Adalimumab in prevention of postoperative recurrence of Crohn's disease in high-risk patients

AIM: To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn’s disease in high-risk patients.METHODS: A multicenter, prospective, observational study was conducted from June 2009 until June 2010. We consecutively included high-risk Crohn’s disease patients who had undergone an ileal/ileocolonic resection. High-risk patients were defined as two or more criteria: smokers, penetrating pattern, one or more previous surgical resections or prior extensive resection. Subcutaneous adalimumab was administered 2 wk (± 5 d) after surgery at a dose of 40 mg eow, with an initial induction dose of 160/80 mg at weeks 0 and 2. Demographic data, previous and concomitant treatments (antibiotics, 5-aminosalicylates, corticosteroids, immunomodulators or biologic therapies), smoking status at the time of diagnosis and after the index operation and number of previous resections (type and reason for surgery) were all recorded. Biological status was assessed with C-reactive protein, erythrocyte sedimentation rate and fecal calprotectin. One year (± 3 mo) after surgery, an ileocolonoscopy and/or magnetic resonance enterography was performed. Endoscopic recurrence was defined as Rutgeerts score ≥ i2. Morphological recurrence was based on magnetic resonance (MR) score ≥ MR1.RESULTS: Twenty-nine patients (55.2% males, 48.3% smokers at diagnosis and 13.8% after the index operation), mean age 42.3 years and mean duration of the disease 13.8 years were included in the study. A mean of 1.76 (range: 1-4) resections previous to adalimumab administration and in 37.9% was considered extensive resection. 51.7% had previously received infliximab. Immunomodulators were given concomitantly to 17.2% of patients. Four of the 29 (13.7%) developed clinical recurrence, 6/29 (20.7%) endoscopic recurrence and 7/19 (36.8%) morphological recurrence after 1-year. All patients with clinical recurrence showed endoscopic and morphological recurrence. A high degree of concordance was found between clinical-endoscopic recurrence (κ = 0.76, P < 0.001) and clinical-morphological recurrence (κ = 0.63, P = 0.003). Correlation between endoscopic and radiological findings was good (comparing the 5-point Rutgeerts score with the 4-point MR score, a score of i4 was classified as MR3, i3 as MR2, and i2-i1 as MR1) (P < 0.001, r_s = 0.825). During follow-up, five (17.2%) patients needed adalimumab dose intensification (40 mg/wk); Mean time to intensification after the introduction of adalimumab treatment was 8 mo (range: 5 to 11 mo). In three cases (10.3%), a biological change was needed due to a worsening of the disease after the dose intensification to 40 mg/wk. One patient suffered an adverse event.CONCLUSION: Adalimumab seems to be effective and safe in preventing postoperative recurrence in a selected group of patients who had undergone an intestinal resection for their CD.     

Overlooked Management and Risk Factors for Anemia in Patients with Intestinal Beh?et’s Disease in Actual Clinical Practice

Background/Aims

Anemia in patients with inflammatory bowel disease significantly affects the quality of life. The aim of this study was to investigate the frequency of and risk factors for anemia and to describe the management of anemia in patients with intestinal Behçet’s disease (BD) in actual clinical practice.

Methods

We included 64 patients with intestinal BD who visited the outpatient clinic of a tertiary referral center in June 2011 and had available laboratory data for the subsequent 6 months.

Results

Anemia was detected in 26 patients (40.6%). After 6 months, anemia was still present in 14 of these patients (53.8%). The cause of anemia was investigated in eight patients (30.8%), and oral iron supplementation was prescribed to four patients (15.4%). Of these four patients, two (50%) recovered completely within 6 months. Anemia was associated with a high Disease Activity Index for Intestinal Behçet’s Disease (DAIBD, p=0.024), erythrocyte sedimentation rate (p=0.003), and C-reactive protein (p=0.049) in univariate analysis. In multivariate analysis, the factor predictive for anemia in patients with intestinal BD was a higher DAIBD (≥40; odds ratio, 4.08; 95% confidence interval, 1.21 to 13.71; p=0.023).

