADC histogram parameters were reproducible (intraclass correlation coefficient, 0.830 - 0.999). ADC histogram analysis could be used to evaluate radiation-induced parotid damage noninvasively, and predict late xerostomia degrees of NPC patients treated with radiotherapy.

Local Control After Stereotactic Body Radiation Therapy for Liver Tumors.

PubMed

Ohri, Nitin; Tomé, Wolfgang A; Méndez Romero, Alejandra; Miften, Moyed; Ten Haken, Randall K; Dawson, Laura A; Grimm, Jimm; Yorke, Ellen; Jackson, Andrew

2018-01-06

To quantitatively evaluate published experiences with hepatic stereotactic body radiation therapy (SBRT), to determine local control rates after treatment of primary and metastatic liver tumors and to examine whether outcomes are affected by SBRT dosing regimen. We identified published articles that reported local control rates after SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the linear-quadratic equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy 10 vs >100 Gy 10 ). Comparisons were made using log-rank testing. Thirteen articles met all inclusion criteria and formed the dataset for this analysis. The 1-, 2-, and 3-year actuarial local control rates after SBRT for primary liver tumors (n = 431) were 93%, 89%, and 86%, respectively. Lower 1- (90%), 2- (79%), and 3-year (76%) actuarial local control rates were observed for liver metastases (n = 290, log-rank P = .011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy 10 (3-year local control 93%) than for those treated with BEDs of ≤100 Gy 10 (3-year local control 65%, P < .001). Stereotactic body radiation therapy for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly utilized schedules. Excellent local control rates are also seen after SBRT for liver metastases when BEDs of >100 Gy 10 are utilized. Copyright © 2018

Cevimeline for the treatment of postirradiation xerostomia in patients with head and neck cancer.

PubMed

Chambers, Mark S; Posner, Marshall; Jones, Christopher Uwe; Biel, Merrill A; Hodge, Kenneth M; Vitti, Robert; Armstrong, Ingrid; Yen, Cindy; Weber, Randal S

2007-07-15

To study the efficacy and safety of cevimeline in two double-blind trials (Studies 003 and 004) enrolling patients with head and neck cancer in whom xerostomia developed after radiotherapy. Subjects were randomly assigned to receive cevimeline, 30 mg three times daily, or placebo for 12 weeks, with the possibility of dose escalation to 45 mg three times daily at 6 weeks. The primary efficacy endpoint was the patient's final global evaluation of oral dryness; change in unstimulated salivary flow was a secondary endpoint. Five hundred seventy subjects (284 in Study 003 and 286 in Study 004) were randomized. Significantly more cevimeline-treated subjects than placebo recipients (47.4% vs. 33.3%, p = 0.0162) in Study 003 reported improvement in dry mouth in the final global evaluation of oral dryness. No significant difference between groups in the final global evaluation was seen in Study 004, in which a high placebo response rate of 47.6% was observed. In both studies, cevimeline-treated subjects had significantly greater increases in the objective measure of unstimulated salivary flow than placebo recipients (p = 0.0093 [Study 003] and p = 0.0215 [Study 004]), whereas no significant differences in stimulated salivary flow were observed. The most frequent adverse event was increased sweating. Cevimeline was well tolerated by patients with xerostomia after radiotherapy for head and neck cancer, and oral administration of 30-45 mg of cevimeline three times daily increased unstimulated salivary flow.

Associations between xerostomia, histopathological alterations, and autonomic innervation of labial salivary glands in men in late midlife.

PubMed

Sørensen, Christiane Elisabeth; Larsen, Jytte Overgaard; Reibel, Jesper; Lauritzen, Martin; Mortensen, Erik Lykke; Osler, Merete; Pedersen, Anne Marie Lynge

2014-09-01

One aim of the present study was to investigate whether symptoms of oral dryness (xerostomia) during daytime, assessed in a study group of middle-aged male positive and negative outliers in cognition scores, were associated with age-related degenerative changes in human labial salivary glands and with quantitative measures of the glandular autonomic innervation. Another aim was to study the relation between the autonomic innervation and loss of secretory acinar cells in these glands. Labial salivary gland biopsies were taken from the lower lip from 190 men, born in 1953 and members of the Danish Metropolit birth cohort, who were examined for age-related changes in cognitive function and dental health as part of the Copenhagen University Center for Healthy Aging clinical neuroscience project. The glands were routinely processed and semi-quantitatively analyzed for inflammation, acinar atrophy, fibrosis, and adipocyte infiltration. Sections of labial salivary gland tissue were stained with the panneuronal marker PGP 9.5. In a subsample of 51 participants, the autonomic innervation of the glands was analyzed quantitatively by use of stereology. Labial salivary gland tissue samples from 33% of all participants displayed moderate to severe acinar atrophy and fibrosis (31%). Xerostomia was not significantly associated with structural changes of labial salivary glands, but in the subsample it was inversely related to the total nerve length in the glandular connective tissue. Acinar atrophy and fibrosis were negatively correlated with the parenchymal innervation and positively related to diffuse inflammation. The results from the present study indicate that aspects of the autonomic innervation of labial salivary glands may play a role in the occurrence of xerostomia which in the present study group was not significantly associated with degenerative changes in these glands. The findings further indicate that the integrity of labial salivary gland acini is related to the

Management of radiotherapy-induced salivary hypofunction and consequent xerostomia in patients with oral or head and neck cancer: meta-analysis and literature review.

PubMed

Lovelace, Tiffany L; Fox, Nyssa F; Sood, Amit J; Nguyen, Shaun A; Day, Terry A

2014-05-01

To analyze the efficacy of various treatment options for radiation-induced hyposalivation in patients with head and neck cancer. A literature review and meta-analysis was performed on all appropriate literature identified via MEDLINE/PubMed. Fourteen articles were identified that met inclusion criteria for review, and 8 articles qualified for inclusion in the meta-analysis. The available literature addressed both objective and subjective responses of hyposalivation, xerostomia, or both to cholinergic agonists (such as pilocarpine and cevimeline), salivary substitutes, hyperbaric oxygen, and acupuncture. This analysis indicated that cholinergic agonists were more effective in treating radiation-induced hyposalivation compared with salivary substitutes, hyperbaric oxygen, and acupuncture. However, other treatment modalities, such as salivary substitutes and hyperbaric oxygen, were also found to subjectively improve patients' perception of xerostomia. Copyright © 2014 Elsevier Inc. All rights reserved.

Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor.

PubMed

Barrow, Alexander D; Edeling, Melissa A; Trifonov, Vladimir; Luo, Jingqin; Goyal, Piyush; Bohl, Benjamin; Bando, Jennifer K; Kim, Albert H; Walker, John; Andahazy, Mary; Bugatti, Mattia; Melocchi, Laura; Vermi, William; Fremont, Daved H; Cox, Sarah; Cella, Marina; Schmedt, Christian; Colonna, Marco

2018-01-25

Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumor cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumors expressing PDGF-DD more effectively than control mice, an effect enhanced by blockade of the inhibitory receptor CD96 or CpG-oligonucleotide treatment. Thus, while cancer cell production of PDGF-DD supports tumor growth and stromal reaction, it concomitantly activates innate immune responses to tumor expansion. Copyright © 2017 Elsevier Inc. All rights reserved.

An Automatic Occlusion Device for Remote Control of Tumor Tissue Ischemia

PubMed Central

El-Dahdah, Hamid; Wang, Bei; He, Guanglong; Xu, Ronald X.

2015-01-01

We developed an automatic occlusion device for remote control of tumor tissue ischemia. The device consists of a flexible cannula encasing a shape memory alloy wire with its distal end connected to surgical suture. Regional tissue occlusion was tested on both the benchtop and the animal models. In the benchtop test, the occlusion device introduced quantitative and reproducible changes of blood flow in a tissue simulating phantom embedding a vessel simulator. In the animal test, the device generated a cyclic pattern of reversible ischemia in the right hinder leg tissue of a black male C57BL/6 mouse. We also developed a multimodal detector that integrates near infrared spectroscopy and electron paramagnetic resonance spectroscopy for continuous monitoring of tumor tissue oxygenation, blood content, and oxygen tension changes. The multimodal detector was tested on a cancer xenograft nude mouse undergoing reversible tumor ischemia. The automatic occlusion device and the multi-modal detector can be potentially integrated for closed-loop feedback control of tumor tissue ischemia. Such an integrated occlusion device may be used in multiple clinical applications such as regional hypoperfusion control in tumor resection surgeries and thermal ablation processes. In addition, the proposed occlusion device can also be used as a research tool to understand tumor oxygen transport and hemodynamic characteristics. PMID:20082532

Phase 2 results from Radiation Therapy Oncology Group Study 0537: a phase 2/3 study comparing acupuncture-like transcutaneous electrical nerve stimulation versus pilocarpine in treating early radiation-induced xerostomia.

PubMed

Wong, Raimond K W; James, Jennifer L; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M; Berk, Lawrence

2012-09-01

In this phase 2 component of a multi-institutional, phase 2/3, randomized trial, the authors assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Patients with cancer of the head and neck who were 3 to 24 months from completing radiotherapy with or without chemotherapy (RT ± C) and who were experiencing xerostomia symptoms with basal whole saliva production ≥0.1 mL per minute and were without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 sessions over 12 weeks) using a proprietary electrical stimulation unit. The primary study objective was to assess the feasibility of ALTENS treatment. Patients were considered compliant if 19 of 24 ALTENS sessions were delivered, and the targeted compliance rate was 85%. Secondary objectives measured treatment-related toxicities and the effect of ALTENS on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Of 48 accrued patients, 47 were evaluable. The median age was 60 years, 84% of patients were men, 70% completed RT ± C for >12 months, and 21% had previously received pilocarpine. Thirty-four patients completed all 24 ALTENS sessions, 9 patients completed 20 to 23 sessions, and 1 patient completed 19 sessions, representing a 94% total compliance rate. Six-month XeQOLS scores were available for 35 patients and indicated that 30 patients (86%) achieved a positive treatment response with a mean ± standard deviation reduction of 35.9% ± 36.1%. Five patients developed grade 1 or 2 gastrointestinal toxicity, and 1 had a grade 1 pain event. The current results indicated that ALTENS treatment for radiation-induced xerostomia can be delivered uniformly in a cooperative, multicenter setting and produces possible beneficial treatment response. Given these results, the phase 3 component of this study was initiated

Datamining approaches for modeling tumor control probability.

PubMed

Naqa, Issam El; Deasy, Joseph O; Mu, Yi; Huang, Ellen; Hope, Andrew J; Lindsay, Patricia E; Apte, Aditya; Alaly, James; Bradley, Jeffrey D

2010-11-01

Tumor control probability (TCP) to radiotherapy is determined by complex interactions between tumor biology, tumor microenvironment, radiation dosimetry, and patient-related variables. The complexity of these heterogeneous variable interactions constitutes a challenge for building predictive models for routine clinical practice. We describe a datamining framework that can unravel the higher order relationships among dosimetric dose-volume prognostic variables, interrogate various radiobiological processes, and generalize to unseen data before when applied prospectively. Several datamining approaches are discussed that include dose-volume metrics, equivalent uniform dose, mechanistic Poisson model, and model building methods using statistical regression and machine learning techniques. Institutional datasets of non-small cell lung cancer (NSCLC) patients are used to demonstrate these methods. The performance of the different methods was evaluated using bivariate Spearman rank correlations (rs). Over-fitting was controlled via resampling methods. Using a dataset of 56 patients with primary NCSLC tumors and 23 candidate variables, we estimated GTV volume and V75 to be the best model parameters for predicting TCP using statistical resampling and a logistic model. Using these variables, the support vector machine (SVM) kernel method provided superior performance for TCP prediction with an rs=0.68 on leave-one-out testing compared to logistic regression (rs=0.4), Poisson-based TCP (rs=0.33), and cell kill equivalent uniform dose model (rs=0.17). The prediction of treatment response can be improved by utilizing datamining approaches, which are able to unravel important non-linear complex interactions among model variables and have the capacity to predict on unseen data for prospective clinical applications.

Short-term tumor control and acute toxicity after stereotactic radiosurgery for glomus jugulare tumors.

PubMed

Poznanovic, Sheri A; Cass, Stephen P; Kavanagh, Brian D

2006-03-01

Glomus jugulare tumors (GJT) have traditionally been treated by surgery or fractionated external beam radiation therapy (XRT). This study evaluates acute toxicity and short-term efficacy of single-fraction stereotactic radiosurgery (SRS) for the treatment of GJT. Eight patients (age range 28-74) with GJT underwent SRS (Brainlab linear accelerator) as primary treatment. A nominal dose of 15-16 Gy was prescribed. After undergoing SRS, 7 of 8 patients (87.5%) reported complete resolution of presenting symptoms. Follow-up MRIs showed tumor stabilization in 100% of patients. Transient vertigo occurred in one patient. One patient suffered acute GI upset and transient lower cranial neuropathy. Stereotactic radiosurgery is an effective alternative for patients with GJT in achieving tumor control and resolution of symptoms. C-4.

Open-label, long-term safety study of cevimeline in the treatment of postirradiation xerostomia.

PubMed

Chambers, Mark S; Jones, Christopher Uwe; Biel, Merrill A; Weber, Randal S; Hodge, Kenneth M; Chen, Y; Holland, John M; Ship, Jonathan A; Vitti, Robert; Armstrong, Ingrid; Garden, Adam S; Haddad, Robert

2007-12-01

To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness on a scale of 0 (none) to 3 (severe). Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.

Therapeutic profile of single-fraction radiosurgery of vestibular schwannoma: unrelated malignancy predicts tumor control

PubMed Central

Wowra, Berndt; Muacevic, Alexander; Fürweger, Christoph; Schichor, Christian; Tonn, Jörg-Christian

2012-01-01

Radiosurgery has become an accepted treatment option for vestibular schwannomas. Nevertheless, predictors of tumor control and treatment toxicity in current radiosurgery of vestibular schwannomas are not well understood. To generate new information on predictors of tumor control and cranial nerve toxicity of single-fraction radiosurgery of vestibular schwannomas, we conducted a single-institution long-term observational study of radiosurgery for sporadic vestibular schwannomas. Minimum follow-up was 3 years. Investigated as potential predictors of tumor control and cranial nerve toxicity were treatment technology; tumor resection preceding radiosurgery; tumor size; gender; patient age; history of cancer, vascular disease, or metabolic disease; tumor volume; radiosurgical prescription dose; and isodose line. Three hundred eighty-six patients met inclusion criteria. Treatment failure was observed in 27 patients. History of unrelated cancer (strongest predictor) and prescription dose significantly predicted tumor control. The cumulative incidence of treatment failure was 30% after 6.5 years in patients with unrelated malignancy and 10% after ≥15 years in patients without such cancer (P < .02). Tumor volume was the only predictor of trigeminal neuropathy (observed in 6 patients). No predictor of facial nerve toxicity was found. On the House and Brackmann scale, 1 patient had a permanent one-level drop and 7 a transient drop of 1 to 3 levels. Serviceable hearing was preserved in 75.1%. Tumor hearing before radiosurgery, recurrence, and prescription isodose predicted ototoxicity. Unrelated malignancy is a strong predictor of tumor control. Tumor recurrence predominantly predicts ototoxicity. These findings potentially will aid future clinical decision making in ambiguous cases. PMID:22561798

Self-reported oral health and xerostomia in adult patients with celiac disease versus a comparison group.

PubMed

van Gils, Tom; Bouma, Gerd; Bontkes, Hetty J; Mulder, Chris J J; Brand, Henk S

2017-08-01

This study aimed to assess the impact of celiac disease (CD) on oral health and xerostomia. Members of the Dutch Celiac Society (n = 5522) were invited to complete an online questionnaire based on the Oral Health Impact Profile 14 (OHIP-14) and Xerostomia Inventory (XI). Acquaintances and partners of the CD respondents served as the comparison group. In total, data of 740 patients with CD and 270 comparison participants were evaluated. The median age of the responding patients with CD (55 years) was similar to the median age in the comparison group (53 years). Oral health problems, including aphthous stomatitis, painful mouth, and gingival problems, were more frequently reported by patients with CD. Mean OHIP-14 score (4.9 vs 2.6; P < .001) and the mean XI score (22.2 vs 17.2; P < .001) were higher in the CD group than in the comparison group. No significant effects of gender, age at CD diagnosis, or time on a gluten-free diet in mean OHIP-14 and XI scores were observed. This study showed that oral health problems are more commonly experienced in adult patients with CD than in the comparison group. Collaboration between dentists and gastroenterologists is recommended to increase detection of undiagnosed CD. Copyright © 2017 Elsevier Inc. All rights reserved.

CT image biomarkers to improve patient-specific prediction of radiation-induced xerostomia and sticky saliva.

PubMed

van Dijk, Lisanne V; Brouwer, Charlotte L; van der Schaaf, Arjen; Burgerhof, Johannes G M; Beukinga, Roelof J; Langendijk, Johannes A; Sijtsema, Nanna M; Steenbakkers, Roel J H M

2017-02-01

Current models for the prediction of late patient-rated moderate-to-severe xerostomia (XER 12m ) and sticky saliva (STIC 12m ) after radiotherapy are based on dose-volume parameters and baseline xerostomia (XER base ) or sticky saliva (STIC base ) scores. The purpose is to improve prediction of XER 12m and STIC 12m with patient-specific characteristics, based on CT image biomarkers (IBMs). Planning CT-scans and patient-rated outcome measures were prospectively collected for 249 head and neck cancer patients treated with definitive radiotherapy with or without systemic treatment. The potential IBMs represent geometric, CT intensity and textural characteristics of the parotid and submandibular glands. Lasso regularisation was used to create multivariable logistic regression models, which were internally validated by bootstrapping. The prediction of XER 12m could be improved significantly by adding the IBM "Short Run Emphasis" (SRE), which quantifies heterogeneity of parotid tissue, to a model with mean contra-lateral parotid gland dose and XER base . For STIC 12m , the IBM maximum CT intensity of the submandibular gland was selected in addition to STIC base and mean dose to submandibular glands. Prediction of XER 12m and STIC 12m was improved by including IBMs representing heterogeneity and density of the salivary glands, respectively. These IBMs could guide additional research to the patient-specific response of healthy tissue to radiation dose. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Salivary function and glycemic control in older persons with diabetes.

PubMed

Chavez, E M; Taylor, G W; Borrell, L N; Ship, J A

2000-03-01

There is no consensus on the possible association between diabetes and salivary dysfunction in older persons with diabetes. This study's purpose was to investigate the effect of diabetes and glycemic control on salivary function in an older population. Twenty nine persons with type 2 diabetes and 23 nondiabetic control subjects participated (age range, 54-90 years). Diabetic status was determined by a glycosylated hemoglobin (HbA(1c)) test and a 2-hour glucose tolerance test. Poor glycemic control was defined as HbA(1c) >9%. Unstimulated whole saliva, unstimulated parotid, and stimulated parotid flow rates were measured, and subjects completed a standardized xerostomia questionnaire. Persons with poorly controlled diabetes had lower (P =.01) stimulated parotid flow rates than persons with well-controlled diabetes and nondiabetic control subjects. There were no significant differences in xerostomic complaints based on diabetic or glycemic control status or salivary flow rates. These results provide some evidence that poorly controlled diabetes may be associated with salivary dysfunction in older adults who have no concomitant complaints of xerostomia.

The tumor suppressor CDKN3 controls mitosis

PubMed Central

Nalepa, Grzegorz; Barnholtz-Sloan, Jill; Enzor, Rikki; Dey, Dilip; He, Ying; Gehlhausen, Jeff R.; Lehmann, Amalia S.; Park, Su-Jung; Yang, Yanzhu; Yang, Xianlin; Chen, Shi; Guan, Xiaowei; Chen, Yanwen; Renbarger, Jamie; Yang, Feng-Chun; Parada, Luis F.

2013-01-01

Mitosis is controlled by a network of kinases and phosphatases. We screened a library of small interfering RNAs against a genome-wide set of phosphatases to comprehensively evaluate the role of human phosphatases in mitosis. We found four candidate spindle checkpoint phosphatases, including the tumor suppressor CDKN3. We show that CDKN3 is essential for normal mitosis and G1/S transition. We demonstrate that subcellular localization of CDKN3 changes throughout the cell cycle. We show that CDKN3 dephosphorylates threonine-161 of CDC2 during mitotic exit and we visualize CDC2pThr-161 at kinetochores and centrosomes in early mitosis. We performed a phosphokinome-wide mass spectrometry screen to find effectors of the CDKN3-CDC2 signaling axis. We found that one of the identified downstream phosphotargets, CKβ phosphorylated at serine 209, localizes to mitotic centrosomes and controls the spindle checkpoint. Finally, we show that CDKN3 protein is down-regulated in brain tumors. Our findings indicate that CDKN3 controls mitosis through the CDC2 signaling axis. These results have implications for targeted anticancer therapeutics. PMID:23775190

TU-CD-304-06: Using FFF Beams Improves Tumor Control in Radiotherapy of Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vassiliev, O; Wang, H

Purpose: Electron disequilibrium at the lung-tumor interface results in an under-dosage of tumor regions close to its surface. This under-dosage is known to be significant and can compromise tumor control. Previous studies have shown that in FFF beams, disequilibrium effects are less pronounced, which is manifested in an increased skin dose. In this study we investigate the improvement in tumor dose coverage that can be achieved with FFF beams. The significance of this improvement is evaluated by comparing tumor control probabilities of FFF beams and conventional flattened beams. Methods: The dosimetric coverage was investigated in a virtual phantom representing themore » chest wall, lung tissue and the tumor. A range of tumor sizes was investigated, and two tumor locations – central and adjacent to the chest wall. Calculations were performed with BEAMnrc Monte Carlo code. Parallel-opposed and multiple coplanar 6-MV beams were simulated. The tumor control probabilities were calculated using the logistic model with parameters derived from clinical data for non-small lung cancer patients. Results: FFF beams were not entirely immune to disequilibrium effects. They nevertheless consistently delivered more uniform dose distribution throughout the volume of the tumor, and eliminated up to ∼15% of under-dosage in the most affected by disequilibrium 1-mm thick surface region of the tumor. A voxel-by-voxel comparison of tumor control probabilities between FFF and conventional flattened beams showed an advantage of FFF beams that, depending on the set up, was from a few to ∼9 percent. Conclusion: A modest improvement in tumor control probability on the order of a few percent can be achieved by replacing conventional flattened beams with FFF beams. However, given the large number of lung cancer patients undergoing radiotherapy, these few percent can potentially prevent local tumor recurrence for a significant number of patients.« less

Open-Label, Long-Term Safety Study of Cevimeline in the Treatment of Postirradiation Xerostomia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chambers, Mark S.; Jones, Christopher Uwe; Biel, Merrill A.

Purpose: To assess the safety of long-term cevimeline treatment of radiation-induced xerostomia in patients with head-and-neck cancer; and to assess the efficacy of cevimeline in these patients. Methods and Materials: A total of 255 adults with head-and-neck cancer who had received more than 40 Gy of radiation 4 months or more before entry and had clinically significant salivary gland dysfunction received cevimeline hydrochloride 45 mg t.i.d. orally for 52 weeks. Adverse events (AEs), their severity, and their relationship to the study medication were assessed by each investigator. The efficacy assessment was based on subjects' global evaluation of oral dryness onmore » a scale of 0 (none) to 3 (severe). Results: Overall, 175 subjects (68.6%) experienced expected treatment-related AEs, most mild to moderate. The most frequent was increased sweating (47.5%), followed by dyspepsia (9.4%), nausea (8.2%), and diarrhea (6.3%). Fifteen subjects (5.9%) experienced Grade 3 treatment-related AEs, of which the most frequent was increased sweating. Eighteen subjects (7.1%) reported at least one serious AE, and 45 subjects (17.6%) discontinued study medication because of an AE. The global efficacy evaluation at the last study visit showed that cevimeline improved dry mouth in most subjects (59.2%). Significant improvement was seen at each study visit in the mean change from baseline of the numeric global evaluation score (p < 0.0001). Conclusions: Cevimeline 45 mg t.i.d. was generally well tolerated over a period of 52 weeks in subjects with xerostomia secondary to radiotherapy for cancer in the head-and-neck region.« less

High risk of brain tumors in military personnel: a case control study.

PubMed

Fallahi, P; Elia, G; Foddis, R; Cristaudo, A; Antonelli, A

2017-01-01

Scientific literature suggests a relationship between military occupation and the development of brain tumors, but no italian study has investigated on the impact of this job on the brain cancer morbidity. In this a study information were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 1999. The study has been conducted as a case-control study. 161, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 483 controls (with other non tumoral neurologic diseases: trauma, hemorrhagic brain disorders, aneurism, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (military vs. non-military occupation). A statistically significant association was seen between brain tumors and military occupation among evaluated patients (p=0.013). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

Outcomes of xerostomia-related quality of life for nasopharyngeal carcinoma treated by IMRT: based on the EORTC QLQ-C30 and H&N35 questionnaires.

PubMed

Bian, Xiuhua; Song, Tao; Wu, Shixiu

2015-01-01

The aim of this study was to review the published literature addressing the question of whether intensity-modulated radiotherapy (IMRT) resulted in an improvement of quality of life (QoL), especially xerostomia-related QoL of all nasopharyngeal carcinoma patients as time progressed. A literature search of PubMed, Embase and Google Scholar was performed, only reports containing original data of the QoL scores after treated by IMRT were included. Two independent reviewers extracted information of study design, study population, interventions, outcome measures and conclusions for each article. The inclusion criteria were met by 14 articles covering outcomes based on the questionnaires treated by IMRT. Data from same questionnaires (European Organization of Research and Treatment of Cancer QLQ-C30 and H&N35 questionnaires) were exacted and we analyzed four items (global health status, dry mouth and sticky saliva, swallowing, social eating and social contact), which have a close relationship with xerostomia-related QoL. Results indicated that a maximal deterioration of most QoL scales including global health status developed during treatment or at the end of the treatment course and then followed by a gradual recovery to 1 year, 1-2 years after IMRT, compared with their baseline level, some specific head and neck items, most in the EORTC QLQ H&N35, remained worse for the surviving patients. In conclusion, the published data reasonably support the benefits of IMRT in improving QoL, but xerostomia-related items still had a significantly negative effect in 2 years to impact a survivor's QoL.

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

PubMed Central

Nutting, Christopher M; Morden, James P; Harrington, Kevin J; Urbano, Teresa Guerrero; Bhide, Shreerang A; Clark, Catharine; Miles, Elizabeth A; Miah, Aisha B; Newbold, Kate; Tanay, MaryAnne; Adab, Fawzi; Jefferies, Sarah J; Scrase, Christopher; Yap, Beng K; A'Hern, Roger P; Sydenham, Mark A; Emson, Marie; Hall, Emma

2011-01-01

Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse

Clinical characterization of women with burning mouth syndrome in a case-control study.

PubMed

Acharya, Shikha; Carlén, Anette; Wenneberg, Bengt; Jontell, Mats; Hägglin, Catharina

2018-05-01

Burning mouth syndrome (BMS) is a chronic orofacial pain disorder that is defined by a burning sensation in the oral mucosa. The aim of this study was to investigate the underlying factors, clinical characteristics and self-reported oral and general health factors associated with BMS. Fifty-six women with BMS (mean age: 67.7) and their age-matched controls were included in the study. A general questionnaire, an OHRQL index and BMS-specific questionnaires were used. Each subject underwent an oral examination. The mean severity of the BMS symptoms (VAS, 0-100) was 66.2 (SD 19.7). Overall, 45% of the patients reported taste disturbances. More of the patients than the controls rated their general health, oral health and life situation as 'less satisfactory'. The patients also reported more frequently on-going medications, diseases/disorders, xerostomia, allergy and skin diseases. Except for more bruxofacets among the patients, there were no significant differences regarding signs of parafunction. In a multiple logistic regression analysis, xerostomia and skin diseases showed the strongest prediction for BMS and no significant effect was found for medication, allergy or bruxofacets. Skin diseases and xerostomia but not parafunction were strongly associated with BMS. Our findings provide the basis for additional studies to elucidate the causal factors of BMS.

