Myelin histology:a key tool in nervous system research

The myelin sheath is a lipoprotein-rich,multilayered structure capable of increasing conduction velocity in central and peripheral myelinated nerve fibers.Due to the complex structure and composition of myelin,various histological techniques have been developed over the centuries to evaluate myelin under normal,pathological or experimental conditions.Today,methods to assess myelin integrity or content are key tools in both clinical diagnosis and neuroscience research.In this review,we provide an updated summary of the composition and structure of the myelin sheath and discuss some histological procedures,from tissue fixation and processing techniques to the most used and practical myelin histological staining methods.Considering the lipoprotein nature of myelin,the main features and technical details of the different available methods that can be used to evaluate the lipid or protein components of myelin are described,as well as the precise ultrastructural techniques.

Retrospective analysis of discordant results between histology and other clinical diagnostic tests on helicobacter pylori infection

BACKGROUND A reliable test is essential for diagnosing Helicobacter pylori(H.pylori)infection,and crucial for managing H.pylori-related diseases.Serving as an excellent method for detecting H.pylori infection,histologic examination is a test that clinicians heavily rely on,especially when complemented with immunohistochemistry(IHC).Additionally,other diagnostic tests for H.pylori,such as the rapid urease test(CLO test)and stool antigen test(SA),are also highly sensitive and specific.Typically,the results of histology and other tests align with each other.However,on rare occasions,discrepancy between histopathology and other H.pylori diagnostic tests occurs.AIM To investigate the discordance between histology and other H.pylori tests,the underlying causes,and the impact on clinical management.METHODS Pathology reports of gastric biopsies were retrieved spanning August 2013 and July 2018.Reports were included in the study only if there were other H.pylori tests within seven days of the biopsy.These additional tests include CLO test,SA,and H.pylori culture.Concordance between histopathology and other tests was determined based on the consistency of results.In instances where histology results were negative while other tests were positive,the slides were retrieved for re-assessment,and the clinical chart was reviewed.RESULTS Of 1396 pathology reports were identified,each accompanied by one additional H.pylori test.The concordance rates in detecting H.pylori infection between biopsy and other tests did not exhibit significant differences based on the number of biopsy fragments.117 discrepant cases were identified.Only 20 cases(9 with CLO test and 11 with SA)had negative biopsy but positive results in other tests.Four cases initially stained with Warthin-Starry turned out to be positive for H.pylori with subsequent IHC staining.Among the remaining 16 true discrepant cases,10 patients were on proton pump inhibitors before the biopsy and/or other tests.Most patients underwent treatment,except for two who were untreated,and two patients who were lost to follow-up.CONCLUSION There are rare discrepant cases with negative biopsy but positive in SA or CLO test.Various factors may contribute to this inconsistency.Most patients in such cases had undergone treatment.

Long-term antiviral efficacy of entecavir and liver histology improvement in Chinese patients with hepatitis B virus-related cirrhosis

