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Transurethral incision for hematospermia caused by ejaculatory duct obstruction.

Hematospermia is supposed to be derived from pathological conditions in the seminal vesicle, prostate, testis, epididymis, or urethra. A recent advance in diagnostic procedures has demonstrated the seminal vesicle, the prostate, and midline cyst as potential sources of hematospermia. The authors describe a case of hematospermia caused by ejaculatory duct obstruction, in which a transurethral technique was successful. A 51-year-old male was referred to the authors' clinic with a chief complaint of hematospermia. Transurethral ultrasonography showed a cystic lesion surrounded with hyperechoic area in the middle of the prostate. Vasography demonstrated the distal dilation of the ejaculatory duct. Magnetic resonance imaging demonstrated a high signal intensity area in the middle of the prostate. Urethrocystoscopy showed an enlarged cystic lesion with an orifice at the prostatic urethra, which was incised endoscopically. There was no complication observed postoperatively. Seven months after the technique, hematospermia resolved completely. A midline cyst should be considered a cause of hematospermia and the incidence of such cysts may be higher than that previously recognized. The transurethral technique is expected to be a successful treatment approach.

Blood↗

Colon cancer in aged captive rhesus monkeys (Macaca mulatta).

The age-related incidence of malignant neoplasia was surveyed from a total of 301 necropsy cases of rhesus monkeys ranging in age from 13-37 years performed in the Pathology Service Unit of the Wisconsin Regional Primate Research Center during the past 15 years. All our aged monkeys lived in indoor cages and were fed with monkey chow and supplemental fruits during the past decades. In this survey, we found a total of 51 malignant neoplasms, and among them 25 cases were colon cancer. The incidence of colon cancer increased with advancing age: 3.2% at 13-19 years, 9.2% at 20-25 years, 13.5% at 26-29 years, and 20.7% at 30-37 years. Most cancers were located in the cecum and transverse regions with a unicentric origin. Two multicentric cases were associated with chronic hypertrophic colitis. Precancerous polypous lesions were not found in all cases. Histologically, all cases were mucinous adenocarcinoma and had local invasion to the muscular wall. Metastasis to the mesenteric lymph nodes was found in only two cases. As in humans, colon cancer is a common outcome of aging in nonhuman primates.

Adenocarcinoma, Mucinous↗

[Stenosis of the main trunk of the left coronary artery. Apropos of 54 cases].

In the 54 patients studied coronary arteriography alone showed stenosis of the left main coronary artery (a lesion observed in 5.2 p. 100 of pathological coronary arteriographies), associated with other coronary lesions, 72.2 p. 100 of which involved all three major vessels. Ventriculography was abnormal in 53 p. 100 of the cases, with a less than 45 p. 100 left ventricular ejection fraction in 37.4 p. 100 of them. Nine patients were considered inoperable; 4 of these died during a 40-month follow-up period under medical treatment. Forty-five patients underwent coronary bypass; there were 4 peri-operative deaths (8.9 p. 100), 8 post-operative myocardial infarctions (17.8 p. 100) and one late death (2.2 p. 100). These patients were followed up for a mean period of 26.4 months. All authors who have studied the subject agree that surgery is beneficial: not only does it improve cardiac function, but it also prolongs survival. In spite of the peri-operative risks, surgery must be contemplated in patients with a more than 50 p. 100 stenosis of the left main coronary artery, provided the cardiac vascular bed is accessible to revascularization.

Arteriosclerosis↗

Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly.

Vascular remodeling, defined as any enduring change in the size and/or composition of an adult blood vessel, allows adaptation and repair. On the other hand, inappropriate remodeling, including its absence, underlies the pathogenesis of major cardiovascular diseases, such as atherosclerosis and restenosis. Since degradation of the extracellular matrix scaffold enables reshaping of tissue, participation of specialized enzymes called matrix metalloproteinases (MMPs) has become the object of intense recent interest in relation to physiological ("good") and pathological ("bad") vascular remodeling. Experimental evidence acquired in vitro and in vivo suggests that the major drivers of vascular remodeling, hemodynamics, injury, inflammation, and oxidative stress, regulate MMP expression and activity. Alternatively, nonspecific MMP inhibition seems to oppose remodeling, as suggested by the inhibition of intimal thickening and outward arterial remodeling. An emerging concept is that MMP-related genetic variations may contribute to heterogeneity in the presentation and natural history of atherosclerosis. The hypothesis that MMPs contribute to weakening of atherosclerotic plaques is especially attractive for the potential development of therapeutic interventions aimed at preventing plaque disruption ("the ugly"), a major cause of acute cardiovascular events. However, the current lack of appropriate experimental tools, including availability of specific MMP inhibitors and pertinent animal models, still limits our understanding of the many actions and relative contributions of specific MMPs. Our future potential ability to control vascular remodeling via regulation of MMPs will also depend on reaching a consensus of what is indeed "good" or "bad" vascular remodeling, concepts that have continued to evolve and change.

