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Diagnosis of different breast cancer stages using histopathology whole slide images (WSI) is the gold standard in determining the grade of tissue metastasis. Computer-aided diagnosis (CAD) assists medical experts as a second opinion tool in early detection to prevent further proliferation. The field of pathology has advanced so rapidly that it is possible to obtain high-quality images from glass slides. Patches from the region of interest in histopathology images are extracted and trained using artificial neural network models. The trained model primarily analyzes and predicts the histology images for the benign or malignant class to which it belongs. Classification of medical images focuses on the training of models with layers of abstraction to distinguish between these two classes with less false-positive rates. The learning rate is the crucial hyperparameter used during the training of deep convolutional neural networks (DCNN) to improve model accuracy. This work emphasizes the relevance of the dynamic learning rate than the fixed learning rate during the training of networks. The dynamic learning rate varies with preset conditions between the lower and upper boundaries and repeats at different iterations. The performance of the model thus improves and attains comparatively high accuracy with fewer iterations., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Anil Johny and K. N. Madhusoodanan.)

Introduction: Incidence of gastric carcinoma and gastric polyps is on rise all over the world. Chronic atrophic gastritis to intestinal metaplasia progressing to adenocarcinoma has been documented pathway for gastric carcinogenesis. Another pathway for gastric carcinoma is adenoma carcinoma sequence similar to colon cancer., Aim: To study prevalence, endoscopic, and histomorphological features of gastric polyps., Methods and Material: This was retrospective analysis of gastric polyps from 2012 to 2019 in consecutive 10,800 upper gastrointestinal endoscopies. Demographic, endoscopic, and histopathological data were obtained from hospital records. All gastric polyps were classified as per standard histologic criteria. Additional histological features noted were presence of dysplasia, focus of adenoma, or malignancy., Results: The prevalence of gastric polyps was 434 (4%) of 10,800 upper gastrointestinal endoscopies. Majority of polyps were found in the last 4 years (277: 63.8%). Mean age was 55.4 years with male to female ratio 1:1.2. Most of the polyps (94.9%) were less than 1 cm, located in gastric antrum. Multiple polyps were seen in 20.9% cases. On histopathology, fundic gland polyps were most common (147: 33.8%), followed by hyperplastic (128: 29.4%) polyps. Adenomatous polyps were nine (2%); of these, two cases of hyperplastic polyps and one each of fundic gland polyp and benign epithelial polyp showed adenomatous foci., Conclusion: Fundic gland polyps were the most common polyps. With rising incidence of gastric carcinoma, identification of gastric polyps on endoscopy with biopsy can prevent progression to carcinogenesis., Competing Interests: None

Background: The optimal ulcerative colitis biopsy protocol is unclear., Aim: To evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitis METHODS: Biopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4-biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item-level ratings from four biopsies, was compared to 1-, 2- and 3-biopsy estimates. Agreement was determined using bivariate errors-in-variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed., Results: Forty-six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2-biopsy (tolerance interval: -7.66, 4.79) and 3-biopsy (tolerance interval: -4.86, 3.46) RHI scores demonstrated acceptable agreement with 4-biopsy scores. One-biopsy scores demonstrated unacceptable agreement (tolerance interval: -13.99, 7.78). Mean RHI scores using the 2-, 3- and 4-biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1-biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2-, 3- and 4-biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1)., Conclusions: A minimum of two - conservatively, three - biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice., (© 2020 John Wiley & Sons Ltd.)

Background: Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized., Methods: A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions., Results: Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39)., Conclusion: Substantial variability exists among pathologists in utilizing IHC., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Reproducible and unbiased methods to quantify alveolar structure are important for research on many lung diseases. However, manually estimating alveolar structure through stereology is time consuming and inter-observer variability is high. The objective of this work was to develop and validate a fast, reproducible and accurate (semi-)automatic alternative. A FIJI-macro was designed that automatically segments lung images to binary masks, and counts the number of test points falling on tissue and the number of intersections of the air-tissue interface with a set of test lines. Manual selection remains necessary for the recognition of non-parenchymal tissue and alveolar exudates. Volume density of alveolar septa ([Formula: see text]) and mean linear intercept of the airspaces (Lm) as measured by the macro were compared to theoretical values for 11 artificial test images and to manually counted values for 17 lungs slides using linear regression and Bland-Altman plots. Inter-observer agreement between 3 observers, measuring 8 lungs both manually and automatically, was assessed using intraclass correlation coefficients (ICC). [Formula: see text] and Lm measured by the macro closely approached theoretical values for artificial test images (R2 of 0.9750 and 0.9573 and bias of 0.34% and 8.7%). The macro data in lungs were slightly higher for [Formula: see text] and slightly lower for Lm in comparison to manually counted values (R2 of 0.8262 and 0.8288 and bias of -6.0% and 12.1%). Visually, semi-automatic segmentation was accurate. Most importantly, manually counted [Formula: see text] and Lm had only moderate to good inter-observer agreement (ICC 0.859 and 0.643), but agreements were excellent for semi-automatically counted values (ICC 0.956 and 0.900). This semi-automatic method provides accurate and highly reproducible alveolar morphometry results. Future efforts should focus on refining methods for automatic detection of non-parenchymal tissue or exudates, and for assessment of lung structure on 3D reconstructions of lungs scanned with microCT., Competing Interests: The authors have declared that no competing interests exist.

