Diagnosis Of High-grade Dysplasia Research Articles

Intraoperative Frozen Section Evaluation of Pancreatic Specimens and Related Liver Lesions.

Frozen sections are essential in the surgical management of patients, especially those with pancreatic masses, because frozen sections can provide answers intraoperatively and aid in treatment decisions. Pancreas frozen sections are challenging because of the small tissue size, processing artifacts, neoadjuvant treatment effects, and concurrent pancreatitis-like obstructive changes. The authors present a review of intraoperative evaluation of pancreatic specimens. To provide an approach to the diagnosis of pancreatic adenocarcinoma on frozen sections and to discuss commonly encountered pitfalls. Indications for pancreas frozen sections and specific margin evaluation will be discussed. We will also review frozen section diagnosis of subcapsular liver lesions and tumors other than metastases of pancreatic ductal adenocarcinoma. Data sources included a literature review and the personal experiences of the authors. The features for diagnosis of pancreatic adenocarcinoma include disordered architecture, glands at abnormal locations, and atypical cytology. It is important to be aware of the pitfalls and clues on frozen section. The evaluation of resection margins can be challenging, and in the setting of the resection of cystic tumors, the key is the diagnosis of high-grade dysplasia or cancer. Finally, it is vital to remember the differential diagnosis for subcapsular liver lesions because not all lesions will be metastases of adenocarcinomas or bile duct adenomas. Frozen sections remain a useful tool for the intraoperative management of patients with pancreatic tumors.

The Outcome of Local Excision of Rectal Adenomas with High-Grade Dysplasia by Transanal Endoscopic Microsurgery: A Single-Center Experience.

Background: Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods: Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results: Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence (p = 0.03). Conclusions: HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions.

Diagnosis and management of Barrett esophagus: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

MR1 : ESGE recommends the following standards for Barrett esophagus (BE) surveillance:- a minimum of 1-minute inspection time per cm of BE length during a surveillance endoscopy- photodocumentation of landmarks, the BE segment including one picture per cm of BE length, and the esophagogastric junction in retroflexed position, and any visible lesions- use of the Prague and (for visible lesions) Paris classification- collection of biopsies from all visible abnormalities (if present), followed by random four-quadrant biopsies for every 2-cm BE length.Strong recommendation, weak quality of evidence. MR2: ESGE suggests varying surveillance intervals for different BE lengths. For BE with a maximum extent of ≥ 1 cm and < 3 cm, BE surveillance should be repeated every 5 years. For BE with a maximum extent of ≥ 3 cm and < 10 cm, the interval for endoscopic surveillance should be 3 years. Patients with BE with a maximum extent of ≥ 10 cm should be referred to a BE expert center for surveillance endoscopies. For patients with an irregular Z-line/columnar-lined esophagus of < 1 cm, no routine biopsies or endoscopic surveillance are advised.Weak recommendation, low quality of evidence. MR3: ESGE suggests that, if a patient has reached 75 years of age at the time of the last surveillance endoscopy and/or the patient's life expectancy is less than 5 years, the discontinuation of further surveillance endoscopies can be considered. Weak recommendation, very low quality of evidence. MR4: ESGE recommends offering endoscopic eradication therapy using ablation to patients with BE and low grade dysplasia (LGD) on at least two separate endoscopies, both confirmed by a second experienced pathologist.Strong recommendation, high level of evidence. MR5: ESGE recommends endoscopic ablation treatment for BE with confirmed high grade dysplasia (HGD) without visible lesions, to prevent progression to invasive cancer.Strong recommendation, high level of evidence. MR6: ESGE recommends offering complete eradication of all remaining Barrett epithelium by ablation after endoscopic resection of visible abnormalities containing any degree of dysplasia or esophageal adenocarcinoma (EAC).Strong recommendation, moderate quality of evidence. MR7: ESGE recommends endoscopic resection as curative treatment for T1a Barrett's cancer with well/moderate differentiation and no signs of lymphovascular invasion.Strong recommendation, high level of evidence. MR8: ESGE suggests that low risk submucosal (T1b) EAC (i. e. submucosal invasion depth ≤ 500 µm AND no [lympho]vascular invasion AND no poor tumor differentiation) can be treated by endoscopic resection, provided that adequate follow-up with gastroscopy, endoscopic ultrasound (EUS), and computed tomography (CT)/positrion emission tomography-computed tomography (PET-CT) is performed in expert centers.Weak recommendation, low quality of evidence. MR9: ESGE suggests that submucosal (T1b) esophageal adenocarcinoma with deep submucosal invasion (tumor invasion > 500 µm into the submucosa), and/or (lympho)vascular invasion, and/or a poor tumor differentiation should be considered high risk. Complete staging and consideration of additional treatments (chemotherapy and/or radiotherapy and/or surgery) or strict endoscopic follow-up should be undertaken on an individual basis in a multidisciplinary discussion.Strong recommendation, low quality of evidence. MR10 A: ESGE recommends that the first endoscopic follow-up after successful endoscopic eradication therapy (EET) of BE is performed in an expert center.Strong recommendation, very low quality of evidence. B: ESGE recommends careful inspection of the neo-squamocolumnar junction and neo-squamous epithelium with high definition white-light endoscopy and virtual chromoendoscopy during post-EET surveillance, to detect recurrent dysplasia.Strong recommendation, very low level of evidence. C: ESGE recommends against routine four-quadrant biopsies of neo-squamous epithelium after successful EET of BE.Strong recommendation, low level of evidence. D: ESGE suggests, after successful EET, obtaining four-quadrant random biopsies just distal to a normal-appearing neo-squamocolumnar junction to detect dysplasia in the absence of visible lesions.Weak recommendation, low level of evidence. E: ESGE recommends targeted biopsies are obtained where there is a suspicion of recurrent BE in the tubular esophagus, or where there are visible lesions suspicious for dysplasia.Strong recommendation, very low level of evidence. MR11: After successful EET, ESGE recommends the following surveillance intervals:- For patients with a baseline diagnosis of HGD or EAC:at 1, 2, 3, 4, 5, 7, and 10 years after last treatment, after which surveillance may be stopped.- For patients with a baseline diagnosis of LGD:at 1, 3, and 5 years after last treatment, after which surveillance may be stopped.Strong recommendation, low quality of evidence.