Animals↗

Diagnosis and treatment of strictures and kinks in salivary gland ducts.

PURPOSE: This article describes the use of sialoendoscopy for diagnosis and treatment of strictures and kinks in the major salivary glands ducts. PATIENTS AND METHODS: Thirty-four salivary glands with obstruction were diagnosed as having ductal kinks or strictures. Strictures were diagnosed by sialography and sialoendoscopy, kinks were diagnosed mainly by sialography, whereas endoscopy was used to rule out other pathology and to locate the kink. There were strictures in 25 salivary glands (14 male and 11 females; aged 25 to 60 years), 14 in the parotid and 11 in the submandibular gland, and kinks in 9 salivary glands (5 males 4 females; aged 40 to 55 years). Seven kinks were found in the submandibular gland and 2 in the parotid. Treatment of strictures was performed by dilatation procedures with saline under pressure, balloon techniques, and forced manipulation. After these procedures, a polyethylene stent was inserted for 2 weeks. Kinks were treated by advancement ductoplasty and balloon contouring to overcome the acute angle. RESULTS: Twenty of 25 cases of stricture became completely asymptomatic in a follow-up of 8 to 36 months after treatment. In 4 cases, further revisional dilatation was needed, and in 1 case treatment failed and the gland had to be removed. All 9 cases of kinks became completely asymptomatic in a follow-up of 6 to 24 months after treatment. CONCLUSION: Strictures and kinks should be considered when salivary gland obstruction is present without sialolithiasis.

Adult↗

Popliteal artery entrapment syndrome.

Popliteal artery entrapment syndrome (PAES) is a rare cause of exercise-induced leg pain. Entrapment occurs because of an abnormal relationship between the popliteal artery and the surrounding myofascial structures in the popliteal fossa. Arterial insufficiency in the affected limb arises with entrapment of the artery, commonly giving leg symptoms with exertion. The true incidence of PAES in the general population is not known. The aetiology of PAES has an embryological basis related to the development of the popliteal artery and the surrounding musculature. Many different classification schemes have been developed to differentiate the various types of abnormal anatomy that are associated with the syndrome. Repeated popliteal artery compression causes trauma to the arterial wall, leading to premature localised atherosclerosis. The pathology of PAES is believed to be progressive, with arterial thrombosis occurring in some individuals as a natural progression of the disease process. Acute ischaemia can occur if there is an occlusion of the artery or thrombosis within an aneurysm. Clinically, up to 85% of individuals diagnosed with the syndrome are males. The mean age of individuals in a large series was 28 years. The condition can be found bilaterally in 25% of cases. Most individuals present with exercise-induced leg pain, the remainder presenting with acute or chronic ischaemia. The condition can result in significant functional loss for active individuals. Surgery has been advocated to prevent the progression of the disease that is believed to be the natural history of untreated PAES. However, the little research that has been done to determine the prognosis for individuals who have undergone surgery has focused on the patency rate of the arteries after surgery and the presence or absence of complications. Research needs to be done to look at the natural history of untreated PAES and the functional status of athletes after undergoing PAES surgery.

Arterial Occlusive Diseases↗

Duodenal atresia and stenosis: reassessment of treatment and outcome based on antenatal diagnosis, pathologic variance, and long-term follow-up.

Duodenal atresia and stenosis was observed in 103 infants and children from 1972 to 1991. There were 59 girls and 44 boys. Atresia was noted in 79 instances and stenosis in 24. Maternal hydramnios was detected in 33 cases, 46 babies were premature, and 31 had Down's syndrome. Fifty-four infants had significant associated anomalies including 35 with cardiac defects. Diagnosis was achieved by prenatal ultrasound examination in 14 cases, observation of a double-bubble sign on abdominal radiograph in 73, and contrast studies in 30 infants including 24 with stenosis. At operation annular pancreas was noted in 37 cases, malrotation in 37 cases, anterior portal vein in 4, and a second web in 3. Surgical treatment included duodenoduodenostomy in 85, duodenotomy and web excision in 8, and duodenojejunostomy in 10. Operative survival was 95%. Deaths were related to complex cardiac defects. Despite antenatal diagnosis, prompt intervention, and apparent early surgical success (95% survival), late deaths (5%) and late complications including motility disorders, megaduodenum, gastroesophageal reflux, duodenal-gastric reflux, gastritis, peptic ulcer disease, blind loop syndrome, and biliary-pancreatic conditions may be observed months to years after management during the neonatal period. Modifications in surgical technique including early tapering duodenoplasty may be useful, and close long-term follow-up is an essential component of patient care.

