Showing papers by "Dale C. Snover published in 2019"

Calcium and vitamin D supplementation and increased risk of serrated polyps: results from a randomised clinical trial

Abstract: Objective Serrated lesions such as sessile serrated adenomas or polyps (SSA/Ps) are important colorectal cancer precursors, but aetiological factors for these lesions are largely unknown. We aimed to determine the effects of calcium and vitamin D supplementation on the incidence of serrated polyps (SPs) in general and hyperplastic polyps and SSA/Ps specifically. Design Participants with one or more adenoma at baseline were randomised to receive 1200 mg/day of elemental calcium, 1000 IU/day of vitamin D 3 , both or neither agent. Treatment continued for 3 or 5 years, when risk of polyps was determined from surveillance colonoscopy (treatment phase). Outcomes after treatment ceased were also assessed (observational phase). Adjusted risk ratios (aRRs) of SPs were determined via multivariable generalised linear models. Results SPs were diagnosed in 565 of 2058 (27.5%) participants during the treatment phase and 329/1108 (29.7%) during the observational phase. In total, 211 SSA/Ps were identified during follow-up. In the treatment phase, there was no effect of either calcium or vitamin D on incidence of SSA/Ps. However, during the later observational phase, we observed elevated risks of SSA/Ps associated with calcium alone and calcium+vitamin D treatment (aRR (95% CI): 2.65 (1.43 to 4.91) and 3.81 (1.25 to 11.64), respectively). Conclusion In a large multicentre chemoprevention study, we found evidence that calcium and vitamin D supplementation increased the risk of SSA/Ps. This appeared to be a late effect: 6–10 years after supplementation began. These possible risks must be weighed against the benefits of calcium and vitamin D supplementation. Trial registration number NCT00153816; Results.

Histology of portal vascular changes associated with idiopathic non-cirrhotic portal hypertension: nomenclature and definition.

Abstract: Idiopathic non-cirrhotic portal hypertension (INCPH) is a rare vascular liver disease that has attracted new interest in recent years. It is characterised by clinical signs of portal hypertension in the absence of cirrhosis or severe fibrosis and any known cause of portal hypertension. As much uncertainty exists about INCPH pathophysiology, and no definite diagnostic tests are available, liver biopsy is an essential tool for achieving a definite diagnosis. Unfortunately, the histological diagnosis of INCPH is not always straightforward, as the characteristic lesions are unevenly distributed, vary greatly in their severity, are often very subtle, and are not all necessarily present in a single case. Furthermore, specifically for the characteristic portal vessel changes observed in INCPH, the terminology and definition are ambiguous, which adds complexity to the already complex clinicopathological scenario. An international study group of liver pathologists and hepatologists pursued a consensus on nomenclature for the portal vascular lesions of INCPH. Such standardisation may assist pathologists in the recognition of such lesions, and will possibly facilitate further advancement in this field.

Patterns of Immunohistochemistry Utilization in Metastases to the Liver.

Abstract: Immunohistochemistry (IHC) is a well-established morphology adjunct enabling pathologists to make accurate diagnoses. Metastases to the liver is a common scenario where pathologists may rely heavily on IHC in their interpretation. We conducted this study to audit the patterns of IHC utilization in malignant liver biopsies in 3 practice types (academic, community, and expert) as an initial step toward developing best practice guidelines. A total of 1100 specimens were analyzed and the association between the availability of history of other malignancies and the practice type on IHC utilization was studied. Community pathologists were twice as likely to use IHC and to use more markers per case than academic pathologists or the expert pathologist. When history of another malignancy was available, pathologists were not only 1.5 times more likely to use IHC but they also used more markers per case. IHC was still deemed necessary to reach the diagnosis in 67% of cases with a given history of other malignancy. This study described several variables for consideration in our effort to develop IHC utilization guidelines and its results quantify the variance noted among practice types.

Deep neural networks for automated classification of colorectal polyps on histopathology slides: A multi-institutional evaluation.

