From hepatomegaly to POEMS syndrome: A case report.

We present a case of POEMS syndrome from Turkiye, a rare, multisystemic condition resulting from plasma cell dyscrasia. POEMS is an acronym representing its cardinal features: Peripheral neuropathy; Organomegaly; Endocrinopathy; Monoclonal plasma-cell proliferative disorder; and Skin changes. The syndrome has an estimated prevalence of 0.3 per 100,000 individuals and typically manifests in the fifth or sixth decade of life. Progressive peripheral neuropathy is the syndrome's most prominent symptom. To ensure an accurate diagnosis, a thorough medical history, physical examination, and comprehensive diagnostic evaluations are essential. These evaluations should include serum immunoelectrophoresis, serum cytokines, and growth factors, a skeletal survey, and a bone marrow biopsy. Early recognition and treatment of POEMS syndrome are crucial to prevent debilitating progression and to optimize clinical outcomes.

The role of endobronchial and endoscopic ultrasound guided fine needle aspiration for mediastinal nodal staging of non-small-cell lung cancer.

INTRODUCTION: Mediastinal and hilar nodal staging is one of the key points for differentiating treatment modalities in patients with non-small-cell lung cancer (NSCLC). The aim of the present study was to determinate the diagnostic yields of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and combined EBUS-TBNA and EUS-FNA modalities for nodal staging in potentially operable NSCLC patients. MATERIALS AND METHODS: Twenty consecutive patients were prospectively enrolled in the study between March 2014 and November 2015. All patients had a potentially operable NSCLC diagnosis before endosonographic procedures. RESULT: Thirty lymph nodes were sampled by EBUS-TBNA and 17 lymph nodes were sampled by EUS-FNA in all 20 patients. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of F-18 fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT), EBUS-TBNA, EUS-FNA and combined EBUS-TBNA and EUS-FNA were 100%, 33.3%, 64.7%, 100% and 70.0%; 81.8%, 100%, 100%, 81.8% and 90%; 81.8%, 100%, 100%, 75% and 88.2%; 90.9%, 100%, 100%, 90.0% and 95.0%, respectively. CONCLUSIONS: The combined EBUS-TBNA and EUS-FNA technique is a successful procedure for nodal staging in potentially operable NSCLC patients.

Ipilimumab-associated cholestatic hepatitis: a case report and literature review.

Ipilimumab is a monoclonal antibody that exerts its effects by inhibiting the cytotoxic T-lymphocyte-associated protein 4 receptor on cytotoxic T lymphocytes. It is frequently used for the treatment of unresectable or metastatic melanoma. Ipilimumab may lead to several immune-related disease including colitis, thyroiditis, pneumonia, hepatitis, or pancreatitis as a side effect. Limited number of cases with hepatic damage as an ipilimumab-related adverse event has been reported in the literature. This agent has been implicated in causing acute hepatitis-like liver injury. Here, we presented a case in which cholestatic hepatitis developed during ipilimumab use for the treatment of metastatic melanoma.

Best prognostic factor of neuroendocrine tumors: Grade or Stage? A multidisciplinary single-center study.

BACKGROUND/AIMS: Currently, there is no definite consensus about the prognostic factors of neuroendocrine tumors (NETs). We evaluate epidemiology, survival and especially prognostic factors in NETs. MATERIALS AND METHODS: Patients who had a NET and were diagnosed between 2000 and 2014 at a tertiary care center were included. Demographic data, tumor characteristics and survival rates were evaluated, retrospectively. RESULTS: Two-hundred and thirty-three patients (123 male, 110 female; median age, 55 years [16-92 years]) took part in the study. Primary NET sites were the lung (n=56), stomach (n=50), pancreas (n=39), colorectal (n=21), small intestine (n=19), and appendix (n=19). According to the NET classification by the WHO in 2010, 60% (n=140) of patients were grade-1, 15% (n=35) were grade-2, and 25% (n=58) were grade-3. According to TNM staging, 88 patients (37.8%) were stage I, 30 patients (12.8%) were stage II, 22 patients (9.5%) were stage III, and 93 patients (39.9%) were stage IV. Univariate analysis revealed significant associations between gender, age, grade, lymph node metastasis, distant metastasis, stage, and the number of organs impacted by metastases and overall survival. However, with multivariate analysis only age greater than 55 years, advancing grade, and inoperable tumors were significantly associated with shortened survival. Five-year survival was 81% in grade-1, 34% in grade-2, and 9% in grade-3 NETs. CONCLUSION: This study is the most comprehensive study in Turkey that has evaluated NETs using a multidisciplinary approach. Also, we suggest that age, operability and especially grade rather than stage are the most important prognostic factors in NETs.

