Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations.

BACKGROUND: Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. DESIGN: In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). RESULTS: The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. CONCLUSION: Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.

Epidermal Inclusion Cysts following Dupuytren's Percutaneous Needle Fasciotomy: A Case Report.

Percutaneous needle fasciotomy (PNF) is a favorable approach to Dupuytren's contracture management, usually reserved for Tubiana stage 1-2, uncomplicated disease. It is growing in popularity globally. Epidermal inclusion cysts are benign, commonly encountered cavities usually found on acral skin, rarely glabrous skin, and often following trauma. We present a 43-year-old laborer with two incidentally found epidermal inclusion cysts in the open excision of painful, Tubiana 3 and 2 Dupuytren's recurrence of his middle and ring fingers. He had undergone PNF to same 4 years prior. One cyst had ruptured. Both seemed to have migrated distally over time from the initial PNF site with progression of the Dupuytren's disease. This may be the only case of multiple epidermal inclusion cysts post PNF for Dupuytren's disease in the literature. The authors discuss factors contributing to epidermal inclusion cyst formation, and postulate whether needle choice may impact the risk of their development as a complication of PNF.

Intestinal Adenocarcinoma Arising from a Mature Cystic Teratoma.

Mature cystic teratomas are the most common ovarian germ cell tumour and account for 10-20% of all ovarian neoplasms. Malignant transformation of mature cystic teratomas is rare and has an incidence rate of less than 1%. The most common malignancy are squamous cell carcinomas. Here we present the case of an intestinal adenocarcinoma which is an exceedingly rare malignant entity arising within a mature cystic teratoma. Clinical presentation, imaging and histopathological diagnosis are discussed and previously presented cases in the literature reviewed.

The Association of BRAF V600E Mutation With Tissue Inhibitor of Metalloproteinase-3 Expression and Clinicopathological Features in Papillary Thyroid Cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The aim of this study was to investigate the association of tissue inhibitor metalloproteinase-3 (TIMP3) mRNA and protein levels in thyroid tissues, based on BRAF V600E status with the clinicopathologic characteristics of PTC. METHODS: A total of 60 fresh frozen tissue samples of PTC patients (15 male and 45 female) were collected during thyroidectomy. All clinicopathological information was obtained and samples were reviewed as well as confirmed by a pathologist; exon 15 of the BRAF gene was genotyped by sequencing, TIMP3 mRNA level was assessed using SYBR-Green Real-Time PCR, and TIMP3 protein level was measured using ELISA. RESULTS: Of 60 cases, BRAF mutation was found in 24 (40%). Larger tumor size and higher lymph node metastasis frequency were observed, significant in BRAF (+), compared to the BRAF (-) PTC group (P = 0.039 and P = 0.03, respectively). No significant difference was seen in the tumoral tissues of the TIMP3 mRNA level in BRAF (+), compared to BRAF (-) PTC samples. However, the mean TIMP3 protein level was significantly lower in tumoral tissues, compared to matched non-tumoral tissues in BRAF (+) PTC (P=0.003); TIMP3 protein level was significantly lower in tumoral tissues compared to matched non-tumoral tissues in BRAF (+), in subjects who had no lymph node metastasis and also in subjects with lymph node metastasis in both BRAF positive and negative PTC cases. CONCLUSION: Our results showed that BRAF mutation was associated with a larger tumor size, higher frequency of lymph node metastasis, and lower TIMP3 protein levels. Lower TIMP3 protein level was associated with the lymph node metastasis in PTC patients.

The Effects of Onion Consumption on Prevention of Nonalcoholic Fatty Liver Disease.

It is well known that dietary intakes play a pivotal role in pathogenesis of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH); however, the role of each component of diet has not yet been elucidated. Our objective was to evaluate the effects of onion consumption on prevention of NAFLD/NASH development. Sprague-Dawley rats were fed either high-fat, high sugar diet (model group), or high-fat, high sugar diet plus 7% onion powder (model + onion), or chow diet ad libitum for 7 weeks. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis factor-alpha (TNF-α) gene expression were determined. Hepatic histology was examined by H&E stain. Model + onion group had significantly lower hepatic steatosis, ballooning, lobular inflammation, and portal inflammation (p < 0.001), lower hepatic TNF-α gene expression (p < 0.001), lower plasma levels of ALT (p = 0.026), AST (p = 0.041), insulin (p < 0.001), TG (p = 0.041), and glucose (p = 0.009) compared with model group; however, weight gain, food intake, plasma total cholesterol and LDL levels were not significantly different between these two groups. Our data indicate that regular consumption of onion can prevent NAFLD even in the presence of the other risk factors such as obesity, hypercholesterolemia, and high energy, fat, and sugar intakes.

