bita geramizadeh

Chemokines seriously affecting immune responses to viral infections and allograft rejections.

Therefore, the current study aims to evaluate the expression levels of CXCLs and CXCR3 in liver transplanted (LT) patients with hepatitis B (HBV), hepatitis C (HCV), HBV/HCV co-infection, and noninfected ones.

The mRNA expression levels of studied genes were evaluated in LT patients with HBV (n=69), HCV (n=15), HBV/HCV co-infection (n=16), and non-infected (n=48) patients, compared to the control group (n=25). HBsAg and HBeAg were analyzed using ELISA methods. HBV-DNA and HCV-RNA were evaluated using simple PCR and nested RT-PCR protocols.

The mRNA expression level of CXCL10 was significantly up-regulated in HBV-infected and noninfected groups compared to controls (p≤ 0.05). The CXCL11 and CXCR3 mRNA expression levels were significantly increased in the patient groups compared with controls (p≤ 0.05). The expression levels of CXCL9 and CXCL10 were significantly correlated in the HBV group (r= 0.6, p≤ 0.05). The correlation between CXCL10 and CXCL11 was also significantly positive (r= 0.4, p≤ 0.05). Additionally, CXCL11 mRNA expression significantly associated with CXCR3 (r= 0.4, p≤ 0.05).

The up-regulation of CXCL11, CXCL10, and CXCR3 in HBV and HCV-infected and non-infected liver transplant patients compared to the controls and the direct correlations between the expression levels of CXCLs and CXCR3 in HBV liver transplant patients put more emphasis on the critical function of these molecules in the HBV and HCV infections pathogenesis in post-liver transplantation. However, more investigations are needed.

Cytomegalovirus resistance to ganciclovir with specific mutations in the UL54 gene is a factor in treatment failure and disease progression in organ transplant recipients, particularly kidney and hematopoietic stem cell transplant recipients. This study aimed to determine the mutations leading to resistance in the UL54 gene of human cytomegalovirus.

In this study, after screening 23 kidney transplant and 2 hematopoietic stem cell transplant recipients with a positive initial CMV test, 6 patients were included in the final study based on the inclusion criteria (at least 2 available follow-ups with positive CMV Real-time PCR results). The UL54 gene was amplified using Nested-PCR, and the PCR products were then sequenced using the Sanger sequencing method. Finch software (version 1.4.0) was used to analyze the sequencing results.

After reviewing the sequencing results, no known mutations were observed in 4 kidney transplant recipients. Also, a serine 882 insertion mutation in the UL54 gene was observed in 1 hematopoietic stem cell transplant recipient. Examination of the phylogenetic tree of the UL54 gene showed that the Iranian isolate ancestrally belongs to 20 reference strains, including the Merlin strain.

Given that the emergence of the serine 882 insertion mutation can weaken the potential for treatment and impair response to ganciclovir, it is very important to monitor the patients in question, determine the viral load, and assess their response or lack of response to treatment.

Cytotoxic CD4+ T cells eliminate human cytomegalovirus (HCMV)-infected cells through direct cytotoxic granules exocytosis. We aimed to evaluate the functional cytotoxic gene profile of CD4+ T cells alongside the frequency of the cytotoxic phenotype in renal transplant recipients with cytomegalovirus reactivation. Blood samples were collected from twenty renal recipients with and without HCMV reactivation (HCMV+ and HCMV- groups) and ten healthy adults (control group). CD4+ T cells were isolated to assess the frequency of cytotoxic CD4+ T cells via CD107a surface staining using flow cytometry and to evaluate gene expression of perforin, granzyme B, Runt-related transcription factor 3 (RUNX3), and Eomesodermin (Eomes) by quantitative PCR. The frequency of CD4+ CD107a+ T cells was higher in the HCMV+ group compared to the HCMV- group and significantly higher than in the control group (22.69 ± 3.47 vs 16.41 ± 2.24 and 11.60 ± 1.17, respectively). Perforin gene levels were reduced in the HCMV+ group compared to the other two groups, while granzyme B gene levels were similar between HCMV+ and HCMV- groups but lower than in the control group (0.63 ± 1.24 vs 0.67 ± 2.27 and 1.00 ± 0.00, respectively). This study demonstrated an increased frequency of cytotoxic CD4+ T cells with potentially reduced functionality in kidney transplant patients with HCMV infection. It also suggests that these cells might employ other mechanisms, such as death receptor-mediated killing, or the production of other granules.