Red blood cell distribution width as a non-invasive marker for the assessment of inflammation in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: The aim of this study was to assess the association between red cell distribution width and inflammation in biopsy proven non-alcoholic steatohepatitis. METHODOLOGY: Fifty four subjects with non-alcoholic steatohepatitis and thirty nine controls were enrolled for the study. Liver biopsy specimens were scored by using non-alcoholic fatty liver disease activity score by a single experienced liver pathologist. RESULTS: Red cell distribution width was higher in the severe inflammation group in non-alcoholic steatohepatitis (p < 0.05). The areas under the receiver operating characteristic curves for the predictive performance of aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase and red cell distribution width in identifying inflammation in non-alcoholic steatohepatitis were 0.55 (0.41-0.68), 0.51 (0.37-0.64), 0.53 (0.39-0.67) and 0.73 (0.59-0.84) respectively and the differences of these values between red cell distribution width and other parameters were found to be statistically significant (p < 0.05). To determine the grading of inflammation, the specificity for using the red cell distribution width as an indicator in non-alcoholic steatohepatitis patients was calculated to be 73.3%, with 79.5% sen- sitivity. CONCLUSION: Red cell distribution width was a sensitive and specific method for the assessment of the inflammation in patients with non-alcoholic steatohepatitis.

Effects of ursodeoxycholic acid therapy on carotid intima media thickness, apolipoprotein A1, apolipoprotein B, and apolipoprotein B/A1 ratio in nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease that is increasingly being associated with cardiovascular disease. Ursodeoxycholic acid (UDCA) may have antioxidant and anti-inflammatory activities, and may reduce liver injury in NASH. To date, no studies have assessed the efficacy of UDCA in carotid intima media thickness (CIMT), serum lipids, apolipoprotein A1 (apo A), apolipoprotein B (apo B), and apolipoprotein B/A1 (apo B/A1) ratios in patients with NASH. PATIENTS AND METHODS: In this prospective study, 30 patients with biopsy-proven NASH and 25 healthy adults as a control group were evaluated. None of the participants had diabetes, hypertension, or hyperlipidemia. Patients with NASH received UDCA 15 mg/kg/day for 6 months. BMI, waist circumference, homeostasis model assessment, lipids, apo A1, apo B, apo B/A1 ratios, and CIMT were analyzed before and after the treatment period. RESULTS: At the end of the study, there were no statistically significant changes in BMI or waist circumference. Liver enzymes decreased gradually. The homeostasis model assessment decreased from 3.4 ± 1.89 to 2.06 ± 1.68 (P < 0.001). No significant changes in the mean triglyceride, total cholesterol, low-density lipoprotein, or apo B levels were observed. The mean high-density lipoprotein (42.9 ± 7.1 vs. 45.5 ± 9.8; P = 0.037) and apo A1 (127.6 ± 17.7 vs. 135.9 ± 22.2; P = 0.02) increased significantly. Apo B/A1 ratios tended to decrease, but this decrease was not statistically significant. The mean CIMT decreased significantly (0.56 ± 0.15 vs. 0.47 ± 0.12; P = 0.001). CONCLUSION: UDCA treatment in NASH patients resulted in statistically significant reductions in the mean CIMT over a 6-month period. We believe that this benefit of UDCA may have resulted from decreased insulin resistance and increased serum high-density lipoprotein-apo A1 levels. However, larger, longer-term studies are needed to confirm this effect of UDCA in NASH.

Circulating microRNAs in patients with non-alcoholic fatty liver disease.

