Browsing by Author "Guy, Cynthia D"

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    Does ampullary adenoma size predict invasion on EUS? Does invasion on EUS predict presence of malignancy?
    (Endosc Int Open, 2016-12) Patel, Vaishali; Jowell, Paul; Obando, Jorge; Guy, Cynthia D; Burbridge, Rebecca A
    Background and study aims: It is common practice to perform ampullectomy without endoscopic ultrasound (EUS) for ampullary lesions < 1 cm but no data exists to support it. No studies have explored whether EUS findings of invasion correlate with malignancy or high-grade dysplasia (HGD) on pathology. We explored the association between adenoma size, pathology results, and invasion on EUS.  Patients and methods: This was a single-center retrospective cohort study at a large tertiary care academic hospital. Chart review was performed for 161 patients with benign ampullary lesions on endoscopic biopsy (identified by pathology records). The primary outcomes were mean size (mm) of adenomas and pathology findings with and without intraductal and/or duodenal wall invasion on EUS.  Results: Invasion was identified by EUS in 41 (34.1 %) of 120 patients who underwent EUS. The mean size of the lesion in these patients was 20.9 mm (± 11.6 mm) compared to 13.9 mm (± 11.3 mm, P = 0.0001) in patients without invasion. A receiver operating characteristic (ROC) curve (AUC 0.73, 95 % CI 0.63 - 0.83) revealed 100 % sensitivity for absence of invasion on EUS in lesions less than 6.5 mm. Invasion on EUS had sensitivity of 63.0 % (95 % CI 47.0 % - 77.0 %) and specificity 88.0 % (95 % CI 78.0 % - 95.0 %) for presence of malignancy, HGD or invasion on pathology. Conclusions: EUS should be considered for ampullary lesions > 6.5 mm. This study provides evidence to support the practice of ampullectomy without EUS for smaller adenomas. EUS evidence of invasion is highly specific for pathologic malignancy, HGD, or invasion (which preclude endoscopic ampullectomy).
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    Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease.
    (Hepatology (Baltimore, Md.), 2021-03-16) Alexopoulos, Anastasia-Stefania; Crowley, Matthew J; Wang, Ying; Moylan, Cynthia A; Guy, Cynthia D; Henao, Ricardo; Piercy, Dawn L; Seymour, Keri A; Sudan, Ranjan; Portenier, Dana D; Diehl, Anna Mae; Coviello, Andrea D; Abdelmalek, Manal F

    Background and aims

    Whether glycemic control, as opposed to diabetes status, is associated with the severity of nonalcoholic fatty liver disease (NAFLD) is unknown. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histologic severity of nonalcoholic steatohepatitis (NASH).

    Methods & results

    Using the Duke NAFLD Clinical Database we examined patients with biopsy-proven NAFLD/NASH (n=713) and the association of liver injury with glycemic control as measured by hemoglobin A1c (HbA1c). The study cohort was predominantly female (59%), Caucasian (84%) with median (IQR) age of 50 (42, 58) years; 49% had diabetes (n=348). Generalized linear regression models adjusted for age, sex, race, diabetes, body mass index, and hyperlipidemia were used to assess the association between mean HbA1c over the year preceding liver biopsy and severity of histologic features of NAFLD/NASH. Histologic features were graded and staged according to NASH Clinical Research Network system. Group-based trajectory analysis was used to examine patients with ≥3 HbA1c (n=298) measures over 5 years preceding clinically indicated liver biopsy. Higher mean HbA1c was associated with higher grade of steatosis and ballooned hepatocytes, but not lobular inflammation. Every 1% increase in mean HbA1c was associated with 15% higher odds of increased fibrosis stage (OR 1.15, 95% CI 1.01, 1.31). As compared with good glycemic control, moderate control was significantly associated with increased severity of ballooned hepatocytes (OR 1.74, 95% CI 1.01, 3.01, p=0.048) and hepatic fibrosis (OR 4.59, 95% CI 2.33, 9.06, p<0.01).

