Risk of Malignancy Using the Diagnostic Categories Proposed by the World Health Organization International System for Reporting Pancreaticobiliary Cytopathology.

BACKGROUND: The World Health Organization (WHO) proposed an updated reporting system for pancreaticobiliary cytology, which moves low-grade malignancies to "positive for malignancy" group and serous cystadenoma to "negative for malignancy" group. The WHO system also created two new categories, namely, pancreatic neoplasia-low grade (PaN-Low) and pancreatic neoplasia-high grade (PaN-High), which includes neoplastic mucinous cysts and stratifies them according to their cytologic atypia. The risk of malignancy (ROM) of the new categories of the WHO system needs to be defined. METHODS: Cytologic slides of all patients, who underwent endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy at our institution from January 2010 to December 2021 and had a histopathological or clinical follow-up of at least 6 months, were reviewed and reclassified under the Papanicolaou Society of Cytopathology (PSC) and WHO reporting systems. The absolute ROM was calculated for each category of both reporting systems. RESULTS: A total of 420 EUS-FNA samples from 410 patients were reviewed and reclassified. The absolute ROM for the proposed WHO system was 35% for "nondiagnostic," 1.0% for "negative for malignancy," 69.0% for "atypical," 11% for "PaN-Low," 100% for "PaN-High," 91% for "suspicious for malignancy," and 100% for "malignant." Comparatively, the absolute ROM under the PSC reporting system was 34% for "nondiagnostic," 1.0% for negative (for malignancy), 50.0% for "atypical," 0.0% for "neoplastic: benign," 16% for "neoplastic: other," 88% for "suspicious for malignancy," and 100% for "positive or malignant." CONCLUSION: The proposed WHO international reporting system has advantages regarding risk stratification improvement and case management.

Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis.

BACKGROUND/AIM: This study was designed to identify the effect of pentoxifylline on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Forty-two female Wistar rats were randomly divided into 7 groups: group A, TNBS + intraperitoneal (IP) pentoxifylline; group B, TNBS + IP saline; group C, TNBS + intrarectal (IR) pentoxifylline; group D, TNBS + IR saline; group E, IP pentoxifylline + TNBS; group F, IP saline + TNBS; group G, IR saline. Pentoxifylline was given daily for 3 days before or 6 days after the induction of colitis. Rats were killed after 6 days. RESULTS: IP and IR pentoxifylline similarly and significantly reduced damage and histopathological scores. Pentoxifylline attenuated the accumulation of malonyldialdehyde and transforming growth factor ß1 and the activities of myeloperoxidase, matrix metalloproteinase-3, and tissue inhibitor of metalloproteinases-1, and it also restored superoxide dismutase activity. The IP route was more effective than the IR route in this regard. Administration of IP pentoxifylline before or after induction did not influence all parameters. Conclusions: Pentoxifylline showed a therapeutic effect in this experimental colitis model. IP administration seemed to be better. This effect may occur as a result of inhibition of oxidative stress and metalloproteinase activity.

The efficacy of a through-the-scope sodium phosphate solution with completion colonoscopy on the same day as a salvage option for inadequate bowel cleansing.

BACKGROUND/AIM: The aim of this study was to investigate the efficacy of a through- the-scope sodium phosphate solution with completion colonoscopy on the same day as a salvage option for inadequate bowel preparation. MATERIALS AND METHODS: All participants were instructed to eat a low residual diet for 3 days before the scheduled colonoscopy and a clear liquid diet 18 h before the colonoscopy. The patients were asked to take split doses of an oral sennoside solution at 1800 and 2200 in the evening before the colonoscopy. In cases of inadequate bowel preparation detected during routine colonoscopy, a sodium phosphate solution was administered through the scope on the day of the colonoscopy procedure. The degree of bowel cleansing was assessed by the Boston Bowel Preparation Scale (BPS: 0-9). RESULTS: Almost excellent bowel cleansing was obtained with a statistically significant difference between the degree of bowel cleansing before and after the application of the sodium phosphate (Boston BPS: 5.48 ± 1.01 vs. 8.88 ± 0.33 respectively, P < 0.001). CONCLUSION: Through-the-scope sodium phosphate with completion colonoscopy on the same day was shown to be an efficacious and acceptable method for inadequate bowel preparation.