AIM: To identify novel non-invasive biomarkers for non-alcoholic fatty liver disease (NAFLD). METHODS: Twenty patients with histologically proven NAFLD and 20 controls were included. All NAFLD cases were scored using the NAFLD activity score. The relative expressions of miR-197, miR-146b, miR-10b, miR-181d, miR-34a, miR-122, miR-99a and miR-29a were analyzed using real-time polymerase chain reaction. RESULTS: Serum levels of miR-181d, miR-99a, miR-197 and miR-146b were significantly lower in biopsy-proven NAFLD patients than in the healthy controls. Serum levels of miR-197 and miR-10b were inversely correlated with degree of inflammation and miR-181d and miR-99a were inversely correlated with serum gamma glutamyl transferase levels in non-alcoholic steatohepatitis patients. CONCLUSION: NAFLD is associated with altered serum miRNA expression pattern. This study provides clues for defining the non-invasive diagnosis of NAFLD.

Noninvasive assessment of liver damage in chronic hepatitis B.

AIM: To evaluate the efficacy of the aspartate aminotransferase/platelet ratio index (APRI) and neutrophil-lymphocyte (N/L) ratio to predict liver damage in chronic hepatitis B (CHB). METHODS: We analyzed 89 patients diagnosed with CHB by percutaneous liver biopsy and 43 healthy subjects. Liver biopsy materials were stained with hematoxylin-eosin and Masson's trichrome. Patients' fibrosis scores and histological activity index (HAI) were calculated according to the Ishak scoring system. Fibrosis score was recognized as follows: F0-1 No /early-stage fibrosis, F2-6 significant fibrosis, F0-4 non-cirrhotic and F5-6 cirrhotic. Significant liver fibrosis was defined as an Ishak score of ≥ 2. APRI and N/L ratio calculation was made by blood test results. RESULTS: The hepatitis B and control group showed no difference in N/L ratios while there was a significant difference in terms of APRI scores (P < 0.001). Multiple logistic regression analysis revealed that the only independent predictive factor for liver fibrosis in CHB was platelet count. APRI score was significantly higher in cirrhotic patients than in non-cirrhotic patients. However, this significance was not confirmed by multiple logistic regression analysis. The optimum APRI score cut-off point to identify patients with cirrhosis was 1.01 with sensitivity, specificity, positive predictive value and negative predictive value of 62% (36%-86%), 74% (62%-83%), 29% (13%-49%) and 92% (82%-97%), respectively. In addition, correlation analyses revealed that N/L ratio has a negative and significant relationship with HAI (r = -0.218, P = 0.041). CONCLUSION: N/L ratio was negatively correlated with HAI. APRI score may be useful to exclude cirrhosis in CHB patients.

Mean platelet volume in biopsy-proven non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD has a strong association with metabolic syndrome and its component like insulin resistance (IR). Cardiovascular disease has a relation with NAFLD. Platelet volume is an indicator of platelet function and activation. Mean platelet volume (MPV) has been reported as a risk factor for atherothrombosis. In our study, we aimed to investigate the relation of MPV with NAFLD and IR in the NAFLD patients. A total of 54 patients with histologically proven NAFLD and 41 healthy age-matched control subject were enrolled in this study. The NAFLD subjects were divided into two subgroups: 42 patients in the insulin resistant group (median age 39.5, females 22 [52%]) and 12 patients in the insulin sensitive group (median age 38, females 5 [41.7%]). MPV were significantly higher in the NAFLD group in univariate analysis (p < 0.05). In the NAFLD patients, we did not find any relation between steatosis grade, lobular inflammation, hepatocellular ballooning, NAFLD activity score and fibrosis with MPV value. Among the insulin resistant and sensitive groups in the NAFLD patients MPV values were similar. The results of this study showed that MPV, an indicator of platelet activation, increased in biopsy proven NAFLD patients but MPV is not correlated with the increase of IR in NAFLD patients. MPV is not related with inflammation and steatosis degree, hepatocellular ballooning and fibrosis in NAFLD patients.

Investigation of genome instability in exfoliated colonic epithelial cells and in mitogen-stimulated lymphocytes of patients with ulcerative colitis.

