Head to head: should we adopt the term 'sessile serrated lesion'?

The precursor lesion for the ~30% of colon carcinomas developing along the serrated pathway was first described in detail in 1996, and was named sessile serrated adenoma in 2003. Although the entity itself was controversial initially, over time the concept of a serrated pathway initiated by this lesion has become well accepted in the medical community. The name sessile serrated adenoma, however, has been controversial since the beginning and continues to be controversial. Alternative names, including serrated polyp with abnormal proliferation, sessile serrated polyp and, most recently, sessile serrated lesion, have been proposed. Despite the fact that the term sessile serrated lesion was adopted by the World Health Organization in 2019, none of these terms has received universal acceptance. In this article, arguments for and against adopting the term sessile serrated lesion are discussed in detail.

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

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 D3, 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.

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.

Diagnostic and reporting issues of preneoplastic polyps of the large intestine with early carcinoma.

Premalignant polyps of the large intestine are common specimens in surgical pathology. They consist of several different subtypes identifiable by histological criteria that are associated with different molecular characteristics and with the development of different types of colorectal carcinoma. The most common of these is the conventional adenoma, which most commonly leads to carcinomas with a low degree of methylation (CIMP-L) that are microsatellite stable. In Lynch syndrome patients these polyps lead to CIMP-L carcinomas that are microsatellite instable. The second most common is the sessile serrated adenoma, which leads to carcinomas with a high degree of methylation (CIMP-H) that may be either microsatellite stable or instable. The least common premalignant polyp is the traditional serrated adenoma, which can lead to either CIMP-L or CIMP-H carcinomas, most often microsatellite stable. This paper will review the histological features of these lesions, discuss problems in diagnosis and discuss the role of histology in management.

A Trial of Calcium and Vitamin D for the Prevention of Colorectal Adenomas.

BACKGROUND: Epidemiologic and preclinical data suggest that higher intake and serum levels of vitamin D and higher intake of calcium reduce the risk of colorectal neoplasia. To further study the chemopreventive potential of these nutrients, we conducted a randomized, double-blind, placebo-controlled trial of supplementation with vitamin D, calcium, or both for the prevention of colorectal adenomas. METHODS: We recruited patients with recently diagnosed adenomas and no known colorectal polyps remaining after complete colonoscopy. We randomly assigned 2259 participants to receive daily vitamin D3 (1000 IU), calcium as carbonate (1200 mg), both, or neither in a partial 2×2 factorial design. Women could elect to receive calcium plus random assignment to vitamin D or placebo. Follow-up colonoscopy was anticipated to be performed 3 or 5 years after the baseline examinations, according to the endoscopist's recommendation. The primary end point was adenomas diagnosed in the interval from randomization through the anticipated surveillance colonoscopy. RESULTS: Participants who were randomly assigned to receive vitamin D had a mean net increase in serum 25-hydroxyvitamin D levels of 7.83 ng per milliliter, relative to participants given placebo. Overall, 43% of participants had one or more adenomas diagnosed during follow-up. The adjusted risk ratios for recurrent adenomas were 0.99 (95% confidence interval [CI], 0.89 to 1.09) with vitamin D versus no vitamin D, 0.95 (95% CI, 0.85 to 1.06) with calcium versus no calcium, and 0.93 (95% CI, 0.80 to 1.08) with both agents versus neither agent. The findings for advanced adenomas were similar. There were few serious adverse events. CONCLUSIONS: Daily supplementation with vitamin D3 (1000 IU), calcium (1200 mg), or both after removal of colorectal adenomas did not significantly reduce the risk of recurrent colorectal adenomas over a period of 3 to 5 years. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00153816.).

Increased Risk of Colorectal Cancer Development Among Patients With Serrated Polyps.