Background: An optimal sampling sequence in radial guide sheath endobronchial ultrasound lung biopsy (R-EBUS) is unclear. This prospective single-center pilot randomized controlled trial aimed to determine if the initial method and sequence of sampling affect the diagnostic accuracy of the procedure., Methods: Consecutive patients undergoing R-EBUS for lesions >15 mm with a bronchus sign were randomly assigned (1:1:1) to biopsy first (group A), brushings first (group B) or combination (group C). The primary outcome was a positive diagnosis from any sampling method., Results: Fifty-four patients were randomized. The overall diagnostic yield of the procedure was 77.8% (95% confidence interval: 66%-89%), with no difference between groups. A higher rate of positive cytology from brushings was seen if the biopsies were performed before brushings (77.8% in group A vs. 44.4% in group B, P=0.03). The rate of positive cytology from washings was higher if the washings were obtained just after the brushings (61.1% in group A vs. 11.1% in group B, P=0.02). There was no difference in the rate of positive biopsy histology in the groups (P=0.27). All 3 sampling modalities were more likely to be positive in group A (50.0% vs. 11.1% in group B and 22.2% in group C, P=0.04). Complications rate was low and not significantly different between groups., Conclusion: The overall rate of a positive R-EBUS procedure was not affected by the initial sampling method or sequence. However, all 3 sampling modalities were more likely to be positive if biopsies were performed first, followed by brushings and washings.

Background: Line-field confocal optical coherence tomography (LC-OCT) is an imaging technique providing "optical biopsies" of the skin in real time and non-invasively. At a center optical wavelength of 1.3 µm, this innovative technology can be applied to dermo-cosmetic product development due to both high image resolution (~2 µm) and sufficient penetration (~0.5 mm). Nevertheless, the precise dermal area analyzed with LC-OCT has never been identified. In this study, the objective was to compare LC-OCT images with histological sections of the same area, in order to validate a new method for in vivo and non-invasive quantification of superficial dermis thickness. Once validated, this standardized and quantitative method was used to assess age-related changes of the superficial dermis., Materials and Methods: Ex vivo LC-OCT acquisitions and hematoxylin-eosin-safran staining were performed on a panel of four healthy Caucasian female volunteers. In vivo LC-OCT study of skin aging was performed on a panel of 37 healthy Caucasian female divided into five different age-groups., Results: Comparison with histological sections revealed that LC-OCT images allow the visualization and the quantification of the superficial portion of papillary dermis. Applied to different age-group of volunteers, LC-OCT images show a constant decrease in this superficial dermis thickness with age., Conclusions: In conclusion, we have introduced LC-OCT as a novel technique for in vivo and non-invasive evaluation of superficial dermis thickness. This approach could be used in the future to demonstrate visually and quantitatively the capacity of a dermo-cosmetic active ingredient to renormalize the structural properties of the dermis., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Women diagnosed with breast cancer are offered treatment and therapy based on tumor characteristics, including tumor diameter. There is scarce knowledge whether tumor diameter is accurately reported, or whether it is unconsciously rounded to the nearest half-centimeter (terminal digit preference). This study aimed to assess the precision (number of digits) of breast cancer tumor diameters and whether they are affected by terminal digit preference. Furthermore, we aimed to assess the agreement between mammographic and histopathologic tumor diameter measurements. Material and Methods: This national registry study included reported mammographic and registered histopathologic tumor diameter information from the Cancer Registry of Norway for invasive breast cancers diagnosed during 2012-2016. Terminal digit preference was assessed using histograms. Agreement between mammographic and histopathologic measurements was assessed using the intraclass correlation coefficient (ICC) and Bland-Altman plots. Results: Mammographic, histopathologic, or both tumor measurements were available for 7792, 13,541 and 6865 cases, respectively. All mammographic and 97.2% of histopathologic tumor diameters were recorded using whole mm. Terminal digits of zero or five were observed among 38.7% and 34.8% of mammographic and histopathologic measurements, respectively. There was moderate agreement between the two measurement methods (ICC = 0.52, 95% CI: 0.50-0.53). On average, mammographic measurements were 1.26 mm larger (95% limits of agreement: -22.29-24.73) than histopathologic measurements. This difference increased with increasing tumor size. Conclusion: Terminal digit preference was evident among breast cancer tumor diameters in this nationwide study. Further studies are needed to investigate the potential extent of under-staging and under-treatment resulting from this measurement error.

The National Society for Histotechnology (NSH) Quality Management Committee conducted a Workload Study in response to numerous requests by NSH society members for current information examining productivity and staffing in the clinical histology laboratory. Data collection was conducted between October 11 and 9 November 2018 of 15,848 individuals with deliverable email addresses taken from the NSH database (3.6% net email bounce rate). Survey productivity questions were segmented into key areas including grossing, embedding, microtomy and ancillary duties. From the responses, comparisons of laboratory demographics and productivity were examined by institution type and size. This report presents the data collected from the NSH Workload Study.

