Pathological Scoring System Research Articles

PI-RADS Version 2 Is an Excellent Screening Tool for Clinically Significant Prostate Cancer as Designated by the Validated International Society of Urological Pathology Criteria: A Retrospective Analysis

ObjectivesTo assess the utility of multiparametric MRI in detecting clinically significant prostate cancer (csPCa) by comparing PI-RADSv2 scores with International Society of Urological Pathology (ISUP) pathologic grading criteria. MethodsData from 137 patients were retrospectively analyzed. PI-RADSv2 scores were compared with pathologic grade using ISUP criteria. Pathologic grades were divided into clinically significant (groups 3-5) and clinically insignificant lesions (groups 1-2). Chi-squared analysis was performed for to assess correlation. ResultsSensitivity and specificity of PI-RADSv2 score 3-5 lesions for detecting csPCa was 100% and 18.5%, respectively. Negative predictive value (NPV) is 100% for these lesions. When considering only PI-RADSv2 score 4-5 lesions, sensitivity decreases to 90% and specificity increases to 67.5%, with a NPV of 98.5%. When only PI-RADSv2 score 5 lesions are considered, sensitivity decreases to 50% and specificity increases to 90%, with a NPV of 95%. ConclusionsMultiparametric MRI has excellent sensitivity for detecting csPCa. Specificity is poor for PI-RADSv2 score 3 lesions but improves significantly for PI-RADSv2 score 4 and 5 lesions. Overall, mpMRI is an excellent screening tool for csPCa, as designated by the recently validated ISUP criteria. Advances in KnowledgeMultiple limitations of the longstanding Gleason pathologic scoring system have led to the development of new ISUP pathologic criteria, which is more focused on the clinical significance of lesions. There are currently insufficient studies evaluating and validating the ISUP criteria with PIRADS v2 evaluation of the prostate.

Revisiting the role of the pathological grading in pediatric adrenal cortical tumors: results from a national cohort study with pathological review

The prognosis of malignant pediatric adrenocortical tumors is closely related to disease stage, which is used to guide perioperative treatment recommendations. However, current scoring systems are inadequate to distinguish between benign and malignant adrenocortical tumors. Robust microscopic prognostic features that could help determine perioperative therapy are also lacking. The aim of this national study was to review the prognostic value of the Wieneke scoring criteria and Ki67 labeling index in unselected pediatric adrenocortical tumors. Using strict definitions previously defined by expert pathologists, a Wieneke score was re-attributed to each tumor after an independent and centralized review. In addition, Ki67 proliferation index was performed and reviewed for each case. A total of 95 cases were selected; all were treated between 2000 and 2018 and had histopathologic material and sufficient outcome-related information available. Localized disease was found in 88% of patients. Among those with advanced disease, 6% had tumor extension into adjacent organs and 5% had metastases at diagnosis. Median follow-up was 5 years and 3 months. The 5-year PFS was 82%, 95% CI [73%–91%]. Tumor stage significantly correlated with PFS (p < 0.0001). Tumor weight up to 200 g, extra-adrenal extension and initial non-complete surgical resection were statistically associated with worse outcomes. No recurrences nor metastases occurred when the Ki67 index was < 15%. Up to two of the following five factors including tumor necrosis, adrenal capsular invasion, venous invasion, mitotic count > 15/20 high-power fields, and Ki67 index > 15%, significantly correlated with worse outcomes. We propose a pathological scoring system incorporating the Ki67 index as part of a two-step approach after disease staging to guide adjuvant treatment in pediatric adrenocortical tumors, especially after incomplete resection. These results should be validated in an independent cohort.

Blast-Induced Traumatic Brain Injury Triggered by Moderate Intensity Shock Wave Using a Modified Experimental Model of Injury in Mice.