BACKGROUND & AIMS: Sessile serrated adenomas/polyps (SSA/Ps) and traditional serrated adenomas (TSAs) are now distinguished from hyperplastic polyps and recognized as precursors to colorectal cancer (CRC). We studied CRC risks associated with serrated polyps. METHODS: By using Danish databases (1977-2009), we conducted a nationwide population-based, case-control study nested within individuals who had received colonoscopies (n = 272,342), and identified 2045 CRC cases and 8105 CRC-free individuals (controls). For each case and control, we identified the first colorectal polyp(s) that underwent a biopsy or were excised during or after the initial colonoscopy, and obtained tissue blocks for hyperplastic lesions. Four expert pathologists reviewed these lesions using current terminology for serrated polyps. We used logistic regression to compute odds ratios (ORs) to associate the risk of CRC with polyp type and estimated the absolute risks by multiplying the risk in patients with no polyps by these ORs. RESULTS: Seventy-nine cases and 142 controls had SSA/Ps (OR, 3.07; 95% confidence interval [CI], 2.30-4.10). SSA/Ps with cytology markers of dysplasia were associated with a particularly high OR (4.76; 95% CI, 2.59-8.73). Women with SSA/P had a higher risk for CRC than men with SSA/P (OR for women, 5.05; 95% CI, 3.05-8.37 vs OR for men, 2.18; 95% CI, 1.24-3.82); patients with SSA/P proximal to the splenic flexure had the highest risk for CRC (OR, 12.42; 95% CI, 4.88-31.58). The OR for CRC was 4.84 in the 14 cases vs 17 controls with TSAs (95% CI, 2.36-9.93), 2.51 in the 757 cases vs 1698 controls with conventional adenomas (95% CI, 2.25-2.80), and 1.30 in the 55 cases vs 235 controls with hyperplastic polyps (95% CI, 0.96-1.77). The 10-year risk for CRC was 4.4% for patients with SSA/P with dysplasia, 4.5% for patients with TSAs, and 2.3% for patients with conventional adenomas. CONCLUSION: Patients with SSA/P or TSA are at increased risk for CRC; their level of risk is similar to or higher than that of patients with conventional adenomas.

Prevalence of sessile serrated adenoma/polyp in hyperplastic-appearing diminutive rectosigmoid polyps.

BACKGROUND AND AIMS: The American Society for Gastrointestinal Endoscopy recommends that distal colon hyperplastic lesions can be left in place without resection if adenomatous histology can be excluded with >90% negative predictive value. However, some lesions could be sessile serrated adenomas/polyps (SSA/Ps), which is also precancerous. The aim of this study was to describe the prevalence of SSA/Ps in hyperplastic-appearing diminutive rectosigmoid polyps. METHODS: We prospectively placed 513 consecutive diminutive rectosigmoid polyps that appeared hyperplastic to an expert endoscopist in individual bottles for pathologic. Each polyp was examined by 3 expert GI pathologists. RESULTS: The prevalence of SSA/P in the study polyps ranged from .6% to 2.1%. The lowest negative predictive value found by the endoscopist for the combination of adenomas plus SSA/Ps was 96.7%. CONCLUSIONS: The prevalence of SSA/Ps in diminutive rectosigmoid hyperplastic-appearing polyps is very low. These results support the safety and feasibility of a "do not resect" policy for diminutive hyperplastic-appearing rectosigmoid polyps.

Role of aetiology in the progression, regression, and parenchymal remodelling of liver disease: implications for liver biopsy interpretation.

Clinicopathological concepts on acute and chronic liver disease have evolved rapidly during the last few years, with advances in general and specific treatment options and improved patient outcomes. The old paradigm of 'irreversibility' of cirrhosis had been challenged in major ways, and the validity of the usage of the term 'cirrhosis' has come into question. This paper addresses aetiology-based clinicopathological concepts and features that may deserve attention because they may determine disease outcome and, specifically, patterns of regression and remodelling. A variety of therapeutic interventions may influence remaining disease features after elimination of damaging agents (virus, alcohol, etc.), and determine the final clinical outcome including the risk of hepatocellular carcinoma (HCC). New concepts create new responsibilities and opportunities for the pathologist to contribute to the understanding of liver pathology and communicate this with clinical colleagues and researchers.

Sessile serrated adenomas: an evidence-based guide to management.

The concept of serrated colorectal neoplasia and a serrated pathway to colorectal cancer (CRC) is relatively new and continuing to evolve, but it has become highly relevant to gastroenterologists, pathologist, and oncologists alike. Sessile serrated adenomas (SSA) are now thought to be the major precursor lesion of serrated pathway cancers, which represent up to one-third of all sporadic CRC cases. However, despite their increasingly recognized importance, relatively little is known about the epidemiology and natural history of SSAs, and the molecular and epigenetic aspects are incompletely understood. Endoscopists must be aware of the unique features of SSAs so that the practice of colonoscopic screening for CRC can include optimized detection, removal, and appropriate surveillance of SSAs and other serrated precursor lesions. In this review, we discuss the history, epidemiology, and pathologic aspects of SSAs, as well as a recommended management approach and a discussion of uncertainties and opportunities for future research.

