Neil Parikh

Classical and emerging roles of vitamin D in hepatitis C virus infection.

According to the Institute of Medicine, the risk of clinically significant vitamin D deficiency increases at 25-hydroxyvitamin D levels below 20 ng/mL. By this standard, most cirrhotic hepatitis C virus- (HCV-) positive patients and many noncirrhotic patients are vitamin D-deficient. The high prevalence of vitamin D deficiency among HCV patients is a cause for concern for several specific reasons. Classic studies established the importance of vitamin D and calcium in maintaining bone. Vitamin Ds beneficial effects on bone are likely to be vital for HCV-infected patients because these individuals have a high prevalence of low bone mineral density. Many pharmaceutical agents reduce bone density and exposure to these drugs may increase bone disease in HCV-positive patients. Bone loss occurs following liver transplantation and bone density is often low in patients with HIV/HCV co-infection who are on combination antiretroviral therapy. Some evidence suggests that ribavirin reduces bone density, underscoring the special need to monitor vitamin D in patients receiving HCV treatment and to prescribe supplements, as appropriate. In addition to its role in calcium metabolism, vitamin D is also an immune modulator that reduces inflammation while enhancing protective immune responses. Higher vitamin D levels are associated with less liver fibrosis and less inflammation in HCV patients. Recent studies show that low vitamin D levels are associated with treatment failure among HCV-infected patients receiving pegylated-interferon and ribavirin. If confirmed, these findings will provide an additional reason to ensure adequate levels of vitamin D. Information about how to monitor vitamin D status and how to use vitamin D supplements most effectively in HCV-infected patients is provided.

In vivo diagnostic accuracy of high resolution microendoscopy in differentiating neoplastic from non-neoplastic colorectal polyps: a prospective study

OBJECTIVES:High-resolution microendoscopy (HRME) is a low-cost, “optical biopsy” technology that allows for subcellular imaging. The purpose of this study was to determine the in vivo diagnostic accuracy of the HRME for the differentiation of neoplastic from non-neoplastic colorectal polyps and compare it to that of high-definition white-light endoscopy (WLE) with histopathology as the gold standard.METHODS:Three endoscopists prospectively detected a total of 171 polyps from 94 patients that were then imaged by HRME and classified in real-time as neoplastic (adenomatous, cancer) or non-neoplastic (normal, hyperplastic, inflammatory).RESULTS:HRME had a significantly higher accuracy (94%), specificity (95%), and positive predictive value (PPV, 87%) for the determination of neoplastic colorectal polyps compared with WLE (65%, 39%, and 55%, respectively). When looking at small colorectal polyps (less than 10 mm), HRME continued to significantly outperform WLE in terms of accuracy (95% vs. 64%), specificity (98% vs. 40%) and PPV (92% vs. 55%). These trends continued when evaluating diminutive polyps (less than 5 mm) as HRMEs accuracy (95%), specificity (98%), and PPV (93%) were all significantly greater than their WLE counterparts (62%, 41%, and 53%, respectively).CONCLUSIONS:In conclusion, this in vivo study demonstrates that HRME can be a very effective modality in the differentiation of neoplastic and non-neoplastic colorectal polyps. A combination of standard white-light colonoscopy for polyp detection and HRME for polyp classification has the potential to truly allow the endoscopist to selectively determine which lesions can be left in situ, which lesions can simply be discarded, and which lesions need formal histopathologic analysis.

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

BACKGROUND & AIMS Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugols chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.

Diagnosis of sessile serrated adenomas/polyps with image-enhanced endoscopy: a systematic review and meta-analysis.