Background: The aim of this study was to compare the diagnostic utility of fine needle aspiration cytology (FNAC) in breast lesion with gold standard of histopathological diagnosis., Methods: This descriptive cross-sectional study was conducted in Pathology department of Bannu Medical College in collaboration with Surgery Department of Khalifa Gul Nawaz Teaching Hospital Bannu as well as other private surgical hospitals of the territory. A total of 88 FNAC of palpable breast lesions were performed and compared with their corresponding histopathological reports. Patients age, location of lesion in breast, and other necessary findings were recorded on predesigned proforma, FNAC performed by using 10 ml syringes. Slides prepared and processed for cytological staining and reported by cytopathologist. Corresponding biopsies were processed for histopathological examination and diagnosis. All female patients of any age with breast lesions were included, and those breast lesions for which no histopathological report was available were excluded. Statistical Package for Social Sciences (SPSS) version 20 was used for calculation of frequencies with percentages and mean with standard deviation. Also, specificity, sensitivity, diagnostic accuracy, positive predictive value and negative predictive value were calculated by using formulas., Results: In this study the mean age was 34.44±21.57 years and age range was from 16 to 80 years. The most common age group was 26-35 years followed by 36-45 years. In this study sensitivity was (83.33%), specificity was (100 %), positive predictive value was (100 %), negative predictive value was (99.27%) and diagnostic accuracy was 99.30%., Conclusions: FNAC breast is an easily approachable, less invasive, cheap, rapid and almost accurate diagnostic tool in the diagnosis of palpable as well as non palpable breast lesions.

Objective: Perform a prospective study based on sequential clinical, endoscopic, and histologic evaluations of the foregut late after laparoscopic sleeve gastrectomy (LSG) in obese patients. After LSG, several studies have suggested an increase in the incidence of clinical gastroesophageal reflux (GERD) while others have reported an improvement but based mainly on clinical questionnaires., Methods: Prospective study of 104 consecutive patients submitted to LSG. Several postoperative endoscopic and histologic evaluations of the esophagogastric junction (EGJ) and the gastric tube (GT) were performed and correlated with symptomatic findings., Results: According to clinical preoperative findings, patients were divided into non-refluxers (Group I) and refluxers (Group II). Seven patients were unreachable, leaving 97 (93%) for late evaluation. Among Group I, 58.5% developed de novo GERD, while in Group II just 13.6% showed the disappearance of them. Endoscopic evaluations showed progressive deterioration of the EGJ in Group I, with the development of erosive esophagitis (EE), hiatal hernia (HH), and dilated cardia in a large proportion of them. In the GT, the presence of bile was seen in 40%, and an open immobile pylorus was detected in 82%. Short-segment Barrett's esophagus (BE) appeared in 4%., Conclusions: Patients submitted to LSG showed a significant and progressive increase in the presence of "de novo" GERD. Also, an increased duodenogastric reflux was seen through an open and immobile pylorus. Therefore, based on these results, it seems like LSG is a "pro-reflux" surgical procedure, which should be continuously evaluated late after surgery.

Aims: Machine learning (ML) binary classification in diagnostic histopathology is an area of intense investigation. Several assumptions, including training image quality/format and the number of training images required, appear to be similar in many studies irrespective of the paucity of supporting evidence. We empirically compared training image file type, training set size, and two common convolutional neural networks (CNNs) using transfer learning (ResNet50 and SqueezeNet)., Methods and Results: Thirty haematoxylin and eosin (H&E)-stained slides with carcinoma or normal tissue from three tissue types (breast, colon, and prostate) were photographed, generating 3000 partially overlapping images (1000 per tissue type). These lossless Portable Networks Graphics (PNGs) images were converted to lossy Joint Photographic Experts Group (JPG) images. Tissue type-specific binary classification ML models were developed by the use of all PNG or JPG images, and repeated with a subset of 500, 200, 100, 50, 30 and 10 images. Eleven models were generated for each tissue type, at each quantity of training images, for each file type, and for each CNN, resulting in 924 models. Internal accuracies and generalisation accuracies were compared. There was no meaningful significant difference in accuracies between PNG and JPG models. Models trained with more images did not invariably perform better. ResNet50 typically outperformed SqueezeNet. Models were generalisable within a tissue type but not across tissue types., Conclusions: Lossy JPG images were not inferior to lossless PNG images in our models. Large numbers of unique H&E-stained slides were not required for training optimal ML models. This reinforces the need for an evidence-based approach to best practices for histopathological ML., (© 2019 John Wiley & Sons Ltd.)

Background and Aims: Endoscopy and histopathology are pivotal for evaluating disease activity in ulcerative colitis [UC]; correlation between validated endoscopic and histological indices has not been examined. We aim to correlate the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] with two new validated histological indices in patients with established UC., Methods: This was a single-centre cohort of patients with established UC, who underwent flexible sigmoidoscopy or colonoscopy by a single endoscopist. The UCEIS was scored at the worst affected area in the distal colon, which was biopsied; histological disease activity using Nancy [NI] and Robarts' Histological [RHI] indices was scored by a pathologist blinded to the endoscopy. Spearman correlation between the UCEIS, NI, and RHI, and between NI and RHI, was performed., Results: A total of 125 patients, median age 37 years [range 16-81 years], with UCEIS scores [scale 0-8]: 0, n = 21; 1-3, n = 48; 4-6, n = 51; and 7-8, n = 5, were included. Correlation coefficients between UCEIS and NI [scale 0-4] were r = 0.84 (95% confidence interval [CI] 0.76-0.89, p < 0.001) and between UCEIS and RHI [scale 0-33] r = 0.86 [95% CI 0.80-0.90, p < 0.001]. The difference in correlation was not significant [p = 0.57]. There was excellent correlation between the two histological indices [r = 0.92, 95% CI 0.87-0.95, p < 0.001]. Quiescent disease activity defined as the absence of neutrophils [Nancy 0-1, Robarts 0-3] was most closely correlated with UCEIS = 0., Conclusions: The UCEIS strongly correlates with both NI and RHI. Complete mucosal healing is best defined as a UCEIS = 0/8, since this correlates with the absence of microscopic disease activity.

