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A 43-yr old female with two prior renal transplants for renal failure associated with diabetes, retinopathy and coronary artery disease developed diarrhea. Her medications included mycophenolate mofetil, an immunosuppressive medication documented to cause sprue-like mucosal changes in the small intestine. Later studies revealed a small intestinal mucosal lesion characterized by marked crypt hyperplasia, villous atrophy and increased intra-epithelial lymphocytes. Serological studies for celiac disease were negative and repeated biopsies despite a strict gluten-free diet, revealed histopathological persistence of a severely abnormal sprue-like enteropathy. Eventually, further biopsies of her small intestine revealed superimposed changes characterized by dense sub-epithelial collagen deposits histochemically staining positive for trichrome, typical of collagenous sprue and representing an expansion of published pathological features of mycophenolate-associated small intestinal mucosal disease.

Background The aim of this study is to describe and quantitatively analyze the histopathology of proximal long head biceps (LHB) tendinopathy in patients who have undergone LHB tenodesis. The hypothesis is that severe histopathologic changes of the LHB tendon (LHBT) will most likely be reflected with improved postoperative clinical outcomes. Methods The study included patients with isolated LHB tendinopathy or LHB tendinopathy associated with concomitant shoulder pathologies. All had failed conservative treatment (12 months) and had a positive pain response (> 50% reduction) pre-operatively after LHB tendon injection with local anesthetic. All underwent biceps tenodesis procedure between 2008 and 2014. Tendon specimens were collected and histologically analyzed with the semi-quantitative Bonar scoring system. Minimum follow-up time was 1 year. A subset of patients was retrospectively reviewed postoperatively and evaluated employing visual analogue score (VAS), short form survey (SF-12), American Shoulder and Elbow Surgeon (ASES) score, Disability of Arm, Shoulder and Hand (DASH) score, and Oxford Shoulder Score (OSS) and postoperative return to work status. Results Forty-five biceps tendon specimens were obtained from 44 patients (mean age 50 ± 9.6 years). Histopathological analyses demonstrated advanced degenerative changes with myxoid degeneration and marked collagen disorganization. Minimal inflammation was identified. There were no regional differences in histopathological changes. Clinical outcomes did not correlate significantly with severity of histopathologic changes. Conclusions This study confirms that LHBT specimens in patients undergoing tenodesis demonstrate with the use of the Bonar score histopathologic changes of chronic degeneration and not inflammation. The correct histopathologic terminology for this process is LHB tendinosis. The histopathological changes appear uniform throughout the entire length of the LHBT which may inform the nature of the procedure performed.

There is increasing evidence for a role of early life gut microbiota in later development of asthma in children. In our recent study, children with reduced abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia had an increased risk of development of asthma and addition of these bacteria in a humanized mouse model reduced airway inflammation. In this Addendum, we provide additional data on the use of a humanized gut microbiota mouse model to study the development of asthma in children, highlighting the differences in immune development between germ-free mice colonized with human microbes compared to those colonized with mouse gut microbiota. We also demonstrate that there is no association between the composition of the gut microbiota in older children and the diagnosis of asthma, further suggesting the importance of the gut microbiota-immune system axis in the first three months of life.

Collagenous colitis is an inflammatory mucosal disorder of the colon with distinctive histopathological features, including a thickened subepithelial collagen layer. The clinical course is usually benign, but serious complications, including death, may occur. In the present report, a 69-year-old woman with watery diarrhea and collagenous colitis developed bloody diarrhea that was refractory to treatment medications, including corticosteroids and azathioprine. Endoscopic and histopathological studies showed a focal neutrophilic inflammatory process that progressed to a diffuse and extensive form of colitis, eventually requiring total proctocolectomy. Careful histological review of the resected colon showed no evidence of persistent collagenous colitis. These findings suggest an important need for continued long-term follow-up of patients with collagenous colitis because superimposed and serious colonic complications may occur, including a severe and extensive pancolitis refractory to medications and necessitating total proctocolectomy.

