Comparative Cytological and Histopathological Study of Peri-Implantitis and Periodontitis

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, pose significant challenges to the long-term prognosis of dental implants. This study aimed to comprehensively compare peri-implantitis with periodontitis from cytological and histopathological perspectives, shedding light on the morphological characteristics associated with peri-implantitis. Thirteen patients, including six with peri-implantitis and seven with periodontitis, were included in the study. Cytological examination of affected gingival mucosa revealed distinct differences between the two conditions. Peri-implantitis exhibited an inflammatory background predominantly composed of neutrophils with lobulated nuclei, accompanied by stratified squamous epithelial cells showing signs of keratinization. In contrast, periodontitis showed a similar neutrophilic inflammatory background but with non-keratinized epithelial cells. Histopathological examination further confirmed these differences, with peri-implantitis showing keratinized epithelium in the inner epithelial layer. This histological finding aligns with the notion that peri-implantitis has a distinct mucosal profile compared to periodontitis. Additionally, cytological analysis revealed that peri-implantitis had a lower occurrence rate of Light green-positive cells, indicating a tendency toward keratinization. This finding suggests that the presence of keratinized mucosa might be associated with peri-implant health, although further research is needed to clarify this relationship. Overall, this study demonstrates the potential of cytological examination and Papanicolaou staining for assessing mucosal inflammatory conditions and distinguishing between keratinized and non-keratinized cells. These findings underscore the utility of oral mucosal smears as a valuable tool for diagnosing peri-implantitis and enhancing our understanding of its pathogenesis.

Investigation of Bacteria Species Most Involved in Peri-Implantitis

Purpose: Currently, bacteriological examinations of implant treatments target periodontopathic bacteria such as red complex bacteria, including Porphyromonas gingivalis, and detect them qualitatively or quantitatively. However, it seems that those examinations do not reflect the peri-implant tissue conditions precisely, because periodontopathic bacteria are also frequently detected from healthy peri-implant sites. The purpose of the present study was to investigate bacteria species most involved in peri-implantitis using a PCR method. Methods: Polymerase chain reaction (PCR) primers in this study were designed based on partial sequences of 16S rDNA of bacteria species involved in peri-implantitis that were described in numerous previous studies. Peri-implant sulcus fluid (PISF) samples were collected from thirty periodontally healthy patients with implants (HI) and thirty patients with peri-implantitis (PI). Each detection frequency of bacteria species in PISFs of both groups was investigated using a PCR method, and was compared using Fisher’s exact test. Results: In PI group, detection frequencies of Corynebacterium durum, Fretibacterium fastidiosum and Slackia exigua were significantly higher than those of HI group (p P. gingivalis and Tannerella forsythia belonging to red complex were frequently detected in the PISF samples of HI group (p > 0.05). Conclusion: It was suggested that monitoring C. durum and F. fastidiosum levels in PISF samples was useful as a clinical indicator for the evaluation of peri-implant tissue conditions.

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.

Association between the nutritional status and radiation pharyngeal mucositis in patients with head and neck cancer during radiotherapy:A longitudinal study

Objective Radiation mucositis,especially pharyngeal mucositis,severely affects the oral intake of patients of head and neck cancer(HNC)during radiotherapy.Whether the nutritional status affects the severity of pharyngeal mucositis is currently unknown.This study investigated the incidence of malnutrition and radiation pharyngeal mucositis in patients with HNC during radiotherapy and analyzed the impact of the nutritional status on radiation pharyngeal mucositis.Methods Consecutive patients with HNC receiving radiotherapy were recruited for this longitudinal observational study.Data were collected at baseline(T_(1)),midtreatment(T_(2)),and at the end of treatment(T3).The Common Terminology Criteria for Adverse Events version 4.0 and the Global Leadership Initiative on Malnutrition criteria were used to assess pharyngeal mucositis and the nutritional status,respectively.Results There were 348 HNC patients who completed all assessments.The pharyngeal mucositis of patients with HNC was aggravated during radiotherapy(χ^(2)=553.521,P<0.001).At T3,56.0%of patients had moderate or severe pharyngeal mucositis.The proportion of patients with malnutrition increased significantly during treatment(21.3%at T_(1)vs 46.8%at T_(2)vs 76.1%at T3,χ^(2)=209.768,P<0.001).Both a multivariable analysis of generalized estimating equations and a logistic regression analysis showed that pharyngeal mucositis was associated with malnutrition.Conclusions Malnutrition was common in patients with HNC during radiotherapy,and it was closely related to pharyngeal mucositis.Joint interventions targeting nutrition and symptom management should be considered for patients with HNC.

