Rare extraintestinal manifestations of ulcerative colitis treated with dual biologic therapy:A case report

BACKGROUND Ulcerative colitis(UC)is an idiopathic,chronic inflammatory bowel disease(IBD)most often located in the rectum,but may involve the entire colon.Extra intestinal manifestations(EIMs)occur with varying frequency depending on the affected organ.The most common ones are musculoskeletal EIMs,affecting up to 33%-40%of IBD patients.These include,among others,inflammatory back pain,tendinitis,plantar fasciitis and arthritis.Only a few case reports in literature discuss Achilles tendinitis.CASE SUMMARY This report describes a patient with UC and Achilles tendinitis in whom after many unsuccessful attempts of treatment with sulfasalazine,mesalazine,glucocorticosteroids,infliximab and tofacitinib,a complete UC remission and resolution of Achilles tendinitis were achieved with the use of dual biologic therapy(DBT)-ustekinumab and adalimumab(ADA).CONCLUSION This case mentions rare EIMs of UC and suggests that DBT may be an alternative for patient with ulcerative colitis and EIMs.

Clinical effects of psychological intervention and drug therapy against peptic ulcer

Objective:To evaluate the clinical effects of psychological interventions and drug therapy against peptic ulcer.Methods:96 patients with peptic ulcer were divided into control group with Tagamet 800 mg per evening p.o.and trial group with psychological intervention on the basis of drug treatment.Results:There were significant differences between the two groups(P【0.05), the trial group showed that the anxiety and depression cases declined obviously and effective rate of ulcer therapy was much higlier than control group.Conclusions:In sum,psychological intervention combined with drug therapy provides an effective method for ulcer treatment.

Current medical therapy for ulcerative colitis

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Current gene therapy for stomach carcinoma

Gastric cancer is common in China [1-42],and its early diagnosis and treatment in advanced stage are difficult [31-50].In recent years ,gene study in cancer is a hotspot ,and great progress has been achieved [41-80] .Cancer gene therapy has shifted from the imagination into the laboratory and clinical trials.

Epinephrine injection therapy versus a combination of epinepnrine injection and endoscopic hemoclip in the treatment of bleeding ulcers

AIM: To assess the efficacy of hemoclip application in combination with epinephrine injection in the treatment of bleeding peptic ulcers and to compare the clinical outcomes between patients treated with such a combination therapy and those treated with epinephrine injection alone.METHODS: A total of 293 patients (211 males, 82females) underwent endoscopic therapy for bleeding peptic ulcers. Of these, 202 patients (152 males, 50females) received epinephrine injection therapy while 91patients (59 males, 32 females) received combination therapy. The choice of endoscopic therapy was made by the endoscopist. Hemostatic rates, rebleeding rates, need for emergency surgery and 30-d mortality were the outcome measures studied.RESULTS: Patients who received combination therapy were significantly older (mean age 66±16 years, range24-90 years) and more suffered from chronic renal failure compared to those who received epinephrine injection therapy alone (mean age 61±17 years, range 21-89 years).Failure to achieve permanent hemostasis was 4% in the group who received epinephrine injection alone and 11%in the group who received combination therapy. When the differences in age and renal function between the two treatment groups were taken into account by multivariate analysis, the rates of initial hemostasis,rebleeding rates, need for surgery and 30-d mortality for both treatment options were not significantly different.CONCLUSION: Combination therapy of epinephrine injection with endoscopic hemoclip application is an effective method of achieving hemostasis in bleeding peptic ulcer diseases. However, superiority of combination therapy over epinephrine injection alone, could not be demonstrated.