The current newborn screening for Classic Galactosemia (CG) presents significant challenges, including a low positive rate and a high false-positive rate.

In this study, we aimed to establish new cut-off values (COVs) for CG screening and introduce a novel approach.

Total galactose (TGAL: The sum of galactose (Gal) and galactose-1-phosphate (G-1-P)) levels of all newborns born in Fars, Iran, from August 2006 to December 2020, were reviewed to establish cut-off ranges. A receiver operating characteristic (ROC) curve analysis was performed to define an optimal COV.

Out of 1,187,436 newborns, 4,893 (0.41%) were recalled for further evaluation due to an initial TGAL ≥ 4 mg/dL from a positive screening test, with 160 (3.26%) confirmed to have CG. In the initial negative screening results, nine infants were missed as false negatives. An area under the curve of 0.868 suggested that TGAL is a reliable indicator for distinguishing galactosemia from normal subjects. Receiver operating characteristic curve analysis indicated that a cut-off value (COV) of 5.2 mg/dL provided a sensitivity and specificity of 80.0% and 81.3%, respectively, making it an optimal conservative value for deciding on further recall in the Iranian setting. Additionally, a COV of 7.35 mg/dL demonstrated a sensitivity of 71.3% and specificity of 95.7%, making it a suitable cut-off for immediate referral.

We proposed a novel protocol for newborn screening in Iran, establishing a TGAL level of 5.2 mg/dL as a conservative cut-off for CG screening, showing excellent sensitivity while ensuring specificity for recalling suspicious cases. Furthermore, a cut-off of 7.35 mg/dL was identified for prompt consideration of urgent treatment.

Invasive candidiasis are the most prevalent fungal infections in solid organ transplant (SOT) recipients. In this regards, emerging pathogens and antifungal resistance are concerning issues in transplantation medicine.

Regarding universal prophylaxis in SOT recipients, particularly with fluconazole, and the emergence of azole-resistant species, the present study was conducted to species identification and antifungal susceptibility profiles of yeasts isolated from SOT recipients.

All adults undergone solid organ transplantations between 21 March -22 September 2022 in Abu-Ali Sina transplant center, Shiraz, Iran, were included with 6 months follow-up. Species identification of isolated yeasts from different clinical specimens was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing was determined according to the microbroth dilution method documented by CLSI.

During the study period, 28 of 383 (9.8%) adult SOT recipients developed at least one positive culture of yeasts isolated from different clinical specimens. Candiduria was the most prevalent type of involvement by Candida species. The incidence rate of invasive candidiasis was 2.6%. Of 54 isolated yeasts, C. albicans was the most frequent species (22/54, 40.7%), followed by C. glabrata (11/54, 20.3%), and C. parapsilosis (9/54, 16.7%). Resistance or decreased susceptibility to fluconazole was found in 55% of isolates, and also 13% of isolates were known crossresistant to different azole antifungal drugs.

Our results showed a high incidence of azole- resistant Candida strains causing candidiasis in SOT recipients. Indeed, the findings support the need to perform antifungal susceptibility testing of yeast isolates in immunocompromised patients to guide proper treatment.

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a liver disease. This is a chronic autoimmune disease, which can worsen over time and recur periodically. If left untreated, biliary cirrhosis may lead to liver failure. Considering that PBC is a rare disease in all age groups, especially in children, the purpose of this report was to describe a girl with hepatitis A virus (HAV) who was then diagnosed with PBC. This child is the first case reported in Iran. The patient is a 7-year-old girl with a pale complexion and eyes with a yellowish cross who was referred to the doctor. Considering that this patient had hepatitis, a blood test was requested to check the level of cholesterol and liver enzymes. The absence of cholestatic liver enzymes was observed in tests. Then, an anti-mitochondrial (AMA) test was requested for the patient, the result of which was negative. Finally, with imaging and biopsy, the diagnosis of PBC was confirmed for the patient. After the definite diagnosis of the disease, the child was treated with ursodeoxycholic acid (UDCA). The child in question is suffering from two medical and immunological diseases, HAV and PBC. Since this child was first infected with HAV, it is possible that the cause of PBC was HAV.

Celiac disease (CD) is a multifactorial systemic disease that causes enteropathy and can lead to a wide spectrum of disorders related to infertility.

