Fungal-bacteria interactions provide shelter for bacteria in Caesarean section scar diverticulum.

Caesarean section scar diverticulum (CSD) is a significant cause of infertility among women who have previously had a Caesarean section, primarily due to persistent inflammatory exudation associated with this condition. Even though abnormal bacterial composition is identified as a critical factor leading to this chronic inflammation, clinical data suggest that a long-term cure is often unattainable with antibiotic treatment alone. In our study, we employed metagenomic analysis and mass spectrometry techniques to investigate the fungal composition in CSD and its interaction with bacteria. We discovered that local fungal abnormalities in CSD can disrupt the stability of the bacterial population and the entire microbial community by altering bacterial abundance via specific metabolites. For instance, Lachnellula suecica reduces the abundance of several Lactobacillus spp., such as Lactobacillus jensenii, by diminishing the production of metabolites like Goyaglycoside A and Janthitrem E. Concurrently, Clavispora lusitaniae and Ophiocordyceps australis can synergistically impact the abundance of Lactobacillus spp. by modulating metabolite abundance. Our findings underscore that abnormal fungal composition and activity are key drivers of local bacterial dysbiosis in CSD.

Serotonin Metabolism and Serotonin Receptors Expression Are Altered in Colon Diverticulosis.

Background and Objectives: Diverticulosis is frequently accompanied by altered bowel habits. The biogenic amines within colonic mucosa control bowel motility, and in particular, alterations in serotonin signaling may play a role in colon diverticulosis. The aim of the study was to assess the concentration of biogenic amines and serotonin receptor expression in the colonic mucosa in patients with diverticulosis and healthy controls. Materials and Methods: This prospective, comparative study included 59 individuals: 35 with sigmoid diverticulosis and 24 healthy controls. The study was held at the Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Poland. Mucosal samples were taken from the right and left colon during a colonoscopy in all patients. Concentrations of norepinephrine, 3-methoxy-4-hydroxyphenylglycol, dopamine, homovanillic acid, serotonin, and 5-hydroxyindoleacetic acid were measured with high-performance liquid chromatography. Expressions of human 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 4, 5-hydroxytryptamine receptor 7, solute carrier family 6 member 4 (SERT) for serotonin, as well as the neuroglia activation markers glial fibrillary acidic protein, S100 calcium-binding protein B, and proteolipid protein 1, were assessed with polymerase chain reaction. Results: The median age and sex distribution were comparable in both study groups (median 69 y vs. 52 y; p < 0.455 and males/females in cases 11/17 vs. 18/19 in controls; p < 0.309). In diverticulosis patients, there was a higher concentration of serotonin in the left affected colon compared to the right healthy part of the colon (median 8239 pg/mg vs. 6326 pg/mL; p < 0.01). The SERT expression was lower in the affected left segment compared to the right colon (median 0.88 vs. 1.36; p < 0.01). There was a higher colonic mucosa concentration of serotonin (median 8239 pg/mg vs. 6000 pg/mL; p < 0.02) and 5-hydroxyindoleacetic acid/serotonin ratio (median 0.27 vs. 0.47; p < 0.01) in diverticulosis patients compared to controls in the left side of the colon. Conclusions: The concentration of serotonin in the mucosa of the colon segment affected by diverticula is higher than in the healthy segment in the same individuals and higher than in healthy controls. These results underline serotonin signaling in colon diverticulosis pathophysiology.

Macrophage polarisation in caesarean scar diverticulum.

