OtoRhinoLaryngology News: 01/12/18

Παρασκευή 12 Ιανουαρίου 2018

A case of radiation induced osteosarcoma of the skull presenting as a cutaneous epidermotropic tumour with a short latent period

Abstract

Radiation induced sarcoma is an unusual but well documented tumor. The frequency of radiation induced sarcoma of the head and neck region has been reported as 0.143%. In the literature the median interval between irradiation and development of sarcoma is 11 years. Cases of RIS with a short latent period i.e. less than four years are rare. We report a case of a 34 year-old female who developed an osteosarcoma of the scalp, over a previous craniotomy scar, three years after excision of a frontal anaplastic oligodendroglioma which had been followed by a course of 6 weeks radiotherapy (58 Gy) and 6 cycles of Temozolomide. The histological features were those of a high-grade osteosarcoma with epidermotropism of tumor cells. Lymph nodes were partially replaced by high-grade metastatic osteosarcoma with extra-nodal lymphatic tumor thrombi. To our knowledge the only other case report of post-radiation osteosarcoma with a short latency period was a case of osteosarcoma in the craniofacial bone three years after radiotherapy for maxillary squamous cell carcinoma. The histological finding of prominent replacement of the epidermis by osteosarcoma has not been reported before.

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Dermatomyositis: histopathologic findings of parakeratosis and dermal edema revisited

Abstract

The cutaneous manifestations of dermatomyositis range from classical in the case of heliotrope rash and Gottron papules to less common papulosquamous and edematous/vesiculobullous lesions; histopathologic descriptions are dominated by interface dermatitis. We present a case of dermatomyositis with a combination of common and rare skin findings, both clinically and histologically. Increased awareness of papulosquamous and edematous lesions of dermatomyositis can help direct patient care. Although uncommon, confluent parakeratosis and dermal edema can be manifestations of dermatomyositis.

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Extracorporeal Shockwave Therapy for Treatment of Keloid Scars

Abstract

The purpose of this investigation was to study the effectiveness of extracorporeal shockwave therapy (ESWT) for the treatment of keloid scars, and compared the results with intralesional steroid injection. Thirty-nine patients were randomly divided into 22 in ESWT group and 17 in steroid group. The ESWT group received 3 ESWT treatments in 6 weeks. The steroid group received 3 intra-lesional triamcinolone injections in 6 weeks. The evaluations included gross morphology, functional outcome, local blood flow perfusion, biopsy for histopathological examination and immunohistochemical analysis. Both groups showed significant improvements in appearance with less discoloration, flattening and softer consistency and more elasticity of the lesions. There is a significant reduction in keloid height after treatment in both groups, and significant differences are noticed between two groups after treatment. The volume of keloid was decreased after treatment but there is no statistically significant difference between two groups. Both groups showed comparable functional scores, POSAS patient and observer scales. The blood flow perfusion rates were statistically not significant between two groups before and after treatments. Histopathological findings revealed no significant difference in cell count, cell activity and cell concentration between two groups. After ESWT, the significant decreases in collagen type I, type III and Masson Trichrome stain were observed as compared to steroid group. However, very little changes were noticed in angiogenesis, inflammatory cytokines, proliferating and regeneration, and apoptosis, with no statistical significance noticed between two groups before and after treatment. This study revealed that ESWT showed comparable functional outcome and POSAS patient and observer scales as compared to steroid injection for keloid scars. Treatment of keloid scars with ESWT resulted in significant decreases in collagen fibers and increases in MMP-13 enzyme. This article is protected by copyright. All rights reserved.

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The Identity of “Chromium Malate”

Abstract

Recently, several studies on the effects of a compound named "chromium malate," with the proposed formula "Cr₂malate₃·xH₂O" where x = 3.5 or 5, on the health of healthy and diabetic rats have appeared. However, the compound is poorly characterized, and knowing the identity of this material could be important in the interpretation of the previous and of future studies on the effects of this compound in animals. Consequently, the synthesis, characterization, and identity of this material were explored. A combination of spectroscopic, magnetic, and elemental analyses and mass spectral studies reveal that the compound is probably a polymer, not a discrete molecule, and does not have the composition previously reported. The repeating unit of the polymer possesses an antiferromagnetically coupled trinuclear Cr(III) core. The current study suggests that previous reports on chromium malate and its effects in animals must be viewed with caution.

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Effect of the Zinc Oxide Nanoparticles and Thiamine for the Management of Diabetes in Alloxan-Induced Mice: a Stereological and Biochemical Study

Abstract

This research was carried out to evaluate the antidiabetic effects of zinc oxide nanoparticles (ZnO NPs) and thiamine following experimental diabetes. Fifty-six 6-week-old female mice were used and divided into seven groups of eight animals. Diabetes was induced in fasted mice by using intraperitoneal (IP) injection of alloxan (180 mg/kg). Groups included (I) non-diabetic control, (II) thiamine (30 mg/l, IP), (III) alloxan-induced diabetic mice, (IV) diabetes + ZnO NPs (0.1 mg/kg IP), (V) diabetes + ZnO NPs (0.5 mg/kg IP), (VI) diabetes + ZnO NPs (0.1 mg/kg IP) + thiamine (30 mg/l, IP), and (VII) diabetes + ZnO NPs (0.5 mg/kg IP) + thiamine (30 mg/l, IP). Coincident with pancreas recovery, in diabetic treated mice (groups IV to VII), the mean islet volume, islets per square micrometer, and volume density of the pancreas had increased than in alloxan-induced diabetic mice. ZnO NPs and thiamine induced a decreasing blood glucose, lower serum triglyceride (TG), LDL, and total cholesterol (TC) levels in alloxan-induced diabetic mice treated with ZnO NPs and thiamine, simultaneously increasing HDL as well. In conclusion, ZnO NPs and thiamine are potent antidiabetic factors, and that, these compound supplementation possesses hypoglycemic properties and have effect on serum lipid parameters in diabetes mice.

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Effects of Maternal Zinc Glycine on Mortality, Zinc Concentration, and Antioxidant Status in a Developing Embryo and 1-Day-Old Chick

Abstract

This study was conducted to investigate the effects of maternal zinc glycine (Zn-Gly) supplementation as an alternative for zinc sulfate (ZnSO₄) on mortality, zinc (Zn) concentration, and antioxidant status in a developing embryo and 1-day-old chick. Six hundred 39-week-old broiler breeders were randomly assigned to 6 treatments, each treatment including 5 replicates with 20 birds each. Six treatments received a basal diet (control, 24 mg Zn/kg diet) or a basal diet supplemented with ZnSO₄ (80 mg Zn/kg) or Zn-Gly (20, 40, 60, or 80 mg Zn/kg), respectively. The experiment lasted for 8 weeks after a 4-week pre-experiment with a basal diet. At the last week, 100 eggs per replicate were randomly collected for incubation. Compared with the control treatment, Zn supplementation decreased (P < 0.05) embryo mortalities of the late stage and the whole period, increased (P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick, and improved (P < 0.05) antioxidant status in the embryo of d19 and 1-day-old chick. Compared with the ZnSO₄ treatment, 80 mg Zn/kg Zn-Gly treatment significantly decreased (P < 0.05) the late stage embryo mortality and increased (P < 0.05) liver Zn concentration in the embryo of d9, d19, and 1-day-old chick. The 80 mg Zn/kg Zn-Gly treatment significantly increased (P < 0.05) copper-zinc superoxide dismutase activity in d19 embryo and 1-day-old chick, total superoxide dismutase activity in 1-day-old chick, and copper-zinc superoxide dismutase messenger RNA (mRNA) abundance of d9 embryo and 1-day-old chick than that in ZnSO₄ treatment. The liver metallothionein concentration of the developing embryo and 1-day-old chick and its mRNA abundance of d19 embryo were also significantly increased (P < 0.05) in the 80 mg Zn/kg Zn-Gly treatment in comparison with ZnSO₄ treatment. In conclusion, maternal Zn supplementation decreased embryo mortalities of the late stage and the whole period by increasing liver Zn concentration and antioxidant status in d19 embryo and 1-day-old chick, and 80 mg Zn/kg from Zn-Gly treatment was the optimum choice.

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Maternal Magnesium Restriction Elevates Glucocorticoid Stress and Inflammation in the Placenta and Fetus of WNIN Rat Dams

Abstract

Magnesium plays a major role in many vital functions in the body. We reported earlier that maternal magnesium restriction altered body composition, fat metabolism, and insulin resistance in WNIN rat offspring and was associated with increased glucocorticoid stress in the offspring in their later life. We hypothesize that increased glucocorticoid stress and inflammation which originate in Mg restricted rat dams is transmitted through placenta to the fetus and underlie the metabolic disturbances in the later life of the offspring. Female weanling WNIN rats received ad libitum, a control diet (MgC) or the same with 62% restriction of Mg (MgR) for 3 months, and their plasma magnesium, inflammatory cytokines, and corticosterone were determined (n = 6 per group) before mating. Following mating with control males, placentae, and fetuses were collected on gestational day 15 (GD 15) from MgC and MgR dams (eight dams from each group and three samples from each dam) and used to determine the levels of inflammatory cytokines, corticosterone, and expression of relevant genes. MgR placentae and fetuses had higher (than MgC) levels of corticosterone and proinflammatory cytokines. Expression of Hsd11b1 was increased (sixfold, p < 0.05), while that of Hsd11b2 was decreased (0.4-fold, p < 0.05) in MgR (than MgC) placenta, whereas expression of Hsd11b1was increased (3.4-fold, p < 0.05) in MgR fetus. Chronic dietary magnesium restriction in WNIN female rats increased their levels of corticosterone, leptin, and proinflammatory cytokines which appeared to be transmitted through placenta to the fetus and could thus be associated with increased stress, altered body composition, fat metabolism, and insulin resistance in the later life of the offspring.

