A comparative study of two single-stage oral mucosal substitution urethroplasty(Kulkarni and Asopa)in the surgical treatments of lichen sclerosus urethral strictures

Long-segment lichen sclerosus(LS)urethral stricture is a challenge for urologists.Limited data are available for surgeons to make a surgical decision between Kulkarni and Asopa urethroplasty.In this retrospective study,we investigated the outcomes of these two procedures in patients with LS urethral stricture.Between January 2015 and December 2020,77 patients with LS urethral stricture underwent Kulkarni and Asopa procedures for urethroplasty in the Department of Urology,Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine(Shanghai,China).Of the 77 patients,42(54.5%)underwent the Asopa procedure and 35(45.5%)underwent the Kulkarni procedure.The overall complication rate was 34.2%in the Kulkarni group and 19.0%in the Asopa group,and no difference was observed(P=0.105).Among the complications,no statistical difference was observed in the incidence of urethral stricture recurrence(P=0.724)or glans dehiscence(P=0.246)except for postoperative meatus stenosis(P=0.020).However,the recurrence-free survival rate between the two procedures was significantly different(P=0.016).Cox survival analysis showed that antiplatelet/anticoagulant therapy use(P=0.020),diabetes(P=0.003),current/former smoking(P=0.019),coronary heart disease(P<0.001),and stricture length(P=0.028)may lead to a higher hazard ratio of complications.Even so,these two techniques can still provide acceptable results with their own advantages in the surgical treatment of LS urethral strictures.The surgical alternative should be considered comprehensively according to the patient characteristics and surgeon preferences.Moreover,our results showed that antiplatelet/anticoagulant therapy use,diabetes,coronary heart disease,current/former smoking,and stricture length may be contributing factors of complications.Therefore,patients with LS are advised to undergo early interventions for better therapeutic effects.

Palliative oral care in terminal cancer patients:Integrated review

BACKGROUND Palliative care(PC)aims to improve quality of life in patients and its families against life threatening diseases,through suffering’s prevention and relief.It is the duty of the dental surgeon to possess the knowledge needed to treat a patient with little life span,in order to establish an adequate treatment plan for each situation.AIM To synthesize the published evidence on oral conditions,impact,management and challenges in managing oral conditions among palliative patients.METHODS Articles were selected from PubMed and Scopus electronic platforms,using a research strategy with diverse descriptors related to“palliative care”,“cancer”and“oral health”.The article’s selection was done in two phases.The first one was performed by the main researcher through the reading of the abstracts.In the second phase two researchers selected eligible articles after reading in full those previous selected.Data was tabulated and analyzed,obtaining information about what is found in literature related to this subject and what is necessary to be approached in future researches about PC.RESULTS As results,the total of 15 articles were eligible,being one a qualitative analysis,13(92.8%)clinical trials and one observational study.Of the 15 articles,8(53.4%)involved questionnaires,while the rest involved:one systematic review about oral care in a hospital environment,2 oral exams and oral sample collection,one investigation of terminal patient’s(TP)oral assessment records,2 collection of oral samples and their respective analysis and one treatment of the observed oral complications.CONCLUSION It can be concluded that the oral manifestations in oncologic patients in terminal stage are,oral candidiasis,dry mouth,dysphagia,dysgeusia,oral mucositis and orofacial pain.Determining a protocol for the care of these and other complications of cancer–or cancer therapy–based on scientific evidence with the latest cutting-edge research results is of fundamental importance for the multidisciplinary team that works in the care of patients in PC.To prevent complications and its needed to initial the dentist as early as possible as a multidisciplinary member.It has been suggested palliative care protocol based on the up to date literature available for some frequent oral complications in TP with cancer.Other complications in terminal patients and their treatments still need to have further studying.