Conclusions

Although anemia is common in intestinal BD patients, its clinical importance is overlooked in daily practice. Moderate to severe disease activity is predictive of anemia.     

Multiple Perforations along the Entire Colon as a Complication of Intestinal Behcet's Disease: A Rare Case

Colonic complications of Behcet''s disease due to intestinal involvement are rarely reported in the literature. Ulcers are the most frequently seen intestinal complications that cause bleeding and perforation predominantly in the ileocecal region. In this article, we report a patient with Behcet''s disease who presented with multiple perforations along the entire colon. Postoperative histopathological examination revealed multiple ulcers containing lymphocytic infiltrations in the small peripheral and submucosal venules. Intimal thickening and fresh intraluminal fibrin thrombosis were also seen in these venules.     

RETRACTED: Association between erectile dysfunction and coronary artery disease and it's severity

Background/aims

To investigate the prevalence of erectile dysfunction (ED) in patients with coronary artery disease (CAD), its relationship between the severity of ED and the extent of coronary vessel involvement and to register the mean time interval between them.

Methods

240 patients with CAD divided into three age-matched groups: Group 1 (n = 60), ACS with one-vessel disease (1VD); group 2 (n = 60), ACS with 2,3VD; group 3 (n = 60), CSA. Control group (C, n = 60) was composed of patients with suspected CAD who were found to have entirely normal coronary arteries by angiography. ED as any value <26 according to the Gensini''s scores and according to the International Index of Erectile Function (IIEF).

Results

ED prevalence was 76%. ED prevalence was lower in G1 vs. G3 (22 vs.65%). G2 ED rate [55%, P < 0.0001] IIEF = 24 (17–29) & Gensini''s scores-21 (12.5–32) were significantly different from G1 and similar to G3, ED in ACS differs according to the extent of CAD. G3 patients who had ED symptoms prior to CAD symptoms and time interval between ED and CAD symptom onset in CCS according to number of vessels. Onset of sexual dysfunction occurred before CAD onset with a mean time interval of 24 m [12–36].

Conclusion

Early diagnosis of ED, cardiovascular assessment and aggressive treatment of cardiovascular risk factors might have contributed to prevent the acute events of this patient. Patients should be systematically screened for ED as a part of periodic examination programs. This would lead to early detection of modifiable vascular risk factors, or already existing vascular disease and to prevent ED and vascular disease progression through pharmacological and life style modifications.     

Impact of preceding respiratory viral infections on the clinical severity of patients with pneumococcal pneumonia

Background

This study aimed to investigate the impact of preceding respiratory viral infections (RVI) on the clinical severity of pneumococcal pneumonia patients.

Methods

A retrospective observational study was conducted at a university hospital from January 2009 to March 2013. Study subjects included adults (aged ≥18 years) with pneumococcal pneumonia who had undergone laboratory tests for RVI. Multivariate logistic regression analysis was performed to identify risk factors associated with severe pneumococcal pneumonia, defined as severity with the Pneumonia Severity Index (PSI) score ≥91.

Results

In total, 191 patients with pneumococcal pneumonia were included for analysis and stratified into 2 groups: the severe group with a PSI score ≥91 (n = 99) and the non-severe group with a PSI score <91 (n = 92). Preceding RVIs were detected in 48 patients, including influenza A virus (n = 20), influenza B virus (n = 4), parainfluenza viruses (n = 5), metapneumovirus (n = 4), rhinovirus (n = 4), respiratory syncytial viruses (n = 6), coronaviruses (n = 2), and mixed viral infections (n = 3). In the multivariate logistic regression analysis, preceding RVIs (odds ratio [OR], 2·49; 95% confidence interval [CI], 1·10–5·60), male sex (OR, 2·58; 95% CI, 1·24–5·38), old age (OR, 2·92; 95% CI, 1·37–6·24), hypoalbuminemia (OR, 3·26; 95% CI, 1·56–6·84)], and azotemia (OR, 2·24; 95% CI, 1·08–4·67) were significantly associated with severe pneumococcal pneumonia.

Conclusion

This study suggests that preceding RVIs might be one of the risk factors affecting the clinical severity of pneumococcal pneumonia.     