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Serum and Hair Zinc Levels in Patients with Endemic Osteochondropathy in China: A Meta-analysis

Abstract

A large number of studies have shown growing interest in the zinc (Zn) levels of serum and hair samples collected from patients with Kashin-Beck disease (KBD), an endemic chronic osteochondral disease. However, inconsistent conclusions regarding the serum and hair Zn levels have been made. The aim of this study is to assess and to explore the change in serum and hair Zn levels among KBD patients. Multiple databases, including PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang database and Technology of Chongqing (VIP), were carefully searched for available studies up to January 13, 2017 in this integrated analysis. Standard mean difference (SMD) with a 95% confidence interval (95% CI) was calculated using STATA 11.0. A total of 18 studies, involving 978 KBD cases and 1116 healthy controls, were collected in this analysis. Pooled analysis found the KBD patients had a higher hair Zn level and a lower serum Zn level than the healthy controls (hair Zn (μg/g), SMD = 0.030, 95% CI = −0.315, 0.376; serum Zn (mg/L), SMD = −0.069, 95%CI = −0.924, 0.785). Meta-regression method and sensitivity analysis were utilized to analyze the heterogeneity of data. Positive correlations were separately identified between hair Zn level in KBD patients (r = 0.4639, P = 0.032) and controls (r = 0.4743, P = 0.012) and the survey year. No evidence of publication bias was observed. The available results suggest that increased hair Zn level and decreased serum Zn level are commonly found in KBD patients; however, the role of Zn in the etiology and pathogenesis of KBD could not yet be confirmed.

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Effects of Different Selenium Sources on Growth Performance, Antioxidant Capacity and Meat Quality of Local Chinese Subei Chickens

Abstract

Despite increasing evidence indicating the essential involvement of selenium (Se) on growth performance, antioxidant capacity, and meat quality of commercial broilers, the effects of different Se sources on local Chinese Subei chickens is unclear. A total of 360 50-day-old male chickens were individually weighed and randomly allocated to four treatment groups. Chickens in each of the four groups were fed diets supplemented with 0.3 mg Se/kg as sodium Se (SS), Se-enriched yeast (SY), selenomethionine (Met-Se), or nano red element Se (Nano-Se) for 40 days. At the end of the experiment, one bird of approximately average weight from each cage was selected and slaughtered, and blood and breast muscles samples were collected. The results showed that there was no significant difference in feed intake, body weight gain, or feed to gain ratio among treatments (P > 0.05). Dietary SY, Met-Se, and Nano-Se supplementation increased the activity of glutathione peroxidase in serum and breast muscles and decreased the concentration of malondialdehyde in serum and carbonyl in breast muscles compared with the SS group (P < 0.05). Moreover, SY, Met-Se, and Nano-Se supplementation increased pH_45min, total protein solubility, and myofibrillar protein solubility, as well as decreased the shear force value compared with the SS group (P < 0.05). In addition, birds in the SY and Met-Se groups exhibited lower cooking loss compared with the SS group (P < 0.05). In conclusion, organic Se and Nano-Se supplementation resulted in an improvement of antioxidant capacity and meat quality in local Chinese Subei chickens relative to inorganic Se.

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The Antagonistic Effect of Selenium on Cadmium-Induced Damage and mRNA Levels of Selenoprotein Genes and Inflammatory Factors in Chicken Kidney Tissue

Abstract

Selenium (Se) is a necessary trace mineral in the diet of humans and animals. Cadmium (Cd) is a toxic heavy metal that can damage animal organs, especially the kidneys. Antagonistic interactions between Se and Cd have been reported in previous studies. However, little is known about the effects of Se against Cd toxicity and on the mRNA levels of 25 selenoprotein genes and inflammatory factors in chicken kidneys. In the current study, we fed chickens with a Se-treated, Cd-treated, or Se/Cd treated diet for 90 days. We then analyzed the mRNA expression of inflammatory factors (including prostaglandin E synthase (PTGES), nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and cyclooxygenase-2 (COX-2)) and 25 selenoprotein genes (Gpx1, Gpx2, Gpx3, Gpx4, Txnrd1, Txnrd2, Txnrd3, Dio1, Dio2, Dio3, SPS2, Sepp1, SelPb, Sep15, Selh, Seli, Selm, Selo, Sels, Sepx1, Selu, Selk, Selw, Seln, Selt). The results demonstrated that Cd exposure increased the Cd content in the chicken kidneys, renal tubular epithelial cells underwent denaturation and necrosis, and the tubules became narrow or disappeared. However, Se supplementation reduced the Cd content in chicken kidneys and induced normal development of renal tubular epithelial cells. In addition, we also observed that Se alleviated the Cd-induced increase in the mRNA levels of inflammatory factors and ameliorated the Cd-induced downtrend in the mRNA levels of 25 selenoprotein genes in chicken kidneys.

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Effects of Selenium Supplementation on Gene Expression Levels of Inflammatory Cytokines and Vascular Endothelial Growth Factor in Patients with Gestational Diabetes

Abstract

Selenium is known to exert multiple beneficial effects including anti-inflammatory actions. The aim of the study was to evaluate the effects of selenium supplementation on gene expression levels of inflammatory cytokines and vascular endothelial growth factor (VEGF) in women with gestational diabetes (GDM). This randomized double-blind, placebo-controlled trial was carried out among 40 subjects diagnosed with GDM aged 18–40 years old. Subjects were randomly allocated into two groups to receive either 200 μg/day selenium supplements (n = 20) or placebo (n = 20) for 6 weeks. Gene expression of inflammatory cytokines and VEGF were assessed in lymphocytes of GDM women with RT-PCR method. Results of RT-PCR indicated that after the 6-week intervention, compared with the placebo, selenium supplementation downregulated gene expression of tumor necrosis factor alpha (TNF-α) (P = 0.02) and transforming growth factor beta (TGF-β) (P = 0.01), and upregulated gene expression of VEGF (P = 0.03) in lymphocytes of patients with GDM. There was no statistically significant change following supplementation with selenium on gene expression of interleukin (IL)-1β and IL-8 in lymphocytes of subjects with GDM. Selenium supplementation for 6 weeks in women with GDM significantly decreased gene expression of TNF-α and TGF-β, and significantly increased gene expression of VEGF, but did not affect gene expression of IL-1β and IL-8. Clinical trial registration number http://www.irct.ir: IRCT201612045623N95.

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The Relationship Between Copper, Iron, and Selenium Levels and Alzheimer Disease

Abstract

This study aimed to evaluate the concentrations of copper, iron, and selenium in elderly people with Alzheimer disease (AD), comparing the same parameters in a paired group of healthy people, in order to verify if the amount of these metals may influence the cognitive impairment progression. Patients' cognitive impairment was evaluated by Clinical Dementia Rating (CDR). The elementary quantification of erythrocytes was performed by inductively coupled plasma mass spectrometry technique. The statistical analyses were carried out by SPSS software 20.0 version, employing Shapiro-Wilk, Wilcoxon, Kruskall-Wallis, and Spearman correlation tests, considering significant results of p < 0.05. The sample was composed of 34% (n = 11) of women and 66% (n = 21) of men in each group. The AD group was characterized by a higher concentration of copper (p < 0.0001) and iron (p < 0.0001); however, there is no significant difference in selenium level. The analyses of the metal levels in different stages of AD were not significant in CDR-1, however in CDR-2 and CDR-3, elevated levels of copper and iron were observed; in CDR-3 patients, the level of selenium was lower (p < 0.008) compared to that of healthy controls. Patients with Alzheimer disease studied present increase in biometal blood levels, especially of copper and iron, and such increase can be different according to the disease stage and can cause more impairment cognitive functions in AD.

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Dose-Dependent Differential Effects of In Vivo Exposure of Cadmium on Myometrial Activity in Rats: Involvement of VDCC and Ca 2+ -Mimicking Pathways

Abstract

Present study was undertaken to study the effect of 28-days exposure of female adult rats to cadmium (Cd) in drinking water @ 3, 10 and 30 parts per million (ppm) on myometrial responsiveness to different spasmogens and unravel the possible mechanism of alterations in myometrial activity. Cadmium and Ca²⁺ levels in blood and uterus were measured by atomic absorption spectroscopy while isometric tension in myometrial strips was measured using data acquisition system-based physiograph. Dose-dependent increase in levels of cadmium was observed in both blood and uterus while calcium was increased only in the uterus as compared to those in control. Significant increase in absolute tension and mean integral tension along with non-significant increase in frequency of myometrial contraction was observed in rats of Cd-treated groups. As compared to the control, cadmium decreased and increased the effects of calcium chloride, 80 mM KCl, histamine (0.1 μM) and oxytocin (10⁻² IU/ml) in lower-dose (3 ppm) and higher-dose groups (10 and 30 ppm), respectively. Cadmium potentiated and inhibited the relaxant response to phenylephrine in myometrium of rats at lower-dose (3 ppm) and highest-dose (30 ppm) Cd-treated groups, respectively. Results of our study revealed that Cd accumulates in the myometrium of rats and alters its responsiveness to oxytocin, histamine, 80 mM KCl, calcium chloride and phenylephrine, and these effects are differentially mediated depending on levels of exposure possibly through voltage-dependent calcium channel (VDCC) and Ca²⁺-mimicking pathways.

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Arsenic Induces Thioredoxin 1 and Apoptosis in Human Liver HHL-5 Cells

Abstract

To further characterize the mechanisms underlying liver toxicity induced by arsenic, we examined in this study the effect of arsenic on thioredoxin (Trx) and the apoptotic signaling pathways in human liver HHL-5 cells. The cells were treated with 0, 2, 5, and 10 μM of sodium arsenite for 24 h, and the changes of Trx1 and thioredoxin reductase (TrxR1) as well as intracellular ROS and apoptosis were examined. A concentration-dependent increase in mRNA and protein levels of Trx1 and TrxR1 was observed in arsenic-treated cells. Intracellular ROS levels and apoptosis were also significantly increased in a concentration-dependent manner. In line with this, protein levels of Bax and cytochrome C were increased and Bcl-2 was decreased by arsenic treatments. Increases in caspase 3 activity were observed. These results indicate that Trx is involved in arsenic-induced liver cell injury, probably through the apoptotic signaling pathway. However, further studies are needed to elucidate on these findings.

