Giardia Is Often Overlooked on Histopathologic Examination: A High-Volume, Single-Institution Experience

Aims. Giardia is sometimes missed by the pathologist, and we sought to determine how often this occurs at our institution—a large tertiary care center with a subspecialty gastrointestinal pathology service and what certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection, targeting them for greater scrutiny. Methods and Results We identified a set of patients who tested positive for Giardia with a stool-based test, and who also received a small bowel biopsy at a similar time-point. These biopsies were retrospectively reviewed for Giardia, finding 8 positive cases. The organism was prospectively detected in 4 cases (50%) but overlooked in the remaining 4 cases (50%). Three of the 4 cases missed cases showed only rare organisms. The detected cases tended to more frequently have prominent lymphoid aggregates (3 detected cases, 0 overlooked cases) and intraepithelial lymphocytosis (3 detected cases, 0 overlooked cases). Certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection. Specifically, we found abnormalities of the mucosa (active inflammation, intraepithelial lymphocytosis, villous expansion, prominent lymphoid aggregates) in each case, and 4 of 8 cases were from immunocompromised patients. Finally, 2 of 8 cases were terminal ileum biopsies. Conclusions Biopsies with a histologic abnormality or those from immunocompromised patients should receive greater attention. Routinely looking for Giardia at that terminal ileum is necessary.

High-Output (HO) Ostomy With Histopathologic Abnormality: Examination of 78 Stoma Specimens

Background HO (>2,000 mL output/day) is a serious complication following ostomy procedure. HO may be associated with variable underlying conditions or idiopathic. We encountered an ileostomy case with diffuse subepithelial collagen deposits resembling collagenous colitis from a patient with history of HO without underlying cause. A subset of idiopathic HO may be associated with histopathologic abnormalities of the bowel. Methods Resected stomas from ostomy malfunction were searched using ICD-9 and CPT codes (2003-2018). Archived pathology materials were reviewed and activity, villous blunting, pyloric metaplasia (PM), and subepithelial collagen deposits were assessed. Trichrome stain was performed when necessary. Clinical history was obtained from medical records. Results Sixty-one ileostomies and 17 colostomies were retrieved from 69 patients. Types of ostomy malfunction were stricture/obstruction (n = 21), hernia (n = 10), ischemia/necrosis (n = 4), leak (n = 4), abscess/adhesion (n = 3), skin breakdown (n = 3), prolapse (n = 3), retraction (n = 2), reepithelialization (n = 1), and unclear/not specified (n = 15). Thirty-two patients had inflammatory bowel disease (IBD; 19 Crohn disease [CD], 13 ulcerative colitis [UC]). All HOs were from ileostomy, and 16 had risk factors for HO, including IBD (n = 9 [56%]; 7 CD, 2 UC), short bowel (n = 6, 3 with CD), pelvic/intra-abdominal abscess (n = 2), sepsis (n = 2), and prokinetic (n = 1). Five ileostomies from CD showed PM, while 11 lacked significant histologic abnormalities. Among 5 (24%) idiopathic HOs, 1 was the index case with diffuse subepithelial collagen deposits with subtotal villous blunting, 1 showed PM, and 1 had focal activity. Remaining 2 ileostomies from idiopathic HO were unremarkable. Stomas from patients with other types of ostomy malfunction showed compatible histologic changes. Fifteen cases without ostomy malfunction did not show histologic abnormality. Conclusion Most HO represents functional abnormality without histopathologic abnormality except in IBD. However, idiopathic HO may be associated with histopathologic abnormalities in the stoma suggestive of acute/chronic enteritis and scarring, which may be underrecognized and treatable.

Neurophysiology

The temporal profile that has not been considered is the transient, or rapidly reversible, abnormality. Many diseases that produce signs or symptoms of brief duration may not produce destructive changes in cells and may occur without demonstrable histologic abnormality of the involved structures. To understand transient manifestations of disease, it is necessary to understand the physiology of the cells of the nervous system and the mechanism by which they process information. Cells in the nervous system and muscle communicate by electrical signals. Neurons have the ability to generate, conduct, transmit, and respond to electrical activity. Information is transmitted between cells by neurochemical agents that convey the signals from cell to cell. Information is integrated by the interaction of electrical activity in single cells and in groups of cells.

