BACKGROUND Stapled hemorrhoidopexy(SH)is one of the most commonly used surgical techniques for hemorrhoidal disease,being particularly effective for grade III and IV hemorrhoids.The procedure is associated with better...BACKGROUND Stapled hemorrhoidopexy(SH)is one of the most commonly used surgical techniques for hemorrhoidal disease,being particularly effective for grade III and IV hemorrhoids.The procedure is associated with better short-term outcomes,including less postoperative pain,shorter operative time,faster return to work,and higher patient satisfaction.However,there is a risk-benefit debate surrounding SH due to significant complications from the procedure,such as anal stenosis,rectovaginal fistula,fecal incontinence,and recurrence.AIM To evaluate recurrence rates and factors influencing surgical outcomes following SH in patients with grade III and IV hemorrhoids.METHODS This retrospective,single-center study enrolled a total of 77 patients with grade III/IV hemorrhoids for analysis.Early(less than 7 days after SH)and late(7 or more days after SH)complications were analyzed.Recurrence rates were calculated as well.RESULTS Patients were categorized by hemorrhoid grade and showed no differences in demographic data between the two groups.Recurrence was observed in 4 patients(23.6%)with grade IV hemorrhoids,and no recurrence was noted in patients with grade III hemorrhoids.Postoperative bleeding,incomplete defecation,urgent defecation,incontinence,skin tags,and anal fissure were complications reported by both groups.CONCLUSION Due to the high recurrence rate,SH is not an appropriate treatment option for patients with grade IV hemorrhoids.Open surgery may be a more suitable option for these patients.展开更多
BACKGROUND Stapled hemorrhoidopexy(SH)is currently a widely accepted method for treating the prolapse of internal hemorrhoids.Postoperative anal stenosis is a critical complication of SH.A remedy for this involves the...BACKGROUND Stapled hemorrhoidopexy(SH)is currently a widely accepted method for treating the prolapse of internal hemorrhoids.Postoperative anal stenosis is a critical complication of SH.A remedy for this involves the removal of the circumferential staples of the anastomosis,followed by the creation of a hand-sewn anastomosis.Numerous studies have reported modified SH procedures to improve outcomes.We hypothesized that our modified SH technique may help reduce complications of anal stenosis after SH.AIM To compare outcomes of staple removal at the 3-and 9-o’clock positions during modified SH in patients with mixed hemorrhoids.METHODS This was a single-center,retrospective,observational study.Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015,and January 1,2020,were included.The operation time,blood loss,length of hospital stay,and incidence of minor or major complic-ations were recorded.RESULTS Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015 and January 1,2020,were included.Operation time,blood loss,length of hospital stay,and incidence of minor or major complications were recorded.We investigated 187 patients(mean age,50.9 years)who had undergone our modified SH and 313 patients(mean age,53.0 years)who had undergone standard SH.In the modified SH group,54%of patients had previously undergone surgical intervention for hemorrhoids,compared with the 40.3%of patients in the standard SH group.The modified SH group included five(2.7%)patients with anal stenosis,while 21(6.7%)patients in the standard SH group had complications of anal stenosis.There was a significant relationship between the rate of postoperative anal stenosis and the modified SH:0.251(0.085-0.741)and 0.211(0.069-0.641)in multiple regression analysis.The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.CONCLUSION The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.展开更多
AIM： To compare the results of the anoscope of the PPH kit and a modified anoscope during stapled haemorrhoidopexy. METHODS： The hospital records of 37 patients who underwent stapled haemorrhoidopexy between 2001 an...AIM： To compare the results of the anoscope of the PPH kit and a modified anoscope during stapled haemorrhoidopexy. METHODS： The hospital records of 37 patients who underwent stapled haemorrhoidopexy between 2001 and 2006 were reviewed. The purse-string suture anoscope in the PPH kit was used on 15 patients （Group 1）, and the modified anoscope was used on 22 patients （Group 2）. Demographic characteristics of the patients, operation time, surgeon＇s performance, analgesic requirement, and complications were compared. RESULTS： Operation time was significantly longer in Group 1 （42.0 4- 8.4 min vs 27.7 4- 8.0 min, P = 0.039）. The surgeons reported their operative performance as significantly better in Group 2 （the results of the assessments were poor in ten, medium in four and good in one in Group 1, while good in all patients in Group 2, P 〈 0.001）. The need for haemostatic sutures was significantly higher in Group 1 （six cases） and was needed in two cases in Group 2 （P = 0.034）. CONCLUSION： Operation time decreased and the surgeon＇s satisfaction increased with use of the modified anoscope, and fewer haemostatic sutures were required if the surgeon waited longer before and after firing the stapler.展开更多
AIM: To compare the outcomes of hand-sewn(HS) and linearly stapled(LS) esophagogastric anastomosis for esophageal cancer.METHODS: Before beginning this study, a rigorous protocol was established according to the recom...AIM: To compare the outcomes of hand-sewn(HS) and linearly stapled(LS) esophagogastric anastomosis for esophageal cancer.METHODS: Before beginning this study, a rigorous protocol was established according to the recommendations of the Cochrane Collaboration. Databases and references were searched for all randomizedcontrolled trials and comparative clinical studies that compared LS with HS esophagogastric anastomosis for esophageal cancer. The primary outcomes compared were anastomotic leak and stricture. Subgroup analyses were performed according to site of anastomosis.RESULTS: Fifteen studies were used, comprising 3203 patients(n = 2027 LS and 1176 HS). Primary outcome analysis revealed a significant decrease in anastomotic leakage(RR = 0.51, 95%CI: 0.41-0.65; P < 0.00001) a s s o c i a t e d w i t h L S a n a s t o m o s i s. A s i g n i f i c a n t l y reduced rate of anastomotic stricture associated with LS was also found(RR = 0.56, 95%CI: 0.49-0.64; P < 0.00001). A subgroup analysis according to the site of anastomosis revealed a significantly reduced rate of anastomotic stricture(P < 0.00001). Although there was no significant difference in the decrease in thoracic anastomotic leakage, there was a significant decrease in cervical anastomotic leakage associated with LS(P < 0.00001).CONCLUSION: This meta-analysis indicates that the LS technique contributes to a reduced rate of leakage and stricture compared with the HS method.展开更多
AIM:To evaluate the safety and efficacy of stapled transanal rectal resection(STARR),and to analyze the outcome of the patients 12-mo after the operation.METHODS:From May 2007 to October 2008,50 female patients with r...AIM:To evaluate the safety and efficacy of stapled transanal rectal resection(STARR),and to analyze the outcome of the patients 12-mo after the operation.METHODS:From May 2007 to October 2008,50 female patients with rectocele and/or rectal intussusception underwent STARR.The preoperative status,perioperative and postoperative complications at baseline,3,6 and 12-mo were assessed.Data were collected prospectively from standardized questionnaires for the assessment of constipation[constipation scoring system,Longo’s obstructed defecation syndrome(ODS)score system,symptom severity score],patient satisfaction (visual analogue scale),and quality of life(Patient Assessment of Constipation-Quality of Life Questionnaire).RESULTS:At a 12-mo follow-up,significant improvement in the constipation scoring system,ODS score system,symptom severity score,visual analog scale and quality of life(P<0.0001)was observed.The symptoms of constipation improved in 90%of patients at 12 mo after surgery.The self-reported definitive outcome was excellent in 15(30%)patients,fairly good in 8(16%),good in 22(44%),and poor in 5(10%).CONCLUSION:STARR can be performed safely without major morbidity.Moreover,the procedure seems to be effective for patients with obstructed defecation associated with symptomatic rectocele and rectal intussusception.展开更多