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Associations Between Serum Zinc Levels and Mental Health: Findings from the 2010 Korean National Health and Nutrition Examination Survey

Abstract

Mental health problems are a major public health issue worldwide, and zinc may be associated with psychiatric symptoms, but such associations have not been investigated extensively. This study was conducted to evaluate the relationship between serum zinc levels and mental health problems in Korean adults. We used data from the Korean National Health and Nutrition Examination Survey V-1, a cross-sectional survey of Korean civilians. Data from 1748 subjects were analyzed. Serum zinc levels did not differ significantly according to psychiatric symptoms including sleep duration, stress, depressed mood, suicidal ideation, and whether respondents sought psychiatric consultation. The frequencies and odds ratios of psychiatric symptoms according to serum zinc tertiles were not significantly associated after adjusting for age, smoking, alcohol consumption, physical activity, body mass index, total body fat, and renal function and for daily fat, carbohydrate, and protein intake. Serum zinc levels may not be associated with psychiatric symptoms in Korean adults without psychiatric disorders.

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Microenvironmental Scenario of the Bone Marrow of Inorganic Arsenic-Exposed Experimental Mice

Abstract

Exposure to arsenic on a regular basis, mainly through drinking water, agricultural pesticide, and sometimes therapeutic dose, results in various diseases of different tissues including the bone marrow hematopoietic system. Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally mature blood cells by the support of microenvironmental components. The present study has been aimed to understand stem cell microenvironmental status during arsenic toxicity and the consequent reflection of dysregulation involving the hematopoietic machinery in experimental mice. Swiss albino mice were experimentally exposed to 10 μg arsenic trioxide/g body weight through oral gavage and 5 μg arsenic trioxide/g body weight intraperitoneally for a period of 30 days. Altered hemogram values in peripheral blood reflected the impaired hematopoiesis which was further validated by the reduced BM cellularity along with the deviated BM cell morphology as observed by scanning electron microscopy post arsenic exposure. The stromal cells were unable to establish a healthy matrix and the sustainability of hematopoietic progenitors was drastically affected in arsenic-exposed mouse groups, as observed in in vitro explant culture. The inability of stromal cells to establish supportive matrix was also explained by the decreased adherent colony formation in treated animals. Furthermore, the flow cytometric characterization of CXCR4⁺ and Sca-1⁺ CD44⁺ receptor expressions confirmed the dysregulation in the hematopoietic microenvironment. Thus, considering the importance of microenvironment in the maintenance of HSPC, it can be concluded that arsenic toxicity causes microenvironmental damage, leading to niche derangement and impaired hematopoiesis.

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Evaluation of Dietary Palygorskite Supplementation on Growth Performance, Mineral Accumulations, Antioxidant Capacities, and Meat Quality of Broilers Fed Lead-Contaminated Diet

Abstract

The objective of this study was to evaluate influence of dietary palygorskite (Pal) supplementation on growth performance, mineral accumulations in the tissues (livers, kidneys, and muscles), antioxidant capacities, and meat quality of broilers fed lead (Pb)-contaminated diet. One-hundred forty-four male broiler chicks were randomly divided into three treatment groups, receiving a corn-soybean meal basal diet (the control group), the basal diet contaminated with 10 mg/kg Pb (the Pb group), and the basal diet with 10-g/kg Pal supplementation and 10-mg/kg Pb contamination (the Pal/Pb group) from 1 to 42 days of age, respectively. Treatments did not affect growth performance of broilers in the 42-day study (P > 0.05). Compared with the control group, Pb contamination increased Pb accumulation in the livers, kidneys, and muscles (P < 0.05); elevated malondialdehyde accumulation in the livers, kidneys, and breast muscles; glutathione peroxidase activity in the livers and superoxide dismutase activity in the kidneys (P < 0.05); exacerbated drip loss in the pectoralis muscles (P < 0.05); and reduced glutathione peroxidase activity in the pectoralis muscles (P < 0.05) of broilers at 42 days of age. The values of these parameters were reversed in the Pal/Pb group to levels comparable with those in the control group (P < 0.05). Additionally, Pal supplementation reduced redness value in the pectoralis muscles (P < 0.05), and decreased Cu concentration in the pectoralis muscles and livers at 42 days of age as well as its accumulation in the kidneys at both 21 and 42 days of age compared with the other two groups (P < 0.05). The results suggested that dietary Pal supplementation would decrease Pb residue in the tissues, alleviate oxidative stress, and affect meat quality of broilers exposed to Pb.

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The computed tomography adrenal wash-out analysis properly classifies cortisol secreting adrenocortical adenomas

Abstract

Purpose

Adrenocortical lesions are characterized through imaging, hormonal and histopathological analysis. Our aim was to compare the radiological features of adrenocortical lesions with their cortisol-secreting status and histopathological Weiss score.

Methods

Seventy five patients operated between 2004 and 2016 in the University Hospital of Nancy for either adrenocortical carcinomas (ACC) or adrenocortical adenomas (ACA) were enrolled in this study. We collected cortisol parameters, Computed Tomography (CT) scans (unenhanced density, wash-out (WO) analysis) and ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) datas. The histopathological Weiss score ultimately differentiates ACA (score ≤ 2) from ACC (score ≥ 3). One-way ANOVA, Fisher's exact and unpaired t tests were used for statistical analysis with significancy reached at p < 0.05.

Results

There were 23 ACC and 52 ACA with 40 patients (53%) who had an autonomous secretion of cortisol. On CT scan, ACC were larger compared to ACA (108 vs. 37 mm, p < 0.0001). A roughly similar proportion of cortisol-secreting (22/25) and non-secreting (15/19) ACA were atypical (i.e., unenhanced density value ≥ 10 Hounsfield Units [HU]), however 85% of cortisol-secreting vs. 40% of non-secreting ACA were classified as benigns by the relative WO analysis (p = 0.08). Likewise, there was a trend for a higher ¹⁸F-FDG uptake in cortisol-secreting ACA compared to non-secreting ACA (p = 0.053).

Conclusions

The relative adrenal WO analysis consolidates the benign nature of an ACA, especially in case of cortisol oversecretion, a condition known to compromise the diagnostic accuracy of the 10 HU unenhanced CT attenuation threshold.

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Cover Image

The cover image, by Dajiang Song et al., is based on the Original Article Chimeric thoracoacromial artery perforator flap for one-staged reconstruction of complex pharyngoesophageal defects: A single unit experience, DOI: 10.1002/hed.24962

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Issue Information

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The computed tomography adrenal wash-out analysis properly classifies cortisol secreting adrenocortical adenomas

Abstract

Purpose

Methods

Results

Conclusions

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Prospective trial evaluating the sensitivity and specificity of 3,4-dihydroxy-6-[18F]-fluoro- l -phenylalanine (18F-DOPA) PET and MRI in patients with recurrent gliomas

Abstract

Treatment-related changes can be difficult to differentiate from progressive glioma using MRI with contrast (CE). The purpose of this study is to compare the sensitivity and specificity of 18F-DOPA-PET and MRI in patients with recurrent glioma. Thirteen patients with MRI findings suspicious for recurrent glioma were prospectively enrolled and underwent 18F-DOPA-PET and MRI for neurosurgical planning. Stereotactic biopsies were obtained from regions of concordant and discordant PET and MRI CE, all within regions of T2/FLAIR signal hyperintensity. The sensitivity and specificity of 18F-DOPA-PET and CE were calculated based on histopathologic analysis. Receiver operating characteristic curve analysis revealed optimal tumor to normal (T/N) and SUVmax thresholds. In the 37 specimens obtained, 51% exhibited MRI contrast enhancement (M+) and 78% demonstrated 18F-DOPA-PET avidity (P+). Imaging characteristics included M−P− in 16%, M−P+ in 32%, M+P+ in 46% and M+P− in 5%. Histopathologic review of biopsies revealed grade II components in 16%, grade III in 43%, grade IV in 30% and no tumor in 11%. MRI CE sensitivity for recurrent tumor was 52% and specificity was 50%. PET sensitivity for tumor was 82% and specificity was 50%. A T/N threshold > 2.0 altered sensitivity to 76% and specificity to 100% and SUVmax > 1.36 improved sensitivity and specificity to 94 and 75%, respectively. 18F-DOPA-PET can provide increased sensitivity and specificity compared with MRI CE for visualizing the spatial distribution of recurrent gliomas. Future studies will incorporate 18F-DOPA-PET into re-irradiation target volume delineation for RT planning.

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy

Abstract

This study aimed to compare cervical vestibular-evoked myogenic potentials (cVEMP), ocular vestibular-evoked myogenic potentials (oVEMP) and video head impulse test (vHIT) results between patients with type 2 diabetes mellitus (DM) or diabetic polyneuropathy (DPN) and healthy controls to determine vestibular end-organ pathologies. The participants in the present study consisted of three groups: the type 2 DM group (n = 33 patients), the DPN group (n = 33 patients), and the age- and sex-matched control group (n = 35). Cervical VEMP, oVEMP and vHIT were performed for each participant in the study and test results were compared between the groups. Peak-to-peak amplitudes of cVEMP (p13–n21) and oVEMP (n10–p15) were significantly lower in the DM and DPN groups than the control group. The values of vHIT were not statistically different between the groups. To our knowledge, the present study is the first report investigating oVEMP and cVEMP responses combined with vHIT findings in patients with DM and DPN. Vestibular end-organ pathologies can be determined via clinical vestibular diagnostic tools in spite of prominent vestibular symptoms in patients with type 2 DM as well as patients with DPN.

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Three-year analysis of zirconia implants used for single-tooth replacement and three-unit fixed dental prostheses: A prospective multicenter study

Abstract

Aim

The aim of the present investigation was to evaluate clinically and radiographically the outcome of zirconia oral implants after 3 years in function.

Materials and methods

In 60 patients in need of either a single-tooth replacement or a three-unit fixed dental prosthesis (FDP), a total of 71 one-piece zirconia implants were placed and immediately restored with temporary fixed prostheses. After a period of at least 2 months in the mandible and at least 4 months in the maxilla, zirconia-based reconstructions were cemented. The implants were clinically and radiologically examined at implant insertion, prosthetic delivery, at 6 months and then yearly up to 3 years. A linear mixed model was used to analyze statistically the influence of prognostic factors on changes in the marginal bone level.