Use of Immunohistochemical p53 Mutant-Phenotype in Diagnosis of High-Grade Dysplasia of Esophageal Squamous Epithelia

Background: Mild cellular atypia of esophageal squamous epithelial dysplasia has a risk of progressing to cancer that poses great confusion for pathological diagnosis. There is no research on the diagnosis and differential diagnosis of esophageal squamous dysplasia by the expression of immunohistochemical (IHC) p53. The study aims to conduct a graded diagnosis of esophageal squamous epithelial hyperplasia by combining p53 expressions and microscopic histomorphological characteristics. Methods: The study was conducted from January 2021 to January 2022 and included a total of 208 cases including 262 specimens with atypical hyperplasia or dysplasia of squamous epithelia discovered by esophageal mucosal biopsy. HE staining was used to grade the epithelial hyperplasia degree, and all cases underwent p53 IHC evaluation. Results: Benign lesions: we did not find any p53 IHC mutant-phenotype (0/12 cases) in 12 cases of esophagitis. We found 10 cases (10/80 cases) of p53 IHC mutant-phenotype in 80 cases of low-grade dysplasia, and 158 cases (158/170 cases) of p53 IHC mutant-phenotype of high-grade lesions in 170 cases of high-grade dysplasia and early cancer based on the χ² test results. We found statistically significant differences in p53 IHC mutant-phenotype between the high-grade squamous epithelial lesions and benign lesions. The sensitivity and specificity of p53 in detecting high-grade squamous epithelial lesions were 92.9% and 89.1%, respectively. The positive predictive value was 94.0%, and the negative predictive value was 87.2%. Conclusion: In this study, we found that p53 IHC had high sensitivity and specificity in detecting high-grade esophageal squamous epithelial lesions. Therefore, it has potential to be used as a routine item in pathological detection for auxiliary risk stratification of esophageal squamous epithelial lesions.

Laboratory variation in the grading of dysplasia of duodenal adenomas in familial adenomatous polyposis patients

To prevent duodenal and ampullary cancer in familial adenomatous polyposis (FAP) patients, a diagnosis of high grade dysplasia (HGD) plays an important role in the clinical management. Previous research showed that FAP patients are both over- and undertreated after a misdiagnosis of HGD, indicating unwarranted variation. We aimed to investigate the laboratory variation in dysplasia grading of duodenal adenomas and explore possible explanations for this variation. We included data from all Dutch pathology laboratories between 1991 and 2020 by retrieving histology reports from upper endoscopy specimens of FAP patients from the Dutch nationwide pathology databank (PALGA). Laboratory variation was investigated by comparing standardized proportions of HGD. To describe the degree of variation between the laboratories a factor score was calculated. A funnel plot was used to identify outliers. A total of 3050 specimens from 25 laboratories were included in the final analyses. The mean observed HGD proportion was 9.4%. The top three HGD-diagnosing laboratories diagnosed HGD 3.9 times more often than the lowest three laboratories, even after correcting for case-mix. No outliers were identified. Moderate laboratory variation was found in HGD diagnoses of duodenal tissue of FAP patients after adjusting for case-mix. Despite the fact that no outliers were observed, there may well be room for quality improvement. Concentration of these patients in expertise centers may decrease variation. To further reduce unwarranted variation, we recommend (inter)national guidelines to become more uniform in their recommendations regarding duodenal tissue sampling and consequences of HGD diagnoses.