Background:The increasing frequency of explosive injuries has increased interest in blast-induced traumatic brain injury (bTBI). Various shock tube models have been used to study bTBI. Mild-to-moderate explosions are often overlooked because of the slow onset or mildness of the symptoms. However, heavy gas cylinders and large volume chambers in the model may increase the complexity and danger. This study sought to design a modified model to explore the effect of moderate explosion on brain injury in mice.Methods:Pathology scoring system (PSS) was used to distinguish the graded intensity by the modified model. A total of 160 mice were randomly divided into control, sham, and bTBI groups with different time points. The clinical features, imaging features, neurobehavior, and neuropathology were detected after moderate explosion. One-way analysis of variance followed by Fisher's least significant difference posttest or Dunnett's t 3-test was performed for data analyses.Results:PSS of mild, moderate, and severe explosion was 13.4 ± 2.2, 32.6 ± 2.7 (t = 13.92, P < 0.001; vs. mild group), and 56.6 ± 2.8 (t = 31.37, P < 0.001; vs. mild group), respectively. After moderate explosion, mice showed varied symptoms of malaise, anorexia, incontinence, apnea, or seizure. After bTBI, brain edema reached the highest peak at day 3 (82.5% ± 2.1% vs. 73.8% ± 0.6%, t = 7.76, P < 0.001), while the most serious neurological outcomes occurred at day 1 (Y-maze: 8.25 ± 2.36 vs. 20.00 ± 4.55, t = −4.59, P = 0.048; 29.58% ± 2.84% vs. 49.09% ± 11.63%, t = −3.08, P = 0.008; neurologic severity score: 2.50 ± 0.58 vs. 0.00 ± 0.00, t = 8.65, P = 0.016). We also found that apoptotic neurons (52.76% ± 1.99% vs. 1.30% ± 0.11%, t = 57.20, P < 0.001) and gliosis (2.98 ± 0.24 vs. 1.00 ± 0.00, t = 14.42, P = 0.021) in the frontal were significantly higher at day 3 post-bTBI than sham bTBI.Conclusions:We provide a reliable, reproducible bTBI model in mice that can produce a graded explosive waveform similar to the free-field shock wave in a controlled laboratory environment. Moderate explosion can trigger mild-to-moderate blast damage of the brain.

Reproducibility and Feasibility of Strategies for Morphologic Assessment of Renal Biopsies Using the Nephrotic Syndrome Study Network Digital Pathology Scoring System.

Context Testing reproducibility is critical for the development of methodologies for morphologic assessment. Our previous study using the descriptor-based Nephrotic Syndrome Study Network Digital Pathology Scoring System (NDPSS) on glomerular images revealed variable reproducibility. Objective To test reproducibility and feasibility of alternative scoring strategies for digital morphologic assessment of glomeruli and explore use of alternative agreement statistics. Design The original NDPSS was modified (NDPSS1 and NDPSS2) to evaluate (1) independent scoring of each individual biopsy level, (2) use of continuous measures, (3) groupings of individual descriptors into classes and subclasses prior to scoring, and (4) indication of pathologists' confidence/uncertainty for any given score. Three and 5 pathologists scored 157 and 79 glomeruli using the NDPSS1 and NDPSS2, respectively. Agreement was tested using conventional (Cohen κ) and alternative (Gwet agreement coefficient 1 [AC1]) agreement statistics and compared with previously published data (original NDPSS). Results Overall, pathologists' uncertainty was low, favoring application of the Gwet AC1. Greater agreement was achieved using the Gwet AC1 compared with the Cohen κ across all scoring methodologies. Mean (standard deviation) differences in agreement estimates using the NDPSS1 and NDPSS2 compared with the single-level original NDPSS were -0.09 (0.17) and -0.17 (0.17), respectively. Using the Gwet AC1, 79% of the original NDPSS descriptors had good or excellent agreement. Pathologist feedback indicated the NDPSS1 and NDPSS2 were time-consuming. Conclusions The NDPSS1 and NDPSS2 increased pathologists' scoring burden without improving reproducibility. Use of alternative agreement statistics was strongly supported. We suggest using the original NDPSS on whole slide images for glomerular morphology assessment and for guiding future automated technologies.

A new pathological scoring system by the Japanese classification to predict renal outcome in diabetic nephropathy.

Background and objectivesThe impact of the newly proposed pathological classification by the Japan Renal Pathology Society (JRPS) on renal outcome is unclear. So we evaluated that impact and created a new pathological scoring to predict outcome using this classification.Design, setting, participants, & measurementsA multicenter cohort of 493 biopsy-proven Japanese patients with diabetic nephropathy (DN) were analyzed. The association between each pathological factor—Tervaert’ and JRPS classifications—and renal outcome (dialysis initiation or 50% eGFR decline) was estimated by adjusted Cox regression. The overall pathological risk score (J-score) was calculated, whereupon its predictive ability for 10-year risk of renal outcome was evaluated.ResultsThe J-scores of diffuse lesion classes 2 or 3, GBM doubling class 3, presence of mesangiolysis, polar vasculosis, and arteriolar hyalinosis were, respectively, 1, 2, 4, 1, and 2. The scores of IFTA classes 1, 2, and 3 were, respectively, 3, 4, and 4, and those of interstitial inflammation classes 1, 2, and 3 were 5, 5, and 4 (J-score range, 0–19). Renal survival curves, when dividing into four J-score grades (0–5, 6–10, 11–15, and 16–19), were significantly different from each other (p<0.01, log-rank test). After adjusting clinical factors, the J-score was a significant predictor of renal outcome. Ability to predict 10-year renal outcome was improved when the J-score was added to the basic model: c-statistics from 0.661 to 0.685; category-free net reclassification improvement, 0.154 (-0.040, 0.349, p = 0.12); and integrated discrimination improvement, 0.015 (0.003, 0.028, p = 0.02).ConclusionsMesangiolysis, polar vasculosis, and doubling of GBM—features of the JRPS system—were significantly associated with renal outcome. Prediction of DN patients’ renal outcome was better with the J-score than without it.