AIMS: To determine immunohistochemical features and correlations between M1/M2 polarisation status with disease severity of post-caesarean scar diverticulum (CSD). METHODS: Histological and immunohistological stainings were performed and inflammatory (CD16, CD163 and tumour necrosis factor-α (TNF-α)), fibrosis (α-smooth muscle actin (α-SMA)) and angiogenic (CD31) markers were examined in uterine tissues collected from patients with uterine scar diverticula (CSD) (n=37) and caesarean section (CS) (n=3). RESULTS: CSD tissues have higher expression of α-SMA, TNF-α, CD16 and CD31 and lower expression of CD163 than CS tissue (p<0.05). Compared with adjacent tissues, thick-walled blood vessels, glands and fibrotic sites have higher expression of α-SMA, TNF-α and CD16. Statistical correlation was observed between the expression of CD16 and TNF-α (R=0.693, p<0.001), α-SMA (R=0.404, p<0.05) and CD31 (R=0.253, p<0.05) in CSD tissues, especially with the ratio of CD16/CD163 (R=0.590, p<0.01). A more significant difference was observed between the expression of CD16/CD163 and α-SMA (R=0.556, p<0.001), TNF-α (R=0.633, p<0.0001) and CD31 (R=0.336, p<0.05). CONCLUSIONS: In this study, TNF-α, α-SMA, CD16 and CD31 proteins were overexpressed in all CSD cases, and CD16/CD163 was positively correlated with tissue inflammation, fibrosis and neovascularisation. Abnormal mononuclear macrophage infiltration may be involved in the origin and progression of CSD.

Unsuspected Bladder Diverticulum Resulted in False-Positive 68Ga-DOTATATE Uptake.

ABSTRACT: A 67-year-old woman with medullary thyroid cancer was referred for a 68Ga-DOTATATE PET/CT scan for staging. The images showed abnormal activity in the left thyroid gland and the left cervical lymph nodes. Surprisingly, increased activity was also noted in the posterolateral aspect of the urinary bladder without corresponding anatomical abnormality. This activity disappeared after urination, suggesting false-positive uptake due to bladder diverticulum.

Challenges in the diagnosis of calyceal diverticulum: A report of two cases and review of the literature.

BACKGROUND: Calyceal diverticula outpouchings that occur rarely in the upper collecting system of the kidney and is often difficult to detect. In this study, we present two cases of calyceal diverticula and discuss their clinical characteristics and radiologic features. PATIENTS AND METHODS: In the presented two cases, we applied several imaging examinations, including delayed intravenous pyelography, retrograde pyelography and axial computerized tomographic (CT) scanning of the kidneys with and without contrast. Serum creatinine levels in fluid withdrawn from the diverticula were found to be significantly higher than the simultaneous serum creatinine levels. Intravenous injection of methylene blue through a ureteral catheter was also aided in the diagnosis. Calyceal diverticulum neck dilatation was performed through a percutaneous nephroscope.ResultsThe two cases were diagnosed preoperatively and the operation was successful performed. The nephrostomy tube was removed seven days after surgery without complications. CT scans of the kidney after six months showed that the size of the calyceal diverticulum of two patients were considerably smaller than pre-surgery. There were no reports of pain in the lumbar region or other discomfort. COMMENTS: Diagnosis of calyceal diverticulum mainly depend on a variety of imaging examinations, including the delayed intravenous pyelography, retrograde pyelography, and kidney CT plain scan plus enhanced scan. If the patient cannot be diagnosed by above methods, cyst fluid can be aspirated percutaneously to measure the preoperative creatinine level. If it is significantly higher than the serum creatinine level, the cyst fluid is considered urine, which can assist in the diagnosis of calyceal diverticulum. A ureteral catheter should also be inserted before operation namely, intravenous injection of methylene blue through a ureteral catheter is helpful for diagnosis. The choice of surgical treatment is based on the size and location of calyceal diverticulum and clinical manifestations.

A pilot study of visceral fat and its association with adipokines, stool calprotectin and symptoms in patients with diverticulosis.