Prospective surveillance for cholangiocarcinoma in unselected individuals with primary sclerosing cholangitis

The evidence for hepatobiliary tumour surveillance in patients with primary sclerosing cholangitis (PSC) is scarce. In this study, we aimed to prospectively evaluate cholangiocarcinoma (CCA) surveillance with yearly MRI with cholangiopancreatography (MRI/MRCP) in a nationwide cohort. In total, 512 patients with PSC from 11 Swedish hospitals were recruited. The study protocol included yearly clinical follow-ups, liver function tests and contrast-enhanced MRI/MRCP and carbohydrate antigen (CA) 19-9. Patients with severe/progressive bile duct changes on MRI/MRCP were further investigated with endoscopic retrograde cholangiopancreatography. Patients were followed for 5 years or until a diagnosis of CCA, liver transplantation (LT) and/or death. Risk factors associated with CCA were analysed with Cox regression. Eleven patients (2%) were diagnosed with CCA, and two (0.5%) with high-grade bile duct dysplasia. Severe/progressive bile duct changes on MRI/MRCP were detected in 122 patients (24%), of whom 10% had an underlying malignancy. The primary indication for LT (n= 54) was biliary dysplasia in nine patients (17%) and end-stage liver disease in 45 patients (83%), of whom three patients (7%) had unexpected malignancy in the explants. The median survival for patients with CCA was 13 months (3-22 months). Time to diagnosis of high-grade dysplasia and/or hepatobiliary malignancy was significantly associated with severe/progressive bile duct changes on MRI/MRCP (hazard ratio 10.50; 95% CI 2.49-44.31) and increased levels of CA19-9 (hazard ratio 1.00; 95% CI 1.00-1.01). In an unselected cohort of patients with PSC, yearly CA19-9 and MRI/MRCP surveillance followed by ERCP was ineffective in detecting cancer early enough to support long-term survival. Given the low occurrence of CCA, studies on individualised strategies for follow-up and improved diagnostic methods for PSC-related CCA are warranted. A prospective nationwide 5-year study was conducted to evaluate yearly cholangiocarcinoma surveillance using MRI and CA19-9 in patients with primary sclerosing cholangitis. Only 2% of the patients were diagnosed with cholangiocarcinoma during follow-up and their prognosis remained poor despite surveillance. This surveillance strategy failed to detect cancer early enough to support long-term survival. Therefore, individualised strategies and improved diagnostic methods will be required to improve the early detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.

Incidence and natural history of gastric high-grade dysplasia in patients with familial adenomatous polyposis syndrome

Familial adenomatous polyposis (FAP) is characterized by high risks of colonic and extracolonic tumors. Recent studies have suggested a rising risk for gastric cancer (GC). We sought to define the spectrum of premalignant gastric polyps in FAP, focusing on high-grade dysplasia (HGD). The gastric phenotypes of 118 patients diagnosed with FAP or attenuated FAP in our Hereditary Gastrointestinal Cancer Registry were retrospectively reviewed. To analyze the clinical features associated with the diagnosis of HGD, we established an age- and sex-matched control group of FAP patients from our cohort without gastric HGD in a 4:1 ratio. The spectrum and frequency of gastric polyps in individuals with FAP included fundic gland polyps (67.9%), hyperplastic polyps/foveolar hyperplasia (19.6%), tubular adenomas (15.2%), foveolar adenomas (10.7%), and pyloric gland adenomas (6.3%). Ten patients (8.9%) exhibited gastric HGD at a mean age of 55 ± 13 years, and HGD was seen in all polyp types. When compared with control subjects, HGD was associated with a high diversity of gastric polyp histology, prior low-grade dysplasia, severe gastric polyposis, and prior Whipple surgery (P= 2.0E-5, .003, .024, and .04, respectively). Two patients (1.7%) with HGD were diagnosed with GC. However, the remaining 8 patients with HGD have been under surveillance for an average of 5.8 ± 4.5 years without progression to GC. Gastric HGD in FAP may be more common than previously appreciated. The natural history of HGD is variable, and most patients with HGD do not appear to progress to GC.

PANDA: A prospective study of the prevalence of anal dysplasia among women with high-grade cervical, vaginal, and vulvar dysplasia or cancer (107)