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.

Efficacy and safety of endoscopic submucosal dissection for early gastric cancer and precancerous lesions in elderly patients

BACKGROUND With advancements in the development of endoscopic technologies,the endo-scopic submucosal dissection(ESD)has been one of the gold-standard therapies for early gastric cancer.AIM To investigate the efficacy and safety ESD in the treatment of early gastric cancer and precancerous lesions in the elderly patients.METHODS Seventy-eight elderly patients with early gastric cancer and precancerous lesions admitted to the Third Affiliated Hospital of Qiqihar Medical University were se-lected and classified into two groups according to the different surgical therapies they received between January 2021 and June 2022.Among them,39 patients treated with ESD were included in an experimental group,and 39 patients treated with endoscopic mucosal resection(EMR)were included in a control group.We compared the basic intraoperative conditions,postoperative short-term recovery,long-term recovery effects and functional status of gastric mucosa between the two groups;the basic intraoperative conditions included lesion resection,intra-operative bleeding and operation time;the postoperative short-term recovery assessment indexes were length of hospital stay and incidence of surgical complic-ations;and the long-term recovery assessment indexes were the recurrence rate at 1 year postoperatively and the survival situation at 1 year and 3 years postoper-atively;and we compared the preoperative and predischarge serum pepsinogen I(PG I)and PG II levels and PG I/PG II ratio in the two groups before surgery and discharge.RESULTS The curative resection rate and the rate of en bloc resection were higher in the experimental group than in the control group.The intraoperative bleeding volume was higher in the experimental group than in the control group.The operation time was longer in the experimental group than that in the control group,and the rate for base residual focus was lower in the experimental group than that of the control group,and the differences were all statistically significant(all P<0.05).The length of hospital stay was longer in the experi-mental group than in the control group,and the incidence of surgical complications,1-year postoperative recu-rrence rate and 3-year postoperative survival rate were lower in the experimental group than in the control group,and the differences were statistically significant(all P<0.05).However,the difference in the 1-year postoperative survival rate was not statistically significant between the two groups(P>0.05).Before discharge,PG I and PG I/PG II ratio were elevated in both groups compared with the preoperative period,and the above indexes were higher in the experimental group than those in the control group,and the differences were statistically significant(both P<0.05).Moreover,before discharge,PG II level was lower in both groups compared with the preoperative period,and the level was lower in the experimental group than in the control group,and the differences were all statistically significant(all P<0.05).CONCLUSION Compared with EMR,ESD surgery is more thorough.It reduces the rate of base residual focus,recurrence rate,surgical complications,and promotes the recovery of gastric cells and glandular function.It is safe and suitable for clinical application.

Characteristics of early gastric tumors with different differentiation and predictors of long-term outcomes after endoscopic submucosal dissection

BACKGROUND Gastric cancer is a common malignant tumor of the digestive tract,and endosco-pic submucosal dissection(ESD)is the preferred treatment for early-stage gastric cancer.The analysis of the epidemiological characteristics of gastric mucosal tumors with different differentiation degrees and the influencing factors of long-term ESD efficacy may have certain significance for revealing the development of gastric cancer and ESD.AIM To analyze the features of gastric mucosal tumors at different differentiation levels,and to explore the prognostic factors of ESD.METHODS We retrospectively studied 301 lesions in 285 patients at The Second Affiliated Hospital of Xi'an Jiaotong University from 2014 to 2021,according to the latest Japanese guidelines(sixth edition),and divided them into low-grade intrae-pithelial neoplasia(LGIN),high-grade intraepithelial neoplasia(HGIN),and computed tomography at 3,6 and 12 months after ESD.We compared clinicopathologic characteristics,ESD efficacy,and complications with different degrees of differentiation,and analyzed the related factors associated with ESD.RESULTS HGIN and differentiated carcinoma patients were significantly older compared with LGIN patients(P<0.001)and accounted for more 0-IIc(P<0.001),atrophic gastritis was common(P<0.001),and irregular microvascular patterns(IMVPs)and demarcation lines(DLs)were more obvious(P<0.001).There was more infiltration in the undifferentiated carcinoma tissue(P<0.001),more abnormal folds and poorer mucosal peristalsis(P<0.001),and more obvious IMVPs,irregular microsurface patterns and DLs(P<0.05)than in the LGIN and HGIN tissues.The disease-free survival rates at 2,5,and 8 years after ESD were 95.0%,90.1%,and 86.9%,respectively.Undifferen-tiated lesions(HR 5.066),white moss(HR 7.187),incomplete resection(HR 3.658),and multiple primary cancers(HR 2.462)were significantly associated with poor prognosis.CONCLUSION Differentiations of gastric mucosal tumors have different epidemiological and endoscopic characteristics,which are closely related to the safety and efficacy of ESD.

