Faculty Bibliography

BACKGROUND & AIMS:Strictures in Crohn's disease (CD) are classically attributed to fibromuscular hypertrophy of the intestinal wall. We have identified and characterized CD-related ileal strictures that result instead from mural constriction (ie, reduced external circumference). METHODS:Twenty-four strictures and internal controls from 17 adults with obstructive CD were analyzed by cross-sectional morphometry. RESULTS:The stricture-to-control circumference ratios (CRs) ranged from 0.53 to 1.7. Six strictures with CR ≥1.0, designated hypertrophic, had concentrically thickened walls, mean 3-fold increases in cross-sectional area and stainable fibromucular tissue, and high transmural inflammation scores. In contrast, 18 strictures with CR <1.0, designated constrictive, had thin, pliant walls, cross-sectional areas and stainable fibromuscular tissue comparable with control values, and low transmural inflammation scores. Eight mildly constrictive strictures also showed mild fibromuscular mural expansion that fell short of statistical significance. Twelve of 18 constrictive strictures (67%) occurred multiply (2-4 strictures per specimen) in contrast with hypertrophic strictures, all of which occurred singly (P = .01). Constriction correlated quantitatively with circumferential serosal fat wrapping (P = .003) and was associated with myenteric lymphocytic plexitis (P = .02). Disease duration was shortest among subjects with constrictive strictures and correlated with increasing circumference (CR ≤0.8, 6.3 ± 6.2 years; CR >0.8, 8.7 ± 6.4 years; and CR ≥1.00, 13.7 ± 5.0 years, respectively; P = .03). CONCLUSIONS:Constrictive ileal strictures in CD differ pathologically and clinically from hypertrophic strictures, featuring little or no fibromuscular mural expansion, frequent multiplicity, and earlier onset. Mesenteric fat wrapping and myenteric plexitis may contribute to their pathogenesis. Pathologic manifestations of constriction and hypertrophy can coexist, suggesting that stricture heterogeneity may be shaped in part by the dynamics of constrictive and hypertrophic processes.

INTRODUCTION:Although anal cancer is more common in women, most of the studies on the role of high-risk human papillomavirus (hrHPV) infection in anal squamous lesions have focused on high-risk male patients. Therefore, we compared the genotype profile and clinicopathologic correlation of hrHPV infection in human immunodeficiency virus-positive (HIV+) men and women. MATERIALS AND METHODS:We retrospectively analyzed 2254 HIV+ patients (1931 men and 323 women) who had undergone anal Papanicolaou tests at our institution; 1189 of them also had follow-up biopsy data available. HPV genotyping was performed using the Roche Cobas system and correlated with the cytologic and histologic diagnosis. RESULTS:Compared with the HIV+ men, the HIV+ women had a significantly lower rate of hrHPV infection (67.5% versus 78.5%; P < 0.0001) but a significantly higher rate of high-grade squamous intraepithelial lesions (HSILs) on anal Papanicolaou tests (4.6% versus 2.5%; P < 0.05). Other high-risk HPV (ohrHPV), as a group, is much more common than HPV16 or HPV18 in both genders. HIV+ women had significantly lower HPV16 and ohrHPV infection rates than did HIV+ men. However, the HPV18 infection rates were similar between HIV+ women and HIV+ men. For both genders, the rates of HSILs or high-grade anal intraepithelial neoplasia (AIN2-3) were significantly increased when coinfection of ohrHPV with either HPV16 or HPV18 was present. CONCLUSIONS:Although both HIV+ men and HIV+ women have an increased risk of hrHPV infection, HIV+ women have different hrHPV genotype profiles and higher rates of high-grade lesions. Coinfection with different genotypes of hrHPV can significantly increase the risk of HSILs or AIN2-3 in both genders and could requires vigilant clinical and laboratory follow-up.

Liver injury is a common manifestation of coronavirus disease 2019 (COVID-19), with most injuries manifesting as transient mild hepatocellular injury. Cholestatic injury occurs less commonly and is typically mild. Severe cholestatic injury is rare, with only 4 cases reported in the literature. We present a 70-year-old woman with no known liver disease who presented with severe COVID-19 and developed severe cholestatic hepatitis. A liver biopsy was performed demonstrating bile duct injury, uncommonly reported in patients with COVID-19. This complication needs greater awareness because it has been known to cause progressive liver disease requiring transplantation.

INTRODUCTION:This study was performed to determine the feasibility and safety of creating superficial histotripsy treatment in a live porcine thyroid model. METHODS:The porcine thymus comparable in size, shape and location to the human thyroid was used for this study. This model has been used for thyroid surgery studies due to the diminutive size of the porcine thyroid. Four female swine underwent a total of eight histotripsy treatments performed with a prototype therapy system (HistoSonics, Inc., Ann Arbor, MI). Two treatments were performed in each animal: a spherical 1.0 × 1.0 × 1.0 cm and ovoid 1.0 × 1.0 × 2.0 cm treatment zones. MRI immediately post-procedure was evaluated for histotripsy treatment zone size and imaging appearance, followed immediately by sacrifice. Tissue was then reviewed for percent cellular destruction and precision. RESULTS: > 0.05 vs. prescribed). MRI demonstrated well demarcated treatment zones and imaging findings consistent with cellular destruction. Histology demonstrated sharp transitions to normal tissue (mean 0.33 (+/- 0.13) cm), and high degrees of cellular destruction (mean 76% (+/- 12.5), range of 50-100%) in the treated tissue. Edema within the overlying muscle was seen in 2/8 treatments. CONCLUSION:Histotripsy is capable of safely creating precise histotripsy treatments within the superficial neck of a porcine thyroid model without evidence of considerable complications.

PURPOSE/OBJECTIVE:To determine whether histotripsy can create human-scale transcostal ablations in porcine liver without causing severe thermal wall injuries along the beam path. MATERIALS AND METHODS/METHODS:Histotripsy was applied to the liver using a preclinical prototype robotic system through a transcostal window in six female swine. A 3.0 cm spherical ablation zone was prescribed. Duration of treatment (75 min) was longer than a prior subcostal treatment study (24 min, 15 s) to minimize beam path heating. Animals then underwent contrast-enhanced MRI, necropsy, and histopathology. Images and tissue were analyzed for ablation zone size, shape, completeness of necrosis, and off-target effects. RESULTS:). Edema was noted in the body wall overlying the ablation on T2 MRI in 5/5 (one animal did not receive MRI), though there was no gross or histologic evidence of injury to the chest wall at necropsy. At gross inspection, lung discoloration in the right lower lobe was present in 5/6 animals (mean size: 1 × 2 × 4 cm) with alveolar hemorrhage, preservation of blood vessels and bronchioles, and minor injuries to pneumocytes noted at histology. CONCLUSION/CONCLUSIONS:Transcostal hepatic histotripsy ablation appears feasible, effective, and no severe injuries were identified in an acute porcine model when prolonged cooling time is added to minimize body wall heating.