Novel pathologic scoring tools predict end-stage kidney disease in light chain (AL) amyloidosis

Background and objectives: Light chain (AL) amyloidosis frequently involves the kidney, causing significant morbidity and mortality. A pathologic scoring system with prognostic utility has not been developed. We hypothesized that the extent of amyloid deposition and degree of scarring injury on kidney biopsy, could provide prognostic value, and aimed to develop pathologic scoring tools based on these features.Methods: This is a case-control study of 39 patients treated for AL amyloidosis with biopsy-proven kidney involvement at a large academic medical center. Our novel scoring tools, composite scarring injury score (CSIS) and amyloid score (AS) were applied to each kidney biopsy. The primary outcome was progression to dialysis-dependent end-stage kidney disease (ESKD) using a 12-month landmark analysis.Results: At 12 months, nine patients had progressed to ESKD. Patients with an AS ≥7.5 had a significantly higher cumulative incidence of ESKD than those with AS <7.5 (p = .04, 95% CI 0.13–0.64).Conclusions: Using a 12-month landmark analysis, AS correlated with progression to ESKD. These data suggest that a kidney biopsy, in addition to providing diagnostic information, can be the basis for a pathologic scoring system with prognostic significance.

Prospective Evaluation of PI-RADS™ Version 2 Using the International Society of Urological Pathology Prostate Cancer Grade Group System

The PI-RADS™ (Prostate Imaging Reporting and Data System), version 2 scoring system, introduced in 2015, is based on expert consensus. In the same time frame ISUP (International Society of Urological Pathology) introduced a new pathological scoring system for prostate cancer. Our goal was to prospectively evaluate the cancer detection rates for each PI-RADS, version 2 category and compare them to ISUP group scores in patients undergoing systematic biopsy and magnetic resonance imaging-transrectal ultrasound fusion guided biopsy. A total of 339 treatment naïve patients prospectively underwent multiparametric magnetic resonance imaging evaluated with PI-RADS, version 2 with subsequent systematic and fusion guided biopsy from May 2015 to May 2016. ISUP scores were applied to pathological specimens. An ISUP score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer. Cancer detection rates were determined for each PI-RADS, version 2 category as well as for the T2 weighted PI-RADS, version 2 categories in the peripheral zone. The cancer detection rate for PI-RADS, version 2 categories 1, 2, 3, 4 and 5 was 25%, 20.2%, 24.8%, 39.1% and 86.9% for all prostate cancer, and 0%, 9.6%, 12%, 22.1% and 72.4% for clinically significant prostate cancer, respectively. On T2-weighted magnetic resonance imaging the cancer detection rate in the peripheral zone was significantly higher for PI-RADS, version 2 category 4 than for overall PI-RADS, version 2 category 4 in the peripheral zone (allprostate cancer 36.6% vs 48.1%, p = 0.001, and clinically significant prostate cancer 22.9% vs 32.6%, p= 0.002). The cancer detection rate increases with higher PI-RADS, version 2 categories.

Increased Kidney Biopsy Scarring and Amyloid Deposition Predict Progression to Eskd in Patients with AL Amyloidosis