DR-70 as a novel diagnostic biomarker for gastric cancer.

BACKGROUND/AIMS: To assess the utility of the DR-70 immunoassay in the diagnosis of gastric cancer. MATERIALS AND METHODS: A total of 29 patients with histologically proven malignant gastric tumor and 29 healthy blood donors were enrolled in this study. DR-70 immunoassay was performed using an enzyme-linked immunosorbent assay kit to quantify the serum levels of fibrin degradation products. RESULTS: The DR-70 values in patients with gastric cancer significantly differed from the values in controls (p<0.0001). Receiver operating characteristic curve analysis revealed ≥1.45 µg/mL as the best cut-off value to distinguish between patients with gastric cancer and healthy controls. The area under the receiver operating characteristic curve was 0.871. Using ≥1.45 µg/mL as the cut-off value, the DR-70 immunoassay showed a good clinical performance with a sensitivity of 82.8% and a specificity of 79.3%. The positive predictive value was 80.0%, and the negative predictive value was 82.1%. CONCLUSION: The DR-70 immunoassay reliably differs between gastric cancer and healthy controls, promising to become a useful cancer detection tool in clinical practice.

Measurement and clinical implications of choroidal thickness in patients with inflammatory bowel disease.

PURPOSE: Ocular inflammation is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and may parallel disease activity. In this study, we evaluated the utility of a choroidal thickness measurement in assessing IBD activity. METHODS: A total of 62 eyes of 31 patients with IBD [Crohn's disease (CD), n=10 and ulcerative colitis (UC), n=21] and 104 eyes of 52 healthy blood donors were included in this study. Choroidal thickness was measured using enhanced depth imaging optical coherence tomography. The Crohn's disease activity index (CDAI) and the modified Truelove Witts score were used to assess disease activity in CD and UC, respectively. RESULTS: No significant differences in mean subfoveal, nasal 3000 µm, or temporal 3000 µm choroidal thickness measurements (P>0.05 for all) were observed between IBD patients and healthy controls. Age, smoking, CD site of involvement (ileal and ileocolonic involvement), CDAI, CD activity, and UC endoscopic activity index were all found to be significantly correlated with choroidal thickness by univariate analysis (P<0.05). Smoking (P<0.05) and the CD site of involvement (P<0.01) were the only independent parameters associated with increased choroidal thickness at all measurement locations. CONCLUSIONS: Choroidal thickness is not a useful marker of disease activity in patients with IBD but may be an indicator of ileal involvement in patients with CD.

Measurement and clinical implications of choroidal thickness in patients with inflammatory bowel disease / Determinação da espessura da coróide suas implicações clínicas em pacientes com doença inflamatória intestinal

ABSTRACTPurpose:Ocular inflammation is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) and may parallel disease activity. In this study, we evaluated the utility of a choroidal thickness measurement in assessing IBD activity.Methods:A total of 62 eyes of 31 patients with IBD [Crohn's disease (CD), n=10 and ulcerative colitis (UC), n=21] and 104 eyes of 52 healthy blood donors were included in this study. Choroidal thickness was measured using enhanced depth imaging optical coherence tomography. The Crohn's disease activity index (CDAI) and the modified Truelove Witts score were used to assess disease activity in CD and UC, respectively.Results:No significant differences in mean subfoveal, nasal 3000 μm, or temporal 3000 μm choroidal thickness measurements (P>0.05 for all) were observed between IBD patients and healthy controls. Age, smoking, CD site of involvement (ileal and ileocolonic involvement), CDAI, CD activity, and UC endoscopic activity index were all found to be significantly correlated with choroidal thickness by univariate analysis (P<0.05). Smoking (P<0.05) and the CD site of involvement (P<0.01) were the only independent parameters associated with increased choroidal thickness at all measurement locations.Conclusions:Choroidal thickness is not a useful marker of disease activity in patients with IBD but may be an indicator of ileal involvement in patients with CD.