Effects of Kangfuxin Solution (康复新液) Combined with Low-level Laser on Cytokines and Immune Function in Patients with Radiation-induced Oral Mucositis

Objective:To investigate the effect of Kangfuxin Solution(康复新液)combined with low-level laser therapy(LLLT)on cytokines and immune function in patients with radiation-induced oral mucositis.Methods:There were 84 nasopharyngeal carcinoma patients with oral mucositis after intensity-modulated radiation therapy(IMRT)were randomly divided into the control group(CG)and the observation group(OG),with 42 cases in each group.The CG was given LLLT,and the OG was treated with Kangfuxin Solution in addition to LLLT for 10 consecutive days.The healing time of oral mucosa,mucositis grading,oral pain scores,cytokines(interleukin-6,interleukin-1βand tumor necrosis factor-α)and T lymphocyte subsets were compared between the 2 groups before and after treatment.Results:The healing time of oral mucosa in the OG was(6.8±1.4)d,which was significantly shorter than(8.6±1.9)d in the CG(t=4.943,P<0.01).After treatment,the grading of oral mucositis in the OG was better than that in the CG,with a statistically significant difference(Z=2.942,P<0.05).The oral pain scores of the OG was lower than that in the CG at different time points after treatment,and the difference was statistically significant(t=8.207,11.017,P<0.01).After treatment,the levels of IL-6,IL-1βand TNF-αin peripheral blood of the OG were significantly lower than those in the CG(t=5.217,2.775,4.053,P<0.01).There were statistically significant differences in CD4+,CD8+and CD4+/CD8+between the OG and the CG after treatment(t=5.692,6.093,3.658,P<0.01).Conclusion:Kangfuxin Solution combined with LLLT can significantly shorten the healing time of oral mucosal,reduce the grading of oral mucositis,relieve oral pain,reduce inflammatory response and improve the immune function of patients.

Effects of Yangyin Jiedu Decoction on Acute Oral Mucositis Caused by Radiation

[Objectives] The aim was to observe the clinical effect of Yangyin Jiedu Decoction for acute oral mucositis caused by radiotherapy for nasopharyngeal carcinoma( NPC). [Methods]Total 64 patients with non-keratinizing squamous cell carcinoma of nasopharynx were divided evenly and randomly into two groups,treatment group and control group. In the treatment group,the patients began to take Yangyin Jiedu Decoction one week before radiotherapy; while in the control group,the patients were treated with mixed solution of dexamethasone,lidocaine,recombinant human granulocyte colony stimulating factor and vitamin B12. From the beginning to the end of radiotherapy,the curative effect in the two groups was observed and compared. In addition,the levels of serum CRP,TGF-β1 and IL-6 were measured to detect the inflammatory response. [Results] The incidence of acute oral mucositis in the treatment group was significantly lower than that in the control group( P <0. 05). The effective rate was 96. 88% in the treatment group and 67. 74% in the control group. The levels of serum CRP,TGF-β1 and IL-6 in the treatment group were also lower than those in the control group. [Conclusions]Yangyin Jiedu Decoction has a good effect on prevention and treatment of acute radioactive oral mucositis and it is worthy of clinical application.

Clinical relevance of the use of Dentoxol® for oral mucositis induced by radiotherapy: A phase II clinical trial

BACKGROUND Severe oral mucositis associated with cancer therapy is a frequent complication that may affect a patient's systemic condition,resulting in interruption and/or prolongation of cancer therapy.Dentoxol®is a medical solution in the form of a mouthwash that has been shown to result in statistically significant improvement in the prevention of severe oral mucositis.However,knowing the measures of the clinical significance of this therapy is important for accurate decision-making.To describe the clinical impact of Dentoxol®use in severe oral mucositis.METHODS Clinical significance was measured using the results obtained in a randomized controlled clinical trial previously conducted by the same group of researchers.The measures of clinical significance evaluated were the absolute risk or incidence,relative risk,absolute risk reduction,relative risk reduction,number needed to treat,and odds ratio.RESULTS The data obtained show that the impact of Dentoxol®on reducing the severity of oral mucositis has important clinical relevance.CONCLUSION The results of this study justify the incorporation of Dentoxol®mouth rinse into clinical protocols as a complement to cancer therapy to prevent and/or treat oral mucositis secondary to radiotherapy.

Research progress and comparison of the establishment of animal models of radiotherapy or chemotherapy-induced oral mucositis

The mechanism of radiotherapy or chemotherapy-induced oral mucositis is not yet clear.And model establishment is needed in further study.In order to summarize the methods of model establishment and make a comparison,literature databases including Web of Science、Pubmed and CNKI were searched for related researches from January 2015 to January 2021.Hamsters,mice,rats,guinea pigs and miniature pigs were chosen to be modeling animals and modeling methods could be classified into:chemotherapy,chemotherapy combined with superficial mucosal irritation,radiotherapy,radiotherapy combined with superficial mucosal irritation and chemoradiotherapy.Advantages and disadvantages had been analyzed in this study to provide reference for following studies.

