Search

Intestinal transplant recipients experience a high rate of renal complications secondary to dehydration due to increased ostomy output. It is hypothesized that inclusion of donor colon in the intestinal allograft may improve renal function in patients without functional native colon by improving fluid absorption. A single-center retrospective study of intestinal transplant recipients compared outcomes of patients receiving en bloc colon as part an intestinal allograft (ICTx), and those not receiving colon (CCNTx), as well as a control group of intestinal transplant recipients with functional native colon (ITx). Forty-seven patients (ICTx n = 17, CCNTx n = 15, ITx n = 15) were studied. One-year post-transplant renal function, as measured by change in glomerular filtration rate (GFR) and blood urea nitrogen (BUN) from baseline, was superior in ICTx (mean delta-GFR of -1.31 and delta-BUN of -1.46) compared to CCNTx (-6.54 and 17.54, P = 0.05 and P = 0.17, respectively) and similar to the ITx controls (0.55 and 2.09). Recipients of donor colon experienced a higher rate of ileostomy reversal when compared to CCNTx (62.5% vs. 20%, P = 0.0008), which was similar to the ITx controls (60%). These findings support the inclusion of en bloc donor colon in the intestinal allograft for recipients without functional native colon.

Keratan sulfate (KS) is a sulfated linear polymer of N-acetyllactosamine. Proteoglycans carrying keratan sulfate epitopes were majorly observed in cornea, cartilage and brain; and mainly involved in embryonic development, cornea transparency, and wound healing process. Recently, expression of KS in cancer has been shown to be highly associated with advanced tumor grade and poor prognosis. Therefore, we aimed to identify the expression of KS epitope in human pancreatic cancer primary and metastatic tumor lesions. Immunohistochemical analysis of KS expression was performed on primary pancreatic tumors and metastatic tissues. We observed an increased expression of KS epitope on primary tumor tissues compared to uninvolved normal and tumor stroma; and is associated with worse overall survival. Moreover, lung metastatic tumors show a higher-level expression of KS compared to primary tumors. Interestingly, KS biosynthesis specific glycosyltransferases expression was differentially regulated in metastatic pancreatic tumors. Taken together, these results indicate that aberrant expression of KS is predictive of pancreatic cancer progression and metastasis and may serve as a novel prognostic biomarker for pancreatic cancer.

Skeletal health consequences associated with inflammatory diseases of the airways significantly contribute to morbidity. Sex differences have been described independently for lung and bone diseases. Repetitive inhalant exposure to lipopolysaccharide (LPS) induces bone loss and deterioration in male mice, but comparison effects in females are unknown. Using an intranasal inhalation exposure model, 8-week-old C57BL/6 male and female mice were treated daily with LPS (100 ng) or saline for 3 weeks. Bronchoalveolar lavage fluids, lung tissues, tibias, bone marrow cells, and blood were collected. LPS-induced airway neutrophil influx, interleukin (IL)-6 and neutrophil chemoattractant levels, and bronchiolar inflammation were exaggerated in male animals as compared to female mice. Trabecular bone micro-CT imaging and analysis of the proximal tibia were conducted. Inhalant LPS exposures lead to deterioration of bone quality only in male mice (not females) marked by decreased bone mineral density, bone volume/tissue volume ratio, trabecular thickness and number, and increased bone surface-to-bone volume ratio. Serum pentraxin-2 levels were modulated by sex differences and LPS exposure. In proof-of-concept studies, ovarectomized female mice demonstrated LPS-induced bone deterioration, and estradiol supplementation of ovarectomized female mice and control male mice protected against LPS-induced bone deterioration findings. Collectively, sex-specific differences exist in LPS-induced airway inflammatory consequences with significant differences found in bone quantity and quality parameters. Male mice demonstrated susceptibility to bone loss and female animals were protected, which was modulated by estrogen. Therefore, sex differences influence the biologic response in the lung-bone inflammatory axis in response to inhalant LPS exposures.