Parotid gland sparing in patients undergoing bilateral head and neck irradiation: techniques and early results.

PubMed

Eisbruch, A; Ship, J A; Martel, M K; Ten Haken, R K; Marsh, L H; Wolf, G T; Esclamado, R M; Bradford, C R; Terrell, J E; Gebarski, S S; Lichter, A S

1996-09-01

of 15 patients (67%). Partial parotid gland sparing is feasible by using three-dimensional planning in patients undergoing bilateral head and neck radiation. Approximately 50% of the saliva flow from the spared glands may be retained, and most patients thus treated have no or mild xerostomia in the early period after the completion of radiation. Whether tumor control and late complications are comparable to standard radiation will be assessed as more experience is gained.

Mobile phone use and the risk for malignant brain tumors: a case-control study on deceased cases and controls.

PubMed

Hardell, Lennart; Carlberg, Michael; Hansson Mild, Kjell

2010-08-01

We investigated the use of mobile or cordless phones and the risk for malignant brain tumors in a group of deceased cases. Most previous studies have either left out deceased cases of brain tumors or matched them to living controls and therefore a study matching deceased cases to deceased controls is warranted. Recall error is one issue since it has been claimed that increased risks reported in some studies could be due to cases blaming mobile phones as a cause of the disease. This should be of less importance for deceased cases and if cancer controls are used. In this study brain tumor cases aged 20-80 years diagnosed during 1997-2003 that had died before inclusion in our previous studies on the same topic were included. Two control groups were used: one with controls that had died from another type of cancer than brain tumor and one with controls that had died from other diseases. Exposure was assessed by a questionnaire sent to the next-of-kin for both cases and controls. Replies were obtained for 346 (75%) cases, 343 (74%) cancer controls and 276 (60%) controls with other diseases. Use of mobile phones gave an increased risk, highest in the >10 years' latency group yielding odds ratio (OR) = 2.4, and 95% confidence interval (CI) = 1.4-4.1. The risk increased with cumulative number of lifetime hours for use, and was highest in the >2,000 h group (OR = 3.4, 95% CI = 1.6-7.1). No clear association was found for use of cordless phones, although OR = 1.7, 95% CI = 0.8-3.4 was found in the group with >2,000 h of cumulative use. This investigation confirmed our previous results of an association between mobile phone use and malignant brain tumors. Copyright 2010 S. Karger AG, Basel.

Cryoablation of Bone Metastases from Renal Cell Carcinoma for Local Tumor Control.

PubMed

Gardner, Carly S; Ensor, Joe E; Ahrar, Kamran; Huang, Steven Y; Sabir, Sharjeel H; Tannir, Nizar M; Lewis, Valerae O; Tam, Alda L

2017-11-15

Patients with bone metastases from renal cell carcinoma often are not surgical candidates and have a poor prognosis. There are limited data on the use of cryoablation as a locoregional therapy for bone metastases. Our objective was to assess the local tumor-control rate following cryoablation of bone metastases in the setting of renal cell carcinoma. We retrospectively reviewed the medical records of patients with metastatic renal cell carcinoma who underwent cryoablation for bone metastases between 2007 and 2014. We excluded patients if the intent of treatment was for pain palliation only, if cryoablation was performed without an attempt for complete tumor control (cytoreduction), or if the patient had no further follow-up beyond the cryoablation procedure. We recorded patient demographics, procedural variables, and complications. Cross-sectional imaging and clinical follow-up were reviewed to determine disease recurrence. The median overall survival and recurrence-free survival were determined using the Kaplan-Meier method. Forty patients (30 male and 10 female) with 50 bone metastases were included for analysis. The mean patient age was 62 years (range, 47 to 82 years). The median follow-up was 35 months (95% confidence interval [CI], 22.7 to 74.4 months). Twenty-five (62.5%) of the 40 patients had oligometastatic disease, defined as ≤5 metastases at the time of ablation. The mean tumor size was 3.4 ± 1.5 cm. Metastases in the pelvic region represented 68% of the treated tumors (34 of 50). The overall local tumor-control rate per lesion was 82% (41 of 50). Patients with oligometastatic disease experienced better local tumor control (96% [24 of 25]) compared with patients who had >5 metastases (53.3% [8 of 15]) (p = 0.001). The local tumor-control rate was better for lesions for which a larger mean difference between maximum ice-ball diameter and maximum lesion diameter was achieved (2.2 ± 0.9 cm for those without recurrence versus 1.35 ± 1.2 cm for those

A switching control law approach for cancer immunotherapy of an evolutionary tumor growth model.

PubMed

Doban, Alina I; Lazar, Mircea

2017-02-01

We propose a new approach for tumor immunotherapy which is based on a switching control strategy defined on domains of attraction of equilibria of interest. For this, we consider a recently derived model which captures the effects of the tumor cells on the immune system and viceversa, through predator-prey competition terms. Additionally, it incorporates the immune system's mechanism for producing hunting immune cells, which makes the model suitable for immunotherapy strategies analysis and design. For computing domains of attraction for the tumor nonlinear dynamics, and thus, for deriving immunotherapeutic strategies we employ rational Lyapunov functions. Finally, we apply the switching control strategy to destabilize an invasive tumor equilibrium and steer the system trajectories to tumor dormancy. Copyright © 2016 Elsevier Inc. All rights reserved.

NK cell heparanase controls tumor invasion and immune surveillance

PubMed Central

Putz, Eva M.; Mayfosh, Alyce J.; Barkauskas, Deborah S.; Nakamura, Kyohei; Town, Liam; Goodall, Katharine J.; Yee, Dean Y.; Poon, Ivan K.H.; Baschuk, Nikola; Souza-Fonseca-Guimaraes, Fernando; Hulett, Mark D.; Smyth, Mark J.

2017-01-01

NK cells are highly efficient at preventing cancer metastasis but are infrequently found in the core of primary tumors. Here, have we demonstrated that freshly isolated mouse and human NK cells express low levels of the endo-β-D-glucuronidase heparanase that increase upon NK cell activation. Heparanase deficiency did not affect development, differentiation, or tissue localization of NK cells under steady-state conditions. However, mice lacking heparanase specifically in NK cells (Hpsefl/fl NKp46-iCre mice) were highly tumor prone when challenged with the carcinogen methylcholanthrene (MCA). Hpsefl/fl NKp46-iCre mice were also more susceptible to tumor growth than were their littermate controls when challenged with the established mouse lymphoma cell line RMA-S-RAE-1β, which overexpresses the NK cell group 2D (NKG2D) ligand RAE-1β, or when inoculated with metastatic melanoma, prostate carcinoma, or mammary carcinoma cell lines. NK cell invasion of primary tumors and recruitment to the site of metastasis were strictly dependent on the presence of heparanase. Cytokine and immune checkpoint blockade immunotherapy for metastases was compromised when NK cells lacked heparanase. Our data suggest that heparanase plays a critical role in NK cell invasion into tumors and thereby tumor progression and metastases. This should be considered when systemically treating cancer patients with heparanase inhibitors, since the potential adverse effect on NK cell infiltration might limit the antitumor activity of the inhibitors. PMID:28581441

Local control of brain metastases by stereotactic radiosurgery in relation to dose to the tumor margin.

PubMed

Vogelbaum, Michael A; Angelov, Lilyana; Lee, Shih-Yuan; Li, Liang; Barnett, Gene H; Suh, John H

2006-06-01

The maximal tolerated dose (MTD) for stereotactic radiosurgery (SRS) for brain tumors was established by the Radiation Therapy Oncology Group (RTOG) in protocol 90-05, which defined three dose groups based on the maximal tumor diameter. The goal in this retrospective study was to determine whether differences in doses to the margins of brain metastases affect the ability of SRS to achieve local control. Between 1997 and 2003, 202 patients harboring 375 tumors that met study entry criteria underwent SRS for treatment of one or multiple brain metastases. The median overall follow-up duration was 10.7 months (range 3-83 months). A dose of 24 Gy to the tumor margin had a significantly lower risk of local failure than 15 or 18 Gy (p = 0.0005; hazard ratio 0.277, confidence interval [CI] 0.134-0.573), whereas the 15- and 18-Gy groups were not significantly different from each other (p = 0.82) in this regard. The 1-year local control rate was 85% (95% CI 78-92%) in tumors treated with 24 Gy, compared with 49% (CI 30-68%) in tumors treated with 18 Gy and 45% (CI 23-67%) in tumors treated with 15 Gy. Overall patient survival was independent of dose to the tumor margin. Use of the RTOG 90-05 dosing scheme for brain metastases is associated with a variable local control rate. Tumors larger than 2 cm are less effectively controlled than smaller lesions, which can be safely treated with 24 Gy. Prospective evaluations of the relationship between dose to the tumor margin and local control should be performed to confirm these observations.

Controlling cytoplasmic c-Fos controls tumor growth in the peripheral and central nervous system.

PubMed

Gil, Germán A; Silvestre, David C; Tomasini, Nicolás; Bussolino, Daniela F; Caputto, Beatriz L

2012-06-01

Some 20 years ago c-Fos was identified as a member of the AP-1 family of inducible transcription factors (Angel and Karin in Biochim Biophys Acta 1072:129-157, 1991). More recently, an additional activity was described for this protein: it associates to the endoplasmic reticulum and activates the biosynthesis of phospholipids (Bussolino et al. in FASEB J 15:556-558, 2001), (Gil et al. in Mol Biol Cell 15:1881-1894, 2004), the quantitatively most important components of cellular membranes. This latter activity of c-Fos determines the rate of membrane genesis and consequently of growth in differentiating PC12 cells (Gil et al. in Mol Biol Cell 15:1881-1894, 2004). In addition, it has been shown that c-Fos is over-expressed both in PNS and CNS tumors (Silvestre et al. in PLoS One 5(3):e9544, 2010). Herein, it is shown that c-Fos-activated phospholipid synthesis is required to support membrane genesis during the exacerbated growth characteristic of brain tumor cells. Specifically blocking c-Fos-activated phospholipid synthesis significantly reduces proliferation of tumor cells in culture. Blocking c-Fos expression also prevents tumor progression in mice intra-cranially xeno-grafted human brain tumor cells. In NPcis mice, an animal model of the human disease Neurofibromatosis Type I (Cichowski and Jacks in Cell 104:593-604, 2001), animals spontaneously develop tumors of the PNS and the CNS, provided they express c-Fos (Silvestre et al. in PLoS One 5(3):e9544, 2010). Treatment of PNS tumors with an antisense oligonucleotide that specifically blocks c-Fos expression also blocks tumor growth in vivo. These results disclose cytoplasmic c-Fos as a new target for effectively controlling brain tumor growth.

HPMA Copolymer-Drug Conjugates with Controlled Tumor-Specific Drug Release.

PubMed

Chytil, Petr; Koziolová, Eva; Etrych, Tomáš; Ulbrich, Karel

2018-01-01

Over the past few decades, numerous polymer drug carrier systems are designed and synthesized, and their properties are evaluated. Many of these systems are based on water-soluble polymer carriers of low-molecular-weight drugs and compounds, e.g., cytostatic agents, anti-inflammatory drugs, or multidrug resistance inhibitors, all covalently bound to a carrier by a biodegradable spacer that enables controlled release of the active molecule to achieve the desired pharmacological effect. Among others, the synthetic polymer carriers based on N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers are some of the most promising carriers for this purpose. This review focuses on advances in the development of HPMA copolymer carriers and their conjugates with anticancer drugs, with triggered drug activation in tumor tissue and especially in tumor cells. Specifically, this review highlights the improvements in polymer drug carrier design with respect to the structure of a spacer to influence controlled drug release and activation, and its impact on the drug pharmacokinetics, enhanced tumor uptake, cellular trafficking, and in vivo antitumor activity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Orbit-associated tumors: navigation and control of resection using intraoperative computed tomography.

PubMed

Terpolilli, Nicole A; Rachinger, Walter; Kunz, Mathias; Thon, Niklas; Flatz, Wilhelm H; Tonn, Jörg-Christian; Schichor, Christian

2016-05-01

OBJECT Treatment of skull base lesions is complex and usually requires a multidisciplinary approach. In meningioma, which is the most common tumor entity in this region, resection is considered to be the most important therapeutic step to avoid tumor recurrence. However, resection of skull base lesions with orbital or optic nerve involvement poses a challenge due to their anatomical structure and their proximity to eloquent areas. Therefore the main goal of surgery should be to achieve the maximum extent of resection while preserving neurological function. In the postoperative course, medical and radiotherapeutic strategies may then be successfully used to treat possible tumor residues. Methods to safely improve the extent of resection in skull base lesions therefore are desirable. The current study reports the authors' experience with the use of intraoperative CT (iCT) combined with neuronavigation with regard to feasibility and possible benefits of the method. METHODS Those patients with tumorous lesions in relationship to the orbit, sphenoid wing, or cavernous sinus who were surgically treated between October 2008 and December 2013 using iCT-based neuronavigation and in whom an intraoperative scan was obtained for control of resection were included. In all cases a second iCT scan was performed under sterile conditions after completion of navigation-guided microsurgical tumor resection. The surgical strategy was adapted accordingly; if necessary, resection was continued. RESULTS Twenty-three patients (19 with WHO Grade I meningioma and 4 with other lesions) were included. The most common clinical symptoms were loss of visual acuity and exophthalmus. Intraoperative control of resection by iCT was successfully obtained in all cases. Intraoperative imaging changed the surgical approach in more than half (52.2%) of these patients, either because iCT demonstrated unexpected residual tumor masses or because the second scan revealed additional tumor tissue that was not

Hypoxia-Inducible Factor Pathway Inhibition Resolves Tumor Hypoxia and Improves Local Tumor Control After Single-Dose Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Helbig, Linda; Department of Radiation Oncology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden; Koi, Lydia

2014-01-01

Purpose: To study the effects of BAY-84-7296, a novel orally bioavailable inhibitor of mitochondrial complex I and hypoxia-inducible factor 1 (HIF-1) activity, on hypoxia, microenvironment, and radiation response of tumors. Methods and Materials: UT-SCC-5 and UT-SCC-14 human squamous cell carcinomas were transplanted subcutaneously in nude mice. When tumors reached 4 mm in diameter BAY-84-7296 (Bayer Pharma AG) or carrier was daily administered to the animals. At 7 mm tumors were either excised for Western blot and immunohistologic investigations or were irradiated with single doses. After irradiation animals were randomized to receive BAY-84-7296 maintenance or carrier. Local tumor control was evaluatedmore » 150 days after irradiation, and the dose to control 50% of tumors (TCD{sub 50}) was calculated. Results: BAY-84-7296 decreased nuclear HIF-1α expression. Daily administration of inhibitor for approximately 2 weeks resulted in a marked decrease of pimonidazole hypoxic fraction in UT-SCC-5 (0.5% vs 21%, P<.0001) and in UT-SCC-14 (0.3% vs 19%, P<.0001). This decrease was accompanied by a significant increase in fraction of perfused vessels in UT-SCC-14 but not in UT-SCC-5. Bromodeoxyuridine and Ki67 labeling indices were significantly reduced only in UT-SCC-5. No significant changes were observed in vascular area or necrosis. BAY-84-7296 before single-dose irradiation significantly decreased TCD{sub 50}, with an enhancement ratio of 1.37 (95% confidence interval [CI] 1.13-1.72) in UT-SCC-5 and of 1.55 (95% CI 1.26-1.94) in UT-SCC-14. BAY-84-7296 maintenance after irradiation did not further decrease TCD{sub 50}. Conclusions: BAY-84-7296 resulted in a marked decrease in tumor hypoxia and substantially reduced radioresistance of tumor cells with the capacity to cause a local recurrence after irradiation. The data suggest that reduction of cellular hypoxia tolerance by BAY-84-7296 may represent the primary biological mechanism underlying the observed enhancement

Oral toxicity management in head and neck cancer patients treated with chemotherapy and radiation: Xerostomia and trismus (Part 2). Literature review and consensus statement.

PubMed

Buglione, Michela; Cavagnini, Roberta; Di Rosario, Federico; Maddalo, Marta; Vassalli, Lucia; Grisanti, Salvatore; Salgarello, Stefano; Orlandi, Ester; Bossi, Paolo; Majorana, Alessandra; Gastaldi, Giorgio; Berruti, Alfredo; Trippa, Fabio; Nicolai, Pietro; Barasch, Andrei; Russi, Elvio G; Raber-Durlacher, Judith; Murphy, Barbara; Magrini, Stefano M

2016-06-01

Radiotherapy alone or in combination with chemotherapy and/or surgery is a well-known radical treatment for head and neck cancer patients. Nevertheless acute side effects (such as moist desquamation, skin erythema, loss of taste, mucositis etc.) and in particular late toxicities (osteoradionecrosis, xerostomia, trismus, radiation caries etc.) are often debilitating and underestimated. A multidisciplinary group of head and neck cancer specialists from Italy met in Milan with the aim of reaching a consensus on a clinical definition and management of these toxicities. The Delphi Appropriateness method was used for this consensus and external experts evaluated the conclusions. The paper contains 20 clusters of statements about the clinical definition and management of stomatological issues that reached consensus, and offers a review of the literature about these topics. The review was split into two parts: the first part dealt with dental pathologies and osteo-radionecrosis (10 clusters of statements), whereas this second part deals with trismus and xerostomia (10 clusters of statements). Copyright © 2016. Published by Elsevier Ireland Ltd.

Tumor-based case-control studies of infection and cancer: muddling the when and where of molecular epidemiology.

PubMed

Engels, Eric A; Wacholder, Sholom; Katki, Hormuzd A; Chaturvedi, Anil K

2014-10-01

We describe the "tumor-based case-control" study as a type of epidemiologic study used to evaluate associations between infectious agents and cancer. These studies assess exposure using diseased tissues from affected individuals (i.e., evaluating tumor tissue for cancer cases), but they must utilize nondiseased tissues to assess control subjects, who do not have the disease of interest. This approach can lead to exposure misclassification in two ways. First, concerning the "when" of exposure assessment, retrospective assessment of tissues may not accurately measure exposure at the key earlier time point (i.e., during the etiologic window). Second, concerning the "where" of exposure assessment, use of different tissues in cases and controls can have different accuracy for detecting the exposure (i.e., differential exposure misclassification). We present an example concerning the association of human papillomavirus with various cancers, where tumor-based case-control studies likely overestimate risk associated with infection. In another example, we illustrate how tumor-based case-control studies of Helicobacter pylori and gastric cancer underestimate risk. Tumor-based case-control studies can demonstrate infection within tumor cells, providing qualitative information about disease etiology. However, measures of association calculated in tumor-based case-control studies are prone to over- or underestimating the relationship between infections and subsequent cancer risk. ©2014 American Association for Cancer Research.

[Cevimeline hydrochloride hydrate (Saligren capsule 30 mg): a review of its pharmacological profiles and clinical potential in xerostomia].

PubMed

Shiozawa, Akira

2002-10-01

Cevimeline hydrochloride hydrate is a muscarinic receptor agonist with a chemical structure of a quinuclidine. Intraduodenal administration of cevimeline hydrochloride hydrate dose-dependently increased salivary secretion in normal mice and rats, two strains of autoimmune disease mice, and X-irradiated rats. The clinical efficacy of the cevimeline hydrochlide hydrate at 30 mg t.i.d. during 4 weeks has been demonstrated in double blind comparative study with placebo. In addition, its treatments in 52 weeks have increased salivary flow and improved subjective and objective symptoms of patients with xerostomia in Sjögren's syndrome.

Histology-Stratified Tumor Control and Patient Survival After Stereotactic Radiosurgery for Pineal Region Tumors: A Report From the International Gamma Knife Research Foundation.

PubMed

Iorio-Morin, Christian; Kano, Hideyuki; Huang, Marshall; Lunsford, L Dade; Simonová, Gabriela; Liscak, Roman; Cohen-Inbar, Or; Sheehan, Jason; Lee, Cheng-Chia; Wu, Hsiu-Mei; Mathieu, David

2017-11-01

Pineal region tumors represent a rare and histologically diverse group of lesions. Few studies are available to guide management and the outcomes after stereotactic radiosurgery (SRS). Patients who underwent SRS for a pineal region tumor and for whom at least 6 months of imaging follow-up was available were retrospectively assessed in 5 centers. Data were collected from the medical record and histology level analyses were performed, including actuarial tumor control and survival analyses. A total of 70 patients were treated between 1989 and 2014 with a median follow-up of 47 months. Diagnoses were pineocytoma (37%), pineoblastoma (19%), pineal parenchymal tumor of intermediate differentiation (10%), papillary tumor of the pineal region (9%), germinoma (7%), teratoma (3%), embryonal carcinoma (1%), and unknown (14%). Median prescription dose was 15 Gy at the 50% isodose line. Actuarial local control and survival rates were 81% and 76% at 20 years for pineocytoma, 50% and 56% at 5 years for pineal parenchymal tumor of intermediate differentiation, 27% and 48% at 5 years for pineoblastoma, 33% and 100% at 5 years for papillary tumor of the pineal region, 80% and 80% at 20 years for germinoma, and 61% and 67% at 5 years for tumors of unknown histology. New focal neurological deficit, Parinaud syndrome, and hydrocephalus occurred in 9%, 7%, and 3% of cases, respectively. SRS is a safe modality for the management of pineal region tumors. Its specific role is highly dependent on tumor histology. As such, all efforts should be made to obtain a reliable histologic diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Cellular and Tumor Radiosensitivity is Correlated to Epidermal Growth Factor Receptor Protein Expression Level in Tumors Without EGFR Amplification;Epidermal growth factor receptor; Radiotherapy; Squamous cell carcinoma; Biomarker; Local tumor control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kasten-Pisula, Ulla; Saker, Jarob; Eicheler, Wolfgang

2011-07-15

Purpose: There is conflicting evidence for whether the expression of epidermal growth factor receptor in human tumors can be used as a marker of radioresponse. Therefore, this association was studied in a systematic manner using squamous cell carcinoma (SCC) cell lines grown as cell cultures and xenografts. Methods and Materials: The study was performed with 24 tumor cell lines of different tumor types, including 10 SCC lines, which were also investigated as xenografts on nude mice. Egfr gene dose and the length of CA-repeats in intron 1 were determined by polymerase chain reaction, protein expression in vitro by Western blotmore » and in vivo by enzyme-linked immunosorbent assay, and radiosensitivity in vitro by colony formation. Data were correlated with previously published tumor control dose 50% data after fractionated irradiation of xenografts of the 10 SCC. Results: EGFR protein expression varies considerably, with most tumor cell lines showing moderate and only few showing pronounced upregulation. EGFR upregulation could only be attributed to massive gene amplification in the latter. In the case of little or no amplification, in vitro EGFR expression correlated with both cellular and tumor radioresponse. In vivo EGFR expression did not show this correlation. Conclusions: Local tumor control after the fractionated irradiation of tumors with little or no gene amplification seems to be dependent on in vitro EGFR via its effect on cellular radiosensitivity.« less

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

PubMed

Ambrosio, Maria R; Rocca, Bruno J; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T; Tripodi, Sergio A; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma

PubMed Central

Ambrosio, Maria R.; Rocca, Bruno J.; Barone, Aurora; Onorati, Monica; Mundo, Lucia; Crivelli, Filippo; Di Nuovo, Franca; De Falco, Giulia; del Vecchio, Maria T.; Tripodi, Sergio A.; Tosi, Piero

2015-01-01

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis. PMID:26425551

Gamma knife radiosurgery for vestibular schwannomas: tumor control and functional preservation in 70 patients.

PubMed

Arthurs, Benjamin J; Lamoreaux, Wayne T; Mackay, Alexander R; Demakas, John J; Giddings, Neil A; Fairbanks, Robert K; Cooke, Barton S; Elaimy, Ameer L; Peressini, Ben; Lee, Christopher M

2011-06-01

We present the previously unreported outcomes of 70 patients treated with Gamma knife radiosurgery for vestibular schwannoma (VS), including comprehensive analysis of clinical outcomes and the effects of lower marginal doses. We performed a retrospective study of patients treated for VS at Gamma knife of Spokane between 2003 and 2008. Endpoints measured include tumor control, hearing preservation, and facial nerve preservation, including the effect of tumor size and marginal dose. Statistical analysis was performed with Wilcoxon signed-rank test, paired Student t test, Mann-Whitney U test, Kendall's rank correlation, Fisher exact test, and Liddell's exact χ(2) test for matched pairs. With a mean follow-up of 26 months, 93.8% of tumors either shrank or remained static after receiving a mean marginal dose of 12.7 Gy. Tumor control was independent of marginal dose or tumor size. Hearing preservation was achieved in 64% of patients with serviceable function before the treatment. Hearing changes were independent of dose or tumor size. Preservation of good facial nerve function was achieved in 95% of patients. Post-treatment hydrocephalus occurred in 4.4% of patients, but no other significant morbidities were elucidated. In the treatment of VS, contemporary radiosurgical techniques and the use of marginal doses below 13 Gy offer excellent tumor control, at high rates relative to surgical intervention. These findings are independent of marginal dose and tumor size. Patients should be informed about the benefits and risks of radiosurgery and microsurgery before choosing an intervention. Further analysis of post-treatment outcomes should be encouraged as follow-up times increase and the treatment protocols continue to evolve.

Controlled release microspheres loaded with BMP7 suppress primary tumors from human glioblastoma

PubMed Central

González-Gómez, P.; de la Fuente, M.; Hernández-Laín, Aurelio; Mira, H.; Sánchez-Gómez, P.; Garcia-Fuentes, M.

2015-01-01

Glioblastoma tumor initiating cells are believed to be the main drivers behind tumor recurrence, and therefore therapies that specifically manage this population are of great medical interest. In a previous work, we synthesized controlled release microspheres optimized for intracranial delivery of BMP7, and showed that these devices are able to stop the in vitro growth of a glioma cell line. Towards the translational development of this technology, we now explore these microspheres in further detail and characterize the mechanism of action and the in vivo therapeutic potential using tumor models relevant for the clinical setting: human primary glioblastoma cell lines. Our results show that BMP7 can stop the proliferation and block the self-renewal capacity of those primary cell lines that express the receptor BMPR1B. BMP7 was encapsulated in poly (lactic-co-glycolic acid) microspheres in the form of a complex with heparin and Tetronic, and the formulation provided effective release for several weeks, a process controlled by carrier degradation. Data from xenografts confirmed reduced and delayed tumor formation for animals treated with BMP7-loaded microspheres. This effect was coincident with the activation of the canonical BMP signaling pathway. Importantly, tumors treated with BMP7-loaded microspheres also showed downregulation of several markers that may be related to a malignant stem cell-like phenotype: CD133+, Olig2, and GFAPδ. We also observed that tumors treated with BMP7-loaded microspheres showed enhanced expression of cell cycle inhibitors and reduced expression of the proliferation marker PCNA. In summary, BMP7-loaded controlled release microspheres are able to inhibit GBM growth and reduce malignancy markers. We envisage that this kind of selective therapy for tumor initiating cells could have a synergistic effect in combination with conventional cytoreductive therapy (chemo-, radiotherapy) or with immunotherapy. PMID:25860932

[Applicability of syalometry and other instruments to evaluate xerostomia and xerophtalmia in a Sjögren's Syndrome outpatient clinic].