RESUMOObjetivos:Inflamação ocular é uma manifestação extra-intestinal comum de doença inflamatória do intestino (IBD) e pode ser paralela a atividade da doença. Neste estudo, investigamos se a espessura da coroideia pode ser útil para avaliar a atividade da IBD.Método:Um total de 62 olhos de 31 pacientes com IBD [10 com doença de Crohn (CD) e 21 colite ulcerosa (UC)] além de 104 olhos de 52 doadores de sangue saudáveis foram incluídos neste estudo. A espessura da coróide foi medida utilizando-se imagens de tomografia de coerência óptica com profundidade aprimorada. O índice de atividade da doença Crohn (CDAI) e o índice de Truelove Witts modificado foram usados para avaliar atividade da doença em CD e UC, respectivamente.Resultados:Não houve diferença significativa entre os pacientes com IBD e controles saudáveis em termos de medições da espessura da coróide subfoveal média em região 3000 μm nasal e 3000 μm temporal (p>0,05). Com base na análise univariada; idade, tabagismo, local do envolvimento em CD (ileal ou íleo-cecal), CDAI, atividade CD e índice de atividade endoscópica da UC foram significativamente correlacionados com a espessura da coróide (p<0,05). No entanto, fumar (p<0,05) e o local de envolvimento em CD (p<0,01) foram os únicos parâmetros independentes associados com um aumento na espessura da coroideia em todos os pontos de medida.Conclusões:A espessura da coroide não é um marcador útil para refletir a atividade da doença em pacientes com IBD, mas pode ser um indicador de envolvimento ileal em pacientes com CD.

Rivaroxaban Induces Mucosal Healing in a Rat Model of Trinitrobenzene Sulfonic Acid-Induced Colitis.

OBJECTIVE: This study was designed to identify the effect of rivaroxaban, a direct factor Xa inhibitor, on trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. MATERIALS AND METHODS: Twenty-four female Wistar rats were divided into 4 groups of 6 each. Group 1 received TNBS + rivaroxaban, group 2 received TNBS + methylprednisolone, group 3 received TNBS and group 4 received a saline enema. Colitis was induced in the rats by the intracolonic administration of TNBS. Rivaroxaban and methylprednisolone were given by oral gavage daily for 7 days. The rats were killed 7 days after the induction of colitis. RESULTS: Rivaroxaban and methylprednisolone significantly reduced gross damage and histopathological scores. Rivaroxaban was more effective than methylprednisolone in terms of microscopic mucosal healing. Rivaroxaban attenuated the accumulation of malonyldialdehyde (MDA) and transforming growth-factor ß1 (TGF-ß1) and the activities of myeloperoxidase (MPO), matrix metalloproteinase-3 and tissue inhibitor of metalloproteinases-1. Methylprednisolone reduced only the activity of MPO and the accumulation of MDA and TGF-ß1. Superoxide dismutase activity showed a restoration to normal levels after rivaroxaban and methylprednisolone administration. CONCLUSIONS: Rivaroxaban showed a therapeutic effect in the TNBS model of experimental colitis, and it seemed to be at least as effective as methylprednisolone. This effect may be brought about by the inhibition of oxidative stress and metalloproteinase activity associated with tissue injury and remodeling.

Tuberculosis and Crohn's Disease Revisited.