Results

Seventy-one implants (48 in the mandible, 23 in the maxilla) inserted in 60 patients were restored with 49 crowns and 11 FDP. One patient lost his implant after 5 weeks. Five patients with one implant each could not be evaluated after 3 years. Based on 55 patients with a total of 66 implants, the mean survival rate was 98.5% after 3 years in function. A statistically significant mean marginal bone loss (0.70 mm ± 0.72 mm) has been detected from implant insertion to the 3-year follow-up. The largest marginal bone loss occurred between implantation and prosthetic delivery (0.67 mm ± 0.56 mm). After delivery, no statistically significant bone level change was observed (0.02 mm ± 0.59 mm). None of the investigated prognostic factors had a significant influence on changes in the marginal bone level.

Conclusions

After 3 years in function, the investigated one-piece zirconia implant showed a high survival rate and a low marginal bone loss. The implant system was successful for single-tooth replacement and three-unit FDPs. Further investigations with long-term data are needed to confirm these findings.

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Delayed Hypoxemia After Traumatic Brain Injury Exacerbates Long-Term Behavioral Deficits

Journal of Neurotrauma , Vol. 0, No. 0.

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Traumatic Brain Injury Impairs Myogenic Constriction of Cerebral Arteries: Role of Mitochondria-Derived H2O2 and TRPV4-Dependent Activation of BKca Channels

Journal of Neurotrauma , Vol. 0, No. 0.

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Metal Concentrations in Tissues of Gadwall and Common Teal from Miankaleh and Gomishan International Wetlands, Iran

Abstract

Miankaleh and Gomishan International Wetlands are important wintering areas for waterbirds in the Caspian Sea region. Previous studies revealed increased exposure to metals in some species of waterbirds using these wetlands. In this study, we examined concentrations of cadmium (Cd), chromium (Cr), iron (Fe), lead (Pb), and zinc (Zn) in kidneys, liver, and pectoral muscle of wintering Gadwall (Anas strepera) and Common Teal (Anas crecca) collected in 2012. In addition, we measured concentrations of these elements in water and sediments from the collection sites. The genders differed in only one element/tissue combination, i.e., concentrations of Fe were greater in the livers of males. Concentrations of elements observed in Gadwall were generally higher than in Common Teal; only renal Cr and muscle Zn did not differ between species. Mean Cd concentrations in Gadwall exceeded background levels, reaching 1.94 μg/g ww in kidneys and 1.09 μg/g ww in liver. Similarly, Pb concentrations in Gadwall were also elevated (4.14 μg/g ww in kidneys, 3.22 μg/g ww in liver). Concentrations of other metals were within ranges commonly found in waterfowl. Concentrations of elements in the environment were elevated above background and comparable with the data obtained for this region by other scientists. However, these levels were deemed to not be great enough to pose an acute health risk to waterfowl. Given increased concentrations of some metals in duck tissues, further inquiry into the source of the exposure is needed for this area.

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Delayed Hypoxemia After Traumatic Brain Injury Exacerbates Long-Term Behavioral Deficits

Journal of Neurotrauma , Vol. 0, No. 0.

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Traumatic Brain Injury Impairs Myogenic Constriction of Cerebral Arteries: Role of Mitochondria-Derived H2O2 and TRPV4-Dependent Activation of BKca Channels

Journal of Neurotrauma , Vol. 0, No. 0.

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Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress disorder

Abstract

Purpose

The purpose of this study was to determine the impact of insomnia in Veterans with post-traumatic stress disorder (PTSD) and obstructive sleep apnea (OSA) on health-related outcomes before and after 12 weeks of continuous positive airway pressure (CPAP) treatment.

Methods

We conducted a prospective cohort study of Veterans with PTSD and documented apnea hypopnea index (AHI) ≥ 5 with and without clinically significant insomnia as determined by the Insomnia Severity Index (ISI). Health-related outcomes including PTSD checklist (PCL-M), SF-36, and Pittsburgh Sleep Quality Index (PSQI) were assessed at baseline and 12 weeks after initiation of OSA treatment. CPAP adherence was retrieved at each visit.

Results

Seventy-two Veterans including 36 with comorbid insomnia and OSA (COMISA) and 36 OSA-only were enrolled. Veterans with COMISA were younger (p = 0.03), had lower BMI (p < 0.001), and were more likely to report depression than those with OSA-only (p = 0.004). Although AHI was higher in the COMISA (p = 0.01), both groups expressed comparable daytime sleepiness (p = 0.16). The COMISA group had no significant change in SF-36 and PSQI after 12 weeks of treatment and used CPAP much less frequently than OSA-only group (p = 0.001).

Conclusions

COMISA in Veterans with PTSD is associated with worse quality of life than those with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not adherent to CPAP treatment.

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy

Abstract

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Effects of Loosely Bound EPS Release and Floc Reconstruction on Sludge Dewaterability

Abstract

Loosely bound extracellular polymeric substances (LB-EPS) are highly hydrated biopolymers and play important roles in sludge biofloccualtion and dewaterability. Disruption or solubilization of LB-EPS will promote the alternation of sludge structure and the release of trapped water. In the present study, ultrasonication was employed to extract LB-EPS into the supernatant and release trapped water within them. Excellent performance in enhancing ultrasonicated sludge dewatering was observed under the combined Fe³⁺(20 mg/g dry sludge (DS)) and Ca²⁺ (30 mg/g DS) addition. The above fact highlighted the probability to enhance the sludge dewaterability by the dosage of small amount of cations. Further, the combined effects of ultrasonication and multivalent cation addition on floc regrowth on sludge dewaterability were investigated and the possible mechanisms involved in the reorganization of sludge structure and the biofloccualtion process were also explored. In conclusion, the combination of ultrasonication and multivalent cation addition was promising to improve sludge dewaterability.

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Microfluidic co-culture of pancreatic tumor spheroids with stellate cells as a novel 3D model for investigation of stroma-mediated cell motility and drug resistance

Pancreatic stellate cells (PSCs), a major component of the tumor microenvironment in pancreatic cancer, play roles in cancer progression as well as drug resistance. Culturing various cells in microfluidic (mic...

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Comorbid insomnia and sleep apnea in Veterans with post-traumatic stress disorder

Abstract

Purpose

Methods

Results

Conclusions

COMISA in Veterans with PTSD is associated with worse quality of life than those with OSA-only. Insomnia should be assessed in Veterans with PTSD who are not adherent to CPAP treatment.

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Continuous Positive Airway Pressure Thresholds for Nasolacrimal Air Regurgitation in a Cadaveric Model

Purpose: To elucidate the mechanisms underlying nasolacrimal air regurgitation (AR) in the setting of continuous positive airway pressure therapy. Methods: Twelve nasolacrimal systems of 6 fresh female human cadavers were evaluated individually for AR using continuous positive airway pressure therapy before any nasolacrimal procedure. Cadavers were then randomly assigned to undergo nasolacrimal duct probing or endoscopic dacryocystorhinostomy and then each hemisystem was again evaluated for AR. The pressure where AR was first observed (discovery pressure) or maximum possible pressure in systems without AR was recorded. In systems that demonstrated AR, the pressure was then gradually decreased to the lowest pressure where regurgitation persisted. This pressure was recorded as the secondary threshold pressure. Results: None of the 12 unoperated nasolacrimal systems or the 6 systems that underwent nasolacrimal duct probing demonstrated AR through the maximum continuous positive airway pressure therapy (30 cm H2O). After endoscopic dacryocystorhinostomy, all 6 nasolacrimal systems demonstrated AR. The mean discovery pressure was 16.0 cm H2O (range, 14.0–18.0 cm H2O) and mean secondary threshold pressure was 7.25 cm H2O (range, 6.5–8.0 cm H2O). Conclusions: Air regurgitation during continuous positive airway pressure therapy in the setting of prior endoscopic dacryocystorhinostomy can be replicated in a cadaver model. The secondary threshold pressures required for AR in this model were similar to AR pressures reported clinically. Prior to dacryocystorhinostomy, patients using continuous positive airway pressure therapy should be counseled on AR, and physicians should consider this phenomenon when evaluating ophthalmic complaints in postoperative patients on positive airway pressure therapy. Accepted for publication November 5, 2017. Supported in part by the NIH-NEI P30 Core Grant (IP30EY025585-01A1) and Unrestricted Grant from The Research to Prevent Blindness, Inc, awarded to the Cole Eye Institute. The authors have no conflicts of interest to disclose. Address correspondence and reprint requests to Alexander D. Blandford, M.D., Cole Eye Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue i-13, Cleveland, OH 44195. E-mail: blandfa@ccf.org © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Symmetry of Upper Eyelid Contour After Unilateral Blepharoptosis Repair With a Single-strip Frontalis Suspension Technique

Purpose: To analyze the upper eyelid contour of patients with unilateral congenital ptosis who underwent single-strip frontalis suspension. Methods: The authors compared the upper eyelid shape of the right and left eyes of 10 patients who underwent unilateral frontalis suspension with a single strip of autogenous fascia. At a mean postoperative time of 10.1 ± 4.01 months, the image J software was used to measure the ratio between the nasal and temporal areas of the upper half of the palpebral fissure. The midpupil upper eyelid distance (MRD1) was also measured on the photos with the same software. The nonparametric Wilcoxon signed-rank test was used to compare the data. Results: Postoperative MRD1 ranged from 2.5 to 4.7 mm (median = 3.8) on the affected side. The MRD1 for nonoperated eyelid ranged from 1.8 to 5.0 mm (median = 3.5). On the operated side, the temporal areas ranged from 50.3 to 85.7 mm2 (median 65.2) and nasal areas ranged from 41.5 to 72.3 (the median was 60.1). In the contralateral, nonoperated palpebral fissures, the temporal areas ranged from 42.7 to 94.3 mm2 (median = 54.5) and the nasal areas ranged from 36.8 to 86.1 mm2 (median 52.3). The T/N ratio distributions were almost identical between groups, ranging from 0.9 to 1.2 (median = 1.1) in the operated eyes and from 0.9 to 1.3 (median = 1.1) in the fellow eyes. Conclusions: In autogenous fascia frontalis suspension procedures, the upper eyelid contour of the ptotic eyelids can be adequately normalized with a single area of traction on the tarsal plate. Accepted for publication November 5, 2017. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Patricia Akaishi, Department of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Hospital das Clínicas-Campus, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, 14049-900 São Paulo, Brazil. E-mail: patriciamitiko@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Clinical Features and Outcomes of Post-Traumatic Silent Sinus Syndrome