AIM: To evaluate the clinical outcomes of 240-wk treatment with entecavir(0.5 mg) in Chinese nucleosidenaive patients with cirrhosis.METHODS: A total of 204 nucleoside-naive patients with compensated(n = 96) or decompensated(n = 108) hepatitis B virus(HBV)-induced cirrhosis at the Department of Gastroenterology of the China-Japan Union Hospital(Jilin University, Changchun, China) who were treated with entecavir(0.5 mg) for 240 wk were enrolled in this study. Liver biopsy samples obtained from 38 patients prior to treatment(baseline) and at week 240 were evaluated by different independent histopathologists. Efficacy assessments included the proportions of patients who achieved an HBV DNA level < 500 copies/m L, the association of interleukin-28 B genetic variation with antivirus therapy, clinical outcomes, and histologic improvement. Changes in liver disease severity were analyzed, and liver histologic evaluation was performed in 38 patients with paired biopsies. Student t tests were used to compare the means of continuous variables between the groups, and the proportions of patients who achieved the endpoints were compared using the χ2 test.RESULTS: At week 240, 87.5% of the patients with compensated cirrhosis and 92.6% of the patients with decompensated cirrhosis achieved a HBV DNA level < 500 copies/m L. Three patients had genotypic entecavir resistance within the 240-wk period. No significant association was observed between virologic response and interleukin-28 genotype(CT, 88.2% vs CC, 90.6%). The proportion of patients with Child-Pughclass A disease was significantly increased at week 240(68%) from the baseline(47%; P < 0.01). The proportion of patients with Child-Pugh class B disease was significantly decreased at week 240(25%) from the baseline(39%; P = 0.02). In the patients with paired liver biopsies, the mean reduction in the Knodell necroinflammatory score from the baseline was 3.58 ± 1.03 points(7.11 ± 1.80 vs 3.53 ± 1.35, P < 0.01). The mean reduction in Ishak fibrosis score from the baseline was 1.26 ± 0.64 points(5.58 ± 0.50 vs 4.32 ± 0.81, P < 0.01).CONCLUSION: Entecavir is an effective treatment option for patients with HBV-related compensated or decompensated cirrhosis that can result in sustained virologic suppression and histologic improvement.

Shear wave elastography results correlate with liver fibrosis histology and liver function reserve

AIM: To evaluate the correlation of shear wave elastography (SWE) results with liver fibrosis histology and quantitative function reserve. METHODS: Weekly subcutaneous injection of 60% carbon tetrachloride (1.5 mL/kg) was given to 12 canines for 24 wk to induce experimental liver fibrosis, with olive oil given to 2 control canines. At 24 wk, liver condition was evaluated using clinical biochemistry assays, SWE imaging, lidocaine metabolite monoethylglycine-xylidide (MEGX) test, and histologic fibrosis grading. Clinical biochemistry assays were performed at the institutional central laboratory for routine liver function evaluation. Liver stiffness was measured in triplicate from three different intercostal spaces and expressed as mean liver stiffness modulus (LSM). Plasma concentrations of lidocaine and its metabolite MEGX were determined using high-performance liquid chromatography repeated in duplicate. Liver biopsy samples were fixed in 10% formaldehyde, and liver fibrosis was graded using the modified histological activity index Knodell score (F0-F4). Correlations among histologic grading, LSM, and MEGX measures were analyzed with the Pearson linear correlation coefficient. RESULTS: At 24 wk liver fibrosis histologic grading was as follows: F0, n = 2 (control); F1, n = 0; F2, n = 3; F3, n = 7; and F4, n = 2. SWE LSM was positively correlated with histologic grading (r = 0.835, P < 0.001). Specifically, the F4 group had a significantly higher elastic modulus than the F3, F2, and F0 groups (P = 0.002, P = 0.003, and P = 0.006, respectively), and the F3 group also had a significantly higher modulus than the control F0 group (P = 0.039). LSM was negatively associated with plasma MEGX concentrations at 30 min (r = -0.642; P = 0.013) and 60 min (r = -0.651; P = 0.012), time to 1/2 of the maximum concentration (r = -0.538; P = 0.047), and the area under the curve (r = -0.636; P = 0.014). Multiple comparisons showed identical differences in these three measures: significantly lower with F4 (P = 0.037) and F3 (P = 0.032) as compared to F0 and significantly lower with F4 as compared to F2 (P = 0.032). CONCLUSION: SWE LSM shows a good correlation with histologic fibrosis grading and pharmacologic quantitative liver function reserve in experimental severe fibrosis and cirrhosis.

Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease

AIM: To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease.METHODS: Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis.RESULTS: Fifty-four participants aged 37.02 &#x000b1; 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-&#x003b1; levels were associated independently with steatosis grade of more than 33% [&#x003b2; = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P &#x0003c; 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [&#x003b2; = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P &#x0003c; 0.05]. Similarly, higher TNF-&#x003b1;, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [&#x003b2; = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P &#x0003c; 0.05]. Serum IL-8 and TNF-&#x003b1; values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [&#x003b2; = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P &#x0003c; 0.05].CONCLUSION: Certain adipokines may determine the severity of NAFLD histology accurately.