BACKGROUND: Complications of diverticular disease are increasingly common, possibly linked to increasing obesity. Visceral fat could contribute to the development of symptomatic diverticular disease through its pro-inflammatory effects. OBJECTIVE: The study had 2 aims. A) to develop a semi-automated algorithm to measure abdominal adipose tissue from 2-echo magnetic resonance imaging (MRI) data; B) to use this to determine if visceral fat was associated with bowel symptoms and inflammatory markers in patients with symptomatic and asymptomatic diverticular disease. DESIGN: An observational study measuring visceral fat using MRI together with serum adiponectin, leptin, stool calprotectin and patient-reported somatisation and bowel habit. SETTING: Medical and imaging research centres of a university hospital. PARTICIPANTS: MRI scans were performed on 55 patients after an overnight fast measuring abdominal subcutaneous and visceral adipose tissue volumes together with small bowel water content (SBWC). Blood and stool samples were collected and patients kept a 2 week stool diary and completed a somatisation questionnaire. MAIN OUTCOME MEASURES: Difference in the volume of visceral fat between symptomatic and asymptomatic patients. RESULTS: There were no significant differences in visceral (p = 0.98) or subcutaneous adipose (p = 0.60) tissue between symptomatic and asymptomatic patients. However measured fat volumes were associated with serum adipokines. Adiponectin showed an inverse correlation with visceral adipose tissue (VAT) (Spearman ρ = -0.5, p = 0.0003), which correlated negatively with SBWC (ρ = -0.3, p = 0.05). Leptin correlated positively with subcutaneous adipose tissue (ρ = 0.8, p < 0.0001). Overweight patients (BMI > 25 kgm-2) showed a moderate correlation between calprotectin and VAT (ρ = 0.3, p = 0.05). Somatization scores were significantly higher in symptomatic patients (p < 0.0003). CONCLUSIONS: Increasing visceral fat is associated with lower serum adiponectin and increased faecal calprotectin suggesting a pro-inflammatory effect which may predispose to the development of complications of diverticulosis.

Differential expression of epidermal growth factor receptor (EGFR) in stomach and diverticulum of Otocinclus affinis (Steindachner, 1877) as a potential element of the epithelium remodeling mechanism.

It is suggested that due to the several stomach modifications, Otocinculus affinis (dwarf sucking catfish) possess the ability to breathe air during hypoxia, however, the exact mechanism remains unknown. The aim of this study was detailed analysis of the expression of EGFR in the stomach and diverticulum of the O. affinis at the mRNA and protein levels together with the immunohistochemical localization of EGFR in these organs. The intensity of band fluorescence corresponding to the EGFR gene expression level is significantly higher in the stomach than in the diverticulum. Further, quantitative analysis of EGFR protein abundance also revealed its higher synthesis in the stomach than in the diverticulum and the immunohistochemistry method confirmed these results. As regional localization of respiratory function in gut air-breathing fishes seems to be connected with "morphological remodeling" of the epithelium of their gut, the present research demonstrated the potential efficiency of the O. affinis stomach as a respiratory organ. Having the potential possibility to create an air-blood barrier in the gastrointestinal tract allowing gas diffusion and respiration in hypoxic states seems to be very beneficial for these fish. It seems that facultative gut air breathing fish species are a relevant vertebrate model for high throughput screening, vascular biology and evolution.

The left-right asymmetry of liver lobation is generated by Pitx2c-mediated asymmetries in the hepatic diverticulum.

Internal organs exhibit left-right asymmetric sizes, shapes and anatomical positions, but how these different lateralities develop is poorly understood. Here we use the experimentally tractable Xenopus model to uncover the morphogenetic events that drive the left-right asymmetrical lobation of the liver. On the right side of the early hepatic diverticulum, endoderm cells become columnar and apically constricted, forming an expanded epithelial surface and, ultimately, an enlarged right liver lobe. In contrast, the cells on the left side become rounder, and rearrange into a compact, stratified architecture that produces a smaller left lobe. Side-specific gain- and loss-of-function studies reveal that asymmetric expression of the left-right determinant Pitx2c elicits distinct epithelial morphogenesis events in the left side of the diverticulum. Surprisingly, the cellular events induced by Pitx2c during liver development are opposite those induced in other digestive organs, suggesting divergent cellular mechanisms underlie the formation of different lateralities.

Intense 68Ga-PSMA Uptake in Diverticulum of the Sigmoid Colon.

