| Literature DB >> 35634190 |
Hiroshi Sawayama1, Yuji Miyamoto1, Naoya Yoshida1, Hideo Baba1.
Abstract
The development of new drugs for inflammatory bowel disease (IBD) is remarkable, and treatment strategies using multiple agents and various techniques are required; however, the treatment strategy is likely to be complex. Therefore, appropriate evaluation of traditional surgical treatment strategies and accurate knowledge of the efficacy and limitations of novel treatments are required. Total infectious complications were found to be associated with the use of corticosteroids and anti-tumor necrosis factor-α agents, but not with immunomodulators, anti-integrin agents, and 5-aminosalicylic acid. Regarding surgical procedures for IBD, conceived anastomosis methods, including Kono-S for Crohn's disease stenosis, are associated with better outcomes than conventional techniques. Autologous cell transplantation for Crohn's fistulae has been shown to have a favorable outcome. Diverticulitis is increasing and will be treated more frequently in the future. Risk factors for the incidence of diverticulitis and differences in pathogenesis according to right or left side diverticulitis have been reported. Antibiotic therapy may be omitted for uncomplicated diverticulitis. Moreover, regarding surgical procedures, both bowel resection and anastomosis are associated with favorable short-term outcomes, higher stoma closure rate, and superior medical economy compared to Hartmann's procedure. Risk factors for recurrence after diverticulitis surgery may provide better postoperative follow-up. In this review, we explore the current topics of colorectal benign diseases, focusing on IBD and diverticulitis, based on clinical trials and meta-analyses from 2020-2021. This review consolidates the available knowledge and improves the quality of surgical procedures and perioperative management for IBD and diverticulitis.Entities:
Keywords: Crohn's disease; diverticulitis; inflammatory bowel disease; surgery; ulcerative colitis
Year: 2022 PMID: 35634190 PMCID: PMC9130914 DOI: 10.1002/ags3.12548
Source DB: PubMed Journal: Ann Gastroenterol Surg ISSN: 2475-0328
FIGURE 1Summary of key articles on clinical trials and meta‐analyses of inflammatory bowel disease and diverticulitis
Meta‐analyses of characteristics and markers inflammatory bowel disease
| Focus | Main results | Reference |
|---|---|---|
| Periodontitis | The association between periodontitis and UC: present (OR 5.37) |
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| Periodontitis | The relation between periodontitis and IBD: OR: 2.10 (CD 1.72, UC: 2.39) | Biomed Res Int. 2021 Mar 12;2021:6692420 |
| Periodontal disease (PD) | The presence of PD was associated with IBD: OR: 2.78 (CD: 3.41, UC 3.98) |
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| Pyoderma gangrenosum (PG) | The incidence of PG in IBD: 0.4 to 2.6%. PG was associated with female gender (RR: 1.33), CD (RR: 1.19), erythema nodosum (RR: 9.28), and ocular extra‐intestinal manifestation (RR: 4.55) | Dig Dis Sci. 2020 Sep;65(9):2675‐2685 |
| Psoriasis | The prevalence of psoriasis: CD 3.6% and UC 2.8%. |
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| Herpes zoster (HZ) infection |
Risk of HZ infection: CD: RR: 1.74 (steroid users RR: 1.78). UC: RR: 1.40 (steroid users RR: 1.99, anti‐TNFα users RR: 2.29) IBD patients with high risk of HZ infection may benefit from an HZ vaccine |
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| Rheumatoid arthritis | The association between IBD and the risk of RA: higher risk of RA among patients with IBD: RR 2.59 (CD, RR: 3.14, UC, RR: 2.29) |
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| Elderly onset (EO) and adult onset (AO) IBD |
EO = AO: 5‐year risk of surgery, overall exposure to corticosteroids EO < AO: exposure to immunomodulators, biologic agents |
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| Anxiety and depression |
Anxiety symptoms: 32.1%, depression symptoms: 25.2% CD > UC: anxiety symptoms (OR 1.2), depression symptoms (OR 1.2) |
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| Opioid use | Prevalence of opioid use: outpatients setting 21%, hospitalized 62% female (RR 1.20), depression (RR 1.99), substance abuse (RR 4.67), prior surgery (RR 2.33), biologic use (RR 1.36), steroid use (RR 1.41) |