Background: AL amyloidosis frequently involves the kidney and causes significant morbidity and mortality. Many patients have a diagnostic kidney biopsy; however, there are no well-established techniques for deriving prognostic information from these biopsies. We hypothesized that the extent of amyloid and/or scarring in the kidney could be used to develop a pathologic scoring system to predict renal outcomes.Methods: In a case control study, 39 consecutive patients treated for AL amyloidosis had kidney biopsies reviewed by two independent pathologists, including an expert renal pathologist at our facility. Kidney injury was assessed using novel scoring tools we developed for evaluating the severity of kidney AL amyloidosis. A Composite Scarring Injury Score (CSIS), a quantitative measure of scarring injury in glomeruli and tubulointerstitium, and an Amyloid Score (AS), a summation of assessments of extent of amyloid in the mesangium, glomerular capillary loops, interstitium, and vasculature, were generated. The scores were analyzed for correlation with baseline characteristics and the following outcomes: progression to end-stage kidney disease (ESKD), kidney response, kidney relapse in responders, and duration of kidney response.Results: AS increased with the number of organs involved by AL amyloidosis (median AS: 5.0 for 1-2 organs involved, 7.25 for 3 organs, 9.75 for 4 organs, 10.75 for 5 organs, P=0.039). AS also correlated with initial troponin I (Spearman rho 0.432, P=0.024). There were no statistically significant differences in CSIS and AS between patients treated with autologous hematopoietic stem cell transplantation (n=23) or chemotherapy alone (n=16), those achieving (n=19) and not achieving (n=20) a hematological response, and in patients with (n=19) and without (n=20) cardiac involvement. CSIS and AS did not have a statistically significant correlation with baseline proteinuria, serum albumin, or brain natriuretic peptide.Both CSIS (Spearman rho -0.359, P=0.025) and AS (Spearman rho -0.43, P=0.005) correlated with initial estimated glomerular filtration rate. Compared with patients who did not progress to ESKD (n=29), patients who progressed to ESKD (n=10) had significantly higher median CSIS (5.75 v. 3.30, P=0.048) and AS (9.75 v. 5.5, P=0.01). Receiver operator characteristic (ROC) curves associating progression to ESKD demonstrated that area under the curve was 71% for CSIS and 77% for AS, suggesting that CSIS and AS are useful indicators to predict progression to ESKD. CSIS and AS did not correlate with rates of kidney response (P=0.135 and 0.096), kidney relapse in responders (P=0.069 and 0.829), or duration of kidney response (P=0.06 and 0.06).Conclusions: CSIS and AS correlated with progression to ESKD, demonstrating that a kidney biopsy, in addition to providing diagnostic information, can form the basis for a pathologic scoring system with prognostic significance in renal AL amyloidosis. A larger sample size is necessary to validate the predictive value of CSIS and AS, which should be considered in upcoming AL amyloidosis trials. DisclosuresLenihan:BMS, Roche, Amgen (Consultancy); Takeda (Research Funding): Consultancy, Research Funding.

Reproducibility of the NEPTUNE descriptor-based scoring system on whole-slide images and histologic and ultrastructural digital images

The multicenter Nephrotic Syndrome Study Network (NEPTUNE) digital pathology scoring system employs a novel and comprehensive methodology to document pathologic features from whole-slide images, immunofluorescence and ultrastructural digital images. To estimate inter- and intra-reader concordance of this descriptor-based approach, data from 12 pathologists (eight NEPTUNE and four non-NEPTUNE) with experience from training to 30 years were collected. A descriptor reference manual was generated and a webinar-based protocol for consensus/cross-training implemented. Intra-reader concordance for 51 glomerular descriptors was evaluated on jpeg images by seven NEPTUNE pathologists scoring 131 glomeruli three times (Tests I, II, and III), each test following a consensus webinar review. Inter-reader concordance of glomerular descriptors was evaluated in 315 glomeruli by all pathologists; interstitial fibrosis and tubular atrophy (244 cases, whole-slide images) and four ultrastructural podocyte descriptors (178 cases, jpeg images) were evaluated once by six and five pathologists, respectively. Cohen's kappa for inter-reader concordance for 48/51 glomerular descriptors with sufficient observations was moderate (0.40<kappa≤0.60) for 17 and good (0.60<kappa≤0.80) for 8, for 52% with moderate or better kappas. Clustering of glomerular descriptors based on similar pathologic features improved concordance. Concordance was independent of years of experience, and increased with webinar cross-training. Excellent concordance was achieved for interstitial fibrosis and tubular atrophy. Moderate-to-excellent concordance was achieved for all ultrastructural podocyte descriptors, with good-to-excellent concordance for descriptors commonly used in clinical practice, foot process effacement, and microvillous transformation. NEPTUNE digital pathology scoring system enables novel morphologic profiling of renal structures. For all histologic and ultrastructural descriptors tested with sufficient observations, moderate-to-excellent concordance was seen for 31/54 (57%). Descriptors not sufficiently represented will require further testing. This study proffers the NEPTUNE digital pathology scoring system as a model for standardization of renal biopsy interpretation extendable outside the NEPTUNE consortium, enabling international collaborations.