BACKGROUND AND STUDY AIMS Distinguishing sessile serrated adenomas/polyps (SSA/Ps) from non-neoplastic tissue may be challenging when white-light endoscopy (WLE) is used. Image-enhanced endoscopy (IEE) has shown accuracy in differentiating adenomas from hyperplastic polyps. The aim of this systematic review and meta-analysis was to evaluate the utility of IEE in diagnosis of SSA/Ps. METHODS Studies were eligible if: they included patients undergoing colonoscopy with an endoscopy-based image-enhancement modality; endoscopic diagnoses, including SSA/P, were based on the appearance of polyps at IEE; and the corresponding histologic diagnoses of polyps were provided. The primary outcome was sensitivity of IEE for SSA/Ps differentiated from non-neoplastic lesions (primary convention) and differentiated from all non-SSA/P lesions, including adenomas (secondary convention). RESULTS 13 studies met inclusion criteria. Sensitivity ranged from 38 % to 100 % but sensitivity ≥ 90 % was seen in 4 of 10 narrow band imaging (NBI) or magnification-NBI studies. Pooled sensitivities for discriminating SSA/Ps from non-neoplastic lesions were 80 % for magnification-NBI, 60 % for NBI, 49 % for autofluorescence, and 47 % for flexible spectral imaging color enhancement. In head-to-head comparisons with WLE, NBI (89 % vs. 75 %) and magnification-NBI (78 % vs. 63 %) demonstrated significantly greater sensitivity, while autofluorescence imaging (56 % vs. 66 %), flexible spectral imaging color enhancement (100 % vs. 100 %), and high-resolution endomicroscopy (88 % vs. 100 %) did not. CONCLUSION IEE currently cannot be recommended as a diagnostic tool for SSA/P. While NBI studies showed promise, more IEE studies employing validated SSA/P criteria in well-defined polyp populations are needed. IEE studies assessing SSA/P detection rates at colonoscopy are also needed.

Low-cost high-resolution microendoscopy for the detection of esophageal squamous cell neoplasia

BACKGROUND & AIMS Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugols chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.

Clinical Factors That Predict Noncirrhotic Portal Hypertension in HIV-Infected Patients: A Proposed Diagnostic Algorithm

Noncirrhotic portal hypertension (NCPH) is a rare but important clinical entity in human immunodeficiency virus (HIV) populations. The purpose of this study was to describe the clinical factors associated with the condition in an effort to formulate a diagnostic algorithm for easy and early diagnosis. We performed a multicenter, retrospective case-control study of 34 patients with NCPH and 68 control HIV patients. The study found that thrombocytopenia, splenomegaly, didanosine use, elevated aminotransferases, and an elevated alkaline phosphatase level were all significantly more prevalent in the NCPH cohort. Using these easily available clinical parameters, we developed an algorithm for early diagnosis of NCPH in HIV.

Quantitative analysis of high-resolution microendoscopic images for diagnosis of neoplasia in patients with Barrett’s esophagus

BACKGROUND AND AIMS Previous studies show that microendoscopic images can be interpreted visually to identify the presence of neoplasia in patients with Barretts esophagus (BE), but this approach is subjective and requires clinical expertise. This study describes an approach for quantitative image analysis of microendoscopic images to identify neoplastic lesions in patients with BE. METHODS Images were acquired from 230 sites from 58 patients by using a fiberoptic high-resolution microendoscope during standard endoscopic procedures. Images were analyzed by a fully automated image processing algorithm, which automatically selected a region of interest and calculated quantitative image features. Image features were used to develop an algorithm to identify the presence of neoplasia; results were compared with a histopathology diagnosis. RESULTS A sequential classification algorithm that used image features related to glandular and cellular morphology resulted in a sensitivity of 84% and a specificity of 85%. Applying the algorithm to an independent validation set resulted in a sensitivity of 88% and a specificity of 85%. CONCLUSIONS This pilot study demonstrates that automated analysis of microendoscopic images can provide an objective, quantitative framework to assist clinicians in evaluating esophageal lesions from patients with BE. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01384227 and NCT02018367.).

In vivo classification of colorectal neoplasia using high-resolution microendoscopy: Improvement with experience.

High‐resolution microendoscopy (HRME) is a novel, low‐cost “optical biopsy” technology that allows for subcellular imaging. The study aim was to evaluate the learning curve of HRME for the differentiation of neoplastic from non‐neoplastic colorectal polyps.