Context: Unnecessary imaging and pathology procedures represent low-value care and can harm children and the health care system., Objective: To perform a systematic review of interventions designed to reduce unnecessary pediatric imaging and pathology testing., Data Sources: We searched Medline, Embase, Cinahl, PubMed, Cochrane Library, and gray literature., Study Selection: Studies we included were: reports of interventions to reduce unnecessary imaging and pathology testing in pediatric populations; from developed countries; written in the English language; and published between January 1, 1996, and April 29, 2017., Data Extraction: Two researchers independently extracted data and assessed study quality using a Cochrane group risk of bias tool. Level of evidence was graded using the Oxford Centre for Evidence-Based Medicine grading system., Results: We found 64 articles including 44 before-after, 14 interrupted time series, and 1 randomized controlled trial. More effective interventions were (1) multifaceted, with 3 components (mean relative reduction = 45.0%; SD = 28.3%) as opposed to 2 components (32.0% [30.3%]); or 1 component (28.6%, [34.9%]); (2) targeted toward families and clinicians compared with clinicians only (61.9% [34.3%] vs 30.0% [32.0%], respectively); and (3) targeted toward imaging (41.8% [38.4%]) or pathology testing only (48.8% [20.9%]), compared with both simultaneously (21.6% [29.2%])., Limitations: The studies we included were limited to the English language., Conclusions: Promising interventions include audit and feedback, system-based changes, and education. Future researchers should move beyond before-after designs to rigorously evaluate interventions. A relatively novel approach will be to include both clinicians and the families they manage in such interventions., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Stain colour estimation is a prominent factor of the analysis pipeline in most of histology image processing algorithms. Providing a reliable and efficient stain colour deconvolution approach is fundamental for robust algorithm. In this paper, we propose a novel method for stain colour deconvolution of histology images. This approach statistically analyses the multi-resolutional representation of the image to separate the independent observations out of the correlated ones. We then estimate the stain mixing matrix using filtered uncorrelated data. We conducted an extensive set of experiments to compare the proposed method to the recent state of the art methods and demonstrate the robustness of this approach using three different datasets of scanned slides, prepared in different labs using different scanners., Competing Interests: The authors have declared that no competing interests exist.

Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.

Introduction: Inguinal hernia repair is one of the most common operations performed by pediatric surgeons. Although the practice of sending the hernia sac for histologic examination after routine hernia repair is common, the indications and practice patterns for this have not been evaluated. The objective of this survey was to determine practice patterns and indications for histologic analysis of the pediatric inguinal hernia sac., Materials and Methods: A 9-question online survey was sent to all members of the International Pediatric Endosurgery Group (IPEG). A Kruskal-Wallis test was used to determine whether practice patterns of sending the hernia sac for histologic evaluation were associated with respondent characteristics. The chi-squared test with Yates's correction was used where appropriate., Results: The survey was completed by 315 IPEG members, for a response rate of 54.4%. Hernia sacs were sent for histologic evaluation always by 23.9%, often by 5.1%, rarely by 17.5%, and never by 53.5%. The respondent characteristics were not associated with whether or not specimens were sent for histology review. Of the 128 who reported sending the inguinal hernia sac, the most common reasons were hospital/state requirements (47.6%), followed by routine practice (25.7%) and concern for missed pathology (24.2%)., Conclusions: The majority of IPEG respondents report never sending the inguinal hernia sac for histologic analysis. Of those that do, most are influenced by hospital/state requirements. The value of sending the hernia sac after routine inguinal hernia repair should be validated if it is to remain an institutional requirement.

Background/aims: Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of gallbladder carcinoma (GBC). However, there is no evidence for the benefit of this costly practice. Our aim was to determine whether a selective strategy based on macroscopic appearance of gallbladder specimens is a reliable strategy to exclude them from histopathological examination., Methods: A retrospective study was conducted from January 2007 until November 2011 in a large community hospital in The Netherlands. All gallbladder specimen reports (n = 1,393) after cholecystectomy were included and searched for abnormal findings. Reports were excluded when a full histopathological report was not available (n = 18)., Results: Out of the 1,375 patients, 185 had a macroscopically abnormal gallbladder specimen. Of these patients, 6 had GBC. All patients with GBC had macroscopic abnormalities, giving a negative predictive value of 100% to exclude gallbladder specimens from histopathological examination based on macroscopic abnormalities., Conclusions: Based on our study it seems justified to exclude gallbladder specimens from histopathological examination based on the absence of macroscopic abnormalities. A more selective policy will reduce medical costs, saving EUR 1.3 million a year in The Netherlands alone, whilst maintaining patient safety., (2014 S. Karger AG, Basel.)

Limited data exist in regard to productivity and staffing in the anatomic pathology laboratory. In 2004, the National Society for Histotechnology (NSH) conducted a pilot study to examine productivity and staffing in the histology laboratory. After review of the data, The College of American Pathologists (CAP)/NSH Histotechnology Committee concluded that a larger survey was required to further address and expand on the pilot study findings. In 2007, a total of 2674 surveys were sent out to North American laboratories. From the responses, comparisons of laboratory demographics and productivity were examined by institution type and workload volume. Productivity was measured as the number of paraffin-embedded tissue blocks processed per full-time equivalent per year. This manuscript presents and discusses the data collected from the CAP/NSH Workload Study.

