stricture formation
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Pathobiology ◽  
2022 ◽  
pp. 1-11
Author(s):  
Omar Bushara ◽  
David Joseph Escobar ◽  
Samuel Edward Weinberg ◽  
Leyu Sun ◽  
Jie Liao ◽  
...  

<b><i>Background:</i></b> Crohn’s disease (CD) is a condition on the spectrum of inflammatory bowel disease that affects up to 20 people per 100,000 in the US annually, and with incidence increasing. One of the most significant sources of morbidity in CD is the formation of strictures, with resultant intestinal blockage a common indication for hospitalization and surgical intervention in these patients. The pathophysiology of stricture formation is not fully understood. However, the fibroplasia that leads to fibrostenotic stricture formation may have shared pathophysiology with IgG4-related fibrosis. <b><i>Summary:</i></b> Initial intestinal inflammation recruits innate immune cells, such as neutrophils, that secrete IL-1β and IL-23, which induces a type 17 CD4+ T-helper T-cell (Th17)-mediated adaptive immune response. These CD4+ Th17 T cells also contribute to inflammation by secreting proinflammatory cytokines such as IL-17 and IL-21. IL-21 recruits and stimulates CD4+ T follicular helper (Tfh) cells, which secrete more IL-21. This causes ectopic germinal center formation, recruiting and stimulating naïve B cells. The IL-17 and IL-21 produced by Th17 cells and Tfh cells also induce IgG4 plasmablast differentiation. Finally, these IgG4-producing plasmablasts secrete platelet-derived growth factor (PDGF), which activates local PDGF-receptor expressing fibroblasts and myofibroblasts, resulting in uncontrolled fibroplasia.


Author(s):  
U Krafft ◽  
O Mahmoud ◽  
J Hess ◽  
J.P Radtke ◽  
A Panic ◽  
...  

Abstract Purpose Ureteroenteric anastomosis after cystectomy is usually performed using the Bricker or Wallace technique. Deterioration of renal function is the most common long-term complication of urinary diversion (UD). To improve surgical care and optimize long-term renal function, we compared the Bricker and Wallace anastomotic techniques and identified risk factors for ureteroenteric strictures (UES) in patients after cystectomy. Material and methods Retrospective, monocentric analysis of 135 patients who underwent cystectomy with urinary diversion at the University Hospital Essen between January 2015 and June 2019. Pre- and postoperative renal function, relevant comorbidities, prior chemo- or radiotherapy, pathological findings, urinary diversion, postoperative complications, and ureteroenteric strictures (UES) were analyzed. Results Of all 135 patients, 69 (51.1%) underwent Bricker anastomosis and 66 (48.9%) Wallace anastomosis. Bricker and Wallace groups included 134 and 132 renal units, respectively. At a median follow-up of 14 (6–58) months, 21 (15.5%) patients and 30 (11.27%) renal units developed UES. We observed 22 (16.6%) affected renal units in Wallace versus 8 (5.9%) in Bricker group (p < 0.001). A bilateral stricture was most common in Wallace group (69.2%) (p < 0.001). Previous chemotherapy and 90-day Clavien-Dindo grade ≥ III complications were independently associated with stricture formation, respectively (OR 9.74, 95% CI 2–46.2, p = 0.004; OR 4.01, 95% CI 1.36–11.82, p = 0.013). Conclusion The results of this study show no significant difference in ureteroenteric anastomotic techniques with respect to UES development regarding individual patients but suggest a higher risk of bilateral UES formation in patients undergoing Wallace anastomosis. This is reflected in the increased UES rate under consideration of the individual renal units.


Author(s):  
Giorgos Bamias ◽  
Theresa T Pizarro ◽  
Fabio Cominelli

Abstract Intestinal fibrosis is a late-stage phenotype of inflammatory bowel disease (IBD), which underlies most of the long-term complications and surgical interventions in patients, particularly those with Crohn’s disease. Despite these issues, antifibrotic therapies are still scarce, mainly due to the current lack of understanding concerning the pathogenetic mechanisms that mediate fibrogenesis in patients with chronic intestinal inflammation. In the current review, we summarize recent evidence regarding the cellular and molecular factors of innate and adaptive immunity that are considered critical for the initiation and amplification of extracellular matrix deposition and stricture formation. We focus on the role of cytokines by dissecting the pro- vs antifibrotic components of the immune response, while taking into consideration their temporal association to the progressive stages of the natural history of IBD. We critically present evidence from animal models of intestinal fibrosis and analyze inflammation-fibrosis interactions that occur under such experimental scenarios. In addition, we comment on recent findings from large-scale, single-cell profiling of fibrosis-relevant populations in IBD patients. Based on such evidence, we propose future potential targets for antifibrotic therapies to treat patients with IBD.