Life style modification improves insulin resistance and liver histology in patients with non-alcoholic fatty liver disease

AIM: To study the effect of regular aerobic exercise on insulin resistance, serum aminotransferase and liver histology in nonalcoholic fatty liver disease (NAFLD) patients. METHODS: Sixty (mean age 40.0 ± 8.5 years, 75% male) NAFLD patients were included in the study. After baseline anthropometric measurement i.e., body mass index (BMI), waist circumference (WC); all patients were advised regular aerobic exercise for 30 min/d, for at least 5 d/wk and trained to achieve around 70% of his maximal heart rate. In addition, moderately energy restricted diet was advised to patients with high BMI (> 25 kg/m 2 ). Monthly follow up was done by measuring BMI, WC, aspartate aminotransferase, and alanine aminotransferase (ALT). Insulin resistance was calculated using homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) model, at baseline and after 6mo. Insulin resistance was arbitrarily considered altered when it was ≥ 2. Liver biopsy was done in a section of patients at baseline and after 6 mo. RESULTS: Seventy percent (42/60) patients were overweight or obese; 95% (57/60) had central obesity (WC > 90 cm in men, > 80 cm in women). In the 45 exercise compliant patients insulin resistance decreased from 6.4 ± 6.1 to 1.3 ± 1.0, BMI from 26.7 ± 3.3 kg/m 2 to 25.0 ± 3.3 kg/m 2 , WC from 95.7 ± 8.9 cm to 90.8 ± 7.3 cm and ALT from 84.8 ± 43.5 U/L to 41.3 ± 18.2 U/L (P < 0.01). In 15 exercise noncompliant patient's insulin resistance, BMI, WC and ALT did not show significant change at 6 mo follow up. Six of 8 patients in compliant group on repeat liver biopsy showed significant change in steatosis and necroinflammation. Nonalcoholic steatohepatitis scores improved form 5.3 ± 1.5 to 3.35 ± 1.5. The decline in insulin resistance correlated with decline in ALT (P = 0.01, r s = 0.90) and liver histology (P = 0.03, r s = 0.73). CONCLUSION: Life style modification improves insulin resistance resulting in improvement in ALT and liver histology in NAFLD patients.

Pediatric nonalcoholic fatty liver disease:Overview with emphasis on histology

Nonalcoholic fatty liver disease(NAFLD) is a disease in which excessive fat accumulates in the liver of a patient without a history of alcohol abuse.This disease includes simple steatosis and nonalcoholic steatohepatitis(NASH).NAFLD/NASH is recognized as a hepatic manifestation of metabolic syndrome.In recent years,pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity.The estimated prevalence of pediatric NAFLD is 2.6%-9.6%,and it is associated with sex,age,and ethnicity.With regard to the pathogenesis of NAFLD,the "two-hit" hypothesis is widely accepted and oxidative stress is thought to play an important role in the second hit.Although clinical symptoms,laboratory data,and imaging findings are important,liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH.In addition,liver biopsy is essential for assessing the degree of necro-inflammatory change and fibrosis in NASH.Two different types of steatohepatitis(type 1 and type 2 NASH) have been reported,with type 2 NASH being present in as many as 51% of pediatric NAFLD patients.However,we and others have observed that type 1 and 2 patterns commonly overlap.Although pharmacotherapy has been studied in clinical trials,lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

Ultrasound detection of abdominal lymphadenomegaly in subjects with hepatitis C virus infection and persistently normal transaminases:a predictive index of liver histology severity