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Novel agents for inflammatory bowel disease
| Agents | Target | Endpoints | Main results | Reference |
|---|---|---|---|---|
| Crohn's disease | ||||
| Upadacitinib | Janus kinase 1 inhibitor | Clinical remission (16 wk) and endoscopic remission (12 wk) | Endoscopic (not clinical) remission increased |
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| Ozanimod | Sphingosine‐1‐phosphate receptor subtypes 1 and 5 | Endoscopic Score for Crohn's Disease (SES‐CD) from baseline to 12 wk | The mean change SES‐CD: 2.2, endoscopic, histological, clinical improvements |
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| Mongersen | Antisense oligodeoxynucleotide to Smad7 | Clinical remission CD Activity Index score <150 (12 wk) | NS |
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| Ulcerative colitis | ||||
| Etrasimod | Sphingosine 1‐phosphate receptor modulator | Improvement in modified MCS (etrasimod vs placebo) | Etrasimod favorable ( |
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| Ozanimod | Sphingosine‐1‐phosphate receptor subtypes 1 and 5 | Induction and maintenance therapy (ozanimod vs placebo) | Clinical remission (18.4% vs 6.0%, |
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| Vedolizumab | Inhibits the gut‐selective α4β7 integrin | Maintenance treatment, intravenous vedolizumab vs placebo groups | Clinical remission: 46.2%, 42.6%, and 14.3%, respectively |
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| Cobitolimod | Activates Toll‐like receptor 9 | The proportion of clinical remission | Cobitolimod: 21% vs placebo: 7% (OR 3.8) |
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Clinical trials of inflammatory bowel disease
| Factor | Endpoints | Main results | Reference |
|---|---|---|---|
| Markers of inflammatory bowel disease | |||
| Disease activity miR‐320a levels | Appropriate clinical disease indices and endoscopic scoring systems | MiR‐320a expression (peripheral blood) are associated with the clinical and endoscopic disease activities of IBD |
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| Response to infliximab in CD | Predicting mucosal healing | Oncostatin M can predict the outcome of infliximab treatment. (AUC = 0.91) |
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| Vedolizumab | Variables response to vedolizumab (against the α4β7 integrin heterodimer) | Markers associated with vedolizumab ‐induced clinical remission: CD: IL17A, TNF, CXCL1, CCL19, UC: G‐CSF and IL7 |
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| Anxiety/depression | The risk factors of anxiety/depression in IBD |
CD: CD‐related surgery and CDAI/depression in IBD UC: corticosteroid use |
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| Microbial factors | Maintenance of remission | Favorable: Lac unfavorable: Enterobacteriaceae (OR 6.35) Lachnospiraceae family (OR 0.47) |
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| Faecal calprotectin (Fcal) | Prediction of postoperative recurrence after ileocolonic resection (CD) | Fcal variation: predictor of early endoscopic postoperative recurrence AUC = 0.73, sensitivity = 64.7%, specificity = 87.5% |
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| Nonoperative treatment for IBD | |||
| HBO for chronic antibiotic‐refractory pouchitis (CARP) | The efficacy and safety of HBO for CARP |
mPDAI symptom score: 3.19 to 1.91 mPDAI endoscopy scores: 2.34 to 1.29 improving CARP |
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| Nonoperative treatment for Crohn's disease | |||
| Oral Sucrosomial® Iron | Intravenous ferric carboxy ‐maltose (FMC) vs Sucrosomial® Iron (SI) |
FCM = SI: Hemoglobin, Iron (4, 8, 12 wk) FCM > SI: Ferritin levels |
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| Vitamin D | Endoscopic recurrence (26 wk) | Vitamin D vs placebo (58% vs 66%, NS) |
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| Hyperbaric oxygen therapy (HBO) | Efficacy, safety, and feasibility of HBO in CD |
Clinical response: 60% Clinical remission: 20% |
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| Nonoperative treatment for ulcerative colitis | |||
| Deep remission (a tight control strategy) | Major adverse outcomes that indicate CD progression | Favorable: deep remission CD endoscopic index of severity scores below 4, with no deep ulcerations or steroid use |