Findings in the distal colorectum are not associated with proximal advanced serrated lesions.

BACKGROUND & AIMS: Serrated lesions are an important contributor to colorectal cancer (CRC), notably in the proximal colon. Findings in the distal colorectum are markers of advanced proximal adenomatous neoplasia. However, it is not known whether they affect the odds of advanced proximal serrated lesions. METHODS: We performed a retrospective cross-sectional study of data from 1910 patients (59.3 ± 8.0 years, 53.8% female) who underwent an average-risk screening colonoscopy from August 2005 through April 2012 at Indiana University Hospital and an associated ambulatory surgery center. Colonoscopies were performed by an endoscopist with high rates of detection of adenomas and serrated polyps. Tissue samples of all serrated polyps (hyperplastic, sessile serrated adenoma/polyp [SSA/P], or traditional serrated adenoma) proximal to the sigmoid colon and serrated polyps >5 mm in the rectum or sigmoid colon were reviewed by a gastrointestinal pathologist and reclassified on the basis of World Health Organization criteria. Advanced serrated lesion (ASL) was defined as SSA/P with cytologic dysplasia, SSA/P ≥10 mm, or traditional serrated adenoma. Advanced conventional adenomatous neoplasia (ACN) was defined as tubular adenoma ≥10 mm, villous histology, high-grade dysplasia, or cancer. The prevalence of proximal ASL and ACN was calculated on the basis of distal colorectal findings. Multivariable logistic regression analysis was performed to determine the age-adjusted and sex-adjusted odds of advanced proximal adenomatous and serrated lesions. Secondary analyses were performed to examine the effect of variable ASL definitions. RESULTS: Fifty-two patients (2.7%) had proximal ASL, and 99 (5.2%) had proximal ACN. Of the 52 patients with proximal ASL, 27 (52%) had no distal polyps. Of the 99 patients with proximal ACN, 40 (40%) had no distal polyps. Age and type of distal adenomas were significantly associated with proximal ACN. There were no significant associations between distal polyp type and proximal ASL. In secondary analyses, distal SSA/Ps (P = .008) but not distal hyperplastic polyps or conventional adenomas were associated with any proximal SSA/P. CONCLUSIONS: The findings at flexible sigmoidoscopy that traditionally serve as indications for colonoscopy (conventional adenomas) are likely to be ineffective for detection of proximal ASL. This finding, plus the observation that most patients with proximal ASL have no distal polyps, favors screening colonoscopy over sigmoidoscopy, especially in the elderly. The observation that non-advanced distal SSA/Ps are associated with any proximal SSA/P warrants further study.

Modeling complexity in pathologist workload measurement: the Automatable Activity-Based Approach to Complexity Unit Scoring (AABACUS).

Pathologists provide diagnoses relevant to the disease state of the patient and identify specific tissue characteristics relevant to response to therapy and prognosis. As personalized medicine evolves, there is a trend for increased demand of tissue-derived parameters. Pathologists perform increasingly complex analyses on the same 'cases'. Traditional methods of workload assessment and reimbursement, based on number of cases sometimes with a modifier (eg, the relative value unit (RVU) system used in the United States), often grossly underestimate the amount of work needed for complex cases and may overvalue simple, small biopsy cases. We describe a new approach to pathologist workload measurement that aligns with this new practice paradigm. Our multisite institution with geographically diverse partner institutions has developed the Automatable Activity-Based Approach to Complexity Unit Scoring (AABACUS) model that captures pathologists' clinical activities from parameters documented in departmental laboratory information systems (LISs). The model's algorithm includes: 'capture', 'export', 'identify', 'count', 'score', 'attribute', 'filter', and 'assess filtered results'. Captured data include specimen acquisition, handling, analysis, and reporting activities. Activities were counted and complexity units (CUs) generated using a complexity factor for each activity. CUs were compared between institutions, practice groups, and practice types and evaluated over a 5-year period (2008-2012). The annual load of a clinical service pathologist, irrespective of subspecialty, was ∼40,000 CUs using relative benchmarking. The model detected changing practice patterns and was appropriate for monitoring clinical workload for anatomical pathology, neuropathology, and hematopathology in academic and community settings, and encompassing subspecialty and generalist practices. AABACUS is objective, can be integrated with an LIS and automated, is reproducible, backwards compatible, and future adaptable. It can be applied as a robust decision support tool for the assessment of overall and targeted staffing needs as well as utilization analyses for resource allocation.