Anastomosis, Surgical↗

Salpingitis isthmica nodosa: technical success and outcome of fluoroscopic transcervical fallopian tube recanalization.

PURPOSE: To evaluate the technical success and outcome of fallopian tube recanalization (FTR) in salpingitis isthmica nodosa (SIN). METHODS: SIN is a well-recognized pathological condition affecting the proximal fallopian tube and is associated with infertility and ectopic pregnancy. We reviewed the presentations, films, and case records of all patients attending for FTR for infertility from 1990 to 1994. Technical success and total, intrauterine, and ectopic pregnancy rates at follow-up were determined. RESULTS: SIN was observed in 22 of 349 (6%) patients. FTR was attempted in 34 tubes in these 22 patients. Technical success was achieved in 23 of 34 (68%) tubes affected by SIN. In 5 of the 11 failed recanalizations, failure was due to distal obstruction. At least one tube was patent on selective postprocedural salpingography in 17 of 22 (77%) patients. There were no recorded perforations or complications. At follow-up (mean 14 months), total, intrauterine, and ectopic pregnancy rates were 23%, 18%, and 4.5%, respectively. CONCLUSION: FTR in SIN is technically successful and, compared with previously reported results in unselected infertility patients, is associated with only a slightly less favorable intrauterine pregnancy rate and a comparable ectopic pregnancy rate. The findings of SIN at FTR should not discourage attempted fluoroscopic transcervical recanalization.

Adult↗

Reliability of a Crohn's disease clinical classification scheme based on disease behavior.

Classification of Crohn's disease (CD) by disease behavior--either inflammatory (INF), fibrostenotic (FS), or fistulizing/perforating (FP)--has been proposed as a means of assisting management decisions and predicting outcomes for subgroup analysis in clinical trials and for making phenotype/genotype associations in molecular genetic studies. Accurate and reproducible classification of CD patient subgroups is of paramount importance in such studies but to be useful, the classification scheme must have good interrater agreement. We sought to assess the interrater agreement associated with the disease-behavior classification scheme of CD. Twelve patients with CD were randomly selected from a database of 964 patients with CD undergoing medical or surgical treatment or both. Clinical details of the 12 cases, along with their radiographs and surgical and pathological reports, were presented to a panel of 20 experts who were asked to classify each case based on the patient's overall disease course (scenario A) and as if the patient were being entered into a clinical trial on that day (scenario B). Calculations of strength of interrater agreement were made and were expressed as the kappa statistic (kappa), with kappa < 0.2 = poor strength of agreement; kappa 0.21 - 0.4 = fair; kappa 0.41 - 0.6 = moderate; kappa 0.61 - 0.8 = good; and kappa 0.81 - 1.0 = very good. Five panel participants did not complete the study, and three clinical vignettes were excluded because of incomplete scoring, leaving a total of 15 panel experts assessing nine cases. Overall interrater agreement was only fair with kappa = 0.353 for scenario A and kappa = 0.291 for scenario B. Interrater agreement was less when only the most straightforward case in each disease category was evaluated. Classification of CD by pattern of disease behavior yields only fair interrater agreement. This raises concerns regarding its applicability, particularly in ongoing studies of genotype/phenotype associations. Further refinement of disease subtypes and clear operational definitions are required.

Adult↗

Subclavian vein repair in patients with an ipsilateral arteriovenous fistula.