Altered Epigenetic Mechanisms in Thyroid Cancer Subtypes.

Thyroid carcinoma (TC) is the most frequent malignant neoplasm of the endocrine system. Molecular methods for diagnosis of invasive thyroid disease can be effectively adopted. Epigenetic factors play an important role in the diversity patterns of gene expression and the phenotypic and biological characteristics of TC subtypes. We aimed to review epigenetic changes in the main subtypes of TC, along with a presentation of the methods that have examined these changes, and active clinical trials for the treatment of advanced TCs targeting epigenetic changes. A literature analysis was performed in MEDLINE using PubMed, Elsevier, and Google Scholar for studies published up to 2016, using the keywords: "Epigenetic alterations" OR "Epigenetic changes", "thyroid cancers", "papillary thyroid cancer", "medullary thyroid cancer", "follicular thyroid cancer", and "anaplastic thyroid cancer", which resulted in 310 articles in English. All related abstracts were reviewed and studies were included that were published in English, had available full text, and determined the details of the methods and materials associated with the epigenetic patterns of TC and its subtypes (100 articles). Analysis of epigenetic alterations in TC subtypes helps to identify pathogenesis and can play an important role in the classification and diagnosis of tumors. Epigenetic mechanisms, especially aberrant methylation of DNA and microRNAs (miRs), are likely to play an important role in thyroid tumorigenesis. Further studies are required to elucidate the role of histone modification mechanisms in TC development.

Histologic Variants of Calcifying Odontogenic Cyst: A Study of 52 Cases.

AIM: This study aimed at evaluating histological features of 52 cases of calcifying odontogenic cyst (COC), which is an uncommon benign odontogenic lesion. The World Health Organization (WHO) classified COC as a neoplasm and used the term calcifying cystic odontogenic tumor (CCOT) for benign cystic type and the dentinogenic ghost cell tumor (DGCT) for the benign solid-type lesions. There is no agreement regarding COC classification. MATERIALS AND METHODS: A total of 52 cases of COC were selected and reviewed from the archive of the Pathology Department of Taleghani Educational Hospital, Tehran, Iran. To better understand the pathogenesis of COC, the cases were classified. RESULTS: There were 52 cases (31 males and 21 females). The lesion was found in all age groups, and patients' age from 8 to 61 years. Nineteen cases affected the maxilla, and 33 cases affected the mandible. Except two cases, all were intraosseous lesions. Radiographically, 30 cases showed a unilocular radiolucent area, and 22 cases showed a mixed radiolucent/ radiopaque region. Histopathologically, 43 cases were cystic type and 9 cases were neoplastic. CONCLUSION: There are two different histopathological entities. In view of these findings, it is very difficult to determine every lesion that has a cystic architecture is truly cystic or is a neoplastic one in nature. It is believed that the solid variants may be neoplastic. CLINICAL SIGNIFICANCE: A better understanding of the histological type of the lesion can provide a classification across patients. This can help in treatment planning to improve patient outcomes.

High-fat diet effects on metabolic responses to chronic stress.

CONTEXT: High-fat diets and chronic stress are prevalent risk factors for various chronic diseases in modern societies. OBJECTIVE: This study investigated the effect of high-fat diet on glucose-related metabolic responses to chronic foot-shock stress. MATERIALS AND METHODS: Male rats were divided into high-fat diet (containing 54.21% saturated and 44.89% unsaturated fatty acids) and normal diet groups and then into stress and non-stress subgroups. The diets were applied for 5 weeks, and stress was induced during the last week of the diet course. Plasma levels of metabolic parameters, HOMA-IR index, intra-abdominal fat weight, and islets' insulin secretion were assessed. RESULTS: High-fat diet increased abdominal fat weight and plasma leptin, and insulin levels in response to stress without affecting HOMA-IR index and islets' insulin secretion. CONCLUSIONS: High proportion of unsaturated fat may not lead to deleterious metabolic responses; however combined with chronic stress has a synergistic and adverse effect on visceral adiposity and results in elevated plasma leptin.

An Accessible and Pragmatic Experimental Model of Nonalcoholic Fatty Liver Disease.