Zinc has been shown to be accumulated in N-methyl-N-nitrosourea (MNU)-induced rat mammary tumors. Zinc is required for cell proliferation and tumorigenesis is characterized by dysregulation of cell proliferation. An accumulation of zinc in mammary tumors perhaps indicates a reliance on zinc to sustain tumor growth. Limiting zinc supply by means such as reduced zinc intake should negatively modulate mammary tumorigenesis. Our objective was to determine the effects of zinc status on MNU-induced mammary tumorigenesis in sexually mature female rats. Twenty-one-day-old Sprague-Dawley rats were assigned to low-zinc (3 mg zinc/kg diet) or adequate-zinc (12 mg zinc/kg diet) ad libitum or pair-fed control group (n = 25-33 rats/ group). On day 50 of age, all rats were intraperitoneally injected with MNU (50 mg/kg body wt) to induce mammary tumorigenesis. Rats were further maintained on their assigned diet until 14 weeks post-MNU injection. Total food intake and overall body weight gain were lower in low-zinc rats than in adequate-zinc ad libitum control rats, but were similar to adequate-zinc pair-fed control rats. Plasma zinc concentration was lower in low-zinc rats than in adequate-zinc ad libitum and pair-fed control rats, confirming moderately low-zinc status in low-zinc rats. Tumor incidence (46 versus 84 and 80%; P < 0.05) and tumor multiplicity (0.8 versus 5.0 and 2.6 tumors/rat; P < 0.05) and tumor number (28 versus 123 and 66 tumors) were reduced in low-zinc rats compared with that in adequate-zinc ad libitum and pair-fed control rats, respectively. Tumor latency in low-zinc and adequate-zinc pair-fed control rats was not significantly different, but was longer than in adequate-zinc ad libitum control rats (P < 0.05), suggesting that reduced food intake associated with low-zinc intake prolonged tumor latency. Tumor burden and size were not affected by zinc intake. Overall, our observations showed that moderately low-zinc status suppressed MNU-induced rat mammary tumorigenesis.

A previously well, 24-year-old male resident of Vancouver, British Columbia, presented to the emergency department with a two-month history of gradual onset of painless jaundice, dark urine and pale stool. At the time of presentation, he experienced a dramatic rise in the levels of the following liver enzymes: alkaline aminotransferase 272 U/L; alanine aminotransferase 244 U/L; gamma-glutamyl transferase 487 U/L; and alkaline phosphatase 1085 U/L, with an international normalized ratio of 1.0 and an albumin level of 39 g/L. His serum bilirubin level was highly elevated (367 μmol/L) with a conjugated fraction of 282 μmol/L. Hepatitis was the presumptive diagnosis based on positive serology for hepatitis A. However, a computed tomography scan of the abdomen revealed a complex, cystic mass 10.9 cm × 17.9 cm in size in the epigastric region with rim calcifications (Figure 1). This was concerning for a malignant or infective process and the patient was referred to the hepatobiliary surgery service. Figure 1) Coronal contrast-enhanced computed tomography image demonstrating a large complex mass arising from the liver with a central cystic component and an irregular, thick enhancing wall containing punctate calcifications The patient experienced no fever, cough, nausea, vomiting or abdominal pain. He had no known contacts with similar symptoms. He had travelled to Belgium, but had not travelled to the tropics or Northern Canada. There was no known exposure to animals, including canines. He underwent an endoscopic retrograde cholangiopancreatography with placement of bilateral biliary stents and ultrasound-guided percutaneous drainage of the hepatic abscess. The subsequent culture of the abscess fluid grew Candida albicans, which was treated with fluconazole. The patient became febrile and his jaundice did not improve and, thus, a right hepatectomy and cholecystectomy was performed. The surgical specimen contained a complex hydatid cyst 12 cm in diameter (Figure 2). There were numerous hyalinized profiles in the cyst wall consistent with daughter cysts (Figure 3). The final histological diagnosis was echinococcus with features suggestive of Echinococcus multilocularis. The patient was treated postoperatively with albendazole, 400mg/day orally. Subsequent serology was positive for serum immunoglobulin G antibodies to echinococcus confirmed by immunoblot. He remains asymptomatic without evidence of recurrence and his liver enzyme levels have normalized. Figure 2) A Lining of echinococcal cyst demonstrating the thick laminated layer produced by the parasite with adjacent degenerated and inflamed tissue (hematoxylin and eosin stain, original magnification ×100). B Internal aspect of a cyst with parasite ... Figure 3) Multiple collapsed small cysts in the hepatic parenchyma. A The wall is composed of carbohydrates as demonstrated by periodic acid-Schiff positivity (original magnification ×100). B The presence of multiple small cysts produces an infiltrating ...