Promising biological therapies for ulcerative colitis: A review of the literature

Ulcerative colitis(UC) is a chronic lifelong condition characterized by alternating flare-ups and remission. There is no single known unifying cause, and the pathogenesis is multifactorial, with genetics, environmental factors, microbiota, and the immune system all playing roles. Current treatment modalities for UC include 5-aminosalicylates, corticosteroids, immunosuppressants(including purine antimetabolites, cyclosporine, and tacrolimus), and surgery. Therapeutic goals for UC are evolving. Medical treatment aims to induce remission and prevent relapse of disease activity. Infliximab, an anti-tumor necrosis factor(TNF)-α monoclonal antibody, is the first biological agent for the treatment of UC. Over the last decade, infliximab and adalimumab(anti-TNF-α agents) have been used for moderate to severe UC, and have been shown to be effective in inducing and maintaining remission. Recent studies have indicated that golimumab(another anti-TNF-α agent), tofacitinib(a Janus kinase inhibitor), and vedolizumab and etrolizumab(integrin antagonists), achieved good clinical remission and response rates in UC. Recently, golimumab and vedolizumab have been approved for UC by the United States Food and Drug Administration. Vedolizumab may be used as a first-line alternative to anti-TNF-α therapy in patients with an inadequate response to corticosteroids and/or immunosuppressants. Here, we provide updated information on various biological agents in the treatment of UC.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

Does Helicobacter pylori eradication therapy for peptic ulcer prevent gastric cancer?

AIM:To investigate the effects of Helicobacter pylori (H pylori)eradication therapy for treatment of peptic ulcer on the incidence of gastric cancer. METHODS:A multicenter prospective cohort study was conducted between November 2000 and December 2007 in Yamagata Prefecture,Japan.The study included patients with H pylori-positive peptic ulcer who decided themselves whether to receive H pylori eradication(eradication group)or conventional antacid therapy(non-eradication group).Incidence of gastric cancer in the two groups was determined based on the results of annual endoscopy and questionnaire surveys,as well as Yamagata Prefectural Cancer Registry data,and was compared between the two groups and by results of H pylori therapy.RESULTS:A total of 4133 patients aged between 13 and 91 years(mean 52.9 years)were registered,and 56 cases of gastric cancer were identified over a mean follow-up of 5.6 years.The sex-and age-adjusted incidence ratio of gastric cancer in the eradication group, as compared with the non-eradication group,was 0.58 (95%CI:0.28-1.19)and ratios by follow-up period(<1 year,1-3 years,>3 years)were 1.16(0.27-5.00),0.50 (0.17-1.49),and 0.34(0.09-1.28),respectively.Longer follow-up tended to be associated with better prevention of gastric cancer,although not to a significant extent.No significant difference in incidence of gastric cancer was observed between patients with successful eradication therapy(32/2451 patients,1.31%)and those with treatment failure(11/639 patients,1.72%).Among patients with duodenal ulcer,which is known to be more prevalent in younger individuals,the incidence of gastric cancer was significantly less in those with successful eradication therapy(2/845 patients,0.24%)than in those with treatment failure(3/216 patients,1.39%). CONCLUSION:H pylori eradication therapy for peptic ulcer patients with a mean age of 52.9 years at registration did not significantly decrease the incidence of gastric cancer.