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| HBO 2.4 atmospheres (90 min) | Day 3 responders: 5 days vs 3 days of HBO | HBO favorable: low rates of re‐hospitalization, colectomy at 3 mo (0% vs 66%) |
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| Fecal microbiota transplantation (FMT) | T regulatory and mucosal associated invariant T (MAIT) cell populations | Changes in MAIT cell cytokine production were observed in cFMT |
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| Apheresis selective removal of leukocytes | Clinical remission (Mayo score ≤2) at 12 mo | Apheresis: 46.6%, control: 36.4% (NS) |
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| Cannabis 80 mg tetra ‐hydrocannabinol | Lichtiger disease activity index, CRP, calprotectin, Mayo endoscopic score and QOL |
Cannabis favorable: Lichtiger index, QOL Cannabis = placebo: Mayo endoscopic score |
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| Surgical treatment for Crohn's disease | |||
| Surgery vs Infliximab | Need for surgery or repeat surgery or anti‐TNF therapy |
Treatment effect was similar Laparoscopic ileocecal resection: not successful |
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| Kono‐S anastomotic methods |
Kono‐S vs stapled ileocolic side‐to‐side anastomosis Endoscopic recurrence (ER) | 22.2% in the Kono‐S group and 62.8% in the Conventional group presented an ER |
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| Autologous subcutaneous adipose tissue | Clinical and radiographic healing at 6 mo |
All patient: reduction in the size of fistula tracts 3 of 5: cessation of drainage None: complete healing |
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| Autologous adipose‐derived stem cells | The closure of fistulas at months 3, 6, and 12 | Healing rate (3, 6, 12m): the observation vs control, 90.9% vs 45.5%, 72.7% vs 54.5%, and 63.6% vs 54.5%, respectively (NS) |
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| Allogeneic mesenchymal stem cells | Follow‐up 1 y after the procedure | Perianal abscess (15%), complete closure (69%) |
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| Allogeneic mesenchymal stromal cells | Fistula closure using bone marrow‐derived mesenchymal stromal cells | Fistulas with closure at 24 wk were still closed after 4 y |
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| Fibrin glue | The rate of complete clinical remission at 1 y | Complete clinical remission (1 y): 45.4% |
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Abbreviations: ACU, area under the curve; OR, odds ratio; TNF: tumor necrosis factor.
Meta‐analyses of nonoperative treatment for inflammatory bowel disease
| Focus | Endpoints | Main results | Reference |
|---|---|---|---|
| Nonoperative treatment for inflammatory bowel disease | |||
| Sleep quality | The relation between sleep quality and disease activity | Subjective sleep quality and disease activity (OR 3.52), sleep efficiency and disease activity (OR 4.55) |
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| Iron supplementation | Ferric carboxymaltose (FCM), iron isomaltoside (IIM), iron sucrose (IS), oral iron (OI) |
Response rates with FCM, IIM, IS, OI: 81%, 74%, 75%, 69% FCM: the most cost‐effective |
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| Hyperbaric oxygen therapy (HBO) | Response rate and complete healing of fistula | Response rate of HBO, UC: 83.2%, CD: 81.9%, the complete healing of fistula: 47.6% |
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| Antibiotic refractory pouchitis | The safety and efficacy of various biological agents for antibiotic refractory pouchitis | Clinical improvement: IFX 71.4%, ADA 58.2%, VDZ 47.9%, remission: IFX 65.7%, ADA 31%, VDZ 47.4% |
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| Nonoperative treatment for ulcerative colitis | |||
| Adjuvant curcumin therapy | Clinical and endoscopic remission |
Clinical remission (OR 5.18) Endoscopic remission (OR 17.05) Clinical improvement (OR 4.79 NS) |
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| Infliximab (IFX) vs cyclosporine and tacrolimus (TAC) | Short‐term remission, short‐term, colectomy rate | IFX favorable: lower short‐term (OR 0.59), 1 y colectomy rate (OR 0.53), 3 y colectomy rate (OR 0.41) |
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| Faecal microbiota transplantation (FMT) | Safety and effectiveness of treating UC |