This case-control study aimed to evaluate the frequency of celiac disease (CD) and its association with infertility in women.

This study was conducted on women referred to Ghadir Mother and Child Hospital in Shiraz. Women with infertility served as the case group, while fertile women comprised the control group. Blood samples were collected from participants, and tissue anti-transglutaminase (Anti-TTG Ab) levels were measured. Patients with elevated Anti-TTG Ab levels were referred for duodenal biopsy.

One hundred subjects were enrolled in the case group and 200 in the control group. Eight patients in the case group tested positive for serology, and four of these had duodenal biopsies confirming CD. In the control group, one individual tested positive for serology, but the duodenal biopsy was negative (P for between-group differences: 0.001 for serology and 0.012 for biopsy results). There was a significant association between high levels of Anti-TTG Ab and infertility (odds ratio = 17.30, 95 % CI: 2.13 - 140.39), which remained even after adjusting for age and body mass index (odds ratio = 9.92, 95 % CI: 1.17 - 84.21).

The frequency of CD was higher among infertile women compared to fertile women. Increased levels of Anti-TTG Ab were independently associated with infertility.

 Gastric cancer is the fourth leading cause of cancer-related deaths in the world. The identification of gastric cancer subtypes related to recognizable microbial agents may play a pivotal role in the targeted prevention and treatment of this cancer. The current study is conducted to define the frequency of Epstein-Barr virus (EBV) infection in gastric cancers of four major provinces, with different incidence rates of gastric cancers, in Iran.

 Paraffin blocks of 682 cases of various types of gastric cancer from Tehran, South and North areas of Iran were collected. Twelve tissue microarray (TMA) blocks were constructed from these blocks. Localization of EBV in tumors was assessed by in situ hybridization (ISH) for EBV-encoded RNA (EBER). Chi-squared test was used to evaluate the statistical significance between EBV-associated gastric cancer (EBVaGC) and clinicopathologic tumor characteristics.

 Fourteen out of 682 cases (2.1%) of gastric adenocarcinoma were EBER-positive. EBER was positive in 8 out of 22 (36.4%) of medullary carcinomas and 6 out of 660 (0.9%) of non-medullary type, which was a statistically significant difference (P<0.001). The EBVaGCs were more frequent in younger age (P=0.009) and also showed a trend toward the lower stage of the tumor (P=0.075).

 EBV-associated gastric adenocarcinoma has a low prevalence in Iran. This finding can be due to epidemiologic differences in risk factors and exposures, and the low number of gastric medullary carcinomas in the population. It may also be related to gastric tumor heterogeneity not detected with the TMA technique.

In liver transplant recipients, human Cytomegalovirus (CMV) infection is a significant concern. Ganciclovir is the preferred medication for treating widespread CMV infections. In some cases, patients might require high doses of treatment for CMV infections that are resistant to ganciclovir, although liver transplant patients who have received extended ganciclovir and valganciclovir prophylaxis have reported infrequent cases of ganciclovir-resistant CMV infections. Mutations in the UL54 gene, responsible for encoding deoxyribonucleic acid (DNA) polymerase, can result in resistance.

In this study, the focus was on UL54 mutations and their association with ganciclovir resistance.

In this study, 23 liver transplant recipients who were admitted to the transplant departments of Namazi and Abu Ali Sina hospitals within 2015 and 2017 were examined. Cytomegalovirus infection was then confirmed in them using the quantitative real-time polymerase chain reaction (PCR) method. The UL54 mutations were found after electrophoresis using the nested PCR method, and the PCR products were subsequently sequenced using the Sanger method. Sequence analysis and locating of UL54 mutations were performed using Finch software (version 1.4.0).

After sequencing 52 samples from 23 patients, 25 mutations in the UL54 gene were identified in 9 patients who were CMV-infected, occurring at a median of 32 days after transplant. These mutations, including S655L (10/9, 40%), N685S (8/9, 32%), F669L (4/9, 16%), A688V (2/9, 8%), and the novel AK124703.1: p.V668-G672dup (1/9, 4%), were detected in 9 liver transplant recipients over a median period of 2 years in the UL54 gene. Furthermore, a phylogenetic analysis was conducted to investigate the origins of these mutations in CMV isolated from the Iranian population.