STEROID-INDUCED VERSUS CRYOINSULT-INDUCED FEMORAL HEAD OSTEONECROSIS: STATISTICAL MEASUREMENT OF HISTOLOGIC ABNORMALITY FOCALIZATION

Systematic studies of treatment options for femoral head osteonecrosis have been hindered by the lack of an animal model that mimics the human event of femoral head collapse. The (bipedal) emu model of osteonecrosis has proven to progress to collapse following an external insult. Since osteonecrosis clinically has multiple etiologies, various alternatives are seemingly appropriate to initiate lesions for research purposes. This study compared osteonecrosis initiated by a local cryoinsult, to that initiated by a large systemic dose of steroid (methylprednisolone acetate), and by a combination of steroid and cryoinsult. One year post-insult, the animals were sacrificed and their femoral heads harvested. A custom-written computer program was used to expedite analysis of the global distribution of histologically apparent osteonecrosis, as determined by the Ficat scale. Following whole-head analysis, grade distributions were calculated, and a measure of spatial clustering of histologic abnormality was calculated using Moran's I statistic. Normal femoral heads showed very small amounts of histological abnormality, and no significant spatial clustering. Femoral heads receiving isolated cryoinsult had a greater incidence of high-grade abnormality, as well as statistically significant spatial clustering of that abnormality. Steroid-only animals had a higher percentage of diffuse, low-grade abnormality. The group receiving both steroid and cryoinsult showed the highest overall abnormality, with statistically significant clustering of that high-grade abnormality. Cryoinsult, both in isolation and in combination with a steroid regimen, appeared necessary to mimic the clinically typical focal lesions of osteonecrosis.

Recovery from heart failure: structural and functional analysis in a canine model

Chronic, rapid ventricular pacing produces congestive heart failure in the dog. Using echocardiography, the features of developing heart failure were analysed and the capacity of this model for recovery was assessed once pacing had been discontinued. Fifteen dogs were studied; nine were paced at 250 beats/min (bpm) to severe heart failure (5.0 ± 1.8 weeks) and six served as sham controls. In the paced animals at severe heart failure, two-dimensional echocardiography demonstrated a significant increase in diastolic cross-sectional cardiac area (from 11 ± 3 to16 ± 2 cm2, p < 0.05), associated with a marked fall in area ejection fraction (54 ± 8 to 21 ± 8%, p < 0.05), and significant left ventricular wall thinning (from 6.0 ± 0.7to4.7 ± 0.9 mm, p < 0.05). In addition, significant increases in heart rate (77 ± 7 to 126 ± 13 bpm, sinus rhythm; p < 0.05), respiratory rate (41 ± 13 to 80 ± 20 cycles/min, p < 0.05), and body weight (21 ± 1 to 24 ± 3 kg, p < 0.05) were noted. Serum sodium fell (146 ± 3 to 140 ± 8 mmol/L, p < 0.05), while blood urea nitrogen (6 ± 2 to 10 ± 2 mmol/L, p < 0.05) and creatinine (86 ± 12 to 101 ± 15 mmol/d, p < 0.05) increased. Recovery was characterized by rapid improvement such that all measured parameters normalized by 1 week, except for cross-sectional cardiac area which remained dilated up to 4 weeks (14 ± 3 cm2, p < 0.05 versus control). Necropsy data obtained from paced dogs after 4 weeks of recovery demonstrated cardiac hypertrophy when compared with sham controls (9.4 ± 1.2 versus 7.7 ± 0.9 g/kg, p < 0.05), but no histologic abnormality was revealed under light microscopy. Left ventricular norepinephrine levels were similar to those of sham controls (617 ± 323 versus 676 ± 177 ng/g wet weight, not significant). The rapid recovery of ventricular systolic performance demonstrated in this heart failure model suggests that reversible substrate depletion is the mechanism responsible. Despite this recovery, there is persistent diastolic enlargement of the left ventricle indicating that structural remodeling has taken place.