2021 ◽  
Vol 11 (23) ◽  
pp. 11536
Author(s):  
Min-Tae Kim ◽  
Kun-Yung Kim

Corrosive burns lead to progressive esophageal stricture and dysphagia. There are many trials to prevent esophageal stricture formation after corrosive burn. EW-7197 has been proven in several animal models of fibrosis to have antifibrotic and antiproliferative effect. This study aimed to assess the effects of EW-7197 on prevention for esophageal stricture formation after corrosive esophageal burn. An animal study was carried out, where the animals were divided into three groups: a healthy group, a control group (corrosive burn without EW-7197), and a treatment group (corrosive burn with EW-7197). Corrosive esophageal burns were induced using 30% NaOH on the lower esophagus. For 3 weeks, the control group received vehicle and the treatment group received 20 mg/kg/day EW-7197. Treatment efficacy was assessed by measuring the stenosis ratio by esophagogram with contrast media on day 21. Histologic staining was performed to evaluate the fibrosis area ratio, and Western blotting was performed to evaluate fibrotic markers. Among 20 rats that underwent surgery, 14 survived. Three in the treatment group died because of esophageal perforation, and three in the control group died due to their debilitating status. The esophageal stenosis ratio was significantly lower in the treatment group than in the control group (12.1 ± 9.5% and 42.2 ± 8.3%, respectively; p = 0.001). The histologic fibrosis area ratio was also significantly lower in the treatment group (12.5 ± 3.0% and 21.6 ± 2.1%, respectively; p = 0.001). The treatment group showed lower expressions of profibrogenic proteins such as TGF-β1, pSmad3, and α-SMA. EW-7197 may be a good alternative for the prevention esophageal stricture formation after corrosive burn.


2021 ◽  
Vol 108 (Supplement_9) ◽  
Author(s):  
Zeeshan Afzal ◽  
Stavros Gourgiotis ◽  
Richard Hardwick ◽  
Peter Safranek ◽  
Vijayendran Sujendran ◽  
...  

Abstract Background Endoluminal vacuum therapy (EVT) is an emerging treatment strategy for the management of anastomotic leaks following oesophagectomy. However, patients are often critically unwell with mediastinitis and established sepsis by the time the leak is diagnosed. This results in a protracted recovery period regardless of the effectiveness of EVT in treating the leak. Prophylactic EVT to protect the anastomosis following oesophagectomy may reduce the incidence of anastomotic leak, and/or mediastinitis and sepsis if the anastomosis does fail. We report the outcomes of two patients considered high risk for anastomotic leak who were managed with prophylactic EVT following esophagectomy for cancer. Methods Two patients received prophylactic EVT following oesophagectomy between May and July 2021. The patients were considered high risk for anastomotic leak due to technical concerns with, or complications during, the operation. In both cases the oesophagogastric anastomosis (OGA) was fashioned with a circular stapler. The endoluminal vacuum device (EVD) was constructed using an 18F nasogastric tube and a piece of open cell foam, and placed intraluminally across the anastomosis under endoscopic guidance at the time of surgery. Continuous negative pressure (125mmHg) was applied. Information relating to treatment and outcome was recorded prospectively. Results Patient-1, a 72-year-old female, ASA 2, underwent minimally invasive oesophgectomy for an adenocarcinoma at the gastro-oesophageal junction. After creating the stapled OGA, inspection revealed the proximal (oesophageal) tissue doughnut was complete but attenuated. Patient 2, a 67-year-old male, ASA 3, underwent a hybrid Ivor Lewis oesophgectomy for a lower 1/3 oesophageal adenocarcinoma. Surgery was complicated by significant intra-abdominal bleeding requiring blood transfusion and pressor support. In both cases, endoscopic assessment of the anastomosis following removal of the prophylactic EVD was performed day seven post-operatively. The anastomoses were healthy with no evidence of a leak, dehiscence, or early stricture formation. Conclusions In this limited case series, prophylactic EVT of the OGA following oesophagectomy was delivered safely with no complications related to insertion of the EVD or delivery of EVT. This intervention should be considered in cases where the risk of anastomotic leak is high. An intraluminal EVD situated across the OGA may minimise the extent of extraluminal contamination, and the systemic consequences of sepsis associated with this, should an anastomotic breakdown occur. Further studies are required to determine the safety of prophylactic EVT following oesophagectomy, and whether this improves surgical outcomes by reducing the incidence and impact of anastomotic leaks.