Abstract: Histological classification of colorectal polyps plays a critical role in both screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathology slides could benefit clinicians and patients. Evaluate the performance and assess the generalizability of a deep neural network for colorectal polyp classification on histopathology slide images using a multi-institutional dataset. In this study, we developed a deep neural network for classification of four major colorectal polyp types, tubular adenoma, tubulovillous/villous adenoma, hyperplastic polyp, and sessile serrated adenoma, based on digitized histopathology slides from our institution, Dartmouth-Hitchcock Medical Center (DHMC), in New Hampshire. We evaluated the deep neural network on an internal dataset of 157 histopathology slide images from DHMC, as well as on an external dataset of 238 histopathology slide images from 24 different institutions spanning 13 states in the United States. We measured accuracy, sensitivity, and specificity of our model in this evaluation and compared its performance to local pathologists' diagnoses at the point-of-care retrieved from corresponding pathology laboratories. For the internal evaluation, the deep neural network had a mean accuracy of 93.5% (95% CI 89.6%-97.4%), compared with local pathologists' accuracy of 91.4% (95% CI 87.0%-95.8%). On the external test set, the deep neural network achieved an accuracy of 87.0% (95% CI 82.7%-91.3%), comparable with local pathologists' accuracy of 86.6% (95% CI 82.3%-90.9%). If confirmed in clinical settings, our model could assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings.

Microforceps-Assisted Diagnosis of Cystic Pancreatic Neuroendocrine Tumor.

Abstract: A 72-year-old white woman with a history of hyperparathyroidism with previous parathyroidectomy was persistent vomiting. Contrast-enhanced computed tomography revealed a 2.9-cm complex cystic mass with a thickened irregular enhancing wall in the pancreatic tail (Fig. 1A). Endoscopic ultrasonography (EUS) revealed a 29-mm anechoic lesion with asymmetric wall thickening (Fig. 1B). EUS-guided fine-needle aspiration (EUS-FNA) with a 19-G needle (Expect Needle; Boston Scientific, Natick, MA, USA) showed a cyst fluid carcinoembryonic antigen (CEA) level of 1.6 ng/mL and amylase level of 67 U/L, and cytological analysis revealed scant cellularity negative for malignancy. Under direct EUS visualization, the Moray microforceps (US Endoscopy, Mentor, OH, USA) was advanced through the 19-G needle and biopsy of the cyst wall was performed (Fig. 1C). Biopsy revealed a pancreatic epithelium with strongly positive staining for chromogranin and synaptophysin, consistent with pancreatic neuroendocrine tumor (PNET; Fig. 2), with 3%–20% of tumor cells positive for Ki-67. She was referred for distal pancreatectomy. Though typically solid, PNETs may present as cystic lesions and account for <10% of all pancreatic cystic neoplasms (PCNs). They usually appear as isolated, non-functional tumors in the body or tail of the pancreas, often associated with MEN-1 as suspected in our case. Given the risk of malignant potential, management involves surgical resection. Accurate preoperative diagnosis is seldom made with cross-sectional imaging alone, warranting the need for EUS-FNA. The EUS morphology of PNET includes a unilocular cyst, septated cysts, cysts with a microcystic appearance, or mixed solid-cystic masses, and are unlikely to reliably distinguish PNETs from other PCNs. Cystic fluid CEA levels are usually low, but amylase levels are variable. The cytology of PNET shows monomorphic plasmacytoid cells with granular cytoplasm and round nuclei with finely stippled and uniformly dispersed (“solid and pepper”) chromatin. The diagnostic yield of cyst fluid cytological analysis is variable, as cystic PNETs may not generate as much neoplastic cells in the cyst lining as their solid counterparts. Currently, newer procurement devices such as the microforceps biopsy device can be introduced through a 19-G needle to sample tissue from the cyst wall, septations, and/or mural nodules, which can be processed as a cellblock. Microforceps biopsy is associated with high technical success in providing tissue with preserved architecture for ancillary testing, carries an excellent safety profile, and can serve as a useful adjunctive tool to complement existing diagnostic protocols for PCNs. In our case, microforceps biopsy drastically changed the diagnosis, which was otherwise not suggested by cytology or cyst fluid CEA level, thereby enabling appropriate management. Though not observed in this case, intracystic bleeding and postprocedural pancreatitis have been reported. Currently, whether postprocedural pancreatitis was a consequence of EUS-FNA could not be discerned using a 19-G needle or the results of the microforceps biopsy. Future studies should evaluate the minimal number of passes needed with the microforceps biopsy to optimize tissue acquisition yield without Received: October 1, 2018 Revised: January 2, 2019 Accepted: January 8, 2019 Correspondence: Guru Trikudanathan Division of Gastroenterology, University of Minnesota, 406 Harvard St SE, MMC36, Minneapolis, MN 55455, USA Tel: +1-860-380-0048, Fax: +1-612-625-5620, E-mail: triku001@umn.edu ORCID: https://orcid.org/0000-0003-3661-4496