<b>Objectives:</b> Infection with high-risk human papillomavirus (HR HPV) is a risk factor for anal cancer, yet no evidence-based anal cancer screening guidelines exist for women with lower genital tract HPV-related dysplasia and/or cancer. We sought to describe the prevalence of anal dysplasia in women with cervical, vaginal, and vulvar dysplasia or cancer. <b>Methods:</b> This cross-sectional study was performed at a tertiary cancer center and its partner public safety-net hospital. Inclusion criteria were ≥21 years of age and a diagnosis of high-grade dysplasia or cancer of the cervix, vagina, or vulva. Women with a history of anal dysplasia or cancer were excluded. Participants underwent anal cytology, as well as anal and cervical HR HPV testing. Participants also underwent cervical cytology and/or colposcopy indicated as part of their standard of care management. Women with abnormal anal cytology were referred for high-resolution anoscopy (HRA). <b>Results:</b> A total of 275 evaluable women were prospectively enrolled between October 2018 and June 2021. The median age was 45 years (range: 21-78). Primary diagnosis was high-grade dysplasia/cancer of the cervix (<i>n</i>=209, 76.0%), vagina (<i>n</i>=25, 9.1%), and vulva (<i>n</i>=41, 14.9%). Five participants (2.0%) were HIV positive. Anal cytology was abnormal in 62 patients (23.8%) and included HSIL (<i>n</i>=1, 1.6%), ASC-H (<i>n</i>=7, 11.3%), ASCUS (<i>n</i>=48,77.4%), and LSIL (<i>n</i>=6, 9.7%). HR anal HPV was detected in 81 patients (32.3%), and included HPV16 in 15 (18.5%), HPV18 in three (3.7%), and other HR HPV types in 63 (77.8%) patients. Nine patients (11.1%) had more than one type of HR anal HPV. HR cervical HPV was detected in 129 patients (47.1%) and included HPV16 in 37 (28.7%), HPV18 in five (3.9%), and other high-risk HPV types in 87 (67.4%) patients. Twelve patients (9.3%) had more than one type of HR cervical HPV. Of those who tested positive for HR HPV, 55 patients (38.5%) had both anal and cervical HR HPV detected. In contrast, 26 (18.2%) had positive anal but negative cervical HR HPV, and 62 (43.4%) had negative anal but positive cervical HR HPV. Anal samples were insufficient for cytology in seven patients (2.6%) and HR HPV testing in 21 patients (7.7%). Of the 62 patients with abnormal anal cytology, 44 (71.0%) underwent HRA. Anal biopsies were performed in 12 patients and showed high-grade anal dysplasia in two patients and were negative in ten patients. Both patients with high-grade anal dysplasia had a primary diagnosis of high-grade cervical dysplasia. There was no association between abnormal anal cytology or positive anal HR HPV testing and the primary site of disease (cervix, vagina, or vulva). There were no cases of anal cancer diagnosed. <b>Conclusions:</b> Our results suggest a high prevalence of anal HR HPV infection and cytologic abnormalities in women with lower genital tract dysplasia or cancer. Further study is needed to determine the rate of progression to high-grade anal dysplasia and cancer to inform appropriate screening guidelines in this population.

Adequacy in Endocervical Curettage.

Specimen adequacy is an important quality assurance component of a cervical Papanicolaou test. Although consensus exists on minimal acceptable cellularity for cervical Papanicolaou tests, no such criteria exist for endocervical curettage (ECC) specimens. We sought to identify minimum acceptable cellularity for accurate diagnosis of high-grade dysplasia (HGD) on ECC. All patients with HGD diagnosed in a loop electrosurgical excision procedure (LEEP) from May 8, 2018, to December 18, 2019, and an ECC in the preceding 6 months at our institution were included (n = 51). All ECCs performed before the LEEP were evaluated for cellularity of squamous cells using Aperio eSlide Manager (Leica Biosystems). Biopsy results concurrent with the ECC were noted. We compared the number of squamous cells in positive and negative ECC specimens using a t-test. The proportion of ECC specimens and concurrent biopsies undergoing immunohistochemical (IHC) staining for p16 were compared using the χ2 test. P < .05 was considered significant. Endocervical curettage specimens positive for HGD have increased cellularity compared with negative ECC specimens (mean cellularity, 10,165 vs 1,055; P < .05). Further, IHC staining for p16 was more likely to be performed on an ECC specimen positive for HGD than on a negative ECC specimen (50% vs 3%; P < .05). Biopsies performed concurrently with a negative ECC finding were more likely to undergo p16 IHC than biopsies performed concurrently with a positive ECC finding (51% vs 7%; P < .05). Finally, we observed no difference in the proportion of biopsies undergoing IHC staining for p16 when comparing biopsies positive for HGD with negative biopsies (37% vs 46%; P = .33). We find cellularity of approximately 10,000 cells adequate to diagnose HGD in an ECC specimen and cellularity of approximately 1,000 cells to be inadequate. Further, we find p16 IHC commonly used as a "rule-in" test on ECC specimens at our institution. Biopsies accompanying an ECC specimen negative for HGD are more likely to undergo p16 IHC than those accompanying an ECC specimen positive for HGD, but there is no difference in the proportion of biopsies undergoing p16 IHC when comparing positive and negative results in the biopsies themselves. These findings further support the need for adequate cellularity for diagnosis in ECC, especially when a biopsy is technically difficult. Further areas for exploration include investigating laboratory procedures to maximize the cellularity of ECC specimens.

Use of a Cytosponge biomarker panel to prioritise endoscopic Barrett's oesophagus surveillance: a cross-sectional study followed by a real-world prospective pilot.