Alkaline sphingomyelinase deficiency impairs intestinal mucosal barrier integrity and reduces antioxidant capacity in dextran sulfate sodium-induced colitis

BACKGROUND Ulcerative colitis is a chronic inflammatory disease of the colon with an unknown etiology.Alkaline sphingomyelinase(alk-SMase)is specifically expressed by intestinal epithelial cells,and has been reported to play an anti-inflammatory role.However,the underlying mechanism is still unclear.AIM To explore the mechanism of alk-SMase anti-inflammatory effects on intestinal barrier function and oxidative stress in dextran sulfate sodium(DSS)-induced colitis.METHODS Mice were administered 3%DSS drinking water,and disease activity index was determined to evaluate the status of colitis.Intestinal permeability was evaluated by gavage administration of fluorescein isothiocyanate dextran,and bacterial translocation was evaluated by measuring serum lipopolysaccharide.Intestinal epithelial cell ultrastructure was observed by electron microscopy.Western blotting and quantitative real-time reverse transcription-polymerase chain reaction were used to detect the expression of intestinal barrier proteins and mRNA,respectively.Serum oxidant and antioxidant marker levels were analyzed using commercial kits to assess oxidative stress levels.RESULTS Compared to wild-type(WT)mice,inflammation and intestinal permeability in alk-SMase knockout(KO)mice were more severe beginning 4 d after DSS induction.The mRNA and protein levels of intestinal barrier proteins,including zonula occludens-1,occludin,claudin-3,claudin-5,claudin-8,mucin 2,and secretory immunoglobulin A,were significantly reduced on 4 d after DSS treatment.Ultrastructural observations revealed progressive damage to the tight junctions of intestinal epithelial cells.Furthermore,by day 4,mitochondria appeared swollen and degenerated.Additionally,compared to WT mice,serum malondialdehyde levels in KO mice were higher,and the antioxidant capacity was significantly lower.The expression of the transcription factor nuclear factor erythroid 2-related factor 2(Nrf2)in the colonic mucosal tissue of KO mice was significantly decreased after DSS treatment.mRNA levels of Nrf2-regulated downstream antioxidant enzymes were also decreased.Finally,colitis in KO mice could be effectively relieved by the injection of tertiary butylhydroquinone,which is an Nrf2 activator.CONCLUSION Alk-SMase regulates the stability of the intestinal mucosal barrier and enhances antioxidant activity through the Nrf2 signaling pathway.

Editorial article to:Animal experimental study on magnetic anchor technique-assisted endoscopic submucosal dissection of early gastric cancer

In this editorial we comment on the article published in the recent issue of the World Journal of Gastrointestinal Endoscopy 2023;15(11):634-680.Gastric cancer(GC)remains the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide.The overall prevalence of GC has declined,although that of proximal GC has increased over time.Thus,a significant proportion of GC cases and deaths can be avoided if preventive interventions are taken.Early GC(EGC)is defined as GC confined to the mucosa or submucosa.Endoscopic resection is considered the most appropriate treatment for precancerous gastrointestinal lesions improving patient quality of life,with reduced rates of complications,shorter hospitalization period,and lower costs when compared to surgical resection.Endoscopic mucosal resection(EMR)and endoscopic sub-mucosal dissection(ESD)are representative endoscopic treatments for EGC and precancerous gastric lesions.Standard EMR implies injection of a saline solution into the sub-mucosal space,followed by excision of the lesion using a snare.Complete resection rates vary depending on the size and severity of the lesion.When using conventional EMR methods for lesions less than 1 cm in size,the complete resection rate is approximately 60%,whereas for lesions larger than 2 cm,the complete resection rate is low(20%-30%).ESD can be used to remove tumors exceeding 2 cm in diameter and lesions associated with ulcers or submucosal fibrosis.Compared with EMR,ESD has higher en bloc resection rates(90.2%vs 51.7%),higher complete resection rates(82.1 vs 42.2%),and lower recurrence rates(0.65%vs 6.05%).Thus,innovative techniques have been introduced.