Considering that treatment with the drug ganciclovir has led to resistance mutations, particularly the new AK124703.1:p.V668-G672dup mutation, and inefficiency in treatment, it is necessary to determine drug-resistant CMV strains and closely monitor these patients. This includes determining viral load, assessing response to treatment, and identifying non-response at regular intervals until the viral load is completely eradicated in order to ensure the effectiveness of the treatment.

Liver diseases in children and adolescents are a significant and arising public health issue and should be surveyed from different dimensions (clinical and para-clinical, psychological, socio-economic) and in diverse populations. Shiraz Liver Transplant Center, Shiraz, Iran is the only center for pediatric liver transplantation and its pre-operative evaluations. This provides a unique and valuable situation for studying this vulnerable population. The Shiraz Pediatric Liver Cirrhosis Cohort Study (SPLCCS) was established to assess cirrhotic children, the course of their disease, and treatment over time. This cohort study aimed to prospectively evaluate the natural course and factors that contributed to complications and death of children with chronic liver disease in the region. SPLCCS was launched in September 2018 after obtaining ethical approval; until August 2022, 370 children with end-stage liver disease were enrolled and followed every six months. Here, the cohort’s features, the included population’s baseline characteristics, and primary outcomes are reported.

 Type 1 diabetes is an autoimmune disorder characterized by the loss of pancreatic islets. Islet allotransplantation is a potentially beneficial therapeutic approach for diabetes. Islets suffer a variety of cellular insults including ischemia and partial vascular loss during isolation, resulting in a significant reduction in viability prior to transplantation. The present study aimed to investigate the effect of angiogenic microRNA (miRNA)-126 and -210 on islet function and viability in an indirect way.

 Poly Ethylenimine (PEI)-miRNA-126 and -210 polyplexes were constructed at various Nitrogen/Phosphate (N/P) ratios. After confirmation by gel retardation and ethidium bromide dye exclusion assay, its cytotoxicity and transfection efficiency were analyzed by MTT and fluorescent assays, respectively. After that, the selected polyplexes were used to transfect Human Umbilical Vein Endothelial Cells (HUVECs) in vitro and were indirectly co-cultured with islet cells for three days. Real-time polymerase chain reaction and enzyme-linked immunoassay were conducted to verify the regulation of target genes and the functionality of the islets.

 The findings showed that PEI could condense miRNAs at N/P=5. The viability of the HUVECs was decreased by increasing the amount of PEI. Additionally, ployplex-126 and -210 led to a decrease in the expressions of target genes, phosphoinositol-3 kinase regulatory subunit 2, sprouty-related EVH1 domain-containing protein 1, and ephrin-A3 in the islets. Moreover, the expressions of Bax and Bcl2 and their ratio in the treated groups by polyplex-126 and -210 led to better survival and function of the islets, with a higher expression of insulin and response to glucose stimulations. Furthermore, polyplex-210 could downregulate the anti-angiogenic protein, thrombospondin 1, compared to the other groups. Finally, the secretion of C-peptide was higher in polyplex-210 than in the other groups, adjusted for insulin secretion.

 The results indicated that angiogenic miRNAs could promote the survival and function of islet cells by interacting with their targets.

Model for end-stage liver disease (MELD) is currently used for liver transplantation (LT) allocation, however, it is not a sufficient criterion. 

This current study aims to perform a hybrid neural network analysis of different data, make a decision tree and finally design a decision support system for improving LT prioritization.

In this cohort follow-up-based study, baseline characteristics of 1947 adult patients, who were candidates for LT in Shiraz Organ Transplant Center, Iran, were assessed and followed for two years and those who died before LT due to the end-stage liver disease were considered as dead cases, while others considered as alive cases. A well-organized checklist was filled for each patient. Analysis of the data was performed using artificial neural networks (ANN) and support vector machines (SVM). Finally, a decision tree was illustrated and a user friendly decision support system was designed to assist physicians in LT prioritization. 

Between all MELD types, MELD-Na was a stronger determinant of LT candidates’ survival. Both ANN and SVM showed that besides MELD-Na, age and ALP (alkaline phosphatase) are the most important factors, resulting in death in LT candidates. It was cleared that MELD-Na <23, age <53 and ALP <257 IU/L were the best predictors of survival in LT candidates. An applicable decision support system was designed in this study using the above three factors.  

Therefore, Meld-Na, age and ALP should be used for LT allocation. The presented decision support system in this study will be helpful in LT prioritization by LT allocators.