Differences in clinical features of Crohn’s disease and intestinal tuberculosis

AIM: To investigate the clinical features of Crohn’s disease(CD) and intestinal tuberculosis(ITB) with a scoring system that we have developed.METHODS: A total of 25 CD and 40 ITB patients were prospectively enrolled from August 2011 to July 2012.Their characteristics and clinical features were recorded. Laboratory, endoscopic, histologic and radiographic features were determined. The features with a high specificity were selected to establish a scoring system. The features supporting CD scored +1, and those supporting ITB scored-1; each patient received a final total score. A receiver operating characteristic(ROC) curve was used to determine the best cut-off value for distinguishing CD from ITB.RESULTS: Based on a high specificity of differentiating between CD and ITB, 12 features, including longitudinal ulcers, nodular hyperplasia, cobblestone-like mucosa, intestinal diseases, intestinal fistula, the target sign, the comb sign, night sweats, the purified protein derivative test, the interferon-γ release assay(T-SPOT.TB), ring ulcers and ulcer scars, were selected for the scoring system. The results showed that the average total score of the CD group was 3.12 ± 1.740, the average total score of the ITB group was-2.58 ± 0.984, the best cutoff value for the ROC curve was-0.5, and the diagnostic area under the curve was 0.997, which was statistically significant(P < 0.001). The patients whose total scores were higher than-0.5 were diagnosed with CD; otherwise, patients were diagnosed with ITB. Overall, the diagnostic accuracy rate and misdiagnosis rate of this scoring system were 97% and 3%, respectively. CONCLUSION: Some clinical features are valuable for CD and ITB diagnosis. The described scoring system is key to differentiating between CD and ITB.     

Different risk factors influence peptic ulcer disease development in a Brazilian population

AIM: To investigate age, sex, histopathology and Helicobacter pylori (H. pylori) status, as risk factors for gastroduodenal disease outcome in Brazilian dyspeptic patients.tients submitted to upper gastroscopy at Hospital das Clinicas of Marilia, antral biopsy specimens were obtained and subjected to histopathology and H. pylori diagnosis. All patients presenting chronic gastritis (CG) and peptic ulcer (PU) disease localized in the stomach, gastric ulcer (GU) and/or duodenal ulcer (DU) were included in the study. Gastric biopsies (n = 668) positive for H. pylori by rapid urease test were investigated for vacuolating cytotoxin A (vacA ) medium (m) region mosaicism by polymerase chain reaction. Logistic regression analysis was performed to verify the association of age, sex, histopathologic alterations, H. pylori diagnosis and vacA m region mosaicism with the incidence of DU, GU and CG in patients. RESULTS: Of 1466 patients submitted to endoscopy, 1060 (72.3%) presented CG [male/female = 506/554; mean age (year) ± SD = 51.2 ± 17.81], 88 (6.0%) presented DU [male/female = 54/34; mean age (year) ± SD = 51.4 ± 17.14], and 75 (5.1%) presented GU [male/female = 54/21; mean age (year) ± SD = 51.3 ± 17.12] and were included in the comparative analysis. Sex and age showed no detectable effect on CG incidence (overall c 2 = 2.1, P = 0.3423). Sex [Odds ratios (OR) = 1.8631, P = 0.0058] but not age (OR = 0.9929, P = 0.2699) was associated with DU and both parameters had a highly significant effect on GU (overall c 2 = 30.5, P 0.0001). The histopathological results showed a significant contribution of ageing for both atrophy (OR = 1.0297, P 0.0001) and intestinal metaplasia (OR = 1.0520, P 0.0001). Presence of H. pylori was significantly associated with decreasing age (OR = 0.9827, P 0.0001) and with the incidence of DU (OR = 3.6077, P 0.0001). The prevalence of m1 in DU was statistically significant (OR = 2.3563, P = 0.0018) but not in CG (OR = 2.678, P = 0.0863) and GU (OR = 1.520, P = 0.2863). CONCLUSION: In our population, male gender was a risk factor for PU; ageing for GU, atrophy and metapla-sia; and H. pylori of vacA m1 genotype for DU.     