AIM The indications for liver biopsy in anti HCV positive patients with persistently normal alanine aminotransferase levels are not clearly established. Recent studies have correlated the presence of abdominal lymphoadenomegaly with disease severity in patients with chronic hepatitis C. Our study aimed to evaluate the frequency of abdominal lymphoadenomegaly in an anti HCV positive blood donor population with persistently normal alanine aminotransferase and the relationship of abdominal lymphoadenomegaly with the severity of liver changes. METHODS Eighty six anti HCV positive blood donors (58 M, 28 F) with normal alanine aminotransferase were followed up for a median of 31 months (range 12-50). To evaluate the frequency of abdominal lymphoadenomegaly, all patients underwent ultrasound scan. The common parameters of liver function as well as serum HCV RNA levels were determined. Histological changes were evaluated both in a conventional manner and using the numerical scoring systems of Knodell and Desmet. RESULTS Of the 86 donors, 68 (79%) maintained persistently normal alanine aminotransferase levels during follow up, and abdominal lymphoadenomegaly was present in 15 of them (22 0%). The remaining 18 donors (21%) showed rises in alanine aminotransferase above normal levels during the follow up and seven of them (38%) had abdominal lymphoadenomegaly ( P =n.s.). In the subjects with normal alanine aminotransferase, there were no significant differences in the common parameters of liver function and the serum presence of HCV RNA between those with or without abdominal lymphoadenomegaly. Normal liver was found in five patients without abdominal lymphoadenomegaly, but never in patients with abdominal lymphoadenomegaly. Analysis with the Mantel Haenszel test showed a trend toward more serious changes in patients with abdominal lymphoadenomegaly (chi square MH=9 5, P <0 003). Histological changes did not differ when Knodell′s score was used; in contrast, staging, evaluated by Desmet′s score, and periportal necrosis were significantly higher in subjects with abdominal lymphoadenomegaly ( P <0 01 and P <0 004, respectively). Multiple logistic regression showed a significant relation between histological changes and the presence in serum of HCV RNA ( P <0 004) and gamma globulin ( P <0 002), and abdominal lymphoadenomegaly ( P <0 003). CONCLUSION Our study shows a prevalence of 22 0% of abdominal lymphoadenomegaly in anti HCV positive subjects with normal alanine aminotransferase values and a relationship with the degree of liver histology change. Therefore, we suggest that the evidence of abdominal lymphoadenomegaly in these patients could be an indication to perform liver biopsy.

From histology to micro-CT:Measuring and modeling resorption cavities and their relation to bone competence

The process of bone remodelling plays an essential role in the emergence and maintenance of bone geometry and its internal structure.Osteoclasts are one of the three main bone cell types that play a crucial role in the bone remodelling cycle.At the microstructural level,osteoclasts create bone deficits by eroding resorption cavities.Understanding how these cavities impair the mechanical quality of the bone is not only relevant in quantifying the impact of resorption cavities in healthy bone and normal aging,but maybe even more so in quantifying their role in metabolic bone diseases.Meta-bolic bone diseases and their treatment are both known to affect the bone remodelling cycle;hence,the bone mechanical competence can and will be affected.How-ever,the current knowledge of the precise dimensions of these cavities and their effect on bone competence is rather limited.This is not surprising considering the difficulties in deriving three-dimensional(3D)properties from two-dimensional(2D)histological sections.The measurement difficulties are reflected in the evalua-tion of how resorption cavities affect bone competence.Although detailed 3D models are generally being used to quantify the mechanical impact of the cavities,the representation of the cavities themselves has basicallybeen limited to simplified shapes and averaged cavityproperties.Qualitatively,these models indicate that cav-ity size and location are important,and that the effectof cavities is larger than can be expected from simplebone loss.In summary,the dimensions of osteoclastresorption cavities were until recently estimated from2D measures;hence,a careful interpretation of resorp-tion cavity dimensions is necessary.More effort needsto go into correctly quantifying resorption cavities usingmodern 3D imaging techniques like micro-computedtomography(micro-CT)and synchrotron radiation CT.Osteoclast resorption cavities affect bone competence.The structure-function relationships have been ana-lysed using computational models that,on one hand,provide rather detailed information on trabecular bonestructure,but on the other incorporate rather crudeassumptions on cavity dimensions.The use of high-resolution representations and parametric descriptionscould be potential routes to improve the quantitativefidelity of these models.