PubMed

Barcelos, Filipe; Patto, José Vaz; Parente, Manuela; Medeiros, Dina; Sousa, Miguel; Figueiredo, Rui; Miguel, Cláudia; Teixeira, Ana

2009-01-01

To evaluate the applicability and utility of unstimulated syalometry and instruments of evaluation of sicca complaints in a Sjögren's syndrome outpatient clinic. We performed unstimulated syalometry to 45 consecutive Primary Sjögren's Syndrome patients (PSS) and 21 healthy asymptomatic individuals age and sex-matched. PSS patients were further evaluated with Schirmer's test. We applied 3 published questionnaires to PSS patients: Xerostomia Inventory (XI), Oral Health Impact Profile-short form (OHIP) and Ocular Surface Disease Index (OSDI), and correlated the results with syalometry and Schirmer's test. Statistical analysis was performed with SPSS (Mann-Whitney U-test and Spearman's correlation). Salivary flux was significantly lower in PSS patients, as compared to controls (0.08+/-0.01 ml/min versus 0.38+/-0.25 ml/min, p=0.000), and decreased with age. Syalometry didn't correlate with Schirmer's test. OHIP scores (mean 26.8 points, ranging from 2 to 43 for a maximum of 56 points) didn't correlate with syalometry neither with Schirmer's test, but showed an association with the XI (p<0.0005) and OSDI (p<0.0005) tests. The XI questionnaire (mean 28.4 points, ranging from 11 to 41 for a maximum of 44 points) correlated with syalometry (p=0.018), with the OHIP questionary (p<0.0005) and with the OSDI scale (p=0.004), although it didn't correlate with Schirmer's test. OSDI scores (mean 56.5 points, ranging from 7 to 90 for a maximum of 100 points) didn't correlate with Schirmer's test neither with syalometry, but associated with the XI (p=0.004) and OHIP (p<0.0005) scales. Unstimulated syalometry is useful in the evaluation of patients suspected of suffering from Sjögren's syndrome, since it can confirm salivary hypofunction in a quick and cheap manner, allowing to differentiate between healthy individuals and patients. In a specialized clinic, the immediate availability of a salivary functional test is important in the classification of PSS or sicca syndrome. The

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study.

PubMed

Asante, Albert; Leonard, Phoebe H; Weaver, Amy L; Goode, Ellen L; Jensen, Jani R; Stewart, Elizabeth A; Coddington, Charles C

2013-06-01

To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Case-control study (Mayo Clinic Ovarian Cancer Study). Ongoing academic study of ovarian cancer. A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. None. Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. Published by Elsevier Inc.

Impact of Salivary Gland Dosimetry on Post-IMRT Recovery of Saliva Output and Xerostomia Grade for Head-and-Neck Cancer Patients Treated With or Without Contralateral Submandibular Gland Sparing: A Longitudinal Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhonghe; Yan Chao; Zhang Zhiyuan

Purpose: To observe the recovery of saliva output and effect on xerostomia grade after intensity-modulated radiotherapy (IMRT) with or without contralateral submandibular gland (cSMG) sparing and to assess the impact of salivary gland dosimetry on this recovery among patients with head-and-neck cancer. Methods and Materials: Between May 2007 and May 2008, 52 patients with head-and-neck cancer received definitive (n = 5 patients) and postoperative (n = 47 patients) IMRT at our institution, with at least one parotid gland spared. Of these patients, 26 patients with a low risk of recurrence in the cSMG region underwent IMRT and had their cSMGsmore » spared (cSMG-sparing group). The remaining 26 high-risk patients had no cSMGs spared (cSMG-unspared group). Xerostomia grades and salivary flow rates were monitored at five time points (before IMRT and at 2, 6, 12, and 18 months after IMRT). Results: Average mean doses and mean volumes receiving 30 Gy (V30) of the cSMGs were lower in the cSMG-sparing group than in the cSMG-unspared group (mean dose, 20.4 Gy vs. 57.4 Gy; mean V30, 14.7% vs. 99.8%, respectively). Xerostomia grades at 2 and 6 months post-IMRT were also significantly lower among patients in the cSMG-sparing group than in the cSMG-unspared group, but differences were not significant at 12 and 18 months after IMRT. Patients in the cSMG-sparing group had significantly better mean unstimulated salivary flow rates at each time point post- IMRT as well as better mean stimulated salivary flow rates at 2 months post-IMRT. Conclusions: Recovery of saliva output and grade of xerostomia post-IMRT in patients whose cSMGs were spared were much better than in patients whose cSMGs were not spared. The influence of the mean doses to the cSMG and parotid gland on the recovery of saliva output was equivalent to that of the mean V30 to the glands.« less

Computational evaluation of new homologous down regulators of Translationally Controlled Tumor Protein (TCTP) targeted for tumor reversion.

PubMed

Nayarisseri, Anuraj; Yadav, Mukesh; Wishard, Rohan

2013-12-01

The Translationally Controlled Tumor Protein (TCTP) has been investigated for tumor reversion and is a target of cancer therapy. Down regulators which suppress the expression of TCTP can trigger the process of tumor reversion leading to the transformation of tumor cells into revertant cells. The present investigation is a novel protein-protein docking approach to target TCTP by a set of proteins similar to the protein: sorting nexin 6 (SNX6) which is an established down regulator of TCTP. The established down regulator along with its set of most similar proteins were modeled using the PYTHON based software - MODELLER v9.9, followed by structure validation using the Procheck Package. Further TCTP was docked with its established and prospective down regulators using the flexible docking protocol suite HADDOCK. The results were evaluated and ranked according to the RMSD values of the complex and the HADDOCK score, which is a weighted sum of van der Waal's energy, electrostatic energy, restraints violation energy and desolvation energy. Results concluded the protein sorting nexin 6 of Mus musculus to be a better down regulator of TCTP, as compared to the suggested down regulator (Homo sapiens snx6).

Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

DOE PAGES

Zhang, Pengju; Lo, Alvin; Huang, Yurong; ...

2015-03-09

The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

Identification of genetic loci that control mammary tumor susceptibility through the host microenvironment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Pengju; Lo, Alvin; Huang, Yurong

The interplay between host genetics, tumor microenvironment and environmental exposure in cancer susceptibility remains poorly understood. Here we assessed the genetic control of stromal mediation of mammary tumor susceptibility to low dose ionizing radiation (LDIR) using backcrossed F1 into BALB/c (F1Bx) between cancer susceptible (BALB/c) and resistant (SPRET/EiJ) mouse strains. Tumor formation was evaluated after transplantation of non-irradiated Trp53-/- BALB/c mammary gland fragments into cleared fat pads of F1Bx hosts. Genome-wide linkage analysis revealed 2 genetic loci that constitute the baseline susceptibility via host microenvironment. However, once challenged with LDIR, we discovered 13 additional loci that were enriched for genesmore » involved in cytokines, including TGFβ1 signaling. Surprisingly, LDIR-treated F1Bx cohort significantly reduced incidence of mammary tumors from Trp53-/- fragments as well as prolonged tumor latency, compared to sham-treated controls. We demonstrated further that plasma levels of specific cytokines were significantly correlated with tumor latency. Using an ex vivo 3-D assay, we confirmed TGFβ1 as a strong candidate for reduced mammary invasion in SPRET/EiJ, which could explain resistance of this strain to mammary cancer risk following LDIR. Our results open possible new avenues to understand mechanisms of genes operating via the stroma that affect cancer risk from external environmental exposures.« less

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE PAGES

De Pillis, L. G.; Radunskaya, A.

2001-01-01

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Pillis, L. G.; Radunskaya, A.

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

Microprocessor-controlled Nd:YAG laser for hyperthermia induction in the RIF-1 tumor.

PubMed

Waldow, S M; Russell, G E; Wallner, P E

1992-01-01

Near-infrared radiation from a Nd:YAG laser at 1,064 nm was used interstitially or superficially to induce hyperthermia in RIF-1 tumors in C3H male mice. A single 600-microns quartz fiber with a 0.5-cm cylindrical diffusor or a weakly diverging microlens at its distal end was used to deliver laser energy to tumors in the hind leg (mean volume = 100 mm3). Two thermocouples were inserted into each tumor. One thermocouple controlled a microprocessor-driven hyperthermia program (maximum output of 3.5 Watts) to maintain the desired temperature. Tumors were exposed to various temperature-time combinations (42-45 degrees C/30 min). Our initial results indicated that excellent temperature control to within 0.2 degrees C of the desired temperature at the feedback thermocouple was achievable during both superficial and interstitial heat treatments. Temperatures at the second thermocouple, however, were found to be lower by as much as 2.3 degrees C (using the cylindrical diffusor) or higher by up to 4.6 degrees C (using the microlens) when compared to the feedback thermocouple temperature. Several correlations were seen between total dose, tumor growth delay, percent skin necrosis, and temperature at the second thermocouple after several superficial and interstitial treatments. Statistically significant improvements in tumor growth delay (at 42 and 45 degrees C) and increased percent skin necrosis at all temperatures were observed after superficial versus interstitial treatment.

Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

PubMed

Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

2016-12-01

The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, p<0.001 and t=-3.69, p<0.001, respectively). The D r-l was not different between brain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Optimal distributed control of a diffuse interface model of tumor growth

NASA Astrophysics Data System (ADS)

Colli, Pierluigi; Gilardi, Gianni; Rocca, Elisabetta; Sprekels, Jürgen

2017-06-01

In this paper, a distributed optimal control problem is studied for a diffuse interface model of tumor growth which was proposed by Hawkins-Daruud et al in Hawkins-Daruud et al (2011 Int. J. Numer. Math. Biomed. Eng. 28 3-24). The model consists of a Cahn-Hilliard equation for the tumor cell fraction φ coupled to a reaction-diffusion equation for a function σ representing the nutrient-rich extracellular water volume fraction. The distributed control u monitors as a right-hand side of the equation for σ and can be interpreted as a nutrient supply or a medication, while the cost function, which is of standard tracking type, is meant to keep the tumor cell fraction under control during the evolution. We show that the control-to-state operator is Fréchet differentiable between appropriate Banach spaces and derive the first-order necessary optimality conditions in terms of a variational inequality involving the adjoint state variables. The financial support of the FP7-IDEAS-ERC-StG #256872 (EntroPhase) and of the project Fondazione Cariplo-Regione Lombardia MEGAsTAR ‘Matematica d’Eccellenza in biologia ed ingegneria come accelleratore di una nuona strateGia per l’ATtRattività dell’ateneo pavese’ is gratefully acknowledged. The paper also benefited from the support of the MIUR-PRIN Grant 2015PA5MP7 ‘Calculus of Variations’ for PC and GG, and the GNAMPA (Gruppo Nazionale per l’Analisi Matematica, la Probabilità e le loro Applicazioni) of INdAM (Istituto Nazionale di Alta Matematica) for PC, GG and ER.

Ixeris dentata extract regulates salivary secretion through the activation of aquaporin-5 and prevents diabetes-induced xerostomia

PubMed Central

Bhattarai, Kashi Raj; Lee, Sang-Won; Kim, Seung Hyun; Kim, Hyung-Ryong; Chae, Han-Jung

2017-01-01

The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na+/H+ exchangers in the salivary gland, which suggests that Na+/H+ exchangers modulate salivary secretions and aid in the fluid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia. PMID:28814903

Ixeris dentata extract regulates salivary secretion through the activation of aquaporin-5 and prevents diabetes-induced xerostomia.

PubMed

Bhattarai, Kashi Raj; Lee, Sang-Won; Kim, Seung Hyun; Kim, Hyung-Ryong; Chae, Han-Jung

2017-01-01

The aim of this study was to investigate the effects of Ixeris dentata (IXD) extract to improve the salivation rate in dry mouth induced by diabetes. Both control and diabetic rats were treated with a sublingual spray of either water or IXD extract to determine the effects of IXD on salivation. During the study, we observed that IXD extract treatment increased the salivary flow rate in diabetic rats. The expression of α-amylase was increased significantly in both saliva and glandular tissue lysates of IXD-treated diabetic rats. Aquaporin-5 protein expression was abnormally low in the salivary glands of diabetic rats, which increased hyposalivation and led to salivary dysfunction. However, a single oral spray of IXD extract drastically increased the expression of aquaporin-5 in salivary gland acinar and ductal cells in diabetic rats. Moreover, IXD extract induced expression of Na + /H + exchangers in the salivary gland, which suggests that Na + /H + exchangers modulate salivary secretions and aid in the fluid-secretion mechanism. Furthermore, transient treatment with IXD extract increased the intracellular calcium in human salivary gland cells. Taken together, these results suggest the potential value of an IXD extract for the treatment of diabetes-induced hyposalivation and xerostomia.

Long-term Use of the Sialogogue Medications Pilocarpine and Cevimeline Can Reduce Xerostomia Symptoms and Increase Salivary Flow in Head and Neck Cancer Survivors After Radiotherapy.

PubMed

Barbe, Anna Greta

2017-09-01

Interventions for the management of radiotherapy-induced xerostomia and hyposalivation: A systematic review and meta-analysis. Mercadante V, Hamad AA, Lodi G, Porter S, Fedele S. Oral Oncol 2017;66:64-74. The authors reported that no external funding sources directly supported this study TYPE OF STUDY/DESIGN: Systematic review and meta-analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

Antigen localization controls T cell-mediated tumor immunity.

PubMed

Zeelenberg, Ingrid S; van Maren, Wendy W C; Boissonnas, Alexandre; Van Hout-Kuijer, Maaike A; Den Brok, Martijn H M G M; Wagenaars, Jori A L; van der Schaaf, Alie; Jansen, Eric J R; Amigorena, Sebastian; Théry, Clotilde; Figdor, Carl G; Adema, Gosse J

2011-08-01

Effective antitumor immunotherapy requires the identification of suitable target Ags. Interestingly, many of the tumor Ags used in clinical trials are present in preparations of secreted tumor vesicles (exosomes). In this study, we compared T cell responses elicited by murine MCA101 fibrosarcoma tumors expressing a model Ag at different localizations within the tumor cell in association with secreted vesicles (exosomes), as a nonsecreted cell-associated protein, or as secreted soluble protein. Remarkably, we demonstrated that only the tumor-secreting vesicle-bound Ag elicited a strong Ag-specific CD8(+) T cell response, CD4(+) T cell help, Ag-specific Abs, and a decrease in the percentage of immunosuppressive regulatory T cells in the tumor. Moreover, in a therapeutic tumor model of cryoablation, only in tumors secreting vesicle-bound Ag could Ag-specific CD8(+) T cells still be detected up to 16 d after therapy. We concluded that the localization of an Ag within the tumor codetermines whether a robust immunostimulatory response is elicited. In vivo, vesicle-bound Ag clearly skews toward a more immunogenic phenotype, whereas soluble or cell-associated Ag expression cannot prevent or even delay outgrowth and results in tumor tolerance. This may explain why particular immunotherapies based on these vesicle-bound tumor Ags are potentially successful. Therefore, we conclude that this study may have significant implications in the discovery of new tumor Ags suitable for immunotherapy and that their location should be taken into account to ensure a strong antitumor immune response.

Protection of Salivary Function by Concomitant Pilocarpine During Radiotherapy: A Double-Blind, Randomized, Placebo-Controlled Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burlage, Fred R.; Roesink, Judith M.; Kampinga, Harm H.

2008-01-01

Purpose: To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head-and-neck squamous cell carcinoma (HNSCC) on postradiotherapy xerostomia. Methods and Materials: A prospective, double blind, placebo-controlled randomized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gland dysfunction. The primary objective endpoint was parotid flow rate complication probability (PFCP) scored 6 weeks, 6 months, and 12 months after radiotherapy. Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale (LENT SOMA) and patient-rated xerostomia scores. For all parotid glands, dose-volume histograms were assessed because the dosemore » distribution in the parotid glands is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction. Results: Although no significant differences in PFCP were found for the two treatments arms, a significant (p = 0.03) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy. The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group. Conclusions: Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores. In a subgroup of patients with a mean dose above 40 Gy, pilocarpine administration resulted in sparing of parotid gland function. Therefore, pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable.« less

Effect of a 2% topical chamomile application for treating burning mouth syndrome: a controlled clinical trial.

PubMed

Valenzuela, Sara; Pons-Fuster, Alvaro; López-Jornet, Pia

2016-08-01

The treatments for burning mouth syndrome (BMS) proposed to date have been varied but have only achieved limited efficacy. Chamomile has analgesic and anti-inflammatory properties. The aim of this study was to evaluate the efficacy of topical applications of 2% chamomile gel in comparison with a placebo for the treatment of BMS. The study was designed as a prospective randomized placebo-controlled double-blind monocentric study. A total of 62 patients with idiopathic BMS were divided into two groups: Group A received applications of a 2% chamomile gel, and Group B (placebo) were administered a placebo; both treatments were applied twice daily for 1 month. Three variables were evaluated at base line, 15 and 30 days: pain (assessed using a visual analogue scale [VAS]), xerostomia severity (Xerostomia Inventory), and oral quality of life (assessed by means of the Oral Health Impact Profile-14). A total of 57 patients completed the study. Pain, xerostomia, and quality of life underwent improvements with statistical significance at 15 and 30 days in both groups (P < 0.001). But when the two groups were compared, differences in VAS pain were not significant (P = 0.847), nor were xerostomia severity (P = 0.536), or oral quality of life (P = 0.076). The chamomile gel product was well tolerated. As treatment with chamomile and the placebo produced similar outcomes, the efficacy of 2% chamomile gel for treating BMS appears questionable. However, further studies with larger patient samples are needed to confirm this. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

P97/CDC-48: proteostasis control in tumor cell biology.

PubMed

Fessart, Delphine; Marza, Esther; Taouji, Saïd; Delom, Frédéric; Chevet, Eric

2013-08-28

P97/CDC-48 is a prominent member of a highly evolutionary conserved Walker cassette - containing AAA+ATPases. It has been involved in numerous cellular processes ranging from the control of protein homeostasis to membrane trafficking through the intervention of specific accessory proteins. Expression of p97/CDC-48 in cancers has been correlated with tumor aggressiveness and prognosis, however the precise underlying molecular mechanisms remain to be characterized. Moreover p97/CDC-48 inhibitors were developed and are currently under intense investigation as anticancer drugs. Herein, we discuss the role of p97/CDC-48 in cancer development and its therapeutic potential in tumor cell biology. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Histones: Controlling Tumor Signaling Circuitry

PubMed Central

Martins, Manoela D.; Castilho, Rogerio M.

2014-01-01

Epigenetic modifications constitute the next frontier in tumor biology research. Post-translation modification of histones dynamically influences gene expression independent of alterations to the DNA sequence. These mechanisms are often mediated by histone linkers or by proteins associated with the recruitment of DNA-binding proteins, HDAC I and II interacting proteins and transcriptional activators, coactivators or corepressors. Early evidence suggested that histones and their modifiers are involved in sophisticated processes that modulate tumor behavior and cellular phenotype. In this review, we discuss how recent discoveries about chromatin modifications, particularly histone acetylation, are shaping our knowledge of cell biology and our understanding of the molecular circuitry governing tumor progression and consider whether recent insights may extend to novel therapeutic approaches. Furthermore, we discuss the latest oncogenomic findings in Head and Neck Squamous Cell Carcinoma (HNSCC) from studies using Next Generation Sequencing (NGS) technology and highlight the impact of mutations identified in histones and their modifiers. PMID:25177526

Predictors of Individual Tumor Local Control After Stereotactic Radiosurgery for Non-Small Cell Lung Cancer Brain Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garsa, Adam A.; Badiyan, Shahed N.; DeWees, Todd

2014-10-01

Purpose: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). Methods and Materials: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. Amore » P value <.05 was considered statistically significant. Results: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. Conclusions: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a

Combination of a fusogenic glycoprotein, prodrug activation, and oncolytic herpes simplex virus for enhanced local tumor control.

PubMed

Simpson, Guy R; Han, Ziqun; Liu, Binlei; Wang, Yibing; Campbell, Gregor; Coffin, Robert S

2006-05-01

We have previously developed an oncolytic herpes simplex virus-1 based on a clinical virus isolate, which was deleted for ICP34.5 to provide tumor selected replication and ICP47 to increase antigen presentation as well as tumor selective virus replication. A phase I/II clinical trial using a version of this virus expressing granulocyte macrophage colony-stimulating factor has shown promising results. The work reported here aimed to develop a version of this virus in which local tumor control was further increased through the combined expression of a highly potent prodrug activating gene [yeast cytosine deaminase/uracil phospho-ribosyltransferase fusion (Fcy::Fur)] and the fusogenic glycoprotein from gibbon ape leukemia virus (GALV), which it was hoped would aid the spread of the activated prodrug through the tumor. Viruses expressing the two genes individually or in combination were constructed and tested, showing (a) GALV and/or Fcy::Fur expression did not affect virus growth; (b) GALV expression causes cell fusion and increases the tumor cell killing at least 30-fold in vitro and tumor shrinkage 5- to 10-fold in vivo; (c) additional expression of Fcy::Fur combined with 5-fluorocytosine administration improves tumor shrinkage further. These results indicate, therefore, that the combined expression of the GALV protein and Fcy::Fur provides a highly potent oncolytic virus with improved capabilities for local tumor control. It is intended to enter the GALV/Fcy::Fur expressing virus into clinical development for the treatment of tumor types, such as pancreatic or lung cancer, where local control would be anticipated to be clinically advantageous.

Leukemia and brain tumors in Norwegian railway workers, a nested case-control study.

PubMed

Tynes, T; Jynge, H; Vistnes, A I

1994-04-01

In an attempt to assess whether exposure to electromagnetic fields on Norwegian railways induces brain tumors or leukemia, the authors conducted a nested case-control study of railway workers based on incident cases from the Cancer Registry of Norway in a cohort of 13,030 male Norwegian railway workers who had worked on either electric or non-electric railways. The cohort comprised railway line, outdoor station, and electricity workers. The case series comprised 39 men with brain tumors and 52 men with leukemia (follow-up, 1958-1990). Each case was matched on age with four or five controls selected from the same cohort. The exposure of each study subject to electric and magnetic fields was evaluated from cumulative exposure measures based on present measurements and historical data. Limited information on potential confounders such as creosote, solvents, and herbicides was also collected; information on whether the subject had smoked was obtained by interviews with the subjects or work colleagues. The case-control analysis showed that men employed on electric railways, compared with non-electric ones, had an odds ratio for leukemia of 0.70 (adjusted for smoking) and an odds ratio for brain tumor of 0.87. No significant trend was shown for exposure to either magnetic or electric fields. These results do not support an association between exposure to 16 2/3-Hertz electric or magnetic fields and the risk for leukemia or brain tumors.

Controlled Drug Release and Chemotherapy Response in a Novel Acoustofluidic 3D Tumor Platform.

PubMed

Zervantonakis, Ioannis K; Arvanitis, Costas D

2016-05-01

Overcoming transport barriers to delivery of therapeutic agents in tumors remains a major challenge. Focused ultrasound (FUS), in combination with modern nanomedicine drug formulations, offers the ability to maximize drug transport to tumor tissue while minimizing toxicity to normal tissue. This potential remains unfulfilled due to the limitations of current approaches in accurately assessing and quantifying how FUS modulates drug transport in solid tumors. A novel acoustofluidic platform is developed by integrating a physiologically relevant 3D microfluidic device and a FUS system with a closed-loop controller to study drug transport and assess the response of cancer cells to chemotherapy in real time using live cell microscopy. FUS-induced heating triggers local release of the chemotherapeutic agent doxorubicin from a liposomal carrier and results in higher cellular drug uptake in the FUS focal region. This differential drug uptake induces locally confined DNA damage and glioblastoma cell death in the 3D environment. The capabilities of acoustofluidics for accurate control of drug release and monitoring of localized cell response are demonstrated in a 3D in vitro tumor mode. This has important implications for developing novel strategies to deliver therapeutic agents directly to the tumor tissue while sparing healthy tissue. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.

PubMed

Aydin, Denis; Feychting, Maria; Schüz, Joachim; Tynes, Tore; Andersen, Tina Veje; Schmidt, Lisbeth Samsø; Poulsen, Aslak Harbo; Johansen, Christoffer; Prochazka, Michaela; Lannering, Birgitta; Klæboe, Lars; Eggen, Tone; Jenni, Daniela; Grotzer, Michael; Von der Weid, Nicolas; Kuehni, Claudia E; Röösli, Martin

2011-08-17

It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents. CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models. Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure. The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.

Atopic conditions and brain tumor risk in children and adolescents--an international case-control study (CEFALO).

PubMed

Shu, X; Prochazka, M; Lannering, B; Schüz, J; Röösli, M; Tynes, T; Kuehni, C E; Andersen, T V; Infanger, D; Schmidt, L S; Poulsen, A H; Klaeboe, L; Eggen, T; Feychting, M

2014-04-01

A number of epidemiological studies indicate an inverse association between atopy and brain tumors in adults, particularly gliomas. We investigated the association between atopic disorders and intracranial brain tumors in children and adolescents, using international collaborative CEFALO data. CEFALO is a population-based case-control study conducted in Denmark, Norway, Sweden, and Switzerland, including all children and adolescents in the age range 7-19 years diagnosed with a primary brain tumor between 2004 and 2008. Two controls per case were randomly selected from population registers matched on age, sex, and geographic region. Information about atopic conditions and potential confounders was collected through personal interviews. In total, 352 cases (83%) and 646 controls (71%) participated in the study. For all brain tumors combined, there was no association between ever having had an atopic disorder and brain tumor risk [odds ratio 1.03; 95% confidence interval (CI) 0.70-1.34]. The OR was 0.76 (95% CI 0.53-1.11) for a current atopic condition (in the year before diagnosis) and 1.22 (95% CI 0.86-1.74) for an atopic condition in the past. Similar results were observed for glioma. There was no association between atopic conditions and risk of all brain tumors combined or of glioma in particular. Stratification on current or past atopic conditions suggested the possibility of reverse causality, but may also the result of random variation because of small numbers in subgroups. In addition, an ongoing tumor treatment may affect the manifestation of atopic conditions, which could possibly affect recall when reporting about a history of atopic diseases. Only a few studies on atopic conditions and pediatric brain tumors are currently available, and the evidence is conflicting.

Xerostomia and quality of life after intensity-modulated radiotherapy vs. conventional radiotherapy for early-stage nasopharyngeal carcinoma: Initial report on a randomized controlled clinical trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pow, Edmond; Kwong, Dora; McMillan, Anne S.

2006-11-15

Purpose: To compare directly the effect of intensity-modulated radiotherapy (IMRT) vs. conventional radiotherapy (CRT) on salivary flow and quality of life (QoL) in patients with early-stage nasopharyngeal carcinoma (NPC). Methods and Materials: Fifty-one patients with T2, N0/N1, M0 NPC took part in a randomized controlled clinical study and received IMRT or CRT. Stimulated whole (SWS) and parotid (SPS) saliva flow were measured and Medical Outcomes Short Form 36 (SF-36), European Organization for Research and Treatment of Cancer (EORTC) core quetionnaire, and EORTC head-and-neck module (QLQ-H and N35) were completed at baseline and 2, 6, and 12 months after radiotherapy. Results:more » Forty-six patients (88%) were in disease remission 12 months after radiotherapy. At 12 months postradiotherapy, 12 (50.0%) and 20 patients (83.3%) in the IMRT group had recovered at least 25% of preradiotherapy SWS and SPS flow respectively, compared with 1 (4.8%) and 2 patients (9.5%), respectively, in the CRT group. Global health scores showed continuous improvement in QoL after both treatments (p < 0.001). However, after 12 months subscale scores for role-physical, bodily pain, and physical function were significantly higher in the IMRT group, indicating a better condition (p < 0.05). Dry mouth and sticky saliva were problems in both groups 2 months after treatment. In the IMRT group, there was consistent improvement over time with xerostomia-related symptoms significantly less common than in the CRT group at 12 months postradiotherapy. Conclusions: IMRT was significantly better than CRT in terms of parotid sparing and improved QoL for early-stage disease. The findings support the case for assessment of health-related QoL in relation to head-and-neck cancer using a site-specific approach.« less

Tumor-Specific Chromosome Mis-Segregation Controls Cancer Plasticity by Maintaining Tumor Heterogeneity

PubMed Central

Hu, Yuanjie; Ru, Ning; Xiao, Huasheng; Chaturbedi, Abhishek; Hoa, Neil T.; Tian, Xiao-Jun; Zhang, Hang; Ke, Chao; Yan, Fengrong; Nelson, Jodi; Li, Zhenzhi; Gramer, Robert; Yu, Liping; Siegel, Eric; Zhang, Xiaona; Jia, Zhenyu; Jadus, Martin R.; Limoli, Charles L.; Linskey, Mark E.; Xing, Jianhua; Zhou, Yi-Hong

2013-01-01

Aneuploidy with chromosome instability is a cancer hallmark. We studied chromosome 7 (Chr7) copy number variation (CNV) in gliomas and in primary cultures derived from them. We found tumor heterogeneity with cells having Chr7-CNV commonly occurs in gliomas, with a higher percentage of cells in high-grade gliomas carrying more than 2 copies of Chr7, as compared to low-grade gliomas. Interestingly, all Chr7-aneuploid cell types in the parental culture of established glioma cell lines reappeared in single-cell-derived subcultures. We then characterized the biology of three syngeneic glioma cultures dominated by different Chr7-aneuploid cell types. We found phenotypic divergence for cells following Chr7 mis-segregation, which benefited overall tumor growth in vitro and in vivo. Mathematical modeling suggested the involvement of chromosome instability and interactions among cell subpopulations in restoring the optimal equilibrium of tumor cell types. Both our experimental data and mathematical modeling demonstrated that the complexity of tumor heterogeneity could be enhanced by the existence of chromosomes with structural abnormality, in addition to their mis-segregations. Overall, our findings show, for the first time, the involvement of chromosome instability in maintaining tumor heterogeneity, which underlies the enhanced growth, persistence and treatment resistance of cancers. PMID:24282558

LYSOPHOSPHATIDIC ACID INHIBITS CD8 T CELL ACTIVATION AND CONTROL OF TUMOR PROGRESSION

PubMed Central

Oda, Shannon K.; Strauch, Pamela; Fujiwara, Yuko; Al-Shami, Amin; Oravecz, Tamas; Tigyi, Gabor; Pelanda, Roberta; Torres, Raul M.