Application of the theory of“conducting fire back to its origin”in treating radiotherapy or chemotherapy induced oral mucositis

Oral mucositis is a common adverse reaction of radiotherapy and chemotherapy in cancer patients,which reduces the quality of life of patients and affects the progress of cancer treatment.Most of the patients with malignant tumor belong to the syndrome of deficiency in root case and excess in manifestation.When undergoing radiotherapy or chemotherapy,the patients’ministerial fire becomes hyperactive,which may cause oral mucositis.With the method of“conducting fire back to its origin”,ministerial fire can be led to vital gate,as well as recovering its physiological functions.In the treatment of oral mucositis,instead of attacking ministerial fire with too much heat-clearing herbs,we should,under the guidance of the theory of“conducting fire back to its origin”,differentiate the syndrome,and then we can use the methods of treatment of clearing and lowering heart fire,warmly invigorating spleen and stomach,nourishing liver and kidney,or warmly invigorating vital gate,to conduct ministerial fire back to vital gate.This article aims to provide theoretical reference for Traditional Chinese Medicine treatment of radiotherapy or chemotherapy induced oral mucositis.

Glycine supplementation reduces the severity of chemotherapy-induced oral mucositis in hamsters

Objective: Oral mucositis (OM) is a devastating toxicity associated with cytotoxic cancer therapy. The OM pathogenesis and the complex interactions occur in response to tissue insult. Application of this evolving model has aided in the development of mechanistically based therapies for the prevention and treatment of mucositis. The present study was to assess the effects of glycine supplementation on chemotherapy-induced oral mucositis. Methods: In a hamster cheek pouch model of chemotherapy-induced oral mucositis, one group of 20 animals received systemic glycine supplementation for 7 days, while another similar control group did not. Clinical mucositis severity and neutrophil infiltrate (on histology) were assessed by blinded examiners. Free radical production was measured as malondialdehyde (MDA) levels. Results: As compared to control animals, glycine-treated animals demonstrated a highly significant reduction in clinical severity of oral mucositis, neutrophil infiltrate, and MDA levels (p < 0.001 for all). Conclusions: Glycine supplementation reduces the severity of chemotherapy-induced oral mucositis in an animal model. This effect is at least partly mediated through inhibition of the inflammatory response and reduced production of damaging free radicals.

Observation on Efficacy of Lanzhou Formula (兰州方) with Bingpeng Powder (冰硼散) Mouthwash in Preventing and Treating Radiation-induced Oral Mucositis

Objective:To observe clinical efficacy of Lanzhou Formula(兰州方)with Bingpeng Powder(冰硼散)mouthwash in preventing and treating radiation-induced oral mucositis.Methods:A total of 200 patients with malignant tumors in the head and neck who received radiotherapy in our hospital from April 2018 to April 2020 were selected as research objects,and they were randomly divided into the study group and control group.The control group was given radiotherapy combined with mouthwash,which consisted of 500 mL of normal saline,125 mg of vitamin B12,400000 U of gentamicin and 1 g of lidocaine.The study group was given radiotherapy combined with Lanzhou Formula with Bingpeng Powder mouthwash.Incidences of radiation-induced oral mucositis,chewing and swallowing functions,and Karnofsky(KPS)scores were compared between the 2 groups.Results:At the end of the radiotherapy,there was no Grade 4 radiation-induced oral mucositis in the 2 groups.Compared with the control group,the radiation-induced oral mucositis in the study group basically belonged to Grade 1 and Grade 2,with a lower incidence of Grade 3(P<0.05).At the end of the radiotherapy,the chewing and swallowing functions in the 2 groups were decreased,but patients with 2-point chewing and swallowing functions in the study group were more than those in the control group,and patients with the 3-point were less than those in the control group(P<0.05).At the end of the radiotherapy,the KPS scores were decreased,but those in the study group were higher than those in the control group(P<0.05).Conclusion:During radiotherapy for patients with malignant tumors in the head and neck,Lanzhou Formula with Bingpeng Powder mouthwash can decrease the severity of radiation-induced oral mucositis,protect chewing and swallowing functions of patients to a certain extent,and improve the general condition of patients.It is worthy of clinical application and promotion.