Smoking-associated risks of conventional adenomas and serrated polyps in the colorectum.

PURPOSE: Prior studies suggest cigarette smoking is associated with 1.5- to twofold increased risk of colorectal adenomas and possibly a higher risk of serrated polyps. Further clarification of risk differences between adenomas and serrated polyps is needed with regard to co-occurrence and polyp location. METHODS: We conducted a combined analysis of conventional adenoma and serrated polyp occurrence using individual-level data from 2,915 patients participating in three colonoscopy-based clinical trials. All participants had ≥1 adenomas removed at baseline and were followed for up to 4 years. Smoking habits and other lifestyle factors were collected at baseline using questionnaires. We used generalized linear regression to estimate risk ratios and 95 % confidence intervals. RESULTS: Smokers were at slightly increased risk of adenomas compared to never smokers [current: RR 1.29 (95 % CI 1.11-1.49) and former: RR 1.18 (1.05-1.32)]. Smoking was associated with greater risk of serrated polyps [current: RR 2.01 (1.66-2.44); former: RR 1.42 (1.20-1.68)], particularly in the left colorectum. Associations between current smoking and occurrence of serrated polyps only [RR 2.33 (1.76-3.07)] and both adenomas and serrated polyps [RR 2.27 (1.68-3.06)] were more pronounced than for adenomas only [RR 1.31 (1.08-1.58)]. Results were similar for other smoking variables and did not differ by gender or for advanced adenomas. CONCLUSIONS: Cigarette smoking has only a weak association with adenomas, but is associated with a significantly increased risk of serrated polyps, particularly in the left colorectum. Since a minority of left-sided serrated polyps is thought to have malignant potential, the role of smoking in initiation phases of carcinogenesis is uncertain.

Sessile serrated polyp prevalence determined by a colonoscopist with a high lesion detection rate and an experienced pathologist.

BACKGROUND: The prevalence of sessile serrated adenomas and/or polyps (SSA/Ps) is uncertain. OBJECTIVE: To determine the prevalence of SSA/Ps and SSA/Ps with cytologic dysplasia (SSA/P-CD) by using a colonoscopist with a high lesion detection rate and an expert in serrated lesion pathology. DESIGN: Retrospective screening colonoscopy study. SETTING: Academic endoscopy unit. PATIENTS: A total of 1910 average risk, asymptomatic patients aged ≥50 years underwent screening colonoscopy between August 2005 and April 2012 by a single colonoscopist with a high lesion detection rate. INTERVENTIONS: Slides of all lesions in the serrated class proximal to the sigmoid colon and all rectal and sigmoid colon serrated lesions >5 mm in size were reviewed by an experienced GI pathologist. MAIN OUTCOME MEASUREMENTS: Prevalence of SSA/Ps, defined as the proportion of patients with ≥1 SSA/P. RESULTS: There were 1910 patients, of whom 389 had 656 lesions in the serrated class. Review by the experienced GI pathologist determined a prevalence of SSA/Ps without cytologic dysplasia of 7.4% and SSA/Ps-CD of 0.6% (total SSA/P prevalence 8.1%). SSA/Ps and SSA/Ps-CD comprised 5.6% and 0.3%, respectively, of all resected polyps. The mean size of SSA/Ps was 7.13 mm (standard deviation [SD] 4.66), and 51 of 77 (66.2%) polyps ≥10 mm in the serrated class were SSA/Ps. LIMITATIONS: Retrospective design. CONCLUSION: A colonoscopist with a high lesion detection rate and an experienced pathologist identified a high prevalence (8.1%) of SSA/Ps in a screening population. SSA/Ps are more common than previously believed.

Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer.