Antioxidant effects of captopril against lead acetate-induced hepatic and splenic tissue toxicity in Swiss albino mice.

Considering that lead caused a lot of health problems in the world, the present study was carried out to investigate the protective effect of captopril as antioxidants to reduce liver and spleen toxicity induced by lead. Animals were divided into 3 groups, the 1st group served as control group, the 2nd group received 20 mg/kg of lead acetate and the 3rd group received 50 mg/kg of captopril one hour prior to lead administration for 5 days. Results showed that lead intake caused severe alterations in the liver and spleen manifested by hepatocytes degeneration, leukocytic infiltration, fibrosis in liver and moderate to severe liver pathological score. Spleen showed ill-defined architecture, presence of large macrophages and lymphoid necrosis. Administration of captopril reduced hepatotoxicity, liver fibrosis and decrease in pathological scoring system. Moreover, reduced toxicity in spleen is represented by reduction in necrotic areas, more or less healthy lymphoid follicles and decreasing in pathological scoring system.

A pathological scoring system in the diagnosis and judgment of prognosis of biliary atresia

ObjectiveThe purpose of this study was to evaluate the diagnostic and prognostic value of a histological scoring system in biliary atresia (BA). MethodsFrom June 2013 to July 2014, 86 wedge liver biopsy specimens were obtained from infants with neonatal cholestasis (58 patients with biliary atresia and 28 patients with non-obstructive cholestasis as control) in our center. A pathologist, single-blinded to the final diagnosis, made the histological diagnosis individually based on an 8-feature (liver fibrosis, portal ductal proliferation, bile plugs in portal ductules, cholestasis, hepatocellular changes inflammatory cells infiltration in portal region, extramedullary hematopoiesis, and ductal plate malformation), 21-point (0 to 21) scoring system. ResultsIn this retrospective study, ductular reaction (bile ductular proliferation) and liver fibrosis in the portal area, bile plugs, and ductal plate malformation were the best indicators of BA. With the scoring system, a score of ≥8 had the best diagnostic utility to differentiate BA from other intrahepatic cholestasis histologically (sensitivity 94.7%, specificity 86.2%, accuracy 91.9%). Liver fibrosis and ductal plate malformation were confirmed to be related with the prognosis. ConclusionsAn 8-feature, 21-point histological scoring system has a good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis. The use of liver fibrosis and ductal plate malformation are also feasible to assess the prognosis.

Abstract 5271: Hepatic hypoxia-activated intra-arterial therapy: effect of selective targeting of hypoxia in a rabbit liver tumor model

Abstract Purpose: Tumor hypoxia is considered a challenge of anticancer therapy. The use of hypoxia-activated prodrugs (HAPs) in the setting of transarterial chemoembolization (TACE) is particularly appealing by allowing the locoregional delivery of high-doses of chemotherapy which has the potential to reach distal hypoxic tumor regions. Moreover, the embolic effect provided by TACE constitutes an attractive setting for the selective activation of HAPs. We aimed to evaluate the safety and characterize the anticancer efficacy of hepatic hypoxia-activated intraarterial therapy (HAIAT) in a rabbit liver tumor model. Experimental Design: Twenty-eight animals bearing VX2-tumors were randomly assigned to 4 intraarterial therapy (IAT) groups: (1) saline (control); (2) TH-302; (3) doxorubicin-Lipiodol emulsion followed by bland embolization with 100-300μm beads (conventional TACE - cTACE); or (4) cTACE in combination with TH-302 (cTACE+TH-302). Blood samples were collected at baseline and 24 hours, 48 hours, 7 days, and 14 days post-IAT to evaluate treatment-related toxicity. A semi-quantitative pathologic scoring system was used to assess hepatocellular damage. Tumor volumes were segmented on multidetector computed tomography (baseline, 7 days, and 14 days post-IAT). Tumor necrosis was quantified in the whole tumor using a slide-by-slide histosegmentation. Hypoxic fraction (HF) and hypoxic compartment (HC) was determined by pimonidazole staining. Tumor DNA damage, apoptosis, cell proliferation, endogenous hypoxia and metabolism were quantified using color deconvolution analysis (including γ-H2AX, annexin V, caspase-3, Ki-67, HIF1α, VEGF, MCT4 and LDH). Results: cTACE+TH-302 showed similar profile in liver enzyme elevation and pathologic scores compared to cTACE. Neither hematologic nor renal toxicity was observed. Animals treated with cTACE+TH-302 demonstrated smaller tumor volumes, lower tumor growth rate and higher necrotic fraction compared to cTACE. cTACE+TH-302 resulted in a pronounced reduction in the HF and HC. Negative correlation was found between tumor necrosis and the magnitude of HF or HC. cTACE+TH-302 treatment increased the expression of γ-H2A.X, apoptotic biomarkers and decreased the proliferative potential of VX-2 tumor cells. Increased expression level of HIF1α/VEGF and tumor glycolysis biomarkers supports the HAIAT mechanism of action. TH-302 demonstrated a bystander effect with antitumor activity observed beyond hypoxic tumor regions. Conclusion: HAIAT achieved a promising step towards the locoregional targeting of tumor hypoxia. The favorable toxicity profile and strong anticancer effects of TH-302 in combination with cTACE support further investigation in clinical trials in patients with liver cancer. Citation Format: Rafael Duran, Sahar Mirpour, Vasily Pekurovsky, Shanmugasundaram Ganapathy-Kanniappan, Cory F. Brayton, Toby C. Cornish, Boris Gorodetski, Julius Chapiro, Rüdiger Schernthaner, Constantine Frangakis, MingDe Lin, Jessica D. Sun, Charles P. Hart, Jean-François H. Geschwind. Hepatic hypoxia-activated intra-arterial therapy: effect of selective targeting of hypoxia in a rabbit liver tumor model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5271. doi:10.1158/1538-7445.AM2015-5271