We present a case of a diverticulum of the sigmoid colon with intense prostate-specific membrane antigen (PSMA) activity on Ga-PSMA PET/CT. CT scan and colonoscopy showed no signs of inflammation or malignancy. This case presents an addition to the collection of benign pitfalls when reporting PSMA PET/CT; however, a Ga-PSMA up-taking focus in the colon should always cause further examination, as malignant etiology must be ruled out.

Percutaneous Management of Stone Containing Calyceal Diverticula: Associated Factors and Outcomes.

PURPOSE: We evaluated the outcomes of percutaneous treatment and metabolic evaluation of calyceal diverticula with associated stones. MATERIALS AND METHODS: We retrospectively identified 51 patients with a calyceal diverticulum in our prospectively maintained percutaneous nephrolithotomy database. Patients with complete data were separated into 14 with stones isolated to the diverticulum and 15 with renal stones in and outside the diverticulum. A total of 571 patients with renal stones but no diverticulum were used for comparison. Statistical differences were assessed using the chi-square test and the t-test. RESULTS: Patients with stones isolated to the diverticulum were younger (44 vs 54 years, p = 0.024), had a lower body mass index (23.2 vs 27 kg/m2, p = 0.032) and were more often female (71% vs 44%, p = 0.046) compared to patients with renal stones but no diverticulum. Calyceal diverticula were anterior in 19 of 29 cases and in the upper pole in 15. Average diverticular size was 2.5 cm with a 1.5 cm stone burden. Percutaneous treatment was successful in 96% of patients with a 4% complication rate. The diverticular neck was dilated in 22 of 51 patients (43%). During 5-year followup in the 51 patients there was 1 stone recurrence, which was managed by ureteroscopy, while 46 and 5 patients showed complete absence and reduction of the diverticulum, respectively. Of the calyceal diverticular stones 82% contained calcium phosphate compared to only 33% in patients with renal stones but no diverticulum. All patients with a diverticulum had at least 1 metabolic derangement. CONCLUSIONS: Percutaneous treatment of calyceal diverticula is safe and effective regardless of size or location, including anterior diverticula. Infundibular neck dilation does not appear to be necessary. There are metabolic abnormalities in a significant proportion of patients with a calyceal diverticulum.

[Juxtapapillary duodenal diverticulum causing pancreatobiliary problems - case report and literature review]. / Juxtapapilární divertikl duodena jako prícina pankreatobiliárních potízí - kazuistika a prehled literatury.

UNLABELLED: Juxtapapillary duodenal diverticula are reported as a potential cause of many pancreatobiliary diseases. However, data concerning this association is inconsistent and the role of the diverticulum is often underestimated or even denied in clinical practice. This case report and literature review is aimed at pointing out this problem.Obstruction of the diverticulum with a food bezoar can be considered as an important clinical clue of the etiological role of the diverticulum in pancreatobiliary disease development.Endoscopic sphincterotomy is considered to be the treatment of the first choice, with surgery (diverticulectomy and/or biliodigestive anastomosis) reserved for cases where the minimally invasive approach fails. KEY WORDS: juxtapapillary duodenal diverticulum obstructive jaundice acute pancreatitis endoscopic papilosphincterotomy biliodigestive anastomosis.

Breath Methane Levels Are Increased Among Patients with Diverticulosis.

BACKGROUND: Diverticulosis and its complications are important healthcare problems in the USA and throughout the Western world. While mechanisms as to how diverticulosis occurs have partially been explored, few studies examined the relationship between colonic gases such as methane and diverticulosis in humans. AIM: This study aimed to demonstrate a significant relationship between methanogenic Archaea and development of diverticulosis. METHODS: Subjects who consecutively underwent hydrogen breath test at Rush University Medical Center between 2003 and 2010 were identified retrospectively through a database. Medical records were reviewed for presence of a colonoscopy report. Two hundred and sixty-four subjects were identified who had both a breath methane level measurement and a colonoscopy result. Additional demographic and clinical data were obtained with chart review. RESULTS: Mean breath methane levels were higher in subjects with diverticulosis compared to those without diverticulosis (7.89 vs. 4.94 ppm, p = 0.04). Methane producers (defined as those with baseline fasting breath methane level >5 ppm) were more frequent among subjects with diverticulosis compared to those without diverticulosis (50.9 vs. 34 %, p = 0.0025). When adjusted for confounders, breath methane levels and age were the two independent predictors of diverticulosis on colonoscopy with logistic regression modeling. CONCLUSIONS: Methanogenesis is associated with the presence of diverticulosis. Further studies are needed to confirm our findings and prospectively evaluate a possible etiological role of methanogenesis and methanogenic archaea in diverticulosis.

