Epinephrine in the Prevention of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis: A Preliminary Study.

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP). The incidence of post-ERCP pancreatitis (PEP) ranges between 15 and 20% among patients at high risk of developing PEP. The efficacy of indomethacin administration in the prevention of PEP is rather debatable. In the present randomized trial study, we evaluated whether or not the combination of indomethacin and epinephrine in comparison to the single administration of indomethacin differs in the pathogenesis and prevention of post-ERCP pancreatitis. PATIENTS AND METHODS: One hundred and ninety-two patients were randomized in a double-blinded manner into 3 groups: the epinephrine group (group A), the indomethacin group (group B), and the combined epinephrine and indomethacin group (group C). After the procedure, patients were evaluated for the PEP development. RESULTS: During the procedure, 66 patients were randomized to the epinephrine group (group A), 68 cases to the indomethacin group (group B), and 58 individuals to the indomethacin-epinephrine group (group C). The mean age of patients in the epinephrine group was 59.59 ± 15.680 years, in the indomethacin group it was 58.06 ± 17.125 years, and in the combination group it was 59.62 ± 15.369 years. In the present study, we did not observe a significant difference between the 3 groups in sex, age, pre-ERCP amylase, lipase, and patient and procedure risk factors including pancreatic duct (PD) dilation (p = 0.404), PD cannulation (p = 0.329), and difficult cannulation (p = 0.076) among others. PEP developed in 7 of the 192 individuals (3.6%), 6 PEP cases occurred in the indomethacin group and 1 in the epinephrine group (p = 0.016). Univariate analysis of risk factors for PEP in patients with and without pancreatitis revealed no significant difference between the pancreatitis group and the non-pancreatitis group. CONCLUSION: In comparison to the administration of indomethacin alone, a single application of epinephrine and the combination of epinephrine and indomethacin seem to be effective in reducing the cases of PEP. A further randomized clinical trial with a larger sample size is required to confirm the efficacy of our medication in the prevention of pancreatitis after ERCP.

Morphological alterations of cultured human colorectal matched tumour and healthy organoids.

Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention. Therefore, the current work focused on culturing matched healthy and tumour organoids from the same patient with colorectal cancer (CRC) and assessed their timed growth and structural differences on a daily basis. The healthy organoids underwent proliferation and branching morphogenesis, while the tumour organoids did not follow the same pattern, and the majority of them developed cystic structures instead. However, the number and size of tumour organoids were different from one patient to another. The differential morphological changes of the healthy versus human colonic tumour organoids likely linked to distinct molecular and cellular events during each day. Thus, while their specific structural features provide valuable in vitro models to study various aspects of human intestinal/colon tissue homeostasis and CRC which avoid or replace the use of animals in research, this model may also hold a great promise for the transplantation and regenerative medicine applications.

Acute Myeloid Leukemia as the Main Cause of Pancytopenia in Iranian Population.

BACKGROUND & OBJECTIVE: Pancytopenia is the reduction in the number of all 3 major cellular elements of blood and leads to anemia, leukopenia, and thrombocytopenia. A wide variety of etiologies result in pancytopenia including leukemia, aplastic anemia, and megaloblastic anemia. The current study identified the different etiologies of pancytopenia based on bone marrow examination in Iranian patients with pancytopenia. METHODS: A total of 683 cases of pancytopenia with various etiologies were selected for this retrospective study. Bone marrow biopsy was performed with the standard technique using Jamshidi needle. The inclusion criteria for patients with pancytopenia were hemoglobin (Hb) <10 g/dL, total leukocyte count (TLC) <4 x 109/L, and platelet count <140 x 109/L. RESULTS: In the present study acute leukemia was the first most common etiology detected in 235 (35.4%) patients in which acute myeloid leukemia (AML) comprised the majority of cases 142 (21.4%), followed by myelodysplastic syndrome (MDS) 100 (15%). In patients less than 20 years old, acute leukemia was also the commonest cause identified in 56 (57.7%) cases in which acute lymphoblastic leukemia (ALL) with 38.7% was the most common etiology; however in adults (>45 year old), AML accounted for the majority of cases 76 (53.5%). CONCLUSION: Since acute leukemia was the commonest etiology in both young and adults in which AML accounted for the majority of cases with pancytopenia in Iranian population, there was an urgent need to identify the underlying molecular or genetic mechanism of this malignancy for better further medical management and patients` survival.

Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients.

The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location.

Coexistence of splenic hemangioma and vascular malformation of the vertebrae.