Role of alkaline phosphatase intestine-isomerase in acute mesenteric ischemia diagnosis.

The aim of the present study was to investigate the diagnostic value of alkaline phosphatase (ALP) intestine-isomerase, plasma lactate dehydrogenase (LDH), and D-dimer levels in acute mesenteric ischemia. Thirty Wistar rats were divided into 5 groups of 6 rats each. In Group 1, blood samples were obtained to determine normal parameter levels. In the sham group, Group 2, blood samples were obtained following laparotomy. In Group 3, blood samples were obtained 2 hours after ligation. In Groups 4 and 5, blood samples were obtained at 4 and 6 hours after ligation, respectively. Ischemic damage was assessed using a pathological scoring system. Blood samples were analyzed for hourly changes in parameters. No statistically significant difference in D-dimer levels was found between ischemia groups (p=0.337). A statistically significant difference in LDH levels was found between the control group, Group 1, and Group 4 (p=0.018). ALP intestine-isomerase enzyme levels were not statistically significant in other groups (p=0.077). Findings indicate that plasma LDH levels higher than 1900 IU/L may be a useful marker in the early diagnosis of acute mesenteric obstruction. However, ALP intestine-isomerase enzyme and D-dimer plasma levels were not found to contribute to the diagnosis.

Pathological changes of the three clinical types of laryngeal burns based on a canine model

ObjectiveThe study was designed to examine pathological changes of inhalational laryngeal burns of three clinical types: congestive, oedematous and obstructive. MethodsA total of 18 healthy, male, adult Beagle dogs were randomly assigned to inhale hot dry air at room temperature (group C), 80°C (Group 1), 160°C (Group 2) or 320°C (Group 3) for 20min to induce inhalation injury. Each larynx was evaluated and scored based on the ‘clinical scoring and typing system of laryngeal burns at early stage’. Tissue samples of the epiglottis, laryngeal vestibule, vocal folds and infraglottic cavity of the larynx were observed microscopically and evaluated based on a ‘pathological scoring system’. ResultsPathological changes of the larynxes of groups 1 and 2 were primarily characterised by slight atrophy of the mucosa and mild oedema of the submucosal tissues. Group 3 larynxes showed two distinct pathological changes: oedematous and atrophic types. The larynxes of the atrophic type showed lower clinical scores (29.5±0.7 vs. 44.3±2.1) but higher pathological scores (18.6±3.2 vs. 13.7±1.8) than the larynxes of the oedematous type. ConclusionSevere laryngeal burns could manifest as severe laryngeal oedema or atrophic change. The laryngeal burns of the atrophic type might suggest an unsatisfactory prognosis, although it had less risk of laryngeal obstruction at an early stage.