Despite developing strategies for antiviral treatment, cytomegalovirus (CMV) infection remains one of the most common challenges in kidney transplant recipients (KTRs). The evaluation of CMV viral load is still the most practical main clinical approach for CMV assessment and guides decision-making in recipient antiviral treatment. However, there is not a specific viral load cut off for initiating treatment yet. On the other hand, the cellular immune system and the innate immune response prove their roles in diagnosing CMV reinfection and monitoring the therapeutic regime to control CMV. Interactions among the components of cellular immunity encounter CMV reactivation provide a strong treatment management plan for clinical decisions about antiviral therapy against CMV. Natural killer (NK) cells, as essential effector cells, present potentially antiviral activity through distinct subpopulations. CCR7expressing NK cells were identified by high cytotoxicity and functionality among NK cell subsets. Here, we explored the correlation between CCR7+ expressing NK cells with viral load in CMV reactivated-kidney transplant recipients.

A cross-sectional study was conducted among ten CMV reactivated KTRs. The CMV DNA copy number was evaluated utilizing real-time PCR.NK cell phenotypic profiling was done using flow cytometry.

Increasing of CMV viral load in CMV reactivated KTRs had a negative correlation with CCR7+CD57+ CD56/CD16+ NK cell (P < .05 r = -0.7) after CMV reactivation. Significantly increased level of CCR7-CD57- CD56/CD16+ NK cell was associated with CMV viral load within CMV reactivated KTRs (P < .05, r = 0.68).

CCR7 expression is associated with CMV reactivation, which offers a new aspect of CMV-associated immunity within the NK cell compartment.

Chromogranin is a marker that can be detected in the tissue of the neuroendocrine tumors (NET) by immunohistochemistry and as a biomarker for the diagnosis and follow-up of NET. In this study, we evaluated the correlation of prognostic characteristics of NETs (Ki67, location, and size) with the chromogranin level.

In this case-control study, we measured the serum level of chromogranin in 50 cases of NETs from different locations of the gastrointestinal tract, liver, and pancreas as well as 30 healthy individuals for one year (2016). The correlation of this level was evaluated with Ki67, size, and location of the tumors (main prognostic predictors of NETs).

The level of chromogranin in the above-mentioned 80 tumoral and healthy cases was 37 to 2585 ng/ml (242.3±439.4). The level of chromogranin in NETs and normal cases was 326.3±525.3 and 51.5±16.7, respectively. This level showed a statistically significant correlation with the Ki67 percentage and the tumor grade (P-value <0.05). There was no correlation between size and chromogranin level, but the highest level was detected in liver NETs. The cut-off level of 61.2 ng/ml correlated with the presence of NET with a sensitivity of 80% and specificity of 70%.

Chromogranin level can be used as a prognostic biomarker that is correlated with the grade of NETs and very high levels of this marker can be indicative of liver involvement. The cut-off level of 61.2 ng/ml can be considered as one of the predictors of the NET in the gastrointestinal, liver, or pancreas.

Natural killer (NK) cells are essential for controlling certain viral infections, including cytomegalovirus (CMV). In particular, the importance of NK cells in the context of CMV infection is underscored by the adaptive capabilities of these cells. Evidence suggests that some viruses can directly interfere with NK cell compartments and their activation and lead to shape-shifting the NK cell receptor repertoire. Still, it remains unknown whether the CMV can interact with NK cells without intermediaries. Here, we examined whether the direct effects of CMV lysate alter phenotypical properties of NK cells. To investigate this issue, NK cells were isolated from the blood of CMV seropositive healthy donors by negative magnetic separation. Isolated NK cells were cultured in the presence of CMV lysate and analyzed for the expression of NKG2A, NKG2C, and CD57 by FACS caliber. The results showed that NKG2C expression is significantly upregulated in the presence of CMV lysate compared to without stimulated group (mean increase, 6.65 %; 95% CI, 0.2582 to 13.02; p=0.043; R square: 0.38). Likewise, results have shown a significant decrease in the frequency of NKG2A+CD57- NK cell subsets (p=0.005; 95% CI, -13.49 to -3.151; R square: 0.5957) in the stimulated group compared to without stimulated ones. According to these results, CMV may drive a direct influence on NK cell receptor repertoire, including the expansion of NK cells expressing NKG2C receptor, which is needed for further studies.