AIM: To compare outcome of stapled hemorrhoidopexy (SH) vs LigaSure hemorrhoidectomy (LH) by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane...AIM: To compare outcome of stapled hemorrhoidopexy (SH) vs LigaSure hemorrhoidectomy (LH) by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index updated to December 2012, were searched. The main outcomes measured were operating time, early postoperative pain, postoperative urinary retention and bleeding, wound problems, gas or fecal incontinence, anal stenosis, length of hospital stay, residual skin tags, prolapse, and recurrence. The meta-analysis was performed using the free software Review Manager. Differences observed between the two groups were expressed as the odds ratio (OR) with 95%CI. A fixedeffects model was used to pool data when statistical heterogeneity was not present. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified 10 publica-tions. After screening, five RCTs published as full articles were included in this meta-analysis. Among the five studies, all described a comparison of the patient baseline characteristics and showed that there was no statistically significant difference between the two groups. Although most of the analyzed outcomes were similar between the two operative techniques, the operating time for SH was significantly longer than for LH (P < 0.00001; OR= -6.39, 95%CI: -7.68 -5.10). The incidence of residual skin tags and prolapse was significantly lower in the LH group than in the SH group [2/111 (1.8%) vs 16/105 (15.2%); P = 0.0004; OR= 0.17, 95%CI: 0.06-0.45). The incidence of recurrence after the procedures was significantly lower in the LH group than in the SH group [2/173 (1.2%) vs 13/174 (7.5%); P = 0.003; OR= 0.21, 95%CI: 0.07-0.59]. CONCLUSION: Both SH and LH are probably equally valuable techniques in modern hemorrhoid surgery. However, LigaSure might have slightly favorable immediate postoperative results and technical advantages.展开更多
AIM:To assess midterm results of stapled transanal rectal resection(STARR)for obstructed defecation syndrome(ODS)and predictive factors for outcome.METHODS:From May 2007 to May 2009,75 female patients underwent STARR ...AIM:To assess midterm results of stapled transanal rectal resection(STARR)for obstructed defecation syndrome(ODS)and predictive factors for outcome.METHODS:From May 2007 to May 2009,75 female patients underwent STARR and were included in the present study.Preoperative and postoperative workup consisted of standardized interview and physical examination including proctoscopy,colonoscopy,anorectal manometry,and defecography.Clinical and functional results were assessed by standardized questionnaires for the assessment of constipation constipation scoring system(CSS),Longo’s ODS score,and symptom severity score(SSS),incontinence Wexner incontinence score(WS),quality of life Patient Assessment of Constipation-Quality of Life Questionnaire(PAC-QOL),and patient satisfaction visual analog scale(VAS).Data were collected prospectively at baseline,12 and 30 mo.RESULTS:The median follow-up was 30 mo(range,30-46 mo).Late postoperative complications occurred in 11(14.7%)patients.Three of these patients required procedure-related reintervention(one diverticulectomy and two excision of staple granuloma).Although the recurrence rate was 10.7%,constipation scores(CSS,ODS score and SSS)significantly improved after STARR(P<0.0001).Significant reduction in ODS symptoms was matched by an improvement in the PAC-QOL and VAS(P<0.0001),and the satisfaction index was excellent in 25(33.3%)patients,good in 23(30.7%),fairly good in 14(18.7%),and poor in 13(17.3%).Nevertheless,the WS increased after STARR(P=0.0169).Incontinence was present or deteriorated in 8(10.7%)patients;6(8%)of whom were new onsets.Univariate analysis revealed that the occurrence of fecal incontinence(preoperative,postoperative or new-onset incontinence;P=0.028,0.000,and 0.007,respectively)was associated with the success of the operation.CONCLUSION:STARR is an acceptable procedure for the surgical correction of ODS.However,its impact on symptomatic recurrence and postoperative incontinence may be problematic.展开更多
AIM:To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy(PpPD).METHODS:In October 2010,we intro...AIM:To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy(PpPD).METHODS:In October 2010,we introduced a mechanical anastomotic technique of gastro-or duodenojejunostomy using staplers during PpPD.We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy(stapled anastomosis group)and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy(hand-sewn anastomosis group).RESULTS:The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group(186.0±29.4 min vs 219.7±50.0 min,P=0.02).In addition,intraoperative blood loss was significantly less(391.0±212.0 mL vs 647.1±482.1 mL,P=0.03)and the time to oral intake was significantly shorter(5.4±1.7d vs 11.3±7.9 d,P=0.002)in the stapled anastomosis group than in the hand-sewn anastomosis group.There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups.CONCLUSION:These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.展开更多
BACKGROUND Obstructed defecation syndrome(ODS) is a widespread disease in the world.Rectocele is the most common cause of ODS in females. Multiple procedures have been performed to treat rectocele and no procedure has...BACKGROUND Obstructed defecation syndrome(ODS) is a widespread disease in the world.Rectocele is the most common cause of ODS in females. Multiple procedures have been performed to treat rectocele and no procedure has been accepted as the gold-standard procedure. Stapled transanal rectal resection(STARR) has been widely used. However, there are still some disadvantages in this procedure and its effectiveness in anterior wall repair is doubtful. Therefore, new procedures are expected to further improve the treatment of rectocele.AIM To evaluate the efficacy and safety of a novel rectocele repair combining Khubchandani's procedure with stapled posterior rectal wall resection.METHODS A cohort of 93 patients were recruited in our randomized clinical trial and were divided into two different groups in a randomized manner. Forty-two patients(group A) underwent Khubchandani's procedure with stapled posterior rectal wall resection and 51 patients(group B) underwent the STARR procedure.Follow-up was performed at 1, 3, 6, and 12 mo after the operation. Preoperative and postoperative ODS scores and depth of rectocele, postoperative complications, blood loss, and hospital stay of each patient were documented. All data were analyzed statistically to evaluate the efficiency and safety of our procedure.RESULTS In group A, 42 patients underwent Khubchandani's procedure with stapled posterior rectal wall resection and 34 were followed until the final analysis. In group B, 51 patients underwent the STARR procedure and 37 were followed until the final analysis. Mean operative duration was 41.47 ± 6.43 min(group A) vs39.24 ± 6.53 min(group B). Mean hospital stay was 3.15 ± 0.70 d(group A) vs 3.14± 0.54 d(group B). Mean blood loss was 10.91 ± 2.52 mL(group A) vs 10.14 ± 1.86 m L(group B). Mean ODS score in group A declined from 16.50 ± 2.06 before operation to 5.06 ± 1.07 one year after the operation, whereas in group B it was17.11 ± 2.57 before operation and 6.03 ± 2.63 one year after the operation. Mean depth of rectocele decreased from 4.32 ± 0.96 cm(group A) vs 4.18 ± 0.95 cm(group B) preoperatively to 1.19 ± 0.43 cm(group A) vs 1.54 ± 0.82 cm(group B)one year after operation. No other serious complications, such as rectovaginal fistula, perianal sepsis, or deaths, were recorded. After 12 mo of follow-up, 30 patients'(30/34, 88.2%) final outcomes were judged as effective and 4(4/34,11.8%) as moderate in group A, whereas in group B, 30(30/37, 81.1%) patients' outcomes were judged as effective, 5(5/37, 13.5%) as moderate, and 2(2/37,5.4%) as poor.CONCLUSION Khubchandani's procedure combined with stapled posterior rectal wall resection is an effective, feasible, and safe procedure with minor trauma to rectocele.展开更多