OBJECTIVE: The present study aimed to evaluate the micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in the mitogen-stimulated lymphocytes of patients with ulcerative colitis (UC). In addition, we assessed MN frequency in exfoliated colonic epithelial cells obtained from both the diseased and healthy colonic mucosa of patients. DESIGN: The study was conducted in 22 newly diagnosed patients with UC and in 22 healthy controls. MN, NPB and NBUD values scored in binucleated (BN) cells were obtained from the mitogen-stimulated lymphocytes of patients and control subjects. In addition, the MN values in exfoliated epithelial cells obtained from the diseased and healthy colonic mucosa of patients were evaluated. RESULTS: We found significantly higher MN, NPB and NBUD frequencies in the BN cells of patients with UC than in those of the control subjects (1.61 ± 0.75 vs. 0.89 ± 0.29, 3.93 ± 1.91 vs. 1.39 ± 1.10, and 1.55 ± 0.89 vs. 0.64 ± 0.48, p = 0.001). Also, a statistically significant difference was found between MN frequencies obtained from the diseased and healthy colonic mucosa of patients (1.07 ± 0.46 vs. 0.59 ± 0.21, p = 0.001). No significant relationship was found between age and MN frequency in patients with UC (r = 0.076, p = 0.735). CONCLUSION: Increased MN, NPB and NBUD frequencies observed in both the lymphocytes and exfoliated colonic epithelial cells obtained from patients with UC may reflect genomic instability.

Endoscopic topical application of Ankaferd Blood Stopper® in gastrointestinal bleeding.

AIM: This was a prospective study investigating the efficacy of Ankaferd Blood Stopper(®) (ABS), an herbal preparation, in patients with upper gastrointestinal (UGI) bleeding. MATERIALS AND METHODS: A total of 30 patients (22 male, 8 female) who had UGI bleeding (with differing causes) were included in the study. ABS was used to stop the bleeding. RESULTS: Primary hemostasis was achieved in 26 of the 30 cases. CONCLUSIONS: ABS is an effective and safe agent to use in patients with UGI bleeding.

Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis.

INTRODUCTION: Hypogonadism characterized by low serum testosterone level, loss of libido, small testes, impotence and gynecomastia is a common clinical situation in male patients with advanced chronic liver disease. The aim of the study was to assess the efficacy and safety of testosterone replacement on muscle strength, bone mineral density (BMD), body composition and gynecomastia in hypogonadal men with liver cirrhosis. METHODS: Sixteen hypogonadal male cirrhotic patients were included and twelve completed the study. Abdominal USG and/or MRI were performed to exclude hepatocellular cancer. Testogel 50mg/day was administered for 6 months. Liver enzymes, hormone profiles and muscle strength were evaluated monthly. Body composition parameters, BMD and gynecomastia were evaluated before and after 6 months. RESULTS: Serum free testosterone level was higher (20.13 ± 10.06 pmol/L; 57.26 ± 39.56 pmol/L, P=0.002) after treatment. Testosterone replacement resulted in an increase in muscle strength (34.03 ± 7.24 kg; 39.18 ± 5.99 kg, P<0.001), the subscapular site subcutaneous fat tissue (P=0.012) and the sum of the four regions (P=0.04). Subareolar breast tissue was lower (28.83 ± 17.18 mm; 15.00 ± 6.74 mm, P=0.007) after treatment. No significant adverse effects were detected. DISCUSSION: Testosterone gel 50mg/day raises free testosterone to values below supraphysiological levels in cirrhotic men. Transdermal testosterone replacement improves muscle strength, ameliorates gynecomastia, alters body fat distribution and causes upper body adiposity in hypogonadal men with cirrhosis. Application of testosterone gel, which undergoes no hepatic first-pass metabolism, seems as a safe and well-tolerated agent in liver cirrhosis as compared to other anabolic steroids, which may be associated with various adverse events.

Is increased colon subepithelial collagen layer thickness in diabetic patients related to collagenous colitis? An immunohistochemical study.