Keratinocyte growth factor gene therapy ameliorates ulcerative colitis in rats

AIM:To investigate the effect of keratinocyte growth factor(KGF) gene therapy in acetic acid-induced ulcerative colitis in rat model.METHODS:The colitis of Sprague-Dawley rats was induced by intrarectal infusion of 1 mL 5%(v/v) acetic acid.Twenty-four hours after exposed to acetic acid,rats were divided into three experimental groups:control group,attenuated Salmonella typhimurium Ty21a strain(SP) group and SP strain carrying human KGF gene(SPK) group,and they were separately administered orally with 10% NaHCO3,SP or SPK.Animals were sacrificed and colonic tissues were harvested respectively on day 3,5,7 and 10 after administration.Weights of rats,colonic weight/length ratio and stool score were evaluated.Histological changes of colonic tissues were examined by hematoxylin and eosin(HE) staining method.The expression of KGF,KGF receptor(KGFR) and TNF-α were measured either by enzyme-linked immunosorbent assay or Western blotting.Immunohistochemistry was used to detect the cellular localization of KGFR and Ki67.In addition,superoxide dismutase(SOD) activity and malondialdehyde(MDA) contents in the homogenate were measured.RESULTS:Body weight and colonic weight/length ratio were declined in SPK group compared with SP and control groups(body weight:272.78 ± 17.92 g vs 243.72 ± 14.02 g and 240.68 ± 12.63 g,P < 0.01;colonic weight/length ratio:115.76 ± 7.47 vs 150.32 ± 5.99 and 153.67 ± 5.50 mg/cm,P < 0.01).Moreover,pathological changes of damaged colon were improved in SPK group as well.After administration of SPK strain,KGF expression increased markedly from the 3rd d,and remained at a high level till the 10th d.Furthermore,KGFR expression and Ki67 expression elevated,whereas TNF-α expression was inhibited in SPK group.In the group administered with SPK,SOD activity increased significantly(d 5:26.18 ± 5.84 vs 18.12 ± 3.30 and 18.79 ± 4.74 U/mg,P < 0.01;d 7:35.48 ± 3.35 vs 22.57 ± 3.44 and 21.69 ± 3.94 U/mg,P < 0.01;d 10:46.10 ± 6.23 vs 25.35 ± 4.76 and 27.82 ± 6.42 U/mg,P < 0.01) and MDA contents decreased accordingly(d 7:7.40 ± 0.88 vs 9.81 ± 1.21 and 10.45 ± 1.40 nmol/mg,P < 0.01;d 10:4.36 ± 0.62 vs 8.41 ± 0.92 and 8.71 ± 1.27 nmol/mg,P < 0.01),compared with SP and control groups.CONCLUSION:KGF gene therapy mediated by attenuated Salmonella ameliorates ulcerative colitis induced by acetic acids,and it may be a safe and effective treatment for ulcerative colitis.

Healing property of the Piper betel phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action

AIM：To evaluate the protective activity of allylpyrocatechol （APC）, the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties.METHODS： Male Sprague-Dawley rats were divided into five groups. Normal control rats （group Ⅰ ） were given the vehicle oral dose of gum acacia in distilled water （1 mL per rat）; ulcerated control and treated rats （groups Ⅱ-V） were given a single dose of indomethacin （30 mg/kg body wt.）; group Ⅱ rats were sacrificed 4 h after indomethacin administration; groups Ⅲ-Ⅴ rats were given the vehicle （1 mL per rat） or APC （2 mg/kg body wt.） or misoprostol （1.43 μg/kg body wt.） once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis. RESULTS： Treatment with APC （2 mg/kg body wt per day） and misoprostol （1.43 μg/kg body wt per day） for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively （P 〈 0.05）. Both APC and misoprostol accelerated ulcer healing observed in natural recovery （P 〈 0.05）, their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the rnucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and rnisoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively （P 〈 0.05）. Likewise, both APC and rnisoprostol increased the SOD, catalase, and rnucin levels significantly （P 〈 0.05）, the effect of APC being better. CONCLUSION： APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Does physical therapy and rehabilitation improve outcomes for diabetic foot ulcers?

One of the most common and serious complications of diabetes mellitus is ulceration of the foot. Among persons with diabetes, 12%-25% will present to a healthcare institution for a foot disorder during their lifespan. Despite currently available medical and surgical treatments, these are still the most common diabetes-related cause of hospitalization and of lower extremity amputations. Thus, many adjunctive and complementary treatments have been developed in an attempt to improve outcomes. We herein review the available literature on the effectiveness of several treatments, including superficial and deep heaters, electro-therapy procedures, prophylactic methods, exercise and shoe modifications, on diabetic foot wounds. Overall, although physical therapy modalities seem to be useful in the treatment of diabetic foot wounds, further randomized clinical studies are required.