 Prevention of death in patients on the waiting list for liver transplantation (LT) is a major concern to prioritize organ allocation. Since the model for the end-stage liver disease (MELD) and its modifications have many shortages, there is a need for further refinement of the allocation strategy.

 The current study aimed at assessing the predictors of mortality in LT candidates in a more comprehensive manner with the possible implications to improve the care of such patients and assist in developing better strategies for organ allocation.

 In the current cohort study, 544 adult LT candidates with end-stage liver disease were followed up for a mean of 12 months in three-month intervals. Data analysis was performed in Nutritionist, SPSS, and R software, using Kaplan-Meier, Cox proportional hazard (HRC), and LASSO Cox regression hazard (HRL) tests.

 The mean age of the patients was 46.7 ± 13.7 years; the majority were male (n = 336, 61.7%). At the end of the study, 414 (76.1%) subjects were still alive and 130 (23.9%) dead. The cumulative percentages of death were 33.1%, 57.7%, and 79.2% after 3, 6, and 12 months of waiting for a donor, respectively. Although there was a strong association between having hepatopulmonary syndrome (HPS) (HRC = 4.7, HRL = 1.8), a history of myocardial infarction (MI) (HRC = 3.3, HRL = 1.6), low-carbohydrate (CHO) diet (HRC = 2.7, HRL = 1.5), and mortality, it was weak for MELD score. Moreover, a serum level of CA 125, high polymorphonuclear (PMN) count, weight loss, a high level of alanine aminotransferase (ALT), positive hepatitis B virus (HBV) markers, high mean corpuscular volume (MCV) of red blood cells, ascites, and edema of gallbladder wall had association with mortality in LT patients.

 In addition to MELD score, HPS, a history of MI, low CHO intake, weight loss, ascites, PMN, CA 125, ALT, hepatitis B surface antigen, MCV, blood urea nitrogen, and gallbladder wall thickness are predictors of mortality in LT candidates and need to be considered in the LT allocation system.

Differential diagnosis between cholangiocarcinoma (CCA) and metastatic pancreatic ductal adenocarcinoma (PDA) in the liver is difficult and so far, no specific immunohistochemical marker is reported to differentiate these two tumors. Considering the existing literature, the level of expression of Annexins (Annexin A1, 10 and 13) have been studied for differential diagnosis between these two tumors by molecular methods and promising results have been reported. Therefore, in this study, we tried to investigate the immunohistochemical value of these three Annexins for the differential diagnosis of CCA and PDA in the liver.

The articles that reported the research subject in 10 years (2009-2019), including 45 cases of CCA and 50 cases of metastatic PDA in the liver were evaluated considering the presence or absence of AnnexinA1 (ANXA1), Annexin A10 (ANXA10) and Annexin A13 (ANXA13) expression by immunohistochemistry, were investigated.

This study showed, ANXA1 was positive both in PDA and CCA, ANXA10 was positive in ~60% of PDA cases and ~40% of CCA cases, and ANXA13 was mostly negative in both groups. The best sensitivity was found in cytoplasmic and nuclear ANXA1 (80% and 84%, respectively) to distinguish PDA from CCA and vice versa. The best specificity was observed in ANXA10 and ANXA13 to distinguish PDA from CCA. Also, ANXA13 had the best specificity to distinguish CCA from PDA. Our investigations showed that, ANXA1 probably can classify positive cases correctly, but it cannot discriminate PDA from CCA. ANXA10 had fair sensitivity and specificity to discriminate PDA from CCA. ANXA13 apparently had a high specificity that can help to narrow-down the differential diagnoses.

Microsatellite instability is common in familial colorectal cancers. It can be tested by the molecular and immunohistochemical methods. There are very few studies which address comparing the clinicopathological characteristics of microsatellite stable (MSS) and microsatellite unstable (MSI) colorectal cancers from Iran. n this study, we aimed to evaluate the clinicopathological and immunohistochemical findings of MSS and MSI colorectal cancers in our Center as the largest Center of gastrointestinal surgery and oncology in the South of Iran. We also compared the immunohistochemical method vs. molecular study using DNA sequencing.

For 5 years (2015-2019), 34 patients who underwent operation in the affiliated Hospitals of Shiraz University of Medical Sciences were clinically suspected to microsatellite instability (MSI). The molecular diagnostic tests with DNA sequencing were performed. Clinicopathological and immunohistochemical findings of MSI colorectal cancers were compared with those who were stable.