In this study, we evaluated immunohistochemically whether increased thickness of the colon subepithelial collagen layer in diabetic patients relates to collagenous colitis. A total of 100 patients (25 in each group) were included in this study. There were diabetic patients with chronic diarrhea in the first group, diabetic patients without chronic diarrhea in the second group, non-diabetic patients with chronic diarrhea in the third group, and control patients in the fourth group. The endoscopic biopsy specimens were obtained from the rectum, sigmoid colon, and descending colon. The thickness of the subepithelial collagen layer was measured using the ocular micrometer method. The immunohistochemical staining was performed with type 1 collagen and fibronectin antibody. The thickness of the colon subepithelial collagen layer in diabetic patients with or without diarrhea was significantly greater than that in control patients. This thickened subepithelial collagen layer in diabetic patients was stained with fibronectin antibody, but not with type 1 collagen antibody in the immunohistochemical study. These immunohistochemical staining characteristics were not similar to those in collagenous colitis, but were similar to those in normal subjects. Increased colon subepithelial collagen layer thickness in diabetic patients does not relate to collagenous colitis.

Clostridium difficile infection frequency in patients with nosocomial infections or using antibiotics.

BACKGROUND/AIMS: Clostridium difficile is the most common cause of nosocomial infectious diarrhea. The frequency of colonization in hospitalized patients varies between 10 and 43%. METHODOLOGY: Clostridium difficile common antigen was investigated in stool samples of 50 patients who developed nosocomial diarrhea (group 1), 65 outpatients who attended the clinic after development of diarrhea during antibiotic use (group 2), 18 patients with active chronic inflammatory bowel disease (group 3), and 30 control patients were studied. The Latex agglutination test and the toxin A was performed to investigate the presence of the Clostridium difficile common antigen in stool samples. The possible predisposing factors for nosocomial infection were analyzed. RESULTS: Clostridium difficile common antigen was found positive in 27.7% and 14% of group 2 and group 1, respectively while negative in stools of patients with inflammatory bowel disease. Asymptomatic fecal Clostridium difficile carriage in healthy volunteers was 3.3%. The antibiotic that induced diarrhea the most was clindamycin in group 1, and ampicillin-sulbactam in group 2. Enema was found to be the most important risk factor for C. difficile in hospitalized patients. CONCLUSIONS: The Clostridium difficile common antigen was detected more frequently in antibiotic-associated diarrhea patients than in nosocomial diarrhea patients. Clostridium difficile-associated diarrhea was also more frequent in immunosuppressive patients with uremia and diabetes mellitus.

Clinicopathologic characteristics and therapeutic outcomes of primary gastrointestinal non-Hodgkin's lymphomas in central Anatolia, in Turkey.

Primary gastrointestinal lymphoma is a common presentation of non-Hodgkin's lymphoma. The main controversy arises when many aspects of its classification and management are under discussion, particularly regarding roles for surgical resection. The aim of this study was to evaluate clinicopathologic characteristics and the therapeutic outcome of primary gastrointestinal non-Hodgkin's lymphoma. We carried out a retrospective analysis of 74 patients who were presented to our center with histopathological diagnosis of primary gastro-intestinal non-Hodgkin's lymphoma between 1990 and 2001. All patients have been staged according to Lugano Staging System. For histopathological classification, International Working Formulation was applied. The treatment choice concerning the surgical or non-surgical management was decided by the initially acting physician. Treatment modalities were compared using the parameters of age, sex, histopathological results, stage, and the site of disease. Of the 74 patients, 31 were female and 43 were male, with a median age of 49 years (range 15-80). The stomach was the most common primary site and was seen in 51 of 74 patients (68.9%). The intermediate and high grade lymphomas constituted 91.9% of the all cases. In a median follow-up of 29 months (range 2-128), 20 out of 74 patients died. There was a three year overall survival rate in 65.4% of all patients. The three year overall survival rate was better in stage I and II1 patients who were treated with surgery plus chemotherapy (+/-RT) than those treated with chemotherapy alone (93.7% vs. 55.6%, p < 0.05). The stage and presence of B symptoms affected the disease free survival and overall survival significantly, but the histopathologic grade only affected the overall survival. On the basis of these results, we suggest that surgical resection is necessary before chemotherapy in early stage (stage I and II1) patients with gastrointestinal non-Hodgkin's lymphomas because of the significant survival advantage it would bring to the patient.