BACKGROUND: As screening methods for colorectal cancer (CRC) are limited by uptake and adherence, further options are sought. A blood test might increase both, but none has yet been tested in a screening setting. OBJECTIVE: We prospectively assessed the accuracy of circulating methylated SEPT9 DNA (mSEPT9) for detecting CRC in a screening population. DESIGN: Asymptomatic individuals ≥50 years old scheduled for screening colonoscopy at 32 US and German clinics voluntarily gave blood plasma samples before colon preparation. Using a commercially available assay, three independent blinded laboratories assayed plasma DNA of all CRC cases and a stratified random sample of other subjects in duplicate real time PCRs. The primary outcomes measures were standardised for overall sensitivity and specificity estimates. RESULTS: 7941 men (45%) and women (55%), mean age 60 years, enrolled. Results from 53 CRC cases and from 1457 subjects without CRC yielded a standardised sensitivity of 48.2% (95% CI 32.4% to 63.6%; crude rate 50.9%); for CRC stages I-IV, values were 35.0%, 63.0%, 46.0% and 77.4%, respectively. Specificity was 91.5% (95% CI 89.7% to 93.1%; crude rate 91.4%). Sensitivity for advanced adenomas was low (11.2%). CONCLUSIONS: Our study using the blood based mSEPT9 test showed that CRC signal in blood can be detected in asymptomatic average risk individuals undergoing screening. However, the utility of the test for population screening for CRC will require improved sensitivity for detection of early cancers and advanced adenomas. CLINICAL TRIAL REGISTRATION NUMBER: NCT00855348.

Endoscopic detection of proximal serrated lesions and pathologic identification of sessile serrated adenomas/polyps vary on the basis of center.

BACKGROUND & AIMS: We investigated rates of detection of proximal serrated lesions in a cohort of average-risk patients undergoing screening colonoscopies. METHODS: We reviewed results from screening colonoscopies performed by attending gastroenterologists at 32 endoscopy centers from 2008-2010. Pathology slides were interpreted at the individual centers. For this analysis, serrated lesions included hyperplastic polyps larger than 10 mm, those interpreted as sessile serrated adenomas (or sessile serrated polyp), and traditional serrated adenomas. Rates of detection for conventional adenomas and serrated lesions were compared among centers. RESULTS: A total of 5778 lesions were detected in 7215 screening colonoscopies. Of the 5548 lesions with pathology results, 3008 (54.2%) were conventional adenomas, 350 (6.3%) were serrated, and 232 (4.2%) were proximal serrated. The proportion of colonoscopies with at least 1 proximal serrated lesion was 2.8% (range among centers, 0%-9.8%). The number of serrated lesions per colonoscopy ranged from 0.00-0.11 (average, 0.05 ± 0.25). Overall lesion detection rates correlated with proximal serrated lesion detection rates (R = 0.91, P < .0001); conventional adenoma and proximal serrated lesion detection rates also correlated (R = .43, P = .025). The detection rate of proximal serrated lesions differed significantly among centers (P < .0001); odds ratios for detection ranged from 0-0.79. Some centers' pathologists never identified proximal serrated lesions as sessile serrated adenomas/polyps. CONCLUSIONS: In an average-risk screening cohort, detection of proximal serrated lesions varied greatly among endoscopy centers. There was also substantial variation among pathologists in identification of sessile serrated adenomas/polyps. Nationally, a significant proportion of proximal serrated lesions may be missed during colonoscopy examination or incorrectly identified during pathology assessment. ClinicalTrials.gov Number: NCT00855348.

In Search of Nodular Gastric Antral Vascular Ectasia: A Distinct Entity or Simply Hyperplastic Polyps Arising in Gastric Antral Vascular Ectasia?

CONTEXT.­: Nodular gastric antral vascular ectasia (GAVE) is a reported phenotype of GAVE that has histologic features overlapping with gastric hyperplastic polyps (GHPs), with additional features often seen in flat mucosa of GAVE. OBJECTIVE.­: To determine if nodular GAVE and GHPs are distinct lesions by evaluating the prevalence of features reported in nodular GAVE in GHPs with or without associated GAVE. DESIGN.­: A review of all lesions diagnosed as GHPs between 2014 and 2017 was performed. Slides were analyzed for a number of features including established histologic features of GAVE without knowledge of clinical or endoscopic features. RESULTS.­: A total of 90 polyps were analyzed including 18 from patients with GAVE (20%). GAVE polyps were larger than non-GAVE polyps (average size, 1.3 cm versus 0.68 cm; P < .001), with more common extensive ulceration and associated granulation tissue (61.11% [n = 11] versus 4.17% [n = 3]; P = .004), fibrin thrombi (50% [n = 9] versus 15% [n = 11]; P = .003), moderate to marked vascular ectasia (83% [n = 15] versus 35% [n = 11]; P = .001), and fibrohyalinosis (72% [n = 13] versus 28% [n = 20]; P = .001). All polyps showed foveolar hyperplasia and smooth muscle proliferation. There were no features that were exclusively found in GAVE or non-GAVE cases. CONCLUSIONS.­: Nodular GAVE appears to represent GHPs arising in a background of GAVE, with superimposed features found in flat mucosa of GAVE stomachs. The presence of fibrin thrombi, marked vascular ectasia, fibrohyalinosis, and/or ulceration in a GHP is suggestive but not diagnostic of GAVE, and the absence of these features does not rule out GAVE.

