Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM:To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.METHODS:A multicenter,prospective,observational study was conducted from June 2009 until June 2010.We consecutively included high-risk Crohn's disease patients who had undergone an ileal/ileocolonic resection.High-risk patients were defined as two or more criteria:smokers,penetrating pattern,one or more previous surgical resections or prior extensive resection.Subcutaneous adalimumab was administered 2 wk(± 5 d) after surgery at a dose of 40 mg eow,with an initial induction dose of 160/80 mg at weeks 0 and 2.Demographic data,previous and concomitant treatments(antibiotics,5-aminosalicylates,corticosteroids,immunomodulators or biologic therapies),smoking status at the time of diagnosis and after the index operation and number of previous resections(type and reason for surgery) were all recorded.Biological status was assessed with C-reactive protein,erythrocyte sedimentation rate and fecal calprotectin.One year(± 3 mo) after surgery,an ileocolonoscopy and/or magnetic resonance enterography was performed.Endoscopic recurrence was defined as Rutgeerts score ≥ i2.Morphological recurrence was based on magnetic resonance(MR) score ≥ MR1.RESULTS:Twenty-nine patients(55.2% males,48.3% smokers at diagnosis and 13.8% after the index operation),mean age 42.3 years and mean duration of the disease 13.8 years were included in the study.A mean of 1.76(range:1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection.51.7% had previously received infliximab.Immunomodulators were given concomitantly to 17.2% of patients.Four of the 29(13.7%) developed clinical recurrence,6/29(20.7%) endoscopic recurrence and 7/19(36.8%) morphological recurrence after 1-year.All patients with clinical recurrence showed endoscopic and morphological recurrence.A high degree of concordance was found between clinical-endoscopic recurrence(k = 0.76,P < 0.001) and clinical-morphological recurrence(k = 0.63,P = 0.003).Correlation between endoscopic and radiological findings was good(comparing the 5-point Rutgeerts score with the 4-point MR score,a score of i4 was classified as MR3,i3 as MR2,and i2-i1 as MR1)(P < 0.001,r s = 0.825).During follow-up,five(17.2%) patients needed adalimumab dose intensification(40 mg/wk);Mean time to intensification after the introduction of adalimumab treatment was 8 mo(range:5 to 11 mo).In three cases(10.3%),a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk.One patient suffered an adverse event.CONCLUSION:Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.

The effects of intravesical therapy with elemene in preventing postoperative recurrence of bladder cancer

To investigate the effects of intravesical therapy with elemene in preventing postoperative recurrence of superficial bladder cancer and its toxic and side effects.Methods This series included 123 patients with superficial bladder cancer (T1),consisting of transitional cell carcinoma GⅠ in 37 cases,GⅡ in 73 and GⅢ in 13.They all underwent surgical treatment.Postoperatively,they were randomly assigned to 2 groups;63 patients in elemene group received instillation of elemene (400 mg,once a week) 2 weeks after operation and 60 patients in mitomycin C (MMC) group received instillation of MMC (40 mg,once a week) 2 weeks after operation.The instillations were repeated for 6 weeks and thereafter monthly for 1 year.The recurrence rates,side effects,and NK cell activity before and after treatment were evaluated.Results The recurrence rate of elemene group (mean follow-up of 19.7 months) was 7.9% (5 cases),which was significantly lower than that (25.0%,15 cases) of MMC group (mean follow-up of 19.4 months;P<0.05).The side effect in elemene group (3.2%,2 cases) was significantly milder than that in MMC group (25.0%,15 cases)(P<0.05).In elemene group,the NK cell activity after treatment (28±2)% was significantly higher than that before treatment(20±2)%(P<0.05).Conclusion Instillation of elemene after operation is effective and safe in preventing postoperative recurrence of bladder cancer.8 refs.

Prevention strategies of postoperative adhesion in soft tissues by applying biomaterials:Based on the mechanisms of occurrence and development of adhesions

