Investigation of Clinical, Laboratory, Imaging Findings and Histopathological Features of Patients with Gastric Neuroendocrine Cell Hyperplasia.

BACKGROUND/AIMS: Neuroendocrine cell hyperplasia is a non-neoplastic proliferation of enterochromaffin-like cells and is considered a premalignant lesion because of their potential to progress to neuroendocrine tumor. In this study, we aimed to evaluate the demographic and clinical features, laboratory, radiological and endoscopic findings, gastric biopsy histopathological features, follow-up frequency, and histopathological findings of patients diagnosed with gastric neuroendocrine cell hyperplasia as well as to investigate the factors that play a role in the development of neuroendocrine tumors on the basis of neuroendocrine cell hyperplasia. MATERIALS AND METHODS: The study has been conducted in 2 centers with 282 patients that were grouped as those with and without neuroendocrine tumor. Individuals with control endoscopy were separated as those with regression of neuroendocrine cell hyperplasia and those without regression, and the determined parameters were evaluated between the groups. RESULTS: The most common histological subtype of neuroendocrine cell hyperplasia was linear+micronodular (50.4%). Neuroendocrine tumor developed in 4.3% (12/282) of the patients with neuroendocrine cell hyperplasia after a mean of 36 months. The presence of polyps as confirmed via endoscopy and dysplasia as confirmed via histopathological examination was significantly higher in favor of the group with neuroendocrine tumor (P = .01). In patients with neuroendocrine cell hyperplasia regressed and patients in whom it did not regress were examined, the rate of asymptomatic patients and increased sedimentation rate were found in favor of the group that did not regress (P = .02 and P = .02), but no difference was found in other parameters. CONCLUSION: Neuroendocrine tumor development rate was found to be 4.3% in the background of neuroendocrine cell hyperplasia. Two factors predicting progression from neuroendocrine cell hyperplasia to neuroendocrine tumor can be elaborated as the presence of polypoid appearance due to neuroendocrine cell hyperplasia as confirmed via endoscopy and dysplasia as confirmed via histopathological examination.

Quantitative real-time PCR analysis of bacterial biomarkers enable fast and accurate monitoring in inflammatory bowel disease.

Inflammatory bowel diseases (IBD) affect millions of people worldwide with increasing incidence. Ulcerative colitis (UC) and Crohn's disease (CD) are the two most common IBDs. There is no definite cure for IBD, and response to treatment greatly vary among patients. Therefore, there is urgent need for biomarkers to monitor therapy efficacy, and disease prognosis. We aimed to test whether qPCR analysis of common candidate bacteria identified from a patient's individual fecal microbiome can be used as a fast and reliable personalized microbial biomarker for efficient monitoring of disease course in IBD. Next generation sequencing (NGS) of 16S rRNA gene region identified species level microbiota profiles for a subset of UC, CD, and control samples. Common high abundance bacterial species observed in all three groups, and reported to be associated with IBD are chosen as candidate marker species. These species, and total bacteria amount are quantified in all samples with qPCR. Relative abundance of anti-inflammatory, beneficial Faecalibacterium prausnitzii, Akkermansia muciniphila, and Streptococcus thermophilus was significantly lower in IBD compared to control samples. Moreover, the relative abundance of the examined common species was correlated with the severity of IBD disease. The variance in qPCR data was much lower compared to NGS data, and showed much higher statistical power for clinical utility. The qPCR analysis of target common bacterial species can be a powerful, cost and time efficient approach for monitoring disease status and identify better personalized treatment options for IBD patients.

Post COVID-19 irritable bowel syndrome.