UNLABELLED: BACKGROUND There is no convenient cheap pragmatic experimental model for Nonalcoholic Fatty Liver Disease (NAFLD)/Nonalcoholic Steatohepatitis (NASH). OBJECTIVE: Our objective was to create a pragmatic model of NAFLD/NASH. METHODS Sprague-Dawley rats were fed a high-fat, high sugar homemade diet ad libitum for seven weeks. The high-fat, high sugar diet included 59% of energy derived from fat, 30% from carbohydrates, and 11% from protein. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis factor-alpha (TNF-α) gene expression were determined. Hepatic histology was examined by H&E stain. RESULTS Rats fed the high-fat, high sugar diet developed hepatic steatosis, and a moderate inflammation, which was associated with increased serum levels of liver enzymes, glucose, insulin, triglyceride, cholesterol, and hepatic TNF-α gene expression. CONCLUSION This rat model resembles the key features of human NAFLD/NASH and provides a simple pragmatic experimental model for elucidating the disease prevention and treatment.

"Googling" for Cancer: An Infodemiological Assessment of Online Search Interests in Australia, Canada, New Zealand, the United Kingdom, and the United States.

BACKGROUND: The infodemiological analysis of queries from search engines to shed light on the status of various noncommunicable diseases has gained increasing popularity in recent years. OBJECTIVE: The aim of the study was to determine the international perspective on the distribution of information seeking in Google regarding "cancer" in major English-speaking countries. METHODS: We used Google Trends service to assess people's interest in searching about "Cancer" classified as "Disease," from January 2004 to December 2015 in Australia, Canada, New Zealand, the United Kingdom, and the United States. Then, we evaluated top cities and their relative search volumes (SVs) and country-specific "Top searches" and "Rising searches." We also evaluated the cross-country correlations of SVs for cancer, as well as rank correlations of SVs from 2010 to 2014 with the incidence of cancer in 2012 in the abovementioned countries. RESULTS: From 2004 to 2015, the United States (relative SV [from 100]: 63), Canada (62), and Australia (61) were the top countries searching for cancer in Google, followed by New Zealand (54) and the United Kingdom (48). There was a consistent seasonality pattern in searching for cancer in the United States, Canada, Australia, and New Zealand. Baltimore (United States), St John's (Canada), Sydney (Australia), Otaika (New Zealand), and Saint Albans (United Kingdom) had the highest search interest in their corresponding countries. "Breast cancer" was the cancer entity that consistently appeared high in the list of top searches in all 5 countries. The "Rising searches" were "pancreatic cancer" in Canada and "ovarian cancer" in New Zealand. Cross-correlation of SVs was strong between the United States, Canada, and Australia (>.70, P<.01). CONCLUSIONS: Cancer maintained its popularity as a search term for people in the United States, Canada, and Australia, comparably higher than New Zealand and the United Kingdom. The increased interest in searching for keywords related to cancer shows the possible effectiveness of awareness campaigns in increasing societal demand for health information on the Web, to be met in community-wide communication or awareness interventions.

Biliary mucinous cystic neoplasm: a case report and review of the literature.

Hepatobiliary cystadenomas (HBC) is a rare neoplasm which comprising less than one percent of liver cystic neoplasms. Although it's known as a benign tumor, but they have a potential for neoplastic transformation. Making a proper diagnosis and ruling out of other differential diagnosis is important because of different treatment. In the present study, we described a case of HBC manifested as idiopathic dominant biliary stricture in common hepatic duct (CHD), on the basis of spiral CT scan and MRI, and elevated CA19-9. With a probable diagnosis of malignant biliary stricture, she underwent ERCP and cholangioscopy that were non-diagnostic and final diagnosis was made surgically. HBCs usually found incicentally as a cystic lesion and biliary stricture without visible cyst in imaging like that seen in cholangiocarcinoma is very unlikely. In truth, this patient is an unusual manifestation of one rare disease.

The effects of onion consumption on treatment of metabolic, histologic, and inflammatory features of nonalcoholic fatty liver disease.