Histology and Ultrastructure of Incompatible Combination Between Puccinia striiformis and Wheat Cultivars with Low Reaction Type Resistance

The incompatible combinations between races of Puccinia striiformis and wheat cultivars with low reaction type resistance were examined by means of fluorescent microscopy, differential interference contrast microscopy and electron microscopy. The incompatible combinations consisted of wheat cultivar Niuzhute plus CY28, Hybrid46 plus CY29 and Tianxuan882 plus CY29, while the compatible combination was wheat cultivar Huixianhong plus CY28. The observation revealed a striking difference in the fungal development and the host responses between susceptible and resistant wheat cultivars following infection by the pathogen. The main histological manifestation of the pathogen development in the resistant wheat cultivars include inhibition of hyphal growth, delay of hyphal branching and colony formation, decrease of formation of haustorial mother cells and haustoria, and occurrence of host cell necrosis. The observation by electron microscopy demonstrated that a series of abnormal changes occurred in intercellular hyphae, haustorial mother cells and haustoria during pathogen development in the resistant wheat cultivars. The cytoplasm became more electron-dense and vacuoles in the cytoplasm increased in number and size. The cell walls of hyphae, haustorial mother cells were thickened irregularly. The organelles were disorderly distributed in the cytoplasm and the haustorial mother cells and haustoria lost their physiological function. In the final stage of the pathogen development, the intercellular hyphae, haustorial mother cells and haustoria became necrotic and collapsed. The structural defense reactions such as formation of cell wall apposition, collar and encasement of haustorium were essentially more pronounced in the infected wheat leaves of the resistant cultivars than in the susceptible one. In addition, the relationship between the host resistance expression and the histological and cytological features occurred in the incompatible combination was discussed in this paper.

Real-time histology with the endocytoscope

Endoscopic Imaging has progressed tremendously over the last few decades. Novel imaging technologies such as high-resolution and high-magnification white light endoscopy, narrow band imaging, optimal band imaging, auto? ourescence imaging and optical coherence tomography not only aid the endoscopist in detecting malignant or pre-malignant lesions but also assist in predicting histology. Recently, the introduction of Endocytoscopy (EC) and Confocal Endomicroscopy has taken us into a new realm of diagnostic endoscopy. With the ability to magnify up to 1000 ×, cellular structures can be visualized in real-time. This advance in technology could potentially lead to a paradigm shift negating the need to obtain biopsies. EC is, however, still in the early stages of development and further research needs to be carried out before it can be accepted as standard practice. This review will focus on the diagnostic utility of the Endocytoscope.

Normal liver stiffness: a study in living donors with normal liver histology

AIM: To define the normal range of liver stiffness(LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50(16 women, 34 men) healthy potential donors(mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m2. All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes.RESULTS: The mean LS was 4.3 ± 1.2 k Pa(range: 1.8-7.1 k Pa). The 5th and 95 th percentiles of normal LS were 2.6 k Pa and 6.8 k Pa, respectively, with a median of 4 k Pa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women(4.4 ± 1.1 k Pa vs 3.9 ± 1.3 k Pa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m2 compared to those with an index ≥ 26 kg/m2(4.0 ± 1.1 k Pa vs 4.6 ± 1.2 k Pa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels(at discharge) between donors with livers stiffness ≤ 4 k Pa and those with stiffness > 4 k Pa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 k Pa. Stiffness values are elevated relative to increase in body mass index.