Giant Brunner's gland hyperplasia of the duodenum successfully resected en bloc by endoscopic mucosal resection: A case report

BACKGROUND Duodenal Brunner's gland hyperplasia(BGH)is a therapeutic target when complications such as bleeding or gastrointestinal obstruction occur or when malignancy cannot be ruled out.Herein,we present a case of large BGH treated with endoscopic mucosal resection(EMR).CASE SUMMARY An 83-year-old woman presented at our hospital with dizziness.Blood tests revealed severe anemia,esophagogastroduodenoscopy showed a 6.5 cm lesion protruding from the anterior wall of the duodenal bulb,and biopsy revealed the presence of glandular epithelium.Endoscopic ultrasonography(EUS)demonstr-ated relatively high echogenicity with a cystic component.The muscularis propria was slightly elevated at the base of the lesion.EMR was performed without complications.The formalin-fixed lesion size was 6 cm×3.5 cm×3 cm,showing nodular proliferation of non-dysplastic Brunner's glands compartmentalized by fibrous septa,confirming the diagnosis of BGH.Reports of EMR or hot snare polypectomy are rare for duodenal BGH>6 cm.In this case,the choice of EMR was made by obtaining information on the base of the lesion as well as on the internal characteristics through EUS.CONCLUSION Large duodenal lesions with good endoscopic maneuverability and no evident muscular layer involvement on EUS may be resectable via EMR.

Rhubarb extract partially improves mucosal integrity in chemotherapy-induced intestinal mucositis

AIM To investigate the effects of orally gavaged aqueous rhubarb extract(RE) on 5-fluorouracil(5-FU)-induced intestinal mucositis in rats. METHODS Female Dark Agouti rats(n = 8/group) were gavaged daily(1 mL) with water, high-dose RE(HDR; 200 mg/kg) or low-dose RE(LDR; 20mg/kg) for eight days. Intestinal mucositis was induced(day 5) with 5-FU(150 mg/kg) via intraperitoneal injection. Intestinal tissue samples were collected for myeloperoxidase(MPO) activity and histological examination. Xenopus oocytes expressing aquaporin 4 water channels were prepared to examine the effect of aqueous RE on cell volume, indicating a potential mechanism responsible for modulating net fluid absorption and secretion in the gastrointestinal tract. Statistical significance was assumed at P < 0.05 by one-way ANOVA. RESULTS B o d y w e i g h t w a s s i g n i f i c a n t l y r e d u c e d i n r a t s administered 5-FU compared to healthy controls(P < 0.01). Rats administered 5-FU significantly increased intestinal MPO levels(≥ 307%; P < 0.001), compared to healthy controls. However, LDR attenuated this effect in 5-FU treated rats, significantly decreasing ileal MPO activity(by 45%; P < 0.05), as compared to 5-FU controls. 5-FU significantly reduced intestinal mucosal thickness(by ≥ 29% P < 0.001) as compared to healthy controls. LDR significantly increased ileal mucosal thickness in 5-FU treated rats(19%; P < 0.05) relative to 5-FU controls. In xenopus oocytes expressing AQP4 water channels, RE selectively blocked water influx into the cell, induced by a decrease in external osmotic pressure. As water efflux was unaltered by the presence of extracellular RE, the directional flow of water across the epithelial barrier, in the presence of extracellular RE, indicated that RE may alleviate water loss across the epithelial barrier and promote intestinal health in chemotherapy-induced intestinal mucositis.CONCLUSION In summary, low dose RE improves selected parameters of mucosal integrity and reduces ileal inflammation, manifesting from 5-FU-induced intestinal mucositis.

Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia: a case–control study

The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition （P=0.002）, duration of mucositis （P= 0.003） and the average grade of mucositis （P= 0.03）. The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering： from leukaemia.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation

BACKGROUND Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients.However,they can also damage normal cells and cause serious intestinal toxicity,leading to gastrointestinal mucositis[1].Traditional Chinese medicine is effective in improving the side effects of chemotherapy.Wumei pills(WMP)was originally documented in the Treatise on Exogenous Febrile Diseases.It has a significant effect on chronic diarrhea and other gastrointestinal diseases,but it is not clear whether it affects chemotherapy induced intestinal mucositis(CIM).AIM To explore the potential mechanism of WMP in the treatment of CIM through experimental research.METHODS We used an intraperitoneal injection of 5-fluorouracil(5-Fu)to establish a CIM mouse model and an oral gavage of WMP decoction(11325 and 22650 mg/kg)to evaluate the efficacy of WMP in CIM.We evaluated the effect of WMP on CIM by observing the general conditions of the mice(body weight,food intake,spleen weight,diarrhea score,and hematoxylin and eosin stained tissues).The expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β,and myeloperoxidase(MPO),as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB(TLR4/MyD88/NF-κB)signaling pathway proteins and tight junction proteins(zonula occludens-1,claudin-1,E-cadherin,and mucin-2)was determined.Furthermore,intestinal permeability,intestinal flora,and the levels of short-chain fatty acids(SCFA)were also assessed.RESULTS WMP effectively improved the body weight,spleen weight,food intake,diarrhea score,and inflammatory status of the mice with intestinal mucositis,which preliminarily confirmed the efficacy of WMP in CIM.Further experiments showed that in addition to reducing the levels of TNF-α,IL-1β,IL-6,and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins,WMP also repaired the integrity of the mucosal barrier of mice,regulated the intestinal flora,and increased the levels of SCFA(such as butyric acid).CONCLUSION WMP can play a therapeutic role in CIM by alleviating inflammation,restoring the mucosal barrier,and regulating gut microbiota.

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.

A Retrospective Match Controlled Study of Supersaturated Calcium Phosphate Oral Rinse vs. Supportive Care for Radiation Induced Oral Mucositis

Oral mucositis is a common morbidity induced by radiation therapy and chemo-radiotherapy for head and neck malignancies. This often results in treatment delays, premature treatment cessation and increased cost. New treatments of oral mucositis are emerging but effective remedies remain limited. Between February 2007 and May 2008, 21 patients with head and neck malignancies were treated with a supersaturated calcium phosphate oral rinse (Caphosol) that was performed for 4-10 times daily, each consisting of two one-minute rinses. There were 21 matched patients who received supportive care without the oral rinse. All patients in the two groups were treated with intensity modulated radiation therapy (IMRT) for average prescription doses of 66 Gy in 33 fractions. The effects of this rinse vs. supportive care on mucositis, PEG tube requirements, hospitalization, xerostomia, analgesic requirements and weight was respectively evaluated. We have observed statistically significant decreases in the incidence of radiation induced oral mucositis (p=0.0002) with WHO grade 3 (38% vs. 52%) and 4 mucositis (0% vs. 19%), need for PEG tube placement (33% vs. 57%) and hospitalization (0% vs 19%). There was also a favorable impact on the incidence of grade 3 (29% vs. 43%) xerostomia in the treated patients but it was statistically insignificant (p=0.58). Incremental costs related to treatment of oral mucositis were reduced considerably. Our data suggest that use of a supersaturated calcium phosphate oral rinse is an effective treatment for mucositis in patients undergoing IMRT. It may also be helpful in the reduction of hospitalization and PEG tube requirements.

High-potency sucralfate prevents and rapidly reverses chemo-radiation mucositis in a patient with stage 4b head and neck cancer

AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.