Endoscopic findings in patients with Schatzki rings: Evidence for an association with eosinophilic esophagitis

AIM: To investigate endoscopic findings in patients with Schatzki rings (SRs) with a focus on evidence for eosinophilic esophagitis (EoE).METHODS: We consecutively approached all adult patients scheduled for elective outpatient upper endoscopy for a variety of indications at the German Diagnostic Clinic, Wiesbaden, Germany between July 2007 and July 2010. All patients with endoscopically diagnosed SRs, defined as thin, symmetrical, mucosal structures located at the esophagogastric junction, were prospectively registered. Additional endoscopic findings, clinical information and histopathological findings with a focus on esophageal eosinophilia (≥ 20 eosinophils/high power field) were recorded. The criteria for active EoE were defined as: (1) eosinophilic tissue infiltration ≥ 20 eosinophils/hpf; (2) symptoms of esophageal dysfunction; and (3) exclusion of other causes of esophageal eosinophilia. Gastroesophageal reflux disease was excluded by proton pump inhibitor treatment prior to endoscopy. The presence of ≥ 20 eosinophils/hpf in esophageal biopsies in patients that did not fulfil the criteria of EoE was defined as esophageal hypereosinophilia.RESULTS: A SR was diagnosed in 171 (3.3%; 128 males, 43 females, mean age 66 ± 12.9 years) of the 5163 patients that underwent upper gastrointestinal-endoscopy. Twenty of the 116 patients (17%) from whom esophageal biopsies were obtained showed histological hypereosinophilia (≥ 20 eosinophils/hpf). Nine of these patients (8 males, 1 female, mean age 49 ± 10 years) did not fulfill all diagnostic criteria of EoE, whereas in 11 (9%) patients with ≥ 20 eosinophils/hpf, a definite diagnosis of EoE was made. Three of the 11 patients (27%) with definite EoE had no suspicious endoscopic features of EoE. In contrast, in the 25 patients in whom EoE was suspected by endoscopic features, EoE was only confirmed in 7 (28%) patients. Patients with EoE were younger (mean age 41.5 ± 6.5 vs 50.5 ± 11.5 years, P = 0.012), were more likely to have a history of allergies (73% vs 29%, P = 0.007) and complained more often of dysphagia (91% vs 34%, P = 0.004) and food impaction (36% vs 6%, P = 0.007) than patients without EoE. Endoscopically, additional webs were found significantly more often in patients with EoE than in patients without EoE (36% vs 11%, P = 0.04). Furthermore, the SR had a tendency to be narrower in patients with EoE than in those without EoE (36% vs 18%, P = 0.22). The percentage of males (73% vs 72%, P = 1.0) and frequency of heartburn (27% vs 27%, P = 1.0) were not significantly different in both groups. The 9 patients with esophageal hypereosinophilia that did not fulfil the diagnostic criteria of EoE were younger (mean age 49 ± 10 years vs 58 ± 6 years, P = 0.0008) and were more likely to have a history of allergies (78% vs 24%, P = 0.003) than patients with < 20 eosinophils/hpf. Predictors of EoE were younger age, presence of dysphagia or food impaction and a history of allergies.CONCLUSION: A significant proportion of patients with SRs also have EoE, which may not always be suspected according to other endoscopic features.     

Eosinophil associated genes in the inflammatory bowel disease 4 region: Correlation to inflammatory bowel disease revealed