INTRODUCTION: SARS-CoV-2 most commonly presents with respiratory symptoms and fever A significant proportion of patients are also experiencing gastrointestinal (GI) symptoms with loss of appetite, nausea, vomiting and diarrhea (variable, up to 10%);however, there is limited data about the associated histologic findings in the GI tract CASE DESCRIPTION/METHODS: A 71 year old male presented with fever for past five days after going on a cruise two days prior Antibiotics were initiated along with self-quarantine Over the next few days, he developed cough, shortness of breath, fever and myalgia SARS-CoV-2 infection was confirmed on nasopharyngeal swab He was intubated for ARDS and started on Remdesivir, which was stopped due to acute kidney injury Over the next month he developed septic shock, arrythmias, spontaneous venous bleeds, acalculous cholecystitis, ventilator associated pneumonia and profuse diarrhea GI pathogen panel and Clostridium difficile testing were negative CT of the abdomen showed colonic and distal small bowel wall thickening with adjacent inflammatory changes EGD and colonoscopy demonstrated ulceration of the duodenum, splenic flexure, sigmoid colon and rectum (Figure 1) Biopsies from the terminal ileum showed increased apoptotic bodies (>10 apoptosis per 10 crypts), mild villous blunting, patchy crypt dropout and crypt abscess (Figure 2) Colon biopsies had similar features along with mucosal erosion and focal crypt abscess formation No significant increase in intra-epithelial lymphocytes was identified Viral stains for CMV and Adenovirus were negative DISCUSSION: Limited data on GI specimens from SARS-CoV-2 positive patients have showed no significant damage with few infiltrating plasma cells and lymphocytes in lamina propria along with interstitial edema In our case, we observed extensive apoptotic injury with acute inflammation Although confirmatory stool testing was not performed, SARS CoV-2 was favored as the etiology due a long gap between the administration of Remdesivir and lack of any other identifiable causes Further studies are needed to characterize SARS-CoV-2 associated gastrointestinal disease (Figure Presented)

Rheumatoid arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint-lung inflammatory outcomes. DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on days 1 and 21. Treatment groups included sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE), and CIA + ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed. In DBA/1J male mice, arthritis was increased in CIA + ODE > CIA > ODE versus sham. Micro-computed tomography (µCT) demonstrated that loss of BMD and volume and deterioration of bone microarchitecture was greatest in CIA + ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE > CIA + ODE versus sham. Activated lung CD11c+ CD11b+ macrophages were increased in ODE > CIA + ODE > CIA pattern, whereas lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA + ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared with male mice, female mice showed less articular and pulmonary disease. The interaction of inhalation-induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response, but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This coexposure model could be exploited to better understand and treat RA-lung disease. © 2019 American Society for Bone and Mineral Research.

Objective The aim of this study is to determine the diagnostic accuracy of preoperative evaluation to detect main pancreatic duct involvement in pancreatic cystic lesions thus differentiating mixed intraductal papillary mucinous neoplasm (IPMN) from branch duct (BD)-IPMN. Methods The pathology database of pancreatic resections from 2000 to 2014 was reviewed. Main pancreatic duct-IPMNs and IPMNs with intracystic mass/nodules were excluded. The preoperative test characteristics were analyzed using surgical histopathology as the "gold standard." Results Sixty BD-IPMNs and 23 mixed-IPMNs were identified. Mixed-IPMNs were larger (mean [standard deviation], 4.14 [2.9] vs 2.74 [1.9] mm; P = 0.03) and demonstrated frequent high-grade dysplasia/adenocarcinoma (43% vs 12%, P = 0.004) than BD-IPMNs. Endoscopic ultrasound (EUS) (sensitivity, 80%; specificity, 78%; accuracy, 79%) had the best diagnostic accuracy, whereas magnetic resonance imaging (MRI) (sensitivity, 83%; specificity, 63%; accuracy, 68%) had the highest sensitivity for the diagnosis of mixed-IPMN. A combination of EUS and MRI reached maximum sensitivity but with decreased accuracy (sensitivity, 100%; specificity, 64%; accuracy, 67%). The area under the curve for receiver operation curve was 0.71 whereas the optimal cyst size to detect main duct involvement was 3 cm. Conclusions For preoperative evaluation of pancreatic cystic lesions without evidence of intracystic nodules, a combination of MRI and EUS should be considered for improved detection of main duct involvement.