OBJECTIVES: The long-term consequences of COVID-19 infection on the gastrointestinal tract remain unclear. Here, we aimed to evaluate the prevalence of gastrointestinal symptoms and post-COVID-19 disorders of gut-brain interaction after hospitalisation for SARS-CoV-2 infection. DESIGN: GI-COVID-19 is a prospective, multicentre, controlled study. Patients with and without COVID-19 diagnosis were evaluated on hospital admission and after 1, 6 and 12 months post hospitalisation. Gastrointestinal symptoms, anxiety and depression were assessed using validated questionnaires. RESULTS: The study included 2183 hospitalised patients. The primary analysis included a total of 883 patients (614 patients with COVID-19 and 269 controls) due to the exclusion of patients with pre-existing gastrointestinal symptoms and/or surgery. At enrolment, gastrointestinal symptoms were more frequent among patients with COVID-19 than in the control group (59.3% vs 39.7%, p<0.001). At the 12-month follow-up, constipation and hard stools were significantly more prevalent in controls than in patients with COVID-19 (16% vs 9.6%, p=0.019 and 17.7% vs 10.9%, p=0.011, respectively). Compared with controls, patients with COVID-19 reported higher rates of irritable bowel syndrome (IBS) according to Rome IV criteria: 0.5% versus 3.2%, p=0.045. Factors significantly associated with IBS diagnosis included history of allergies, chronic intake of proton pump inhibitors and presence of dyspnoea. At the 6-month follow-up, the rate of patients with COVID-19 fulfilling the criteria for depression was higher than among controls. CONCLUSION: Compared with controls, hospitalised patients with COVID-19 had fewer problems of constipation and hard stools at 12 months after acute infection. Patients with COVID-19 had significantly higher rates of IBS than controls. TRIAL REGISTRATION NUMBER: NCT04691895.

Evaluation of colon mucosa using screening colonoscopy and flexible spectral imaging color enhancement in patients with long lasting ulcerative colitis.

AIM: To determine which flexible spectral imaging color enhancement (FICE) channel best visualizes colon mucosa in ulcerative colitis (UC) and to compare FICE imaging with standard imaging. METHODS: The study enrolled patients with ulcerative colitis in remission who had inflammatory bowel disease for at least 8 years. All patients underwent screening colonoscopy. The entire colon, especially the suspicious areas in terms of dysplasia, were imaged with standard endoscopy and FICE. Random and target biopsies were obtained. Histopathological diagnosis was made and image patterns were evaluated. Seven endoscopists evaluated normal, colitis, and polyp images obtained with FICE. RESULTS: One hundred and twenty-three colon segments were evaluated and 1831 images were obtained from 18 patients. A total of 1652 images were FICE and 179 were standard images. Separate FICE images were obtained for normal colon mucosa, polypoid lesions, and colitis areas. Normal colon mucosa was best visualized using the second, sixth, and ninth FICE channel; polyps using the third, seventh, and ninth channel; and colitis using the second, third, and ninth channel. When all images were analyzed, the second and ninth channel were significantly better than the other channels. A total of 584 biopsies were obtained, including 492 (84.2%) random biopsies and 92 (15.7%) target biopsies. Random biopsies detected no dysplasia, but target biopsies detected low-grade dysplasia in three diminutive polyps. CONCLUSION: FICE was not significantly better at dysplasia screening than the standard procedure, but it effectively detected diminutive polyps and evaluated surface patterns without using magnification. FICE might contribute to the assessment of inflammation severity in patients with UC in clinical remission. However, more extensive studies are necessary to confirm these findings.

Molecular characteristics of colorectal hyperplastic polyp subgroups.