Liver histology in ICU patients dying from sepsis:A clinico-pathological study

AIM:To determine end-stage pathologic changes in the liver of septic patients dying in the intensive care unit. METHODS: Needle liver biopsies obtained immediately after death from 15 consecutive patients with sepsis and no underlying liver disease were subjected to routine histological examination. Liver function tests and clinical monitoring measurements were also recorded. RESULTS: Liver biochemistries were increased in the majority of patients before death. Histology of liver bi- opsy specimens showed portal inflammation in 73.3%, centrilobular necrosis in 80%, lobular inflammation in 66.7%, hepatocellular apoptosis in 66.6% and cholan- gitis/cholangiolitis in 20% of patients. Mixed hepatitic/ cholestatic type of liver injury was observed in 6/15 (40%) patients and hepatitc in 9/15 (60%). Steatosis was ob- served in 11/15 (73.3%) patients affecting 5%-80% of liver parenchyma. Among the histological features, the presence of portal inflammation in liver biopsy was as- sociated with increased hospitalization in the ICU prior death (P = 0.026). CONCLUSION: Features of hepatitis and steatosis arethe main histological findings in the liver in the majority of patients dying from sepsis.

Relationship between hepatitis B virus DNA levels and liver histology in patients with chronic hepatitis B

AIM： To study the relationship between hepatitis B virus （HBV） DNA levels and liver histology in patients with chronic hepatitis B （CHB） and to determine the prevalence and characteristics of hepatitis B e antigen （HBeAg） negative patients.METHODS： A total of 213 patients with CHB were studied, and serum HBV DNA levels were measured by the COBAS Amplicor HBV Monitor test. All patients were divided into two groups according to the HBeAg status.The correlation between serum HBV DNA levels and liver damage （liver histology and biochemistry） was explored.RESULTS： Of the 213 patients with serum HBV DNA levels higher than 10^5 copies/mL, 178 （83.6%） were HBeAg positive, 35 （16.4%） were HBeAg negative. The serum HBV DNA levels were not correlated to the age,history of CHB, histological grade and stage of liver disease in either HBeAg negative or HBeAg positive patients. There was no correlation between serum levels of HBV DNA and alanine aminotransferanse （ALT）,aspartate aminotrans-ferase （AST） in HBeAg positive patients. In HBeAg negative patients, there was no correlation between serum levels of HBV DNA and AST,while serum DNA levels correlated with ALT （r = 0.351, P = 0.042）. The grade （G） of liver disease correlated with ALT and AST （P 〈 0.05, r = 0.205, 0.327 respectively）in HBeAg positive patients. In HBeAg negative patients,correlations were shown between ALT, AST and the G （P 〈 0.01, and r = 0.862, 0.802 respectively）. HBeAg negative patients were older （35 ± 9 years vs 30 ±9 years, P 〈 0.05 ） and had a longer history of HBV infection （8 ± 4 years vs 6 ± 4 years, P 〈 0.05） and a lower HBV DNA level than HBeAg positive patients （8.4± 1.7 Log HBV DNA vs 9.8 ± 1.3 Log HBV DNA, P 〈0.001）. There were no significant differences in sex ratio,ALT and AST levels and liver histology between the two groups.CONCLUSION： Serum HBV DNA level is not correlated to histological grade or stage of liver disease in CHB patients with HBV DNA more than 10^5 copies/mL.Compared to HBeAg positive patients, HBeAg negative patients are older and have a lower HBV DNA level and a longer HBV infection history. There is no significant difference in sex ratio, ALT and AST levels and liver histology between the two groups.

Usefulness of a scoring system in the interpretation of histology in neonatal cholestasis