Hepatic steatosis estimated microscopically versus digital image analysis.

BACKGROUND & AIMS: Evaluate in liver biopsies: (i) interobserver agreement of estimates of fat proportionate area (eFPA) and steatosis grading, (ii) the relationship between steatosis grades and measured fat proportionate area (mFPA, digital image analysis), (iii) the accuracy of eFPA, (iv) to present images to aid standardization and accuracy of eFPA. METHODS: Twenty-one liver biopsies were selected from the Royal Free Hospital (RFH) histopathology archive to represent the full range of histopathological steatosis severity. As many non-overlapping fields of parenchyma as possible were photographed at ×20 objective magnification from the biopsies (n = 651). A total of 15 sample images were selected to represent the range of steatosis seen. Twelve hepatopathologists from 11 sites worldwide independently evaluated the sample images for steatosis grade [normal (none)/mild/moderate/severe], and eFPA (% area of liver parenchyma occupied by fat). RESULTS: The hepatopathologists had good linear correlation between eFPA and mFPA for sample images (r = 0.924, P < .001) and excellent concordance (kappa = 0.91, P < 0.001). Interobserver concordance of steatosis grade showed 'substantial agreement' (kappa = 0.64). There was significant difference between eFPA and mFPA in the sample images for mild, moderate and severe steatosis (P = 0.024, P < 0.001, P < 0.001 respectively): the observers consistently over-estimated the eFPA. CONCLUSION: Hepatopathologists showed 'excellent' interobserver agreement in eFPA and 'substantial' agreement in assigning steatosis grade (precision was high). However, compared with mFPA, eFPA was inaccurate. eFPA systematically exceeds mFPA; generally the overestimation increases with severity of steatosis. Considering that non-invasive technologies for estimating liver fat utilize histopathology as reference, such assessments would benefit from quantitative validation of visually estimated microscopic liver fat percentages.

Editorial: sessile serrated adenomas and their pit patterns: we must first see the forest through the trees.

Serrated lesions of the colorectum include hyperplastic polyps, which are non-neoplastic, and sessile serrated adenomas (SSAs, also known as sessile serrated polyps) and traditional serrated adenomas, which are premalignant. It is believed that up to 30% of colon cancers and many post-colonoscopy cancers arise from serrated neoplasms. Post-colonoscopy cancers have been found to have a molecular signature similar to SSAs, including CpG island methylation, BRAF mutations, and microsatellite instability. A novel pit pattern, Type II-O, has been demonstrated to have a high specificity for SSAs. Unfortunately, the sensitivity is too low to utilize a Type II-O pit pattern to determine which serrated lesion is neoplastic and needs resection. Moreover, there is significant endoscopist-related variability in the detection of serrated lesions of the colon. Efforts to improve the detection of serrated neoplasms are warranted.

Serrated lesions of the colorectum: review and recommendations from an expert panel.

Serrated lesions of the colorectum are the precursors of perhaps one-third of colorectal cancers (CRCs). Cancers arising in serrated lesions are usually in the proximal colon, and account for a disproportionate fraction of cancer identified after colonoscopy. We sought to provide guidance for the clinical management of serrated colorectal lesions based on current evidence and expert opinion regarding definitions, classification, and significance of serrated lesions. A consensus conference was held over 2 days reviewing the topic of serrated lesions from the perspectives of histology, molecular biology, epidemiology, clinical aspects, and serrated polyposis. Serrated lesions should be classified pathologically according to the World Health Organization criteria as hyperplastic polyp, sessile serrated adenoma/polyp (SSA/P) with or without cytological dysplasia, or traditional serrated adenoma (TSA). SSA/P and TSA are premalignant lesions, but SSA/P is the principal serrated precursor of CRCs. Serrated lesions have a distinct endoscopic appearance, and several lines of evidence suggest that on average they are more difficult to detect than conventional adenomatous polyps. Effective colonoscopy requires an endoscopist trained in the endoscopic appearance of serrated lesions. We recommend that all serrated lesions proximal to the sigmoid colon and all serrated lesions in the rectosigmoid > 5 mm in size, be completely removed. Recommendations are made for post-polypectomy surveillance of serrated lesions and for surveillance of serrated polyposis patients and their relatives.