Scintigraphic comparison of renal ischemia–reperfusion injury models in rats: correlations with biochemical and histopathological findings

This study aimed to compare the effect on renal functions of ischemia-reperfusion (I-R) injury models by renal scintigraphy and to investigate possible correlations among scintigraphic, biochemical and pathological findings. An experimental I-R injury was performed on the left kidneys of 40 Wistar rats: pedincular continuous clamping in Group 1 (n = 10), pedincular cyclic clamping in Group 2 (n = 10), arterial continuous clamping in Group 3 (n = 10) and arterial cyclic clamping in Group 4 (n = 10). A functional and morphological assessment was made by (99m)Tc-MAG3 scintigraphy, biochemical tests and histopathological examination in the late period of I-R injury. Data were analyzed statistically. Statistically significant differences were found in the peak counting (C max), normalized residual activity (NORA), renal retention (RR), split renal function (SRF) and the time to the C max (T max) parameters between the right and left kidneys in each group (p < 0.001). In multiple group comparisons for the left kidney statistically significant differences were determined for C max (F = 4.75, df = 3, p < 0.05), NORA (F = 4.362, df = 3, p < 0.05), RR (F = 10.49, df = 3, p < 0.001) and SRF (F = 4.17, df = 3, p < 0.05) but not T max (F = 1.13, df = 3, p > 0.05). The total scores of Groups 1, 2, 3, and 4 were, respectively, found to be 18, 30, 20 and 24 by grading of renogram curves and 22, 28, 23 and 25 by pathological scoring system. There was a significant correlation among the two score data (r = 0.867, p < 0.001). (99m)Tc-MAG3 scintigraphy was a reliable method to evaluate renal dysfunction in the late period of I-R injury. Cyclic clamping, especially pedincular type was compatible with higher tubular dysfunction and structural damage.

Early surgical outcomes and pathological scoring values of older infants (≥ 90 d old) with biliary atresia

PurposeThis study aimed to analyze the impact of age at Kasai operation on the short-term outcome of type III biliary atresia (BA) and to discuss if pathological scoring can be the prediction of effect in the Kasai procedure for the older (≥90days) infant. MethodsDuring the period 2004 through 2010, 452 infants with type III BA were reviewed. The relationship between ages at Kasai operation and jaundice clearance rates and two year native liver survival rates were assessed, retrospectively. Pathological slides were analyzed with a histological scoring system. ResultsAll of the patients were divided into 3 groups according to their ages at operation (group A: aged 60days or less (n=146), group B: age between 60 and 90days (n=222) , and group C: age on or over 90days (n=84)). The worst outcome of clearance of jaundice was found in group A but not in group C 2weeks after the operation (P<0.05). Jaundice clearance rates showed no difference among the three groups either at 3-months or 6-months after operation. Moreover, in group C patients, the pathological scores showed no difference between the jaundice clearance group and jaundice persistence group 6months after surgery. In group C, two year survival rate of patients with native livers was 36.1%. ConclusionSome patients over 90days of age at surgery can still benefit from a Kasai procedure. The pathological scoring system does not play a role in predicting jaundice clearance in patients over 90days of age at surgery.

Measuring surface temperature and grading pathological changes of airway tissue in a canine model of inhalational thermal injury

BackgroundAirway tissue shows unexpected invulnerability to heated air. The mechanisms of this phenomenon are open to debate. ObjectiveThis study was designed to measure the surface temperatures at different locations of the airway, and to explore the relationship between the tissue's surface temperature and injury severity. MethodTwenty dogs were randomly divided into four groups, including three experimental groups (six dogs in each) to inhale heated air at 70–80°C (group I), 150–160°C (group II) and 310–320°C (group III) and a control group (two dogs, only for histological observation). Injury time was 20min. Mucosal surface temperatures of the epiglottis (point A), cricoid cartilage (point B) and lower trachea (point C) were measured. Dogs in group I–III were divided into three subgroups (two in each), to be assayed at 12, 24 and 36h after injury, respectively. For each dog, four tissue parts (epiglottis, larynx, lower trachea and terminal bronchiole) were microscopically observed and graded according to an original pathological scoring system (score range: 0–27). ResultSurface temperatures of the airway mucosa increased slowly to 40.60±3.29°C, and the highest peak temperature was 48.3°C (group III, point A). The pathological score of burned tissues was 4.12±4.94 (0.0–18.0), suggesting slight to moderate injuries. Air temperature and airway location both influenced mucosal temperature and pathological scores very significantly, and there was a very significant positive correlation between tissue temperature and injury severity. ConclusionCompared to the inhalational air hyperthermia, airway surface temperature was much lower, but was still positively correlated with thermal injury severity.