SummaryBackgroundEndoscopic surveillance is recommended for patients with Barrett's oesophagus because, although the progression risk is low, endoscopic intervention is highly effective for high-grade dysplasia and cancer. However, repeated endoscopy has associated harms and access has been limited during the COVID-19 pandemic. We aimed to evaluate the role of a non-endoscopic device (Cytosponge) coupled with laboratory biomarkers and clinical factors to prioritise endoscopy for Barrett's oesophagus.MethodsWe first conducted a retrospective, multicentre, cross-sectional study in patients older than 18 years who were having endoscopic surveillance for Barrett's oesophagus (with intestinal metaplasia confirmed by TFF3 and a minimum Barrett's segment length of 1 cm [circumferential or tongues by the Prague C and M criteria]). All patients had received the Cytosponge and confirmatory endoscopy during the BEST2 (ISRCTN12730505) and BEST3 (ISRCTN68382401) clinical trials, from July 7, 2011, to April 1, 2019 (UK Clinical Research Network Study Portfolio 9461). Participants were divided into training (n=557) and validation (n=334) cohorts to identify optimal risk groups. The biomarkers evaluated were overexpression of p53, cellular atypia, and 17 clinical demographic variables. Endoscopic biopsy diagnosis of high-grade dysplasia or cancer was the primary endpoint. Clinical feasibility of a decision tree for Cytosponge triage was evaluated in a real-world prospective cohort from Aug 27, 2020 (DELTA; ISRCTN91655550; n=223), in response to COVID-19 and the need to provide an alternative to endoscopic surveillance.FindingsThe prevalence of high-grade dysplasia or cancer determined by the current gold standard of endoscopic biopsy was 17% (92 of 557 patients) in the training cohort and 10% (35 of 344) in the validation cohort. From the new biomarker analysis, three risk groups were identified: high risk, defined as atypia or p53 overexpression or both on Cytosponge; moderate risk, defined by the presence of a clinical risk factor (age, sex, and segment length); and low risk, defined as Cytosponge-negative and no clinical risk factors. The risk of high-grade dysplasia or intramucosal cancer in the high-risk group was 52% (68 of 132 patients) in the training cohort and 41% (31 of 75) in the validation cohort, compared with 2% (five of 210) and 1% (two of 185) in the low-risk group, respectively. In the real-world setting, Cytosponge results prospectively identified 39 (17%) of 223 patients as high risk (atypia or p53 overexpression, or both) requiring endoscopy, among whom the positive predictive value was 31% (12 of 39 patients) for high-grade dysplasia or intramucosal cancer and 44% (17 of 39) for any grade of dysplasia.InterpretationCytosponge atypia, p53 overexpression, and clinical risk factors (age, sex, and segment length) could be used to prioritise patients for endoscopy. Further investigation could validate their use in clinical practice and lead to a substantial reduction in endoscopy procedures compared with current surveillance pathways.FundingMedical Research Council, Cancer Research UK, Innovate UK.

A computer-aided diagnosis system using white-light endoscopy for the prediction of conventional adenoma with high grade dysplasia

ObjectivesWe developed a computer-aided diagnosis system called ECRCCAD using standard white-light endoscopy (WLE) for predicting conventional adenomas with high-grade dysplasia (HGD) to optimise the patients' management decisions during colonoscopy. MethodsPretraining model was used to fine-tune the model parameters by transfer learning. 2,397 images of HGD and 2,487 low-grade dysplasia (LGD) images were randomly assigned (8:1:1) to the training, optimising, and internal validation dataset. The prospective validation dataset is the frames accessed from colonoscope videoes. One independent rural hospital provided an external validation dataset. Histopathological diagnosis was used as the standard criterion. The capability of the ECRCCAD to distinguish HGD was assessed and compared with two expert endoscopists. ResultsThe accuracy, sensitivity and specificity for diagnosis of HGD in the internal validation set were 90.5%, 93.2%, 87.9%, respectively. While 88.2%, 85.4%, 89.8%, respectively, for the external validation set. For the prospective validation set, ECRCCAD achieved an AUC of 93.5% in diagnosing HGD. The performance of ECRCCAD in diagnosing HGD was better than that of the expert endoscopist in the external validation set (88.2% vs. 71.5%, P < 0.0001). ConclusionECRCCAD had good diagnostic capability for HGD and enabled a more convenient and accurate diagnosis using WLE.

Contact endoscopy with narrow-band imaging for detection of perpendicular vascular changes in benign, dysplastic, and malignant lesions of the vocal folds

HintergrundPerpendikuläre Gefäßveränderungen (PGV) sind Marker der tumorinduzierten Neoangiogenese der Stimmlippen. Die Kontaktendoskopie mit Narrow Band Imaging (KE-NBI) ermöglicht eine detaillierte Analyse solcher Gefäßveränderungen.Ziel der ArbeitIn dieser Arbeit wurde das Potenzial der KE-NBI bei der Diagnostik benigner, dysplastischer und maligner Veränderungen der Stimmlippen untersucht. Außerdem sollte bei der Detektion von PGV die Aussagekraft des KE-NBI im Vergleich zur Weißlichtendoskopie (WLE) und zur alleinigen Narrow-Band-Imaging-Endoskopie (NBI) bestimmt werden.Material und MethodenDazu befundeten 3 Untersucher histopathologisch verifizierte benigne, dysplastische oder maligne Läsionen der Stimmlippen (n = 60) jeweils im Modus WLE, NBI und KE-NBI. Die Läsionen wurden auf PGV hin untersucht und ihre Dignität beurteilt. Ermittelt wurden der Anteil der Läsionen mit detektierten PGV sowie die diagnostische Güte für jeden Modus und die Interratervariabilität bei der Erkennung von höhergradigen Dysplasien und Karzinomen.ErgebnisseDie KE-NBI zeigte sich den anderen Modi bei der Detektion von PGV und hinsichtlich Sensitivität und Genauigkeit bei der Erkennung von höhergradigen Dysplasien und Karzinomen überlegen. Die Autoren sahen eine deutliche Assoziation dieser pathologischen Veränderungen mit PGV.SchlussfolgerungMittels KE-NBI werden PGV häufiger und zuverlässiger als mit den anderen Methoden erkannt. Die Assoziation dieser Gefäßveränderungen mit höhergradigen Dysplasien und Karzinomen der Stimmlippen wurde bestätigt. Im Vergleich zu WLE und NBI zeigte sich eine erhöhte diagnostische Güte. Somit kann die KE-NBI durch bessere Detektion der PGV die endoskopische Differenzierung zwischen benignen und malignen Läsionen der Stimmlippen verbessern.