BACKGROUND: Cavernous hemangioma is an encapsulated mass of dilated, endothelial lined vascular channels filled with slowly flowing blood. Cavernous hemangioma of the spleen is a rare condition with less than 100 reports so far. Hemangioma of the vertebral is a benign vascular legion around one or two vertebrae. These are usually asymptomatic and discovered incidentally. In this study we reported an extreme rare case of splenic hemangioma coexistence with vascular malformation of the vertebrae. To our knowledge this is the first report of coexistence of splenic hemangioma and hemangioma of the vertebra. CASE PRESENTATION: A 20-year-old iranian male with splenomegaly, abdominal pain, diarrhea and pancytopenia who was first highly suspicious for malignancy referred to our center for evaluation of the diagnostic workup. After full examination we detected a very rare case with a giant, solitary cavernous hemangioma of the spleen and multiple hemangiomas in his vertebrae. Histopathology of the spleen showed a large cavernous hemangioma occupying almost the entire spleen with large areas of infarction necrosis with multiple hemangiomas of the vertebrae. CONCLUSION: It is extremely rare to have a splenic hemangioma concurrent with vertebra hemangioma and this is clinically very important to consider splenic hemangioma in differential diagnosis of splenomegaly for a better therapeutic management in related patients.

Interleukin-16 polymorphisms as new promising biomarkers for risk of gastric cancer.

Gastric cancer (GC) is the second cause of cancer-related death worldwide. Interleukin (IL)-16 has a vital role in the development and homeostasis of the immune system. In the present study, we evaluated an exon variant rs4072111 C/T polymorphism and 3' UTR variant rs1131445 C/T within the miRNA binding with gastric cancer susceptibility in Iranian population. Genomic DNA was isolated from peripheral blood samples according to phenol chloroform extraction. The genotypes of IL-16 polymorphisms rs1131445 T/C and rs4072111 T/C were determined by polymerase chain reaction-restriction fragment length polymorphism method. In this case control study, a total of 256 patients with gastric cancer (238 cases (92.9 %) non-cardia and 18 cases (7.1 %) cardia) and 300 healthy control subjects were evaluated. In the present study, we found a significant association between rs4072111 of IL-16 gene and risk of GC in Iranian population. Individuals with CT genotype showed a significant association with 1.79-fold increased risk of GC (P = 0.008; adjusted OR 1.792; 95 % CI 1.164-2.759). The significant association was also detected for T allele of rs4072111 and increased risk of GC (P < 0.001; adjusted OR 1.981; 95 % CI 1.354-2.900). We also observed statistically a significant relationship between rs1131445 of IL-16 CT genotype and GC risk. Carriers of IL-16 CT genotype compared with TT genotype had 1.44 times higher increased likelihood of GC (P = 0.048; adjusted OR 1.445; 95 % CI 1.003-2.084). After stratification according to gender, we observed that in rs1131445, CT and CC male carriers had a higher risk of GC than females (P = 0.08; adjusted OR 1.608; 95 % CI 0.945-2.737 and P = 0.08; adjusted OR 2.186; 95 % CI 0.897-5.325, respectively). We also observed that for male carriers with C allele in rs1131445, there was a 1.53-fold higher risk of GC risk than female subjects (P = 0.029; adjusted OR 1.53; 95 % CI 1.04.4-2.248). We found that the rs1131445 T/C and rs4072111 T/C variants of IL-16 were significantly associated with increased risk of GC in Iranian population.

Prognostic Significance of Nuclear ß-Catenin Expression in Patients with Colorectal Cancer from Iran.

BACKGROUND: Beta catenin plays a key role in cancer tumorigenesis. However, its prognostic significance in patients with colorectal cancer (CRC) remains controversial. It has been demonstrated that 90% of all tumors have a mutation in individual components of multiple oncogenes in Wnt/ß-catenin pathway. Accumulation of nuclear ß-catenin in cytoplasm leads to uncontrolled cell proliferation. Thus, nuclear ß-catenin accumulation may be a valuable biomarker associated with invasion, metastasis and poor prognosis of CRC. OBJECTIVES: In this study the prognostic value of beta catenin expression in 165 Iranian CRC patients was evaluated. PATIENTS AND METHODS: In this cross sectional retrospective study immunohistochemistry analyses of formalin-fixed paraffin-embedded (FFPE) tumor tissues were performed to characterize the expression of nuclear ß-catenin in a series of 165 Iranian patients with colorectal carcinoma. Heat-induced antigen retrieval using the microwave method was applied for all staining procedures. Staining was scored independently by two observers, and a high level of concordance (90%) was achieved. Statistical analysis was done using the SPSS software for Windows, version 13.0.0 (SPSS Inc., Chicago, IL). Two-tailed P < 0.05 was considered statistically significant. RESULTS: The patients consisted of 85 males and 80 females. Eighty-eight patients had primary tumor of the rectum and sigmoid, while 77 patients had primary tumor of the colon. The mean period of follow-up was 47.2 ± 10 months and the median period of follow-up was 38 months (range 6 - 58) for each patient. Of 165 tumors, 32 tumors (19.39 %) showed expression of ß-catenin and 133 (80.6 %) were negative for ß-catenin expression. Based on our findings the distribution of Microsatellite Instability (MSI) status differed between patients with nuclear ß-catenin positive and negative tumors and this difference was significant (P = 0.001). Patients with nuclear ß-catenin positive expression profile were found to be younger than patients with negative nuclear ß-catenin expression (P = 0.010). Univariate and multivariate analysis showed that tumors with ß-catenin expression had a poorer prognosis compared to tumors without ß-catenin expression. CONCLUSIONS: According to our findings, the distribution of nuclear b-catenin expression is a poor prognostic marker in patients with colon cancer.