2013-01-01

CD8 T lymphocytes are able to eliminate nascent tumor cells through a process referred to as immune surveillance. However, multiple inhibitory mechanisms within the tumor microenvironment have been described that impede tumor rejection by CD8 T cells, including increased signaling by inhibitory receptors. Lysophosphatidic acid (LPA) is a bioactive lysophospholipid that has been shown repeatedly to promote diverse cellular processes benefiting tumorigenesis. Accordingly, the increased expression of LPA and LPA receptors is a common feature of diverse tumor cell lineages and can result in elevated systemic LPA levels. LPA is recognized by at least 6 distinct G-protein-coupled receptors and several of which are expressed by T cells, although the precise role of LPA signaling in CD8 T cell activation and function has not been defined. Here, we demonstrate that LPA signaling via the LPA5 receptor expressed by CD8 T cells suppresses antigen receptor signaling, cell activation and proliferation in vitro and in vivo. Importantly, in a mouse melanoma model tumor-specific CD8 T cells that are LPA5-deficient are able to control tumor growth significantly better than wild-type tumor-specific CD8 T cells. Together, these data suggest that the production of LPA by tumors serves not only in an autocrine manner to promote tumorigenesis but also as a mechanism to suppress adaptive immunity and highlights a potential novel target for cancer treatment. PMID:24455753

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system

PubMed Central

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-01-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. PMID:23834399

Risk Factors for Preoperative Seizures and Loss of Seizure Control in Patients Undergoing Surgery for Metastatic Brain Tumors.

PubMed

Wu, Adela; Weingart, Jon D; Gallia, Gary L; Lim, Michael; Brem, Henry; Bettegowda, Chetan; Chaichana, Kaisorn L

2017-08-01

Metastatic brain tumors are the most common brain tumors in adults. Patients with metastatic brain tumors have poor prognoses with median survival of 6-12 months. Seizures are a major presenting symptom and cause of morbidity and mortality. In this article, risk factors for the onset of preoperative seizures and postoperative seizure control are examined. Adult patients who underwent resection of one or more brain metastases at a single institution between 1998 and 2011 were reviewed retrospectively. Of 565 patients, 114 (20.2%) patients presented with seizures. Factors independently associated with preoperative seizures were preoperative headaches (P = 0.044), cognitive deficits (P = 0.031), more than 2 intracranial metastatic tumors (P = 0.013), temporal lobe location (P = 0.031), occipital lobe location (P = 0.010), and bone involvement by tumor (P = 0.029). Factors independently associated with loss of seizure control after surgical resection were preoperative seizures (P = 0.001), temporal lobe location (P = 0.037), lack of postoperative chemotherapy (P = 0.010), subtotal resection of tumor (P = 0.022), and local recurrence (P = 0.027). At last follow-up, the majority of patients (93.8%) were seizure-free. Thirty patients (5.30%) in total had loss of seizure control, and only 8 patients (1.41%) who did not have preoperative seizures presented with new-onset seizures after surgical resection of their metastases. The brain is a common site for metastases from numerous primary cancers, such as breast and lung. The identification of factors associated with onset of preoperative seizures as well as seizure control postoperatively could aid management strategies for patients with metastatic brain tumors. Patients with preoperative seizures who underwent resection tended to have good seizure control after surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

FXR controls the tumor suppressor NDRG2 and FXR agonists reduce liver tumor growth and metastasis in an orthotopic mouse xenograft model.

PubMed

Deuschle, Ulrich; Schüler, Julia; Schulz, Andreas; Schlüter, Thomas; Kinzel, Olaf; Abel, Ulrich; Kremoser, Claus

2012-01-01

The farnesoid X receptor (FXR) is expressed predominantly in tissues exposed to high levels of bile acids and controls bile acid and lipid homeostasis. FXR(-/-) mice develop hepatocellular carcinoma (HCC) and show an increased prevalence for intestinal malignancies, suggesting a role of FXR as a tumor suppressor in enterohepatic tissues. The N-myc downstream-regulated gene 2 (NDRG2) has been recognized as a tumor suppressor gene, which is downregulated in human hepatocellular carcinoma, colorectal carcinoma and many other malignancies.We show reduced NDRG2 mRNA in livers of FXR(-/-) mice compared to wild type mice and both, FXR and NDRG2 mRNAs, are reduced in human HCC compared to normal liver. Gene reporter assays and Chromatin Immunoprecipitation data support that FXR directly controls NDRG2 transcription via IR1-type element(s) identified in the first introns of the human, mouse and rat NDRG2 genes. NDRG2 mRNA was induced by non-steroidal FXR agonists in livers of mice and the magnitude of induction of NDRG2 mRNA in three different human hepatoma cell lines was increased when ectopically expressing human FXR. Growth and metastasis of SK-Hep-1 cells was strongly reduced by non-steroidal FXR agonists in an orthotopic liver xenograft tumor model. Ectopic expression of FXR in SK-Hep1 cells reduced tumor growth and metastasis potential of corresponding cells and increased the anti-tumor efficacy of FXR agonists, which may be partly mediated via increased NDRG2 expression. FXR agonists may show a potential in the prevention and/or treatment of human hepatocellular carcinoma, a devastating malignancy with increasing prevalence and limited therapeutic options.

SU-E-T-471: Improvement of Gamma Knife Treatment Planning Through Tumor Control Probability for Metastatic Brain Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Z; Feng, Y; Lo, S

2015-06-15

Purpose: The dose–volume histogram (DVH) has been normally accepted as a tool for treatment plan evaluation. However, spatial information is lacking in DVH. As a supplement to the DVH in three-dimensional treatment planning, the differential DVH (DDVH) provides the spatial variation, the size and magnitude of the different dose regions within a region of interest, which can be incorporated into tumor control probability model. This study was to provide a method in evaluating and improving Gamma Knife treatment planning. Methods: 10 patients with brain metastases from different primary tumors including melanoma (#1,#4,#5, #10), breast cancer (#2), prostate cancer (#3) andmore » lung cancer (#6–9) were analyzed. By using Leksell GammaPlan software, two plans were prepared for each patient. Special attention was given to the DDVHs that were different for different plans and were used for a comparison between two plans. Dose distribution inside target and tumor control probability (TCP) based on DDVH were calculated, where cell density and radiobiological parameters were adopted from literature. The plans were compared based on DVH, DDVH and TCP. Results: Using DVH, the coverage and selectivity were the same between plans for 10 patients. DDVH were different between two plans for each patient. The paired t-test showed no significant difference in TCP between the two plans. For brain metastases from melanoma (#1, #4–5), breast cancer (#2) and lung cancer (#6–8), the difference in TCP was less than 5%. But the difference in TCP was about 6.5% for patient #3 with the metastasis from prostate cancer, 10.1% and 178.7% for two patients (#9–10) with metastasis from lung cancer. Conclusion: Although DVH provides average dose–volume information, DDVH provides differential dose– volume information with respect to different regions inside the tumor. TCP provides radiobiological information and adds additional information on improving treatment planning as well as

Immunohistochemical localization of translationally controlled tumor protein in the mouse digestive system.

PubMed

Sheverdin, Vadim; Jung, Jiwon; Lee, Kyunglim

2013-09-01

Translationally controlled tumor protein (TCTP) is a housekeeping protein, highly conserved among various species. It plays a major role in cell differentiation, growth, proliferation, apoptosis and carcinogenesis. Studies reported so far on TCTP expression in different digestive organs have not led to any understanding of the role of TCTP in digestion, so we localized TCTP in organs of the mouse digestive system employing immunohistochemical techniques. Translationally controlled tumor protein was found expressed in all organs studied: tongue, salivary glands, esophagus, stomach, small and large intestines, liver and pancreas. The expression of TCTP was found to be predominant in epithelia and neurons of myenteric nerve ganglia; high in serous glands (parotid, submandibular, gastric, intestinal crypts, pancreatic acini) and in neurons of myenteric nerve ganglia, and moderate to low in epithelia. In epithelia, expression of TCTP varied depending on its type and location. In enteric neurons, TCTP was predominantly expressed in the processes. Translationally controlled tumor protein expression in the liver followed porto-central gradient with higher expression in pericentral hepatocytes. In the pancreas, TCTP was expressed in both acini and islet cells. Our finding of nearly universal localization and expression of TCTP in mouse digestive organs points to the hitherto unrecognized functional importance of TCTP in the digestive system and suggests the need for further studies of the possible role of TCTP in the proliferation, secretion, absorption and neural regulation of the digestive process and its importance in the physiology and pathology of digestive process. © 2013 Anatomical Society.

Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy

PubMed Central

Crittenden, Marka R.; Baird, Jason; Friedman, David; Savage, Talicia; Uhde, Lauren; Alice, Alejandro; Cottam, Benjamin; Young, Kristina; Newell, Pippa; Nguyen, Cynthia; Bambina, Shelly; Kramer, Gwen; Akporiaye, Emmanuel; Malecka, Anna; Jackson, Andrew; Gough, Michael J.

2016-01-01

Radiation therapy provides a means to kill large numbers of cancer cells in a controlled location resulting in the release of tumor-specific antigens and endogenous adjuvants. However, by activating pathways involved in apoptotic cell recognition and phagocytosis, irradiated cancer cells engender suppressive phenotypes in macrophages. We demonstrate that the macrophage-specific phagocytic receptor, Mertk is upregulated in macrophages in the tumor following radiation therapy. Ligation of Mertk on macrophages results in anti-inflammatory cytokine responses via NF-kB p50 upregulation, which in turn limits tumor control following radiation therapy. We demonstrate that in immunogenic tumors, loss of Mertk is sufficient to permit tumor cure following radiation therapy. However, in poorly immunogenic tumors, TGFb inhibition is also required to result in tumor cure following radiation therapy. These data demonstrate that Mertk is a highly specific target whose absence permits tumor control in combination with radiation therapy. PMID:27602953

Cryotherapy with concurrent CpG oligonucleotide treatment controls local tumor recurrence and modulates HER2/neu immunity.

PubMed

Veenstra, Jesse J; Gibson, Heather M; Littrup, Peter J; Reyes, Joyce D; Cher, Michael L; Takashima, Akira; Wei, Wei-Zen

2014-10-01

Percutaneous cryoablation is a minimally invasive procedure for tumor destruction, which can potentially initiate or amplify antitumor immunity through the release of tumor-associated antigens. However, clinically efficacious immunity is lacking and regional recurrences are a limiting factor relative to surgical excision. To understand the mechanism of immune activation by cryoablation, comprehensive analyses of innate immunity and HER2/neu humoral and cellular immunity following cryoablation with or without peritumoral CpG injection were conducted using two HER2/neu(+) tumor systems in wild-type (WT), neu-tolerant, and SCID mice. Cryoablation of neu(+) TUBO tumor in BALB/c mice resulted in systemic immune priming, but not in neu-tolerant BALB NeuT mice. Cryoablation of human HER2(+) D2F2/E2 tumor enabled the functionality of tumor-induced immunity, but secondary tumors were refractory to antitumor immunity if rechallenge occurred during the resolution phase of the cryoablated tumor. A step-wise increase in local recurrence was observed in WT, neu-tolerant, and SCID mice, indicating a role of adaptive immunity in controlling residual tumor foci. Importantly, local recurrences were eliminated or greatly reduced in WT, neu tolerant, and SCID mice when CpG was incorporated in the cryoablation regimen, showing significant local control by innate immunity. For long-term protection, however, adaptive immunity was required because most SCID mice eventually succumbed to local tumor recurrence even with combined cryoablation and CpG treatment. This improved understanding of the mechanisms by which cryoablation affects innate and adaptive immunity will help guide appropriate combination of therapeutic interventions to improve treatment outcomes. ©2014 American Association for Cancer Research.

Anthropometric and Laboratory Variables Related to Weight Loss-Comparison of Heart Failure Patients with Tumor Patients and Control Population.

PubMed

Letilovic, Tomislav; Vrhovac, Radovan; Krznarić, Željko

2017-01-01

Body weight loss is an important feature of heart failure (HF) and tumors. It is related to both reduced survival and adverse reactions to therapy in both of these conditions. The mechanisms of body weight loss in patients with HF and tumors are considered to be similar. Yet, studies comparing those two populations are generally lacking. The aim of this study was to compare anthropometric and laboratory data, related to weight loss, between patients with chronic HF and patients with different tumors as well as control population. Laboratory and anthropometric data on 143 consecutive patients with chronic HF and malignant diseases as well as data for 20 controls were collected. Patients with HF had lower levels of C-reactive protein (CRP) and albumin compared to controls. Anthropometric measurements revealed lower body mass index (BMI), muscle strength, mid-arm circumference, and waist circumference in patients with HF compared to controls. Measurements of biceps, triceps, subscapular, and suprailiac skinfolds were also lower in HF group. Compared to solid tumor group, HF patients had lower levels of CRP and higher levels of hemoglobin. Solid tumor patients had lower values of BMI and subscapular skinfold thickness, as well as higher muscle strength compared to HF group. Finally, compared to patients with solid hematological tumors, HF group had lower levels of albumin, lower muscle strength, as well as lower mid-arm circumference. We found differences in anthropometric and laboratory features, related to weight loss, in patients with HF compared to control population that were expected. On the other hand, observed differences in HF group compared to patients with various tumors could imply different pathophysiological mechanisms of weight loss between those groups. Such data could serve as a cornerstone for studies with larger numbers of patients and deeper pathophysiological insight.

Quality of life after parotid-sparing IMRT for head-and-neck cancer: a prospective longitudinal study.

PubMed

Lin, Alexander; Kim, Hyungjin M; Terrell, Jeffrey E; Dawson, Laura A; Ship, Jonathan A; Eisbruch, Avraham

2003-09-01

Parotid-sparing intensity-modulated radiotherapy (IMRT) for head-and-neck cancer reduces xerostomia compared with standard RT. To assess potential improvements in broader aspects of quality of life (QOL), we initiated a study of patient-reported QOL and its predictors after IMRT. This was a prospective longitudinal study of head-and-neck cancer patients receiving multisegmental static IMRT. Patients were given a validated xerostomia questionnaire (XQ), and a validated head-and-neck cancer-related QOL questionnaire consisting of four multi-item domains: Eating, Communication, Pain, and Emotion. The Eating domain contains one question (total of six) asking directly about xerostomia. In both questionnaires, higher scores denote worse symptoms or QOL. The questionnaires and measurements of salivary output from the major glands were completed before RT started (pre-RT) and at 3, 6, and 12 months after RT. The association between the QOL scores and patient-, tumor-, and therapy-related factors was assessed using the random effects model. Thirty-six patients participating in the study completed the questionnaires through 12 months. The XQ scores worsened significantly at 3 months compared with the pre-RT scores, but later they improved gradually through 12 months (p = 0.003), in parallel with an increase in the salivary output from the spared salivary glands. The QOL summary scores were stable between the baseline (pre-RT) and 3 months after RT scores. Patients receiving postoperative RT (whose pre-RT questionnaires were taken a few weeks after surgery) tended to have improved scores after RT, reflecting the subsidence of acute postoperative sequelae, compared with a tendency toward worsened scores in patients receiving definitive RT. After 3 months, statistically significant improvement was noted in the summary QOL scores for all patients, through 12 months after RT (p = 0.01). The salivary flow rates, tumor doses, mean oral cavity dose, age, gender, sites or stages of

Current therapies for xerostomia and salivary gland hypofunction associated with cancer therapies.

PubMed

Nieuw Amerongen, A V; Veerman, E C I

2003-04-01

In cancer patients, as in the general population, medication is the most common cause of xerostomia. In general, saliva flow in these patients can be stimulated by mechanical or pharmacological stimulation of the salivary glands. Painful damaged oral mucosa can be treated by softening, lubricating mouthwashes or gels. A specific group of patients are those receiving radiotherapy for malignant tumours in the head and neck region. This treatment is inevitably associated with damages to the oral tissues, including the salivary glands, resulting in salivary gland hypofunction. When residual secretory capacity is present, it is advisable to stimulate the salivary glands by mechanical or gustatory stimuli regularly in these patients as supportive oral care. Alternatively, salivary flow can be stimulated by the use of cholinergic pharmaceutical preparations, such as pilocarpine or cevimeline. After the radiation therapy is ended, a dental check-up should be done every 3 months to allow control of any incipient oral inflammation and dental decay. For daily use, a special dentifrice (e.g. children's toothpaste) is recommended, since the taste of a regular dentifrice may be too strong for these patients. Nocturnal oral dryness can be alleviated by spraying the oral surfaces with water, or by applying a small amount of dentifrice on the dental smooth surfaces. When stimulation of salivary secretion fails, patients can be given palliative oral care in the form of application of mouthwashes and saliva substitutes. The daily use of a mouthwash, e.g. Biotène, Oral Balance or Zendium, or one of the saliva substitutes is indicated. Different types of saliva substitutes are now commercially available, containing different polymers as thickening agents, e.g. carboxymethylcellulose (Oralube and Glandosane), polyacrylic acid, and xanthan gum (Xialine). Recent developments, which are, however, still in the experimental stage, are bio-active saliva substitutes and mouthwashes containing

TH-CD-202-10: Tumor Metabolic Control Probability & Dose Response Mapping for Adaptive Dose Painting by Number

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, S; Wilson, G; Krauss, D

Purpose: Adaptive dose-painting-by-number (DPbN) requires a dose-response-mapping (DRM) obtained early in the treatment course. To obtain DRM, voxel-by-voxel tumor dose response needs to be quantified. Our recent study has demonstrated that voxel-by-voxel radio-sensitivity of patient tumor can be determined using tumor-metabolic-ratio measured early during the treatment using FDG-PET images. In this study, the measurements were utilized to construct tumor metabolic control probability (TMCP) and DRM for DPbN. Methods: FDG-PET/CT images of 18 HN cancer patients obtained pre- and weekly during the treatment were used. Spatial parametric images of tumor-metabolic-ratio (dSUV) were constructed following voxel-by-voxel deformable image registration. Each voxel valuemore » in dSUV was a function of baseline SUV and delivered dose. Utilizing all values of dSUV in the controlled tumor group at the last treatment week, a cut-off function between the baseline SUV and dSUV was formed, and applied in early treatment days on dSUV of all tumors to model the TMCP. At the treatment week k, TMCP was constructed with respect to the tumor voxel dSUV appeared at the week using the maximum likelihood estimation for all dose levels, and used for DRM construction. Results: TMCPs estimated in the week 2 & 3 have D{sub 50}=11.1∼47.6Gy; γ{sub 50}=0.55∼0.92 respectively with respect to dSUV=0.3∼1.2. The corresponding DRM between tumor voxel dSUV and the expected treatment dose has sigmoid shape. The expected treatment dose are 26∼40Gy (for 95% TMCP) for high sensitive tumor voxels with dSUV=0.3∼0.5; and 65∼110Gy for low sensitive tumor voxels with the dSUV>1.0 depending on the time of the estimation. Conclusion: TMCP can be constructed voxel-by-voxel in human tumor using multiple FDG-PET imaging obtained in early treatment days. TMCP provides a potential quantitative objective of tumor DRM for DPbN to plan the best dose, escalate or de-escalate, in tumor adaptively based on

Local control of metastatic lung tumors treated with SBRT of 48 Gy in four fractions: in comparison with primary lung cancer.

PubMed

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro; Shinkai, Tetsu; Kubo, Yoshiro; Sugawara, Yoshifumi; Inoue, Takeshi; Sakai, Shinya; Aono, Shoji; Takahashi, Tadaaki; Semba, Takatoshi; Uwatsu, Kotaro

2010-02-01

The optimal dose of stereotactic body radiotherapy (SBRT) for metastatic lung tumors has not been clarified. Local control rates of metastatic lung tumors treated with SBRT of 48 Gy in four fractions, which is one of the common dose schedules for Stage I primary lung cancer in Japan, were examined. Between 2006 and 2008, 12 metastatic lung tumors (colorectal cancer, 7; others, 5) in 10 patients and 56 lesions of Stage I primary lung cancer (T1, 43; T2, 13) in 52 patients were treated with SBRT of 48 Gy in four fractions at the isocenter. Two-year overall survival rates were 86% for patients with metastatic lung tumors and 96% for patients with Stage I primary lung cancer (P = 0.4773). One- and 2-year local control rates were 48% and 25% for metastatic lung tumors, and 91% and 88% for Stage I primary lung cancer, respectively (P < 0.0001). The local control rates after SBRT of 48 Gy in four fractions were significantly worse in metastatic lung tumors compared with Stage I primary lung cancer. In SBRT, metastatic lung tumors should be clearly differentiated from primary lung cancer and should be given higher doses.

Combined modality treatment improves tumor control and overall survival in patients with early stage Hodgkin’s lymphoma: a systematic review

PubMed Central

Herbst, Christine; Rehan, Fareed A.; Brillant, Corinne; Bohlius, Julia; Skoetz, Nicole; Schulz, Holger; Monsef, Ina; Specht, Lena; Engert, Andreas

2010-01-01

Combined modality treatment (CMT) of chemotherapy followed by localized radiotherapy is standard treatment for patients with early stage Hodgkin’s lymphoma. However, the role of radiotherapy has been questioned recently and some clinical study groups advocate chemotherapy only for this indication. We thus performed a systematic review with meta-analysis of randomized controlled trials comparing chemotherapy alone with CMT in patients with early stage Hodgkin’s lymphoma with respect to response rate, tumor control and overall survival (OS). We searched Medline, EMBASE and the Cochrane Library as well as conference proceedings from January 1980 to February 2009 for randomized controlled trials comparing chemotherapy alone versus the same chemotherapy regimen plus radiotherapy. Progression free survival and similar outcomes were analyzed together as tumor control. Effect measures used were hazard ratios for OS and tumor control as well as relative risks for complete response (CR). Meta-analyses were performed using RevMan5. Five randomized controlled trials involving 1,245 patients were included. The hazard ratio (HR) was 0.41 (95% confidence interval (CI) 0.25 to 0.66) for tumor control and 0.40 (95% CI 0.27 to 0.59) for OS for patients receiving CMT compared to chemotherapy alone. CR rates were similar between treatment groups. In sensitivity analyses another 6 trials were included that did not fulfill the inclusion criteria of our protocol but were considered relevant to the topic. These trials underlined the results of the main analysis. In conclusion, adding radiotherapy to chemotherapy improves tumor control and OS in patients with early stage Hodgkin’s lymphoma. PMID:19951972

Enhanced tumor control with combination mTOR and PD-L1 inhibition in syngeneic oral cavity cancers

PubMed Central

Moore, Ellen C.; Cash, Harrison A.; Caruso, Andria M.; Uppaluri, Ravindra; Hodge, James W.; Van Waes, Carter; Allen, Clint T.

2016-01-01

Significant subsets of patients with oral cancer fail to respond to single-agent programmed death (PD) blockade. Syngeneic models of oral cancer were used to determine if blocking oncogenic signaling improved in vivo responses to PD-L1 monoclonal antibody (mAb). Anti-PD-L1 enhanced durable primary tumor control and survival when combined with mTOR (rapamycin), but not in combination with MEK inhibition (PD901) in immunogenic MOC1 tumors. Conversely, PD-L1 mAb did not enhance tumor control in poorly immunogenic MOC2 tumors. Rapamycin enhanced expansion of peripheral antigen-specific CD8 T cells and IFNγ production following ex vivo antigen stimulation. More CD8 T cells infiltrated and were activated after PD-L1 mAb treatment in mice with immunogenic MOC1 tumors, which was stable or increased by the addition of rapamycin, but suppressed when PD901 was added. Rapamycin increased IFNγ production capacity in peripheral and tumor-infiltrating CD8 T cells. In vivo antibody depletion revealed a CD8 T cell, and not NK cell, -dependent mechanism of tumor growth inhibition after treatment with rapamycin and PD-L1 mAb, ruling out significant effects from NK cell–mediated antibody-dependent cellular cytotoxicity. Rapamycin also enhanced IFNγ or PD-L1 mAb treatment–associated induction of MHC class I expression on MOC1 tumor cells, an effect abrogated by depleting infiltrating CD8 T cells from the tumor microenvironment. This data conflicts with traditional views of rapamycin as a universal immunosuppressant, and when combined with evidence of enhanced antitumor activity with the combination of rapamycin and PD-L1 mAb, suggests that this treatment combination deserves careful evaluation in the clinical setting. PMID:27076449

Radiotherapy-induced xerostomia, pre-clinical promise of LMS-611.

PubMed

Paterson, Claire; Caldwell, B; Porteous, S; McLean, A; Messow, C M; Thomson, M

2016-02-01

Radiotherapy-induced xerostomia (RIX) is the most common permanent side effect of radiotherapy (RT) to the head and neck (H&N). There is no effective topical treatment. LMS-611 is a mimetic of a natural lamellar body which prevents thick secretions like saliva from congesting organs. The primary objective of this study was to assess saliva properties before and during RT to the H&N. The secondary objectives were to re-assess saliva properties with the addition of LMS-611, measure inter-patient variability, correlate patient-reported symptoms with laboratory measurements and design subsequent first-in-human clinical trial of LMS-611. Patients with H&N cancer receiving RT as primary treatment were recruited. Patients completed the Groningen RIX (GRIX) questionnaire and provided saliva samples at baseline and weeks 2, 4 and 6 of RT. Saliva adhesiveness and viscosity were tested by measuring time taken to travel 5 cm down an inclined plane. Thirty patients were enrolled. The inclined plane test (IPT) results (s) were as follows: baseline 31.3, week 2 49.7, week 4 51.1 and week 6 55.7. Wide inter-patient variability was seen at baseline. GRIX scores increased as RT progressed. Spearman rank correlation coefficient of inclined plane tests with GRIX scores was -0.06 at baseline, 0.25 at week 2, 0.12 at week 4 and 0.08 at week 6. LMS-611 concentrations of 10 and 20 mg/ml significantly reduced IPT times on saliva samples. Saliva becomes more visco-adhesive and RIX worsens as RT progresses. There is little correlation between objective and subjective measures of RIX. The addition of LMS-611 to thick, sticky saliva restores its fluidity ex vivo. This warrants in vivo analysis of the effect of LMS-611 upon RIX.

Proton beam radiosurgery for vestibular schwannoma: tumor control and cranial nerve toxicity.