BACKGROUND/AIMS: The importance of hyperplastic polyps during colorectal carcinogenesis is appreciated related to the understanding of serrated pathway. The morphologic subtypes of hyperplastic polyps in carcinogenesis and the nomenculature of lesions with both hyperplastic and adenomatous areas are controversial. We aimed to reveal the molecular properties of hyperplastic polyp subtypes and the molecular changes in polyps containing both hyperplastic and adenomatous areas. Matherial and Methods: 49 hyperplastic polyps [19 microvesicular (MVHP), 19 goblet-rich (GRHP), 11 mucin-poor (MPHP)] and 10 mixed hyperplastic and adenomatous polyps were analysed for KRAS, BRAF mutations and MSI with real-time PCR. RESULTS: 68,4% of MVHPs and 81% of MPHPs which were localized in right colon had BRAF mutations. While none of the GRHPs showing a KRAS mutation with a rate of 73% was localized in the ascending colon, 63% of them were localized in the rectosigmoid area. In five (50%) of the mixed polyps, KRAS mutation was detected both in the hyperplastic and adenoma components. There was no BRAF mutation in any of the mixed polyps. However, in two cases, the hyperplastic component was MSI-H and the adenoma area was MSS. CONCLUSION: Hyperplastic polyps, even if smaller than 5 mm, are precancerous lesions bearing different mutations. GRHPs with predominant KRAS mutations and MVHPs and MPHSs with predominant BRAF mutations are precancerous. Although the molecular investigations for HPP/SP are not necessary the morphological subtyping should be included if the case is diagnosed with HPP/SP as it will be useful for attracting the gastroenterologist's attention.

Comparison of radiological scoring systems, clinical scores, neutrophil-lymphocyte ratio and serum C-reactive protein level for severity and mortality in acute pancreatitis

SUMMARY Comparison of radiological scoring systems, clinical scores, neutrophil-lymphocyte ratio and serum C-reactive protein level for severity and mortality in acute pancreatitis BACKGROUND/AIMS To compare radiological scoring systems, clinical scores, serum C-reactive protein (CRP) levels and the neutrophil-lymphocyte ratio (NLR) for predicting the severity and mortality of acute pancreatitis (AP). MATERIALS AND METHODS Demographic, clinical, and radiographic data from 80 patients with AP were retrospectively evaluated. The harmless acute pancreatitis score (HAPS), systemic inflammatory response syndrome (SIRS), bedside index for severity in acute pancreatitis (BISAP), Ranson score, Balthazar score, modified computed tomography severity index (CTSI), extrapancreatic inflammation on computed tomography (EPIC) score and renal rim grade were recorded. The prognostic performance of radiological and clinical scoring systems, NLR at admission, and serum CRP levels at 48 hours were compared for severity and mortality according to the revised Atlanta Criteria. The data were evaluated by calculating the receiver operator characteristic (ROC) curves and area under the ROC (AUROC). RESULTS Out of 80 patients, 19 (23.8%) had severe AP, and 9 (11.3%) died. The AUROC for the BISAP score was 0.836 (95%CI: 0.735-0.937), with the highest value for severity. With a cut-off of BISAP ≥2, sensitivity and specificity were 68.4% and 78.7%, respectively. The AUROC for NLR was 0.915 (95%CI: 0.790-1), with the highest value for mortality. With a cut-off of NLR >11.91, sensitivity and specificity were 76.5% and 94.1%, respectively. Of all the radiological scoring systems, the EPIC score had the highest AUROC, i.e., 0.773 (95%CI: 0.645-0.900) for severity and 0.851 (95%CI: 0.718-0.983) for mortality, with a cut-off value ≥6. CONCLUSION The BISAP score and NLR might be preferred as early determinants of severity and mortality in AP. The EPIC score might be suggested from the current radiological scoring systems.

