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Efficacy of a traditional Persian medicine preparation for radiation-induced xerostomia:a randomized,open-label,active-controlled trial

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Journal of Integrative Medicine 2017年第3期15卷 201-208页

作者： Ghazaleh Heydarirad Hossein Rezaeizadeh Rasool Choopani Seyed Hamdollah Mosavat Ahmad Ameri Department of Traditional Medicine School of Traditional Medicine Shahid Beheshti University of Medical Sciences Tehran 15167-45811 Iran Department of Traditional Medicine School of Traditional Medicine Tehran University of Medical Science Tehran 16687-53961 Iran Research Center for Traditional Medicine and History of Medicine Shiraz University of Medical SciencesShiraz 71356-44144 Iran Essence of Parsiyan Wisdom Institute Traditional Medicine and Medicinal Plant Incubator Shiraz University of Medical Sciences Shiraz 71356-44144 Iran Department of Radiation Oncology Imam Hossein Hospital Shahid Beheshti University of Medical SciencesTehran 19946-15611 Iran

BACKGROUND： xerostomia is one of the most common side effects of radiation therapy among patients with head and neck cancers （HNC）. However, conventional medicine lacks an effective treatment for radiation-induced xerostomia. OBJECTIVE： Synthesizing the traditional use ofAIcea digitata and Malva sylvestris with their known beneficial effects from recent studies, we evaluated the efficacy of the herbs in the quality of life （QOL） of HNC patients with radiation-induced xerostomia. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： This study is a randomized, double-arm, open-label active-controlled clinical trial. We evaluated the effect ofA. digitata and M. sy/vestris on QOL of HNC patients with radiation-induced xerostomia compared with Hypozalix （artificial saliva）. Patients were enrolled from the Imam Hossein Hospital＇s oncology clinic in Shahid Beheshti University of Medica Sciences. Tehran, Iran. MAIN OUTCOME MEASURES： Primary outcome measures in this trial were changes in patients＇ QOL assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Module （EORTC QLQ-H＆N 35）. RESULTS： Between-group analysis showed that the intervention group patients obtained significantly lower （better） total EORTC QLQ-H＆N 35 scores as compared to the control group at the end of the intervention period （P = 0.007）. Mean scores of dry mouth of EORTC QLQ-H＆N 35 was also significantly lower （better） in the intervention group as compared to the control group （P = 0.017）.

关键词： xerostomia medicine Persian traditional hollyhocks common mallow cancer

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Long-term outcomes of interventions for radiation-induced xerostomia:A review

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World Journal of Clinical Oncology 2019年第1期10卷 1-13页

作者： Sung Jun Ma Charlotte I Rivers Lucas M Serra Anurag K Singh University at Buffalo The State University of New York Jacobs School of Medicine and Biomedical Sciences Department of Radiation Medicine Roswell Park Comprehensive Cancer Center

xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen,submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine(three); cevimeline(one); amifostine(eleven);submandibular gland transfer(five); acupuncture like transcutaneous electrical nerve stimulation(ALTENS)(one); hyperbaric oxygen(one); and acupuncture(one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical.The use of intensity-modulated radiation therapy, in addition to dose deescalation in select patients, may result in fewer patients with late xerostomia,reducing the need for additional interventions.

关键词： xerostomia Radiation therapy Radiotherapy Head and neck cancer Quality of life

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Bone marrow-derived mesenchymal stem cells migrate to healthy and damaged salivary glands following stem cell infusion

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International Journal of Oral Science 2014年第3期6卷 154-161页

作者： Silke Schwarz Ralf Huss Michaela Schulz-Siegmund Breda Vogel Sven Brandau Stephan Lang Nicole Rotter Department of Otorhinolaryngology Ulm University Medical Center Apceth Munich Germany Institute of Pharmaceutical Technology University of Leipzig Department of Otorhinolaryngology University of Duisburg–Essen