Discussion on pathological scoring system of drug-induced liver injury

由于肝脏是药物代谢的重要脏器,因此随着各种新药的不断涌现,药物性肝损害(drug-induced liver injury,DILI)逐年增多,已知超过600多种药物可引起DILI[1].由于肝穿刺是一种创伤性的诊断措施,标本来之不易,所以临床对病理诊断的期望值过高,被誉为“金标准”,然而DILI的病理学变化均为非特异性,可见“金标准”在DILI面前显得含金量不足.受慢性肝炎计分[2-3]评估,非酒精性脂肪性肝病活动度评分[4]和国际自身免疫性肝炎组评分[5]的启示,笔者自2000年起注意收集DILI的种种病理学变化资料[1,6-10];并对各病理变化逐一加以评分,形成DILI评分系统(pathological scoring system of DILI,DILI-PSS).自本文第一稿2010年发表于《肝脏》杂志[1]以来,受到广大肝病临床医师关注,并提出很多宝贵意见,经综合后对第一稿作适当修正,希望在应用中再不断加以筛选调整,以期更客观地评估DILI病理因果关系,现介绍如下: 关键词：病理学;药物性肝损伤;评分

Pediatric adrenocortical tumors: morphological diagnostic criteria and immunohistochemical expression of matrix metalloproteinase type 2 and human leucocyte-associated antigen (HLA) class II antigens: Results from the Italian Pediatric Rare Tumor (TREP) Study project

Pediatric adrenocortical tumors are neoplasms that only rarely occur in pediatric patients. Their clinical behavior is often unpredictable, and the histologic criteria of malignancy used in adults are not always useful in children. The aim of this study was to validate the prognostic value of the pathologic criteria of Wieneke et al and to evaluate the potential prognostic expression of matrix metalloproteinase 2 and human leucocyte-associated antigen (HLA) class II antigens in a series of 20 pediatric patients affected by adrenocortical tumors, who were enrolled in the Italian Pediatric Rare Tumor (TREP) Study between 2000 and 2007. The age range was 0 to 17.5 years (mean, 7.28 years) with a male-female ratio of 1:2. The mean follow-up was 64.4 months. The histologic diagnoses were reviewed, and the cases were classified using the criteria for malignancy proposed by Wieneke et al. The immunohistochemical expression of matrix metalloproteinase 2 and HLA class II antigens was scored by semiquantitative analysis and compared with the clinicopathologic parameters and outcome. Based on the scoring system of Wieneke et al, 7 tumors were classified as malignant; 12 tumors, as benign; and only 1 tumor, with "unpredictable behavior." In all cases, the clinical behavior was consistent with the pathologic criteria of Wieneke et al. Notably, areas of regressive myxoid changes, not included among the criteria of Wieneke et al, were observed in all but 1 case of malignant tumors and only in 2 cases of benign tumors. Matrix metalloproteinase 2 was focally to diffusely expressed in all malignant and in most benign tumors. HLA class II antigens immunoreactivity was absent in all benign tumors and restricted to rare isolated cells in most malignant tumors. Our findings confirm that the pathologic scoring system of Wieneke et al is a simple and reproducible diagnostic tool to predict prognosis in pediatric adrenocortical tumors. Unlike in their adult counterpart, the expression of matrix metalloproteinase 2 or the loss of HLA class II antigens does not discriminate between benign and malignant tumors in children. Although pediatric adrenocortical tumors seem to be similar histologically to their adult counterparts, it is likely that they have distinctive molecular features.

Pathology of gastritis and gastric ulceration in the horse. Part 2: A scoring system

High numbers of racehorses in training are reported to have gastric ulceration. Gross lesion scoring systems exist, but there is no fixed protocol with which to record gastric microscopic findings. In man, the histological classification of stomach lesions helps in the identification of recognised and emerging aetiologies of gastric disease and aids accurate comparison of findings between studies. In horses, the development of such a system would therefore be of benefit. To develop a pathological scoring system that can be applied to examine samples of the equine stomach at biopsy and post mortem. The equine gastritis grading (EGG) system was developed initially using horse stomachs at post mortem. The protocol involved sampling tissue from 5 fixed locations within the squamous and glandular regions. Histological examination recorded both type and degree of inflammatory infiltrate and the presence of erosions, ulceration or any other reactive change in each slide. These results were combined and an overall diagnosis of gastritis type given for each stomach. This is the first example of a complete pathological scoring system developed specifically for recording gastric lesions in the horse. It provides a thorough and repeatable method with which to examine the equine stomach in microscopic detail. It can be used in diagnostic or research situations and the consistency of the information gathered will enable accurate comparison of data between different studies. It aims to give an indication as to the currently undetermined pathological variations seen in the stomach of healthy and diseased horses, as well as increasing the understanding of the pathogenesis of gastritis and gastric ulceration. Using this information, interpretation of biopsy samples is improved.