Diagnostic performance of narrow-band imaging international colorectal endoscopic and Japanese narrow-band imaging expert team classification systems for colorectal cancer and precancerous lesions.

BACKGROUNDIn recent years, two new narrow-band imaging (NBI) classifications have been proposed: The NBI international colorectal endoscopic (NICE) classification and Japanese NBI expert team (JNET) classification. Most validation studies of the two new NBI classifications were conducted in classification setting units by experienced endoscopists, and the application of use in different centers among endoscopists with different endoscopy skills remains unknown.AIMTo evaluate clinical application and possible problems of NICE and JNET classification for the differential diagnosis of colorectal cancer and precancerous lesions.METHODSSix endoscopists with varying levels of experience participated in this study. Eighty-seven consecutive patients with a total of 125 lesions were photographed during non-magnifying conventional white-light colonoscopy, non-magnifying NBI, and magnifying NBI. The three groups of endoscopic pictures of each lesion were evaluated by the six endoscopists in randomized order using the NICE and JENT classifications separately. Then we calculated the six endoscopists’ sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for each category of the two classifications.RESULTSThe sensitivity, specificity, and accuracy of JNET classification type 1 and 3 were similar to NICE classification type 1 and 3 in both the highly experienced endoscopist (HEE) and less-experienced endoscopist (LEE) groups. The specificity of JNET classification type 1 and 3 and NICE classification type 3 in both the HEE and LEE groups was > 95%, and the overall interobserver agreement was good in both groups. The sensitivity of NICE classification type 3 lesions for diagnosis of SM-d carcinoma in the HEE group was significantly superior to that in the LEE group (91.7% vs 83.3%; P = 0.042). The sensitivity of JNET classification type 2B lesions for the diagnosis of high-grade dysplasia or superficial submucosal invasive carcinoma in the HEE and LEE groups was 53.8% and 51.3%, respectively. Compared with other types of JNET classification, the diagnostic ability of type 2B was the weakest.CONCLUSIONThe treatment strategy of the two classification type 1 and 3 lesions can be based on the results of endoscopic examination. JNET type 2B lesions need further examination.

Eflornithine plus Sulindac for Prevention of Progression in Familial Adenomatous Polyposis

BackgroundThe efficacy and safety of combination therapy with eflornithine and sulindac, as compared with either drug alone, in delaying disease progression in patients with familial adenomatous polyposis are unknown.MethodsWe evaluated the efficacy and safety of the combination of eflornithine and sulindac, as compared with either drug alone, in adults with familial adenomatous polyposis. The patients were stratified on the basis of anatomical site with the highest polyp burden and surgical status; the strata were precolectomy (shortest projected time to disease progression), rectal or ileal pouch polyposis after colectomy (longest projected time), and duodenal polyposis (intermediate projected time). The patients were then randomly assigned in a 1:1:1 ratio to receive 750 mg of eflornithine, 150 mg of sulindac, or both once daily for up to 48 months. The primary end point, assessed in a time-to-event analysis, was disease progression, defined as a composite of major surgery, endoscopic excision of advanced adenomas, diagnosis of high-grade dysplasia in the rectum or pouch, or progression of duodenal disease.ResultsA total of 171 patients underwent randomization. Disease progression occurred in 18 of 56 patients (32%) in the eflornithine–sulindac group, 22 of 58 (38%) in the sulindac group, and 23 of 57 (40%) in the eflornithine group, with a hazard ratio of 0.71 (95% confidence interval [CI], 0.39 to 1.32) for eflornithine–sulindac as compared with sulindac (P=0.29) and 0.66 (95% CI, 0.36 to 1.24) for eflornithine–sulindac as compared with eflornithine. Among 37 precolectomy patients, the corresponding values in the treatment groups were 2 of 12 patients (17%), 6 of 13 (46%), and 5 of 12 (42%) (hazard ratios, 0.30 [95% CI, 0.07 to 1.32] and 0.20 [95% CI, 0.03 to 1.32]); among 34 patients with rectal or ileal pouch polyposis, the values were 4 of 11 patients (36%), 2 of 11 (18%), and 5 of 12 (42%) (hazard ratios, 2.03 [95% CI, 0.43 to 9.62] and 0.84 [95% CI, 0.24 to 2.90]); and among 100 patients with duodenal polyposis, the values were 12 of 33 patients (36%), 14 of 34 (41%), and 13 of 33 (39%) (hazard ratios, 0.73 [95% CI, 0.34 to 1.52] and 0.76 [95% CI, 0.35 to 1.64]). Adverse and serious adverse events were similar across the treatment groups.ConclusionsIn this trial involving patients with familial adenomatous polyposis, the incidence of disease progression was not significantly lower with the combination of eflornithine and sulindac than with either drug alone. (Funded by Cancer Prevention Pharmaceuticals; ClinicalTrials.gov number, NCT01483144; EudraCT number, 2012-000427-41.)