Management of subclavian vein occlusive disease in persons with an ipsilateral arteriovenous fistula can be challenging. From July 1991 to May 1993, nine patients underwent direct exploration and repair of an obstructed subclavian vein following medial claviculectomy. Eight patients had polytetrafluoroethylene (PTFE) grafts; one patient had a Brescia-Cimino fistula. Intractable arm edema was the major symptom in five of eight. The site of the occlusive disease ranged from the midsubclavian vein to the proximal innominate vein. Pathology varied from a focal occluding web to a long segment of intimal fibroplasia. Five veins were occluded; four were stenotic. Surgical procedures consisted of endovenectomy and vein patch (four), endovenectomy and PTFE patch (one), resection of a focal stricture with end-to-end anastomosis (two), resection with PTFE interposition (one), and end-to-end internal jugular to subclavian vein transposition (one). Postoperative contrast venograms revealed a patent subclavian vein in eight of eight patients. One patient died postoperatively from unrelated causes; two patients died with a functioning fistula 8 and 12 months, respectively, after surgery. Two grafts were removed for infection and one deteriorated graft was abandoned because of repeated thrombosis. Only three of nine original grafts are currently in use, including one in which the ipsilateral subclavian vein rethrombosed. Although stent placement may now be the preferred treatment for subclavian vein stenosis, vein repair may still have a role in the treatment of subclavian vein occlusion, particularly in patients with a Brescia-Cimino fistula.

Adult↗

Haemostatic changes in the loin pain and haematuria syndrome: secondary to renal vasospasm?

Twenty-five patients (seven male, 18 female) were diagnosed as having the loin pain and haematuria syndrome. Presenting symptoms were either loin pain alone or pain associated with macroscopic or microscopic haematuria, and were longstanding, having been present for mean of 9.3 years in males, and 10 years in females. Ten patients described symptoms of passing gravel or renal stones but these were only demonstrated radiologically in two patients. Investigation of all patients showed anatomically normal renal tracts, normal renal function, and no significant proteinuria. Phase-contrast microscopy during episodes of haematuria revealed dysmorphic red cells in all 10 patients studied. Renal biopsies were performed in 20 patients and showed no glomerular pathology, but arteriolar and arterial hyalinosis was seen in 13 of 20 (65 per cent), fibro-elastosis in larger vessels in eight of 20 (40 per cent) and red blood cells in tubules in 13 of 20 (65 per cent) patients. The histological appearance in vessels was similar to that seen in cyclosporin A nephrotoxicity and would be consistent with the hypothesis that regional vasospasm occurs in the cortical circulation. Haematological studies in 22 patients, when compared with age and sex matched controls, showed the presence of circulating platelet aggregates, elevation of plasma beta-thromboglobulin (p less than 0.001), and increased platelet aggregation in response to serotonin and ADP (p less than 0.05 and p less than 0.03, respectively). Plasma concentrations of D dimer (p less than 0.02) and C-reactive protein (p less than 0.03) were also significantly elevated in the patient group. There was no deterioration of renal function during a mean observation period of 3.7 years and no patients developed proteinuria. Treatment was largely supportive; seven patients with intractable loin pain underwent surgical denervation with the relief of pain in four.

Adult↗

Management of benign stenoses of the large airways in the university hospital in Prague, Czech Republic, in 1998-2003.

BACKGROUND: Clinically significant benign stenoses of the large airways develop in about 1% of patients after intubation. The management of benign stenoses is not unified around the world, nor are there any accepted methods for their screening. OBJECTIVES: The purpose of this study is to describe and compare results of interventional bronchoscopy and surgical therapy of benign stenoses as well as to propose an algorithm for the management of this airways disorder. METHODS: Prospective study on 80 consecutive patients with benign stenoses of the large airways admitted to the Pulmonary Department of the University Hospital of Prague-Motol. RESULTS: Sixty-two patients developed stenoses after endotracheal intubation or tracheostomy, in 18 patients the stenosis was caused by other diseases or pathological situations. Thirty-eight patients were sent for surgical resection of the stenotic part of the airways. 2 surgically treated patients developed recurrence of the stenosis and had to be reoperated on. Narrowing of the trachea at the site of end-to-end anastomosis developed in 6 other patients and was cured by interventional bronchoscopy. The remaining 42 patients were treated by interventional bronchoscopy (Nd-YAG laser, electrocautery, stent) which was curative in 35 patients. Sixty-five patients were alive at the time of evaluation, 15 patients died. Five of them died between 3 and 14 (median 4) months after surgery from a disease other than airway stenosis. Ten nonresected patients also died, with 1 exception, due to a disease other than airway stenosis; the median survival was 9 months. CONCLUSIONS: We recommend to assess the patient for surgery after the initial diagnosis and therapeutic bronchoscopy with dilatation of the stenosis. If the patient is not a suitable candidate for resection, interventional bronchoscopy is an appropriate alternative for the management of benign stenoses of the large airways.

Adolescent↗

Obstructive lesions of the inferior vena cava: clinical features and endovenous treatment.