Cell-based therapies for limbal stem cell deficiency: a literature review

Background and Objective:Limbal stem cell deficiency(LSCD)is characterized by the insufficiency of limbal stem cells to maintain the corneal epithelium.Severe cases of LSCD may be treated with limbal transplantation from healthy autologous or allogeneic limbal tissue.Multiple cell-based therapies have been studied as alternative treatments to improve success rates and minimize immunosuppressive regimens after allogeneic transplants.In this review,we describe the success rates,and complications of different cell-based therapies for LSCD.We also discuss each therapy’s relative strengths and weaknesses,their history in animal and human studies,and their effectiveness compared to traditional transplants.Methods:PubMed was searched for publications using the terms LSCD,cell-based therapy,cultivated limbal epithelial transplantation(CLET),cultivated oral mucosal epithelial transplantation(COMET),and mesenchymal stem cells from 1989 to August 2022.Inclusion criteria were English language articles.Exclusion criteria were non-English language articles.Key Content and Findings:current cell-based therapies for LSCD are CLET and non-limbal epithelial cells.Non-limbal epithelial cell methods include COMET,conjunctival epithelial autografts,and mesenchymal stem/stromal cells(MSCs).Moreover,several alternative potential sources of non-limbal cells have described,including induced pluripotent stem cells(iPSCs),human embryonic stem cells(hESCs),human dental pulp stem cells,hair follicle bulge-derived epithelial stem cells,amniotic membrane epithelial cells,and human umbilical cord lining epithelial cells.Conclusions:Cell-based therapies are a promising treatment modality for LSCD.While CLET is currently the only approved cell-based therapy and is only approved in the European Union,more novel methods have also been shown to be effective in human or animal studies thus far.Non-limbal epithelial cells such as COMET are also an alternative treatment to allogeneic transplants especially as a surface stabilizing procedure.iPSCs are currently being studied in early phase trials and have the potential to revolutionize the way LSCD is treated.Lastly,cell-based therapies for restoring the limbal niche such as mesenchymal stem cells have also shown promising results in the first human proof-of-concept study.Several potential sources of non-limbal cells are under investigation.

A Review of Radiation-Induced Oral Mucositis in Traditional Chinese and Western Medicine Research

Radiation therapy is one of the main treatments for head and neck tumors,and radiationinduced oral mucositis(RIOM)is a common serious adverse effect of radiation therapy.We summarized the pathogenesis,prevention and treatment methods of RIOM related to traditional Chinese and Western medicine in recent years.The treatment of RIOM in traditional Chinese medicine should be based on clearing heat and detoxifying,nourishing Yin and promoting fluid,tonifying spleen and stomach,cooling blood and removing blood stasis.Osteopontin,immunoglobulin A and saliva flow tests may be effective clinical indicators in the future.Through analysis,the author believes that the use of integrated intervention of traditional Chinese and western medicine can better benefit patients,and the prevention and predictive diagnostic tools of RIOM should become the future focus of attention.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis

Oral mucositis(OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life.Shuanghua Baihe Tablet(SBT) is a traditional Chinese medicine(TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg;·d;. In order to search for SBT targets and related metabolites, the dysregulated genes and metabolites were detected by transcriptomics and metabolomics. Immune related indicators such as interleukin-17(IL-17) and tumor necrosis factor-α(TNF-α) were detected by ELISA. Treg cell disorders was analyzed by flow cytometry. Our results showed that SBT significantly alleviated the symptoms of OM rats and the inflammatory infiltration of ulcer tissues.After SBT administration, inflammatory related metabolic pathways including linoleic acid metabolism, valine, leucine and isoleucine biosynthesis were significantly altered. Furthermore, the production of proinflammatory factors like IL-17 and TNF-α, were also dramatically reduced after SBT administration. Besides, the infiltration degree of Treg cells in the spleen of OM modeling rats was significantly improved by SBT administration, thus maintaining the immune balance of the body. The current study demonstrates that SBT regulates inoleic acid metabolism, glycerophospholipid metabolism and amino acid metabolism, and inhibits IL-17/TNF signal transduction to restore Treg and Th17 cell homeostasis in OM rats, thereby alleviating chemotherapy-induced OM.