Crohn's Disease (CD) and Intestinal Tuberculosis (ITB) share confusingly similar clinical, endoscopic, radiological and pathological manifestations. There is no simple test for differentiating ITB from CD. Although there are a number of sensitive and specific parameters for distinguishing between CD and ITB, the differential diagnosis still remains challenging and both clinical suspicion and appropriate clinical and laboratory studies are required to establish the diagnosis. Correct diagnosis is crucial because the therapy strategies of the two diseases are dramatically different. Treatment of ITB with immunosuppressive agents would lead to worsening of the patients' condition. Likewise, unnecessary antituberculosis therapy would delay the treatment of CD. Another important consideration is the risk of reactivation TB in patients with inflammatory bowel diseases which has been significantly increased following the widespread use of anti-Tumor Necrosis Factor Alpha (TNF-α) therapy. The majority of reactivation cases are extrapulmonary or disseminated TB. And it is widely recommended that patients with IBD who are to receive TNF inhibitor therapy should be screened for evidence of latent TB. This paper mainly reviews current literature on differential diagnosis between CD and ITB, and summarizes strategies to reduce the TB risk among candidates for TNF antagonist therapy in this specific patient population.

Lidocaine versus lidocaine plus benzydamine as a topical anesthesia regimen for unsedated upper gastrointestinal endoscopy: A comparison study.

BACKGROUND/AIMS: The aim was to assess the efficacy of adding benzydamine (B) spray to standard treatment with a lidocaine (L) spray before upper gastrointestinal endoscopy (UGE) as a topical anaesthetic regimen. MATERIALS AND METHODS: A total of 118 adult patients undergoing outpatient UGE were randomly assigned to receive L (n=44), LB (n=38) or B (n=36) before the procedure. The primary outcome was the patient tolerance score, which represents a summative evaluation of the taste of the anesthetic agent, the intensity of pharyngeal numbness, the amount of coughing or gagging and the degree of discomfort during oesophageal intubation. RESULTS: The median (min-max) patient tolerance scores were comparable between groups LB (10.5; range 5-12) and L (10; range 4-13) (p=0.235) and significantly lower in group B (7.5; range 3-12) (p<0.01). LB improved several secondary outcomes. Oesophageal intubation was less difficult (5 [range 2-10] vs 3 [range 0-8], p<0.001), and a lower proportion of patients developed postprocedural sore throat (4 [10.5%] vs 15 [34.1%], p=0.011) in LB compared to L. CONCLUSION: LB is not superior to L in terms of overall patient tolerance, but LB may be preferred over L in cases with difficult oesophageal intubation or a previous history of postprocedural sore throat.

Pancreatic metastasis in a case of small cell lung carcinoma diagnosed by EUS.

Small-cell lung carcinoma represents a group of highly malignant tumors characterized by early and widespread metastais even at the time of diagnosis. However, the pancreas is a relatively infrequent site of metastasis by this neoplasm. A 57-year-old patient was admitted with an intense cough and complaints of abdominal discomfort. A chest X-Ray showed no evidence of lung mass but did show signs of lymphadenopathy. In addition, there was little evidence for malignancy based on a transbronchial needle aspiration. In contrast, there was a mass in the head portion of the pancreas. We diagnosed a case of small-cell lung carcinoma metastasis in the pancreas by using an endoscopic ultrasound-guided fine-needle aspiration biopsy. This case demonstrates that endoscopic ultrasound-guided fine-needle aspiration biopsy is an important tool in the diagnosis of metastatic pancreatic neoplasms.

Lamivudine treatment failure risks in chronic hepatitis B patients with low viral load.