BACKGROUND Currently,rectovaginal fistula(RVF)continues to be a surgical challenge worldwide,with a relatively low healing rate.Unclosed intermittent suture and poor suture materials may be the main reasons for this.A...BACKGROUND Currently,rectovaginal fistula(RVF)continues to be a surgical challenge worldwide,with a relatively low healing rate.Unclosed intermittent suture and poor suture materials may be the main reasons for this.AIM To evaluate the efficacy and safety of stapled transperineal repair in treating RVF.METHODS This was a retrospective cohort study conducted in the Coloproctology Department of The Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China).Adult patients presenting with RVF who were surgically managed by perineal repair between May 2015 and May 2020 were included.Among the 82 total patients,37 underwent repair with direct suturing and 45 underwent repair with stapling.Patient demographic data,Wexner faecal incontinence score,and operative data were analyzed.Recurrence rate and associated risk factors were assessed.RESULTS The direct suture and stapled repair groups showed similar clinical characteristics for aetiology,surgical history,fistula features,and perioperative Wexner score.The stapled repair group did not show superior results over the suture repair group in regard to operative time,blood loss,and hospital stay.However,the stapled repair group showed better postoperative Wexner score(1.04±1.89 vs 2.73±3.75,P=0.021),less intercourse pain(1/45 vs 17/37,P=0.045),and lower recurrence rate(6/45 vs 17/37,P=0.001).There was no protective effect from previous repair history,smaller diameter of fistula(<0.5 cm),better control of defecation(Wexner<10),or stapled repair.Direct suture repair and preoperative high Wexner score(>10)were risk factors for fistula recurrence.Furthermore,stapled repair gave better efficacy in treating complex RVFs(i.e.,multiple transperineal repair history,mid-level fistula position,and poor control of defecation).CONCLUSION Stapled transperineal repair is advantageous for management of RVF,providing a high primary healing rate and low recurrence rate.展开更多
AIM:To prospectively assess the eff icacy and safety of stapled trans-anal rectal resection(STARR) compared to standard conservative treatment,and whether preoperative symptoms and findings at defecography and anorect...AIM:To prospectively assess the eff icacy and safety of stapled trans-anal rectal resection(STARR) compared to standard conservative treatment,and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR.METHODS:Thirty patients(Female,28;age:51 ± 9 years) with rectocele or rectal intussusception,a defecation disorder,and functional constipation were submitted for STARR.Thirty comparable patients(Female,30;age 53 ± 13 years),who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol,were assessed.Patients were interviewed with a standardized questionnaire at study enrollment and 38 ± 18 mo after the STARR procedure or during macrogol treatment.A responder was def ined as an absence of the Rome Ⅲ diagnostic criteria for functional constipation.Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients,respectively.RESULTS:After STARR,53% of patients were responders;during conservative treatment,75% were responders.After STARR,30% of the patients reported the use of laxatives,17% had intermittent anal pain,13% had anal leakage,13% required digital facilitation,6% experienced defecatory urgency,6% experienced fecal incontinence,and 6% required re-intervention.During macrogol therapy,23% of the patients complained of abdominal bloating and 13% of borborygmi,and 3% required digital facilitation.No preoperative symptom,defecographic,or manometric finding predicted the outcome of STARR.Post-operative defecography showed a statistically significant reduction(P < 0.05) of the rectal diameter and rectocele.The postoperative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified,and that rectal compliance was reduced(P = 0.01).CONCLUSION:STARR is not better and is less safe than macrogol in the treatment of defecation disorders.It could be considered as an alternative therapy in patients unresponsive to macrogol.展开更多
A rare case of a severely constipated patient with rectal aganglionosis is herein reported.The patient,who had no megacolon/megarectum,underwent a STARR,i.e.,stapled transanal rectal resection,for obstructed defecatio...A rare case of a severely constipated patient with rectal aganglionosis is herein reported.The patient,who had no megacolon/megarectum,underwent a STARR,i.e.,stapled transanal rectal resection,for obstructed defecation,but her symptoms were not relieved.She started suffering from severe chronic proctalgia possibly due to peri-retained staples fibrosis.Intestinal transit times were normal and no megarectum/megacolon was found at barium enema.A diverting sigmoidostomy was then carried out,which was complicated by an early parastomal hernia,which affected stoma emptying.She also had a severe diverting proctitis,causing rectal bleeding,and still complained of both proctalgia and tenesmus.A deep rectal biopsy under anesthesia showed no ganglia in the rectum,whereas ganglia were present and normal in the sigmoid at the stoma site.As she refused a Duhamel procedure,an intersphincteric rectal resection and a refashioning of the stoma was scheduled.This case report shows that a complete assessment of the potential causes of constipation should be carried out prior to any surgical procedure.展开更多
HIV fusion inhibitors are promising therapeutic agents for AIDS treatment. One fusion inhibitor has been approved as anti-HIV drug, while more of them are in preclinical studies or clinical trials. Highly active fusio...HIV fusion inhibitors are promising therapeutic agents for AIDS treatment. One fusion inhibitor has been approved as anti-HIV drug, while more of them are in preclinical studies or clinical trials. Highly active fusion inhibitors with excellent pharmacokinetic properties are still needed for development of anti-HIV drugs. We found that all-hydrocarbon staples inserted in SC34 EK could not only enhance the inhibitory activity of inhibitors against HIV-1, but also improve protease resistance. Further study revealed that SC34 EK-1 containing a staple was a potent fusion inhibitor with IC;value of 0.04-6.4 nmol/L towards diverse HIV-1 subtypes and half-life value of 112 min against protease hydrolysis. X-ray crystallography studies indicated that introduction of a hydrocarbon staple in SC34 EK could make the amino acid at the interaction surface form perfect conformation to promote inhibitor peptide interacting with target.展开更多
AIM:To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy.METHODS:From January 2002 to March 2011,fourtyfive patients underwent ileal ...AIM:To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy.METHODS:From January 2002 to March 2011,fourtyfive patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were reviewed.RESULTS:Patients with ulcerative colitis(n = 29) and familial adenomatous polyposis(n = 16) underwent ileal pouch-anal anastomosis with modified doublestapled mucosectomy.Twenty-eight patients underwent one-stage restorative proctocolectomy,ileal pouch anal anastomosis,protective ileostomy and the ileostomy was closed 4-12 mo postoperatively.Two-stage procedures were performed in seventeen urgent patients,proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with ileostomy.Morbidity within the first 30 d of surgery occurred in 10(22.2%) patients,all of them could be treated conservatively.During the median follow-up of 65 mo,mild to moderate anastomotic narrowing was occurred in 4 patients,one patient developed persistent anastomotic stricture and need surgical intervention.Thirtyfive percent of patients developed at least 1 episode of pouchitis.There was no incontinence in our patients,the median functional Oresland score was 6,3 and 2 after 1 year,2.5 years and 5 years respectively.Nearly half patients(44.4%) reported "moderate functioning",37.7% reported "good functioning",whereas in 17.7% of patients "poor functioning" was observed after 1 year.Five years later,79.2% of patients with good function,16.7% with moderate function,only 4.2% of patients with poor function.CONCLUSION:The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising,with a low complication rate and good long-term functional results.展开更多
Stapled hemorrhoidopexy is a surgical procedure used worldwide for the treatment of grade Ⅲ and N hemorrhoids in all age groups. However, lifethreatening complications occur occasionally. The following case report de...Stapled hemorrhoidopexy is a surgical procedure used worldwide for the treatment of grade Ⅲ and N hemorrhoids in all age groups. However, lifethreatening complications occur occasionally. The following case report describes the development of pelvic sepsis after stapled hemorrhoidopexy. A literature review of techniques used to manage major septic complications after stapled hemorrhoidopexy was performed. There is no standardized treatment currently available. Stapled hemorrhoidopexy is a safe, effective and time-efficient procedure in the hands of experienced colorectal surgeons.展开更多
BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to...BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to predict preoperatively the need for multiple linear stapler cartridges during DST anastomosis.AIM To develop a deep learning model to predict multiple firings during DST anastomosis based on pelvic magnetic resonance imaging(MRI).METHODS We collected 9476 MR images from 328 mid-low rectal cancer patients undergoing LAR with DST anastomosis,which were randomly divided into a training set(n=260)and testing set(n=68).Binary logistic regression was adopted to create a clinical model using six factors.The sequence of fast spin-echo T2-weighted MRI of the entire pelvis was segmented and analyzed.Pure-image and clinical-image integrated deep learning models were constructed using the mask region-based convolutional neural network segmentation tool and three-dimensional convolutional networks.Sensitivity,specificity,accuracy,positive predictive value(PPV),and area under the receiver operating characteristic curve(AUC)was calculated for each model.RESULTS The prevalence of≥3 linear stapler cartridges was 17.7%(58/328).The prevalence of AL was statistically significantly higher in patients with≥3 cartridges compared to those with≤2 cartridges(25.0%vs 11.8%,P=0.018).Preoperative carcinoembryonic antigen level>5 ng/mL(OR=2.11,95%CI 1.08-4.12,P=0.028)and tumor size≥5 cm(OR=3.57,95%CI 1.61-7.89,P=0.002)were recognized as independent risk factors for use of≥3 linear stapler cartridges.Diagnostic performance was better with the integrated model(accuracy=94.1%,PPV=87.5%,and AUC=0.88)compared with the clinical model(accuracy=86.7%,PPV=38.9%,and AUC=0.72)and the image model(accuracy=91.2%,PPV=83.3%,and AUC=0.81).CONCLUSION MRI-based deep learning model can predict the use of≥3 linear stapler cartridges during DST anastomosis in laparoscopic LAR surgery.This model might help determine the best anastomosis strategy by avoiding DST when there is a high probability of the need for≥3 linear stapler cartridges.展开更多
In recent years, the strategy of inhibiting the interactions of p53 with murine double minute 2(MDM2)and murine double minute X(MDMX) has been proved to be a promising approach for tumor therapy.However, the poor prot...In recent years, the strategy of inhibiting the interactions of p53 with murine double minute 2(MDM2)and murine double minute X(MDMX) has been proved to be a promising approach for tumor therapy.However, the poor proteolytical stability and low intracellular delivery efficiency of peptide inhibitors limit their clinical application. Here, we designed and synthesized the bicyclic stapled peptides based on p53 by combining all-hydrocarbon stapling and lactam stapling strategies. We demonstrated that bicyclic stapled peptide p53-16 significantly improved α-helicity and proteolytic stability. Especially, p53-16showed nanomolar binding affinity for MDM2 and MDMX. In addition, p53-16 could penetrate the cell membrane, and selectively inhibited the activity of tumor cells via activating p53 pathway in vitro. Our data suggest that p53-16 is a potential dual inhibitor of MDM2 and MDMX interactions. The bicyclic stapling strategy is a promising drug design strategy for protein–protein interactions inhibitors.展开更多
Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydroc...Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydrocarbon peptide stapling technique has already widely adopted with great success,yielding numerous potent peptide-based molecules.Based on our prior efforts,we conceived and prepared a double-stapled peptide in this study,termed FRNC-1,which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β.The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form.Additionally,FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized(OVX)mice after intravenous injection and importantly,after oral(intragastric)administration.The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis(PMOP).展开更多
Objective:The present study was designed to evaluate the functional outcome of stapled transanal rectal resection(STARR)and to examine the relationship between the population density of the interstitial cells of Cajal...Objective:The present study was designed to evaluate the functional outcome of stapled transanal rectal resection(STARR)and to examine the relationship between the population density of the interstitial cells of Cajal(ICC)and the efficacy of the STARR operation in the management of obstructed defecation syndrome(ODS)patients.Methods:Full-thickness rectal samples were obtained from 50 ODS patients who underwent STARR.Samples were analysed using ICC immunohistochemistry.Clinical and functional parameters obtained with defecography and anorectal manometry were compared with 20 controls.Results:ICCs were significantly decreased in patients in the submucosal(SM),intramuscular(IM)andmyenteric(MY)regions when compared with the control group(P<0.05).The mean pre-operative Cleveland Constipation Score(CCS)was 24.264.1,whilst the CCS at 1,2,3,4 and 5 years post-operatively decreased significantly(P<0.05).At 3 post-operative years,58.3%(28/48)of the patients reported a favorable outcome(CCS10).On univariate analysis,the functional results were worse in those with pre-operative digitation(P=0.017),a decreased ICC-MY cell population(P=0.067),a higher resting anal canal pressure(P=0.039)and a higher rectal sensory threshold(P=0.073).Multivariate analysis showed the decreased ICC-MY cell population was an independent predictor for low unfavorable functional outcome(odds ratio=0.097,95%confidence interval:0.012–0.766).Conclusions:STARR achieved acceptable results at the cost of a slight deterioration over amore prolonged follow-up.Patients with a decreased ICC number in the rectal specimen showed an unfavorable functional outcome where pre-operative histological assessment of a full-thickness rectal samplemight predict for the functional outcome following STARR.展开更多
Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health.Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying80%of all lung cancer subtypes...Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health.Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying80%of all lung cancer subtypes.Except for other mutations (e.g.,KRAS^(G12V/D)) that are also vital for the occurrence,KRAS^(G12C) gene mutation is a significant driving force of NSCLC,with a prevalence of approximately 14% of all NSCLC patients.However,there are only a few therapeutic drugs targeting KRAS^(G12C) mutations currently.Here,we synthesized hydrocarbon-stapled peptide 3 that was much shorter and more stable with modest KRAS^(G12C) binding affinity and the same anti-tumor effect based on the a-helical peptide mimic SAH-SOS1_(A).The stapled peptide 3 effectively induced G2/M arrest and apoptosis,inhibiting cell growth in KRAS-mutated lung cancer cells via disrupting the KRASmediated RAF/MEK/ERK signaling,which was verified from the perspective of genomics and proteomics.Peptide 3 also exhibited strong anti-trypsin and anti-chymotrypsin abilities,as well as good plasma stability and human liver microsomal metabolic stability.Overall,peptide 3 retains the equivalent anti-tumor activity of SAH-SOS1_(A) but with improved stability and affinity,superior to SAH-SOS1_(A).Our work offers a structural optimization approach of KRAS^(G12C) peptide inhibitors for cancer therapy.展开更多
文摘BACKGROUND Stapled hemorrhoidopexy(SH)is one of the most commonly used surgical techniques for hemorrhoidal disease,being particularly effective for grade III and IV hemorrhoids.The procedure is associated with better short-term outcomes,including less postoperative pain,shorter operative time,faster return to work,and higher patient satisfaction.However,there is a risk-benefit debate surrounding SH due to significant complications from the procedure,such as anal stenosis,rectovaginal fistula,fecal incontinence,and recurrence.AIM To evaluate recurrence rates and factors influencing surgical outcomes following SH in patients with grade III and IV hemorrhoids.METHODS This retrospective,single-center study enrolled a total of 77 patients with grade III/IV hemorrhoids for analysis.Early(less than 7 days after SH)and late(7 or more days after SH)complications were analyzed.Recurrence rates were calculated as well.RESULTS Patients were categorized by hemorrhoid grade and showed no differences in demographic data between the two groups.Recurrence was observed in 4 patients(23.6%)with grade IV hemorrhoids,and no recurrence was noted in patients with grade III hemorrhoids.Postoperative bleeding,incomplete defecation,urgent defecation,incontinence,skin tags,and anal fissure were complications reported by both groups.CONCLUSION Due to the high recurrence rate,SH is not an appropriate treatment option for patients with grade IV hemorrhoids.Open surgery may be a more suitable option for these patients.