RESUMO Comparação dos sistemas de escores radiológicos, escores clínicos razão neutrófilo/linfócito e níveis séricos de proteína C-reativa para determinação da gravidade e mortalidade em casos de pancreatite aguda OBJETIVO Comparar sistemas de escores radiológicos, escores clínicos, os níveis séricos de proteína C-reativa (PCR) e a razão neutrófilo/linfócitos (RNL) como métodos de previsão de gravidade e mortalidade em casos de pancreatite aguda (PA). MATERIAIS E MÉTODOS Dados demográficos, clínicos e radiográficos de 80 pacientes com PA foram avaliados retrospectivamente. Os valores de Harmless Acute Pancreatitis Score (HAPS), Síndrome da Resposta Inflamatória Sistêmica (SIRS), Índice de Gravidade na Pancreatite Aguda à Beira do Leito (BISAP), escore de Ranson, escore de Balthazar, Índice Modificado de Gravidade por Tomografia Computadorizada (CTSI), escore de Inflamação Extrapancreática em Tomografia Computadorizada (EPIC) e grau renal foram registrados. O desempenho prognóstico dos sistemas de escores clínicos e radiológicos e RNL no momento da internação e os níveis séricos de PCR após 48 horas foram comparados quanto à gravidade, de acordo com os critérios de Atlanta revisados e mortalidade. Os dados foram avaliados pelo cálculo das curvas ROC e da área sob a curva ROC (AUROC). RESULTADOS De 80 pacientes, 19 (23,8%) tinham PA grave e 9 (11,3%) morreram. A AUROC para o escore BISAP foi de 0,836 (95%CI: 0.735-0.937), com o valor mais alto de gravidade. Com um valor de corte de BISAP ≥ 2 , a sensibilidade e a especificidade foram de 68,4% e 78,7%, respectivamente. A AUROC para o a RNL foi de 0,915 (95%CI: 0.790-1), com o valor mais alto de mortalidade. Com um valor de corte de RNL > 11,91, a sensibilidade e a especificidade foram de 76,5% e 94,1%, respectivamente. Entre os sistemas de escore radiológico, o EPIC apresentou o maior valor de AUROC, 0,773 (95%CI: 0.645-0.900) para gravidade e 0,851 (95%CI: 0.718-0.983) para mortalidade com um valor de corte ≥6. CONCLUSÃO O escore BISAP e a RNL podem ser preferíveis como determinantes precoces de gravidade e mortalidade na PA. O escore EPIC pode ser sugerido entre os atuais sistemas de escores radiológicos.

Analysis of socioeconomic status and other factors affecting patient-graft survival in patients undergoing liver transplantation.

Background and Aim: Liver transplantation is performed in increasing numbers due to advances in surgical techniques and the introduction of diverse immunosuppressive drugs. The present study aims to analyze the effects of socioeconomic status and education level on patient and graft survival, in addition to all these factors. Material and Methods: All patients aged 18 years and above who underwent consecutive liver transplantation at the Liver Transplantation Unit of Department of General Surgery at the Dokuz Eylül University Hospital and whose data were available were included in this study. Results: Incompliance was noted in 68.3% of the 278 patients. On the other hand, patient compliance did not have a significant effect on graft and patient survival. However, decreased levels in the parameters, such as education status, vocational status and socioeconomic status, were found to be correlated with patient compliance. A significant correlation was not found between these factors and patient and graft survival. Conclusion: Although a direct effect of socioeconomic status on patient and graft survival could not be shown the significant association of vocational status and education status which determine socioeconomic level with parameters other than patient and graft survival may affect the success of liver transplants.

C-reactive protein may be a prognostic factor for the whole gastroenteropancreatic neuroendocrine tumor group.

BACKGROUND: Long non-coding RNAs (lncRNAs) are a kind of single-stranded RNA of more than 200 nucleotides in length and have no protein-coding function. Amounting studies have indicated that lncRNAs could play a vital role in the initiation and development of cancers, including gastric cancer (GC). Considering the crucial functions of lncRNAs, the identification and exploration of novel lncRNAs in GC is necessary. AIM: To identify independent prognostic markers for the whole gastroenteropancreatic neuroendocrine tumor (GEP-NET) group. METHODS: Ninety-three patients diagnosed with GEP-NETs within a specified period were included in this study. Patient data were retrospectively analyzed. The relationships between all independent variables and 5-year survival status calculated during the follow-up period (months) were assessed. In addition, the relationships between the independent variables were investigated. RESULTS: When 5-year survival rate was compared, a statistically significant relationship between the age at diagnosis, male gender, tumor size, tumor stage, liver and/or distant metastasis, and tumor grade determined by the Ki-67 level and mitotic count, and the level of C-reactive protein (CRP), was observed. The mean survival (overall survival) of the study group was 102.5 ± 6.3 (SD) mo. The percentages of 1, 3 and 5-year survival were 90%, 72%, and 61%, respectively. In 63 of 93 patients, Ki-67 and the mitotic count determined the same grade. The Ki-67 levels in 29 patients and the mitotic count in only 1 patient were in the higher grade. The risk of death increased by 4% for every 1 year increase at the diagnosis age and was 2.0-fold higher for male patients, 3.0-fold higher for G3 according to the mitotic count, 3.7-fold higher for G3 according to the Ki-67 level, 12.7-fold higher for cases with tumor stage 3 or 4 by a 1 cm increase in the ratio of 9% in tumor size, and 6.1-fold higher for patients with liver metastasis for every 1 mg/dL increase in the ratio of 1.5% in CRP level. There was a significant difference between pancreatic and stomach NETs in favor of stomach tumors in terms of survival. CONCLUSION: Tumor site, stage, grade and Ki-67 level affected patient survival, and it was observed that CRP affected disease progression (particularly if it was > 20 mg/dL). However, a relationship between surgical resection of the lesion and survival was not shown. Larger scale prospective studies are required to determine whether CRP level may be a poor prognostic factor for the entire GEP-NET group.