Purpose: To identify demographic features and clinical outcomes associated with post-traumatic silent sinus syndrome. Methods: A retrospective review was carried out at 3 academic medical centers to identify all cases of post-traumatic silent sinus syndrome. Clinical features and management strategies were recorded. Postoperative outcomes were assessed, and statistical analyses were performed via a dedicated computerized software package. Results: Twenty cases were identified (14 men and 6 women, mean age = 44.2 years). Seven patients underwent sinus surgery as the sole means of treatment, and the mean pre- and postoperative enophthalmos measurements were 2.86 and 1.93 mm. Alternatively, 13 patients underwent combined orbital reconstruction and sinus surgery, respectively; the mean pre- and postoperative enophthalmos measurements were 3.42 and 0.39 mm, respectively. The change in enophthalmos was statistically significantly greater in patients who underwent sinus surgery and orbital reconstruction (p = 0.00028). Among patients who underwent sinus surgery alone, one patients (14.2%) experienced complete resolution of enophthalmos, as compared with 10 patients (76.9%) who underwent combined procedures. Conclusions: This study represents the largest published cohort of patients with post-traumatic silent sinus syndrome. Combined orbital reconstruction and sinus surgery results in greater reductions of enophthalmos and a markedly improved chance of postoperative symmetry of globe position. Accepted for publication September 28, 2017. The authors have no financial or conflicts of interest to disclose. Correspondence address and reprint requests to Edward J. Wladis, M.D., F.A.C.S., Ophthalmic Plastic Surgery, 1220 New Scotland Road, Suite 302, Slingerlands, NY 12159. E-mail: tedwladis@gmail.com © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Clinical Description, Molecular Analysis of TWIST2 Gene, and Surgical Treatment in a Patient With Barber-Say Syndrome

Barber-Say syndrome is a rare autosomal dominant disease characterized by dysmorphic features, mainly of the eyelids and skin. It is caused by heterozygous mutations in gene TWIST2, localized in chromosome 2q37.3. The authors present the case of a pediatric patient with a clinical diagnosis of Barber-Say syndrome with ocular symptoms related to exposure keratitis. Molecular analysis of her DNA revealed a mutation on TWIST2 gene confirming the diagnosis of Barber-Say syndrome. Surgical treatment of the patient's eyelids resolved her signs and symptoms. Accepted for publication October 29, 2017. The authors F.Z. and M.C.A. contributed equally to the study in this article and are considered first authors. The authors have no financial or conflicts of interest to disclose. Address correspondence and reprint requests to Juan C. Zenteno, M.D., Ph.D., Genetics Department, Institute of ophthalmology Conde de Valenciana, Chimalpopoca 14, Col. Obrera, CP 06800, Cuauhtemoc, Mexico City, Mexico. E-mail: jczenteno@institutodeoftalmologia.org. © 2018 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

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Assessment of vestibular-evoked myogenic potentials and video head impulse test in type 2 diabetes mellitus patients with or without polyneuropathy

Abstract

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High-risk TP53 mutations are associated with extra nodal extension (ENE) in oral cavity squamous cell carcinoma (OSCC).

Purpose: Development of extra-nodal extension (ENE) has been associated with poor survival in patients with oral cavity squamous cell carcinoma (OSCC). Here we sought to confirm the role of ENE as a poor prognostic factor, and identify genomic and epigenetic markers of ENE in order to develop a predictive model and improve treatment selection. Experimental design: An institutional cohort (University of Texas MD Anderson Cancer Center) was utilized to confirm the impact of ENE on clinical outcomes and evaluate the genomic signature of primary and ENE containing tissue. OSCC data from The Cancer Genome Atlas (TCGA) were analyzed for the presence of molecular events associated with nodal and ENE status. Results: ENE was associated with decreased overall and disease free survival. Mutation of the TP53 gene was the most common event in ENE+ OSCC. The frequency of TP53 mutation in ENE+ tumors was higher compared to ENE- tumors and wild-type (wt) TP53 was highly-represented in pN0 tumors. pN+ENE+ patients had the highest proportion of high-risk TP53 mutations. Both primary tumors (PT) and lymph nodes with ENE (LN) exhibited a high rate of TP53 mutations (58.8%, 58.8% respectively) with no significant change in allele frequency between the two tissue sites. Conclusions: ENE is one of the most significant markers of OSCC OS and DFS. There is a shift toward a more aggressive biological phenotype associated with high-risk mutations of the TP53 gene. Prospective clinical trials are required to determine whether TP53 mutational status can be used for personalized treatment decisions.

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Pazopanib Exposure Relationship with Clinical Efficacy and Safety in the Adjuvant Treatment of Advanced Renal Cell Carcinoma

Purpose: PROTECT, a phase III randomized placebo-controlled study, evaluated pazopanib efficacy and safety in the adjuvant RCC setting. The relationship between pazopanib exposure (C_trough) and efficacy and safety was evaluated. Experimental Design: Evaluable steady-state blood trough concentrations were collected from 311 patients at week 3 or 5 (early C_trough), and 250 patients at week 16 or 20 (late C_trough). Pazopanib pharmacokinetic (PK) data was analyzed via a population model approach. Relationship between C_trough or dose intensity and disease-free survival (DFS) was explored via Kaplan-Meier and multivariate analysis. Adverse events (AEs) and AE-related treatment discontinuation proportions were summarized by C_trough quartiles. Results: Most (>90%) patients with early or late C_trough data started on 600 mg. Mean early and late C_trough overlapped across dose levels. Patients with higher early C_trough quartiles achieved longer DFS (adjusted hazard ratio [HR], 0.58; 95% CI, 0.42-0.82; P = 0.002). Patients achieving early or late C_trough >20.5 µg/mL had significantly longer DFS, not estimable (NE) vs 29.5 months, P = 0.006, and NE vs 29.9 months, P = 0.008, respectively. Dose intensity up to week 8 did not correlate with DFS, consistent with population PK model-based simulations showing overlapping pazopanib exposure with 600 mg and 800 mg doses. The proportion of AE-related treatment discontinuation and grade 3/4 AEs, with the exception of hypertension, was not correlated to C_trough. Conclusions: In the adjuvant setting, higher pazopanib C_trough was associated with improved DFS, and did not increase treatment discontinuations or grade 3/4 AEs with the exception of hypertension.

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Personalized RNA-medicine for pancreatic cancer

Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21 was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy.

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Clinical utility of a STAT3-regulated microRNA-200 family signature with prognostic potential in early gastric cancer

Purpose: The majority of gastric cancer (GC) patients are diagnosed with late stage disease, for which distinct molecular subtypes have been identified that are potentially amenable to targeted therapies. However, there exists no molecular classification system with prognostic power for early stage GC (EGC) because the molecular events promoting GC initiation remain ill-defined. Experimental Design: miRNA microarrays were performed on gastric tissue from the gp130^F/F preclinical EGC mouse model, prior to tumor initiation. Computation prediction algorithms were performed on multiple datasets and independent GC patient cohorts. Quantitative real-time PCR expression profiling was undertaken in gp130^F/F-based mouse strains and human GC cells genetically-engineered for suppressed activation of the oncogenic latent transcription factor, STAT3. Human GC cells with modulated expression of the miR-200 family member, miR-429, were also assessed for their proliferative response. Results: Increased expression of miR-200 family members is associated with both tumor initiation in a STAT3-dependent manner in gp130^F/F mice, and EGC (i.e. Stage IA) in patient cohorts. Over-expression of miR-429 also elicited contrasting pro- and anti-proliferative responses in human GC cells dependent upon their cellular histological subtype. We also identified a miR-200 family-regulated 15-gene signature which integrates multiple key current indicators of EGC, namely tumor invasion depth, differentiation, histology and stage, and provides superior predictive power for overall survival compared to each EGC indicator alone. Conclusions: Collectively, our discovery of a STAT3-regulated, miR-200 family-associated gene signature specific for EGC, with predictive power, provides a molecular rationale to classify and stratify EGC patients for endoscopic treatment.

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Early Assessment of Lung Cancer Immunotherapy Response via Circulating Tumor DNA

Purpose: Decisions to continue or suspend therapy with immune checkpoint inhibitors are commonly guided by tumor dynamics seen on serial imaging. However, immunotherapy responses are uniquely challenging to interpret because tumors often shrink slowly or can appear transiently enlarged due to inflammation. We hypothesized that monitoring tumor cell death in real-time by quantifying changes in circulating tumor DNA (ctDNA) levels could enable early assessment of immunotherapy efficacy. Experimental Design: We compared longitudinal changes in ctDNA levels with changes in radiographic tumor size and with survival outcomes in 28 metastatic non-small cell lung cancer patients receiving immune checkpoint inhibitor therapy. CtDNA was quantified by determining the allele fraction of cancer-associated somatic mutations in plasma using a multi-gene next-generation sequencing assay. We defined a ctDNA response as a >50% decrease in mutant allele fraction from baseline, with a second confirmatory measurement. Results: Strong agreement was observed between ctDNA response and radiographic response (Cohen's kappa, 0.753). Median time to initial response among patients who achieved responses in both categories was 24.5 days by ctDNA vs. 72.5 days by imaging. Time on treatment was significantly longer for ctDNA responders vs. non-responders (median 205.5 vs. 69 days; P<0.001). A ctDNA response was associated with superior progression-free survival (hazard ratio [HR], 0.29; 95% CI, 0.09-0.89; P=0.03), and superior overall survival (HR, 0.17; 95% CI, 0.05-0.62; P=0.007). Conclusions: A drop in ctDNA level is an early marker of therapeutic efficacy and predicts prolonged survival in patients treated with immune checkpoint inhibitors for non-small cell lung cancer.