PubMed

Weber, Damien C; Chan, Annie W; Bussiere, Marc R; Harsh, Griffith R; Ancukiewicz, Marek; Barker, Fred G; Thornton, Allan T; Martuza, Robert L; Nadol, Joseph B; Chapman, Paul H; Loeffler, Jay S

2003-09-01

We sought to determine the tumor control rate and cranial nerve function outcomes in patients with vestibular schwannomas who were treated with proton beam stereotactic radiosurgery. Between November 1992 and August 2000, 88 patients with vestibular schwannomas were treated at the Harvard Cyclotron Laboratory with proton beam stereotactic radiosurgery in which two to four convergent fixed beams of 160-MeV protons were applied. The median transverse diameter was 16 mm (range, 2.5-35 mm), and the median tumor volume was 1.4 cm(3) (range, 0.1-15.9 cm(3)). Surgical resection had been performed previously in 15 patients (17%). Facial nerve function (House-Brackmann Grade 1) and trigeminal nerve function were normal in 79 patients (89.8%). Eight patients (9%) had good or excellent hearing (Gardner-Robertson [GR] Grade 1), and 13 patients (15%) had serviceable hearing (GR Grade 2). A median dose of 12 cobalt Gray equivalents (range, 10-18 cobalt Gray equivalents) was prescribed to the 70 to 108% isodose lines (median, 70%). The median follow-up period was 38.7 months (range, 12-102.6 mo). The actuarial 2- and 5-year tumor control rates were 95.3% (95% confidence interval [CI], 90.9-99.9%) and 93.6% (95% CI, 88.3-99.3%). Salvage radiosurgery was performed in one patient 32.5 months after treatment, and a craniotomy was required 19.1 months after treatment in another patient with hemorrhage in the vicinity of a stable tumor. Three patients (3.4%) underwent shunting for hydrocephalus, and a subsequent partial resection was performed in one of these patients. The actuarial 5-year cumulative radiological reduction rate was 94.7% (95% CI, 81.2-98.3%). Of the 21 patients (24%) with functional hearing (GR Grade 1 or 2), 7 (33.3%) retained serviceable hearing ability (GR Grade 2). Actuarial 5-year normal facial and trigeminal nerve function preservation rates were 91.1% (95% CI, 85-97.6%) and 89.4% (95% CI, 82-96.7%). Univariate analysis revealed that prescribed dose (P = 0

Salivary gland ultrasonography as a primary imaging tool for predicting efficacy of xerostomia treatment in patients with Sjögren's syndrome.

PubMed

Takagi, Yukinori; Sumi, Misa; Nakamura, Hideki; Sato, Shuntaro; Kawakami, Atsushi; Nakamura, Takashi

2016-02-01

To evaluate ultrasonography (US) grading of salivary gland disease as a predictor of treatment efficacy for impaired salivary function in xerostomia patients with or without Sjögren's syndrome (SS). We retrospectively analysed the prognostic importance of salivary US grading in 317 patients (168 with SS and 149 without SS). US images of the parotid and submandibular glands in each patient were individually categorized into grades 0-4 based on the extent of damage to the gland; and the sum total grade of the two gland types on either side was assigned a US score of 0-8 for each patient. The relative importance of US score and demographic and clinical variables was assessed using stepwise multiple regression analysis after various durations of xerostomia treatment. Multiple regression analysis indicated that the baseline US score before treatment was the most important factor [standardized regression coefficient (β) = -0.523, t-statistic (t) = -7.967, P < 0.001] in predicting negative outcomes in SS patients. Treatment duration (β = 0.277, t = 4.225, P < 0.001) was also a significant but less important positive variable. On the other hand, US grading did not effectively predict treatment outcomes in non-SS patients, with treatment duration (β = 0.199, t = 2.486, P = 0.014) and baseline salivary flow rate before treatment (β = -0.172, t = -2.159, P = 0.032) being significant but weak predictors of positive and negative outcome, respectively. Salivary gland US grading may help to predict outcomes of treatment for impaired salivary function in patients with SS. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Insights into the regulation of tumor dormancy by angiogenesis in experimental tumors.

PubMed

Indraccolo, Stefano

2013-01-01

While it is well established that an angiogenic switch marks escape from tumor dormancy in xenograft models, the molecular pathways involved in the control of tumor cell proliferation or survival by angiogenesis remain substantially uncharted. We recently demonstrated that signals stemming from angiogenic endothelial cells (EC) regulate the behavior of dormant cancer cells. Specifically, we observed that the Notch ligand Dll4, induced by angiogenic factors in EC, triggers Notch3 activation in neighboring tumor cells and promotes a tumorigenic phenotype. Evidence that Notch signaling is involved in tumor dormancy was further strengthened by the observation that MKP-1 levels-a broadly expressed phosphatase-are controlled by Notch3 by regulation of protein ubiquitination and stability. Notch3 and MKP-1 levels are consistently low in dormant tumors, and this is accompanied by relatively high levels of phosphorylated p38, a canonical MKP-1 target previously associated with maintenance of tumor dormancy. These results elucidate a novel angiogenesis-driven mechanism involving the Notch and MAPK pathways that controls tumor dormancy. More in general, angiogenic EC could form part of the vascular niche, a specialized microenvironment which appears to regulate metastatic outgrowth and future studies are needed to clarify the contribution of EC in the regulation of cancer stem cell behavior in the niche.The notion that EC could communicate signals to tumor cells raises questions about the possibility of achieving tumor dormancy by counteracting angiogenesis. In experimental tumors, anti-VEGF drugs typically prune the newly formed vasculature, thus reducing microvessel density, blood flow, and perfusion. These drugs eventually increase hypoxia and cause tumor necrosis but dormancy is rarely observed. Our group recently reported that anti-VEGF therapy causes a dramatic depletion of glucose and an exhaustion of ATP levels in tumors. Moreover, we found that the central metabolic

uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors.

PubMed

Sobrevals, Luciano; Mato-Berciano, Ana; Urtasun, Nerea; Mazo, Adela; Fillat, Cristina

2014-01-01

Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133(+) population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells. © 2013.

Effects of pilocarpine hydrochloride and cevimeline on submandibular/sublingual salivation in rat xerostomia model produced by X-ray irradiation.

PubMed

Omori, Yasuhiro; Asari, Tetsuya; Maruyama, Kazuyasu; Kusama, Hiroshi; Kojima, Masami; Shibata, Nobuo

2003-01-01

The present study was performed to assess the effects of pilocarpine hydrochloride ((3S,4R)-3-ethyl-dihydro-4-[(1-methyl-1H-imidazole-5-yl)methyl]-2(3H)-furanone monohydrochloride, CAS 54-71-7) and cevimeline ((+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] hydrochloride, hemihydrate, CAS 153504-70-2), muscarinic receptor agonists, on salivary secretion from the submandibular/sublingual (SM/SL) glands in normal rats and in rats with xerostomia induced by X-ray (15 Gy) irradiation. To clarify their pharmacological safety profiles, the two drugs were further compared with regard to subtype selectivity for muscarinic receptors (M1, M2, and M3) and central nervous, respiratory, and cardiovascular effects. Pilocarpine hydrochloride (0.1-0.8 mg/kg i.d.) and cevimeline (3-30 mg/kg i.d.) dose-dependently increased salivary flow rate and total salivary volume in a 120-min period from SM/SL glands in both normal and irradiated rats, the minimum effective doses for their sialagogic effects being 0.2 and 10 mg/kg, respectively. Both drugs also increased protein output from SM/SL glands to a degree that depended on the increase in salivary volume in normal and irradiated rats. In a binding study using radiolabeled antagonists, neither pilocarpine hydrochloride nor cevimeline displayed subtype selectivity for muscarinic receptors, indicating non-selective muscarinic agonism. Effects on the central nervous system (CNS) were assessed by monitoring changes in body temperature in conscious normal rats. Pilocarpine hydrochloride (0.4-4 mg/kg p.o.) had no effect on body temperature, but cevimeline (30 and 100 mg/kg p.o.) caused a significant hypothermia. In terms of respiratory and cardiovascular effects in anesthetized normal rats, there was no clear difference in safety margin between pilocarpine hydrochloride and cevimeline, both drugs inducing significant changes in respiratory rate, heart rate, and blood pressure at doses close to those inducing sialagogic effects

[Immune system and tumors].

PubMed

Terme, Magali; Tanchot, Corinne

2017-02-01

Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

Hyperthermia treatment of spontaneously occurring oral cavity tumors using a computer-controlled Nd:YAG laser system

NASA Astrophysics Data System (ADS)

Panjehpour, Masoud; Overholt, Bergein F.; Frazier, Donita L.; Klebanow, Edward R.

1991-05-01

Conventional hyperthermia treatment of superficial tumors in the oral cavity is difficult due to inability in accessing the lesion. A new hyperthermia technique employing near infrared Nd:YAG irradiation delivered through an optical fiber is introduced for heating oral and nasal tumors in animals. This system consisted of an Nd:YAG laser, a He-Ne laser, a computer controlled optical shutter, an interstitial thermometer, computer and a printer. The tumors were heated via surface illumination of the lesion. A thermocouple implanted in the base of the tumor provided temperature feedback for laser energy regulation. Three spontaneously occurring canine (two squamous cell carcinoma on the gum, one pigmented melanoma on the hard palate) and one feline tumor (squamous cell carcinoma on the nose) have been treated with the Nd:YAG laser-induced hyperthermia delivered following radiation therapy. The tumor temperature was maintained between 43.2-43.5 degree(s)C for one hour. Nd:YAG hyperthermia allowed efficient delivery of heat to veterinary oral and nasal lesions otherwise impossible to treat with conventional heating techniques.

IMRT for Sinonasal Tumors Minimizes Severe Late Ocular Toxicity and Preserves Disease Control and Survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duprez, Frederic, E-mail: frederic.duprez@ugent.be; Madani, Indira; Morbee, Lieve

2012-05-01

Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages weremore » T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and

Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

PubMed

Easter, Stephanie L; Mitchell, Elizabeth H; Baxley, Sarah E; Desmond, Renee; Frost, Andra R; Serra, Rosa

2014-01-01

Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-catenin signaling. To this end, we characterized tumor and non-tumor mammary tissue from MMTV-Wnt1 and double transgenic MMTV-Wnt1;MMTV-Wnt5a mice. Wnt5a containing mice demonstrated fewer tumors with increased latency when compared to MMTV-Wnt1 controls. Expression of markers for basal-like tumors was down-regulated in the tumors that formed in the presence of Wnt5a indicating a phenotypic switch. Reduced canonical Wnt signaling was detected in double transgenic tumors as a decrease in active β-catenin protein and a decrease in Axin2 mRNA transcript levels. In non-tumor tissues, over-expression of Wnt5a in MMTV-Wnt1 mammary glands resulted in attenuation of phenotypes normally observed in MMTV-Wnt1 glands including hyperbranching and increased progenitor and basal cell populations. Even though Wnt5a could antagonize Wnt/β-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/β-catenin signaling was not detected in non-tumor MMTV-Wnt1;Wnt5a tissue in vivo. The data demonstrate that Wnt5a suppresses tumor formation and promotes a phenotypic shift in MMTV-Wnt1 tumors.

Reliability of Task-Based fMRI for Preoperative Planning: A Test-Retest Study in Brain Tumor Patients and Healthy Controls

PubMed Central

Morrison, Melanie A.; Churchill, Nathan W.; Cusimano, Michael D.; Schweizer, Tom A.; Das, Sunit; Graham, Simon J.

2016-01-01

Background Functional magnetic resonance imaging (fMRI) continues to develop as a clinical tool for patients with brain cancer, offering data that may directly influence surgical decisions. Unfortunately, routine integration of preoperative fMRI has been limited by concerns about reliability. Many pertinent studies have been undertaken involving healthy controls, but work involving brain tumor patients has been limited. To develop fMRI fully as a clinical tool, it will be critical to examine these reliability issues among patients with brain tumors. The present work is the first to extensively characterize differences in activation map quality between brain tumor patients and healthy controls, including the effects of tumor grade and the chosen behavioral testing paradigm on reliability outcomes. Method Test-retest data were collected for a group of low-grade (n = 6) and high-grade glioma (n = 6) patients, and for matched healthy controls (n = 12), who performed motor and language tasks during a single fMRI session. Reliability was characterized by the spatial overlap and displacement of brain activity clusters, BOLD signal stability, and the laterality index. Significance testing was performed to assess differences in reliability between the patients and controls, and low-grade and high-grade patients; as well as between different fMRI testing paradigms. Results There were few significant differences in fMRI reliability measures between patients and controls. Reliability was significantly lower when comparing high-grade tumor patients to controls, or to low-grade tumor patients. The motor task produced more reliable activation patterns than the language tasks, as did the rhyming task in comparison to the phonemic fluency task. Conclusion In low-grade glioma patients, fMRI data are as reliable as healthy control subjects. For high-grade glioma patients, further investigation is required to determine the underlying causes of reduced reliability. To maximize

Tumor Endothelial Cells

PubMed Central

Dudley, Andrew C.

2012-01-01

The vascular endothelium is a dynamic cellular “organ” that controls passage of nutrients into tissues, maintains the flow of blood, and regulates the trafficking of leukocytes. In tumors, factors such as hypoxia and chronic growth factor stimulation result in endothelial dysfunction. For example, tumor blood vessels have irregular diameters; they are fragile, leaky, and blood flow is abnormal. There is now good evidence that these abnormalities in the tumor endothelium contribute to tumor growth and metastasis. Thus, determining the biological basis underlying these abnormalities is critical for understanding the pathophysiology of tumor progression and facilitating the design and delivery of effective antiangiogenic therapies. PMID:22393533

Definitive Radiotherapy for Ewing Tumors of Extremities and Pelvis: Long-Term Disease Control, Limb Function, and Treatment Toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Indelicato, Daniel J.; Keole, Sameer R.; Shahlaee, Amir H.

2008-11-01

Purpose: More than 70% of Ewing tumors occur in the extremities and pelvis. This study identified factors influencing local control and functional outcomes after management with definitive radiotherapy (RT). Patients and Methods: A total of 75 patients with a localized Ewing tumor of the extremity or pelvis were treated with definitive RT at the University of Florida between 1970 and 2006 (lower extremity tumors in 30, pelvic tumors in 26, and upper extremity tumors in 19). RT was performed on a once-daily (40%) or twice-daily (60%) basis. The median dose was 55.2 Gy in 1.8-Gy daily fractions or 55.0 Gymore » in 1.2-Gy twice-daily fractions. The median observed follow-up was 4.7 years. Functional outcome was assessed using the Toronto Extremity Salvage Score. Results: The 10-year actuarial overall survival, cause-specific survival, freedom from relapse, and local control rate was 48%, 48%, 42%, and 71%, respectively. Of the 72 patients, 3 required salvage amputation. Inferior cause-specific survival was associated with larger tumors (81% for tumors <8 cm vs. 39% for tumors {>=}8 cm, p <0.05). No patient characteristics or treatment variables were predictive of local failure. No fractures occurred in patients treated with hyperfractionation or with tumors of the distal extremities. Severe late complications were more frequently associated with use of <8-MV photons and fields encompassing the entire bone or hemipelvis. A significantly better Toronto Extremity Salvage Score was associated with a late-effect biologically effective dose of <91.7 Gy{sub 3}. Conclusions: Limb preservation was effectively achieved through definitive RT. Treating limited field sizes with hyperfractionated high-energy RT could minimize long-term complications and provides superior functional outcomes.« less

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins

PubMed Central

Arvola, René M.

2017-01-01

ABSTRACT Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control. PMID:28318367

Combinatorial control of messenger RNAs by Pumilio, Nanos and Brain Tumor Proteins.

PubMed

Arvola, René M; Weidmann, Chase A; Tanaka Hall, Traci M; Goldstrohm, Aaron C

2017-11-02

Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of 3 Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurologic processes. Here we synthesize 30 y of research with new insights into their molecular functions and mechanisms of action. First, we provide an overview of the key properties of each RBP. Next, we present a detailed analysis of their collaborative regulatory mechanism using a classic example of the developmental morphogen, hunchback, which is spatially and temporally regulated by the trio during embryogenesis. New biochemical, structural and functional analyses provide insights into RNA recognition, cooperativity, and regulatory mechanisms. We integrate these data into a model of combinatorial RNA binding and regulation of translation and mRNA decay. We then use this information, transcriptome wide analyses and bioinformatics predictions to assess the global impact of Pumilio, Nanos and Brain Tumor on gene regulation. Together, the results support pervasive, dynamic post-transcriptional control.

A comprehensive quality control workflow for paired tumor-normal NGS experiments.

PubMed

Schroeder, Christopher M; Hilke, Franz J; Löffler, Markus W; Bitzer, Michael; Lenz, Florian; Sturm, Marc

2017-06-01

Quality control (QC) is an important part of all NGS data analysis stages. Many available tools calculate QC metrics from different analysis steps of single sample experiments (raw reads, mapped reads and variant lists). Multi-sample experiments, as sequencing of tumor-normal pairs, require additional QC metrics to ensure validity of results. These multi-sample QC metrics still lack standardization. We therefore suggest a new workflow for QC of DNA sequencing of tumor-normal pairs. With this workflow well-known single-sample QC metrics and additional metrics specific for tumor-normal pairs can be calculated. The segmentation into different tools offers a high flexibility and allows reuse for other purposes. All tools produce qcML, a generic XML format for QC of -omics experiments. qcML uses quality metrics defined in an ontology, which was adapted for NGS. All QC tools are implemented in C ++ and run both under Linux and Windows. Plotting requires python 2.7 and matplotlib. The software is available under the 'GNU General Public License version 2' as part of the ngs-bits project: https://github.com/imgag/ngs-bits. christopher.schroeder@med.uni-tuebingen.de. Supplementary data are available at Bioinformatics online. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

The effects of swallowing disorders, dysgeusia, oral mucositis and xerostomia on nutritional status, oral intake and weight loss in head and neck cancer patients: A systematic review.

PubMed

Bressan, Valentina; Stevanin, Simone; Bianchi, Monica; Aleo, Giuseppe; Bagnasco, Annamaria; Sasso, Loredana

2016-04-01

Combined-modality treatment of head and neck cancer is becoming more common, driven by the idea that organ(s) preservation should maintain patient appearance and the function of organ(s) involved. Even if treatments have improved, they can still be associated with acute and late adverse effects. The aim of this systematic review was to retrieve current data on how swallowing disorders, dysgeusia, oral mucositis, and xerostomia affect nutritional status, oral intake and weight loss in head and neck cancer (HNC) patients. A systematic literature search covered four relevant electronic databases from January 2005 to May 2015. Retrieved papers were categorised and evaluated considering their methodological quality. Two independent reviewers reviewed manuscripts and abstracted data using a standardised form. Quality assessment of the included studies was performed using the Edwards Method Score. Of the 1459 abstracts reviewed, a total of 25 studies were included. The most studied symptom was dysphagia, even if symptoms were interconnected and affected one other. In most of the selected studies the level of evidence was between 2 and 3, and their quality level was from medium to low. There are limited data about dysgeusia, oral mucositis and xerostomia outcomes available for HNC patients. There is a lack of well-designed clinical trials and multicenter-prospective cohort studies, therefore further research is needed to ascertain which aspects of these symptoms should be measured. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solid tumors.

PubMed

Richardson, R C

1985-05-01

Soft-tissue tumors are similar in their behavior. Benign tumors can be easily resected in most cases, whereas malignant tumors are relentless in their locally invasive characteristics. A clear understanding of the constraints of the pathologist in reaching a confirmed diagnosis and a logical plan utilizing surgery as the major modality of therapy are necessary for successful management of these tumors. It appears that radiation combined with hyperthermia is beginning to play a significant role in the local control of soft-tissue sarcomas and that single or multi-agent chemotherapy may be of benefit in treatment of nonresectable or metastatic soft-tissue sarcomas. For the immediate future, surgery remains the only nonexperimental modality of therapy, but the rapid advances in the other therapy methods are encouraging.

Disease Control and Ototoxicity Using Intensity-Modulated Radiation Therapy Tumor-Bed Boost for Medulloblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polkinghorn, William R.; Dunkel, Ira J.; Souweidane, Mark M.

2011-11-01

Purpose: We previously reported excellent local control for treating medulloblastoma with a limited boost to the tumor bed. In order to decrease ototoxicity, we subsequently implemented a tumor-bed boost using intensity-modulated radiation therapy (IMRT), the clinical results of which we report here. Patients and Methods: A total of 33 patients with newly diagnosed medulloblastoma, 25 with standard risk, and 8 with high risk, were treated on an IMRT tumor-bed boost following craniospinal irradiation (CSI). Six standard-risk patients were treated with an institutional protocol with 18 Gy CSI in conjunction with intrathecal iodine-131-labeled monoclonal antibody. The majority of patients received concurrentmore » vincristine and standard adjuvant chemotherapy. Pure-tone audiograms were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. Results: Median age was 9 years old (range, 4-46 years old). Median follow-up was 63 months. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) rates for standard-risk patients who received 23.4 or 36 Gy CSI (not including those who received 18 Gy CSI with radioimmunotherapy) were 81.4% and 88.4%, respectively, at 5 years; 5-year PFS and OS rates for high-risk patients were both 87.5%. There were no isolated posterior fossa failures outside of the boost volume. Posttreatment audiograms were available for 31 patients, of whom 6%, at a median follow-up of 19 months, had developed Grade 3 hearing loss. Conclusion: An IMRT tumor-bed boost results in excellent local control while delivering a low mean dose to the cochlea, resulting in a low rate of ototoxicity.« less

Inter-Regional, Epidemiological Study of Childhood Cancer (IRESCC): case-control study in children with germ cell tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnston, H.E.; Mann, J.R.; Williams, J.

In 1980-1983 members of IRESCC interviewed parents of 555 children with newly diagnosed cancer on topics of possible etiological significance. Identical questions were asked of the parents of 1100 control children chosen from hospital admissions and general practitioner lists. Medical information was confirmed whenever possible by cross-checking with NHS records. Data for the 41 children with germ cell tumors and their 82 controls are reported here. The cases had more major congenital malformations than controls, including one neural tube defect. More case than control mothers and fathers reported occupational exposure to chemicals. Nine close relatives of cases had multiple primarymore » tumors, which were often benign or of low-grade malignancy, compared with 1 hospital control and 3 general practitioner control relatives. Cases and controls differed with respect to birth weight and paternal age. No case-control differences were shown for: birth rank, maternal age, chronic illnesses and smoking, mothers reproductive histories and oral contraceptive usage. In index pregnancies there were no case-control differences for maternal illness, infections, alcohol intake and X-ray and ultrasound exposure. There was no difference between cases and controls for the frequency of twinning the families.« less

Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model.

PubMed

Jablonska, Jadwiga; Leschner, Sara; Westphal, Kathrin; Lienenklaus, Stefan; Weiss, Siegfried

2010-04-01

Angiogenesis is a hallmark of malignant neoplasias, as the formation of new blood vessels is required for tumors to acquire oxygen and nutrients essential for their continued growth and metastasis. However, the signaling pathways leading to tumor vascularization are not fully understood. Here, using a transplantable mouse tumor model, we have demonstrated that endogenous IFN-beta inhibits tumor angiogenesis through repression of genes encoding proangiogenic and homing factors in tumor-infiltrating neutrophils. We determined that IFN-beta-deficient mice injected with B16F10 melanoma or MCA205 fibrosarcoma cells developed faster-growing tumors with better-developed blood vessels than did syngeneic control mice. These tumors displayed enhanced infiltration by CD11b+Gr1+ neutrophils expressing elevated levels of the genes encoding the proangiogenic factors VEGF and MMP9 and the homing receptor CXCR4. They also expressed higher levels of the transcription factors c-myc and STAT3, known regulators of VEGF, MMP9, and CXCR4. In vitro, treatment of these tumor-infiltrating neutrophils with low levels of IFN-beta restored expression of proangiogenic factors to control levels. Moreover, depletion of these neutrophils inhibited tumor growth in both control and IFN-beta-deficient mice. We therefore suggest that constitutively produced endogenous IFN-beta is an important mediator of innate tumor surveillance. Further, we believe our data help to explain the therapeutic effect of IFN treatment during the early stages of cancer development.

Integration of Oncogenes via Sleeping Beauty as a Mouse Model of HPV16+ Oral Tumors and Immunologic Control.

PubMed

Lin, Yi-Hsin; Yang, Ming-Chieh; Tseng, Ssu-Hsueh; Jiang, Rosie; Yang, Andrew; Farmer, Emily; Peng, Shiwen; Henkle, Talia; Chang, Yung-Nien; Hung, Chien-Fu; Wu, T-C

2018-01-23

Human papillomavirus type 16 (HPV16) is the etiologic factor for cervical cancer and a subset of oropharyngeal cancers. Although several prophylactic HPV vaccines are available, no effective therapeutic strategies to control active HPV diseases exist. Tumor implantation models are traditionally used to study HPV-associated buccal tumors. However, they fail to address precancerous phases of disease progression and display tumor microenvironments distinct from those observed in patients. Previously, K14-E6/E7 transgenic mouse models have been used to generate spontaneous tumors. However, the rate of tumor formation is inconsistent, and the host often develops immune tolerance to the viral oncoproteins. We developed a preclinical, spontaneous, HPV16 + buccal tumor model using submucosal injection of oncogenic plasmids expressing HPV16-E6/E7, NRas G12V , luciferase, and sleeping beauty (SB) transposase, followed by electroporation in the buccal mucosa. We evaluated responses to immunization with a pNGVL4a-CRT/E7(detox) therapeutic HPV DNA vaccine and tumor cell migration to distant locations. Mice transfected with plasmids encoding HPV16-E6/E7, NRas G12V , luciferase, and SB transposase developed tumors within 3 weeks. We also found transient anti-CD3 administration is required to generate tumors in immunocompetent mice. Bioluminescence signals from luciferase correlated strongly with tumor growth, and tumors expressed HPV16-associated markers. We showed that pNGVL4a-CRT/E7(detox) administration resulted in antitumor immunity in tumor-bearing mice. Lastly, we demonstrated that the generated tumor could migrate to tumor-draining lymph nodes. Our model provides an efficient method to induce spontaneous HPV + tumor formation, which can be used to identify effective therapeutic interventions, analyze tumor migration, and conduct tumor biology research. Cancer Immunol Res; 6(3); 1-15. ©2018 AACR. ©2018 American Association for Cancer Research.

Lecithin-based emulsions for potential use as saliva substitutes in patients with xerostomia--viscoelastic properties.

PubMed

Hanning, Sara M; Yu, Tao; Jones, David S; Andrews, Gavin P; Kieser, Jules A; Medlicott, Natalie J

2013-11-18

The purpose of the present study was to investigate lecithin-rice bran oil rheological properties with the view to consider these as potential saliva substitutes in patients with severe xerostomia and salivary hypofunction. Pseudo-ternary phase diagrams of rice bran oil, lecithin and water mixtures were constructed and characterised using polarising light microscopy. Viscoelastic properties, which we hypothesise are important determinants in product performance, were analysed using both flow and oscillatory rheology. Rheological properties were influenced by composition, frequency and shear stress. Frequency-dependent viscoelasticity was observed in some formulations where viscosity dominated (tanδ>1) at frequencies under 5 Hz and elasticity dominated (tanδ<1) at higher frequencies. Threshold frequencies were determined for each formulation, where a peak in loss tangent was observed, coinciding with a reduction in the storage modulus and increase in loss modulus. The frequency-dependent behaviour of emulsions are of interest because these combinations exhibit viscous behaviour at low frequencies, which may improve lubrication of the oral cavity at rest, whereas increased elasticity at higher frequencies may improve retention during higher-shear tasks such as swallowing and speaking. Copyright © 2013 Elsevier B.V. All rights reserved.

The effect of CT26 tumor-derived TGF-β on the balance of tumor growth and immunity.