文摘BACKGROUND Stapled hemorrhoidopexy(SH)is currently a widely accepted method for treating the prolapse of internal hemorrhoids.Postoperative anal stenosis is a critical complication of SH.A remedy for this involves the removal of the circumferential staples of the anastomosis,followed by the creation of a hand-sewn anastomosis.Numerous studies have reported modified SH procedures to improve outcomes.We hypothesized that our modified SH technique may help reduce complications of anal stenosis after SH.AIM To compare outcomes of staple removal at the 3-and 9-o’clock positions during modified SH in patients with mixed hemorrhoids.METHODS This was a single-center,retrospective,observational study.Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015,and January 1,2020,were included.The operation time,blood loss,length of hospital stay,and incidence of minor or major complic-ations were recorded.RESULTS Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1,2015 and January 1,2020,were included.Operation time,blood loss,length of hospital stay,and incidence of minor or major complications were recorded.We investigated 187 patients(mean age,50.9 years)who had undergone our modified SH and 313 patients(mean age,53.0 years)who had undergone standard SH.In the modified SH group,54%of patients had previously undergone surgical intervention for hemorrhoids,compared with the 40.3%of patients in the standard SH group.The modified SH group included five(2.7%)patients with anal stenosis,while 21(6.7%)patients in the standard SH group had complications of anal stenosis.There was a significant relationship between the rate of postoperative anal stenosis and the modified SH:0.251(0.085-0.741)and 0.211(0.069-0.641)in multiple regression analysis.The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.CONCLUSION The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.
文摘AIM： To compare the results of the anoscope of the PPH kit and a modified anoscope during stapled haemorrhoidopexy. METHODS： The hospital records of 37 patients who underwent stapled haemorrhoidopexy between 2001 and 2006 were reviewed. The purse-string suture anoscope in the PPH kit was used on 15 patients （Group 1）, and the modified anoscope was used on 22 patients （Group 2）. Demographic characteristics of the patients, operation time, surgeon＇s performance, analgesic requirement, and complications were compared. RESULTS： Operation time was significantly longer in Group 1 （42.0 4- 8.4 min vs 27.7 4- 8.0 min, P = 0.039）. The surgeons reported their operative performance as significantly better in Group 2 （the results of the assessments were poor in ten, medium in four and good in one in Group 1, while good in all patients in Group 2, P 〈 0.001）. The need for haemostatic sutures was significantly higher in Group 1 （six cases） and was needed in two cases in Group 2 （P = 0.034）. CONCLUSION： Operation time decreased and the surgeon＇s satisfaction increased with use of the modified anoscope, and fewer haemostatic sutures were required if the surgeon waited longer before and after firing the stapler.
文摘AIM: To compare the outcomes of hand-sewn(HS) and linearly stapled(LS) esophagogastric anastomosis for esophageal cancer.METHODS: Before beginning this study, a rigorous protocol was established according to the recommendations of the Cochrane Collaboration. Databases and references were searched for all randomizedcontrolled trials and comparative clinical studies that compared LS with HS esophagogastric anastomosis for esophageal cancer. The primary outcomes compared were anastomotic leak and stricture. Subgroup analyses were performed according to site of anastomosis.RESULTS: Fifteen studies were used, comprising 3203 patients(n = 2027 LS and 1176 HS). Primary outcome analysis revealed a significant decrease in anastomotic leakage(RR = 0.51, 95%CI: 0.41-0.65; P < 0.00001) a s s o c i a t e d w i t h L S a n a s t o m o s i s. A s i g n i f i c a n t l y reduced rate of anastomotic stricture associated with LS was also found(RR = 0.56, 95%CI: 0.49-0.64; P < 0.00001). A subgroup analysis according to the site of anastomosis revealed a significantly reduced rate of anastomotic stricture(P < 0.00001). Although there was no significant difference in the decrease in thoracic anastomotic leakage, there was a significant decrease in cervical anastomotic leakage associated with LS(P < 0.00001).CONCLUSION: This meta-analysis indicates that the LS technique contributes to a reduced rate of leakage and stricture compared with the HS method.
文摘AIM:To evaluate the safety and efficacy of stapled transanal rectal resection(STARR),and to analyze the outcome of the patients 12-mo after the operation.METHODS:From May 2007 to October 2008,50 female patients with rectocele and/or rectal intussusception underwent STARR.The preoperative status,perioperative and postoperative complications at baseline,3,6 and 12-mo were assessed.Data were collected prospectively from standardized questionnaires for the assessment of constipation[constipation scoring system,Longo’s obstructed defecation syndrome(ODS)score system,symptom severity score],patient satisfaction (visual analogue scale),and quality of life(Patient Assessment of Constipation-Quality of Life Questionnaire).RESULTS:At a 12-mo follow-up,significant improvement in the constipation scoring system,ODS score system,symptom severity score,visual analog scale and quality of life(P<0.0001)was observed.The symptoms of constipation improved in 90%of patients at 12 mo after surgery.The self-reported definitive outcome was excellent in 15(30%)patients,fairly good in 8(16%),good in 22(44%),and poor in 5(10%).CONCLUSION:STARR can be performed safely without major morbidity.Moreover,the procedure seems to be effective for patients with obstructed defecation associated with symptomatic rectocele and rectal intussusception.
文摘AIM: To compare outcome of stapled hemorrhoidopexy (SH) vs LigaSure hemorrhoidectomy (LH) by a meta-analysis of available randomized controlled trials (RCTs). METHODS: Databases, including PubMed, EMBASE, the Cochrane Library, and the Science Citation Index updated to December 2012, were searched. The main outcomes measured were operating time, early postoperative pain, postoperative urinary retention and bleeding, wound problems, gas or fecal incontinence, anal stenosis, length of hospital stay, residual skin tags, prolapse, and recurrence. The meta-analysis was performed using the free software Review Manager. Differences observed between the two groups were expressed as the odds ratio (OR) with 95%CI. A fixedeffects model was used to pool data when statistical heterogeneity was not present. If statistical heterogeneity was present (P < 0.05), a random-effects model was used. RESULTS: The initial search identified 10 publica-tions. After screening, five RCTs published as full articles were included in this meta-analysis. Among the five studies, all described a comparison of the patient baseline characteristics and showed that there was no statistically significant difference between the two groups. Although most of the analyzed outcomes were similar between the two operative techniques, the operating time for SH was significantly longer than for LH (P < 0.00001; OR= -6.39, 95%CI: -7.68 -5.10). The incidence of residual skin tags and prolapse was significantly lower in the LH group than in the SH group [2/111 (1.8%) vs 16/105 (15.2%); P = 0.0004; OR= 0.17, 95%CI: 0.06-0.45). The incidence of recurrence after the procedures was significantly lower in the LH group than in the SH group [2/173 (1.2%) vs 13/174 (7.5%); P = 0.003; OR= 0.21, 95%CI: 0.07-0.59]. CONCLUSION: Both SH and LH are probably equally valuable techniques in modern hemorrhoid surgery. However, LigaSure might have slightly favorable immediate postoperative results and technical advantages.