High resolution, multispectral, and multimodal imagery of tissue biopsies is an indispensable source of information for diagnosis and prognosis of diseases. Automatic extraction of relevant features from these imagery is a valuable assistance for medical experts. A primary step in computational histology is accurate image segmentation to detect the number and spatial distribution of cell nuclei in the tissue, along with segmenting other structures such as lumen and epithelial regions which together make up a gland structure. This chapter presents an automatic segmentation system for histopathology imaging. Spatial constraint fuzzy C-means provides an unsupervised initialization. An active contour algorithm that combines multispectral edge and region informations through a vector multiphase level set framework and Beltrami color metric tensors refines the segmentation. An improved iterative kernel filtering approach detects individual nuclei centers and decomposes densely clustered nuclei structures. The obtained results show high performances for nuclei detection compared to the human annotation.

Histology is the study of the structure of biological tissue using microscopy techniques. As digital imaging technology advances, high resolution microscopy of large tissue volumes is becoming feasible; however, new interactive tools are needed to explore and analyze the enormous datasets. In this paper we present a visualization framework that specifically targets interactive examination of arbitrarily large image stacks. Our framework is built upon two core techniques: display-aware processing and GPU-accelerated texture compression. With display-aware processing, only the currently visible image tiles are fetched and aligned on-the-fly, reducing memory bandwidth and minimizing the need for time-consuming global pre-processing. Our novel texture compression scheme for GPUs is tailored for quick browsing of image stacks. We evaluate the usability of our viewer for two histology applications: digital pathology and visualization of neural structure at nanoscale-resolution in serial electron micrographs.

Trauma laparotomy is the most commonly performed procedure in the acute care setting. As current practice, removed specimens are sent for histological examination. A retrospective review of all trauma laparotomies with specimens removed and sent to pathology during a 12-month period was performed in a Level I trauma center. One hundred five procedures of 244 trauma laparotomies yielded specimens sent for examination. Eighty-six patients were male and 19 patients were female with an average age of 34 +/- 14 years. Fifty-six per cent of the injuries resulted from penetrating trauma and 44 per cent were from blunt trauma. Gunshot wound and motor vehicle crash were the most common penetrating and blunt injuries, respectively. One hundred thirteen specimens were sent to pathology. Forty-three per cent of the specimens were spleen, 24 per cent small bowel, 16 per cent large bowel, 4 per cent kidney, 2 per cent omentum, 3 per cent appendix, 3 per cent pancreas, and 1 per cent for gallbladder and lung. One hundred twelve of 113 grossly normal specimens had normal pathology. One grossly normal specimen exposed abnormal pathology revealing benign appendiceal mucocele. Therefore, 99.1 per cent of grossly normal specimens sent for histological examination after trauma laparotomy were normal. Based on our review, in select patients routine histological examination of tissues removed for traumatic injury is unnecessary.

Background: P16(INK4a) is a biomarker for transforming HPV infections that could act as an adjunct to current cytological and histological assessment of cervical smears and biopsies, allowing the identification of those women with ambiguous results that require referral to colposcopy and potentially treatment., Material and Methods: We conducted a systematic review of all studies that evaluated the use of p16(INK4a) in cytological or histological specimens from the uterine cervix. We also estimated the mean proportion of samples that were positive for p16(INK4a) in cytology and histology, stratified by the grade of the lesion., Results: Sixty-one studies were included. The proportion of cervical smears overexpressing p16(INK4a) increased with the severity of cytological abnormality. Among normal smears, only 12% (95% CI: 7-17%) were positive for the biomarker compared to 45% of ASCUS and LSIL (95% CI: 35-54% and 37-57%, respectively) and 89% of HSIL smears (95% CI: 84-95%). Similarly, in histology only 2% of normal biopsies (95% CI: 0.4-30%) and 38% of CIN1 (95% CI: 23-53%) showed diffuse staining for p16(INK4a) compared to 68% of CIN2 (95% CI: 44-92%) and 82% of CIN3 (95% CI: 72-92%)., Conclusion: Although there is good evidence that p16(INK4a) immunostaining correlates with the severity of cytological/histological abnormalities, the reproducibility is limited due to insufficiently standardized interpretation of the immunostaining. Therefore, a consensus needs to be reached regarding the evaluation of p16(INK4a) staining and the biomarker needs to be assessed in various clinical settings addressing specific clinical questions.

Prostate cancer is the most common gender specific cancer. The current gold standard for diagnosis, histopathology, is subjective and limited by variation between different pathologists. The diagnostic problems associated with the correct grading and staging of prostate cancer (CaP) has led to an interest in the development of spectroscopic based diagnostic techniques. FTIR microspectroscopy used in combination with a Principal Component Discriminant Function Analysis (PC-DFA) was applied to investigate FTIR based histopathology for the diagnosis of CaP. In this paper we report the results of a large patient study in which FTIR has been proven to grade CaP tissue specimens to a high degree of sensitivity and specificity., (((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).)