Frequency, types, and treatment of anemia in Turkish patients with inflammatory bowel disease.

AIM: To specify the type and prevalence of anemia along with a treatment approach for inflammatory bowel disease (IBD). METHODS: We conducted a retrospective study on 465 patients who were diagnosed with IBD and followed up at our hospital from June 2015 to June 2016 [male: 254, female: 211; average age: 47 ± 14.4; Crohn's disease (CD): 257, Ulcerative Colitis (UC): 208]. Epidemiological and clinical data, such as sex, age, age of diagnosis, type of IBD, disease extension, disease behavior and duration, treatments for IBD and anemia, and surgical history were obtained for each patient. Per World Health Organization guidelines, anemia was diagnosed for males if hemoglobin values were less than 13 g/dL and for females if hemoglobin values were less than 12 g/dL. RESULTS: We determined that 51.6% of the patients had anemia, which was more frequent in women then men (64% vs 41.3%, P < 0.001). Anemia frequency was higher in CD cases (57.6%) than in UC cases (44.2%) (P = 0.004). CD involvements were as follows: 48.2% in ileal involvement, 19% in colonic involvement, and 32.8% in ileocolonic involvement. Furthermore, 27.5% of UC patients had proctitis (E1) involvement, 41% of them had involvement in left colitis (E2), and 31.5% had pancolitis involvement. There was no significant relationship between anemia frequency and duration of disease (P = 0.55). Iron deficiency anemia (IDA) was the most common type of anemia in this cohort. Moreover, because anemia parameters have not been evaluated during follow-up of 15.3% of patients, the etiology of anemia has not been clarified. Fifty percent of patients with anemia received treatment. Twenty-three percent of IDA patients had oral iron intake and forty-one percent of IDA patients had parenteral iron treatment. Fifty-three percent of patients who were suffering from megaloblastic anemia received B12/folic acid treatment. CONCLUSION: We found out that almost half of all IBD patients (51.6%) had anemia, the most frequent of which was IDA. Almost half of these patients received treatment. We should increase the treatment rate in our IBD patients that have anemia.

Is ileocecal valve intubation essential for routine colonoscopic examination?