Novel Missense Mutation at Codon 2774 (C.8321 G>A) p.S2774N of APC Gene in a Denovo Case of Familial Adenomatous Polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease caused by germline mutation in Adenomatous Polyposis Coli (APC) gene. FAP accounts less than 1% of all colorectal cancers incidence. Patients generally present hundreds to thousands of adenomas in colon and rectum and develop colorectal cancer by age 35 - 40 if left untreated. A milder form of FAP with fewer numbers of polyps (< 100) is Attenuated FAP (AFAP) and in comparison with classical FAP, it usually diagnosed at an older age. Approximately 15% - 20% of FAP patients are ''de novo'' cases without any family history of the disease and novel APC mutations account for approximately 25% of FAP cases. In our study, we reported a novel missense mutation at the APC gene in a denovo patient with AFAP like phenotype.

Evaluation of the left-to-right shift of colon tumors in Iran: Is the trend changing?

BACKGROUND: Colorectal cancer (CRC) is the second cause of cancer-related deaths worldwide. There have been several studies reporting the proximal tumor shift, especially in Western countries. In the present study, we investigated the clinicopathologic and anatomical distributions of colorectal tumors in Iranian CRC patients. MATERIALS AND METHODS: In this retrospective cohort study, 258 patients with CRC from 2008 to 2013 were evaluated. Comparison of variables was performed using Pearson's chi-square test and Fisher's exact test depending on the nature of the data. RESULTS: A total of 258 patients including 124 (48.1%) females and 134 (51.9%) males enrolled in this study. The majority of cancers were detected in the rectosigmoid, i.e., 98 (38%) followed by the left colon, i.e., 84 (32.6%) and the right colon, i.e., 76 (29.5%). In the present study, we observed the significant association between metastases, adjuvant therapy, family history, and history of inflammatory bowel disease (IBD) with tumor, node, and metastasis (TNM) staging (P < 0.001). In univariate analysis, there was a strong association between overall survival (OS) and stage II CRC (P = 0.03). However, the predictive value was lost in multivariate analysis (P = 0.145). CONCLUSION: Unlike the majority of previous studies on Iranian CRC patients, we observed a considerably higher occurrence of right-sided colon cancers (84 versus 76). Although this phenomenon did not reach the statistical significance rate, based on recent studies on Iranian population including the present one, the pattern of anatomical distribution of colorectal tumors has been changed toward the proximal colon. This requires an urgent need to provide other strategies and complementary detecting approaches in order to identify proximal tumors in Iranian CRC patients.

Prevalence and characteristics of colorectal polyps in symptomatic and asymptomatic Iranian patients undergoing colonoscopy from 2009-2013.

BACKGROUND: Colorectal cancer is the third most common type of cancer in males and the second in females in Iran. Males are more likely to develop CRC than women and age is considered as a main risk factor for colorectal cancer. Prevalence of colorectal cancer has been increasing in Asian countries. AIM: The object of this study was to determine the clinical and pathology characteristics of colorectal polyps in Iranian patients and to investigate the variation between our populations with other populations. MATERIALS AND METHODS: A total of 167 patients with colorectal polyps were included in our study. All underwent colonoscopy during 2009-2013 and specimens were taken through polypectomy and transferred to pathology. All data in patient files including pathology reports were collected and analyzed by SPSS 16 software. A two-tailed test was used and a P-value of <0.05 was considered significant. RESULTS: Mean age of participants was 57±15. Some 84 were females (50.3%) and 83 males (49.7%). Total of 225 polyps were detected which 119 (52.9%) were in males and 106 (47.1%) were in females. Solitary polyps were observed in 124 patients (74%), 26 (15.6%) had two polyps and 17 (10.1%) with more than two polyps (three to five). Rectosigmoid was the site of most of the polyps (63.1%), followed by 19.6% in the descending colon, 7.6% in the transverse, 5.8% in the ascending, and 3.1% in the cecum, data being missing in two cases. CONCLUSIONS: Recto sigmoid was site of most of the polyps. The most prevalent type of lesion was adenomatous polyps detected in 78 (34.7%). Mixed hyperplastic adenomatous type observed in 70 (31.1%). This high prevalence of adenomatous polyps in Iranian patients implies the urgent need for screening plans to prevent further healthcare problems with colorectal cancer in the Iranian population.