The first detection of breast cancer micrometastases in lymph nodes by infrared spectral imaging and methods of multivariate analysis is reported. Micrometastases are indicators of early spread of cancer from the organ originally affected by disease, and their detection is of prime importance for the staging and treatment of cancer. Infrared spectral imaging, at a spatial resolution of ca. 10-12 mum, can detect small metastases down to the level of a few cancerous cells. The results presented here add to a rapidly growing database of infrared spectral imaging results for cancer diagnostics., (((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).)

Rapid Raman mapping was carried out on 20 microm sections of oesophageal biopsy samples. Contiguous 7 microm sections were stained with haematoxylin and eosin (H&E) with histopathology provided by an expert pathologist. The step size and acquisition times were varied and the resulting spectra, principal component (PC) score maps and loads were compared. Overall mapping times were also compared to traditional Raman point mapping. The principal component loads for each of the maps were seen to be similar despite varying the acquisition time and number of spectra. Gross biochemical information was extracted showing good correlation with the H&E sections even for short overall mapping times (30-90 minutes for a 2 mm biopsy, 0.5 s acquisition time per 25.3 microm Raman pixel). This demonstrates that low signal to noise spectral maps are sufficient for the identification of histologically relevant biochemistry using principal component analysis as long as the spectral dataset is large enough., (((c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).)

This paper presents a novel two-dimensional (2-D) stochastic method for semantic analysis of the content of histological images Specifically, we propose a 2-D generalization of the traditional hidden Markov model (HMM). The generalization is called spatial-hidden Markov model (SHMM) that captures the contextual characteristics of complex biological features in histological images The model employs a second-order neighborhood system and assumes the conditional independence of vertical and horizontal transitions between hidden states. The notion of 'past' in SHMM is defined as what have been observed in a row-wise raster scan. This paper focuses on two fundamental problems: the best states decoding problem and the estimation of generation probability of an image by a SHMM. Based on our independence assumption of horizontal and vertical transitions, we derive computational tractable solutions to those problems. These solutions are direct extensions of their counterparts, i.e., the Viterbi algorithm and Forward-Backward algorithm, for 1-D HMM. Our experiments were carried on a medical image database with 200 images and compared with a state-of-the-art approach that was run on the same database. The annotation results demonstrated that SHMM consistently outperforms the previous approach and ameliorates many of its drawbacks. In addition, performance comparison with HMM has also validated the superiority of SHMM.

Latent class models provide a useful framework for clustering observations based on several features. Application of latent class methodology to correlated, high-dimensional ordinal data poses many challenges. Unconstrained analyses may not result in an estimable model. Thus, information contained in ordinal variables may not be fully exploited by researchers. We develop a penalized latent class model to facilitate analysis of high-dimensional ordinal data. By stabilizing maximum likelihood estimation, we are able to fit an ordinal latent class model that would otherwise not be identifiable without application of strict constraints. We illustrate our methodology in a study of schwannoma, a peripheral nerve sheath tumor, that included 3 clinical subtypes and 23 ordinal histological measures.

Context: The use of Papanicolaou (Pap) test cytologic-histologic correlation in quality improvement activities is not well studied., Objective: To determine if continuous monitoring of correlation data improves performance., Design: Participants in the College of American Pathologists Q-Tracks program (213 laboratories) self-reported the number of Pap test-histologic biopsy correlation discrepancies every quarter for up to 8 years. A mixed linear model determined if the length of participation in the Q-Tracks program was associated with improved performance. Main outcome measures were predictive value of a positive Pap test, Pap test sensitivity, sampling sensitivity, and proportion of positive histologic diagnoses following a Pap test diagnosis of atypical squamous cells or atypical glandular cells., Results: Institutions evaluated 287,570 paired Pap test-histologic correlation specimens and found 98,424 (34.2%) true-positive Pap test correlations, 19,006 (6.6%) false-positive Pap test correlations, and 6575 (2.3%) false-negative Pap test correlations. The mean predictive value of a positive Pap test, sensitivity, screening and interpretive sensitivity, sampling sensitivity, and proportion of positive histologic diagnoses following a Pap test diagnosis of atypical squamous or glandular cells were 83.6%, 93.7%, 99.2%, 94.2%, 60.3%, and 38.8%, respectively. Longer participation was significantly associated with a higher predictive value of a positive Pap test (P = .01), higher Pap test sensitivity (P = .002), higher Pap test sampling sensitivity (P = .03), and higher proportion of positive histologic diagnoses for a Pap test diagnosis of atypical squamous cells (P < .001)., Conclusions: Long-term monitoring of cytologic-histologic correlation is associated with improvement in cytologic-histologic correlation performance.

An audit was performed to determine the effectiveness of histological sampling of forensic post-mortem cases based on a review of three years' data, which comprised 638 adult autopsy cases. During the study period organs and tissues that appeared macroscopically normal and abnormal were extensively sampled. Histology was regarded as in some way contributory (providing, altering or confirming a cause of death) 53% of the time. The use of histology provided the cause of death in 49 (24%) of the 203 cases not given a cause of death after the completion of the macroscopic examination. When an interim cause of death had been supplied following the completion of the gross examination it was changed in 4.8% of cases, but there were no changes of the manner of death. The majority of the histological diagnoses or discrepancies involved the lungs and the heart. All diagnoses relevant to determining the cause of death would have been made if samples had been taken only from the left ventricle, right ventricle, coronary arteries, lungs, kidneys and brain with any tissue or organ that appeared abnormal macroscopically. A macroscopically identified abnormality that appeared to have been responsible for death was not sampled in 20 cases; consequently, more attention will be paid to sampling macroscopically abnormal tissues. As a result of this audit histology sampling practice has been revised and will be re-audited in the future.