Dysregulation of innate immunity in ulcerative colitis patients who fail anti-tumor necrosis factor therapy

AIM To study the innate immune function in ulcerative colitis(UC) patients who fail to respond to anti-tumor necrosis factor(TNF) therapy.METHODS Effects of anti-TNF therapy, inflammation and medications on innate immune function were assessed by measuring peripheral blood mononuclear cell(PBMC) cytokine expression from 18 inflammatory bowel disease patients pre- and 3 mo post-anti-TNF therapy. Toll-like receptor(TLR) expression and cytokine production post TLR stimulation was assessed in UC "responders"(n = 12) and "non-responders"(n = 12) and compared to healthy controls(n = 12). Erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) levels were measured in blood to assess disease severity/activity and inflammation. Pro-inflammatory(TNF, IL-1β, IL-6), immuno-regulatory(IL-10), Th1(IL-12, IFNγ) and Th2(IL-9, IL-13, IL-17A) cytokine expression was measured with enzyme-linked immunosorbent assay while TLR cellular composition and intracellular signalling was assessed with FACS.RESULTS Prior to anti-TNF therapy, responders and nonresponders had similar level of disease severity and activity. PBMC's ability to respond to TLR stimulation was not affected by TNF therapy, patient's severity of the disease and inflammation or their medication use. At baseline, non-responders had elevated innate but not adaptive immune responses compared to responders(P < 0.05). Following TLR stimulation, nonresponders had consistently reduced innate cytokine responses to all TLRs compared to healthy controls(P < 0.01) and diminished TNF(P < 0.001) and IL-1β(P < 0.01) production compared to responders. This innate immune dysfunction was associated with reduced number of circulating plasmacytoid dendritic cells(p DCs)(P < 0.01) but increased number of CD4+ regulatory T cells(Tregs)(P = 0.03) as well as intracellular accumulation of IRAK4 in non-responders following TLR-2,-4 and-7 activation(P < 0.001). CONCLUSION Reduced innate immunity in non-responders may explain reduced efficacy to anti-TNF therapy. These serological markers may prove useful in predicting the outcome of costly anti-TNF therapy.

Biological therapy for ulcerative colitis:An update

Of the diverse biological agents used for patients with ulcerative colitis, the anti-tumor necrosis factor-&#x003b1; agents infliximab and adalimumab have been used in large-scale clinical trials and are currently widely used in the treatment of inflammatory bowel disease patients. Recent studies have indicated that golimumab, oral tofacitinib and vedolizumab reportedly achieved good clinical response and remission rates in ulcerative colitis patients. Thus, we believe that the detailed investigation of various studies on clinical trials may provide important information for the selection of appropriate biological agents, and therefore, we have extensively reviewed such trials in the present study.

Effects of killing Helicobacter pylori quadruple therapy on peptic ulcer: A randomized double-blind clinical trial

AIM: To study the therapeutic efficacy of a Chinese and Western integrated regimen, killing Helicobacter pylori quadruple therapy on H pylori-associated peptic ulcers(PU).METHODS: With prospective and double-blind controlled method, seventy-five active PU patients with H pylori infection were randomized to receive one of the following three regimens: (1) new triple therapy (group A:lansoprazole 30 mg qd, plus clarithromycin 250 mg bid,plus amoxycillin 500 mg tid, each for 10 d); (2) killing Hp quadruple therapy(group B: the three above drugs plus killing H pylori capsule 6 capsules bid for 4 wk) and (3)placebo(group C: gastropine 3 tablets bid for 4 wk).H pylori eradication and ulcer healing quality were evaluated under an endoscope 4 wk after treatment. The patients were followed up for 5 years.RESULTS: Both the healing rate of PU and H pylori eradication rate in group B were significantly higher than those in group C (100% and 96.4% vs 20% and 0%,respectively, P＜0.005), but there was no significant difference compared to those in group A (88% and92%, P＞0.05). The healing quality of ulcer in group B was superior to that in groups C and A (P＜0.05). The recurrence rate of PU in group B (4%) was lower than that in group A (10%) and group C (100%, P＜0.01).CONCLUSION: Killing Helicobacter pylori quadruple therapy can not only promote the eradication of H pylori and healing quality of ulcer but also reduce recurrence rate of ulcer.