OBJECTIVES Our objective was to delineate predictive factors differentiating groove pancreatitis (GP) from other lesions involving the head of the pancreas (HOP). METHODS A case-control study of patients older than 10 years was performed comparing patients with GP to those with other surgically resected HOP lesions. RESULTS Thirteen patients with GP (mean ± SD age, 51.9 ± 10.5 years; 11 males [84.6%]), all with a history of smoking (mean, 37.54 ± 17.8 pack-years), were identified. Twelve patients (92.3%) had a history of heavy alcohol drinking (heavy alcohol [EtOH]). The mean lesion size was 2.6 ± 1.1 cm, and the CA 19-9 was elevated (>37 IU/mL) in 5 patients (45.5%). The most common histopathologic condition was duodenal wall cyst with myofibroblastic proliferation and changes of chronic pancreatitis in the HOP.Univariate analysis revealed decreasing age, male sex, weight loss, nausea/vomiting, heavy EtOH, smoking, and a history of chronic pancreatitis were predictive of GP. A multivariate analysis among smokers demonstrated that weight loss (P = 0.006; odds ratio, 11.96; 95% confidence interval, 2.1-70.2), and heavy EtOH (P < 0.001; odds ratio, 82.2; 95% confidence interval, 9.16-738.1) were most predictive of GP. Compared to pancreatic adenocarcinoma (n = 183), weight loss and heavy EtOH remained predictive of GP. CONCLUSION Groove pancreatitis in the HOP is associated with a history of heavy EtOH and weight loss. In the absence of these symptoms, it is essential to rule out a malignant lesion.

We report the morphologic description of the bile acid sequestrants (BAS) colesevelam and colestipol, as well as the largest series of cholestyramine. Histologically similar medication resins from 4 institutions were prospectively collected over 1 year (26 specimens, 15 patients). Comorbidities included hyperlipidemia (4/15), hypertension (4/15), inflammatory bowel disease (4/15), coronary artery disease (3/15), diarrhea (7/15), hypothyroidism (2/15), and ischemic bowel (1/15). Sites of involvement included the esophagus (1/26), stomach (1/26), small intestine (1/26), ileocecal valve (1/26), and colorectum (22/26). Associated histologic diagnoses included normal (8/26), chronic mucosal injury (11/26), acute inflammation (9/26), erosion/ulceration (6/26), and cytomegalovirus (2/26). The BAS resins were histologically indistinguishable from each other; they were all eosinophilic on hematoxylin and eosin (HE) and lacked internal "fish-scales." To validate these observations, respective medications were submitted for histologic processing; the processed medications were identical to those in the patient specimens. Rare, irregular "fracture" lines presented diagnostic pitfalls by mimicking the true "fish-scales" of Kayexalate and sevelamer. Clues to the correct identification of BAS include recognition that the "fracture" lines were subtle, irregular, and restricted to large fragments or thick sections, likely representing a processing artifact. Moreover, Kayexalate is violet on HE and black on acid fast bacillus, and sevelamer characteristically displays a 2-tone color on HE and is magenta on acid fast bacillus. An association with inflammatory injury was seen (15/26). We believe that the BAS are innocent bystanders in complicated patients, although we cannot exclude their ability to cause mucosal injury in specific settings.