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Evolution of cytogenetically normal acute myeloid leukemia during therapy and relapse: An exome sequencing study of 50 patients

Purpose: To study mechanisms of therapy-resistance and disease progression, we analyzed the evolution of cytogenetically normal acute myeloid leukemia (CN-AML) based on somatic alterations. Experimental Design: We performed exome-sequencing of matched diagnosis, remission and relapse samples from 50 CN-AML patients treated with intensive chemotherapy. Mutation patterns were correlated with clinical parameters. Results: Evolutionary patterns correlated with clinical outcome. Gain of mutations was associated with late relapse. Alterations of epigenetic regulators were frequently gained at relapse with recurring alterations of KDM6A constituting a mechanism of cytarabine resistance. Low KDM6A expression correlated with adverse clinical outcome, particularly in male patients. At complete remission, persistent mutations representing pre-leukemic lesions were observed in 48% of patients. The persistence of DNMT3A mutations correlated with shorter time to relapse. Conclusion: Chemotherapy resistance might be acquired through gain of mutations. Insights into the evolution during therapy and disease progression lay the foundation for tailored approaches to treat or prevent relapse of CN-AML.

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Cultured allogeneic fibroblast injection versus fibroblasts cultured on amniotic membrane scaffold for dystrophic epidermolysis bullosa treatment

Abstract

Background

Different methods of fibroblast application have been examined to treat recessive dystrophic epidermolysis bullosa (RDEB).

Objective

To compare the effects of intradermal injection of cultured allogeneic fibroblasts in healing RDEB wounds with that of fibroblasts seeded on amniotic membrane scaffolds (FAMS) or standard wound care (SWC) with Vaseline gauze as controls.

Materials &Methods

Seven patients were recruited, and seven wounds were assessed in each patient: three wounds were treated with injection of intradermal fibroblasts, three were treated with FAMS, and one was dressed with SWC. Changes in wound size were assessed after 2 and 12 weeks of treatment. Qualitative wound scores (QWS) were used to assess wound severity. Additionally, biopsies and antigen mapping were performed to detect type-VII collagen in the dermoepidermal junction.

Results

In both treated areas, the QWS and wound size were significantly decreased (P<0.0001), whereas there were no changes in control group (P=0.29). After 2 and 12 weeks of treatment, the wound size was significantly decreased in wounds that were treated with fibroblast injection compared with those treated with FAMS (P<0.0001); but no significant changes were found in control group.

Conclusion

Fibroblast injection has been shown to promote healing of RDEB wounds and is superior to FAMS or the control treatment.

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Differential effects of phototherapy, adalimumab and betamethasone/calcipotriol on effector and regulatory T cells in psoriasis

Summary

Background

Psoriasis is a chronic T cell-mediated skin disease with marked social and economic burdens. Current treatments are unsatisfactory, with unpredictable remission times and incompletely understood modes of action. Recent advances in our understanding of the pathogenesis of psoriasis identify the imbalance between CD4⁺ T effector cells, particularly the T helper (Th) 17 subset, and regulatory T cells (Treg) as key to the development of psoriatic lesions, and therefore a novel therapeutic target.

Objectives

To quantify in patients the effects of three commonly used psoriasis treatment modalities on the Th1, Th2, Th17 and Treg subsets, and test whether any change correlates with clinical response.

Methods

Using flow cytometry to enumerate Th1, Th2, Th17 and Treg subsets in blood and skin of psoriatic patients before and after receiving any of the following treatments; narrow band UVB (NB-UVB), adalimumab and topical betamethasone/calcipotriol combination (Dovobet^®).

Results

All patients responded clinically to treatments. NB-UVB significantly increased the numbers of circulating and skin Treg, while, by contrast, adalimumab reduced Th17 cells in these compartments, and Dovobet had dual effects by both increasing Treg and reducing Th17 cells.

Conclusions

The differential effects reported here for the above-mentioned treatment modalities could be exploited to optimize or design therapeutic strategies to better overcome the inflammatory drivers and restore the Th17/Treg balance in psoriasis.

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Reduction of hyaluronan and increased expression of HYBID (KIAA1199) correlate with clinical symptoms in photoaged skin

Summary

Background

Hyaluronan (HA) metabolism in skin fibroblasts is mediated by HYBID (HYaluronan Binding protein Involved in hyaluronan Depolymerisation, KIAA1199) and HA synthases 1/2 (HAS1/2). However, photoageing-dependent changes in HA and their molecular mechanisms, and the relationship between HA metabolism and clinical symptoms in photoaged skin remain elusive.

Objectives

We examined amount, size and tissue distribution of HA and expression levels of HYBID and HAS1/2 in photoaged skin, and analysed their relationships to the degree of photoageing.

Methods

Photoageing-dependent changes of HA were investigated by studying skin biopsies isolated from photoprotected and photoexposed areas of the same donors, and the relationship between HA and photoageing symptoms such as skin wrinkling and sagging was examined.

Results

Skin biopsy specimens showed that amount and size of HA are decreased in the photoexposed skin compared to the photoprotected skin, and this was accompanied by increased expression of HYBID and decreased expression of HAS1/2, respectively. Histologically, HA staining in the papillary dermis was decreased in photoexposed skin, showing reverse correlation with HYBID expression. HYBID expression in the photoexposed skin directly correlated with skin roughness and sagging parameters, and reduced HA staining in the papillary dermis in the photoexposed skin positively correlated with these symptoms.

Conclusions

These data demonstrate that imbalance between HYBID-mediated HA degradation and HAS-mediated HA synthesis may contribute to enhanced HA catabolism in the photoaged skin, and suggest that HYBID-mediated HA reduction in the papillary dermis is related to skin wrinkling and sagging of photoaged skin.

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Oral propranolol for infantile haemangioma may be associated with transient gross motor delay

Abstract

Oral propranolol, first-line therapy for infantile haemangioma (IH) threatening functional impairment or cosmetic disfigurement, readily crosses the blood-brain barrier. Subsequently therefore, there are concerns about potential effects on infant development. Phillips et al. followed 200 children prescribed propranolol, observing sedative effects during treatment and reported gross motor abnormalities in 13 of 188 children, 7 of whom had delayed age (17-20 months) at first walking.

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A case of xeroderma pigmentosum complementation group C with diverse clinical features

Abstract

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by sensitivity to sunlight and increased risk of skin cancers. XP is classified into seven nucleotide excision repair-deficient types (A–G) and a variant type¹. Differential diagnosis of XP from other genetic pigmentary disorders such as dyschromatosis symmetrica hereditaria (DSH) and dyschromatosis universalis hereditaria (DUH) should be considered, which is sometimes difficult without DNA repair tests or a genetic diagnosis². DSH and DUH are autosomal dominant diseases characterized by hypo-and hyperpigmented maculae. Recently, ABCB6 was identified as a responsible gene for DUH³.

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Expression of YAP and TAZ in molluscum contagiosum virus infected skin

Abstract

The Hippo signaling pathway, which is highly conserved in organisms ranging from Drosophila to mammals, plays a key role in organ size control, cellular proliferation, survival and tumorigenesis¹ Yes-associated protein (YAP) is the major downstream effector of Hippo signaling pathway and transcriptional co-activator with PDZ-binding motif (TAZ) is a YAP paralog. Recently, Zhang et al. found that YAP/TAZ acts as natural inhibitors of TANK binding kinase 1 (TBK1), which is a key component for cytosolic nucleic acid sensing antiviral defense and antiviral physiology²

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Tubular adenomas with clear cell change in the colorectum: A case with four lesions and a review of the literature

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Kindlin-1 promotes pulmonary breast cancer metastasis

In breast cancer, increased expression of the cytoskeletal adaptor protein Kindlin-1 has been linked to increased risks of lung metastasis, but the functional basis is unknown. Here we show that in a mouse model of polyomavirus middle T antigen-induced mammary tumorigenesis, loss of Kindlin-1 reduced early pulmonary arrest and later development of lung metastasis. This phenotype relied on the ability of Kindlin-1 to bind and activate β integrin heterodimers. Kindlin-1 loss reduced α4 integrin-mediated adhesion of mammary tumor cells to the adhesion molecule VCAM-1 on endothelial cells. Treating mice with an anti-VCAM-1 blocking antibody prevented early pulmonary arrest. Kindlin-1 loss also resulted in reduced secretion of several factors linked to metastatic spread, including the lung metastasis regulator tenascin-C, showing that Kindlin-1 regulated metastatic dissemination by an additional mechanism in the tumor microenvironment. Overall, our results show that Kindlin-1 contributes functionally to early pulmonary metastasis of breast cancer.

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Genetic ablation of Rbm38 promotes lymphomagenesis in the context of mutant p53 by downregulating PTEN

Mutant p53 exerts gain-of-function effects that drive metastatic progression and therapeutic resistance, but the basis for these effects remain obscure. The RNA binding protein RBM38 limits translation of mutant p53 and is often ablated in tumors harboring it. Here we show how loss of Rbm38 significantly alters cancer susceptibility in mutant p53 knock-in mice, by shortening lifespan, altering tumor incidence and promoting T cell lymphomagenesis. Loss of Rbm38 enhanced mutant p53 expression and decreased expression of the tumor suppressor Pten, a key regulator of T cell development. Furthermore, Rbm38 was required for Pten expression via stabilization of Pten mRNA through an AU-rich element in its 3'UTR. Our results suggest that Rbm38 controls T cell lymphomagenesis by jointly modulating mutant p53 and Pten, with possible therapeutic implications for treating T cell malignancies.