Trend and risk factors of diverticulosis in Japan: age, gender, and lifestyle/metabolic-related factors may cooperatively affect on the colorectal diverticula formation.

BACKGROUND: Despite the marked increase of diverticulosis, its risk factors have not been adequately elucidated. We therefore aim to identify significantly associated factors with diverticulosis. We also aim to investigate the present state of diverticulosis in Japan. METHODS: We reviewed the medical records from 1990 to 2010 that included the data of consecutive 62,503 asymptomatic colonoscopy examinees from the general population in Japan. Most recent 3,327 examinees were analyzed with 16 background factors. RESULTS: Among the 62,503 subjects (47,325 men and 15,178 women; 52.1 ± 9.2 years old), diverticulosis was detected in 11,771 subjects (18.8%; 10,023 men and 1,748 women). The incidences of diverticulosis in 1990-2000 and 2001-2010 were respectively 13.0% (3,771 of 29,071) and 23.9% (8,000 of 33,432): the latter was much higher than the former in all age groups and for both genders. Considering the anatomical locations of colorectal diverticula, left-sided ones have markedly increased with age but not significantly changed with times. Univariate analyses of the 3,327 subjects showed significant association of diverticulosis with four basic factors (age, sex, body mass index, blood pressure), three life style-related factor (smoking, drinking, severe weight increase in adulthood), and two blood test values (triglyceride, HbA1c). The multiple logistic analysis calculating standardized coefficients (ß) and odds ratio (OR) demonstrated that age (ß = 0.217-0.674, OR = 1.24-1.96), male gender (ß = 0.185, OR = 1.20), smoking (ß = 0.142-0.200, OR = 1.15-1.22), severe weight increase in adulthood (ß = 0.153, OR = 1.17), HbA1c (ß = 0.136, OR = 1.15), drinking (ß = 0.109, OR = 1.11), and serum triglyceride (ß = 0.098, OR = 1.10) showed significantly positive association with diverticulosis whereas body mass index and blood pressure did not. CONCLUSIONS: The large-scale data of asymptomatic colonoscopy examinees from the general population from 1990 to 2010 indicated that the prevalence of diverticulosis is still increasing in Japan. Age, male gender, smoking, severe weight increase in adulthood, serum HbA1c, drinking, and serum triglyceride showed significant positive association with diverticulosis.

Divertículo vesical adquirido. Caso clínico / Acquired bladder diverticulum. A clinical case

El divertículo vesical (DV) puede ser congénito o adquirido. Consiste en una herniación de la mucosa vesical. Los adquiridos se deben a un mecanismo de hiperpresión endovesical generalmente en pacientes con obstrucción infravesical secundaria a hiperplasia benigna de próstata (HBP), patología del cuello vesical o uretral. Cuando los DV son sintomáticos o producen complicaciones se debe plantear tratamiento quirúrgico. En los últimos años la diverticulectomía laparoscópica ha presentado muy buenos resultados aunque la cirugía abierta está indicada en algunos casos más complejos. En DV adquiridos de tamaño pequeño y mediano está indicado el tratamiento transuretral. Se presenta un caso clínico y una revisión de diferentes aspectos diagnósticos y quirúrgicos del DV (AU)