基金Supported by Clinical Research Fund of Beijing Municipal Science and Technology Commission,No.Z111107058811051
文摘AIM:To assess midterm results of stapled transanal rectal resection(STARR)for obstructed defecation syndrome(ODS)and predictive factors for outcome.METHODS:From May 2007 to May 2009,75 female patients underwent STARR and were included in the present study.Preoperative and postoperative workup consisted of standardized interview and physical examination including proctoscopy,colonoscopy,anorectal manometry,and defecography.Clinical and functional results were assessed by standardized questionnaires for the assessment of constipation constipation scoring system(CSS),Longo’s ODS score,and symptom severity score(SSS),incontinence Wexner incontinence score(WS),quality of life Patient Assessment of Constipation-Quality of Life Questionnaire(PAC-QOL),and patient satisfaction visual analog scale(VAS).Data were collected prospectively at baseline,12 and 30 mo.RESULTS:The median follow-up was 30 mo(range,30-46 mo).Late postoperative complications occurred in 11(14.7%)patients.Three of these patients required procedure-related reintervention(one diverticulectomy and two excision of staple granuloma).Although the recurrence rate was 10.7%,constipation scores(CSS,ODS score and SSS)significantly improved after STARR(P<0.0001).Significant reduction in ODS symptoms was matched by an improvement in the PAC-QOL and VAS(P<0.0001),and the satisfaction index was excellent in 25(33.3%)patients,good in 23(30.7%),fairly good in 14(18.7%),and poor in 13(17.3%).Nevertheless,the WS increased after STARR(P=0.0169).Incontinence was present or deteriorated in 8(10.7%)patients;6(8%)of whom were new onsets.Univariate analysis revealed that the occurrence of fecal incontinence(preoperative,postoperative or new-onset incontinence;P=0.028,0.000,and 0.007,respectively)was associated with the success of the operation.CONCLUSION:STARR is an acceptable procedure for the surgical correction of ODS.However,its impact on symptomatic recurrence and postoperative incontinence may be problematic.
文摘AIM:To investigate whether a stapled technique is superior to the conventional hand-sewn technique for gastro/duodenojejunostomy during pylorus-preserving pancreaticoduodenectomy(PpPD).METHODS:In October 2010,we introduced a mechanical anastomotic technique of gastro-or duodenojejunostomy using staplers during PpPD.We compared clinical outcomes between 19 patients who underwent PpPD with a stapled gastro/duodenojejunostomy(stapled anastomosis group)and 19 patients who underwent PpPD with a conventional hand-sewn duodenojejunostomy(hand-sewn anastomosis group).RESULTS:The time required for reconstruction was significantly shorter in the stapled anastomosis group than in the hand-sewn anastomosis group(186.0±29.4 min vs 219.7±50.0 min,P=0.02).In addition,intraoperative blood loss was significantly less(391.0±212.0 mL vs 647.1±482.1 mL,P=0.03)and the time to oral intake was significantly shorter(5.4±1.7d vs 11.3±7.9 d,P=0.002)in the stapled anastomosis group than in the hand-sewn anastomosis group.There were no differences in the incidences of delayed gastric emptying and other postoperative complications between the groups.CONCLUSION:These results suggest that stapled gastro/duodenojejunostomy shortens reconstruction time during PpPD without affecting the incidence of delayed gastric emptying.
文摘BACKGROUND Obstructed defecation syndrome(ODS) is a widespread disease in the world.Rectocele is the most common cause of ODS in females. Multiple procedures have been performed to treat rectocele and no procedure has been accepted as the gold-standard procedure. Stapled transanal rectal resection(STARR) has been widely used. However, there are still some disadvantages in this procedure and its effectiveness in anterior wall repair is doubtful. Therefore, new procedures are expected to further improve the treatment of rectocele.AIM To evaluate the efficacy and safety of a novel rectocele repair combining Khubchandani's procedure with stapled posterior rectal wall resection.METHODS A cohort of 93 patients were recruited in our randomized clinical trial and were divided into two different groups in a randomized manner. Forty-two patients(group A) underwent Khubchandani's procedure with stapled posterior rectal wall resection and 51 patients(group B) underwent the STARR procedure.Follow-up was performed at 1, 3, 6, and 12 mo after the operation. Preoperative and postoperative ODS scores and depth of rectocele, postoperative complications, blood loss, and hospital stay of each patient were documented. All data were analyzed statistically to evaluate the efficiency and safety of our procedure.RESULTS In group A, 42 patients underwent Khubchandani's procedure with stapled posterior rectal wall resection and 34 were followed until the final analysis. In group B, 51 patients underwent the STARR procedure and 37 were followed until the final analysis. Mean operative duration was 41.47 ± 6.43 min(group A) vs39.24 ± 6.53 min(group B). Mean hospital stay was 3.15 ± 0.70 d(group A) vs 3.14± 0.54 d(group B). Mean blood loss was 10.91 ± 2.52 mL(group A) vs 10.14 ± 1.86 m L(group B). Mean ODS score in group A declined from 16.50 ± 2.06 before operation to 5.06 ± 1.07 one year after the operation, whereas in group B it was17.11 ± 2.57 before operation and 6.03 ± 2.63 one year after the operation. Mean depth of rectocele decreased from 4.32 ± 0.96 cm(group A) vs 4.18 ± 0.95 cm(group B) preoperatively to 1.19 ± 0.43 cm(group A) vs 1.54 ± 0.82 cm(group B)one year after operation. No other serious complications, such as rectovaginal fistula, perianal sepsis, or deaths, were recorded. After 12 mo of follow-up, 30 patients'(30/34, 88.2%) final outcomes were judged as effective and 4(4/34,11.8%) as moderate in group A, whereas in group B, 30(30/37, 81.1%) patients' outcomes were judged as effective, 5(5/37, 13.5%) as moderate, and 2(2/37,5.4%) as poor.CONCLUSION Khubchandani's procedure combined with stapled posterior rectal wall resection is an effective, feasible, and safe procedure with minor trauma to rectocele.
基金The Sixth Affiliated Hospital,Sun Yat-sen University Clinical Research 1010 Program,No.1010PY(2020)-18Science and Technology Program of Guangzhou,China,No.202002020081+1 种基金National Natural Science Foundation of China,No.81973847Natural Science Foundation of Guangdong Province of China,No.2020A1515011254.
文摘BACKGROUND Currently,rectovaginal fistula(RVF)continues to be a surgical challenge worldwide,with a relatively low healing rate.Unclosed intermittent suture and poor suture materials may be the main reasons for this.AIM To evaluate the efficacy and safety of stapled transperineal repair in treating RVF.METHODS This was a retrospective cohort study conducted in the Coloproctology Department of The Sixth Affiliated Hospital of Sun Yat-sen University(Guangzhou,China).Adult patients presenting with RVF who were surgically managed by perineal repair between May 2015 and May 2020 were included.Among the 82 total patients,37 underwent repair with direct suturing and 45 underwent repair with stapling.Patient demographic data,Wexner faecal incontinence score,and operative data were analyzed.Recurrence rate and associated risk factors were assessed.RESULTS The direct suture and stapled repair groups showed similar clinical characteristics for aetiology,surgical history,fistula features,and perioperative Wexner score.The stapled repair group did not show superior results over the suture repair group in regard to operative time,blood loss,and hospital stay.However,the stapled repair group showed better postoperative Wexner score(1.04±1.89 vs 2.73±3.75,P=0.021),less intercourse pain(1/45 vs 17/37,P=0.045),and lower recurrence rate(6/45 vs 17/37,P=0.001).There was no protective effect from previous repair history,smaller diameter of fistula(<0.5 cm),better control of defecation(Wexner<10),or stapled repair.Direct suture repair and preoperative high Wexner score(>10)were risk factors for fistula recurrence.Furthermore,stapled repair gave better efficacy in treating complex RVFs(i.e.,multiple transperineal repair history,mid-level fistula position,and poor control of defecation).CONCLUSION Stapled transperineal repair is advantageous for management of RVF,providing a high primary healing rate and low recurrence rate.