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Demethylation-induced overexpression of Shc3 drives c-Raf-independent activation of MEK/ERK in HCC

Invasion and intrahepatic metastasis are major factors of poor prognosis in patients with hepatocellular carcinoma (HCC). In this study, we show that increased Src homolog and collagen homolog 3 (Shc3) expression in malignant HCC cell lines associate with HCC invasion and metastasis. Shc3 was significantly upregulated in tumors of 33 HCC patient samples as compared to adjacent normal tissues. Further analysis of 52 HCC patient samples showed that Shc3 expression correlated with microvascular invasion, cancer staging, and poor prognosis. Shc3 interacted with major vault protein (MVP), resulting in activation of MEK1/2 and ERK1/2 independently of Shc1 and c-Raf; this interaction consequently induced epithelial-mesenchymal transition (EMT) and promoted HCC cell proliferation and metastasis. The observed increase in Shc3 levels was due to demethylation of its upstream promoter, which allowed c-Jun binding. In turn, Shc3 expression promoted c-Jun phosphorylation in a positive feedback loop. Analysis of metastasis using a tumor xenograft mouse model further confirmed the role of Shc3 in vivo. Taken together, our results indicate the importance of Shc3 in HCC progression and identify Shc3 as a novel biomarker and potential therapeutic target in HCC.

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MBD2 ablation impairs lymphopoiesis and impedes progression and maintenance of T-ALL

Aberrant DNA methylation patterns in leukemia might be exploited for therapeutic targeting. In this study, we employed a genetically deficient mouse model to explore the role of the methylated DNA binding protein MBD2 in normal and malignant hematopoiesis. MBD2 ablation led to diminished lymphocytes. Functional defects of the lymphoid compartment were also observed after in vivo reconstitution of MBD2-deficient hematopoietic stem cells (HSC). In an established model of Notch1-driven T cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway. In clinical specimens of human T-ALL, Wnt signaling pathway signatures were significantly enhanced and positively correlated with the expression and function of MBD2. Further, a number of typical Wnt signaling inhibitory genes were abnormally hypermethylated in primary human T-ALL. Abnormal activation of Wnt signaling in T-ALL was switched off by MBD2 deletion, partially by reactivating epigenetically silenced Wnt signaling inhibitors. Taken together, our results define essential roles for MBD2 in lymphopoiesis and T-ALL and suggest MBD2 as a candidate therapeutic target in T-ALL.

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Breast cancer targeting through inhibition of the endoplasmic reticulum-based apoptosis regulator Nrh/BCL2L10

Drug resistance and metastatic relapse remain a top challenge in breast cancer treatment. In this study, we present preclinical evidence for a strategy to eradicate advanced breast cancers by targeting the BCL2 homolog Nrh/BCL2L10, which we discovered to be overexpressed in >45% of a large cohort of breast invasive carcinomas. Nrh expression in these tumors correlated with reduced metastasis-free survival and we determined it to be an independent marker of poor prognosis. Nrh protein localized to the endoplasmic reticulum (ER). Mechanistic investigations showed that Nrh made BH4 domain-dependent interactions with the ligand-binding domain of the inositol-1,4,5-triphosphate receptor (IP3R), a type I/III Ca2+ channel, allowing Nrh to negatively regulate ER-Ca2+ release and mediate anti-apoptosis. Notably, disrupting Nrh/IP3R complexes by BH4 mimetic peptides was sufficient to inhibit the growth of breast cancer cells in vitro and in vivo. Taken together, our results highlighted Nrh as a novel prognostic marker and a candidate therapeutic target for late stage breast cancers that may be addicted to Nrh.

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Acknowledgment to reviewers—2017

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Acknowledgment to reviewers—2017

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Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma

Background: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). Methods: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 − (resected liver weight − tumor volume)/whole liver volume without tumor]. Results: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. Conclusions: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of #x3c;0.755 should be carefully monitored for PHLF.
Eur Surg Res 2018;59:12–22

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Investigation of cancer associated fibroblasts and p62 expression in oral cancer before and after chemotherapy

The aim of this study is to investigate the expression of the autophagy protein p62 in oral squamous cell carcinoma (OSCC) cells before and after chemotherapy. We also detected cancer-associated fibroblasts (CAFs) in these OSCC samples to explore the roles of p62 and CAFs in chemotherapy.

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CD19-negative B-lineage acute lymphoblastic leukemia: A diagnostic and therapeutic challenge

Shashi Bansal, Upendra Sharma, Akansha Jain, Richa Sharma, Bhargav Yagnik

Indian Journal of Pathology and Microbiology 2017 60(4):596-598

B-lineage acute lymphoblastic leukemia (B-ALL) is an aggressive neoplasm of B-lymphocyte precursors that express the pan B-cell marker CD19 in all the cases. Rarely, a case may be assigned as B-lineage even if CD19 is negative. Here, a 16-year-old male presented with complaints of pain abdomen, on and off fever, joint pain, and hepatosplenomegaly for 2 months. Bone marrow examination was suggestive of acute leukemia with numerous leukoblasts on aspiration. On flow cytometry, gated blast population was negative for CD19, cytoCD3, and myeloperoxidase MPO and positive for CD34, TdT, HLA-DR, CD22, CD79a, and CD10. Immunohistochemistry study showed positivity for TdT, CD34, CD10 (focal), and PAX 5 and negativity for CD20, CD3, MPO, CD117, and CD68. Lack of awareness of negative CD19 expression in B-ALL can lead to incorrect immunophenotypic diagnosis, treatment, and monitoring of B-ALL. Proper diagnosis should be based on clinical features, immunophenotypic profiles, immunohistochemistry findings, and molecular analysis.

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Immunohistochemical and molecular markers in urothelial carcinoma

Ranjan Agrawal

Indian Journal of Pathology and Microbiology 2017 60(4):462-463

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From Editor's desk

Vatsala Misra

Indian Journal of Pathology and Microbiology 2017 60(4):461-461

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Role of salivary biomarkers in early detection of oral squamous cell carcinoma

Nidhi Awasthi

Indian Journal of Pathology and Microbiology 2017 60(4):464-468

Introduction: Oral cancer is prevalent worldwide and is a common cause of morbidity and mortality. Despite advances in treatment, the survival of patients with oral cancer has not significantly improved over the past several decades owing to late detection and treatment failures. The present study was undertaken with an objective to explore the role of salivary CYFRA 21-1, CA 19-9, lactate dehydrogenase (LDH), total proteins, and amylase as biochemical markers of oral squamous cell carcinoma (OSCC) and premalignant lesions (PML). Materials and Methods: This was a cross-sectional study for diagnostic test evaluation conducted in KGMC Lucknow, between 2010 and 2011. The study population comprised newly diagnosed cases of OSCC (Group I) and PML of oral cavity (Group II) who had not yet received any definitive therapy along with age- and gender-matched healthy controls (Group III). Unstimulated whole saliva was collected from the cases and controls. CYFRA 21-1 and CA19-9 were estimated by ELISA while LDH, total proteins, and amylase were evaluated as per standard kit method. Results: Both OSCC and PML group showed increased salivary CYFRA 21-1, LDH, and total protein concentrations as compared to controls, but the increase in PML was significantly lower as compared to OSCC. A considerable decrease in concentration of amylase was seen in OSCC and PML as compared to control group. Conclusion: The outcome of this study suggests that concurrent analysis of salivary CYFRA 21-1, LDH, total protein, and amylase can be utilized for early detection of oral cancer.

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Urinary schistosomiasis: Schistosoma haematobium infection diagnosed by histopathology

IndianJPatholMicrobiol_2017_60_4_614_222

Yung-Yao Lin, Victor Chia-Hsiang Lin, I-Wei Chang

Indian Journal of Pathology and Microbiology 2017 60(4):614-615

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Hypoxia-induced factor-1 alpha, vascular endothelial growth factor expression in BRCA1-related breast cancer: A prospective study in tertiary care hospital

Manisha Sharma, Sanjay Piplani, Manas Madan, Mridu Manjari, Saumil Garg, Komalpreet Kaur

Indian Journal of Pathology and Microbiology 2017 60(4):469-474

Introduction: Breast cancer is the commonest cause of death among middle aged women. BRCA1 associated tumors carry a poor prognosis. Angiogenesis is considered necessary for tumor growth and for its metastasis. Hypoxia stimulates HIF-1α which then activates transcription of various proangiogenic cytokines like VEGF. In the present study we examined HIF-1α expression, sVEGF levels and BRCA1 mutations and their relation with clinicopathological parameters. We also determined whether the angiogenic markers have different role in angiogenesis in BRCA1 related cancers as compared to sporadic breast cancers. Materials and Methods: The study was conducted on 50 cases of breast cancer specimens. Histopathological typing and grading was done followed by immunohistochemistry for BRCA1 and HIF-1α. VEGF was done in the serum by ELISA. Results: All the tumors were infiltrating ductal carcinoma NOS. 16 cases were reported grade II and 34 cases as grade III. On immunohistochemistry, 27 cases showed BRCA1 positivity and HIF-1α was positive in 39 cases. sVEGF levels were increased in 21 cases (42%). BRCA1 positivity, HIF-1α expression and increased VEGF levels were significantly associated with higher grade and lymph node metastasis. There was significant correlation of BRCA1 positivity with increased HIF-1α expression (P = 0.009) and increased sVEGF levels (P = 0.005). Conclusion: Our findings suggest that BRCA 1 positive tumors have unique molecular profile and different mechanism of tumorigenesis. Such tumors are associated with increased HIF-1α expression and VEGF levels.

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Primary signet cell adenocarcinoma of bladder

Prateek Kinra, SP Rashmi, Aftab Alam, Harkirat Singh, SC Dash

Indian Journal of Pathology and Microbiology 2017 60(4):584-586

Primary signet cell cancer of the urinary bladder is a relatively rare entity. Since there is no mucinous epithelium in the bladder, It is proposed that the tumor arises from metaplastic urothelium. Two thirds of the tumours are mucin secreting, in most of which the site of the deposition is either extracellular or intracellular displacing the nucleus to a peripheral crescent, giving the cells a signet ring appearance. The tumours are most often infiltrative and diffusely involving the majority of the bladder akin to its name sake in stomach. It is essential to distinguish this carcinoma from gastrointestinal metastases as different therapeutic strategies are often necessary.