The bladder diverticulum (DV) can be congenital or acquired. It consists of a herniation of the bladder mucosa. The acquired is due to a mechanism of intravesical hyperpressure usually in patients with bladder outlet obstruction secondary to BPH, cervical or urethral pathology. When DV are symptomatic or produce complications surgical treatment should be considered. In recent years laparoscopic diverticulectomy has shown very good results although open surgery is indicated in some more complex cases. In small and medium acquired DV transurethral treatment is indicated. One clinical case and a review of various diagnostic and surgical aspects of DV are presented (AU)

Litiasis en divertículo uretral. Diagnóstico y tratamiento / Urethral diverticulum lithiasis. Diagnostic and therapeutic management

Introducción: la incidencia del divertículo uretral es menor en hombres, siendo más frecuentes los casos adquiridos. Es extraordinario encontrar una litiasis ocupando la totalidad del divertículo. Caso clínico: presentamos varón de 34 años con litiasis en divertículo uretral secundaria a intervención quirúrgica previa. Conclusión: mujeres el tratamiento de elección será la diverticulectomía con la técnica más simple posible

Introduction: the urethral diverticulum incidence is lower in men than in women. Acquired cases are more frequent. Is extremely rare to find a diverticulum lithiasis. Case report: we present a 34 years old male with urethral diverticulum lithiasis due to previous urethral surgery. Conclusion: treatment of choice is diverticulectomy with lithiasis removement

Uncomplicated diverticular disease: innate and adaptive immunity in human gut mucosa before and after rifaximin.

BACKGROUND/AIM: Uncomplicated diverticular disease (UDD) is a frequent condition in adults. The pathogenesis of symptoms remains unknown. Bacteria are able to interact with Toll-like receptors (TLRs) and to induce inflammation through both innate immunity and T-cell recruitment. We investigated the pattern of TLRs 2 and 4 and the intestinal homing in patients with UDD before and after a course of Rifaximin. METHODS: Forty consecutive patients with UDD and 20 healthy asymptomatic subjects were enrolled. Among UDD patients, 20 were assigned to a 2-month course of treatment with Rifaximin 1.2 g/day for 15 days/month and 20 received placebo. Blood sample and colonic biopsies were obtained from patients and controls. The samples were collected and analyzed at baseline and at the end of treatment. Flow cytometry was performed using monoclonal antibodies (CD3, CD4, CD8, CD103, TCR-gamma/delta, CD14, TLR2, and TLR4). RESULTS: In UDD, TLR2 and TLR4 expression on immune cell subpopulations from blood and mucosa of the affected colon are altered as compared with controls. Rifaximin treatment induced significant modifications of altered conditions. CONCLUSIONS: Our data show the role of TLRs in the development of inflammation in UDD. TLRs distribution is altered in UDD and these alterations are reversed after antibiotic treatment. This trial is registered with ClinicalTrials.gov: NCT02068482.

Long segmental hyperplasia of interstitial cells of Cajal with giant diverticulum formation.

Sporadic gastrointestinal stromal tumors (GISTs) usually form a well-circumscribed mass. In contrast, diffuse interstitial cell of Cajal (ICC) hyperplasia along the Auerbach plexus without a discrete mass may occur in patients with germline mutations in the NF1, c-KIT or PDGFRA genes. However, sporadic, diffuse ICC hyperplasia without c-KIT or PDGFRA mutations has not been reported. We describe herein one such case, forming a giant diverticulum. A 63-year-old woman with no features of Neurofibromatosis 1 (NF1) presented with increasing abdominal pain for more than 30 years. A large, diverticulum-like mass in the ileum was resected. Microscopically, a diffuse proliferation of bland spindle cells was seen extending for 12 cm, replacing the muscularis propria and lined by intact mucosa. The spindle cells were CD117+/CD34+/DOG1+/SMA+/Desmin-/S100-. Mutation analyses did not reveal any mutations in c-KIT or PDGFRA. The lesion had two silent mutations in the NF1 gene. It is rare of the diffuse form of sporadic ICC hyperplasia showing diffuse longitudinal microscopic growth completely replacing the muscularis propria, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes, but without solid components and no c-KIT or PDGFRA gene mutations. This peculiar form of sporadic ICC hyperplasia may be related to intestinal dysmotility in this ileal segment and giant diverticulum formation.