AIM: To analyze the risk factors of lamivudine treatment failure (LTF) for the long-term use in patients with low viral load (LVL). MATERIAL AND METHODS: In this multicenter study, 548 antiviral naïve noncirrhotic adult patients with LVL (for HBeAg+ patients HBV DNA <10 9 copies/ml and for HBeAg­patients HBV DNA <10 7 copies/ml) were enrolled. As a control group, 46 lamivudine-initiated patients with high viral load (HVL) were included. Primary outcome was switching to or adding on another antiviral drug as a consequence of primary nonresponse, partial response, viral breakthrough or adverse events. Secondary outcomes included LTF rates at 1, 2, 3, 4 and 5 years and LTF-related viral and host factors. RESULTS: Among 594 patients, 294 had to change lamivudine at the follow-up. Primary nonresponse, partial response, viral breakthrough or adverse events frequencies were 6.8, 1.6, 64.5 and 0.1%, respectively. Five-year LTF rates were 61.3 and 84.2% in patients with LVL and HVL, respectively. Among patients with LVL, patients with <100,000 copies/ml and ≥ 100,000 copies/ ml had 54.8 and 67.3% LTF rates at the end of the 5th year, respectively. Logistic regression analysis of risk factors showed HBeAg+, hepatic activity index, HBV DNA, virological response at 6 months and duration of follow-up were independent predictors for LTF (p values were 0.001, 0.008, 0.003, 0.020 and 0.003, respectively). CONCLUSION: Similar to patients with HVL, first-line lamivudine therapy is not efficient for long-term use in patients with LVL. LTF risk is so high even in the absence of worse predictive factors.

Serum nitric oxide levels in patients with benign and malignant biliary disease: a prospective single center study.

BACKGROUND: Despite advances in new diagnostic modalities, the differentiation of malignant from benign causes of biliary obstruction still remains difficult. The nitric oxide (NO) system is considered to be an important component in mediating cytokine activation of macrophages in inflammation. It also modulates tumorigenesis and regulates cell proliferation, angiogenesis, survival, and DNA repair. Although NO and its role in pancreatobiliary disorders has not been studied previously, the present study is designed to evaluate NO synthesis and metabolism in patients with biliary obstruction and to determine its usefulness in differentiating between benign and malignant causes of biliary obstruction. MATERIALS AND METHODS: Seventy-nine consecutive patients (60 malignant and 19 benign) with a history of biliary obstruction either with a benign or a malignant cause and 23 age-matched and sex-matched controls were included in this prospective study. NO metabolites, and conventional inflammation and tumor markers were determined. RESULTS: In patients with malignant biliary obstruction (MBO), serum NO metabolites were found to be significantly elevated (P<0.001). The receiver operating characteristic analysis showed that an NO level of 1.095 was the best cut-off value for predicting a malignant biliary stricture with a sensitivity of 78.3% and a specificity of 84.2% (area under the curve=0.821). Correlation analysis suggested that carbohydrate antigen 19-9 and carcinoembryonic antigen levels were correlated with NO levels for differentiating benign from malignant cause of biliary obstruction. CONCLUSIONS: Serum NO-associated tissue injury might be associated with the development of pancreatobiliary neoplasia by creating a local environment that is enriched with reactive oxygen species, cytokines, and other growth factors that may promote endothelial cell apoptosis. Moreover, serum NO levels may be used as an adjunctive marker to identify malignant causes of the obstructive jaundice.

Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis.