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Assessment of topoisomerase II-alpha gene status by dual color chromogenic in situ hybridization in a set of Iraqi patients with invasive breast carcinoma

Rasha Abd Alraouf Neama, Manal A Habib, Sahira A Ali, Ali H Al-Khafaji, Mohammed F Alqanbar

Indian Journal of Pathology and Microbiology 2017 60(4):475-480

Background: The human epidermal growth factor receptor 2(HER2) proto-oncogene is overexpressed or amplified in approximately 15%–25% of invasive breast cancers. Approximately 35% of HER2-amplified breast cancers have coamplification of the topoisomerase II-alpha (TOP2A) gene encoding an enzyme that is a major target of anthracyclines. Hence, the determination of genetic alteration (amplification or deletion) of both genes is considered as an important predictive factor that determines the response of breast cancer patients to treatment. The aims of this study are to determinate TOP2A status gene amplification in a set of Iraqi patients with breast cancer that have had an equivocal (2+) and positive HER2/neu by immunohistochemistry (IHC) and to compare the results with estrogen receptor (ER) and progesterone receptor (PR) and HER2/neu status. Patients and Methods: A cross-sectional prospective study done on 53 patients with invasive breast carcinoma. Twenty-six out of total 53 cases were positive HER2/neu (3+), the remaining 27 equivocal HER2-IHC (2+) cases reanalyzed using dual-color chromogenic in situ hybridization (ZytoVision) probe kit for further identification of HER2/neu gene amplification. Using chromogenic in situ hybridization (CISH), TOP2A gene status determination was done for all cases. Results: There is a direct significant correlation between TOP2A gene amplification and HER2/neu positivity, P < 0.05 in that 15 (39.4%) out of 38 positive HER2/neu cases were associated with topoisomerase gene amplification. Regarding relation of topoisomerase gene to hormone receptor status (ER and PR), there was a significant negative relationship between the gene and ER receptor status. The higher level of gene amplification was noticed in ER and PR negative cases in about 13 (43.3%) and 14 (48.2%) for ER and PR, respectively. Conclusion: TOP2A gene status has a significantly positive correlation with HER2/neu status while it has a significantly negative correlation with hormone receptor status.

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Gliomatosis peritonei in mature cystic teratoma

IndianJPatholMicrobiol_2017_60_4_606_222

Gaurav Singla, Sufian Zaheer, Swati Singla, Sachin Kolte, Ashish Kumar Mandal

Indian Journal of Pathology and Microbiology 2017 60(4):606-607

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Histological and morphometric analysis of dilated cardiomyopathy with special reference to collagen IV expression

Parul Jain, Sudheer Arava, Sandeep Seth, Sanjeev Lalwani, Ruma Ray

Indian Journal of Pathology and Microbiology 2017 60(4):481-486

Introduction: Collagen distribution alterations are well known in dilated cardiomyopathy. There are also changes in microvasculature along with other histomorphorphological features. Aims and Objectives: To study the histomorphological features of DCM along with their quantitative correlation with LVEF. Alterations in collagen IV distribution pattern and microvasculature in DCM were also evaluated. Materials and Methods: The present study includes 34 right ventricular endomyocardial biopsies, 7 explanted native hearts and 41 autopsy control hearts. Sections were taken from lower half of right interventricular septum and stained for H and E, Masson trichrome and immunohistochemistry for CD34, SMA and Collagen IV to study the histological features, pattern of fibrosis, capillary and arteriolar distribution and collagen IV expression respectively. Morphometric analysis was carried out in all cases and controls using Image analysis software Image pro plus 7 and correlated with left ventricular ejection fraction. Results: The histomorphological changes of DCM include myocyte hypertrophy, nucleomegaly, and interstitial fibrosis. Interfiber fibrosis was the commonest. There was evidence of myocarditis, ischemic change and vessel wall alterations. Considerable alteration in Collagen IV distribution was observed with reduction in intensity and proportion of staining around myocytes quantified using Allred scoring against uniform pericellular staining in controls. Morphometric analysis revealed significant increase in nuclear area, myocyte width, percentage of fibrosis and reduction in capillary myocyte ratio in cases as compared to controls. There was no significant difference in arteriolar density. No significant association was observed between morphometric parameters and LVEF. Conclusion: Histomorphological changes in DCM are non-specific. Quantitation of histological parameters cannot be used to predict the disease progression as there was no significant correlation with LVEF. There is appreciable alteration in Collagen IV distribution in DCM owing to extracellular matrix alterations.

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Balloon cell melanoma metastasis to the temporal lobe

IndianJPatholMicrobiol_2017_60_4_622_222

Alexandros Iliadis, Thomas Zaraboukas, Panagiotis Selviaridis, Athanasios Chatzisotiriou

Indian Journal of Pathology and Microbiology 2017 60(4):622-623

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Spectrum of hepatobiliary cystic lesions: A 7-year experience at a tertiary care referral center in North India and review of literature

Prasenjit Das, Pragya Sharma, Tripti Nakra, Shouriyo Ghosh, Rajni Yadav, Brijnandan Gupta, Gaurav Khanna, KS Madhusudhan, Rajesh Panwar, MK Anoop, Ragini Kilambi, Anand N Singh, Nihar R Dash, Sujoy Pal, Siddhartha Datta Gupta

Indian Journal of Pathology and Microbiology 2017 60(4):487-500

Context: Cysts arising from the hepatobiliary tree are a group of heterogeneous lesions with regard to pathogenesis, clinical presentation, and radiological finding. They can be intrahepatic or extrahepatic, developmental, secondary to infective/inflammatory etiologies, as well as neoplastic. This study was conducted to determine the spectrum of hepatobiliary cysts in surgically intervened cases, with regard to their prevalence, histological spectrum, and clinicoradiological correlation, wherever possible. Methods: In this retrospective observational study, hematoxylin and eosin stained slides of all cases of hepatobiliary cystic lesions, operated between 2009 and 2016 were reviewed. Special stains as reticulin, Masson's trichrome, and periodic acid Schiff were done wherever necessary. Overall prevalence, age-sex distribution, clinical presentation and histopathological patterns were studied. Relevant imaging findings were correlated wherever possible. Results: A total of 312 cases of hepatobiliary cysts were identified, the majority in females. Choledochal cysts (CCs) were the most common type (n = 198,63.5%), followed by hydatid cysts (n = 73,23.3%), simple hepatic cysts (n = 10,3.2%), congenital hepatic fibrosis (n = 10,3.2%), biliary cystadenomas (n = 4,1.2%) hepatic mesenchymal hamartomas (n = 7,2.2%), and cavernous hemangiomas (n = 3,0.9%). Fibropolycystic liver disease (n = 2,0.6%), Caroli's disease (n = 1, 0.3%), liver abscess (n = 2, 0.6%), infantile hemangioendothelioma (n = 1,0.3%), and biliary cystadenocarcinomas (n = 1,0.3%) were rare. Lesions noted mostly in 1st decade of life were: CCs, fibrocystic liver disease, Caroli's syndrome, cystic mesenchymal hamartoma, and infantile hemangioendotheliomas. Conclusion: In our cohort of surgically intervened cases of hepatobiliary cystic lesions from a tertiary care hospital in North India, the CCs, followed by hydatid cyst were the most common lesions. Histology can play vital role in characterization, as often clinical findings and radiology can overlap.

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Immunoglobulin G4-related tubulointerstitial nephritis: A not to be missed diagnosis

Smita Mary Matthai, Anjali Mohapatra, Raiyani Palak, Gopal Basu

Indian Journal of Pathology and Microbiology 2017 60(4):577-580

Immunoglobulin G4-related tubulointerstitial nephritis (IgG4-TIN) is a newly recognized clinicopathological entity characterized by a dense interstitial infiltrate of IgG4-positive plasma cells accompanied by fibrosis and obliterative phlebitis causing acute or chronic renal dysfunction amenable to corticosteroid therapy. IgG4-TIN is the dominant manifestation of renal involvement in IgG4-related disease (IgG4-RD) which is a novel, immune-mediated, fibroinflammatory and multiorgan disorder. We describe a case of IgG4-TIN with isolated renal involvement in an elderly male patient with poor response to corticosteroid therapy. The distinctive serological, histopathological, and ultrastructural features of this condition which can facilitate differential diagnosis of TIN are highlighted to emphasize the need for early diagnosis and preservation of kidney function.

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Accuracy of vascular invasion reporting in hepatocellular carcinoma before and after implementation of subspecialty surgical pathology sign-out

Aaron R Huber, Raul S Gonzalez, Mark S Orloff, Christopher T Barry, Christa L Whitney-Miller

Indian Journal of Pathology and Microbiology 2017 60(4):501-504

Context: Liver cancers (including hepatocellular carcinoma [HCC] and cholangiocarcinoma) are the fifth most common cause of cancer death. The most powerful independent histologic predictor of overall survival after transplantation for HCC is the presence of microscopic vascular invasion (VI). Aims: Given that VI is known to have somewhat high interobserver variability in both HCC and other tumors, we hypothesized that pathologists with special interest and training in liver pathology would be more likely to identify and report VI in HCC than would general surgical pathologists. Settings and Design: We searched our departmental surgical pathology archives for transplant hepatectomies performed for HCC. Subjects and Methods: We identified 143 such cases with available sign-out reports and hematoxylin and eosin-stained slides. Statistical Analysis Used: Kappa results (level of agreement) were calculated. Results: Before surgical pathology subspecialty sign-out (SSSO) implementation, 49 of 88 HCC cases were reported as negative for VI; on rereview, 20 of these had VI. After SSSO implementation, 39 of 55 cases were reported as negative for VI; on our review, 8 of these had VI. Kappa (agreement) between general SO and subspecialty rereview was 0.562 (95% confidence interval [CI] = 0.411–0.714) "weak agreement." Kappa (agreement) between SSSO and rereview by select liver pathologists was 0.693 (95% CI = 0.505–0.880) "moderate agreement." Conclusions: Our study is one of only a few so far that have suggested improved accuracy of certain parameters under SSSO.

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Αρχειοθήκη ιστολογίου

Παρασκευή 12 Ιανουαρίου 2018

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