Author(s):  
Min Tae Kim ◽  
Kun Yung Kim

Corrosive burns lead to progressive esophageal stricture and dysphagia. There are many trials to prevent Esophageal stricture formation after corrosive burn. This study aimed to access the effects of EW-7197 on prevention for esophageal stricture formation after corrosive esophageal burn. animal study were classified divided into three groups: a healthy group, a control group (corrosive burn without EW-7197), and a treatment group (corrosive burn with EW-7197). Corrosive esophageal burns were produced using 30% NaOH on the lower esophagus. For 3 weeks, the control group received vehicle and the treatment group received 20 mg/kg/day EW-7197. Treatment efficacy was assessed by measuring the stenosis ratio by esophagogram with contrast media on day 21. histologic staining was performed to evaluate the fibrosis area ratio, and western blotting was performed to evaluate fibrotic markers. Among 20 rats that underwent surgery, 14 survived. Three in the treatment group died because of esophageal perforation, and three in the control group died due to their debilitating status. The esophageal stenosis ratio was significantly lower in the treatment group than in the control group (12.1 &plusmn; 9.5% and 42.2 &plusmn; 8.3%, respectively; p = 0.001). The histologic fibrosis area ratio was also significantly lower in the treatment group (12.5 &plusmn; 3.0% and 21.6 &plusmn; 2.1%, respectively; p = 0.001). The treatment group showed lower expressions of profibrogenic proteins such as TGF-&beta;1, pSmad3, and &alpha;-SMA. EW-7197 may be a good alternative for the prevention esophageal stricture formation after corrosive burn.


2021 ◽  
pp. 1-2
Author(s):  
Nilanchali Singh ◽  
Nilanchali Singh ◽  
Reva Tripathi ◽  
YM Mala ◽  
Shakun Tyagi

Introduction: Herlyn-Werner-Wunderlich Syndrome is a rare anomaly and exact incidence is not known. It is usually diagnosed in young girls who present with cyclical abdominal pain along with cyclical menstruation. Case Report: We present case of two girls who had this syndrome. An ultrasound was performed in both patients. In first patient, it revealed uterus didelphys with hematocolpos on right side. In the second patient, a large hematometra of size 9.8×12.2 cm, along with hematocolpos was present on the left side. Both the patients underwent examination under anaesthesia and excision of septum. They remained asymptomatic during one year follow-up. Conclusion: Treatment of such cases is excision of septum and to maintain the patency of the outflow tract and prevent stricture formation later. A good follow-up in immediate post-operative period is necessary.


2021 ◽  
pp. 1-6
Author(s):  
Neil O’Moráin ◽  
Jayne Doherty ◽  
Roisin Stack ◽  
Glen A. Doherty

<b><i>Background:</i></b> Crohn’s disease (CD) is a chronic inflammatory disorder affecting the gastrointestinal tract with disease behaviour based on the depth and severity of mucosal injury. Cumulative injury can result in complications including stricture formation and penetrating complications which often require surgical resection of diseased segments of the intestine resulting in significant morbidity. Accurate assessment of disease activity and appropriate treatment is essential in preventing complications. <b><i>Summary:</i></b> Treatment targets in the management of CD have evolved with the advent of more potent immunosuppressive therapy. Targeting the resolution of sub-clinical inflammation and achieving mucosal healing is associated with the prevention of stricturing and penetrating complications. Identifying non-invasive modalities to assess mucosal healing remains a challenge. <b><i>Key Messages:</i></b> Mucosal healing minimizes the risk of developing disease complications, prolongs steroid-free survival, and reduces hospitalization and the need for surgical intervention.


2021 ◽  
Vol 233 (5) ◽  
pp. S65
Author(s):  
Khristian E. Bauer-Rowe ◽  
Michelle Griffin ◽  
Deshka Foster ◽  
Heather E. desJardins-Park ◽  
Shamik Mascharak ◽  
...  
Keyword(s):  

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258256
Author(s):  
Marleen E. Jacobs ◽  
Vincent F. de Kemp ◽  
Maarten Albersen ◽  
Laetitia M. O. de Kort ◽  
Petra de Graaf

Background Urethral stricture disease is a common problem amongst men in Western countries often leading to a decreased quality of life. Current endoscopic treatment procedure shows an unsatisfying stricture recurrence rate which could be improved by addition of local therapies. Objectives To provide an overview of both preclinical and clinical studies in order to investigate current level of evidence on the addition of local therapy to improve urethral stricture recurrence rates after endoscopic procedures. Methods We performed a literature search in December 2020 and August 2021 using Cochrane, Embase, PubMed, Scopus and Web of Science and identified articles through combinations of search terms for ‘urethral stricture disease’, ‘stricture formation’ and ‘local interventions’. We used the SYRCLE, RoB-2 and ROBINS-I tools to assess risk of bias across included studies. We did not perform a meta-analysis due to methodological differences between studies. Results We included 32 articles in the qualitative analysis, 20 of which were preclinical studies and 12 clinical studies. Regarding preclinical articles using an animal model, nearly all interventions showed to have a positive effect on either urethral fibrosis, urethral stricture formation and/or fibrotic protein expression levels. Here, immunosuppressants and chemotherapeutics seemed most promising for possible clinical purposes. Regarding clinical studies, mitomycin-C and hyaluronic acid and carboxymethylcellulose showed positive effects on urethral stricture recurrence rates with low to intermediate risk of bias across studies. However, the positive clinical effects of mitomycin-C and steroids seemed to decrease in studies with a longer follow-up time. Conclusion Although local adjuvant use of mitomycin-C or hyaluronic acid and carboxymethylcellulose may carry clinical potential to improve urethral structure recurrence rates after endoscopic procedures, we believe that a large, well-designed RCT with a yearlong follow-up time is necessary to identify the true clinical value.


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