Efficacy: FMT favorable (OR 2.29) Multiple donors delivered (OR 2.76) Side effects: NS |
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| Nonoperative treatment for Crohn's disease | |||
| Adalimumab | Failure to maintain clinical remission in people with quiescent CD | Adalimumab: 59% vs placebo: 86% Adalimumab is an effective therapy for maintenance of clinical remission |
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| Anti‐tumor necrosis factor (TNF) α | Preventing endoscopic and clinical recurrence | Endoscopic recurrence (RR 0.34) clinical recurrence (RR 0.60, NS) AEs with anti‐TNF therapy (RR 1.75) |
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| Stem cell therapy | CD activity index | Reduce: CD activity index, CD endoscopic index of severity, simplified endoscopy score for CD |
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| Placebo | The rate of response to placebo endoscopic assessment of CD activity | Response: 16.2%, remission 5.2% lower rates of response to placebo increased concentration of CRP |
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| Endoscopic balloon dilation | Small intestinal strictures in CD evaluate endoscopic balloon dilation | Technical success: 94.9%, efficacy: 82.3%, complications: 5.3%, rec.: 48.3% (re‐dilated: 38.8%, surg.: 27.4%) |
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Meta‐analyses of surgical treatment for inflammatory bowel disease
| Focus | Endpoints | Main Results | Reference |
|---|---|---|---|
| Surgical treatment for inflammatory bowel disease | |||
| Urgent surgeries vs elective surg. | Overall postoperative complications (30d) |
Urgent surgery: ~ 40% increase in overall complication (RR: 1.43) Mortality and readmission rates: NS |
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| Robotic vs laparoscopic IPAA | Complications and quality of life outcomes | NS |
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| Rectal stump management | Mortality, complications, Pelvic stump dehiscence | Mortality: 1.7%, wound infection 11.3% Stump leak: 4.9%, pelvic abscess / sepsis 5.7% |
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| IPAA (CD vs UC) | Complications, functional outcome |
CD unfavorable: pouch fistulae (OR 6.08), strictures (OR 1.82), failure, (OR 5.27) CD = UC: pouchitis |
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| IPAA | Outcomes following IPAA with and without proximal stoma diversion | Non‐diverted favorable: Anastomotic strictures (OR 0.40), pouch failures (OR 0.54), diverted favorable: Re‐operation (OR 2.51) |
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| IPAA in the elderly aged >50 years | Perioperative safety and long‐term functional success |
The overall morbidity and mortality rates (30 d): 47.3% and 1.3% Functional outcomes 50‐65 vs >65 years: NS |
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| Bariatric surgery | Adverse events, change in medications |
Early/late adverse events: 15.9%/16.9% IBD medications: decrease 45.6%, increase 11%, no change 57.6% |
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| Bariatric surgery | Wound infection, Clavien‐Dindo grade >II and IBD exacerbation | Wound infection (4.1%), CD grade >II (2.0%) and IBD exacerbation (4.3%). Bariatric surgery is safe in patients with IBD |
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| Bariatric surgery | Quality of life | Half of patients had decrease in their IBD medications after bariatric surgery |
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| Postoperative infectious complications | IBD medications on the risk of postoperative infections within 30 d | Corticosteroids (OR 1.70), immunomodulators (OR 1.29 NS), anti‐TNF (OR 1.60), anti‐integrin (OR 1.04 NS), 5‐ASA (OR 0.76 NS) |
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| Preoperative anti‐TNF | Overall, infectious, and noninfectious postoperative complications | Use of anti‐TNF agents increases in postoperative complications: overall (OR 1.13), infectious (OR 1.44), noninfectious (OR: 1.44) |
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| Vedolizumab | Overall and infectious postoperative complication rates |
Overall complications: NS Infectious complications: NS |
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| Vedolizumab (VDZ) | Postoperative complications |