AIM:To ascertain the usefulness of a histological scoring system devised to assist in the interpretation of liver histology in neonatal cholestasis(NC) .METHODS:Liver biopsy specimens obtained from infants with NC referred to a tertiary pediatric unit in Malaysia were prospectively studied.The first author,blinded to the final diagnosis,devised the histological diagnosis based on a 7-feature(portal ductal proliferation,bile plugs in portal ductules,portoportal bridging,lymphocytic infiltration in portal region,multinucleated hepatocytes,neutrophilic infiltration,hepatocellular swelling) ,15-point(0 to 15) scoring system.The author classified the histological diagnosis as either biliary atresia(BA) or neonatal hepatitis(NH,all other diagnoses) ,and subsequently compared the author's diagnosis with the final diagnosis.RESULTS:Eighty-four biopsy specimens obtained from 78 patients were reviewed.Without the scoring system,BA was correctly diagnosed by the author histologically in 30 cases,labelled as NH in 3.For other diagnoses,BA was excluded correctly in 33 cases and mislabeled as BA in 2 cases.The overall sensitivity for BA was 91%,specificity 86% and accuracy 88%.With the scoring system,a score of ≥ 7 had the best diagnostic utility to differentiate BA from other intrahepatic cholestasis histologically(sensitivity 88%,specificity 94%,accuracy 92%) .Four patients with a score < 7 had BA,and 3 patients with a score ≥ 7 had NH.CONCLUSION:A 7-feature,15-point histological scoring system had good diagnostic accuracy in the interpretation of liver histology in neonatal cholestasis.

Risk factors of gastric cancer specific for tumor location and histology in Cali,Colombia

AIM- To examine histology- and tumor-location specific risk factors of gastric cancer （GC）.METHODS： This was subjects were 216 GC the period 2000-2002 non-cancer patients hospital. We obtained habits, and others by a a case-control study. The study patients newly diagnosed during and 431 controls selected from matching in age, gender, and information on lifestyles, dietary questionnaire.RESULTS： The subjects who were not eldest among his/her siblings were at a slightly elevated GC risk （OR 1.3; 95% CI 0.8-2.0）. Salting meals before tasting was related to an increased GC risk （OR 3.5; 95% CI 1.6- 7.3）. Frequent consumptions of fruits （OR 0.3; 95% CI 0.1-1.0） and vegetables （OR 0.3; 95% CI 0.1-1.0） were related to decreased GC risks. On the other hand, frying foods （OR 1.9; 95% CI 1.0-3.6） and cooking with coal （OR 1.8; 95% CI 1.3-2.6） were related to increased GC risks. Neither Lauren＇s histological classification （intestinal and diffuse types） nor tumor location significantly affected those associations except birth order. The subjects who were not eldest among his/her siblings had an increased risk of GCs in the distal and middle thirds, and their ORs were 1.7 （95% CI 1.0-2.8） and 1.9 （95% CI 0.8-4.3）, respectively. The corresponding OR in the upper third stomach was 0.3 （95% CI 0.1-0.9）. The differences of those three ORs were statistically significant （P = 0.010）.CONCLUSION： The present study shows that birth order, salt intake, consumption of fruits and vegetables, the type of cooking, and cigarette smoking are related to GC risk. In histology and tumor-location specific analyses, non-eldest person among their siblings is related to an increased GC risk in the distal and middle thirds of the stomach, and is related to a decreased GC risk in the cardia.

Liver histology according to the presence of metabolic syndrome in nonalcoholic fatty liver disease cases

AIM:To investigate the histologic features of the liver in nonalcoholic fatty liver disease (NAFLD) cases according to the presence of metabolic syndrome or its individual components. METHODS:We enrolled 81 patients (40 male,41 fe-male) who were diagnosed with fatty liver by ultraso-nographic scan and fulfi lled the inclusion criteria. First anamnesis,anthropometric,clinical,laboratory and imaging features of all participants were recorded and then liver biopsy was performed after gaining consent from patients. Diagnosis of metabolic syndrome was dependent on patients having 3 or more out of 5 risk criteria defined by the WHO. Biopsy specimens were assessed according to Brunt et al's classification. RESULTS:Sixty-nine of the 81 patients had nonalco-holic steatohepatitis (NASH),11 had simple fatty liver and 1 had cirrhosis according to histologic evaluation. Comparisons were made between two groups of NASH patients,those with and without metabolic syndrome. We did not detect statistically significant differences in liver histology between NASH patients with and wit-hout metabolic syndrome. CONCLUSION:NASH can progress without metabolic risk factors or the presence of metabolic syndrome.

Changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer

AIM: To investigate the changes of histology and expression of MMP-2 and nm23-H1 in primary and metastatic gastric cancer. METHODS: One hundred and seventy-seven gastric cancer patients with lymph node and/or distal metastasis between 1997 and 2001 were reviewed. Differences in histology of the primary and metastatic gastric cancer were assessed. MMP-2 and nm23-H1 immunoreactivity was compared in 44 patients with tumor infiltration to the serosa layer. RESULTS: Poorly and moderately differentiated metastatic gastric cancer was found in 88.7% (157/177) and primary gastric cancer in 75.7% (134/177) of the patients. The histological type of metastatic gastric cancer that was not completely in accordance with the preponderant histology of primary gastric cancer was observed in 25 patients (14.1%). MMP-2 immunoreactivity in metastatic gastric cancer was significantly stronger than that in primary gastric cancer, while nm23-H1 immunoreactivity showed no difference in primary and metastatic gastric cancer. CONCLUSION: Metastatic gastric cancer presents more aggressive histological morphology and higher MMP-2 immunoreactivity than primary gastric cancer. This heterogeneity may elicit a possible mechanism of gastric cancer metastasis.

Metastatic pattern in esophageal and gastric cancer:Influenced by site and histology

BACKGROUND Detailed information on metastatic patterns in of patients with esophageal and gastric cancer is limited.Early recognition of metastases is important to avoid futile locoregional treatments.Furthermore,knowledge on metastatic patterns is necessary for further development of personalized treatment modalities.AIM To gain insight into the metastatic pattern of gastroesophageal cancer.METHODS A nationwide retrospective autopsy study of 3876 patients with adenocarcinoma(AC)or squamous cell carcinoma(SCC)of the esophagus or stomach between 1990 and 2017 was performed.Only patient with metastases were included for analysis.The metastatic pattern was analyzed according to the primary tumor location and histological subtype.RESULTS Metastatic disease was found in 268 esophageal and 331 gastric cancer patients.In esophageal cancer,the most common metastatic locations were liver(56%),distant lymph nodes(53%)and lung(50%).Esophageal AC showed more frequently metastases to the peritoneum and bone compared with esophageal SCC.In gastric cancer,the most common metastatic locations were distant lymph nodes(56%),liver(53%)and peritoneum(51%).Intestinal-type AC of the stomach showed metastases to the liver more frequently,whereas metastases to the bone,female reproductive organs and colorectum were observed more frequently in diffuse-type gastric AC.CONCLUSION This study showed differences in metastatic patterns of patients with esophageal and gastric cancer according to the primary tumor location and histological subtype.

Morphology and Histology of Lattice-like Ossified Epaxial Tendons in Psittacosaurus(Dinosauria:Ceratopsia)

Epaxial tendons play an important role in the study of the musculoskeletal system and locomotory style of dinosaurs. Although the ossified epaxial tendon lattice is fairly well known in Iguanodontoidea, only recently has knowledge of this complex been extended to ceratopsians. This study concerns the gross morphology and microstructure of the tendon lattice in Psittacosaurus, a basal ceratopsian. As in the neoceratopsian Chasmosaurus, the ossified tendons of Psittacosaurus form a three -layered, lattice-like structure. The microstructure of the tendons in large psittacosaur individuals retains an early stage of ossification, as in juvenile birds and nestling hadrosaurs, suggesting a slow developmental rate of ossification of the tendons in psittacosaur ontogeny. Comparative study indicates that a lattice-like arrangement of three-layered epaxial tendons is widely distributed in Cerapoda. This pattern also extends to Ankylosauria, implying a similar pattern of the epaxial muscles through the ornithischian clade. In addition, comparison with crocodiles implies that the different morphology of ossified tendons in dinosaurs may be associated with adaptive aspects of their paleobiology, not simply a side effect of skeletal ossification. In contrast to the short tendons in quadrupedal Chasmosaurus and Protoceratops, the elongated tendons in Psittacosaurus may be related to the bipedal locomotion characteristic of this taxon.