Use of p53 immunohistochemistry in conjunction with routine histology improves risk stratification of patients with Barrett's oesophagus during routine clinical care.

Abnormal p53 protein expression detected by immunohistochemistry (IHC) in Barrett's oesophagus (BO) is reported to be a prognostic biomarker for progression to high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC). We evaluated our use of p53 IHC for patients with BO under surveillance from 2010 to 2016 in a single academic institution. We identified 78patients under surveillance for BO who had biopsies evaluated for abnormal p53 expression in conjunction with routine histology and 892patients who had histological evaluation alone. All available p53 IHC slides were rescored as wild-type or abnormal. We evaluated the risk of subsequent diagnosis with HGD and OAC. p53-tested patients were significantly more likely to be diagnosed with indefinite dysplasia (IND) or low-grade dysplasia (LGD), compared to patients who were not tested (79.5 versus 10.8%, P=7.4×10-40 ). Almost half (46.9%) of patients with abnormal p53 expression were diagnosed with HGD or OAC within 5years, compared to 5.9% with wild-type p53, and 7.6% of patients not tested (P=2.6×10-18 ). However, this difference was heavily influenced by other risk factors, including dysplasia grade, in multivariate analyses. In the subgroup of patients diagnosed with IND (n=109), abnormal p53 expression was associated with a fourfold increase (1.2-13.3, P=0.023) in risk of HGD/OAC relative to untested patients diagnosed with IND, independent of other risk factors. In patients under surveillance for BO in a single academic institution, we found evidence that selective use of p53 IHC in conjunction with routine histology modestly improved risk stratification by identifying patients with IND at higher risk of a subsequent diagnosis of HGD or OAC.

DNA content abnormality in oral submucous fibrosis concomitant leukoplakia: A preliminary evaluation of the diagnostic and clinical implications.

Oral submucous fibrosis (OSF) is an insidious chronic oral and oropharyngeal potentially malignant disorder. Our previously studies reported that DNA image cytometry (ICM) using brushing added in the diagnosis of high-grade dysplasia and staging of oral leukoplakia (OLK). This preliminary study aimed to investigate the abnormal rate of DNA content in 30 cases of OSF including three cases of OSF concomitant OLK and evaluate their the diagnostic and clinical implications with special emphasis on the OSF concomitant OLK. Brushing and biopsy sample form each patient was processed by DNA-ICM and histological examination, respectively. The results of DNA-ICM analysis showed that all the lesions from the 27 patients with OSF only were identified as normal DNA content. Strikingly, two of three cases of OSF concomitant OLK were identified as abnormal DNA content, and one case of whom progressed to early oral squamous cell carcinoma at the follow-up of 31 months. Collectively, this preliminary evaluation revealed that DNA content abnormality was hardly observed in OSF only; however, it may be usually observed in OSF concomitant OLK, whom should be monitored on a priority basis for early detection of carcinoma. Multicenter large studies are needed to validate the findings of the current study.

Trends in Patient Demographics and Diagnostic Yield at an Academic Colposcopy Clinic From 2008 to 2018.

The aim of the study was to review trends in colposcopy rates and diagnoses of high-grade dysplasia and cancer for the past 10 years at an academic colposcopy clinic. A registry of patients seen January 2008 to December 2018 at an academic colposcopy clinic was queried to examine trends in patient characteristics, cytology and histology results, and interventions during the study period, which coincided with the implementation of revised national guidelines. Differences in characteristics were examined with analysis of variance and χ tests. Trends in diagnoses were examined with logistic regression. Trends in interventions were modeled with binomial distribution, logit link, Poisson distribution, and log link. Among 5,103 women referred for abnormal pap testing, human papillomavirus, or dysplasia, the mean age increased over time (30.6 in 2008 to 38.4 in 2018, p < .0001) and fewer pregnant patients were served (11.3% in 2008 vs 2.8% in 2018, p < .0001). There were decreased rates of low-grade cytology (81.3% in 2008 vs 73.6% in 2018, p = .006) and increased rates of human papillomavirus positivity (4.1% in 2008 vs. 14.4% in 2018, p < .0001) on referral. Fewer colposcopies were performed per patient per year (1.2 in 2008 vs. 0.7 in 2018, p < .0001), and with this targeted intervention, there was an increased percentage of patients diagnosed with high-grade histology over time (adjusted p = .05). Over time, the number of colposcopies performed per patient decreased, especially in younger and pregnant women. Meanwhile, the percentage of patients diagnosed with high-grade histology increased, suggesting that guidelines decreased unnecessary procedures while increasing the percentage of patients diagnosed with precancerous lesions.