Overall complications (OR 1.25 NS) VDZ favorable: infection (OR 0.49) VDZ unfavorable: SSI (OR 2.97), ileus (OR 2.16), mucocutaneous separation (OR 4.69) |
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| Surgical treatment for ulcerative colitis | |||
| Predict colectomy | Prognostic factors (predict colectomy) | Pediatric Ulcerative Colitis Activity Index score, hemoglobin, hematocrit, albumin, family history of UC, extraintestinal manifestations, disease extension over time |
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| Two‐stage restorative colectomy | Complication rates (modified 2‐stage, classic 2‐stage, 3‐stage approaches) | Pediatric pts: modified 2‐stage approaches leak rates higher, adult cohorts: modified 2‐stage approaches lower leak rates |
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| Surgical treatment for Crohn's disease | |||
| Kono‐S anastomosis | Recurrence (rec.), complications | Surgical rec. 0%, endoscopic rec. 5%, ileus 3%, small bowel obstruction 4%, anastomotic leak 1%, postoperative infection 10% |
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| IPAA |
Long‐term functional outcomes The pouch failure rate | Mean 24‐h stool frequency: 6.3 bowel movement, overall pouch failure rate:15%, no risk factors for pouch failure were identified |
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| Surgery vs initial medical therapy | Early bowel resection (EBR) relapse rate, Newcastle‐ Ottawa and Jadad scales | EBR favorable: overall/surgical relapse (OR 0.53/0.47), requirement biologic therapy (OR 0.24), RFS, (OR 0.62), morbidity (NS) |
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| Strictureplasty (SPX) |
Recurrence‐free survival SPX vs bowel resection (BR) |
SPX alone increased disease recurrence than BR (HR 1.61) No difference in morbidity |
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| Stem cells therapy |
The efficacy and safety for CD fistula Stem cell therapy vs placebo | Stem cell group favorable: fistula healing (61.8% vs 40.5%, OR 2.21) the treatment‐related adverse events (RR 0.58) |
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| Risk of recurrence (rec.) | Risk of clinical, surgical and endoscopic (ES) rec. in positive resection margins, granulomas or plexitis | Positive resection margins: clinical/surgical /ES rec. (RR 1.26/1.87/ND), Granulomas: clinical/surgical /ES rec. (RR 1.31/1.37/NS), Plexitis: ES/clinical rec (RR: 1.31/NS) |
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| Rate of recurrence | Postoperative recurrence (POR) | TNF‐α agents (1 y) endoscopic, clinical, surgical POR: 21.7, 13.1, 3.8%, 5‐y rec. rate: endoscopic, surgical rec.:84.2%, 17.5% |
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Clinical trials of diverticulitis and diverticular disease
| Factor | Endpoints | Main results | Reference |
|---|---|---|---|
| Characteristics | |||
| Right side vs left side diverticulitis | Clinical features | Right side: younger, male, tall, lower BMI, less advanced Hinchey stages, shorter hospital stays, less recurrent |
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| Nonoperative treatment | |||
| Vitamin D vs placebo | Time to diverticular disease hospitalization from randomization | Vitamin D: 1.4% and placebo: 1.5% (NS) |
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| Antibiotic treatment vs placebo | Treatment effect | Antibiotic treatment = placebo: length of hospital stay, adverse events, readmission, intervention, inflammation markers, pain |
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| Surgical treatment | |||
| Primary anastomosis (PRA) vs Hartmann's procedure (HP) | Costs and cost ‐effectiveness | PA favorable: overall costs: PAR vs HP (€20 544 vs €28 670), incremental cost‐effectiveness: €‐39 094 cost‐utility: €‐101 435 |
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| PRA vs HP | Long‐term outcomes and quality of life (QoL) | PA favorable: general QoL (EQ‐VAS), EQ‐5D index scores, PA = HP: GIQLI (intestine‐specific QOL) |
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| Surgery or not | QoL at 5‐year follow‐up | Surgery favorable: potential to improve quality of life |
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| Damage control surgery (DCS) | Rate of stoma at discharge and at 6 mo | DCS 8.3% vs conventional treatment 57% (at discharge), DCS 0% vs conventional treatment 42% (at 6 mo) |
