Dual-Layer Spectral CT Imaging of Upper Aerodigestive Tract Cancer: Analysis of Spectral Imaging Parameters and Impact on Tumor Staging.

BACKGROUND AND PURPOSE: Dual-layer spectral CT is a novel technology that utilized conventional single-tube CT acquisition with a dual-layer detector for the separation of high and low-energy photons to create spectral data for material decomposition. We evaluated the spectral parameters of iodine density and Z-effective values in primary head and neck squamous cell carcinoma and determined its impact on local tumor staging. MATERIALS AND METHODS: Twenty-one patients with primary head and neck squamous cell carcinoma and 15 healthy controls were retrospectively evaluated. Iodine density (milligram/milliliter) and Z-effective values were compared quantitatively between head and neck squamous cell carcinoma and normal neck mucosa. The receiver operating characteristic area under the curve determined the diagnostic performance of the spectral data for local staging. We compared conventional CT images without and with iodine density and Z-effective images to determine its impact on local tumor staging. RESULTS: Primary head and neck squamous cell carcinoma showed higher mean iodine density (2.01 [SD, 0.26] mg/mL, P < .001) and Z-effective values (8.21 [SD, 0.36], P < .001). A high interobserver correlation was demonstrated for ROI measurements for both the control group (iodine density, κ = 0.71, and Z-effective values, κ = 0.78) and head and neck squamous cell carcinoma (iodine density, κ = 0.84, and Z-effective values, κ = 0.75) group. The area under the curve for iodine density and Z-effective values was 0.98 and 0.93, respectively. Optimal thresholds were identified as 1.58 mg/mL (95% CI, 1.45-1.71 mg/mL; P < .001; sensitivity = 1.0; specificity = .0.93) for iodine density and 8.08 (95% CI, 7.96-8.19; P < .001; sensitivity = 0.86; specificity = 0.93) for Z-effective values. Conventional CT with the addition of dual-layer spectral data (iodine density and Z-effective values) improved the accuracy of local tumor staging in 3 of 21 patients (14%) with head and neck squamous cell carcinoma compared with the criterion standard surgical staging/histopathology. CONCLUSIONS: Dual-layer spectral iodine density and Z-effective values provided increased quantitative and qualitative differentiation between upper aerodigestive head and neck squamous cell carcinoma and normal mucosa. Increased tissue differentiation improved the local tumor staging accuracy.

Social stress-enhanced severity of Citrobacter rodentium-induced colitis is CCL2-dependent and attenuated by probiotic Lactobacillus reuteri.

Psychological stressors are known to affect colonic diseases but the mechanisms by which this occurs, and whether probiotics can prevent stressor effects, are not understood. Because inflammatory monocytes that traffic into the colon can exacerbate colitis, we tested whether CCL2, a chemokine involved in monocyte recruitment, was necessary for stressor-induced exacerbation of infectious colitis. Mice were exposed to a social disruption stressor that entails repeated social defeat. During stressor exposure, mice were orally challenged with Citrobacter rodentium to induce a colonic inflammatory response. Exposure to the stressor during challenge resulted in significantly higher colonic pathogen levels, translocation to the spleen, increases in colonic macrophages, and increases in inflammatory cytokines and chemokines. The stressor-enhanced severity of C. rodentium-induced colitis was not evident in CCL2(-/-) mice, indicating the effects of the stressor are CCL2-dependent. In addition, we tested whether probiotic intervention could attenuate stressor-enhanced infectious colitis by reducing monocyte/macrophage accumulation. Treating mice with probiotic Lactobacillus reuteri reduced CCL2 mRNA levels in the colon and attenuated stressor-enhanced infectious colitis. These data demonstrate that probiotic L. reuteri can prevent the exacerbating effects of stressor exposure on pathogen-induced colitis, and suggest that one mechanism by which this occurs is through downregulation of the chemokine CCL2.

Hypervitaminosis D and Metastatic Calcification in a Colony of Inbred Strain 13 Guinea Pigs, Cavia porcellus.