PubMed

Owyang, Stephanie Y; Zhang, Min; Walkup, Grace A; Chen, Grace E; Grasberger, Helmut; El-Zaatari, Mohamad; Kao, John Y

2017-11-01

TGF-β is an important target for many cancer therapies under development. In addition to suppressing anti-tumor immunity, it has pleiotropic direct pro- and anti- tumor effects. The actions of increased endogenous TGF-β production remain unclear, and may affect the outcomes of anti-TGF-β cancer therapy. We hypothesize that tumor-derived TGF-β (td-TGF-β) plays an important role in maintaining tumor remission by controlling tumor proliferation in vivo, and that decreasing td-TGF-β in the tumor microenvironment will result in tumor progression. The aim of this study was to examine the effect of TGF-β in the tumor microenvironment on the balance between its anti-proliferative and immunosuppressive effects. A murine BALB/c spontaneous colon adenocarcinoma cell line (CT26) was genetically engineered to produce increased active TGF-β (CT26-TGF-β), a dominant-negative soluble TGF-β receptor (CT26-TGF-β-R), or the empty neomycin cassette as control (CT26-neo). In vitro proliferation rates were measured. For in vivo studies, the three cell lines were injected into syngeneic BALB/c mice, and tumor growth was measured over time. Immunodeficient BALB/c nude mice were used to investigate the role of T and B cells. In vitro, CT26-TGF-β-R and CT26-TGF-β cells showed increased and suppressed proliferation, respectively, compared to control (CT26-neo), confirming TGF-β has direct anti-tumor effects. In vivo, we found that CT26-TGF-β-R cells displayed slower growth compared to control, likely secondary to reduced suppression of anti-tumor immunity, as this effect was ablated in immunodeficient BALB/c nude mice. However, CT26-TGF-β cells (excess TGF-β) exhibited rapid early growth compared to control, but later failed to progress. The same pattern was shown in immunodeficient BALB/c nude mice, suggesting the effect on tumor growth is direct, with minimal immune system involvement. There was minimal effect on systemic antitumor immunity as determined by peripheral

Captopril improves tumor nanomedicine delivery by increasing tumor blood perfusion and enlarging endothelial gaps in tumor blood vessels.

PubMed

Zhang, Bo; Jiang, Ting; Tuo, Yanyan; Jin, Kai; Luo, Zimiao; Shi, Wei; Mei, Heng; Hu, Yu; Pang, Zhiqing; Jiang, Xinguo

2017-12-01

Poor tumor perfusion and unfavorable vessel permeability compromise nanomedicine drug delivery to tumors. Captopril dilates blood vessels, reducing blood pressure clinically and bradykinin, as the downstream signaling moiety of captopril, is capable of dilating blood vessels and effectively increasing vessel permeability. The hypothesis behind this study was that captopril can dilate tumor blood vessels, improving tumor perfusion and simultaneously enlarge the endothelial gaps of tumor vessels, therefore enhancing nanomedicine drug delivery for tumor therapy. Using the U87 tumor xenograft with abundant blood vessels as the tumor model, tumor perfusion experiments were carried out using laser Doppler imaging and lectin-labeling experiments. A single treatment of captopril at a dose of 100 mg/kg significantly increased the percentage of functional vessels in tumor tissues and improved tumor blood perfusion. Scanning electron microscopy of tumor vessels also indicated that the endothelial gaps of tumor vessels were enlarged after captopril treatment. Immunofluorescence-staining of tumor slices demonstrated that captopril significantly increased bradykinin expression, possibly explaining tumor perfusion improvements and endothelial gap enlargement. Additionally, imaging in vivo, imaging ex vivo and nanoparticle distribution in tumor slices indicated that after a single treatment with captopril, the accumulation of 115-nm nanoparticles in tumors had increased 2.81-fold with a more homogeneous distribution pattern in comparison to non-captopril treated controls. Finally, pharmacodynamics experiments demonstrated that captopril combined with paclitaxel-loaded nanoparticles resulted in the greatest tumor shrinkage and the most extensive necrosis in tumor tissues among all treatment groups. Taken together, the data from the present study suggest a novel strategy for improving tumor perfusion and enlarging blood vessel permeability simultaneously in order to improve

Decoy receptor 3 enhances tumor progression via induction of tumor-associated macrophages.

PubMed

Tai, Shyh-Kuan; Chang, Hsin-Chuan; Lan, Keng-Li; Lee, Chun-Ting; Yang, Chih-Ya; Chen, Nien-Jung; Chou, Teh-Ying; Tarng, Der-Cherng; Hsieh, Shie-Liang

2012-03-01

Tumor-associated macrophages (TAMs) are the major component of tumor-infiltrating leukocytes. TAMs are heterogeneous, with distinct phenotypes influenced by the microenvironment surrounding tumor tissues. Decoy receptor 3 (DcR3), a member of the TNFR superfamily, is overexpressed in tumor cells and is capable of modulating host immunity as either a neutralizing decoy receptor or an effector molecule. Upregulation of DcR3 has been observed to correlate with a poor prognosis in various cancers. However, the mechanisms underlying the DcR3-mediated tumor-promoting effect remain unclear. We previously demonstrated that DcR3 modulates macrophage activation toward an M2-like phenotype in vitro and that DcR3 downregulates MHC class II expression in TAMs via epigenetic control. To investigate whether DcR3 promotes tumor growth, CT26-DcR3 stable transfectants were established. Compared with the vector control clone, DcR3-transfectants grew faster and resulted in TAM infiltration. We further generated CD68 promoter-driven DcR3 transgenic (Tg) mice to investigate tumor growth in vivo. Compared with wild-type mice, macrophages isolated from DcR3-Tg mice displayed higher levels of IL-10, IL-1ra, Ym1, and arginase activity, whereas the expression of IL-12, TNF-α, IL-6, NO, and MHC class II was downregulated. Significantly enhanced tumor growth and spreading were observed in DcR3-Tg mice, and the enhanced tumor growth was abolished by arginase inhibitor N-ω-hydroxy-l-norarginine and histone deacetylase inhibitor sodium valproate. These results indicated that induction of TAMs is an important mechanism for DcR3-mediated tumor progression. Our findings also suggest that targeting DcR3 might help in the development of novel treatment strategies for tumors with high DcR3 expression.

Predictors of poor sleep quality among head and neck cancer patients.

PubMed

Shuman, Andrew G; Duffy, Sonia A; Ronis, David L; Garetz, Susan L; McLean, Scott A; Fowler, Karen E; Terrell, Jeffrey E

2010-06-01

The objective of this study was to determine the predictors of sleep quality among head and neck cancer patients 1 year after diagnosis. This was a prospective, multisite cohort study of head and neck cancer patients (N = 457). Patients were surveyed at baseline and 1 year after diagnosis. Chart audits were also conducted. The dependent variable was a self-assessed sleep score 1 year after diagnosis. The independent variables were a 1 year pain score, xerostomia, treatment received (radiation, chemotherapy, and/or surgery), presence of a feeding tube and/or tracheotomy, tumor site and stage, comorbidities, depression, smoking, problem drinking, age, and sex. Both baseline (67.1) and 1-year postdiagnosis (69.3) sleep scores were slightly lower than population means (72). Multivariate analyses showed that pain, xerostomia, depression, presence of a tracheotomy tube, comorbidities, and younger age were statistically significant predictors of poor sleep 1 year after diagnosis of head and neck cancer (P < .05). Smoking, problem drinking, and female sex were marginally significant (P < .09). Type of treatment (surgery, radiation and/or chemotherapy), primary tumor site, and cancer stage were not significantly associated with 1-year sleep scores. Many factors adversely affecting sleep in head and neck cancer patients are potentially modifiable and appear to contribute to decreased quality of life. Strategies to reduce pain, xerostomia, depression, smoking, and problem drinking may be warranted, not only for their own inherent value, but also for improvement of sleep and the enhancement of quality of life.

Singlet oxygen explicit dosimetry to predict local tumor control for HPPH-mediated photodynamic therapy

NASA Astrophysics Data System (ADS)

Penjweini, Rozhin; Kim, Michele M.; Ong, Yi Hong; Zhu, Timothy C.

2017-02-01

This preclinical study examines four dosimetric quantities (light fluence, photosensitizer photobleaching ratio, PDT dose, and reacted singlet oxygen ([1O2]rx)) to predict local control rate (LCR) for 2-(1-Hexyloxyethyl)-2-devinyl pyropheophorbide (HPPH)-mediated photodynamic therapy (PDT). Mice bearing radiation-induced fibrosarcoma (RIF) tumors were treated with different in-air fluences (135, 250 and 350 J/cm2) and in-air fluence rates (50, 75 and 150 mW/cm2) at 0.25 mg/kg HPPH and a drug-light interval of 24 hours using a 1 cm diameter collimated laser beam at 665 nm wavelength. A macroscopic model was used to calculate ([1O2]rx)) based on in vivo explicit dosimetry of the initial tissue oxygenation, photosensitizer concentration, and tissue optical properties. PDT dose was defined as a temporal integral of drug concentration and fluence rate (φ) at a 3 mm tumor depth. Light fluence rate was calculated throughout the treatment volume based on Monte-Carlo simulation and measured tissue optical properties. The tumor volume of each mouse was tracked for 30 days after PDT and Kaplan-Meier analyses for LCR were performed based on a tumor volume <=100 mm3, for four dose metrics: fluence, HPPH photobleaching rate, PDT dose, and ([1O2]rx)). The results of this study showed that ([1O2]rx)) is the best dosimetric quantity that can predict tumor response and correlate with LCR.

Mitochondrial control by DRP1 in brain tumor initiating cells.

PubMed

Xie, Qi; Wu, Qiulian; Horbinski, Craig M; Flavahan, William A; Yang, Kailin; Zhou, Wenchao; Dombrowski, Stephen M; Huang, Zhi; Fang, Xiaoguang; Shi, Yu; Ferguson, Ashley N; Kashatus, David F; Bao, Shideng; Rich, Jeremy N

2015-04-01

Brain tumor initiating cells (BTICs) co-opt the neuronal high affinity glucose transporter, GLUT3, to withstand metabolic stress. We investigated another mechanism critical to brain metabolism, mitochondrial morphology, in BTICs. BTIC mitochondria were fragmented relative to non-BTIC tumor cell mitochondria, suggesting that BTICs increase mitochondrial fission. The essential mediator of mitochondrial fission, dynamin-related protein 1 (DRP1), showed activating phosphorylation in BTICs and inhibitory phosphorylation in non-BTIC tumor cells. Targeting DRP1 using RNA interference or pharmacologic inhibition induced BTIC apoptosis and inhibited tumor growth. Downstream, DRP1 activity regulated the essential metabolic stress sensor, AMP-activated protein kinase (AMPK), and targeting AMPK rescued the effects of DRP1 disruption. Cyclin-dependent kinase 5 (CDK5) phosphorylated DRP1 to increase its activity in BTICs, whereas Ca(2+)-calmodulin-dependent protein kinase 2 (CAMK2) inhibited DRP1 in non-BTIC tumor cells, suggesting that tumor cell differentiation induces a regulatory switch in mitochondrial morphology. DRP1 activation correlated with poor prognosis in glioblastoma, suggesting that mitochondrial dynamics may represent a therapeutic target for BTICs.

Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice.

PubMed

Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; Macdougall, Mary; Abboud-Werner, Sherry

2012-06-01

Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita ⁻/⁻ mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita ⁻/⁻ and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita ⁻/⁻ mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita ⁻/⁻ teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

Hyperglycemia and xerostomia are key determinants of tooth decay in type 1 diabetic mice

PubMed Central

Yeh, Chih-Ko; Harris, Stephen E; Mohan, Sumathy; Horn, Diane; Fajardo, Roberto; Chun, Yong-Hee Patricia; Jorgensen, James; MacDougall, Mary; Abboud-Werner, Sherry

2012-01-01

Insulin-dependent type 1 diabetes mellitus (DM) and oral diseases are closely interrelated. Poor metabolic control in diabetics is associated with a high risk of gingivitis, periodontitis and tooth loss. Salivary flow declines in diabetics and patients suffer from xerostomia. Reduced saliva predisposes to enamel hypomineralization and caries formation; however, the mechanisms that initiate and lead to progression of tooth decay and periodontitis in type 1 DM have not been explored. To address this issue, we analyzed tooth morphology in Akita −/− mice that harbor a point mutation in the Ins2 insulin gene, which leads to progressive hyperglycemia. Mandibles from Akita −/− and wild-type littermates were analyzed by microCT, scanning EM and histology; teeth were examined for amelogenin (Amel) and ameloblastin (Ambn) expression. Mice were injected with pilocarpine to assess saliva production. As hyperglycemia may alter pulp repair, the effect of high glucose levels on the proliferation/differentiation of cultured MD10-F2 pulp cells was also analyzed. Results showed that Akita −/− mice at 6 weeks of age showed chalky white incisors that correlated with marked hyperglycemia and impaired saliva production. MicroCT of Akita −/− teeth revealed excessive enamel wearing and hypomineralization; immunostaining for Amel and Ambn was decreased. A striking feature was invasion of dentinal tubules with Streptococcus mitis and microabcesses that originated in the coronal pulp and progressed to pulp necrosis and periapical periodontitis. High levels of glucose also inhibited MD10-F2 cell proliferation and differentiation. Our findings provide the first evidence that hyperglycemia in combination with reduced saliva in a model of type1 DM leads to decreased enamel mineralization/matrix proteins and predisposes to excessive wearing and decay. Importantly, hyperglycemia adversely affects enamel matrix proteins and pulp repair. Early detection and treatment of hyperglycemia

Radiofrequency ablation of liver tumors in combination with local OK-432 injection prolongs survival and suppresses distant tumor growth in the rabbit model with intra- and extrahepatic VX2 tumors.

PubMed

Kageyama, Ken; Yamamoto, Akira; Okuma, Tomohisa; Hamamoto, Shinichi; Takeshita, Toru; Sakai, Yukimasa; Nishida, Norifumi; Matsuoka, Toshiyuki; Miki, Yukio

2013-10-01

To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

Efficacy of Traditional Chinese Medicine in Treatment and Prophylaxis of Radiation-Induced Oral Mucositis in Patients Receiving Radiotherapy: A Randomized Controlled Trial.

PubMed

Wang, Cong; Wang, Peiguo; Ouyang, Huaqiang; Wang, Jing; Sun, Lining; Li, Yanwei; Liu, Dongying; Jiang, Zhansheng; Wang, Bin; Pan, Zhanyu

2018-06-01

To estimate the efficacy of traditional Chinese medicine (Chining decoction, CHIN) for radiation-induced oral mucositis in patients with head and neck cancer. From May 2014 to December 2015, 70 consecutive patients were randomly assigned to receive CHIN (treatment group) or recombinant human epidermal growth factor (rhEGF) spray (control group) at a 1:1 ratio. CHIN was administered to treatment group from the first day of radiotherapy until the completion of radiotherapy. Simultaneously, the rhEGF spray was administered to control group on the oral mucosa of irradiated area. The clinical benefit was determined by gradation of mucositis (Common Terminology Criteria for Adverse Events v4.0), oral pain, and xerostomia (visual analysis scale) for each week during radiotherapy. Body mass index was evaluated before and after radiotherapy. Patients in the treatment group had prominent remission of oral pain and grade of mucositis on each observing point compared with those in control group ( P < .01). Xerostomia was decreased notably in treatment group compared with control group ( P < .01). Body mass index in the treatment group exhibited advantage over control group after radiotherapy, but there was no statistical significance (19.8 ± 3.26 vs 18.8 ± 2.5 kg/m 2 , P = .153, >.05). CHIN presented an obvious advantage in preventing radiation-induced oral mucositis compared with rhEGF spray.

Radiographic Local Tumor Control and Pain Palliation of Sarcoma Metastases within the Musculoskeletal System with Percutaneous Thermal Ablation.

PubMed

Vaswani, Devin; Wallace, Adam N; Eiswirth, Preston S; Madaelil, Thomas P; Chang, Randy O; Tomasian, Anderanik; Jennings, Jack W

2018-03-14

To evaluate the effectiveness of percutaneous image-guided thermal ablation in achieving local tumor control and pain palliation of sarcoma metastases within the musculoskeletal system. Retrospective review of 64 sarcoma metastases within the musculoskeletal system in 26 women and 15 men (total = 41) treated with ablation between December 2011 and August 2016 was performed. Mean age of the cohort was 42.9 years ± 16.0 years. Two subgroups were treated: oligometastatic disease (n = 13) and widely metastatic disease (n = 51). A variety of sarcoma histologies were treated with average tumor volume of 42.5 cm 3 (range 0.1-484.7 cm 3 ). Pain scores were recorded before and 4 weeks after therapy for 59% (38/64) of treated lesions. Follow-up imaging was evaluated for local control and to monitor sites of untreated disease as an internal control. Fifty-eight percent (37/64) were lost to imaging follow-up at varying time points over a year. Complication rate was 5% (3/64; one minor and two major events). One-year local tumor control rates were 70% (19/27) in all patients, 67% (12/18) in the setting of progression of untreated metastases, and 100% (10/10) in the setting of oligometastatic disease. Median pain scores decreased from 8 (interquartile range 5.0-9.0) to 3 (interquartile range 0.1-4.0) 1 month after the procedure (P < 0.001). Image-guided percutaneous ablation is an effective option for local tumor control and pain palliation of metastatic sarcomas within the musculoskeletal system. Treatment in the setting of oligometastatic disease offers potential for remission. Level 4, Retrospective Review.

Maximizing Tumor Immunity With Fractionated Radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu; Ratikan, Josephine A.; Iwamoto, Keisuke S.

Purpose: Technologic advances have led to increased clinical use of higher-sized fractions of radiation dose and higher total doses. How these modify the pathways involved in tumor cell death, normal tissue response, and signaling to the immune system has been inadequately explored. Here we ask how radiation dose and fraction size affect antitumor immunity, the suppression thereof, and how this might relate to tumor control. Methods and Materials: Mice bearing B16-OVA murine melanoma were treated with up to 15 Gy radiation given in various-size fractions, and tumor growth followed. The tumor-specific immune response in the spleen was assessed by interferon-{gamma}more » enzyme-linked immunospot (ELISPOT) assay with ovalbumin (OVA) as the surrogate tumor antigen and the contribution of regulatory T cells (Tregs) determined by the proportion of CD4{sup +}CD25{sup hi}Foxp3{sup +} T cells. Results: After single doses, tumor control increased with the size of radiation dose, as did the number of tumor-reactive T cells. This was offset at the highest dose by an increase in Treg representation. Fractionated treatment with medium-size radiation doses of 7.5 Gy/fraction gave the best tumor control and tumor immunity while maintaining low Treg numbers. Conclusions: Radiation can be an immune adjuvant, but the response varies with the size of dose per fraction. The ultimate challenge is to optimally integrate cancer immunotherapy into radiation therapy.« less

Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kageyama, Ken, E-mail: kageyamaken0112@gmail.com; Yamamoto, Akira, E-mail: loveakirayamamoto@gmail.com; Okuma, Tomohisa, E-mail: o-kuma@msic.med.osaka-cu.ac.jp

Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at amore » single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.« less

Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma

PubMed Central

Sekar, Divya; Govene, Luisa; del Río, María-Luisa; Sirait-Fischer, Evelyn; Fink, Annika F.

2018-01-01

Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity. PMID:29518903

Downregulation of BTLA on NKT Cells Promotes Tumor Immune Control in a Mouse Model of Mammary Carcinoma.

PubMed

Sekar, Divya; Govene, Luisa; Del Río, María-Luisa; Sirait-Fischer, Evelyn; Fink, Annika F; Brüne, Bernhard; Rodriguez-Barbosa, José I; Weigert, Andreas

2018-03-07

Natural Killer T cells (NKT cells) are emerging as critical regulators of pro- and anti-tumor immunity, both at baseline and in therapeutic settings. While type I NKT cells can promote anti-tumor immunity, their activity in the tumor microenvironment may be limited by negative regulators such as inhibitory immune checkpoints. We observed dominant expression of B- and T-lymphocyte attenuator (BTLA) on type I NKT cells in polyoma middle T oncogene-driven (PyMT) murine autochthonous mammary tumors. Other immune checkpoint receptors, such as programmed cell death 1 (PD-1) were equally distributed among T cell populations. Interference with BTLA using neutralizing antibodies limited tumor growth and pulmonary metastasis in the PyMT model in a therapeutic setting, correlating with an increase in type I NKT cells and expression of cytotoxic marker genes. While therapeutic application of an anti-PD-1 antibody increased the number of CD8+ cytotoxic T cells and elevated IL-12 expression, tumor control was not established. Expression of ZBTB16, the lineage-determining transcription factor of type I NKT cells, was correlated with a favorable patient prognosis in the METABRIC dataset, and BTLA levels were instrumental to further distinguish prognosis in patents with high ZBTB16 expression. Taken together, these data support a role of BTLA on type I NKT cells in limiting anti-tumor immunity.

Efficacy of phosphorus-32 brachytherapy without external-beam radiation for long-term tumor control in patients with craniopharyngioma.

PubMed

Ansari, Shaheryar F; Moore, Reilin J; Boaz, Joel C; Fulkerson, Daniel H

2016-04-01

OBJECT Radioactive phosphorus-32 (P32) has been used as brachytherapy for craniopharyngiomas with the hope of providing local control of enlarging tumor cysts. Brachytherapy has commonly been used as an adjunct to the standard treatment of surgery and external-beam radiation (EBR). Historically, multimodal treatment, including EBR, has shown tumor control rates as high as 70% at 10 years after treatment. However, EBR is associated with significant long-term risks, including visual deficits, endocrine dysfunction, and cognitive decline. Theoretically, brachytherapy may provide focused local radiation that controls or shrinks a symptomatic cyst without exposing the patient to the risks of EBR. For this study, the authors reviewed their experiences with craniopharyngioma patients treated with P32 brachytherapy as the primary treatment without EBR. The authors reviewed these patients' records to evaluate whether this strategy effectively controls tumor growth, thus avoiding the need for further surgery or EBR. METHODS The authors performed a retrospective review of pediatric patients treated for craniopharyngioma between 1997 and 2004. This was the time period during which the authors' institution had a relatively high use of P32 for treatment of cystic craniopharyngioma. All patients who had surgery and injection of P32 without EBR were identified. The patient records were analyzed for complications, cyst control, need for further surgery, and need for future EBR. RESULTS Thirty-eight patients were treated for craniopharyngioma during the study period. Nine patients (23.7%) were identified who had surgery (resection or biopsy) with P32 brachytherapy but without initial EBR. These 9 patients represented the study group. For 1 patient (11.1%), there was a complication with the brachytherapy procedure. Five patients (55.5%) required subsequent surgery. Seven patients (77.7%) required subsequent EBR for tumor growth. The mean time between the injection of P32 and

Transoral robotic surgery for parapharyngeal space tumors.

PubMed

O'Malley, Bert W; Quon, Harry; Leonhardt, Fernando D; Chalian, Ara A; Weinstein, Gregory S

2010-01-01

To evaluate the outcomes of patients with parapharyngeal space (PPS) tumors treated with a transoral robotic surgery (TORS) approach. We prospectively enrolled well-defined benign PPS tumors accessible from the oropharynx with no carotid encasement or bone erosion. We designated outcome measures that included technical feasibility of the approach, local tumor control and complication rates. Descriptive statistics were used to summarize the outcome data. With a mean follow-up of 29.9 months (range 12-40 months), a total of 10 patients have been enrolled. TORS was completed in 9 of 10 patients with acceptable operative time and blood loss and no significant complications including hemorrhage, infection, trismus or tumor spillage. Local control has been 100% for 7 patients with pleomorphic adenomas. We confirm the safety and feasibility of the TORS approach for PPS tumors that achieves a high local control and low surgical complication rate. TORS is a viable approach for removing benign tumors and lesions of the PPS. Copyright © 2010 S. Karger AG, Basel.

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

PubMed

Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

2016-10-27

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with

Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schoenfeld, Jonathan D., E-mail: jdschoenfeld@partners.org; Sher, David J.; Norris, Charles M.

Purpose: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. Patients and Methods: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. Results: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinomamore » in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Conclusions

Early Oral Tongue Squamous Cell Carcinoma: Sampling of Margins From Tumor Bed and Worse Local Control.

PubMed

Maxwell, Jessica H; Thompson, Lester D R; Brandwein-Gensler, Margaret S; Weiss, Bernhard G; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V; Lai, Chi; Shuai, Yongli; Carroll, William R; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T; Ferris, Robert L; Seethala, Raja; Chiosea, Simion I

2015-12-01

% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen-based margin assessment is recommended.

Association of metabolic syndromes and risk factors with ampullary tumors development: a case-control study in China.

PubMed

He, Xiao-Dong; Wu, Qiao; Liu, Wei; Hong, Tao; Li, Jing-Jing; Miao, Ruo-Yu; Zhao, Hai-Tao

2014-07-28

To evaluate the risk factors for ampullary adenoma and ampullary cancer. This case-control study included ampullary tumor patients referred to Peking Union Medical College Hospital. Controls were randomly selected from an existing database of healthy individuals at the Health Screening Center of the same hospital. Data on metabolic syndromes, medical conditions, and family history were collected by retrospective review of the patients' records and health examination reports, or by interview. A total of 181 patients and 905 age- and sex-matched controls were enrolled. We found that a history of diabetes, cholecystolithiasis, low-density lipoprotein, and apolipoprotein A were significantly related to ampullary adenomas. Diabetes, cholecystolithiasis, chronic pancreatitis, total cholesterol, high-density lipoprotein, and apolipoprotein A were also significantly related to ampullary cancer. Some metabolic syndrome components and medical conditions are potential risk factors for the development of ampullary tumors. Cholelithiasis, diabetes, and apolipoprotein A may contribute to the malignant transformation of benign ampullary adenomas into ampullary cancer.

The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

PubMed

Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

2004-11-15

Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

Predictors of Poor Sleep Quality Among Head and Neck Cancer Patients

PubMed Central

Shuman, Andrew G.; Duffy, Sonia A.; Ronis, David L.; Garetz, Susan L.; McLean, Scott A.; Fowler, Karen E.; Terrell, Jeffrey E.

2013-01-01

Objectives/Hypothesis The objective of this study was to determine the predictors of sleep quality among head and neck cancer patients 1 year after diagnosis. Study Design This was a prospective, multisite cohort study of head and neck cancer patients (N = 457). Methods Patients were surveyed at baseline and 1 year after diagnosis. Chart audits were also conducted. The dependent variable was a self-assessed sleep score 1 year after diagnosis. The independent variables were a 1 year pain score, xerostomia, treatment received (radiation, chemotherapy, and/or surgery), presence of a feeding tube and/or tracheotomy, tumor site and stage, comorbidities, depression, smoking, problem drinking, age, and sex. Results Both baseline (67.1) and 1-year post-diagnosis (69.3) sleep scores were slightly lower than population means (72). Multivariate analyses showed that pain, xerostomia, depression, presence of a tracheotomy tube, comorbidities, and younger age were statistically significant predictors of poor sleep 1 year after diagnosis of head and neck cancer (P < .05). Smoking, problem drinking, and female sex were marginally significant (P < .09). Type of treatment (surgery, radiation and/or chemotherapy), primary tumor site, and cancer stage were not significantly associated with 1-year sleep scores. Conclusions Many factors adversely affecting sleep in head and neck cancer patients are potentially modifiable and appear to contribute to decreased quality of life. Strategies to reduce pain, xerostomia, depression, smoking, and problem drinking may be warranted, not only for their own inherent value, but also for improvement of sleep and the enhancement of quality of life. PMID:20513034

Monitoring circulating prostate tumor cells after tumor resection by in vivo flow cytometry

NASA Astrophysics Data System (ADS)

Ding, Nan; Zhu, Xi; Xie, Chengying; Wei, Dan; Yang, Zhangru; Suo, Yuanzhen; Wei, Xunbin

2018-02-01

Prostate cancer has already become the biggest threat among all cancer types for male people and many people died because of its bone metastases. Circulating tumor cells (CTCs) can be used as early metastasis marker so that the detection of CTCs in blood is meaningful for early diagnosis and treatment. However, the relationship between these therapies and metastasis has not been fully clarified yet. Hence, we built PC3 subcutaneous tumor model and developed in vivo flow cytometer (IVFC) platform to record the dynamics of CTC before and after tumor resection. We found out that tumor resection can reduce CTC quantities instantaneously while having a good control of metastasis. CTC re-occurred 7 days after surgery, which might be correlated with early disseminated and deposited tumors. In conclusion, in vivo flow cytometry (IVFC) is capable of detecting CTC dynamics in prostate subcutaneous tumor model and this method could facilitate further research about relationship between other cancer therapies and circulating tumor cells.