文摘AIM:To prospectively assess the eff icacy and safety of stapled trans-anal rectal resection(STARR) compared to standard conservative treatment,and whether preoperative symptoms and findings at defecography and anorectal manometry can predict the outcome of STARR.METHODS:Thirty patients(Female,28;age:51 ± 9 years) with rectocele or rectal intussusception,a defecation disorder,and functional constipation were submitted for STARR.Thirty comparable patients(Female,30;age 53 ± 13 years),who presented with symptoms of rectocele or rectal intussusception and were treated with macrogol,were assessed.Patients were interviewed with a standardized questionnaire at study enrollment and 38 ± 18 mo after the STARR procedure or during macrogol treatment.A responder was def ined as an absence of the Rome Ⅲ diagnostic criteria for functional constipation.Defecography and rectoanal manometry were performed before and after the STARR procedure in 16 and 12 patients,respectively.RESULTS:After STARR,53% of patients were responders;during conservative treatment,75% were responders.After STARR,30% of the patients reported the use of laxatives,17% had intermittent anal pain,13% had anal leakage,13% required digital facilitation,6% experienced defecatory urgency,6% experienced fecal incontinence,and 6% required re-intervention.During macrogol therapy,23% of the patients complained of abdominal bloating and 13% of borborygmi,and 3% required digital facilitation.No preoperative symptom,defecographic,or manometric finding predicted the outcome of STARR.Post-operative defecography showed a statistically significant reduction(P < 0.05) of the rectal diameter and rectocele.The postoperative anorectal manometry showed that anal pressure and rectal sensitivity were not significantly modified,and that rectal compliance was reduced(P = 0.01).CONCLUSION:STARR is not better and is less safe than macrogol in the treatment of defecation disorders.It could be considered as an alternative therapy in patients unresponsive to macrogol.
文摘A rare case of a severely constipated patient with rectal aganglionosis is herein reported.The patient,who had no megacolon/megarectum,underwent a STARR,i.e.,stapled transanal rectal resection,for obstructed defecation,but her symptoms were not relieved.She started suffering from severe chronic proctalgia possibly due to peri-retained staples fibrosis.Intestinal transit times were normal and no megarectum/megacolon was found at barium enema.A diverting sigmoidostomy was then carried out,which was complicated by an early parastomal hernia,which affected stoma emptying.She also had a severe diverting proctitis,causing rectal bleeding,and still complained of both proctalgia and tenesmus.A deep rectal biopsy under anesthesia showed no ganglia in the rectum,whereas ganglia were present and normal in the sigmoid at the stoma site.As she refused a Duhamel procedure,an intersphincteric rectal resection and a refashioning of the stoma was scheduled.This case report shows that a complete assessment of the potential causes of constipation should be carried out prior to any surgical procedure.
基金supported by the National Natural Science Foundation of China (No. 21602121)the Natural Science Foundation of Inner Mongolia (No. 2016BS0201)+2 种基金the Inner Mongolia Autonomous Region Higher School Youth scientific Talents Support Project(No. NJYT-17-B22)the Research Funds of Baotou Medical College(Nos. BSJJ201620, BYJJ-YF 201707)Beijing Tongzhou District Science and Technology Project(No. KJ2017CX039-14)
文摘HIV fusion inhibitors are promising therapeutic agents for AIDS treatment. One fusion inhibitor has been approved as anti-HIV drug, while more of them are in preclinical studies or clinical trials. Highly active fusion inhibitors with excellent pharmacokinetic properties are still needed for development of anti-HIV drugs. We found that all-hydrocarbon staples inserted in SC34 EK could not only enhance the inhibitory activity of inhibitors against HIV-1, but also improve protease resistance. Further study revealed that SC34 EK-1 containing a staple was a potent fusion inhibitor with IC;value of 0.04-6.4 nmol/L towards diverse HIV-1 subtypes and half-life value of 112 min against protease hydrolysis. X-ray crystallography studies indicated that introduction of a hydrocarbon staple in SC34 EK could make the amino acid at the interaction surface form perfect conformation to promote inhibitor peptide interacting with target.
文摘AIM:To investigate the feasibility and long-term functional outcome of ileal pouch-anal anastomosis with modified double-stapled mucosectomy.METHODS:From January 2002 to March 2011,fourtyfive patients underwent ileal pouch anal anastomosis with modified double-stapled mucosectomy technique and the clinical data obtained for these patients were reviewed.RESULTS:Patients with ulcerative colitis(n = 29) and familial adenomatous polyposis(n = 16) underwent ileal pouch-anal anastomosis with modified doublestapled mucosectomy.Twenty-eight patients underwent one-stage restorative proctocolectomy,ileal pouch anal anastomosis,protective ileostomy and the ileostomy was closed 4-12 mo postoperatively.Two-stage procedures were performed in seventeen urgent patients,proctectomy and ileal pouch anal anastomosis were completed after previous colectomy with ileostomy.Morbidity within the first 30 d of surgery occurred in 10(22.2%) patients,all of them could be treated conservatively.During the median follow-up of 65 mo,mild to moderate anastomotic narrowing was occurred in 4 patients,one patient developed persistent anastomotic stricture and need surgical intervention.Thirtyfive percent of patients developed at least 1 episode of pouchitis.There was no incontinence in our patients,the median functional Oresland score was 6,3 and 2 after 1 year,2.5 years and 5 years respectively.Nearly half patients(44.4%) reported "moderate functioning",37.7% reported "good functioning",whereas in 17.7% of patients "poor functioning" was observed after 1 year.Five years later,79.2% of patients with good function,16.7% with moderate function,only 4.2% of patients with poor function.CONCLUSION:The results of ileal pouch anal anastomosis with modified double-stapled mucosectomy technique are promising,with a low complication rate and good long-term functional results.
文摘Stapled hemorrhoidopexy is a surgical procedure used worldwide for the treatment of grade Ⅲ and N hemorrhoids in all age groups. However, lifethreatening complications occur occasionally. The following case report describes the development of pelvic sepsis after stapled hemorrhoidopexy. A literature review of techniques used to manage major septic complications after stapled hemorrhoidopexy was performed. There is no standardized treatment currently available. Stapled hemorrhoidopexy is a safe, effective and time-efficient procedure in the hands of experienced colorectal surgeons.
基金Shanghai Jiaotong University,No.YG2019QNB24This study was reviewed and approved by Ruijin Hospital Ethics Committee(Approval No.2019-82).