Management of pembrolizumab-induced steroid refractory mucositis with infliximab:A case report

BACKGROUND Pembrolizumab is an anti-programmed death receptor 1(PD-1)that was shown to have a tolerable safety profile with 17%of grade 3-4 drug-related adverse events,notable response rate of 16%with median duration of response of 8 mo,and median overall survival of 8 mo.Severe mucositis is a very rare complication with only two cases of grade 4 mucositis reported,and both cases had good response to intravenous methylprednisolone and subsequent oral prednisone tapering.We report the first case of pembrolizumab-induced severe mucositis that was refractory to steroid treatment.CASE SUMMARY An 80-year-old woman with a past medical history of recurrent right cheek nodular melanoma status post resection and new right lung metastatic melanoma on immunotherapy presented with dysphagia and odynophagia for 2 mo.She initially received 2 doses of ipilimumab 1 year ago with good outcome,but treatment was discontinued after developing severe diarrhea and rash.Pembrolizumab was then initiated 4 mo after disease progression.Significant improvement was noted after 3 doses.However,after 6 cycles of pembrolizumab,patient developed odynophagia and malnutrition.Improvement of symptoms was noted after discontinuation of pembrolizumab and initiation of steroids.3 mo later,patient developed pharyngeal swelling with hoarseness and new oxygen requirement due to impending airway obstruction while being on prednisone tapering regimen,finally ended up with intubation and tracheostomy.Histologic analysis of left laryngeal and epiglottis tissue showed granulation tissue with acute on chronic inflammation,negative for malignancy and infection.Patient achieved marked improvement after 2 doses of infliximab of 5 mg/kg every 2 wk while continuing on prednisone tapering course.CONCLUSION We report the first case of pembrolizumab-induced grade 4 mucositis that had limited recovery with prolonged steroid course but had rapid response with addition of infliximab.The patient had recurrent mucositis symptoms whenever steroids was tapered but achieved complete response after receiving two doses of infliximab while continuing to be on tapering steroids.The success of infliximab in this patient with pembrolizumab-induced severe mucositis presents a potentially safe approach to reduce prolonged steroid course and accelerate recovery in managing this rare complication.

Mucosal healing and inflammatory bowel disease:Therapeutic implications and new targets

Mucosal healing(MH)is vital in maintaining homeostasis within the gut and protecting against injury and infections.Multiple factors and signaling pathways contribute in a dynamic and coordinated manner to maintain intestinal homeostasis and mucosal regeneration/repair.However,when intestinal homeostasis becomes chronically disturbed and an inflammatory immune response is constitutively active due to impairment of the intestinal epithelial barrier autoimmune disease results,particularly inflammatory bowel disease(IBD).Many proteins and signaling pathways become dysregulated or impaired during these pathological conditions,with the mechanisms of regulation just beginning to be understood.Consequently,there remains a relative lack of broadly effective therapeutics that can restore MH due to the complexity of both the disease and healing processes,so tissue damage in the gastrointestinal tract of patients,even those in clinical remission,persists.With increased understanding of the molecular mechanisms of IBD and MH,tissue damage from autoimmune disease may in the future be ameliorated by developing therapeutics that enhance the body’s own healing response.In this review,we introduce the concept of mucosal healing and its relevance in IBD as well as discuss the mechanisms of IBD and potential strategies for altering these processes and inducing MH.

Severe gastrointestinal mucositis following high dose melphalan therapy for multiple myeloma

Mucositis is a known complication following use of chemotherapy,but fatal mucositis is unusual and management of such cases may be challenging.Pathologically there is denudation of mucosa of gastrointestinal tract. Severe cases can develop ileus and even perforation of bowel wall.We report here a case of multiple myeloma who developed World Health Organization grade 4 gut mucositis following the use of high dose melphalan with the expulsion of"intestine-like"material.

Molecular regulation mechanism of intestinal stem cells in mucosal injury and repair in ulcerative colitis

Ulcerative colitis(UC)is a chronic nonspecific inflammatory disease with complex causes.The main pathological changes were intestinal mucosal injury.Leucinerich repeat-containing G protein coupled receptor 5(LGR5)-labeled small intestine stem cells(ISCs)were located at the bottom of the small intestine recess and inlaid among Paneth cells.LGR5+small ISCs are active proliferative adult stem cells,and their self-renewal,proliferation and differentiation disorders are closely related to the occurrence of intestinal inflammatory diseases.The Notch signaling pathway and Wnt/β-catenin signaling pathway are important regulators of LGR5-positive ISCs and together maintain the function of LGR5-positive ISCs.More importantly,the surviving stem cells after intestinal mucosal injury accelerate division,restore the number of stem cells,multiply and differentiate into mature intestinal epithelial cells,and repair the damaged intestinal mucosa.Therefore,in-depth study of multiple pathways and transplantation of LGR5-positive ISCs may become a new target for the treatment of UC.