A commercial diet fed to a colony of inbred strain 13 guinea pigs for approximately 6 weeks was subsequently recalled for excessive levels of vitamin D. Twenty-one of 62 animals exhibited clinical signs, including anorexia, lethargy, and poor body condition. Nine affected and 4 clinically normal animals were euthanized for further evaluation, including serum chemistry, urinalysis, and gross and/or histopathology. Macroscopic findings included white discoloration in multiple organs in 8 animals, and microscopic evaluation confirmed multiorgan mineralization in tissues from 7 animals. Serum 25-hydroxyvitamin D levels were elevated in 10 animals. Serum inorganic phosphorus and alkaline phosphatase levels were increased in all exposed animals; however, total calcium and ionized calcium levels were not significantly higher in exposed animals than in control strain 13 guinea pigs from a different institution. The data support a diagnosis of hypervitaminosis D with metastatic calcification. Following the diet recall, the remaining guinea pigs increased their food intake and regained body condition. Diagnostic testing of 8 animals euthanized approximately 3 months after returning to a normal diet demonstrated that serum parathyroid hormone remained significantly lower, and ionized calcium and ionized magnesium were significantly higher, in recovered animals compared to controls and exposed animals. These results indicate that diagnostic tests other than serum calcium are necessary for a diagnosis of hypervitaminosis D in guinea pigs.

Isolation of a Campylobacter lanienae-like bacterium from laboratory chinchillas (Chinchilla laniger).

Routine necropsies of 27 asymptomatic juvenile chinchillas revealed a high prevalence of gastric ulcers with microscopic lymphoplasmacytic gastroenteritis and typhlocolitis. Polymerase chain reaction (PCR) analysis using Campylobacter genus-specific partial 16S rRNA primers revealed the presence of Campylobacter spp. DNA in the faeces of 12 of 27 animals (44.4%). Species-specific partial 16S rRNA PCR and sequencing confirmed that these animals were colonized with Campylobacter lanienae, a gram-negative, microaerophilic bacterium that was first identified on routine faecal screening of slaughterhouse employees and subsequently isolated from faeces of livestock. Campylobacter lanienae was isolated from the faeces of six PCR-positive animals and identified with species-specific PCR and full 16S rRNA sequencing. Phylogenetic analysis showed that these isolates clustered with C. lanienae strain NCTC 13004. PCR analysis of DNA extracted from gastrointestinal tissues revealed the presence of C. lanienae DNA in the caecum and colon of these chinchillas. Gastrointestinal lesions were scored and compared between C. lanienae-positive and C. lanienae-negative animals. There was no correlation between colonization status and lesion severity in the stomach, liver, duodenum, or colon. Possible routes of C. lanienae infection in chinchillas could include waterborne transmission and faecal-oral transmission from wild mice and rats or livestock. Based on these findings, the authors conclude that C. lanienae colonizes the lower bowel of chinchillas in the absence of clinical disease. This is the first report of C. lanienae in any rodent species. Campylobacter lanienae isolates from different mammalian species demonstrate heterogeneity by 16S rRNA sequence comparison. Analysis using rpoB suggests that isolates and clones currently identified as C. lanienae may represent multiple species or subspecies.

Adenomatous polyp with intestinal metaplasia of the esophagus (Barrett esophagus) in a dog.

Multiple endoscopic biopsy specimens of esophageal mucosa were received from a 13-year-old castrated male standard Poodle. The dog was presented for painful swallowing. Endoscopically, the distal aspect of the esophagus was inflamed with a polypoid mass that protruded into the esophageal lumen. Histologically, the stratified squamous epithelium overlying the mass and lining the adjacent esophageal mucosa was replaced by papillary projections covered by columnar epithelium with goblet cells supported by a fibrous stroma. This article reports a case of spontaneous esophageal adenomatous polyp with intestinal metaplasia (Barrett esophagus) and reviews the pathogenesis of esophageal metaplasia and adenocarcinoma.

Abomasal parasite syndrome in North American elk (Cervus elaphus canadensis).

CASE HISTORY: An 18-month clinical course of chronic ill-thrift, weight loss and emaciation, and eventual death occurred in a group of 520 translocated elk of mixed age and sex. Translocation was carried out without regard to animal welfare or health risks associated with the translocation. Mortality was approximately 84% (436/520) despite supportive nutritional and medical treatment. PATHOLOGICAL FINDINGS: General clinical and postmortem examinations indicated only Se and Cu imbalances and nutritional inadequacy. Additional purposeful post-mortem examination and histological evaluation of tissue sections from four of the affected adult elk demonstrated elevated abomasal pH and proliferative abomasal lesions as the most significant findings, consistent with Type-II ostertagiosis; intra-lesional nematodes were seen in the abomasum of two animals. DIAGNOSIS: Fading elk syndrome, or abomasal parasite syndrome in elk. CLINICAL RELEVANCE: Abomasal parasite syndrome initiated by Type-II ostertagiosis should be considered as a differential diagnosis in cases of ill-thrift and wasting in elk or elk-red deer hybrids. Changes to the architecture and secretory function of the abomasal wall lead to apparently irreversible digestive pathophysiology and nutritional disease.

Anaplastic astrocytoma in the spinal cord of an African pygmy hedgehog (Atelerix albiventris).