Early aggressive therapy for severe extensive ulcerative colitis

The current ulcerative colitis （UC） treatment algorithm involves a step-up therapeutic strategy, mainly aiming at inducing and maintaining its clinical remission. Although this therapeutic strategy may seem to be cost-efficient and reduce the risk of side effects, recent trials and case reports have shown that top-down therapy using infliximab induces a rapid clinical response, enhances patient quality of life, promotes mucosal healing, reduces surgeries and indirect cost of treatment for patients with severe UC. Moreover, since long-term treatment with infliximab is safe and well tolerated, early aggressive top-down therapeutic strategy may be a more effective approach, at least in a subgroup of severe extensive UC patients.

Treatment of diabetic foot ulcer with medicinal leech therapy and honey curcumin dressing: a case report

Background:Diabetic foot ulcers(DFUs)are common in patients with diabetes.The mortality rate of DFUs is ranked the highest after cancer.With advancements in modern medicine,leech therapy,a traditional treatment method for chronic wounds in Iranian medicine,has proven effective in relieving venous congestion.Herein,we aimed to observe the curative effects of leech therapy in combination with honey and curcumin dressing in a 77-year-old patient with a diabetic foot ulcer(UFC).Methods:Two medium-sized medicinal leeches were placed surrounding a grade 2 wound,based on Wagner’s classification system,located on the right first toe.The patient reported a visual analogue scale(VAS)score of 8.After leech therapy,the wound was covered with honey and curcumin,followed by oral administration of ciprofloxacin for 10 days.Results:Pain increased immediately after leech therapy(VAS:9-10)but decreased significantly(VAS:6)2 days after the therapy.At the end of the 2nd day,pain completely disappeared.After 3 weeks,there was no wound on the toe.After 12 weeks,there were no traces of the wound.Conclusion:Leech therapy in combination with honey and curcumin dressing is effective against disease progression in patients with DFUs.

Frequency and prognostic role of mucosal healing in patients with Crohn's disease and ulcerative colitis after one-year of biological therapy

AIM: To assess the endoscopic activity before and after a one-year period of biological therapy and to evaluate the frequency of relapses and need for retreatment after stopping the biologicals in patients with Crohn&#x02019;s disease (CD) and ulcerative colitis (UC).

Efficacy of cytapheresis in patients with ulcerative colitis showing insufficient or lost response to biologic therapy

For the optimal management of refractory ulcerative colitis(UC),secondary loss of response(LOR)and primary non-response to biologics is a critical issue.This article aimed to summarize the current literature on the use of cytapheresis(CAP)in patients with UC showing a poor response or LOR to biologics and discuss its advantages and limitations.Further,we summarized the efficacy of CAP in patients with UC showing insufficient response to thiopurines or immunomodulators(IM).Eight studies evaluated the efficacy of CAP in patients with UC with inadequate responses to thiopurines or IM.There were no significant differences in the rate of remission and steroid-free remission between patients exposed or not exposed to thiopurines or IM.Three studies evaluated the efficacy of CAP in patients with UC showing an insufficient response to biologic therapies.Mean remission rates of biologics exposed or unexposed patients were 29.4%and 44.2%,respectively.Fourteen studies evaluated the efficacy of CAP in combination with biologics in patients with inflammatory bowel disease showing a poor response or LOR to biologics.The rates of remission/response and steroid-free remission in patients with UC ranged 32%-69%(mean:48.0%,median:42.9%)and 9%-75%(mean:40.7%,median:38%),respectively.CAP had the same effectiveness for remission induction with or without prior failure on thiopurines or IM but showed little benefit in patients with UC refractory to biologics.Although heterogeneity existed in the efficacy of the combination therapy with CAP and biologics,these combination therapies induced clinical remission/response and steroid-free remission in more than 40%of patients with UC refractory to biologics on average.Given the excellent safety profile of CAP,this combination therapy can be an alternative therapeutic strategy for UC refractory to biologics.Extensive prospective studies are needed to understand the efficacy of combination therapy with CAP and biologics.