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| Hartmann's reversal | Factors of morbidity and mortality of Hartmann's reversal | Low albuminemia, renal failure, coronary artery disease, corticosteroids |
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Meta‐analyses of diverticulitis and diverticular disease
| Focus | Endpoints | Main results | Reference |
|---|---|---|---|
| Characteristics | |||
| Right‐sided diverticulitis | Characteristic, comorbidity, recurrence (rec.) | Younger, male, smoking, alcohol consumption, less comorbidity, lower rec., less emergency surgery, shorter length of hospital stays |
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| Left‐sided acute diverticulitis | Disease severity, risk of recurrence according to age | Young = elder: need emergency surgery or drainage, recurrence |
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| Preventive medicine Fiber intake | The risk of diverticular according to dietary fiber intake, fiber subtypes | Risk reduction: 23/41/58% (Fiber intake 20/30/40 g/d). Cereal/fruit/vegetable fiber per 10 g/d (RR 0.74/0.56/0.80) |
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| Nonoperative treatment | |||
| Conservative treatment for uncomplicated right‐side diverticulitis | Treatment failure, ES at rec for uncomplicated right‐sided diverticulitis | Treatment failure: 2.5%, rec. rate: 10.9%, complicated diverticulitis at rec: 4.4%, emergency surgery at rec: 9.0% |
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| Observation vs Antibiotic treatment for uncomplicated diverticulitis | Rates of ongoing diverticulitis, rec., complicated diverticulitis, sigmoid resection | NS Observational management of uncomplicated AD is safe |
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| Intravenous antibiotics for Right‐sided diverticulitis (Hinchey I/II) | Rec. rate, morbidity associated with rec. | Rec. rate: 12% (nonoperative management is safe and feasible) required urgent surgery at the time of first rec.: 9.9% |
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| Nonoperative management for sigmoid complicated diverticulitis with abscess | Relapse rate at 30 d, rec. of AD | Relapse rate: 18.9%, rec. of AD: 25.5% (distant abscess: 51% vs pericolic abscess: 18%) |
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| Nonoperative management for complicated diverticulitis with abscess | Treatment failure (time intervals: 1986‐2000, 2000‐2010, 2010‐) | Treatment failure rate at 90 days: 16.4%, (1986‐2000:19.2%, 2000‐2010:18.6%, 2010‐: 15.3%, NS) |
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| Surgical treatment | |||
| Primary anastomosis (PRA) vs Hartmann's procedure (HP) | Mortality, morbidity, stoma reversal after surgery for Hinchey III or IV diverticulitis | PRA favorable: stoma reversal, reversal‐related morbidity, PRA = HP: mortality, morbidity, reintervention rates |
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| PRA vs HP | Mortality, morbidity after surgery for Hinchey III or IV diverticulitis | NS |
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| PRA vs HP for perforated diverticulitis with generalized peritonitis | Stoma rate, 30‐day mortality, overall mortality, major complications | PRA favorable: stoma rate, overall mortality, major complications, PRA = HP: 30‐day mortality |
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| Open vs laparoscopic surg. (LS) for diverticulitis with colovesical fistula | Operative time, stoma rates, complications, mortality | Open = LS: operative time, stoma rates, leakage, SSI, mortality, LS favorable: postoperative complications, length of stay |
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| Open vs LS emergency surgery for complicated diverticulitis | Mortality, morbidity, severe complications, and reoperation rates | Open = LS: postoperative mortality, morbidity, severe complications, and reoperation rates |
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| Damage control surgery for complicated diverticulitis | Leakage, mortality | Major leakage: 4.7%, overall mortality: 9.2% |
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| Surgery for immune‐suppressed patients | Mortality | Elective surgery: immunosuppressed = immunocompetent patients, emergent surgery: immunocompetent patients favorable |
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