xerostomia is a severe side effect of radiation therapy in head and neck cancer patients. To date, no satisfactory treatment option has been established. Because mesenchymal stem cells（MSCs） have been identified as a potential treatment modality, we aimed to evaluate stem cell distribution following intravenous and intraglandular injections using a surgical model of salivary gland damage and to analyse the effects of MSC injections on the recruitment of immune cells. The submandibular gland ducts of rats were surgically ligated. Syngeneic adult MSCs were isolated, immortalised by simian virus 40（SV40） large T antigen and characterized by flow cytometry. MSCs were injected intravenously and intraglandularly. After 1, 3 and 7 days, the organs of interest were analysed for stem cell recruitment. Inflammation was analysed by immunohistochemical staining. We were able to demonstrate that, after intravenous injection, MSCs were recruited to normal and damaged submandibular glands on days 1, 3 and 7. Unexpectedly, stem cells were recruited to ligated and non-ligated glands in a comparable manner. After intraglandular injection of MSCs into ligated glands, the presence of MSCs, leucocytes and macrophages was enhanced, compared to intravenous injection of stem cells. Our data suggest that injected MSCs were retained within the inflamed glands, could become activated and subsequently recruited leucocytes to the sites of tissue damage.

关键词： duct ligation mesenchymal stem cells submandibular gland injury xerostomia

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Stem cell treatments for oropharyngeal dysphagia:Rationale,benefits,and challenges

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World Journal of Stem Cells 2020年第9期12卷 1001-1012页

作者： Eric K Tran Kevin O Juarez Jennifer L Long David Geffen School of Medicine University of California-Los AngelesLos AngelesCA 90095United States Department of Otolaryngology Yale School of MedicineNew HavenCT 06511United States Department of Head and Neck Surgery David Geffen School of MedicineUniversity of California-Los AngelesLos AngelesCA 90095United States Greater Los Angeles VA Healthcare System Los AngelesCA 90073United States

Dysphagia,defined as difficulty swallowing,is a common symptom negatively impacting millions of adults annually.Estimated prevalence ranges from 14 to 33 percent in those over age 65 to over 70 percent in a nursing home setting.The elderly,those with neurodegenerative diseases,head and neck cancer patients,and those with autoimmune conditions such as Sjögren's syndrome are disproportionately affected.Oropharyngeal dysphagia refers specifically to difficulty in initiating a swallow due to dysfunction at or above the upper esophageal sphincter,and represents a large proportion of dysphagia cases.Current treatments are limited and are often ineffective.Stem cell therapy is a new and novel advancement that may fill a much-needed role in our treatment regimen.Here,we review the current literature regarding stem cell treatments for oropharyngeal dysphagia.Topics discussed include tissue regeneration advancements as a whole and translation of these principles into research surrounding tongue dysfunction,xerostomia,cricopharyngeal dysfunction,and finally an overview of the challenges and future directions for investigation.Although this field of study remains in its early stages,initial promising results show potential for the use of stem cell-based therapies to treat oropharyngeal dysphagia and warrant further research.

关键词： Dysphagia xerostomia Hemiglossectomy Stem cells Myoblasts Mesenchymal stem cells

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Evaluation of xerostomia closely associated with systemic diseases using a dental approach

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Open Journal of Stomatology 2012年第4期2卷 269-276页

作者： Hiroshi Mori Noriyuki Hoshi Motoe Taniguchi Masako Banka Katsuhiko Kimoto Division of Fixed Prosthodontics Department of Oral and Maxillofacial Rehabilitation Kanagawa Dental College Yokosuka Japan Maxillofacial Diagnostic Science Department of Oral Diagnosis Kanagawa Dental College Yokosuka Japan

Based on the findings of epidemiological surveys in western countries, the number of person with suspected xerostomia in Japan is estimated to be 30,000,000. xerostomia is caused by: 1) Systemic diseases;2) Medications;3) Tumors or trauma;4) Radiotherapy;and 5) Neurological factors. Its symptoms can be alleviated, and its progression can be stopped by close cooperation between the dental and medical departments. However, at present, symptomatic treatment methods such as water drinking, oral rinsing with water, and administration of Kampo medicines or parasymptomimetic drugs are mainly used, and a standard treatment has not been established. On the other hand, previous studies on xerostomia have reported improvement in dry mouth symptoms using dental approaches or a relationship between the development of candidiasis and the salivary flow rate. Therefore, in this study, to establish a dental method useful for improving xerostomia associated with systemic diseases and medications for them, we restored occlusal function, and as a result, increased the salivary flow rate, and evaluated changes in oral findings.