A 2-year-old, female hedgehog presented with an 8-month history of progressive, ascending paresis/paralysis and was tentatively diagnosed with wobbly hedgehog syndrome. She died awaiting further diagnostic tests, and the owners consented to postmortem examination. Grossly, the bladder was large and flaccid and the cervical and lumbar spinal cord were regionally enlarged, light grey, and friable with multifocal hemorrhages. The thoracic spinal cord was grossly normal. Microscopically all regions of the spinal cord had similar changes, although the cervical and lumbar sections were most severely affected. These regions were completely effaced by a moderately cellular infiltration of highly pleomorphic polygonal to spindle shaped cells, mineralization, and necrosis, which were most consistent with anaplastic astrocytoma. The thoracic spinal cord white matter was similarly infiltrated by the neoplastic cells, with perivascular extension into the otherwise normal grey matter. A diagnosis of anaplastic astrocytoma was confirmed using immunohistochemical stains that were positive for glial fibrillary acidic protein and S100.

Anal sac gland carcinoma in a cat.

A perianal mass in a 15-year-old domestic shorthair cat with a history of a firm, painful swelling in the left ventrolateral perianal region was surgically excised and submitted for light microscopic evaluation. Histologically, this was a poorly demarcated, unencapsulated, multilobulated neoplasm that invaded surrounding perirectal skeletal muscle bundles. Lobules were composed of sheets and acinar arrangements of cuboidal to round neoplastic epithelial cells with scant to moderate eosinophilic to amphophilic cytoplasm and a round or oval nucleus with coarse chromatin. Mitotic figures were 2 per 40 x objective field. Acinar lumina sometimes contained eosinophilic proteinaceous material or cell debris. These microscopic features are consistent with anal sac gland carcinoma. This is the second report of this neoplasm in a cat.

Metal (molybdenum, copper) accumulation and retention in brain, pituitary and other organs of ammonium tetrathiomolybdate-treated sheep.

Ammonium tetrathiomolybdate (TTM) is the treatment of choice for chronic Cu poisoning in sheep and is recommended in Wilson's disease. However, the long-term effects have not been fully evaluated and some evidence questions the long-term safety of the drug. The aim of the present study was to investigate the systemic distribution and retention of Cu and Mo in TTM-treated sheep of different breeds and Cu status. Low-Cu Cambridge sheep were divided into a TTM trial group (3.4 mg/kg, subcutaneously, on three alternate days per month, for 5 months) and a control group, and were killed at the end of the course or 7 months later. High-Cu sheep consisting of a Cu-supplemented (150 mg/kg) Cambridge group and a North Ronaldsay group were administered TTM as before and compared with untreated controls. Brain, liver, kidney, heart, skeletal muscle, pituitary, adrenals, tests and ovaries were retained for metal analysis. Mo accumulated in all organs including brain and pituitary (P < 0.02) in all TTM trial groups and was retained after cessation of treatment, except in liver, kidney and skeletal muscle. Cu was increased (P < 0.02) and retained in the cerebellum and medulla oblongata in the TTM-treated high-Cu Cambridge groups. Brain Cu v. Mo concentrations showed a strongly positive correlation (r. 0.7) in the high-Cu Ronaldsay group 7 months after TTM treatment. It is concluded that TTM is not all excreted but (Mo) is widely distributed and retained in many organs including brain and pituitary. In addition TTM may redistribute some displaced excess liver Cu (Cu-TTM) to the brain. The consequences of these disturbances await clarification.

Molybdenum-induced changes in the epiphyseal growth plate.

Molybdenum (Mo), at high concentrations, induces changes in the epiphyseal growth plate through its effects on copper (Cu) metabolism but it is unclear whether or not Mo can induce changes independent of its effects on copper status. To this end, the effect of Mo on longitudinal bone growth was examined in rats. Dietary Mo was given either as ammonium heptamolybdate or as ammonium tetrathiomolybdate, the latter producing a marked Cu deficiency. There was a significant reduction in longitudinal bone growth in both groups; however, growth plate width was increased only in the Cu-deficient animals due to an increase in the width of the zone of transitional/hypertrophic chondrocytes. Both glucose 6-phosphate dehydrogenase activity and cell proliferation (assessed by bromodeoxyuridine incorporation) were markedly decreased in the proliferating zone of the growth plate in both Mo-treated groups. These changes were not apparently related to changes in circulating vitamin D metabolites or insulin-like growth factor-1. The results indicate that excess Mo impairs cell proliferation within the growth plate, whereas the effects of copper deficiency are more related to chondrocyte differentiation. Thus, Mo can induce changes in longitudinal bone growth which are distinct from those resulting from Cu deficiency.