BACKGROUND: The aim of this study was to evaluate the effects of onion powder consumption on treatment of Non-alcoholic Fatty Liver Disease (NAFLD) in an experimental model of disease. METHODS: Sprague-Dawley rats were fed high-fat (HF) diet for seven weeks to induce the NAFLD. Then, they were treated by either the same diet (HF), or high-fat diet plus 7 % onion powder (HF + onion), or chow diet (control), or chow diet plus 7 % onion powder (control + onion)ad libitum for four weeks. Serum levels of fasting glucose, triglyceride, cholesterol, liver enzymes, insulin, and hepatic tumor necrosis factor-alpha (TNF-α) gene expression were determined. Hepatic histology was examined by Hematoxylin and Eosin stain. RESULTS: Dietary food intakes and weigh gain were significantly more in animals fed control + onion diet in comparison to the other groups. Animals fed control or control + onion diet had significantly lower plasma levels of hepatic enzymes, lipid profile, glycemic indices, and hepatic TNF-α gene expression as compared with HF diet fed groups; however, there was no significant difference in the histopathologic features of NAFLD among different groups. CONCLUSION: Our results indicate that onion consumption can be effective in NAFLD management when it is combined with a healthy diet.

Outcome of subsequent pregnancies in familial molar pregnancy.

Familial recurrent molar pregnancy is an exceedingly rare condition, in which complete hydatidiform moles are mostly diploid but biparental in origin and the outcome of subsequent pregnancies is likely to be a hydatidiform mole or other type of reproductive loss. We previously reported a case of familial molar pregnancy (family K) comprising five affected members (four sisters and one of their cousins) each with at least one hydatidiform mole (HM). In addition to the molar pregnancies, these patients have a total of three miscarriages and 8 normal pregnancies leading to healthy children; but the youngest member of this family has given birth to a boy with Down syndrome. Our second family (case S) includes two sisters with diploid biparental complete moles. They have a total of six molar pregnancies with no living child. Recently the younger sister had a partial molar pregnancy with apparently normal XX fetus accompanying diffuse molar changes of the placenta that led to preeclampsia and preterm delivery. Overall, these families have had 26 pregnancies including 12 molar pregnancies (complete or partial) and three abortions. We concluded that these families are predisposed to various genetic mutations, chromosomal abnormalities and clinical manifestations, which affect their offspring. Further studies of patients are needed to determine any relationship between a history of familial molar pregnancy and trisomy or other chromosomal abnormalities in offspring and genetic mutations in the products of conception to complete the puzzle and manage familial molar pregnancy.

Role of endoscopic ultrasound in evaluation of pancreatic neuroendocrine tumors--report of 22 cases from a tertiary center in Iran.

BACKGROUND: The pancreatic neuroendocrine tumor (pNET) is relatively rare and generally felt to follow an indolent course. EUS has an important role in detection of pNET. This is a review of clinical and radiological presentation and pathologic reports of 22 patients with pNET. PATIENTS AND METHODS: In this study we analyzed clinical and radiological presentations and pathologic reports of all relevant cases who were referred to Taleghani hospital for 3 years since 2008. RESULTS: A total of 22 patients 28-74 years old (mean=49) were enrolled between 2008 and 2011. Among the total, 13 (59%) were male, 9 (41%) were female and 16 (72.7%) had functional tumors. The results of CT were negative in 12 (54%) cases but EUS was capable of detecting the lesions in these patients, cysts being found in 4 (19%) patients. CONCLUSION: EUS is a highly sensitive procedure for the localization of functional pNETs and especially insulinomas. Nonfunctional tumors were detected in more advanced and late stages and cystic lesions were more common in this group.

Encapsulated insular carcinoma of the thyroid arising in graves' disease: report of a case and review of the literature.

Insular carcinoma represents a rather rare form of thyroid cancer. Total encapsulation and history of hyperthyroidism are even extremely rarer events with only a few cases reported in the literature. This article reports an insular carcinoma of the thyroid in a 51-year-old woman, displaying these features and pulmonary metastasis with no cervical lymph node involvement.

Pathologic findings of Whipple pancreaticoduodenectomy: a 5-year review on 51 cases at Taleghani general hospital.