Context: The Clinical Laboratory Improvement Amendments of 1988 require that laboratories perform cytologic-histologic correlation, although the optimal methods and the value of performing correlation have not been determined., Objective: To determine the similarities and differences in how laboratories perform cytologic-histologic correlation., Design: One hundred sixty-two American laboratories were sent a letter requesting copies of the materials they used in the cytologic-histologic correlation process. The returned materials were classified into the categories of forms, logs, and tally sheets. A checklist (derived from the College of American Pathologists Laboratory Accreditation Cytopathology Checklist) was developed to classify the "minimum expected" (15) and "additional" data points that laboratories collected when they performed a correlation., Participants: American pathology laboratories., Main Outcome Measures: Measures were percentage of laboratories that recorded minimum expected and additional data points and the frequency with which specific minimum expected data points were recorded., Results: The response frequency was 32.1%, and a total of 84 cytologic-histologic correlation materials were obtained. The only minimum expected variables recorded on forms or logs by more than 50% of laboratories were cytology case number, sign-out cytology diagnosis, surgical pathology case number, and sign-out surgical pathology diagnosis. Nine (17.3%) laboratories did not record data on forms, logs, or tally sheets. The mean number of minimum expected and additional variables recorded on forms was 6.5 and 8.7, respectively., Conclusions: Laboratories record data from the cytologic-histologic correlation process in a number of ways, indicating the lack of standardization of the data collection process.

Background and Aims: Helicobacter pylori (Hp) infection prevalence increases with age. In elderly patients, who often do not collaborate and who are affected by multiple pathologies, worldwide-recognised invasive and non-invasive methods (histology and Urea Breath Test) are not easy to apply. A new test based on the detection of Hp antigens in the stool (HpSA test) is now available. The aim of our study was to evaluate the sensitivity and specificity of the HpSA test, and the interference of drugs (acid suppression, antibiotics) on test performance., Methods: Hp infection was detected by UBT, HpSA and histology in 122 hospitalised elderly subjects, divided into two groups according to therapy in the last month. Subjects were classified as being Hp-positive if two test results (histology and UBT) were positive, and Hp-negative if the same two test results were negative., Results: The sensitivity and specificity of the HpSA test compared with two tests (histology and UBT) were respectively 76 and 95%. In the group of patients who had not received drugs, the sensitivity and specificity of the HpSA test were respectively 76 and 96%. Instead, in the group of patients who had received pharmacological therapy, sensitivity and specificity values were respectively 67 and 100%. HpSA-positive patients had received acid suppression for 9.2 +/- 8.9 days, and false-negative patients for 27.2 +/- 9.9 days., Conclusions: The HpSA test is simple, inexpensive, and non-invasive for Hp detection, especially in elderly subjects with no compliance. It is influenced only after several days by therapy common in the elderly.

Data from five different Institution of Pathological Anatomy Hospital Services are presented in order to show one (the benchmark) of the multiple existing ways to approach the budget problem and the macroeconomic management of our Services. The aim of this work is not to show the "best" way to work in terms of cost-efficacy but only a methods to compare our results with others. Nevertheless from this study is possible also to make some considerations about medical and technical workload in different services with different habits.

Objective: To use routine data to explore age-related decision making in the hospital management of colorectal cancer., Design: Retrospective analysis of linked Scottish cancer registry and hospital discharge data for colorectal cancer., Setting: All Scottish general hospitals., Participants: All patients on the Scottish colorectal cancer registry 1992-6 (n = 15,299)., Main Results: Histological verification was used to indicate the "gold standard" of investigation. Definitive surgery and chemotherapy were used as indicators of treatment received. After adjusting for demographic factors, tumour sub-site, co-morbidity and route of first admission, increasing age was associated with markedly decreased rates of histological verification, surgery and chemotherapy. It is still not possible to be sure whether there is ageism in the management of older patients with colorectal cancer. However, the rate of histological verification fell markedly with increasing age, making it questionable whether decisions to treat were based on best clinical practice at the time. Differences observed between this study and clinical trial data may represent the margin of ageism between everyday clinical practice and controlled conditions., Conclusions: The value of this analysis lies in the fact that the data come from routine clinical practice rather than special studies. The improved content of Scottish cancer register and the ability to link it to hospital care provides a useful baseline for monitoring adherence to clinical guidelines.

In this article we have presented the application of three region based segmentation techniques namely, seeded volume growing, constrained erosion-dilation techniques and 3-D watershed algorithm. The algorithms are suitably extended to apply on 3-D histo-pathological images. Suitable modifications and extension for each algorithm is done to obtain better segmentation. A quantitative as well as qualitative comparison of the three methods is presented. Modifications to these algorithms for obtaining better results are discussed. The modifications include, (1) design of adaptive similarity measures to control the seeded volume growing and (2) rule-based merging of the over-segmented cells in the case of the 3-D watershed algorithm. Some results and quantitative study is also presented.

The investigation was performed in 120 uterus preparations of the 16-80-yrs women without pathology of the internal sexual organs. A complex of morphological and morphometrical methods was used. The changes of the uterine wall vascularization, connected with ageing and with the functional reconstruction of arterial bed of parous women were described.