In the South of Iran, MSI colorectal cancers were more common in males. These tumors were more common in the right side with more tendencies to produce mucin with lymphocytic infiltration.

It was concluded that immunohistochemistry is a specific method for the diagnosis of MSI colorectal cancers, but false negative rate is high, and sensitivity is low. Therefore, we recommend performing molecular studies by DNA sequencing in colon cancer with clinical suspicion to MSI and negative immunohistochemistry

This study aimed to report an unusual presentation of an advanced gastric adenocarcinoma. Leptomeningeal carcinomatosis is a rare event in gastric adenocarcinoma. It is much more uncommon as the primary manifestation in post-mortem evaluation of the cause of death in a patient presenting with headache and neurological signs and symptoms. Herein, we discuss our experience with a case of gastric adenocarcinoma, who was diagnosed after death, presenting with neurological signs and symptoms of leptomeningeal carcinomatosis. A 52-year-old gentleman presented with intractable headache and neck pain as well as vertigo. His physical examination showed only decreased deep tendon reflexes. He died after a short period of coma. Post-mortem evaluation showed numerous signet ring cells in the subarachnoid space as well as gastric malignant ulcer. In patients with intractable headache with no identifiable cause, meningeal involvement and infiltration should be considered as the probable underlying cause. Radiologic findings are not significant; however, lumbar puncture can be diagnostic.

 Becoming infected with hepatitis A virus (HAV) is deadlier in patients with end-stage liver disease.

 This study aimed to determine the seroprevalence of chronic immunity to HAV in liver transplant (LT) candidates to determine whether HAV vaccination is necessary for them or not.

 This cross-sectional study was conducted on adult LT candidates who were referred to the LT center of Shiraz, Iran. The patients were interviewed for filling the data collection forms. These forms consisted of demographic information, medical backgrounds, etiology of chronic liver disease, a model for end-stage liver disease (MELD) score, laboratory findings, and abdominal sonography report. Furthermore, a 3-cc blood sample was obtained from each patient, and anti-HAV IgG was detected by Enzyme-linked Immunosorbent assay (ELISA) using standard Diapro kits. Univariable and multivariable data analyses were performed using SPSS version 20. A P-value of less than 0.05 was considered the significant cutoff in regression analysis.

 A total of 291 patients with a mean age of 47.73 ± 12.9 years were recruited in this study of whom, 197 (67.7%) patients were males, 237 (81.4%) were married, 229 (78.7%) were educated lower than 12 years, 250 (85.9%) were living in urban areas, and (221) 75.9% had access to sanitary water in their living area. anti-HAV IgG was detected in 269 (92.4%, 95% CI: 89.4 - 95.4%) patients. Multivariable analysis showed that lower knowledge of hepatitis A transmission routes (OR: 11.9, 95% CI: 1.39 - 101.8, P = 0.024), no waterpipe smoking (OR: 9.5, 95% CI: 1.6 - 55.5, P = 0.014), and older age (OR: 1.12, 95% CI: 1 - 1.24, P = 0.03) were the main predictors of HAV immunity, in sequence.

 Most LT candidates are HAV IgG positive, but due to the growing number of LT candidates and high mortality of HAV in non-immune cases, LT candidates should be checked for HAV IgG, especially younger or waterpipe smoking patients who are less immune. Also, all non-immune patients should be vaccinated against HAV, if possible.

Angiosarcoma, originating from vessels, constitutes about 0.2% to 0.3% of all pediatric soft tissue sarcomas. Prognosis of angiosarcoma is poor and depends on patient’s age, tumor location, size, histological grade and extent of tumor progression.

We report a rare case of a congenital angiosarcoma of scalp with dural and skull bone invasion in a one-month-old boy. His mother noticed the mass 2 days after birth as a very small insignificant nodule, but it grew rapidly afterward.

The treatment consisted of only a wide surgical resection. After 15 months there was no sign of local recurrence or metastasis was noticeable and the tumor showed favorable outcome. This case indicates the possibility of a better clinical behavior in congenital angiosarcoma.

Genetic polymorphism in the miRNA sequence might alter miRNA expression and/or maturation, which is associated with the development and progression of hepatocellular carcinoma (HCC) in liver transplant patients.