AIM: The aim of this study was to comprehensively analyze histopathologic parameters of Whipple pancreaticoduodenectomy specimens at Taleghani general hospital pathology department. BACKGROUND: The Whipple procedure is performed for variety of tumors involving the head of the pancreas, ampulla of Vater, common bile duct, or duodenum. PATIENTS AND METHODS: Records of all cases of Whipple pancreaticoduodenectomy between 2007 and 2011were retrospectively reviewed and pathological details of diagnosis and staging were extracted. RESULTS: A total of 51 patients underwent Whipple procedure during a 5-year period, including 37 males and 14 females. The average age was 57 years (18-82 years). The most frequent presenting symptoms were jaundice and weight loss. Forty-four patients (86.3%) had malignant and 7 (13.7%) had benign lesions. Among malignant lesions, 27 (61.4%) were ampullary carcinomas, 12 (27.3%) were pancreatic carcinomas and 5 (11.4%) were cholangiocarcinomas. The pathological stage of most of the tumors was T3 (50%); followed by T2 (29.5%), and T1 (15.9%); only 4.5% were T4. Mean tumor size was 2.8 cm (0.2-7 cm). Duodenal and common bile duct margins were tumor-free in most cases (95.5 %). The pancreatic margin was free in 81.8% of patients; this margin had not been evaluated in 5 patients. Nearly 38.6% of all tumors showed vascular invasion while 68.2% showed perineural invasion. The average number of dissected lymph nodes was 4 (range 1-15); although in 25% of specimens, no lymph nodes had been found. Twelve specimens (35.3%) had lymph node metastases. CONCLUSION: The present study demonstrates that most of our patients are diagnosed with malignancy, at advanced stage, and further research is needed to develop practical methods for earlier diagnosis. The fact that 25% of specimens had no lymph nodes needs more consideration.

CagA status and VacA subtypes of Helicobacter pylori in relation to histopathologic findings in Iranian population.

BACKGROUND/OBJECTIVE: The aim of this study was to detect dominant cagA/vacA genotypes of Helicobacter Pylori (H. pylori) and determine correlations between different cagA/vacA genotypes and histologic features of chronic gastritis in Iranian patients. METHODS: Gastric biopsy was taken from 166 patients with nonulcer dyspepsia. The specimens were processed and DNA from each H. pylori isolate was extracted from multiple colony sweeps for identification of glmM gene. The vacA subtypes and cagA gene were tested by PCR . Histopathological features were recorded and graded according to partial Sydney system. RESULTS: Of the 86 strains, 66 (76.7%) were cagA positive. The proportions of vacA gene subtypes s1, s2, m1 and m2 in the 78 strains isolated were 70.5%, 29.5%, 37.2% and 62.8%, respectively. About 83.3% of the vacA-positive strains had s1 allele. Twenty-six strains (33.3%) were positive for both cagA and m1 allele. Positive cagA status and vacA subtypes were not associated significantly with presence of neutrophil infiltration, intestinal metaplasia or H. pylori density. Only vacA s1 was significantly associated with more severe inflammation (P=0.02). The dominant genotype of H. pylori was vacA plus s1/m2. CagA gene positivity rate was not closely associated with severity of the disease. CONCLUSION: H. pylori strains showing vacA s1 genotype were associated with more severe gastritis. These findings show that vacA genotyping may have clinical relevance in Iran.

Effects of chimerism on graft-versus-host disease, disease recurrence, and survival after HLA-identical marrow transplantation in Iran.

BACKGROUND: The coexistence of recipient's and donor's hematopoietic systems after allogeneic marrow transplantation is called mixed chimerism. OBJECTIVE: The objective of this study was to evaluate the effects of MC on graft-versus-host disease (GVHD), disease recurrence, and survival after HLA identical marrow transplantation in a transplant center in Iran. METHODS: The association of MC with acute GVHD, disease recurrence, survival, and relapse-free survival was investigated in 91 patients who underwent either bone (n = 12) or peripheral blood (n = 79) HLA-identical marrow transplantation. Chimerism was assessed using multiplex amplification of short tandem repeats (STR). Patients had thalassemia (n = 19), acute myelogenous leukemia (AML) (n = 29), acute lymphocytic leukemia (ALL) (n = 20), chronic myelogenous leukemia (CML) (n = 18), and other diseases (n = 5). The median age was 21 (range: 3 - 50) years. There were 38 (42%) female and 53 (58%) male participants. Conditioning was made through busulfan plus cyclophosphamide in 34 patients; busulfan plus fludarabin in 51 patients; and busulfan plus fludarabin plus antithymocyte globulin in 6 patients. The median follow-up was 13 months. RESULTS: On day +30, complete chimerism (CC) was observed in 72 (79%) patients, MC in 15 (17%), and no chimerism in 4 patients. The incidence of acute GVHD was significantly (P = 0.01) lower in mixed chimeras than in complete chimeras. There was no significant difference in acute GVHD grade (I, II vs. III, IV) between the two groups. The incidence of relapse was 18%. There was no difference in relapse rate between MC and CC groups. Overall survival was 89%. There was no significant difference in the overall survival between MC and CC group (96% vs. 85%, respectively). Relapse-free survival was 80% that was not significantly different between the two groups. CONCLUSION: Despite some previous reports, we found no significant difference in the survival and relapse rates between MC and CC groups.