Postoperative adhesion(POA)widely occurs in soft tissues and usually leads to chronic pain,dysfunction of adjacent organs and some acute complications,seriously reducing patients’quality of life and even being life-threatening.Except for adhesiolysis,there are few effective methods to release existing adhesion.However,it requires a second operation and inpatient care and usually triggers recurrent adhesion in a great incidence.Hence,preventing POA formation has been regarded as the most effective clinical strategy.Biomaterials have attracted great attention in preventing POA because they can act as both barriers and drug carriers.Nevertheless,even though much reported research has been demonstrated their efficacy on POA inhibition to a certain extent,thoroughly preventing POA formation is still challenging.Meanwhile,most biomaterials for POA prevention were designed based on limited experiences,not a solid theoretical basis,showing blindness.Hence,we aimed to provide guidance for designing anti-adhesion materials applied in different soft tissues based on the mechanisms of POA occurrence and development.We first classified the postoperative adhesions into four categories according to the different components of diverse adhesion tissues,and named them as“membranous adhesion”,“vascular adhesion”,“adhesive adhesion”and“scarred adhesion”,respectively.Then,the process of the occurrence and development of POA were analyzed,and the main influencing factors in different stages were clarified.Further,we proposed seven strategies for POA prevention by using biomaterials according to these influencing factors.Meanwhile,the relevant practices were summarized according to the corresponding strategies and the future perspectives were analyzed.

Bottlebrush inspired injectable hydrogel for rapid prevention of postoperative and recurrent adhesion

Postsurgical adhesion is a common clinic disease induced by surgical trauma,accompanying serious subsequent complications.Current non-surgical approaches of drugs treatment and biomaterial barrier administration only show limited prevention effects and couldn’t effectively promote peritoneum repair.Herein,inspired by bottlebrush,a novel self-fused,antifouling,and injectable hydrogel is fabricated by the free-radical polymerization in aqueous solution between the methacrylate hyaluronic acid(HA-GMA)and N-(2-hydroxypropyl)methacrylamide(HPMA)monomer without any chemical crosslinkers,termed as H-HPMA hydrogel.The H-HPMA hydrogel can be tuned to perform excellent self-fused properties and suitable abdominal metabolism time.Intriguingly,the introduction of the ultra-hydrophilic HPMA chains to the H-HPMA hydrogel affords an unprecedented antifouling capability.The HPMA chains establish a dense hydrated layer that rapidly prevents the postsurgical adhesions and recurrent adhesions after adhesiolysis in vivo.The H-HPMA hydrogel can repair the peritoneal wound of the rat model within 5 days.Furthermore,an underlying mechanism study reveals that the H-HPMA hydrogel significantly regulated the mesothelial-to-mesenchymal transition(MMT)process dominated by the TGF-β-Smad2/3 signal pathway.Thus,we developed a simple,effective,and available approach to rapidly promote peritoneum regeneration and prevent peritoneal adhesion and adhesion recurrence after adhesiolysis,offering novel design ideas for developing biomaterials to prevent peritoneal adhesion.

A sandwiched patch toward leakage-free and anti-postoperative tissue adhesion sealing of intestinal injuries

Ideal repair of intestinal injury requires a combination of leakage-free sealing and postoperative antiadhesion.However,neither conventional hand-sewn closures nor existing bioglues/patches can achieve such a combination.To this end,we develop a sandwiched patch composed of an inner adhesive and an outer antiadhesive layer that are topologically linked together through a reinforced interlayer.The inner adhesive layer tightly and instantly adheres to the wound sites via-NHS chemistry;the outer antiadhesive layer can inhibit cell and protein fouling based on the zwitterion structure;and the interlayer enhances the bulk resilience of the patch under excessive deformation.This complementary trilayer patch(TLP)possesses a unique combination of instant wet adhesion,high mechanical strength,and biological inertness.Both rat and pig models demonstrate that the sandwiched TLP can effectively seal intestinal injuries and inhibit undesired postoperative tissue adhesion.The study provides valuable insight into the design of multifunctional bioadhesives to enhance the treatment efficacy of intestinal injuries.

Clinical Study of CPD4-PDT for the Prevention of PostoperativeRecurrence in Infiltrative Bladder Cancer

Objective:To assess the efficacy of chlorophyl lderivative（CPD4）-Photodynamic therapy（PDT）in preventing postoperative recurrence of the in filtrativecancer of the urinary bladder-Methods:32 patients were treated with CPD4-PDT postoperationally to prevent therecurrence of can cerall of which being followedup.Results:There currenc erate was42.1%inT2 tumors and 69.2%inT3 tumors（P＜0.05）,and the survival period without tumor has been 19.8±14.8months in T2 tumors,and 22.67±19.72months in T3 tumors（P＞0.05）.There was verysignificant difference inrecurrent rate between grade I and gradeⅡ、Ⅲpatients（0%and66.7%,P<0.001）.ConcIusion:CPD4-PDT is a safe and effectiv emeasureto prevent the recurrence in infiltrative bladder cancer after operation.