Confocal laser endomicroscopy features of sessile serrated adenomas/polyps

Background and aims Sessile serrated adenomas/polyps (SSA/Ps) are difficult to differentiate from non-neoplastic tissue on white-light endoscopy. Confocal laser endomicroscopy (CLE) provides subcellular imaging and real-time “optical biopsy”. The aim of this study was to prospectively describe CLE features of SSA/Ps. Patients and methods Consecutive patients with SSA/Ps were prospectively evaluated with probe-based CLE imaging. CLE images and polyp histology were independently reviewed by three endoscopists and an expert gastrointestinal (GI) pathologist. Distinguishing CLE features of SSA/Ps were identified in conjunction with pathologic correlation. Results In total, 260 CLE images were generated from nine SSA/Ps evaluated in seven patients. Four consensus CLE features of SSA/P were identified: (1) a mucus cap with a bright, cloud-like appearance; (2) thin, branching crypts; (3) increased number of goblet cells and microvesicular mucin-containing cells; and (4) architectural disarray, with dystrophic goblet cells and lack of regular circular crypts Conclusion This is a novel description of characteristic CLE features of SSA/Ps. The four features we identified are easy to detect and may allow for CLE to serve as a diagnostic modality.

Gastric Fundic Gland Adenocarcinoma With Chief Cell Differentiation.

A previously healthy sixty-six year old Caucasian man was referred for an outpatient upper endoscopy and colonoscopy for mild iron deficiency anemia. He had episodic heartburn for which he occasionally took calcium carbonate. He denied any weight loss. His family history was positive for colon cancer in his mother at age 74. He had a twenty pack year tobacco history but quit one year ago. His colonoscopy identified two small tubular adenomas. On upper endoscopy, his esophagus and duodenum appeared normal. On retroflexion in the stomach, there was an irregular 7mm erythematous polypoid lesion in the fundus (Figure 1). Image enhanced endoscopy with narrow band imaging identified increased vascularity and a gyrus-like mucosal pit pattern (Figure 2). Band EMR was performed after initial biopsy revealed dysplasia and the polypoid lesion was removed en bloc. Histologic examination (hematoxylin and eosin stain, Figure 3) revealed well-differentiated gastric adenocarcinoma with chief cell differentiation arising from oxyntic mucosa and invading into the superficial submucosa (arrows). Mucosal and deep resection margins were clear of carcinoma and there was no lymphovascular or perineural invasion. The patient did well post procedure and will undergo a repeat upper endoscopy within six months. Figure 1 Figure 2 Figure 3 While gastric adenocarcinoma is not an uncommon cancer worldwide, gastric adenocarcinoma with chief cell differentiation is a recently described rare epithelial neoplasm of the stomach with unique clinicopathologic characteristics. Unlike conventional types of gastric adenocarcinoma, which typically present with advanced, including metastatic, disease, gastric adenocarcinoma with chief cell differentiation may be a locally curable entity. The initial description in the literature was a case series of twelve Japanese patients.1 More recently, a second case series identified ten additional patients, two of whom were Caucasian.2 Like our patient, all reported patients to date had a solitary polyp, and in the majority, the polyp was located in the gastric fundus. Invasion limited to the submucosa was seen in the initial case series in the majority of patients, but was not identified in the second series, although in that study, specimens examined were superficial biopsy samples only and the submucosa was not evaluated. In both studies, none of the patients developed tumor recurrence or metastasis, leading authors to question if the term oxyntic gland polyp is more appropriate for this lesion, rather than gastric adenocarcinoma with chief cell differentiation. Regardless of the nomenclature, our case highlights that this rare variant of gastric adenocarcinoma may occur in non-Asian patients and emphasizes the utility of narrow band imaging and the importance of endoscopic mucosal resection, given the possibility of submucosal invasion and the ability to achieve curative resection of this rare and unique type of gastric neoplasm.