BACKGROUND: In this study, we aimed to assess the diagnostic yield of terminal ileum intubation during routine colonoscopy. MATERIALS AND METHODS: We routinely performed terminal ileum intubation in all patients who underwent colonoscopy at Dokuz Eylul University Hospital between February 2014 and June 2015. Two gastroenterology fellows performed colonoscopies in the Central Endoscopy Unit. Demographic data of patients, indications of colonoscopies, cecum and ileum intubation rate/time, and endoscopic and histopathologic findings of the terminal ileum were all assessed. RESULTS: A total of 1310 consecutive patients (726 female and 584 male, median age: 55.79±14.29 years) underwent colonoscopy during this study period. The colonoscopy was successfully completed in 1144 (87.3%) cases. The terminal ileum was successfully intubated in 1032 (90.2%) cases. The mean time taken to reach the ileum from the cecum was 63.08±64.16 s. Endoscopic abnormalities on the terminal ileum were present in 62 (6%) cases, and biopsies were taken from these patients. However, endoscopic abnormalities were found in 7 and 3.3% of patients who were symptomatic and asymptomatic, respectively. There were statistically significant differences between symptomatic and asymptomatic patients (P=0.02). Clinically significant histopathologic findings were observed in 22 cases, and 12 of the 22 cases were diagnosed as having Crohn's disease. CONCLUSION: Terminal ileum intubation is particularly indicated in symptomatic patients. In cases of chronic diarrhea, iron-deficiency anemia, abdominal pain, and suspected inflammatory bowel disease, terminal ileum intubation should be done.

A comparison of the effects of infliximab, adalimumab, and pentoxifylline on rats with non-alcoholic steatohepatitis.

BACKGROUND/AIMS: Non-alcoholic steatohepatitis (NASH) lacks effective medical treatment. Since tumor necrosis factor alpha (TNF-α) plays an important role in NASH pathogenesis, we aimed to investigate drugs affecting TNF-α as possible treatment options during the development of NASH. MATERIALS AND METHODS: A total of 35 rats were divided into five groups and evaluated over a 6 week period. One group received a normal diet alone or in combination with the administration of infliximab, adalimumab or pentoxifylline. RESULTS: NASH was successfully established in the MCD diet group. Levels of TNF-α were effectively suppressed in the three groups that received anti-TNF agents. No statistically significant differences were observed between the three agents in terms of the histological NASH score. CONCLUSION: Our study showed that the anti-TNF agents infliximab, adalimumab, and pentoxifylline effectively suppress TNF-α. Although these drugs did not prevent the development of NASH, they were able to slightly reverse the NASH histopathology score and positively affect liver function tests.

Does glucagon like peptide-2 receptor expression have any effect on the development of human colorectal cancer?

BACKGROUND/AIMS: Glucagon like peptide-2 may play an important role in human colon cancer and polyp development because of its proliferative and antiapopitotic effects especially in colon. In this study, we investigated the role of human glucagon like peptide and it's receptor in development of human colorectal carcinogenesis. MATERIAL AND METHODS: The study includes 30 patients in colon cancer group and 20 patients in colonic polyp group who have been diagnosed by endoscopic and pathologic examination in Dokuz Eylül University, Department of Gastroenterology within 2 year-period. For comparison biopsies were taken from normal appearing colonic mucosa of the same patient. The cancer, polyp and normal colon mucosa samples were stained with glucagon like peptide receptor antibody by immunohistochemical method. RESULTS: Glucagon like peptide 2 receptor positivity of colon cancer patients was 20 % (6/30) in focal cytoplasmic coloration while it was 0 % in colonic adenomas and 100 % in enteroendocrine cells of normal colonic mucosa. Statistically significant differences were found by the comparison of colonic polyp and normal colonic tissue (p=0.000), colonic cancer and normal colonic tissue (p=0.000) and colonic polyp and cancer tissues (p= 0.023). CONCLUSION: Glucagon like peptide-2 receptor expression in colonic adenomas was not detected in human in contrary to the study on mice. Our study suggested that Glucagon like peptide-2 receptor expression is not a factor in adenoma-cancer pathogenesis. More studies are needed on this subject with more facts and different methods.

Metastasis of giant cell tumor to the breast: case report and review of the literature.

Breast cancer is the most common type of malignancy in women. Of all breast cancers, 0.5-3% involve metastasis of a non-breast malignancy to the breast. Metastasis of soft tissue tumors to the breast is rarely seen. In particular, metastasis of a giant cell tumor to the breast has never been reported in the literature. We present here a case of breast metastasis in a 44-year-old woman with a diagnosis of malignant giant cell tumor originating from the distal radius and metastatic to the lung, who had been treated with radiotherapy, surgery and chemotherapy.