BACKGROUND & AIMS: Data are limited on the efficacy and safety of tenofovir and entecavir when given for more than 1 year to patients with hepatitis B-related cirrhosis. We investigated the long-term safety and efficacy of these antiviral drugs in patients with chronic hepatitis B virus (HBV) infection, with compensated or decompensated cirrhosis, and compared results with those from lamivudine. METHODS: We performed a retrospective analysis of data from 227 adult patients with chronic HBV infection who were diagnosed with cirrhosis, beginning in 2005, at 18 centers throughout Turkey. There were 104 patients who had decompensated cirrhosis, and 197 patients were treatment naive before. Seventy-two patients received tenofovir (followed up for 21.4 ± 9.7 mo), 77 patients received entecavir (followed up for 24.0 ± 13.3 mo), and 74 patients received lamivudine (followed up for 36.5 ± 24.1 mo). We collected data on patient demographics and baseline characteristics. Laboratory test results, clinical outcomes, and drug-related adverse events were compared among groups. RESULTS: Levels of HBV DNA less than 400 copies/mL were achieved in 91.5%, 92.5%, and 77% of patients receiving tenofovir, entecavir, or lamivudine, respectively. Levels of alanine aminotransferase normalized in 86.8%, 92.1%, and 71.8% of patients who received tenofovir, entecavir, and lamivudine, respectively. Child-Turcotte-Pugh scores increased among 8.5% of patients who received tenofovir, 15.6% who received entecavir, and 27.4% who received lamivudine. Frequencies of complications from cirrhosis, including hepatic encephalopathy, variceal bleeding, hepatocellular carcinoma, and mortality, were similar among groups. Lamivudine had to be changed to another drug for 32.4% of the patients. CONCLUSIONS: Tenofovir and entecavir are effective and safe for long-term use in patients with compensated or decompensated cirrhosis from HBV infection.

The involvement of nitric oxide in the physiopathology of hepatoportal sclerosis.

BACKGROUND AND AIM: Hepatoportal sclerosis (HPS) is a clinical syndrome of unspecified etiology depicted by enlarged spleen and portal hypertension in the lack of other chronic liver disease findings, hematological disorders or any infectious disease in the liver. Nitric oxide (NO) molecule has many important functions in human body including phagocytosis in macrophages, neural transmission and endothelial relaxation. Although there is no data in literature that depicts the role of NO in HPS pathogenesis, this study was conducted in order to evaluate the potential role of NO in patients with HPS. PATIENTS AND METHODS: The study participants included 24 HPS patients and 20 healthy controls. The median age of HPS and control patients was 41.2 ± 13.9 and 46.5 ± 12.4 years, respectively. NO was predicted as nitric oxide metabolites (NOx) by Griess reaction after transformation of nitrate to nitrite by nitrate reductase using the commercially obtainable Nitric Oxide Assay Kit. RESULTS: Serum NOx levels were 2.69 ± 2.98 µmol/L and 0.85 ± 1.05 µmol/L for the HPS patients and controls, respectively. Serum NO levels were significantly higher in patients with HPS compared to the control group (p<0.001). ROC curve analysis suggested that the optimum NOx cut-off point for HPS was 1.305 with sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 83.3%, 90 %, 90.9 %, and 81.8% respectively. CONCLUSION: Circulating NO concentration was notably higher in patients with HPS in comparison to the control group. Our study verified that an elevated level of NO might have a role in the pathogenesis of HPS.

Double balloon enteroscopy: a 3-year experience at a tertiary care center.

BACKGROUND/AIMS: To evaluate the indications, diagnostic yield, therapeutic interventions, complications and safety of double balloon enteroscopy (DBE) in clinical practice. METHODOLOGY: The medical records of the patients who underwent DBE at the Turkiye Yuksek Ihtisas Hospital between October 2007 and January 2010 were examined to note the demographic data, indications for the examination, results of previous non-invasive small bowel imaging and endoscopic procedures and the results of DBE including findings, endoscopic interventions, complications and pathological reports. RESULTS: A total of 139 procedures were performed in 118 patients. DBE was performed 81 times through mouth and 26 times through anus and additionally both approaches were used 16 times in the same patients. Panenteroscopy was successfully performed in 13 of 16 patients (87.5%) in whom it was attempted. The most common indication was obscure gastrointestinal bleeding (28.8%). DBE had an overall diagnostic and/or therapeutic contribution in 63 (53.4%) patients. The main pathologies detected on DBE were polyps (12.7%), infammation (10.7%) and vascular lesions (3.4%). Complications were recognized in four cases (3.4%) but no major complication occured. CONCLUSIONS: Our retrospective analysis showed that DBE is a useful, safe and well-tolerated method with a diagnostic and therapeutic impact for the management of small bowel diseases.