    Conclusions

    Glycemic control predicts severity of ballooned hepatocytes and hepatic fibrosis in NAFLD/NASH, and thus optimizing glycemic control may be a means of modifying risk of NASH-related fibrosis progression.
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    Markers of Tissue Repair and Cellular Aging Are Increased in the Liver Tissue of Patients With HIV Infection Regardless of Presence of HCV Coinfection.
    (Open forum infectious diseases, 2018-07) Naggie, Susanna; Swiderska-Syn, Marzena; Choi, Steve; Lusk, Sam; Lan, Audrey; Ferrari, Guido; Syn, Wing-Kin; Guy, Cynthia D; Diehl, Anna Mae
    Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed paraffin-embedded liver tissue for HIV-infected patients, HCV-infected patients, HIV/HCV-coinfected patients, and controls at Duke University Medical Center. De-identified sections were stained for markers against the wound repair Hedgehog (Hh) pathway, resident T-lymphocytes, and immune activation and cellular aging. HIV infection was independently associated with Hh activation and markers of immune dysregulation in the liver tissue.
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    Metastatic Renal Cell Carcinoma as Solitary Subcentimeter Polypoid Gastric Mucosal Lesions: Clinicopathologic Analysis of Five Cases.
    (Gastroenterology research, 2018-02-23) Hemmerich, Amanda; Shaar, Mohanad; Burbridge, Rebecca; Guy, Cynthia D; McCall, Shannon J; Cardona, Diana M; Zhang, Xuchen; Lai, Jinping; Zhang, Xuefeng
    The stomach is an uncommon site for metastatic carcinoma. Approximately 6% of renal cell carcinomas (RCCs) may metastasize to the stomach. The majority of the reported metastatic RCCs in the stomach presented as large masses or ulcers greater than a centimeter in size. It is very rare to encounter metastatic RCC as a solitary small polypoid gastric mucosal lesion.In this study, we collected surgical pathology cases of gastric metastasis from RCC that measured 1.0 cm or less at the time of endoscopy. The clinicopathological characteristics were analyzed.Five patients with subcentimeter metastatic RCC involving the gastric mucosa were identified. The clinical presentation for upper endoscopic examination was non-specific. Two of the five patients did not have a known history of RCC. In the three patients with a previous history of RCC, the interval from primary RCC diagnosis to the detection of gastric mucosal metastasis was 5, 6, and 10 years, respectively. Endoscopically, all the lesions were solitary, ranging in size from 0.4 to 1 cm. Histologically, all five cases were of the clear cell type consisting of a bland clear cell proliferation within the lamina propria. Although the tumor cells were relatively bland, the presence of clear cytoplasm, nuclear membrane irregularity, occasional enlarged hyperchromatic atypical nuclei, and destructive growth in the center of the lesion should promote immunohistochemical workup. Immunohistochemically, the RCC cells exhibited at least patchy immunoreactivity for cytokeratin and RCC markers. In two cases, there were many CD68 positive foamy histiocytes intermingled with the tumor cells.Metastatic RCC can rarely present as subcentimeter polypoid gastric mucosal lesions. The remote or unknown history of RCC, the non-specific endoscopic appearance, and the bland histological features may lead to a potential diagnostic pitfall. It is of importance to raise the awareness of such an unusual presentation of metastatic RCC in the stomach and to include metastatic RCC in the differential diagnosis for gastric mucosal polyps with clear cell morphology.
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    Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.
    (Gut, 2016-04) Michelotti, Gregory A; Tucker, Anikia; Swiderska-Syn, Marzena; Machado, Mariana Verdelho; Choi, Steve S; Kruger, Leandi; Soderblom, Erik; Thompson, J Will; Mayer-Salman, Meredith; Himburg, Heather A; Moylan, Cynthia A; Guy, Cynthia D; Garman, Katherine S; Premont, Richard T; Chute, John P; Diehl, Anna Mae
    OBJECTIVE: The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell niches produce pleiotrophin (PTN) to inactivate the PTN receptor, protein tyrosine phosphatase receptor zeta-1 (PTPRZ1), thereby augmenting phosphoprotein-dependent signalling. We hypothesised that the DR is regulated by PTN/PTPRZ1 signalling. DESIGN: PTN-GFP, PTN-knockout (KO), PTPRZ1-KO, and wild type (WT) mice were examined before and after bile duct ligation (BDL) for PTN, PTPRZ1 and the DR. RDC and HSC from WT, PTN-KO, and PTPRZ1-KO mice were also treated with PTN to determine effects on downstream signaling phosphoproteins, gene expression, growth, and migration. Liver biopsies from patients with DRs were also interrogated. RESULTS: Although quiescent HSC and RDC lines expressed PTN and PTPRZ1 mRNAs, neither PTN nor PTPRZ1 protein was demonstrated in healthy liver. BDL induced PTN in MF-HSC and increased PTPRZ1 in MF-HSC and RDC. In WT mice, BDL triggered a DR characterised by periportal accumulation of collagen, RDC and MF-HSC. All aspects of this DR were increased in PTN-KO mice and suppressed in PTPRZ1-KO mice. In vitro studies revealed PTN-dependent accumulation of phosphoproteins that control cell-cell adhesion and migration, with resultant inhibition of cell migration. PTPRZ1-positive cells were prominent in the DRs of patients with ductal plate defects and adult cholestatic diseases. CONCLUSIONS: PTN, and its receptor, PTPRZ1, regulate the DR to liver injury by controlling the migration of resident cells in adult liver progenitor niches.
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    Response to Letter: Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis.
    (Clin Gastroenterol Hepatol, 2017-05-11) Yang, Ju Dong; Abdelmalek, Manal F; Guy, Cynthia D; Diehl, Anna Mae; Suzuki, Ayako