A phaseⅡprospective trial of photobiomodulation therapy in limiting oral mucositis in the treatment of locally advanced head and neck cancer patients

Objective:This study aimed to compare the historical incidence rate of severe oral mucositis(OM)in head and neck cancer patients undergoing definitive concurrent chemoradiation therapy(CRT)versus a prospective cohort of patients with locally advanced head and neck squamous cell carcinoma(HNSCC)treated with prophylactic photobiomodulation therapy(PBMT).Methods:This US-based,institutional,single-arm,phaseⅡprospective clinical trial was initiated in 50 patients(age≥18 years,Karnofsky Performance Scale Index>60,with locally advanced HNSCC(excluding oral cavity)receiving definitive or adjuvant radiation therapy(RT)with concurrent platinum-based chemotherapy(CT).PBMT was delivered three times per week throughout RT utilizing both an intraoral as well extraoral delivery system.Primary outcome measure was incidence of severe OM utilizing both the National Cancer Institute Common Toxicity Criteria,version 4.0(NCI-CTCAE)Grade≥3 and the World Health Organization Mucositis Grading Scale(WHO)Grade≥3 versus historical controls;secondary outcome measures included time to onset of severe OM following therapy initiation.Results:At baseline,all patients included in final analysis(N=47)had OM Grade 0.Average RT and CT dose was(66.3±5.1)Gy and(486.1±106.8)mg/m ^(2),respectively.Severe OM was observed in 11 of 47 patients(23%,confidence interval:12,38).OM toxicity grade trended upward during treatment,reaching a maximum at 7 weeks(WHO:1.8 vs.NCI-CTCAE:1.7).Subsequently,OM grade returned to baseline 3 months following completion of RT.The mean time to onset of severe OM was(35±12)days.The mean time to resolution of severe OM was(37±37)days.Conclusions:Compared to historical outcomes,PBMT aides in decreasing severe OM in patients with locally advanced HNSCC.PBMT represents a minimally invasive,prophylactic intervention to decrease OM as a major treatment-related side effect.

Radiation-induced Oral Mucositis is a Critical Dilemma for Patients and Physicians During Radiotherapy for Nasopharyngeal Carcinoma

The combination of radiotherapy(RT)and chemotherapy is associated with a high cure rate but an increased risk of radiation-induced oral mucositis(RIOM)in patients with nasopharyngeal carcinoma(NPC).As a dose-limiting complication,RIOM remains a critical dilemma for patients and physicians,potentially leading to radiation interruptions and compromised tumor control.In this review,we discuss and analyze the pathological mechanisms and factors affecting prevention/treatment of RIOM.RT may induce RIOM via a positive feedback loop,consequently amplifying superoxide production,the immunoinflammatory response,dysbacteriosis,infection,and epithelial basal cell death.Routine interventions for RIOM focus on oral care,oral-pain relief,nutritional support,and infection control;however,recent novel and effective methods have been proposed according to the pathological mechanisms and influencing factors.Some patients with low-recurrence-risk NPCs may be treated with reduced-dose RT,reduced-dose chemotherapy,or RT alone(without chemotherapy)to prevent severe RIOM.Furthermore,traditional herbal medicine extracts,such as Kangfuxin and honey,may help to control RIOM.In addition to the routine application of antibiotics to treat oral dysbacteriosis and hormones to suppress immune inflammatory responses,edaravone and GC4419 can also be used to scavenge oxygen free radicals and reduce superoxide ions to protect the oral mucosa and limit the occurrence of RIOM.

Modeling the oxidative consumption of curcumin from controlled released poly(betaamino ester)microparticles in the presence of a free radical generating system

Despite the promise of its therapeutic benefits,curcumin as a free molecule has failed to demonstrate significant clinical success.Arguably,its inherently poor stability and rapid clearance is a significant reason for these negative outcomes.The incorporation of curcumin into the backbone of a crosslinked hydrogel that utilizes poly(beta-amino ester)(PBAE)chemistry can provide a tunable protective network with the ability to release at a controlled rate while improving its therapeutic potential.Kinetics of curcumin conjugated PBAE microparticles controlled release delivery system in the presence of oxidative environments was studied for the first time,where consumption rates of active curcumin and release products were obtained.The constituent amount of curcumin present in solution was improved by incorporating the active into the network in comparison to curcumin as a free drug.Modeling curcumin conjugated PBAE microparticles will provide a design platform to improve translation and overall success in delivering a therapeutic agent that matches levels of oxidative stress.