The GDNF System Is Altered in Diverticular Disease - Implications for Pathogenesis.

BACKGROUND & AIMS: Absence of glial cell line-derived neurotrophic factor (GDNF) leads to intestinal aganglionosis. We recently demonstrated that patients with diverticular disease (DD) exhibit hypoganglionosis suggesting neurotrophic factor deprivation. Thus, we screened mRNA expression pattern of the GDNF system in DD and examined the effects of GDNF on cultured enteric neurons. METHODS: Colonic specimens obtained from patients with DD (n = 21) and controls (n = 20) were assessed for mRNA expression levels of the GDNF system (GDNF, GDNF receptors GFRα1 and RET). To identify the tissue source of GDNF and its receptors, laser-microdissected (LMD) samples of human myenteric ganglia and intestinal muscle layers were analyzed separately by qPCR. Furthermore, the effects of GDNF treatment on cultured enteric neurons (receptor expression, neuronal differentiation and plasticity) were monitored. RESULTS: mRNA expression of GDNF and its receptors was significantly down-regulated in the muscularis propria of patients with DD. LMD samples revealed high expression of GDNF in circular and longitudinal muscle layers, whereas GDNF receptors were also expressed in myenteric ganglia. GDNF treatment of cultured enteric neurons increased mRNA expression of its receptors and promoted neuronal differentiation and plasticity revealed by synaptophysin mRNA and protein expression. CONCLUSIONS: Our results suggest that the GDNF system is compromised in DD. In vitro studies demonstrate that GDNF enhances expression of its receptors and promotes enteric neuronal differentiation and plasticity. Since patients with DD exhibit hypoganglionosis, we propose that the observed enteric neuronal loss in DD may be due to lacking neurotrophic support mediated by the GDNF system.

Limited smoothelin expression within the muscularis mucosae: validation in bladder diverticula.

Smoothelin, a marker of differentiated smooth muscle, is diffusely expressed by bladder muscularis propria and is negative to only weakly and focally expressed in muscularis mucosae. We used bladder diverticula, which lack muscularis propria and frequently demonstrate hyperplastic muscularis mucosae, to evaluate the use of smoothelin immunoreactivity in diagnostic pathology. Diverticula from 40 patients (21 with benign features, 19 with neoplastic features) were studied. Immunohistochemistry was performed using smoothelin antibody (clone R4A, 1:150 dilution; Abcam, Cambridge, MA); and tissue was scored as 0 (no expression), 1+ (moderate expression b10% of cells), 2+ expression (moderate expression N10% of cells), and 3+ (robust diffuse expression). All diverticula contained muscularis mucosae of varying caliber; staining in diverticular muscularis mucosae was compared with historic results in the muscularis mucosae of cystectomy specimens. Hyperplastic muscularis mucosae occurred in 31 (78%) of 40 cases. Smoothelin immunoreactivity in the diverticular muscularis mucosae included 0 (16/40, or 40%); 1+ (11/40, or 27.5%); 2+ (13/40, or 32.5%); and 3+ (0/40, or 0%), with a slightly higher 2+ expression level in hyperplastic versus nonhyperplastic muscularis mucosae (35% versus 22%). Adjacent normal muscularis propria, present in 12 specimens, demonstrated 3+ muscularis propria immunoreactivity. Comparison between diverticula with benign and neoplastic features showed no significant difference in smoothelin immunoreactivity. No correlation was evident with smoothelin immunohistochemistry and muscle caliber. Smoothelin immunoreactivity in bladder diverticula confirms the limited nature of smoothelin expression in the muscularis mucosae and represents a useful ancillary technique in the proper histopathologic evaluation of diverticular and nondiverticular bladder carcinomas. A strong and robust staining of smooth, rounded muscle with smoothelin remains a useful diagnostic adjunct in the reliable recognition of muscularis propria.