Azithromycin in a triple therapy for H.pylori eradication in active duodenal ulcer

AIM:To assess and compare the efficacy and safety of two triple regimes:A)metronidazole,amoxicillin and omeprazole, which is still widely used in Russia,and B)azithromycin, amoxicillin and omeprazole in healing active duodenal ulcer and H.pylori eradication. METHODS:100 patients with active duodenal ulcer were included in the open,multicentre,randomized study with comparative groups.Patients were randomly assigned to one of the following one-week triple regimes:A) metronidazole 500 mg bid,amoxicillin I g bid and omeprazole 20 mg bid(OAM,n=50)and B)azithromycin 1 god for the first 3 days(total dose 3 g),amoxicillin 1 g bid and omeprazole 20 mg bid(OAA,n=50).Omeprazole 20 mg od was given after the eradication course as a monotherapy for three weeks.The control endoscopy was performed 8 weeks after the entry.H.pyloriinfection was determined in the entry of the study and four weeks after the cessation of treatment by means of histology and CLO-test. RESULTS:97 patients completed the study according to the protocol(1 patient of the OAM group did not come to the control endoscopy,2 patients of the OAA group stopped the treatment because of mild allergic urticaria).Duodenal ulcers were healed in 48 patients of the OAM group(96 %, C190.5-100 %)and in 46 patients of the OAA group(92 %, CI 89.5-94.5 %)(p=ns).H.pyloHinfection was eradicated in 15 out of 50 patients with OAM(30 %,CI 17-43 %)and in 36 out of 50 patients treated with OAA(72 %;CI 59-85 %) (P<0.001)-ITT analysis.CONCLUSION: The triple therapy with omeprazole, amoxicillin and metronidazole failed to eradicate H.pylori'vc\ the majority of patients, which is an essential argument to withdraw this regimen out of the national recommendations. Macrolide with amoxicillin are preferable to achieve higher eradication rates. Azithromycin (1 g od for the first 3 days) can be considered as a successful component of the triple PPI-based regimen.

Experimental study on effect of recombinant human growth hormone combined with chemotherapy on stomach neoplasms implanted in nude mice

Objective: To investigate the effect of different doses of recombined growth hormone (rhGH) on stomach neo- plasms implanted in nude mice, and its efficacy in combining with chemotherapy (flurouracil, 5-FU). Methods: Human stom- ach neoplasms model was established in nude mice. The nude mice were divided into control group, moderate-dose of rhGH group, low-dose rhGH group, 5-FU group, moderate-dose rhGH/5-FU group, and low-dose rhGH/5-FU group. The results of each group were observed after ten days. Results: After therapy, the body mass of rhGH groups was significantly increased compared with control group (P<0.05), the body mass of rhGH/5-FU groups was significantly increased compared with 5-FU group (P<0.05), but it was no significant difference between rhGH/5-FU groups and control group (P>0.05). The average tumor mass and volume of rhGH groups were not significantly increased compared with control group (P>0.05), but they were significantly reduced in 5-FU group and rhGH/5-FU groups (P<0.05). They were no significant difference between rhGH/5- FU groups and 5-FU group (P>0.05). After treatment, the percentages of S, G0/G1 and G2/M phases and proliferation index (PI) were not significantly changed in rhGH groups compared with control group (P>0.05), and the same with rhGH/5-FU groups compared with 5-FU group (P>0.05). The difference caused by dose of rhGH was not significant. Conclusion: rhGH enhances body mass, does not stimulate tumor growth, and has no adverse effects on tumor bearing nude mice. Combined with flurouracil, rhGH does not influence the efficacy of chemotherapy, and has no effect on tumor cell cycle kinetics.