Frameshift Mutations (Deletion at Codon 1309 and Codon 849) in the APC Gene in Iranian FAP Patients: a Case Series and Review of the Literature.

Familial adenomatous polyposis (FAP) is responsible for <1% of colorectal cancer (CRC) cases and is inherited an autosomal dominant trait. Patients generally present hundreds to thousands of adenomas and develop colorectal cancer by age 35- 40 if left untreated. Here we report four patients with germline frameshift mutation (small deletion) at exon 15 of adenomatous polyposis coli (APC) tumor suppressor gene. Peripheral blood samples were collected from patients and Exon 15 of the APC gene was studied by direct sequencing after genomic DNA extraction. Four frameshift mutations were detected. Two patients had 5 bp deletion, c.3927_3931delAAAGA and two siblings presented deletion at codon 849 (c.2547_2548delTA p.Asp849fsX62). This study was the first report of genetic screening in Iranian FAP patients. In contrast to other studies we revealed that one patient with mutation at codon 1309 had an attenuated phenotype.

MUTYH the base excision repair gene family member associated with colorectal cancer polyposis.

COLORECTAL CANCER IS CLASSIFIED IN TO THREE FORMS: sporadic (70-75%), familial (20-25%) and hereditary (5-10%). hereditary colorectal cancer syndromes classified into two different subtypes: polyposis and non polyposis. Familial Adenomatous polyposis (FAP; OMIM #175100) is the most common polyposis syndrome, account for <1% of colorectal cancer incidence and characterized by germline mutations in the Adenomatous polyposis coli (APC, 5q21- q22; OMIM #175100). FAP is a dominant cancer predisposing syndrome which 20-25% cases are de novo. There is also another polyposis syndrome; MUTYH associated polyposis (MAP, OMIM 608456) which it is caused by mutation in human Mut Y homologue MUTYH (MUTYH; OMIM 604933) and it is associated with multiple (15-100) colonic adenomas. In this paper we discuss MUTYH mechanism as an important member of Base Excision Repair (BER) family and its important role in polyposis condition.

Simplified MSI marker panel for diagnosis of colorectal cancer.

BACKGROUND: Colorectal cancers (CRCs) tumors are diagnosed by microsatellite instability (MSI) due to accumulation of insertion/deletion mutations in tandem repeats of short DNA motifs (1-6 bp) called microsatellites. Microsatellite instability (MSI) is not only a hallmark marker for screening of hereditary nonpolyposis colorectal cancer (HNPCC), but also a prognostic and predictive marker for sporadic colorectal cancer. Our objective was to determine and study of five mononucleotide microsatellite markers status among Iranian patients with HNPCC and sporadic colorectal cancer. MATERIALS AND METHODS: In the current investigation 80 sporadic CRC and 80 HNPCC patients were evaluated for MSI. The pentaplex panel including 5 quasimonomorphic mononucleotide repeats (NR-21, BAT-26, BAT-25, NR-27 and NR-24) was used. RESULTS: Our findings showed that the NR-21 was the most frequent instable marker among the other markers. 53% and 25.6% specimens had instability in sporadic CRC and HNPCC, respectively. Furthermore, the frequencies of instability BAT-25 was determined in 20% sporadic CRC and 23% HNPCC samples. Interestingly our results demonstrated that the frequency of instability NR-24 was similar 20% sporadic CRC and 20.5% HNPCC. Moreover, percentage of NR-27 in HNPCC was 19.2 and 0% in sporadic CRC. Finally, BAT-26 was instable in 21.8% HNPCC patients while we could find 6.6% instability for BAT-26 in sporadic cases. CONCLUSION: It seems that among 5 mononucleotides markers NR-21 was the most useful marker for diagnosis HNPCC and sporadic cancer. Following NR-21, BAT-25 and NR-24 are the most reliable markers. Therefore using a triplex panel including 3 aforementioned MSI markers should be more promising markers for identifying MSI status in both patients with HNPCC and/or sporadic colorectal cancer.