文摘BACKGROUND Multiple linear stapler firings during double stapling technique(DST)after laparoscopic low anterior resection(LAR)are associated with an increased risk of anastomotic leakage(AL).However,it is difficult to predict preoperatively the need for multiple linear stapler cartridges during DST anastomosis.AIM To develop a deep learning model to predict multiple firings during DST anastomosis based on pelvic magnetic resonance imaging(MRI).METHODS We collected 9476 MR images from 328 mid-low rectal cancer patients undergoing LAR with DST anastomosis,which were randomly divided into a training set(n=260)and testing set(n=68).Binary logistic regression was adopted to create a clinical model using six factors.The sequence of fast spin-echo T2-weighted MRI of the entire pelvis was segmented and analyzed.Pure-image and clinical-image integrated deep learning models were constructed using the mask region-based convolutional neural network segmentation tool and three-dimensional convolutional networks.Sensitivity,specificity,accuracy,positive predictive value(PPV),and area under the receiver operating characteristic curve(AUC)was calculated for each model.RESULTS The prevalence of≥3 linear stapler cartridges was 17.7%(58/328).The prevalence of AL was statistically significantly higher in patients with≥3 cartridges compared to those with≤2 cartridges(25.0%vs 11.8%,P=0.018).Preoperative carcinoembryonic antigen level>5 ng/mL(OR=2.11,95%CI 1.08-4.12,P=0.028)and tumor size≥5 cm(OR=3.57,95%CI 1.61-7.89,P=0.002)were recognized as independent risk factors for use of≥3 linear stapler cartridges.Diagnostic performance was better with the integrated model(accuracy=94.1%,PPV=87.5%,and AUC=0.88)compared with the clinical model(accuracy=86.7%,PPV=38.9%,and AUC=0.72)and the image model(accuracy=91.2%,PPV=83.3%,and AUC=0.81).CONCLUSION MRI-based deep learning model can predict the use of≥3 linear stapler cartridges during DST anastomosis in laparoscopic LAR surgery.This model might help determine the best anastomosis strategy by avoiding DST when there is a high probability of the need for≥3 linear stapler cartridges.
基金supported by National Natural Science Foundation of China-Shandong Joint Fund (No. U1606403)Innovation Project of Qingdao National Laboratory for Marine Science and Technology (No. 2015ASKJ02)。
文摘In recent years, the strategy of inhibiting the interactions of p53 with murine double minute 2(MDM2)and murine double minute X(MDMX) has been proved to be a promising approach for tumor therapy.However, the poor proteolytical stability and low intracellular delivery efficiency of peptide inhibitors limit their clinical application. Here, we designed and synthesized the bicyclic stapled peptides based on p53 by combining all-hydrocarbon stapling and lactam stapling strategies. We demonstrated that bicyclic stapled peptide p53-16 significantly improved α-helicity and proteolytic stability. Especially, p53-16showed nanomolar binding affinity for MDM2 and MDMX. In addition, p53-16 could penetrate the cell membrane, and selectively inhibited the activity of tumor cells via activating p53 pathway in vitro. Our data suggest that p53-16 is a potential dual inhibitor of MDM2 and MDMX interactions. The bicyclic stapling strategy is a promising drug design strategy for protein–protein interactions inhibitors.
基金supported by Shanghai Rising-Star Program(to Xiang Li)the National Nature Science Foundation of China No.21807112(to Xiang Li),No.91849129(to Honggang Hu),No.22077078(to Honggang Hu)and No.22207065(to Yulei Li)+1 种基金academic promotion program of Shandong First Medical University(No 2019LJ003,China,to Yulei Li)Taishan Scholars Program(to Yulei Li)。
文摘Stapled peptides with significantly enhanced pharmacological profiles have emerged as promising therapeutic molecules due to their remarkable resistance to proteolysis and performance to penetrate cells.The all-hydrocarbon peptide stapling technique has already widely adopted with great success,yielding numerous potent peptide-based molecules.Based on our prior efforts,we conceived and prepared a double-stapled peptide in this study,termed FRNC-1,which effectively attenuated the bone resorption capacity of mature osteoclasts in vitro through specific inhibition of phosphorylated GSK-3β.The double-stapled peptide FRNC-1 displayed notably improved helical contents and resistance to proteolysis than its linear form.Additionally,FRNC-1 effectively prevented osteoclast activation and improved bone density for ovariectomized(OVX)mice after intravenous injection and importantly,after oral(intragastric)administration.The double-stapled peptide FRNC-1 is the first orally effective peptide that has been validated to date as a therapeutic candidate for postmenopausal osteoporosis(PMOP).
基金supported by the National Natural Science Foundation of China(No.81603628),Medical Scientific Research Foundation of Guangdong Province,China(No.A2015180)and Sun Yat-Sen University Clinical Research 5010 Program(No.2017017).
文摘Objective:The present study was designed to evaluate the functional outcome of stapled transanal rectal resection(STARR)and to examine the relationship between the population density of the interstitial cells of Cajal(ICC)and the efficacy of the STARR operation in the management of obstructed defecation syndrome(ODS)patients.Methods:Full-thickness rectal samples were obtained from 50 ODS patients who underwent STARR.Samples were analysed using ICC immunohistochemistry.Clinical and functional parameters obtained with defecography and anorectal manometry were compared with 20 controls.Results:ICCs were significantly decreased in patients in the submucosal(SM),intramuscular(IM)andmyenteric(MY)regions when compared with the control group(P<0.05).The mean pre-operative Cleveland Constipation Score(CCS)was 24.264.1,whilst the CCS at 1,2,3,4 and 5 years post-operatively decreased significantly(P<0.05).At 3 post-operative years,58.3%(28/48)of the patients reported a favorable outcome(CCS10).On univariate analysis,the functional results were worse in those with pre-operative digitation(P=0.017),a decreased ICC-MY cell population(P=0.067),a higher resting anal canal pressure(P=0.039)and a higher rectal sensory threshold(P=0.073).Multivariate analysis showed the decreased ICC-MY cell population was an independent predictor for low unfavorable functional outcome(odds ratio=0.097,95%confidence interval:0.012–0.766).Conclusions:STARR achieved acceptable results at the cost of a slight deterioration over amore prolonged follow-up.Patients with a decreased ICC number in the rectal specimen showed an unfavorable functional outcome where pre-operative histological assessment of a full-thickness rectal samplemight predict for the functional outcome following STARR.
基金supported by projects of the National Natural Science Foundation of China(81803354 and 81773693)the Natural Science Foundation of Jiangsu Province of China(BK20180564)+2 种基金the Fundamental Research Funds for the Central Universities(2632021ZD13,China)Double First-Class Innovation Team of China Pharmaceutical University(CPU2018GY02,China)the Program for Outstanding Scientific and Technological Innovation Team of Jiangsu Higher Education(YY20180315004,China)
文摘Lung cancers are the leading cause of cancer deaths worldwide and pose a grave threat to human life and health.Non-small cell lung cancer (NSCLC) is the most frequent malignancy occupying80%of all lung cancer subtypes.Except for other mutations (e.g.,KRAS^(G12V/D)) that are also vital for the occurrence,KRAS^(G12C) gene mutation is a significant driving force of NSCLC,with a prevalence of approximately 14% of all NSCLC patients.However,there are only a few therapeutic drugs targeting KRAS^(G12C) mutations currently.Here,we synthesized hydrocarbon-stapled peptide 3 that was much shorter and more stable with modest KRAS^(G12C) binding affinity and the same anti-tumor effect based on the a-helical peptide mimic SAH-SOS1_(A).The stapled peptide 3 effectively induced G2/M arrest and apoptosis,inhibiting cell growth in KRAS-mutated lung cancer cells via disrupting the KRASmediated RAF/MEK/ERK signaling,which was verified from the perspective of genomics and proteomics.Peptide 3 also exhibited strong anti-trypsin and anti-chymotrypsin abilities,as well as good plasma stability and human liver microsomal metabolic stability.Overall,peptide 3 retains the equivalent anti-tumor activity of SAH-SOS1_(A) but with improved stability and affinity,superior to SAH-SOS1_(A).Our work offers a structural optimization approach of KRAS^(G12C) peptide inhibitors for cancer therapy.