Expression of pigment epithelium-derived factor and tumor necrosis factor-α is correlated in bladder tumor and is related to tumor angiogenesis.

PubMed

Feng, Chen-Chen; Wang, Pao-Hsun; Ding, Qiang; Guan, Ming; Zhang, Yuan-Fang; Jiang, Hao-Wen; Wen, Hui; Wu, Zhong

2013-02-01

Angiogenesis is a pivotal process on which solid tumor growth is substantially dependent. Pigment epithelium-derived factor (PEDF) is the most potent natural anti-angiogenic factor, which has seldom been studied in bladder tumor, and whose functioning pathway remains unclear. We have thus investigated PEDF expression in relation to tumor necrosis factor-α (TNF-α) and microvessel density (MVD) with immunohistochemistry. Antibodies of PEDF and TNF-α were examined by Western blotting before immunohistochemistry. Sixty-four urothelial tumor sections and 23 normal controls were stained and expression of PEDF, TNF-α, and MVD were studied. Decreased PEDF expression and increased TNF-α expression was noticed in tumorous tissue compared with healthy urothelium. Lower PEDF expression was related to higher tumor grade but stage. Increased TNF-α expression was noticed in recurrent, larger tumors as well as in tumors with progression in grade and stage. Expression of PEDF and TNF-α was correlated in bladder tumor. PEDF or TNF-α was correlated with MVD negatively or positively, respectively, in cancerous tissue and tumorous grouping without correlation in papillary urothelial neoplasm of low malignant potential. Expressional change of PEDF and TNF-α is in relation to angiogenesis of bladder tumor, especially in bladder cancer development. Copyright © 2013 Elsevier Inc. All rights reserved.

High risk of brain tumors in farmers: a mini-review of the literature, and report of the results of a case control study.

PubMed

Fallahi, P; Foddis, R; Cristaudo, A; Antonelli, A

2017-01-01

Even though a relationship between farmer work and the development of brain tumors was suggest by the scientific literature, a small number of italian studies investigate on the impact of this job on the cancer morbidity of farmer population. The informations about this case-control study were obtained from patients recruited in the Neurosurgical Department of the University-Hospital of Pisa, Italy, from 1990 to 2000. One hundred and seventy-four, newly diagnosed cases of brain tumors (glioma and meningiomas, histologically confirmed), were recruited, such as 522 controls (with other non tumoral neurologic diseases: trauma, etc), by matching cases and controls (1:3), for age (± 5 years) and gender. Cases and controls were interviewed in the Neurosurgical Department, University-Hospital of Pisa, Italy, and the occupational histories of cases and controls were compared. Cases and controls have showed a statistically significant difference, based on their occupation (agricultural vs. non-agricultural). We observed a significant association among brain tumors and rural activity in evaluated patients (P=0.008). Further studies regarding this population group are needed, to determine the causes for the increased risk of this cancer, particularly in regions where there is an intense agricultural activity and where pesticides are used. Furthermore, a subsequent reevaluation in other patients collected in more recent years will be needed to evaluate the trend of this association.

Phyllodes Tumor of the Breast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Belkacemi, Yazid; University of Lille II, Lille; Bousquet, Guilhem

Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapymore » (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.« less

Birth characteristics and Wilms tumors in children in the Nordic countries: a register-based case-control study.

PubMed

Schüz, Joachim; Schmidt, Lisbeth Samsø; Kogner, Per; Lähteenmäki, Päivi M; Pal, Niklas; Stokland, Tore; Schmiegelow, Kjeld

2011-05-01

Little is known about causes of Wilms tumor. Because of the young age at diagnosis, several studies have looked at various birth characteristics. We conducted a registry-based case-control study involving 690 cases of Wilms tumor aged 0-14 years, occurring in Denmark, Finland, Norway or Sweden during 1985-2006, individually matched to five controls drawn randomly from the Nordic childhood population. Information on birth characteristics was obtained from the population-based medical birth registries. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression analysis. We observed a distinct association between Wilms tumor and high birth weight (≥4 kg) for girls (OR 1.97, CI 1.50-2.59) but not for boys (1.04, 0.78-1.38); overall, the OR was 1.43 (1.17-1.74). Among girls, risk increased by 28% (15-42%) per 500 g increase in birth weight. Large-for-gestational age girls also had a higher risk (2.48, 1.51-4.05), whereas no effect was seen for boys (1.12, 0.60-2.07). An association was seen with Apgar score at 5 min < 7 for both sexes combined (5.13, 2.55-10.3). ORs close to unity were seen for parental age and birth order. In our large-scale, registry-based study, we confirmed earlier observations of an association between high birth weight and risk of Wilms tumor, but we found an effect only in girls. The higher risk of infants with low Apgar score might reflect hypoxia causing cell damage, adverse side effects of neonatal treatment or reverse causation as low Apgar score might indicate the presence of a tumor. Copyright © 2010 UICC.

Neurofeedback to improve neurocognitive functioning of children treated for a brain tumor: design of a randomized controlled double-blind trial.

PubMed

de Ruiter, Marieke A; Schouten-Van Meeteren, Antoinette Y N; van Mourik, Rosa; Janssen, Tieme W P; Greidanus, Juliette E M; Oosterlaan, Jaap; Grootenhuis, Martha A

2012-12-06

Neurotoxicity caused by treatment for a brain tumor is a major cause of neurocognitive decline in survivors. Studies have shown that neurofeedback may enhance neurocognitive functioning. This paper describes the protocol of the PRISMA study, a randomized controlled trial to investigate the efficacy of neurofeedback to improve neurocognitive functioning in children treated for a brain tumor. Efficacy of neurofeedback will be compared to placebo training in a randomized controlled double-blind trial. A total of 70 brain tumor survivors in the age range of 8 to 18 years will be recruited. Inclusion also requires caregiver-reported neurocognitive problems and being off treatment for more than two years. A group of 35 healthy siblings will be included as the control group. On the basis of a qEEG patients will be assigned to one of three treatment protocols. Thereafter patients will be randomized to receive either neurofeedback training (n=35) or placebo training (n=35). Neurocognitive tests, and questionnaires administered to the patient, caregivers, and teacher, will be used to evaluate pre- and post-intervention functioning, as well as at 6-month follow-up. Siblings will be administered the same tests and questionnaires once. If neurofeedback proves to be effective for pediatric brain tumor survivors, this can be a valuable addition to the scarce interventions available to improve neurocognitive and psychosocial functioning. ClinicalTrials.gov NCT00961922.

Novel tumor-ablation device for liver tumors utilizing heat energy generated under an alternating magnetic field.

PubMed

Sato, Koichi; Watanabe, Yuji; Horiuchi, Atsushi; Yukumi, Shungo; Doi, Takashi; Yoshida, Motohira; Yamamoto, Yuji; Maehara, Tsunehiro; Naohara, Takashi; Kawachi, Kanji

2008-07-01

We have developed a novel tumor-ablation device for liver tumors utilizing heat energy induced by magnesium ferrite (MgFe(2)O(4)) particles under an alternating magnetic field (AMF) produced by electric currents. This novel device can repeatedly heat liver tumors at lower temperature than usual heating devices, such as radiofrequency ablation therapy, with slight infliction of pain. This study assesses its heating effect on rat liver tumors as local therapy. The small needle was manufactured from MgFe(2)O(4) particles by sintering at 1100 degrees C. After a MgFe(2)O(4) needle was inserted into liver tumors comprising of dRLh-84 cells, the tumors were heated for 30 min under an AMF. We examined cellular activity by using nicotinamide adenine dinucleotide (NADH) diaphorase staining and terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) staining, and evaluated the effect of suppressing tumor growth by sequentially comparing the tumor diameter with that of the control group. The mean temperature of the heated tumors was 60.2 +/- 1.8 degrees C. The tumor cells were constricted, and chromatin of nuclei had shrunk immediately after heating. The heat-injury area that contained the tumors was negative for NADH diaphorase activity. After 3 days, the tumor cells in the heat-injury area became positive for TUNEL staining, which detects cell death. At 7 days, the mean tumor diameters were significantly smaller in the heating group than in the control group (6.15 +/- 0.47 mm vs 16.89 +/- 2.69 mm; P < 0.05). This device, utilizing heat energy induced by ferromagnetic metal under an AMF, appears useful as local thermotherapy for human liver cancer.

[Benign bone tumors. General principles].

PubMed

Hillmann, A; Gösling, T

2014-10-01

Benign bone tumors and tumor-like lesions are much more frequent than malignant bone tumors among the total number of tumors of the skeleton. This article gives a presentation of the characteristics and treatment modalities of benign bone tumors. In this article in-house treatment principles are compared with those in the currently available literature. Benign bone tumors are frequently found incidentally; however, the term benign does not always signify that a purely observational role is needed. Benign bone tumors differ in their biological behavior and can be latent, active or aggressive which determines the treatment approach. Some benign bone tumors are just as aggressive locally as malignant tumors. The most important diagnostic feature is still conventional radiography and a thorough systematic analysis is necessary. Therapy options range from ignore, wait and see up to wide resection. In contrast to malignant tumors the radicalism of resection can be weighed against the accompanying local control and loss of function. The treatment of benign bone tumors depends on the histological type and the biological activity. Most benign bone tumors are diagnosed incidentally and do not necessitate any treatment.

Impact of ischemic preconditioning on surgical treatment of brain tumors: a single-center, randomized, double-blind, controlled trial.

PubMed

Sales, Arthur H A; Barz, Melanie; Bette, Stefanie; Wiestler, Benedikt; Ryang, Yu-Mi; Meyer, Bernhard; Bretschneider, Martin; Ringel, Florian; Gempt, Jens

2017-07-25

Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences. Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume. Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm 3 (interquartile range (IR): 0.0-2.35) in the rIPC group compared with 1.30 cm 3 (IR: 0.29-3.66) in the control group (p = 0.09). Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery. German Clinical Trials Register, DRKS00010409 . Retrospectively

Intensity-Modulated Radiotherapy in the Treatment of Oropharyngeal Cancer: An Update of the Memorial Sloan-Kettering Cancer Center Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Setton, Jeremy; Caria, Nicola; Romanyshyn, Jonathan

2012-01-01

Purpose: To update the Memorial Sloan-Kettering Cancer Center's experience with intensity-modulated radiotherapy (IMRT) in the treatment of oropharyngeal cancer (OPC). Methods and Materials: Between September 1998 and April 2009, 442 patients with histologically confirmed OPC underwent IMRT at our center. There were 379 men and 63 women with a median age of 57 years (range, 27-91). The disease was Stage I in 2%, Stage II in 4%, Stage III in 21%, and Stage IV in 73% of patients. The primary tumor subsite was tonsil in 50%, base of tongue in 46%, pharyngeal wall in 3%, and soft palate in 2%.more » The median prescription dose to the planning target volume of the gross tumor was 70 Gy for definitive (n = 412) cases and 66 Gy for postoperative cases (n = 30). A total 404 patients (91%) received chemotherapy, including 389 (88%) who received concurrent chemotherapy, the majority of which was platinum-based. Results: Median follow-up among surviving patients was 36.8 months (range, 3-135). The 3-year cumulative incidence of local failure, regional failure, and distant metastasis was 5.4%, 5.6%, and 12.5%, respectively. The 3-year OS rate was 84.9%. The incidence of late dysphagia and late xerostomia {>=}Grade 2 was 11% and 29%, respectively. Conclusions: Our results confirm the feasibility of IMRT in achieving excellent locoregional control and low rates of xerostomia. According to our knowledge, this study is the largest report of patients treated with IMRT for OPC.« less

Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

PubMed

Zhang, Ming-Kang; Wang, Xiao-Gang; Zhu, Jing-Yi; Liu, Miao-Deng; Li, Chu-Xin; Feng, Jun; Zhang, Xian-Zheng

2018-04-17

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

1H-NMR METABONOMICS ANALYSIS OF SERA DIFFERENTIATES BETWEEN MAMMARY TUMOR-BEARING MICE AND HEALTHY CONTROLS

EPA Science Inventory

Global analysis of 1H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1H-NMR metabonomic analyses on serum samples ob...

Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer.

PubMed

Matsunaga, Shigeo; Shuto, Takashi; Sato, Mitsuru

2016-05-01

The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

PubMed Central

Chen, Zhe (Jay); Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-01-01

Previous studies have shown that the procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations depends strongly on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al. (Int. J. Radiat. Oncol. Biol. Phys. 41, 1069–1077–1998) was used to characterize the edema evolutions observed previously during clinical PIB for prostate cancer. The concept of biologically effective dose (BED), taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not taken into account appropriately, can increase the cell survival and decrease the probability of local control of PIB. The edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life for radioactive decay and decreasing energy of the photons energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days

Early Oral Tongue Squamous Cell Carcinoma Sampling of Margins From Tumor Bed and Worse Local Control

PubMed Central

Maxwell, Jessica H.; Thompson, Lester D. R.; Brandwein-Gensler, Margaret S.; Weiss, Bernhard G.; Canis, Martin; Purgina, Bibianna; Prabhu, Arpan V.; Lai, Chi; Shuai, Yongli; Carroll, William R.; Morlandt, Anthony; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Ferris, Robert L.; Seethala, Raja; Chiosea, Simion I.

2017-01-01

the status of tumor bed margins did not. The status of the tumor bed margin was 24% sensitive (95% CI, 16%-34%) and 92% specific (95% CI, 85%-97%) for detecting a positive glossectomy margin. CONCLUSIONS AND RELEVANCE The margin sampling technique affects local control in patients with oral tongue SCC. Reliance on margin sampling from the tumor bed is associated with worse local control, most likely owing to narrower margin clearance and greater incidence of positive margins. A resection specimen–based margin assessment is recommended. PMID:26225798

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

PubMed Central

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S.; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55–65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

PubMed

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO 2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO 2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training

Selection bias due to differential participation in a case-control study of mobile phone use and brain tumors.

PubMed

Lahkola, Anna; Salminen, Tiina; Auvinen, Anssi

2005-05-01

To evaluate the possible selection bias related to the differential participation of mobile phone users and non-users in a Finnish case-control study on mobile phone use and brain tumors. Mobile phone use was investigated among 777 controls and 726 cases participating in the full personal interview (full participants), and 321 controls and 103 cases giving only a brief phone interview (incomplete participants). To assess selection bias, the Mantel-Haenszel estimate of odds ratio was calculated for three different groups: full study participants, incomplete participants, and a combined group consisting of both full and incomplete participants. Among controls, 83% of the full participants and 73% of the incomplete participants had regularly used a mobile phone. Among cases, the figures were 76% and 64%, respectively. The odds ratio for brain tumor based on the combined group of full and incomplete participants was slightly closer to unity than that based only on the full participants. Selection bias tends to distort the effect estimates below unity, while analyses based on more comprehensive material gave results close to unity.

Tissue engineered tumor models.

PubMed

Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

2010-08-01

Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

Tumor control probability reduction in gated radiotherapy of non-small cell lung cancers: a feasibility study.

PubMed

Siochi, R Alfredo; Kim, Yusung; Bhatia, Sudershan

2014-10-16

We studied the feasibility of evaluating tumor control probability (TCP) reductions for tumor motion beyond planned gated radiotherapy margins. Tumor motion was determined from cone-beam CT projections acquired for patient setup, intrafraction respiratory traces, and 4D CTs for five non-small cell lung cancer (NSCLC) patients treated with gated radiotherapy. Tumors were subdivided into 1 mm sections whose positions and doses were determined for each beam-on time point. (The dose calculation model was verified with motion phantom measurements.) The calculated dose distributions were used to generate the treatment TCPs for each patient. The plan TCPs were calculated from the treatment planning dose distributions. The treatment TCPs were compared to the plan TCPs for various models and parameters. Calculated doses matched phantom measurements within 0.3% for up to 3 cm of motion. TCP reductions for excess motion greater than 5mm ranged from 1.7% to 11.9%, depending on model parameters, and were as high as 48.6% for model parameters that simulated an individual patient. Repeating the worst case motion for all fractions increased TCP reductions by a factor of 2 to 3, while hypofractionation decreased these reductions by as much as a factor of 3. Treatment motion exceeding gating margins by more than 5 mm can lead to considerable TCP reductions. Appropriate margins for excess motion are recommended, unless applying daily tumor motion verification and adjusting thegating window.

Population-based multicase-control study in common tumors in Spain (MCC-Spain): rationale and study design.

PubMed

Castaño-Vinyals, Gemma; Aragonés, Nuria; Pérez-Gómez, Beatriz; Martín, Vicente; Llorca, Javier; Moreno, Victor; Altzibar, Jone M; Ardanaz, Eva; de Sanjosé, Sílvia; Jiménez-Moleón, José Juan; Tardón, Adonina; Alguacil, Juan; Peiró, Rosana; Marcos-Gragera, Rafael; Navarro, Carmen; Pollán, Marina; Kogevinas, Manolis

2015-01-01

We present the protocol of a large population-based case-control study of 5 common tumors in Spain (MCC-Spain) that evaluates environmental exposures and genetic factors. Between 2008-2013, 10,183 persons aged 20-85 years were enrolled in 23 hospitals and primary care centres in 12 Spanish provinces including 1,115 cases of a new diagnosis of prostate cancer, 1,750 of breast cancer, 2,171 of colorectal cancer, 492 of gastro-oesophageal cancer, 554 cases of chronic lymphocytic leukaemia (CLL) and 4,101 population-based controls matched by frequency to cases by age, sex and region of residence. Participation rates ranged from 57% (stomach cancer) to 87% (CLL cases) and from 30% to 77% in controls. Participants completed a face-to-face computerized interview on sociodemographic factors, environmental exposures, occupation, medication, lifestyle, and personal and family medical history. In addition, participants completed a self-administered food-frequency questionnaire and telephone interviews. Blood samples were collected from 76% of participants while saliva samples were collected in CLL cases and participants refusing blood extractions. Clinical information was recorded for cases and paraffin blocks and/or fresh tumor samples are available in most collaborating hospitals. Genotyping was done through an exome array enriched with genetic markers in specific pathways. Multiple analyses are planned to assess the association of environmental, personal and genetic risk factors for each tumor and to identify pleiotropic effects. This study, conducted within the Spanish Consortium for Biomedical Research in Epidemiology & Public Health (CIBERESP), is a unique initiative to evaluate etiological factors for common cancers and will promote cancer research and prevention in Spain. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

Modified model of VX2 tumor overexpressing vascular endothelial growth factor.

PubMed

Pascale, Florentina; Ghegediban, Saida-Homayra; Bonneau, Michel; Bedouet, Laurent; Namur, Julien; Verret, Valentin; Schwartz-Cornil, Isabelle; Wassef, Michel; Laurent, Alexandre

2012-06-01

To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis. The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified. Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012). The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Zachary D.; Batra, Sachin; Limb, Charles J.

2011-11-15

Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data whenmore » Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test. Results: Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.« less

HORMONAL CONTROL OF OVARIAN FUNCTION FOLLOWING CHLOROTRIAZINE EXPOSURE: EFFECT ON REPRODUCTIVE FUNCTION AND MAMMARY GLAND TUMOR DEVELOPMENT

EPA Science Inventory

Hormonal Control of Ovarian Function Following Chlorotriazine Exposure: Effect on Reproductive Function and Mammary Gland Tumor Development.

Ralph L. Cooper, Susan C. Laws, Michael G. Narotsky, Jerome M. Goldman, and Tammy E. Stoker

Abstract
The studies review...

Pathophysiology of Tumor Neovascularization

PubMed Central

Furuya, Mitsuko; Nishiyama, Mariko; Kasuya, Yoshitoshi; Kimura, Sadao; Ishikura, Hiroshi

2005-01-01

Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumor-derived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized. PMID:17315600

The association between glomus tumors and neurofibromatosis.

PubMed

Harrison, Bridget; Moore, Amy M; Calfee, Ryan; Sammer, Douglas M

2013-08-01

To determine whether an epidemiologic association exists between glomus tumors and neurofibromatosis. Using a pathology database, we established a study cohort consisting of all patients who had undergone excision of a glomus tumor of the hand between 1995 and 2010. We created a control cohort by randomly selecting 200 patients who had undergone excision of a ganglion cyst over the same period. We reviewed medical records for each cohort to identify patients with a diagnosis of neurofibromatosis. We calculated the odds ratio was calculated and performed Fisher's exact test to determine the significance of the association. We identified 21 patients with glomus tumors of the hand. Six of these patients carried the diagnosis of neurofibromatosis (29%). In contrast, no patients in the control group carried the diagnosis of neurofibromatosis. The odds ratio for a diagnosis of neurofibromatosis in association with a glomus tumor compared with controls was 168:1. This study provides evidence of a strong epidemiologic association between glomus tumors and neurofibromatosis. Glomus tumor should be included in the differential diagnosis in neurofibromatosis patients who present with a painful lesion of the hand or finger. Diagnostic III. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Use of Concept of Chemotherapy-Equivalent Biologically Effective Dose to Provide Quantitative Evaluation of Contribution of Chemotherapy to Local Tumor Control in Chemoradiotherapy Cervical Cancer Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plataniotis, George A.; Dale, Roger G.

2008-12-01

Purpose: To express the magnitude of the contribution of chemotherapy to local tumor control in chemoradiotherapy cervical cancer trials in terms of the concept of the biologically effective dose. Methods and Materials: The local control rates of both arms of each study (radiotherapy vs. radiotherapy plus chemotherapy) reported from randomized controlled trials of concurrent chemoradiotherapy for cervical cancer were reviewed and expressed using the Poisson model for tumor control probability (TCP) as TCP = exp(-exp E), where E is the logarithm of cell kill. By combining the two TCP values from each study, we calculated the chemotherapy-related log cell killmore » as Ec = ln[(lnTCP{sub Radiotherapy})/(lnTCP{sub Chemoradiotherapy})]. Assuming a range of radiosensitivities ({alpha} = 0.1-0.5 Gy{sup -1}) and taking the calculated log cell kill, we calculated the chemotherapy-BED, and using the linear quadratic model, the number of 2-Gy fractions corresponding to each BED. The effect of a range of tumor volumes and radiosensitivities ({alpha} Gy{sup -1}) on the TCP was also explored. Results: The chemotherapy-equivalent number of 2-Gy fractions range was 0.2-4 and was greater in tumors with lower radiosensitivity. In those tumors with intermediate radiosensitivity ({alpha} = 0.3 Gy{sup -1}), the equivalent number of 2-Gy fractions was 0.6-1.3, corresponding to 120-260 cGy of extra dose. The opportunities for clinically detectable improvement are only available in tumors with intermediate radiosensitivity with {alpha} = 0.22-0.28 Gy{sup -1}. The dependence of TCP on the tumor volume decreases as the radiosensitivity increases. Conclusion: The results of our study have shown that the contribution of chemotherapy to the TCP in cervical cancer is expected to be clinically detectable in larger and less-radiosensitive tumors.« less

Immunology of intraocular tumors.

PubMed

Niederkorn, Jerry Y; Wang, Shixuan

2005-02-01

The immune surveillance hypothesis was introduced over 30 years ago and proposed that neoplasms express novel antigens that subjected them to immune detection and elimination. In order for immune surveillance to be effective in controlling neoplasms, two requirements must be satisfied: 1) the tumor must arise in a body site that permits the induction the full array of immune responses and 2) the immune elements generated must have unfettered access to the tumor and be able to express their entire range of effector functions at the tumor site. The unique immunologic and anatomic features of the eye prevent the induction and expression of conventional immunity--a phenomenon known as 'immune privilege'. Although ocular immune privilege represents a theoretical obstacle to immune surveillance, some highly immunogenic intraocular tumors can circumvent immune privilege and undergo immune rejection. Uveal melanoma is the most common intraocular malignancy in adults, yet it occurs with a frequency that is no higher than neoplasms arising in conventional bodies. The presence of either tumor-infiltrating lymphocytes (TIL) or tumor-infiltrating macrophages (TIM) is associated with poor prognosis in uveal melanoma patients and suggests that some immune responses to intraocular tumors might exacerbate, rather than mitigate, tumor progression. Although counterintuitive, this proposition is consistent with the 'immune stimulation' hypothesis of tumor progression offered by Richmond Prehn over thirty years ago. It remains to be ascertained if immune stimulation affects the malignancy of ocular tumors, but it represents an intriguing explanation for the paradoxes of uveal melanoma.

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

PubMed Central

Rasmussen, Christina B.; Kjaer, Susanne K.; Albieri, Vanna; Bandera, Elisa V.; Doherty, Jennifer A.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Edwards, Robert P.; Schildkraut, Joellen M.; Berchuck, Andrew; Olson, Sara H.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Narod, Steven A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H.; Pearce, Celeste L.; Risch, Harvey A.; Jensen, Allan

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. PMID:27941069

DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors

PubMed Central

Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

2013-01-01

Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA–encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA–mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene

DNA methylation mediated control of gene expression is critical for development of crown gall tumors.

PubMed

Gohlke, Jochen; Scholz, Claus-Juergen; Kneitz, Susanne; Weber, Dana; Fuchs, Joerg; Hedrich, Rainer; Deeken, Rosalia

2013-01-01

Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA-encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA-mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene

The impact of prostate edema on cell survival and tumor control after permanent interstitial brachytherapy for early stage prostate cancers

NASA Astrophysics Data System (ADS)

(Jay Chen, Zhe; Roberts, Kenneth; Decker, Roy; Pathare, Pradip; Rockwell, Sara; Nath, Ravinder

2011-08-01

Previous studies have shown that procedure-induced prostate edema during permanent interstitial brachytherapy (PIB) can cause significant variations in the dose delivered to the prostate gland. Because the clinical impact of edema-induced dose variations strongly depends on the magnitude of the edema, the temporal pattern of its resolution and its interplay with the decay of radioactivity and the underlying biological processes of tumor cells (such as tumor potential doubling time), we investigated the impact of edema-induced dose variations on the tumor cell survival and tumor control probability after PIB with the 131Cs, 125I and 103Pd sources used in current clinical practice. The exponential edema resolution model reported by Waterman et al (1998 Int. J. Radiat. Oncol. Biol. Phys. 41 1069-77) was used to characterize the edema evolutions previously observed during clinical PIB for prostate cancer. The concept of biologically effective dose, taking into account tumor cell proliferation and sublethal damage repair during dose delivery, was used to characterize the effects of prostate edema on cell survival and tumor control probability. Our calculation indicated that prostate edema, if not appropriately taken into account, can increase the cell survival and decrease the probability of local control of PIB. The magnitude of an edema-induced increase in cell survival increased with increasing edema severity, decreasing half-life of radioactive decay and decreasing photon energy emitted by the source. At the doses currently prescribed for PIB and for prostate cancer cells characterized by nominal radiobiology parameters recommended by AAPM TG-137, PIB using 125I sources was less affected by edema than PIB using 131Cs or 103Pd sources due to the long radioactive decay half-life of 125I. The effect of edema on PIB using 131Cs or 103Pd was similar. The effect of edema on 103Pd PIB was slightly greater, even though the decay half-life of 103Pd (17 days) is longer than

Eukaryotic Initiation Factor 4E Binding Protien Family of Protiens: Sentinels at a Translational Control Checkpoint in Lung Tumor Defense

PubMed Central

Kim, Yong Y; Von Weymarn, Linda; Larsson, Ola; Fan, Danhua; Underwood, Jon M; Hecht, Stephen S; Polunovsky, Vitaly A; Bitterman, Peter B

2009-01-01

The usurping of translational control by sustained activation of translation initiation factors is oncogenic. Here we show that the primary negative regulators of these oncogenic initiation factors - the 4E-BP protein family - operate as guardians of a translational control checkpoint in lung tumor defense. When challenged with the tobacco carcinogen NNK, 4ebp1−/−/4ebp2−/− mice showed increased sensitivity to tumorigenesis compared to their wild type counterparts. The 4E-BP deficient state per se creates pro-oncogenic, genome-wide skewing of the molecular landscape - with translational activation of genes governing angiogenesis, growth and proliferation; and translational activation of the precise cytochrome p450 enzyme isoform (CYP2A5) that bioactivates NNK into mutagenic metabolites. Our study provides in vivo proof for a translational control checkpoint in lung tumor defense. PMID:19843855

Tumorous diseases of turkeys - an update

USDA-ARS?s Scientific Manuscript database

This update is primarily focused on addressing various aspects of virus-induced tumorous diseases of turkeys including review of current methods for diagnosis and control of these diseases of turkeys. Virus-induced tumorous diseases of turkeys are caused primarily by retroviruses, namely reticuloend...