Intestinal lymphangiectasia in the adult may be characterized as a disorder with dilated intestinal lacteals causing loss of lymph into the lumen of the small intestine and resultant hypoproteinemia, hypogammaglobulinemia, hypoalbuminemia and reduced number of circulating lymphocytes or lymphopenia. Most often, intestinal lymphangiectasia has been recorded in children, often in neonates, usually with other congenital abnormalities but initial definition in adults including the elderly has become increasingly more common. Shared clinical features with the pediatric population such as bilateral lower limb edema, sometimes with lymphedema, pleural effusion and chylous ascites may occur but these reflect the severe end of the clinical spectrum. In some, diarrhea occurs with steatorrhea along with increased fecal loss of protein, reflected in increased fecal alpha-1-antitrypsin levels, while others may present with iron deficiency anemia, sometimes associated with occult small intestinal bleeding. Most lymphangiectasia in adults detected in recent years, however, appears to have few or no clinical features of malabsorption. Diagnosis remains dependent on endoscopic changes confirmed by small bowel biopsy showing histological evidence of intestinal lymphangiectasia. In some, video capsule endoscopy and enteroscopy have revealed more extensive changes along the length of the small intestine. A critical diagnostic element in adults with lymphangiectasia is the exclusion of entities (e.g. malignancies including lymphoma) that might lead to obstruction of the lymphatic system and "secondary" changes in the small bowel biopsy. In addition, occult infectious (e.g. Whipple's disease from Tropheryma whipplei) or inflammatory disorders (e.g. Crohn's disease) may also present with profound changes in intestinal permeability and protein-losing enteropathy that also require exclusion. Conversely, rare B-cell type lymphomas have also been described even decades following initial diagnosis of intestinal lymphangiectasia. Treatment has been historically defined to include a low fat diet with medium-chain triglyceride supplementation that leads to portal venous rather than lacteal uptake. A number of other pharmacological measures have been reported or proposed but these are largely anecdotal. Finally, rare reports of localized surgical resection of involved areas of small intestine have been described but follow-up in these cases is often limited.

Departments of Medicine (Gastroenterology) and Pathology, University of British Columbia, Vancouver, British Columbia Correspondence: Dr Hugh James Freeman, University of British Columbia Hospital, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 1W5. Telephone 604-822-7216, fax 604-822-7236, e-mail hugfree@shaw.ca Received for publication April 4, 2010. Accepted April 14, 2010 Case presentation and images A 78-year-old woman experienced intermittent watery diarrhea for more than one year. There was no previous antibiotic use, travel or other medical history. The physical examination was normal. Laboratory studies, including bloodwork and fecal cultures, were negative. Colonoscopy revealed sigmoid diverticulosis and a broad-based sessile, ‘carpet-like’ polypoid lesion at the hepatic flexure appearing to occupy approximately 40% to 50% of the colonic circumference; consequently, the lesion was biopsied only (Figure 1) and ink-tattooed (for later laparoscopic removal). Biopsy sections (Figures 2 and 3) showed collagenous colitis with thickening of the basal collagen plate, an irregular lower border, entrapped nuclei, loss of overlying surface epithelium and increased inflammatory cells in the lamina propria. Subepithelial multinucleated giant cells were present (arrows). A trichrome stain highlighted the thickened basal collagen plate with entrapped nuclei (Figure 4). Over the next few weeks, her diarrhea completely resolved on a high-fibre diet regimen alone.