关键词： xerostomia Saliva Prosthetic Treatment

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Oral manifestations in patients with diabetes mellitus

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World Journal of Diabetes 2019年第9期10卷 485-489页

作者： Bita Rohani Department of Oral Medicine Faculty of Dentistry Aja University of Medical Sciences

The purpose of this article was to increase the knowledge about oral manifestations and complications associated with diabetes mellitus.An overview was performed on Google,especially in recent reliable papers in relation to diabetes mellitus and its oral manifestations(keywords were“diabetes mellitus”,“oral manifestations”,and“oral complications”).Data were collected and the results were declared.Diabetes mellitus is one of the most common chronic disorders characterized by hyperglycemia.This disease can have many complications in various regions of the body,including the oral cavity.The important oral manifestations and complications related to diabetes include xerostomia,dental caries,gingivitis,periodontal disease,increased tendency to oral infections,burning mouth,taste disturbance,and poor wound healing.Oral complications in diabetic patients are considered major complications and can affect patients’quality of life.There is evidence that chronic oral complications in these patients have negative effects on blood glucose control,so prevention and management of the oral complications are important.

关键词： Diabetes mellitus Oral complications Oral manifestations Periodontal disease xerostomia

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Influence of the Radiation Dose to Salivary Glands on xerostomia in Patients with Head and Neck Carcinomas

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Journal of Cancer Therapy 2013年第1期4卷 188-194页

作者： Andre Buchali Christina Schroder Dietrich Sidow Eyck Blank Department of Radiation Oncology Ruppiner Kliniken GmbHNeuruppinGermany.

Purpose: Investigation of the influence of radiation dose to salivary glands on xerostomia in patients with head and neck cancers. Methods: From October 2002 to December 2011, 548 patients with head and neck carcinomas were treated in our department using intensity modulated radiotherapy (IMRT). 325 patients were eligible for analysis more than 1 year after irradiation. xerostomia was evaluated according to the criteria of Radiation Therapy and Oncology Group (RTOG) and xerostomia related questionnaire. For statistical analysis grade 1 and 2 were recorded as mild and grade 3 and 4 as severe xerostomia. The dosimetric values for absolute mean dose, biological equivalent mean dose (EQD2), the relative organ volume not exceeding 20 Gy, 25 Gy and 30 Gy (V20, V25, V30) for all 4 major salivary glands or for both parotid glands only were used for analysis. V20 revealed the best discrimination between both patient groups (with vs. without xerostomia), compared to parameters V25 and V30. Therefore the volume of the salivary glands receiving less than 20 Gy (V 20Gy) was analyzed additionally. Mann-Whitney-U-test, Kruskal-Wallis-test and logistic regression were used in statistical analysis. Results: A TD 50 can be determined for the occurrence of xerostomia more than one year after radiotherapy for both parotid glands of 19.3 Gy for the mean dose absolute, 11.2 Gy for the mean dose EQD2, 38.2% for V20, 26.8% for V25, 18.7% for V30, 34.9 ml for V 20Gy. For all major salivary glands theses values were 25.7 Gy for the mean dose absolute, 15.6 Gy for the mean dose EQD2, 51.3% for V20, 41.1% for V25, 33.9% for V30 and 34.8 ml for V 20Gy. Conclusions: The identification of a tolerance dose for the salivary glands for treatment planning appears to be difficult, as the dose-response correlation only shows a flat slope. Additionally, a large interindividual variability seems to exist. We could not found any threshold dose for development of xerostomia.

关键词： xerostomia Salivary Glands Tolerance Dose Irradiation

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Evaluation of xerostomia in Patients with Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy

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Journal of Cancer Therapy 2020年第2期11卷 98-114页

作者： Aya Hossam Mansy Al Siagy Ali Abd Fatma Gharib Khair-Allah Lamiss Mohamed Abd El-Aziz Department of Clinical Oncology and Nuclear Medicine Faculty of Medicine Tanta University Tanta Egypt Department of Diagnostic Radiology Faculty of Medicine Tanta University Tanta Egypt