OBJECTIVE: Chronic obstructions of the inferior vena cava (IVC) are associated with many odd features. Even total occlusions may remain entirely silent or present late with acute symptoms. Renal dysfunction is rare. Many have chronic symptoms, but often only one limb is affected. We describe the clinical features in a series of 120 patients seen over a 10-year period and the results of successful stent placement in 99 limbs. METHODS: Patients with acute onset of symptoms due to distal thromboses underwent catheter-directed thrombolysis. Patients with significant chronic symptoms were investigated by duplex, venous function tests, transfemoral venography and finally intravascular ultrasound (IVUS). Stenotic segments were balloon dilated and occluded segments were recannalized when feasible; stents were placed under IVUS control. RESULTS: In the asymptomatic group, 10 patients with total occlusions had transient or no occlusive symptoms. In the acute symptom group, four patients with chronic IVC occlusions presented with acute onset of deep venous thrombosis distal to the occlusion but became asymptomatic when the clot was lysed. In the chronic symptom group, 97 patients (99 limbs) had symptoms of chronic venous disease of variable distribution and intensity. In two-thirds, limb symptoms were unilateral. Pathology was total occlusion in 14%, and the rest were stenoses. The lesion extended above the renal vein in 18%. Common iliac obstruction was concurrent in 93%. Distal reflux was present in 66%. Modifications of the basic stent technique were required in recanalization of total occlusions (four extending up to the atrium), two bilateral stent deployments, and nine IVC filter cases. Stent deployment across the renal and hepatic veins or the contralateral iliac vein had no adverse sequelae. Stent patency (cumulative) at 2 years was 82%. Complete relief (cumulative) of pain and swelling at 3.5 years was 74% and 51%, respectively. The cumulative rate of complete ulcer healing at 2 years was 63%. Overall clinical outcome was rated as good or excellent in 70%. CONCLUSIONS: The unusual clinical features of IVC obstructions seem related to the rich collateralization, which has an embryonic basis. Common iliac vein patency seems to be a crucial link in collateral function, and its concurrent occlusion produces symptoms. Percutaneous stent placement has an emerging role in the treatment of IVC obstructive lesions, with good mid-term stent patency and clinical results.

Adolescent↗

Subcutaneously tethered temporary filter: pathologic effects in swine.

PURPOSE: To evaluate the histopathologic effects of the Tempo-filter, a temporary caval filter, on the caval wall and determine the feasibility of deployment and removal of the device in swine. MATERIALS AND METHODS: Filters were placed in the infrarenal inferior vena cava of 11 swine. The tethering catheter was sutured in a subcutaneous pocket near the puncture site. The original tethering catheter used in humans and a stiffer catheter designed to prevent migration in swine were evaluated. Postplacement, mid-study, and preexplant vena cavography procedures were performed. Four swine underwent in situ dissection at 3-10 weeks. Filters were removed from seven animals just before they were killed at 1-6 weeks. RESULTS: All filters were successfully placed. All seven filters were successfully removed at up to 6 weeks after placement. Cephalic migration of more than 1 cm was observed in 10 of 11 swine (100% of original catheters, 83% of stiff catheters). Other complications were more common with stiffer tethering catheters, including caval stenosis in 40% of original catheters and 100% of stiff catheters, filter cone thrombus in 0% and 67%, tethering catheter thrombus in 20% and 83%, pulmonary embolism in 0% and 50%, and death in 0% and 17%, respectively. There was mild vessel wall damage in the vena cava. CONCLUSION: Placement of the Tempofilter and removal at up to 6 weeks after placement is feasible.

Animals↗

Histologic comparison of coronary and iliac atherectomy tissue from cases of in-stent restenosis.

Pathologically, restenotic lesions after stenting were investigated by use of atherectomized tissues of seven coronary and seven iliac arteries. The mean interval of the stent deployment to restenosis was 9.1 months for the coronary artery and 33.7 months for the iliac artery, indicating a 3.7-fold longer interval for the latter. This study does not include cases of acute thrombotic occlusion. The atherectomized tissue from restenotic coronary arteries showed abundant neointima with alpha-actin-positive and ultrastructually synthetic-type smooth muscle cells in a rich myxomatous extracellular matrix. In the iliac arteries, the predominant component of restenosis consisted of organized thrombi. The neointima of the iliac arteries was mature, and only a small amount of spindle cells were observed in the hyalinized matrix. The tissue that developed restenosis after stenting was different in the coronary and iliac arteries included in this series. This study on the atherectomized tissue suggests that even in the chronic stage, a major cause of in-stent restenosis among the larger caliber vessels such as the iliac artery is not neointima but stent thrombosis.