BACKGROUND Chronic rejection is a significant barrier to small bowel allograft survival. Although chronic rejection primarily involves vessels of the submucosa, serosa, and mesentery, some mucosal alterations have been suggested to be correlative. METHODS We retrospectively investigated explanted small bowel allografts for clinical characteristics and histological alterations in the mucosa, submucosa, and serosa. RESULTS Crypt epithelial mucin loss, submucosal fibrosis, and length of time to explant were all statistically associated with chronic rejection. Medium-sized and large-sized vessels of the serosa and mesentery preferentially demonstrated histologic changes of chronic rejection. CONCLUSION These results further define chronic vascular rejection and the relationship between the mucosal changes and chronic rejection.

Aim Mucins comprise a family of high-molecular-weight glycoproteins. MUC4, a large transmembrane mucin, has recently emerged as a novel marker for diagnosis, prognosis and therapy in several malignancies. However, its role in skin pathologies remains unknown. The aim of this study was to analyse the expression of MUC4 in cutaneous pathologies by immunohistochemistry for potential diagnostic, prognostic and therapeutic applications. Methods A total of 330 tissue spots representing the normal skin, and benign and malignant cutaneous diseases, were analysed after staining with the monoclonal antibody to human MUC4 (clone 8G7). Results While the normal epidermis showed a negative to weak-positive expression of MUC4, its expression was significantly upregulated in squamous cell carcinomas (SCCs) where the intensity of staining correlated negatively with tumour grade and positively with age. A moderately strong MUC4 expression was also noted in 2/20 cancer adjacent normal skin and 2/21 chronically inflamed skin tissues, while 10/19 cases of vulval condyloma acuminate, 3/12 of vulval hyperplasia and 2 cases of verruca vulgaris also showed strong MUC4 positivity. Malignant melanoma, basal cell carcinoma and cutaneous cysts were negative. Conclusion The results indicate that MUC4 expression is aberrantly upregulated in cutaneous SCCs, vulval condylomas and verruca vulgaris. Further, it appears that MUC4 expression in the skin may be modulated by chronic inflammation and the presence of an adjacent cutaneous malignancy in certain cases. These observations suggest a novel role for MUC4 mucin in the pathogenesis of cutaneous SCC and a possible application as a diagnostic and/or prognostic marker in cutaneous pathologies.

Background & Aims: Endoscopic ultrasound (EUS) is often used as the gold standard to diagnose chronic pancreatitis (CP) despite concerns about its intra-operator reliability and validity. We sought to determine the benefit of repeat EUS in patients suspected of having CP but having an equivocal or negative initial EUS exam for CP. Methods: Patients who underwent at least two EUS exams at our medical center to evaluate for CP from 20012012 were identified. Demographic, procedural and etiologic factors were abstracted via chart review. Specifically, EUS minimal standard criteria (MST) for CP (hyperechoic foci, hyperechoic strands, lobularity, cysts, ectatic duct, hyperechoic ductal wall, dilated side branches, ductal stones, ductal dilation) were abstracted for all exams. Diagnosis of CP was based on physician impression following each EUS. Results: Between the first and second EUS exams, the number of patients diagnosed with CP increased from 49% to 76% (p

Background & Aims: Endoscopic ultrasound (EUS) is often used as the gold standard to diagnose chronic pancreatitis (CP) despite concerns about its intra-operator reliability and validity. We sought to determine the benefit of repeat EUS in patients suspected of having CP but having an equivocal or negative initial EUS exam for CP. Methods: Patients who underwent at least two EUS exams at our medical center to evaluate for CP from 20012012 were identified. Demographic, procedural and etiologic factors were abstracted via chart review. Specifically, EUS minimal standard criteria (MST) for CP (hyperechoic foci, hyperechoic strands, lobularity, cysts, ectatic duct, hyperechoic ductal wall, dilated side branches, ductal stones, ductal dilation) were abstracted for all exams. Diagnosis of CP was based on physician impression following each EUS. Results: Between the first and second EUS exams, the number of patients diagnosed with CP increased from 49% to 76% (p