Background: The sixth most prevalent cancer in the world is head and neck squamous cell carcinoma (HNSCC). In multiple combinations, surgery, radiation and chemotherapy are used in HNC control. As radiation-induced salivary gland damage and xerostomia is one of the most usual and distressing impacts,?diffusion-weighted magnetic resonance imaging (DW-MRI) is a promising technique for the assessment of alterations due to radiation therapy.?The aim of the study is?to evaluate the effect of Chemoradiotherapy either concurrent or sequential/RTH on salivary glands using DW-MRI performed before and after chemoradiotherapy/RTH,?correlation between DW-MRI changes?and delivered radiation dose to salivary glands,?study the acute toxicity of chemoradiotherapy/RTH on salivary glands and assess quality of life for patients with radiation-induced xerostomia.?Patients and Methods: This prospective study included 43 patients with Head and Neck squamous cell carcinoma treated with definitive radiotherapy, sequential therapy or concurrent chemoradiotherapy at Clinical Oncology and Nuclear Medicine Department, MRI diffusion scans were done at Diagnostic Radiology Department Tanta University Hospitals throughout the period from May 2016 to May 2019.?DW-MRI performed before and after RTH. For patients receiving CCRTH, DW sequence will be performed before starting RTH and 2?-?3 months post-RTH once at rest and then repeated continuously during salivary stimulation by ascorbic acid. In case of induction chemotherapy, DW-MRI was done before and after induction and 2?-?3 months post-RTH.?Results:?In all time periods, ADC values were lower for the PG than the SMG.?ADC change of PGs was higher in hypopharyngeal carcinoma, while ADC change of SMGs?were?higher in oropharyngeal carcinoma.?ADC change in PGs & SMGs was higher in advanced stage.?Conclusion:?To assess the radiation-induced xerostomia, DW-MRI can be used as non-invasive tool. xerostomia questionnaire is helpful instrument for evaluating of quality of life for patients with radiatio

关键词： xerostomia Diffusion-Weighted MRI Radiotherapy Toxicity

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Mechanism involved in Danshen-induced fluid secretion in salivary glands

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World Journal of Gastroenterology 2015年第5期21卷 1444-1456页

作者： Fei Wei Mu-Xin Wei Masataka Murakami Division of Physiological Sciences School of Life ScienceGraduate University for Advanced StudiesOkazaki 444-8585Japan Department of Traditional Chinese Medicine The first Affiliated Hospital with Nanjing Medical University Division of Cellular Physiology National Institute for Physiological SciencesNational Institutes of Natural SciencesOkazaki 444-8787Japan

AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or p

关键词： Salivary fluid secretion xerostomia Chinese herb D

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Clinical factors influencing the resting and stimulated salivary flow

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Open Journal of Stomatology 2012年第2期2卷 103-109页

作者： Shigeo Yamachika Ken Yamamoto Yoshiaki Nomura Hiroyuki Yamada Ichiro Saito Yoichi Nakagawa Department of Clinical Pathophysiology School of Dental MedicineTsurumi UniversityYokohamaJapan Department of Oral Medicine and Stomatology School of Dental MedicineTsurumi UniversityYokohamaJapan Department of Geriatric Dentistry School of Dental MedicineTsurumi UniversityYokohamaJapan Department of Translational Research School of Dental MedicineTsurumi UniversityYokohamaJapan Department of Oral and Maxillofacial Surgery School of Dental MedicineTsurumi UniversityYokohamaJapan Department of Pathology School of Dental MedicineTsurumi UniversityYokohamaJapan

Objective: The objective of this study was to examine the clinical and immunological factors influ encing sialometry in xerostomia patients. Method: The association between sialometry and other clinical examinations were investigated in a cross-sectional study. A total of 179 dry mouth patients showing hyposalivation who underwent a clinical examination were enrolled in this study. Multiple regression analyses were employed to examine the relative con-tributions of clinical and immunological factors including age, gender, parotid sialography, labial Salivary gland biopsy, anti-Ro/SS-A antibodies, and anti-La/SS-B antibodies to the resting (RSF) or stimulated saliva flow rate (SSF). Results: An increase of the stage of sialography, the grade of a labial biopsy, and the presence of anti-La/SS-B antibody had a significant correlation with a decrease of sialometry. Results of the multiple regression analysis showed that age (standardized coefficient = -0.244), grade of lip biopsy (-0.189), and anti-SS-B antibody (-0.171), were significantly associated with the RSF. The stage of sialography (?0.423) and age (-0.169) were significantly related to the sialometry in the SSF according to a multiple regression analysis. Conclusion: The results of this study suggest that the measurement of RSF reflects the immunological factors and SSF reflects the damage to the parotid gland.

关键词： xerostomia Sialometry Sialography Labial Minor Salivary Gland Biopsy Sjogren’s Syndrome

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