Aged↗

Prevalence of maxillary sinus disease and abnormalities in patients scheduled for sinus lift procedures.

BACKGROUND: The purpose of the present study was to determine the prevalence of sinus disease and abnormalities among patients scheduled to undergo direct sinus augmentation. METHODS: Forty-five patients attending a private periodontal practice and consecutively treatment planned for sinus augmentation were referred for otorhinolaryngologic evaluation, which included a medical history and radiographic (computed tomography), clinical, and endoscopic examinations. Pathological findings were recorded and otorhinolaryngologic treatment was provided. Six months later the sinus augmentation procedure was performed and followed by postoperative evaluations for 4 to 6 months. RESULTS: Of the 45 subjects, 98% (44) were diagnosed with chronic periodontitis, 51% were smokers, and 27% reported a history of symptoms indicative of sinus disease. Eighteen subjects were diagnosed with sinus disease and/or abnormalities. The diagnosed conditions included chronic sinusitis, sinus cysts, nasal septum deviation, and ostium stenosis. No significant differences in age, gender, or smoking status between patients with and without sinus conditions were found (P >0.05). There was a significant association between history of symptoms and diagnosis of sinus conditions (P <0.0001). Three subjects (one treated for preoperative sinus conditions) experienced notable intra- or postoperative complications related to the sinus augmentation procedure. CONCLUSIONS: The results indicate that, in a population of patients with chronic periodontitis, presence of sinus conditions is strongly associated with a history of indicative symptoms and is independent of age, gender, and smoking status. The results reinforce the importance of careful detailed history taking and thorough clinical and radiographic evaluation prior to performing sinus augmentation.

Adult↗

Fibroblast transplantation in the airway: implications for subglottic stenosis.

OBJECTIVE: Because subglottic stenosis (SGS) represents one of the most challenging pathologies confronting the pediatric otolaryngologist, our laboratory is investigating the role fibroblasts play in mucosal scar formation in the course of SGS development. Our objective is to establish cell transplantation into the subglottic mucosal wound bed as a viable tool for examining the cellular processes that underlie the development of SGS. DESIGN: A series of 2 animal experiments, with animals assigned to a control, vehicle-only, or cell-treated group. SETTING: John G. Rangos Sr Research Center, Children's Hospital of Pittsburgh, Pittsburgh, Pa. SUBJECTS: Twenty-six New Zealand white rabbits. This animal model has been well established in the study of SGS formation. INTERVENTIONS: Fluorescently labeled exogenous fibroblasts were transplanted into the injured subglottis of the rabbits. RESULTS: Exogenous fibroblasts derived from fetal and adult dermis and subglottic mucosa were successfully transplanted into the injured subglottic mucosa of adult rabbits. Transplanted fibroblasts survived into the latter stages of wound healing (at 14 and 21 days) and appeared to be associated with a mild inflammatory cell influx and active remodeling of the mucosal wound bed. CONCLUSION: Cell transplantation is a viable tool for the study of fibroblast activity in the mucosal wound bed.

Animals↗

Tissue-layer-resolved proteome landscape of Crohn's disease strictures highlights potential drivers of fibrosis progression.

The chronic inflammation of Crohn's disease frequently leads to fibrosis and muscular hypertrophy of the intestinal wall. This often culminates in strictures, a serious condition lacking directed therapy. Severe pathological changes occur in the submucosa and muscularis propria intestinal wall layers of strictures, yet stricture-associated proteome changes in these layers is unexplored. We perform unbiased proteomics on submucosa and muscularis propria microdissected from transmural sections of strictured and nonstrictured ileum. Proteome changes in strictured submucosa reflected a transition from homeostasis to tissue remodeling, inflammation, and smooth muscle changes. Top submucosal features included reduced vascular components and lipid metabolism proteins accompanied by increased proteins with immune-, ECM-, or stress-related functions, including CTHRC1, TNC, IL-16, MZB1, and TXNDC5. In parallel, predominant changes in strictured muscularis propria included increased ECM (POSTN) and immune (mast cell CPA3) proteins alongside decreased proteins with lipid metabolic, mitochondrial, or key muscle functions. Finally, trends of differentially expressed proteins along nonstrictured submucosa suggest progressive profibrotic tissue remodeling and muscle expansion as proximity to strictures increases. The comprehensive proteome map presented here offers tissue-layer-resolved insight into the stricture microenvironment and potential drivers of fibrotic disease, providing a valuable resource to fuel biomarker and therapeutic target research.

Humans↗