Elevated VEGF-D Modulates Tumor Inflammation and Reduces the Growth of Carcinogen-Induced Skin Tumors.

PubMed

Honkanen, Hanne-Kaisa; Izzi, Valerio; Petäistö, Tiina; Holopainen, Tanja; Harjunen, Vanessa; Pihlajaniemi, Taina; Alitalo, Kari; Heljasvaara, Ritva

2016-07-01

Vascular endothelial growth factor D (VEGF-D) promotes the lymph node metastasis of cancer by inducing the growth of lymphatic vasculature, but its specific roles in tumorigenesis have not been elucidated. We monitored the effects of VEGF-D in cutaneous squamous cell carcinoma (cSCC) by subjecting transgenic mice overexpressing VEGF-D in the skin (K14-mVEGF-D) and VEGF-D knockout mice to a chemical skin carcinogenesis protocol involving 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate treatments. In K14-mVEGF-D mice, tumor lymphangiogenesis was significantly increased and the frequency of lymph node metastasis was elevated in comparison with controls. Most notably, the papillomas regressed more often in K14-mVEGF-D mice than in littermate controls, resulting in a delay in tumor incidence and a remarkable reduction in the total tumor number. Skin tumor growth and metastasis were not obviously affected in the absence of VEGF-D; however, the knockout mice showed a trend for reduced lymphangiogenesis in skin tumors and in the untreated skin. Interestingly, K14-mVEGF-D mice showed an altered immune response in skin tumors. This consisted of the reduced accumulation of macrophages, mast cells, and CD4(+) T-cells and an increase of cytotoxic CD8(+) T-cells. Cytokine profiling by flow cytometry and quantitative real time PCR revealed that elevated VEGF-D expression results in an attenuated Th2 response and promotes M1/Th1 and Th17 polarization in the early stage of skin carcinogenesis, leading to an anti-tumoral immune environment and the regression of primary tumors. Our data suggest that VEGF-D may be beneficial in early-stage tumors since it suppresses the pro-tumorigenic inflammation, while at later stages VEGF-D-induced tumor lymphatics provide a route for metastasis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Off and back-on again: a tumor suppressor's tale.

PubMed

Acosta, Jonuelle; Wang, Walter; Feldser, David M

2018-06-01

Tumor suppressor genes play critical roles orchestrating anti-cancer programs that are both context dependent and mechanistically diverse. Beyond canonical tumor suppressive programs that control cell division, cell death, and genome stability, unexpected tumor suppressor gene activities that regulate metabolism, immune surveillance, the epigenetic landscape, and others have recently emerged. This diversity underscores the important roles these genes play in maintaining cellular homeostasis to suppress cancer initiation and progression, but also highlights a tremendous challenge in discerning precise context-specific programs of tumor suppression controlled by a given tumor suppressor. Fortunately, the rapid sophistication of genetically engineered mouse models of cancer has begun to shed light on these context-dependent tumor suppressor activities. By using techniques that not only toggle "off" tumor suppressor genes in nascent tumors, but also facilitate the timely restoration of gene function "back-on again" in disease specific contexts, precise mechanisms of tumor suppression can be revealed in an unbiased manner. This review discusses the development and implementation of genetic systems designed to toggle tumor suppressor genes off and back-on again and their potential to uncover the tumor suppressor's tale.

Bioadhesive, rheological, lubricant and other aspects of an oral gel formulation intended for the treatment of xerostomia.

PubMed

Kelly, H M; Deasy, P B; Busquet, M; Torrance, A A

2004-07-08

Xerostomia is commonly known as 'dry mouth' and is characterised by a reduction or loss in salivary production. A bioadhesive gel for its localised treatment was formulated to help enhance the residence time of the product, based on the polymer Carbopol 974P. The bioadhesion of various formulations was evaluated on different mucosal substrates, as simulations of the oral mucosa of xerostomic patients. Depending on the type of model substrate used, the mechanism of bioadhesion could alter. When the rheology of various formulations was examined, changes in bioadhesion were more easily interpreted, as the presence of other excipients caused an alteration in the rheological profile, with a change from a fully expanded and partially cross-linked system to an entangled system. Improving the lubricity of the product was considered important, with optimum incorporation of vegetable oil causing a desirable lowering of the observed friction of the product. The final complex formulation developed also contained salivary levels of electrolytes to help remineralisation of teeth, fluoride to prevent caries, zinc to enhance taste sensation, triclosan as the main anti-microbial/anti-inflammatory agent and non-cariogenic sweeteners with lemon flavour to increase the palatability of the product while stimulating any residual salivary function.

Stochastic modelling of slow-progressing tumors: Analysis and applications to the cell interplay and control of low grade gliomas

NASA Astrophysics Data System (ADS)

Rodríguez, Clara Rojas; Fernández Calvo, Gabriel; Ramis-Conde, Ignacio; Belmonte-Beitia, Juan

2017-08-01

Tumor-normal cell interplay defines the course of a neoplastic malignancy. The outcome of this dual relation is the ultimate prevailing of one of the cells and the death or retreat of the other. In this paper we study the mathematical principles that underlay one important scenario: that of slow-progressing cancers. For this, we develop, within a stochastic framework, a mathematical model to account for tumor-normal cell interaction in such a clinically relevant situation and derive a number of deterministic approximations from the stochastic model. We consider in detail the existence and uniqueness of the solutions of the deterministic model and study the stability analysis. We then focus our model to the specific case of low grade gliomas, where we introduce an optimal control problem for different objective functionals under the administration of chemotherapy. We derive the conditions for which singular and bang-bang control exist and calculate the optimal control and states.

Radiofrequency ablation of pulmonary tumors near the diaphragm.

PubMed

Iguchi, T; Hiraki, T; Gobara, H; Fujiwara, H; Sakurai, J; Matsui, Y; Mitsuhashi, T; Toyooka, S; Kanazawa, S

To retrospectively evaluate the feasibility, safety, and efficacy of radiofrequency ablation (RFA) of lung tumors located near the diaphragm. A total of 26 patients (15 men, 11 women; mean age, 61.5 years±13.0 [SD]) with a total of 29 lung tumors near the diaphragm (i.e., distance<10mm) were included. Mean tumor diameter was 11.0mm±5.3 (SD) (range, 2-23mm). Efficacy of RFA, number of adverse events and number of adverse events with a grade≥3, based on the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, were compared between patients with lung tumors near the diaphragm and a control group of patients with more distally located lung tumors (i.e., distance≥10mm). RFA was technically feasible for all tumors near the diaphragm. Four grade 3 adverse events (1 pneumothorax requiring pleurodesis and 3 phrenic nerve injuries) were observed. No grade≥4 adverse events were reported. The median follow-up period for tumors near the diaphragm was 18.3 months. Local progression was observed 3.3 months after RFA in 1 tumor. The technique efficacy rates were 96.2% at 1 year and 96.2% at 2 years and were not different, from those observed in control subjects (186 tumors; P=0.839). Shoulder pain (P<0.001) and grade 1 pleural effusion (P<0.001) were more frequently observed in patients with lung tumor near the diaphragm. The rates of grade≥3 adverse events did not significantly differ between tumors near the diaphragm (4/26 sessions) and the controls (7/133 sessions) (P=0.083). RFA is a feasible and effective therapeutic option for lung tumors located near the diaphragm. However, it conveys a higher rate of shoulder pain and asymptomatic pleural effusion by comparison with more distant lung tumors. Copyright © 2017 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Gamma knife radiosurgery for cerebellopontine angle epidermoid tumors.

PubMed

El-Shehaby, Amr M N; Reda, Wael A; Abdel Karim, Khaled M; Emad Eldin, Reem M; Nabeel, Ahmed M

2017-01-01

Intracranial epidermoid tumors are commonly found in the cerebellopontine angle where they usually present with either trigeminal neuralgia or hemifacial spasm. Radiosurgery for these tumors has rarely been reported. The purpose of this study is to assess the safety and clinical outcome of the treatment of cerebellopontine epidermoid tumors with gamma knife radiosurgery. This is a retrospective study involving 12 patients harboring cerebellopontine angle epidermoid tumors who underwent 15 sessions of gamma knife radiosurgery. Trigeminal pain was present in 8 patients and hemifacial spasm in 3 patients. All cases with trigeminal pain were receiving medication and still uncontrolled. One patient with hemifacial spasm was medically controlled before gamma knife and the other two were not. Two patients had undergone surgical resection prior to gamma knife treatment. The median prescription dose was 11 Gy (10-11 Gy). The tumor volumes ranged from 3.7 to 23.9 cc (median 10.5 cc). The median radiological follow up was 2 years (1-5 years). All tumors were controlled and one tumor shrank. The median clinical follow-up was 5 years. The trigeminal pain improved or disappeared in 5 patients, and of these, 4 cases stopped their medication and one decreased it. The hemifacial spasm resolved in 2 patients who were able to stop their medication. Facial palsy developed in 1 patient and improved with conservative treatment. Transient diplopia was also reported in 2 cases. Gamma knife radiosurgery provides good clinical control for cerebellopontine angle epidermoid tumors.

Neurocognitive status in patients with newly-diagnosed brain tumors in good neurological condition: The impact of tumor type, volume, and location.

PubMed

Hendrix, Philipp; Hans, Elisa; Griessenauer, Christoph J; Simgen, Andreas; Oertel, Joachim; Karbach, Julia

2017-05-01

Neurocognitive function is of great importance in patients with brain tumors. Even patients in good neurological condition may suffer from neurocognitive dysfunction that affects their daily living. The purpose of the present study was to identify risk factors for neurocognitive dysfunction in patients suffering from common supratentorial brain tumors with minor neurological deficits. A prospective study evaluating neurocognitive dysfunction in patients with a newly-diagnosed brain tumor in good neurological condition was performed at a major German academic institution. Patients underwent extensive neurocognitive testing assessing perceptual speed, executive function, visual-spatial and verbal working memory, short- and long-term memory, verbal fluency, fluid intelligence, anxiety, and depression. For each patient, a healthy control was pair-matched based on age, sex, handedness, and profession. A total of 46 patients and 46 healthy controls underwent neurocognitive testing. Patients suffered from glioblastoma multiforme (10), cerebral metastasis (10), pituitary adenoma (13), or meningioma (13). There was neither any difference in age, educational level, fluid intelligence, neurological deficits, and anxiety nor in any depression scores between tumor subgroups. Overall, neurocognitive performance was significantly worse in patients compared to healthy controls. Larger tumor volume, frontal location, and left/dominant hemisphere were associated with worse executive functioning and verbal fluency. Additionally, larger tumors and left/dominant location correlated with impairments on perceptual speed tasks. Frontal tumor location was related to worse performance in visual-spatial and short- and long-term memory. Tumor type, clinical presentation, and patient self-awareness were not associated with specific neurocognitive impairments. Patients suffering from newly-diagnosed brain tumors presenting in good neurological condition display neurocognitive impairments in

Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy

PubMed Central

Marangon, Iris; Silva, Amanda A. K.; Guilbert, Thomas; Kolosnjaj-Tabi, Jelena; Marchiol, Carmen; Natkhunarajah, Sharuja; Chamming's, Foucault; Ménard-Moyon, Cécilia; Bianco, Alberto; Gennisson, Jean-Luc; Renault, Gilles; Gazeau, Florence

2017-01-01

Tumor stiffening, stemming from aberrant production and organization of extracellular matrix (ECM), has been considered a predictive marker of tumor malignancy, non-invasively assessed by ultrasound shear wave elastography (SWE). Being more than a passive marker, tumor stiffening restricts the delivery of diagnostic and therapeutic agents to the tumor and per se could modulate cellular mechano-signaling, tissue inflammation and tumor progression. Current strategies to modify the tumor extracellular matrix are based on ECM-targeting chemical agents but also showed deleterious systemic effects. On-demand excitable nanomaterials have shown their ability to perturb the tumor microenvironment in a spatiotemporal-controlled manner and synergistically with chemotherapy. Here, we investigated the evolution of tumor stiffness as well as tumor integrity and progression, under the effect of mild hyperthermia and thermal ablation generated by light-exposed multi-walled carbon nanotubes (MWCNTs) in an epidermoid carcinoma mouse xenograft. SWE was used for real-time mapping of the tumor stiffness, both during the two near infrared irradiation sessions and over the days after the treatment. We observed a transient and reversible stiffening of the tumor tissue during laser irradiation, which was lowered at the second session of mild hyperthermia or photoablation. In contrast, over the days following photothermal treatment, the treated tumors exhibited a significant softening together with volume reduction, whereas non-treated growing tumors showed an increase of tumor rigidity. The organization of the collagen matrix and the distribution of CNTs revealed a spatio-temporal correlation between the presence of nanoheaters and the damages on collagen and cells. This study highlights nanohyperthermia as a promising adjuvant strategy to reverse tumor stiffening and normalize the mechanical tumor environment. PMID:28042338

Administration of 6-gingerol greatly enhances the number of tumor-infiltrating lymphocytes in murine tumors.

PubMed

Ju, Seong-A; Park, Sang-Min; Lee, Yea-Sol; Bae, Jun-Hyeong; Yu, Rina; An, Won G; Suh, Jae-Hee; Kim, Byung-Sam

2012-06-01

Tumor-infiltrating lymphocytes (TILs) play critical roles in host antitumor immune responses. It is known that cancer patients with tumor-reactive lymphocyte infiltration in their tumors have better prognoses, while patients with tumors infiltrated by immunosuppressive cells have worse prognoses. We found that administration of 6-gingerol, which is a component of ginger, inhibited tumor growth in several types of murine tumors, such as B16F1 melanomas, Renca renal cell carcinomas and CT26 colon carcinomas, which were established by inoculating tumor cells on the flanks of mice. However, administration of 6-gingerol did not lead to complete eradication of the tumors. 6-Gingerol treatment of tumor-bearing mice caused massive infiltration of CD4 and CD8 T-cells and B220(+) B-cells, but reduced the number of CD4(+) Foxp3(+) regulatory T-cells. The CD8 tumor-infiltrating T lymphocytes in 6-gingerol-treated mice strongly expressed IFN-γ, a marker of activation of cytotoxic T lymphocytes (CTL) CD107a and chemokine receptors that are expressed on T(H) 1 cells, such as CXCR3 and CCR5. To test whether 6-gingerol could promote infiltration of tumor antigen-specific CD8 T-cells into tumors, we adoptively transferred CFSE-labeled OT-1 CD8 T-cells into EG7 tumor-bearing mice. We found that CD8 T cells isolated from 6-gingerol pretreated OT-1 mice, but not from control OT-1 mice, massively infiltrated tumors and tumor draining lymph nodes and divided several times. Our results strongly suggest that 6-gingerol can be used in tumor immunotherapy to increase the number of TILs. Copyright © 2011 UICC.

RITA--Registry of Industrial Toxicology Animal data: the application of historical control data for Leydig cell tumors in rats.

PubMed

Nolte, Thomas; Rittinghausen, Susanne; Kellner, Rupert; Karbe, Eberhard; Kittel, Birgit; Rinke, Matthias; Deschl, Ulrich

2011-11-01

Historical data for Leydig cell tumors from untreated or vehicle treated rats from carcinogenicity studies collected in the RITA database are presented. Examples are given for analyses of these data for dependency on variables considered to be of possible influence on the spontaneous incidence of Leydig cell tumors. In the 7453 male rats available for analysis, only one case of a Leydig cell carcinoma was identified. The incidence of Leydig cell adenomas differed markedly between strains. High incidences of close to 100% have been found in F344 rats, while the mean incidence was 4.2% in Sprague-Dawley rats and 13.7% in Wistar rats. Incidences in Wistar rats were highly variable, primarily caused by different sources of animals. Mean incidences per breeder varied from 2.8 to 39.9%. Analyses for the dependency on further parameters have been performed in Wistar rats. In breeders G and I, the Leydig cell tumor incidence decreased over the observation period and with increasing mean terminal body weight. The incidence of Leydig cell tumors increased with mean age at necropsy and was higher in studies with dietary admixture compared to gavage studies. These parameters had no effect on Leydig cell tumor incidence in breeders A and B. Animals from almost all breeders had a considerably higher mean age at necropsy when bearing a Leydig cell adenoma than animals without a Leydig cell adenoma. Studies with longitudinal trimming of the testes had a higher incidence than studies with transverse trimming. The observed dependencies and breeder differences are discussed and explanations are given. Consequences for the use of historical control data are outlined. With the retrospective analyses presented here we were able to confirm the published features of Leydig cell adenomas and carcinomas. This indicates that the RITA database is a valuable tool for analyses of tumors for their biological features. Furthermore, it demonstrates that the RITA database is highly beneficial for

Brachytherapy Using Elastin-Like Polypeptides with (131)I Inhibit Tumor Growth in Rabbits with VX2 Liver Tumor.

PubMed

Liu, Xinpei; Shen, Yiming; Zhang, Xuqian; Lin, Rui; Jia, Qiang; Chang, Yixiang; Liu, Wenge; Liu, Wentian

2016-10-01

Brachytherapy is a targeted type of radiotherapy utilized in the treatment of cancers. Elastin-like polypeptides are a unique class of genetically engineered peptide polymers that have several attractive properties for brachytherapy. To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides with (131)I so as to provide reliable experimental evidence for a new promising treatment of liver cancer. Elastin-like polypeptide as carrier was labeled with (131)I using the iodogen method. Ten eligible rabbits with VX2 liver tumor were randomly divided into the treatment group (n = 5) and control group (n = 5). The treatment group received brachytherapy using elastin-like polypeptide with (131)I, and in the control group, elastin-like polypeptide was injected into the VX2 liver tumor as a control. Periodic biochemical and imaging surveillances were required to assess treatment efficacy. The stability of elastin-like polypeptide with (131)I in vitro was maintained at over 96.8 % for 96 h. Biochemistry and imaging indicated brachytherapy using elastin-like polypeptide with (131)I for liver tumor can improve liver function and inhibit tumor growth (P < 0.05). Elastin-like polypeptide can be an ideal carrier of (131)I and have high labeling efficiency, radiochemical purity and stability. Brachytherapy using elastin-like polypeptide with (131)I for liver tumor is a useful therapy that possesses high antitumor efficacy advantages.

The tumor microenvironment: An irreplaceable element of tumor budding and epithelial-mesenchymal transition-mediated cancer metastasis

PubMed Central

Li, Hui; Xu, Fangying; Li, Si; Zhong, Anjing; Meng, Xianwen; Lai, Maode

2016-01-01

ABSTRACT Tumor budding occurs at the invasive front of cancer; the tumor cells involved have metastatic and stemness features, indicating a poor prognosis. Tumor budding is partly responsible for cancer metastasis, and its initiation is based on the epithelial-mesenchymal transition (EMT) process. The EMT process involves the conversion of epithelial cells into migratory and invasive cells, and is a profound event in tumorigenesis. The EMT, associated with the formation of cancer stem cells (CSCs) and resistance to therapy, results from a combination of gene mutation, epigenetic regulation, and microenvironmental control. Tumor budding can be taken to represent the EMT in vivo. The EMT process is under the influence of the tumor microenvironment as well as tumor cells themselves. Here, we demonstrate that the tumor microenvironment dominates EMT development and impacts cancer metastasis, as well as promotes CSC formation and mediates drug resistance. In this review, we mainly discuss components of the microenvironment, such as the extracellular matrix (ECM), inflammatory cytokines, metabolic products, and hypoxia, that are involved in and impact on the acquisition of tumor-cell motility and dissemination, the EMT, metastatic tumor-cell formation, tumor budding and CSCs, and cancer metastasis, including subsequent chemo-resistance. From our point of view, the tumor microenvironment now constitutes a promising target for cancer therapy. PMID:26743180

Household Pesticides and the Risk of Wilms Tumor

PubMed Central

Cooney, Maureen A.; Daniels, Julie L.; Ross, Julie A.; Breslow, Norman E.; Pollock, Brad H.; Olshan, Andrew F.

2007-01-01

Background Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor. Objectives In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case–control study. Methods The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child’s age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used. Results A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0–1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null. Conclusions This study is the largest case–control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood. PMID:17366833

Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

PubMed

Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

2013-02-01

The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

An implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release.

PubMed

Sasikala, Arathyram Ramachandra Kurup; Unnithan, Afeesh Rajan; Yun, Yeo-Heung; Park, Chan Hee; Kim, Cheol Sang

2016-02-01

The study describes the design and synthesis of an implantable smart magnetic nanofiber device for endoscopic hyperthermia treatment and tumor-triggered controlled drug release. This device is achieved using a two-component smart nanofiber matrix from monodisperse iron oxide nanoparticles (IONPs) as well as bortezomib (BTZ), a chemotherapeutic drug. The IONP-incorporated nanofiber matrix was developed by electrospinning a biocompatible and bioresorbable polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by exploiting mussel-inspired surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the borate-containing BTZ anticancer drug through a catechol metal binding in a pH-sensitive manner. Thus, an implantable smart magnetic nanofiber device can be exploited to both apply hyperthermia with an alternating magnetic field (AMF) and to achieve cancer cell-specific drug release to enable synergistic cancer therapy. These results confirm that the BTZ-loaded mussel-inspired magnetic nanofiber matrix (BTZ-MMNF) is highly beneficial not only due to the higher therapeutic efficacy and low toxicity towards normal cells but also, as a result of the availability of magnetic nanoparticles for repeated hyperthermia application and tumor-triggered controlled drug release. The current work report on the design and development of a smart nanoplatform responsive to a magnetic field to administer both hyperthermia and pH-dependent anticancer drug release for the synergistic anticancer treatment. The iron oxide nanoparticles (IONPs) incorporated nanofiber matrix was developed by electrospinning a biocompatible polymer, poly (d,l-lactide-co-glycolide) (PLGA), and tumor-triggered anticancer drug delivery is realized by surface functionalization using 2-(3,4-dihydroxyphenyl)ethylamine (dopamine) to conjugate the boratecontaining anticancer drug bortezomib through a catechol metal binding in a p

Cognitive function in children with brain tumors in the first year after diagnosis compared to healthy matched controls.

PubMed

Shortman, Robert I; Lowis, Stephen P; Penn, Anthony; McCarter, Renee J; Hunt, Linda P; Brown, Caroline C; Stevens, Michael C G; Curran, Andrew L; Sharples, Peta M

2014-03-01

Improved survival of children with brain tumors (BTs) has increased focus on ameliorating morbidity. To reduce the risk of progressive cognitive decline, remedial strategies need to be instituted early, based upon accurate appraisal of need, yet few studies have investigated cognition in BT children early post-diagnosis. The study aims were to investigate cognition in children with primary BTs 1, 6, and 12 months post-diagnosis compared with healthy children, exploring the impact of disease and treatment variables. Forty-eight children aged 2-16 years with primary BTs, referred to a Regional Neurosurgical Unit over the 2-year study period were eligible for enrollment. The "best friends" model was used to recruit matched controls. Cognition was assessed using age-appropriate Wechsler Intelligence scales; Children's Memory Scale; Test of Everyday Attention for Children, and Wechsler Quicktest. Patients with BTs had significantly reduced performance compared to controls early post-diagnosis in tests of Performance IQ, processing speed, verbal and visual memory, and selective attention. Improved performance over 12 months was seen in patients with BTs although also, for some measures, in controls. Significant deficits in cognitive performance were seen one year post-diagnosis for Verbal IQ; processing speed, visual and verbal immediate memory, and selective attention. Infratentorial site, high tumor grade, hydrocephalus, radiotherapy, and chemotherapy were associated with poorer functioning. Early cognitive impairment is present in BT children, sometimes prior to radiotherapy/chemotherapy treatment, and is associated with hydrocephalus, high tumor grade and infratentorial site. Future studies should investigate the role of early rehabilitation in improving cognition. © 2013 Wiley Periodicals, Inc.

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PubMed

Eisbruch, A; Dawson, L A; Kim, H M; Bradford, C R; Terrell, J E; Chepeha, D B; Teknos, T N; Anzai, Y; Marsh, L H; Martel, M K; Ten Haken, R K; Wolf, G T; Ship, J A

1999-01-01

To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Cellular phone use and brain tumor: a meta-analysis.

PubMed

Kan, Peter; Simonsen, Sara E; Lyon, Joseph L; Kestle, John R W

2008-01-01

The dramatic increase in the use of cellular phones has generated concerns about potential adverse effects, especially the development of brain tumors. We conducted a meta-analysis to examine the effect of cellular phone use on the risk of brain tumor development. We searched the literature using MEDLINE to locate case-control studies on cellular phone use and brain tumors. Odds ratios (ORs) for overall effect and stratified ORs associated with specific brain tumors, long-term use, and analog/digital phones were calculated for each study using its original data. A pooled estimator of each OR was then calculated using a random-effects model. Nine case-control studies containing 5,259 cases of primary brain tumors and 12,074 controls were included. All studies reported ORs according to brain tumor subtypes, and five provided ORs on patients with > or =10 years of follow up. Pooled analysis showed an overall OR of 0.90 (95% confidence interval [CI] 0.81-0.99) for cellular phone use and brain tumor development. The pooled OR for long-term users of > or =10 years (5 studies) was 1.25 (95% CI 1.01-1.54). No increased risk was observed in analog or digital cellular phone users. We found no overall increased risk of brain tumors among cellular phone users. The potential elevated risk of brain tumors after long-term cellular phone use awaits confirmation by future studies.

NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

PubMed Central

Huergo-Zapico, Leticia; Parodi, Monica; Pedrazzi, Marco; Mingari, Maria Cristina; Sparatore, Bianca; Gonzalez, Segundo; Olive, Daniel; Bottino, Cristina

2016-01-01

Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue. PMID:27294158

Nitric oxide regulates tumor cell cross-talk with stromal cells in the tumor microenvironment of the liver.

PubMed

Decker, Ningling Kang; Abdelmoneim, Soha S; Yaqoob, Usman; Hendrickson, Helen; Hormes, Joe; Bentley, Mike; Pitot, Henry; Urrutia, Raul; Gores, Greg J; Shah, Vijay H

2008-10-01

Tumor progression is regulated through paracrine interactions between tumor cells and stromal cells in the microenvironment, including endothelial cells and myofibroblasts. Nitric oxide (NO) is a key molecule in the regulation of tumor-microenvironment interactions, although its precise role is incompletely defined. By using complementary in vitro and in vivo approaches, we studied the effect of endothelial NO synthase (eNOS)-derived NO on liver tumor growth and metastasis in relation to adjacent stromal myofibroblasts and matrix because liver tumors maintain a rich, vascular stromal network enriched with phenotypically heterogeneous myofibroblasts. Mice with an eNOS deficiency developed liver tumors more frequently in response to carcinogens compared with control animals. In a surgical model of pancreatic cancer liver metastasis, eNOS overexpression in the tumor microenvironment attenuated both the number and size of tumor implants. NO promoted anoikis of tumor cells in vitro and limited their invasive capacity. Because tumor cell anoikis and invasion are both regulated by myofibroblast-derived matrix, we explored the effect of NO on tumor cell protease expression. Both microarray and Western blot analysis revealed eNOS-dependent down-regulation of the matrix protease cathepsin B within tumor cells, and silencing of cathepsin B attenuated tumor cell invasive capacity in a similar manner to that observed with eNOS overexpression. Thus, a NO gradient within the tumor microenvironment influences tumor progression through orchestrated molecular interactions between tumor cells and stroma.