Risk of Development of More-advanced Lesions in Patients With Inflammatory Bowel Diseases and Dysplasia

Patients with inflammatory bowel diseases (IBD) have increased risks of dysplasia and colitis-associated cancer (CAC). We evaluated the risk of development of high-grade dysplasia (HGD) or CAC after diagnosis of dysplasia using data from a national cohort of patients with IBD. We performed a multicenter retrospective analysis of data collected from 7 tertiary referral regional or academic centers in Belgium. In searches of IBD pathology databases, we identified 813 lesions (616 low-grade dysplasias [LGDs], 64 high-grade dysplasias [HGDs], and 133 CACs) in 410 patients with IBD: 299 had dysplasia (73%) and 111 had CAC (27%). The primary aim was to determine the risk of more-advanced lesions after diagnosis of LGD or HGD. Of the 287 patients with LGD, 21 (7%) developed more-advanced lesions (HGD or CAC) after a median time period of 86 months (interquartile range, 34-214). Of the 28 patients with HGD, 4 (14%) developed CAC after a median time period of 180 months (interquartile range, 23-444). The overall cumulative incidence of CAC at 10 years after an initial diagnosis of HGD was 24.3% and after an initial diagnosis of LGD was 8.5% (P <.05). Metachronous lesions, non-polypoid lesions, and colonic stricture were associated with risk of occurrence of more-advanced lesions after LGD (P <.05). Of the 630 dysplastic lesions identified during endoscopy, 545 (86%) were removed during the same procedure or during a follow-up endoscopy or by surgery. Of 111 patients with CAC, 95 (86%) did not have prior detection of dysplasia and 64 of these 95 patients (67%) developed CAC outside of the screening or surveillance period recommended by the European Crohn's and Colitis Organisation. In an analysis of pathology data from 7 medical centers in Belgium, we found a low rate of detection of more-advanced lesions following detection of LGD or HGD-taking into account that most of the lesions were removed. Main risk factors for development of more-advanced lesions after LGD were metachronous lesions, non-polypoid lesions, and colon strictures.

Screening for Barrett's Esophagus: Balancing Clinical Value and Cost-effectiveness.

In predisposed individuals with long standing gastroesophageal reflux disease (GERD), esophageal squamous mucosa can transform into columnar mucosa with intestinal metaplasia, commonly called Barrett’s esophagus (BE). Barrett’s mucosa can develop dysplasia, which can be a precursor for esophageal adenocarcinoma (EAC). However, most EAC cases are identified when esophageal symptoms develop, without prior BE or GERD diagnoses. While several gastrointestinal societies have published BE screening guidelines, these vary, and many recommendations are not based on high quality evidence. These guidelines are concordant in recommending targeted screening of predisposed individuals (eg, long standing GERD symptoms with age > 50 years, male sex, Caucasian race, obesity, and family history of BE or EAC), and against population based screening, or screening of GERD patients without risk factors. Targeted endoscopic screening programs provide earlier diagnosis of high grade dysplasia and EAC, and offer potential for endoscopic therapy, which can improve prognosis and outcome. On the other hand, endoscopic screening of the general population, unselected GERD patients, patients with significant comorbidities or patients with limited life expectancy is not cost-effective. New screening modalities, some of which do not require endoscopy, have the potential to reduce costs and expand access to screening for BE.

Increasing prevalence of high-grade dysplasia and adenocarcinoma on index endoscopy in Barrett’s esophagus over the past 2 decades：data from a multicenter U.S. Consortium

Introduction Data on time trends of dysplasia and esophageal adenocarcinoma (EAC) in Barrett’s esophagus (BE) during the index endoscopy (ie, prevalent cases) are limited. Our aim was to determine the prevalence patterns of BE-associated dysplasia on index endoscopy over the past 25 years. Methods The Barrett’s Esophagus Study is a multicenter outcome project of a large cohort of patients with BE. Proportions of patients with index endoscopy findings of no dysplasia (NDBE), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and EAC were extracted per year of index endoscopy, and 5-yearly patient cohorts were tabulated over years 1990 to 2010+ (2010-current). Prevalent dysplasia and endoscopic findings were trended over the past 25 years using percentage dysplasia (LGD, HGD, EAC, and HGD/EAC) to assess changes in detection of BE-associated dysplasia over the last 25 years. Statistical analysis was done using SAS version 9.4 software (SAS, Cary, NC). Results A total of 3643 patients were included in the analysis with index endoscopy showing NDBE in 2513 (70.1%), LGD in 412 (11.5%), HGD in 193 (5.4%), and EAC in 181 (5.1%). Over time, there was an increase in the mean age of patients with BE (51.7 ± 29 years vs 62.6 ± 11.3 years) and the proportion of males (84% vs 92.6%) diagnosed with BE but a decrease in the mean BE length (4.4±4.3 cm vs 2.9±3.0 cm) as time progressed (1990-1994 to 2010-2016 time periods). The presence of LGD on index endoscopy remained stable over 1990 to 2016. However, a significant increase (148% in HGD and 112% in EAC) in the diagnosis of HGD, EAC, and HGD/EAC was noted on index endoscopy over the last 25 years (P Conclusion Our results suggest that the prevalence of HGD and EAC has significantly increased over the past 25 years despite a decrease in BE length during the same period. This increase parallels an increase in the detection of visible lesions, suggesting that a careful examination at the index examination is crucial.