Therefore, the prevalence of miRNA-146a G > C (rs2910164), miRNA-499A > G (rs3746444), miRNA-149C > T (rs2292832), and miRNA-196a-2 C > T (rs11614913) gene polymorphisms was evaluated in liver recipients with HCC with or without experiencing graft rejection.

In a cross-sectional study, tissue samples were collected from 60 HCC patients who underwent liver transplant surgery at Namazi Hospital, Shiraz, Iran, in 2013 - 2015. A control group consisting of 120 individuals was randomly selected, as well. The genomic DNA was extracted from collected tissues and blood samples. The miRNA-146a (rs2910164), miRNA-499 (rs3746444), miRNA-149 (rs2292832), and miRNA-196a-2 (rs11614913) gene polymorphisms were evaluated in patients with HCC using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

The CC genotype and C allele of the miRNA-146a (rs2910164) polymorphism were significantly associated with the increased risk of transplant rejection in patients with HCC (P = 0.05 and P = 0.05, respectively). The CC genotype and C allele of the miRNA-146a (rs2910164) were also significantly more frequent in male liver transplant patients who experienced acute rejection than in non-rejected ones (P = 0.05 and P = 0.03, respectively). However, no significant association was found between the genotypes and alleles of miRNA-499 (rs3746444), miRNA-149 (rs2292832), and miRNA-196a-2 (rs11614913) polymorphisms and HCC outcomes in liver transplant recipients.

The importance of the CC genotype and C allele of the miRNA-146a (rs2910164) polymorphism in increasing the risk of transplant rejection was confirmed, but it needs further studies in larger populations.

Bilophlia spp. are gram-negative, pleomorphic rod, obligate anaerobe, oxidase-negative, catalase-positive and non-motile bacteria. B. wadsworthia is type species of genus Bilophila with the additional characteristic of urea hydrolysis. B. wadsworthia can be found in a variety of anaerobe infections, particularly appendicitis and intra-abdominal infection that are considered as important opportunistic pathogens.

This study was designed to identify Bilophila spp. in clinical specimens by culture and PCR. We examined 91 DNA samples extracted from infected appendix tissues with specific primers.

Data showed that Bilophila spp. DNA existence in 53.85% (n=49) provided appendiceal tissue.

The pathological and molecular examination of infected appendiceal tissues revealed that B. wadsworthia is able to act as the primary cause of significant lesions in the appendicle tissues.

Metastatic carcinoma to the epididymis is a very rare occurrence. Since the last 20 years, there have been only 13 cases reported in the English literature so far. The majority of the previous case reports presented with scrotal swelling and the most common primary carcinoma metastatic to epididymis has been prostatic adenocarcinoma. The size of the tumors has been small and below 5-cm. The age range has been 50 to 77 years. Herein we report the largest reported metastatic carcinoma to the epididymis (6-cm) in the youngest patient reported (36-year-old). Also, the second case of metastatic cholangiocarcinoma to the epididymis.

Hepatocellular adenoma (HCA) is a tumor with heterogenous molecular pathogenesis and varying malignant potential. Subclassification of HCAs is one of the important issues for the management decision to perform surgery or to follow up the patient. Iran is in intermediate status regarding the incidence of hepatocellular carcinoma, and on the other hand, incidence of viral precursors especially hepatitis B is decreasing, so it can be important to know the frequency of premalignant subtypes of liver cell adenomas in Iran. During the study period (10 years from 2008 to 2018) 40 cases of HCA (35 female and 5 males) were retrieved from the archives of the pathology departments of the affiliated hospitals of Shiraz University of Medical Sciences. The diagnosis was confirmed and the best paraffin block was used for IHC staining for liver fatty acid binding protein (LFABP), glutamine synthetase (GS), β-catenin and serum amyloid A (SAA). Histologic findings were also recorded. In the mean time, clinical charts of the patients were reviewed and clinicopathologic findings were compared. The most common subtype in our cases was hepatocyte nuclear factor-1α inactivated and the least common was β-catenin activated subtype. We didn’t find any cases of mixed subtype. Inflammatory subtype was seen in 10% of the cases. Another 10% of our cases were unclassified because all of the IHC markers were negative. Our results confirmed that immunohistochemistry should be routinely performed to subclassify HCAs. We also showed that frequencies of subtypes differ according to the studied population. For our population (Middle East or west Asia) HCAs with malignant potential are the least common.