The main goal of this paper is to give an overview of the personal experience in the investigation of the hepatic biopsy. There were analyzed liver specimens from 26 children hospitalized in Clinical Hospital "Sf. Maria" Iaşi. The first clinic diagnosis was post-viral chronic hepatitis and most of the cases provided the serologic markers. Histopathological exam revealed 2 cases of active chronic hepatitis and 24 cases of persistent chronic hepatitis. The interpretation of the lesions relied on Ludwig and Metavir scoring systems. The significance of these scores is very important because they allow one to identify the grading of the necro-inflammatory/histological activity and the staging of fibrosis. Thus, the result of these scoring systems make it possible to classify the cases into aggressivity based forms, indicate the therapy approach and estimate the prognosis as well as the clinical course.

We have estimated lung volume, bronchial volume, vessel volume, alveolar surface area and capillary length in patients who died of lung failure due to emphysema and chronic obstructive pulmonary disease (COPD) and in patients with no clinical signs of respiratory disease. Unbiased morphometric methods were applied to the right lung. The patients with emphysema had equal lung volumes and bronchial and vessel volumes compared to the control group. The alveolar surface area and surface density were significantly decreased to about 67%, of control values. The capillary length and length density were significantly decreased to about 68% of control values. The proportional decreases in alveolar surface area and capillary length suggest that compensatory capillary proliferation has not occurred. These unbiased morphometric studies of emphysema have yielded results in end-stage emphysema that are comparable to those previously reported using biased methods. However, the unbiased methods may provide new insights when applied to earlier stages of the disease.

Purpose: The response of arterial wall to endovascular stenting after angioplasty is not well understood. Additionally, changes in the elastic properties of stented vessels are unknown in situ. Vascular compliance was measured in normal canine iliac arteries (n = 11) before and after intravascular ultrasound-guided deployment of self-expandable metallic stents., Methods: Nine animals were restudied and killed 1, 2, and 4 weeks after initial deployment, and two dogs were studied at deployment only. An absolute induction angiometer was used to make in situ measurements of vessel compliance via catheter-based delivery. The angiometer consists of a wire loop probe, which conforms to the diameter of the vessel in which it is placed. Systolic/diastolic changes in loop diameter are translated into measureable changes of induced voltage., Results: Mean compliance of the artery before and immediately after stenting was 4.4 +/- 2.1 and 1.9 +/- 2.0 (x 10(-2) diameter %/mm Hg), respectively. As early as 1 week after deployment, stented arteries began to lose expansile properties, and some were noncompliant. At explantation diminished compliance was accompanied by a periadventitial fibrous reaction around stented vessels. A thin, unobstructing layer of neointimal hyperplasia covered the iliac stents at all intervals, and all vessels remained patent and free of thrombus., Conclusions: The potential advantages provided by a flexible, radially compliant stent are lost within a relatively short time after implantation in nonatherosclerotic canine arteries.

Individual, age, sex, and species differences of morphological shape is treated as a result of general shape formation process. It is assumed that mutual reflections of these differences could be described by continuous and discontinuous transformations. The first type of these reflects equilibrium properties of shape formation, while the second type reflects its non-equilibrium properties. Equilibrium process is strongly canalized and is able to generate quite limited diversity of shapes. Contrary to this, non-equilibrium process can generate a lot of different shapes, as it destroys canalized relations between characters. Idea of equilibrium process provides a background for formulation of null hypothesis about anticipated relations between characters. Statistically significant deviations from these relations allow to recognize characters that mark areas of possibly non-equilibrium transformations. Analysis of localizations of all such characters allows to formulate more meaningful hypothesis about shape transformations for a particular morphological object. Some easily available statistical methods of recognizing characters that reflect either continuous of discontinuous transformations are exposed using mandible of three rat species as an example. It is shown that discontinuous transformations are located mainly in the same areas of mandible in all modes of inter-reflections. Characters (linear measurements between morphometric landmarks) with continuous inter-reflections describe transformations of general shape of the mandible. Characters with discontinuous inter-reflections mark boundaries between functional blocks and areas with the heaviest dynamic loads.

This study evaluates an objective, unbiased, stereologic parameter (volume-weighted mean nuclear volume vV) as a prognostic indicator for survival of neuroblastoma in comparison with three histopathologic grading systems. In this retrospective study 24 consecutive, nonselected patients from the registry of Royal Liverpool Children's Hospital, Alder Hey, England were analyzed. Only primary lesions obtained before chemotherapy were used. Follow-up time in surviving patients (n = 10) was 4.5 to 20 years. All lesions were regraded blind and twice by two pathologists. vV was estimated on routinely processed, hematoxylin and eosin-stained, 5-microns sections, requiring on average less than 20 min per patient. Results show an absolute cut-off point for survival at vV = 270 microns 3. No patient with vV less than this value is alive at present (n = 7). In addition, actuarial survival curves for nonsurvivors show a bimodal pattern of survival time, separating patients with vV greater than (n = 7) and less than (n = 7) 270 microns 3. In comparison with the same analysis for the results of regrading by means of the Hughes or Beckwith system, results of vV estimation were superior. In comparison with the Shimada system the results confirmed the strong dichotomy for survivors and nonsurvivors, although with more overlap. vV has the advantage of predicting length of survival in nonsurvivors. The combination of Shimada grading and vV measurement, on the basis of the material studied, seems to offer useful prediction of biologic behavior. vV was always estimated on the small cell population, reducing the problems of biopsy representability.