AIM: To study the association between inflammatory bowel disease (IBD) and genetic variations in eosinophil protein X (EPX) and eosinophil cationic protein (ECP).METHODS: DNA was extracted from ethylene diamine tetraacetic acid blood of 587 patients with Crohn’s disease (CD), 592 with ulcerative colitis (UC) and 300 healthy subjects. The EPX405 (G > C, rs2013109), ECP434 (G > C, rs2073342) and ECP562 (G > C, rs2233860) gene polymorphisms were analysed, by the 5’-nuclease allelic discrimination assay. For determination of intracellular content of EPX and ECP in granulocytes, 39 blood samples was collected and extracted with a buffer containing cetyltrimethylammonium bromide. The intracellular content of EPX was analysed using an enzyme-linked immunosorbent assay. The intracellular content of ECP was analysed with the UniCAP^® system as described by the manufacturer. Statistical tests for calculations of results were χ² test, Fisher’s exact test, ANOVA, Student-Newman-Keuls test, and Kaplan-Meier survival curve with Log-rank test for trend, the probability values of P < 0.05 were considered statistically significant.RESULTS: The genotype frequency for males with UC and with an age of disease onset of ≥ 45 years (n = 57) was for ECP434 and ECP562, GG = 37%, GC = 60%, CC = 4% and GG = 51%, GC = 49%, CC = 0% respectively. This was significantly different from the healthy subject’s genotype frequencies of ECP434 (GG = 57%, GC = 38%, CC = 5%; P = 0.010) and ECP562 (GG = 68%, GC = 29%,CC = 3%; P = 0.009). The genotype frequencies for females, with an age of disease onset of ≥ 45 years with CD (n = 62), was for the ECP434 and ECP562 genotypes GG = 37%, GC = 52%, CC = 11% and GG = 48%, GC = 47% and CC = 5% respectively. This was also statistically different from healthy controls for both ECP434 (P = 0.010) and ECP562 (P = 0.013). The intracellular protein concentration of EPX and ECP was calculated in μg/10⁶ eosinophils and then correlated to the EPX 405 genotypes. The protein content of EPX was highest in the patients with the CC genotype of EPX405 (GG = 4.65, GC = 5.93, and CC = 6.57) and for ECP in the patients with the GG genotype of EPX405 (GG = 2.70, GC = 2.47 and CC = 1.90). ANOVA test demonstrated a difference in intracellular protein content for EPX (P = 0.009) and ECP (P = 0.022). The age of disease onset was linked to haplotypes of the EPX405, ECP434 and ECP562 genotypes. Kaplan Maier curve showed a difference between haplotype distributions for the females with CD (P = 0.003). The highest age of disease onset was seen in females with the EPX405CC, ECP434GC, ECP562CC haplotype (34 years) and the lowest in females with the EPX405GC, ECP434GC, ECP562GG haplotype (21 years). For males with UC there was also a difference between the highest and lowest age of the disease onset (EPX405CC, ECP434CC, ECP562CC, mean 24 years vs EPX405GC, ECP434GC, ECP562GG, mean 34 years, P = 0.0009). The relative risk for UC patients with ECP434 or ECP562-GC/CC genotypes to develop dysplasia/cancer was 2.5 (95%CI: 1.2-5.4, P = 0.01) and 2.5 (95%CI: 1.1-5.4, P = 0.02) respectively, compared to patients carrying the GG-genotypes.CONCLUSION: Polymorphisms of EPX and ECP are associated to IBD in an age and gender dependent manner, suggesting an essential role of eosinophils in the pathophysiology of IBD.     

Efficacy of MK615 for the treatment of patients with liver disorders

AIM:To investigate the hepatoprotective effect of MK615,a Japanese apricot extract,in an animal model,and its clinical therapeutic effect.METHODS:Wistar rats were administered physiological saline(4 mL/kg) or MK615 solution(4 mL/kg) for 7 d.On the sixth d,acute hepatic injury was induced by administering a single intraperitoneal injection(ip) of D-galactosamine hydrochloride(D-GalN)(600 mg/kg).Plasma levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined,and liver tissues were used for histopathological analysis.Fifty-eight patients with liver disorders [hepatitis C(n = 40),non-alcoholic fatty liver disease(n = 15),and autoimmune liver disease(n = 3)] were orally administered commercially available Misatol ME-containing MK615(13 g/d) daily for 12 wk.Blood and urine were sampled immediately before and 6 wk,12 wk,and 16 wk after the start of intake to measure various biochemical parameters.The percentage change in ALT and AST levels after 12 wk from the pre-intake baseline served as a primary endpoint.RESULTS:D-GalN effectively induced acute hepatic injury in the rats.At 48 h after the ip injection of D-GalN,the plasma levels of ALT(475.6 ± 191.5 IU/L vs 225.3 ± 194.2 IU/L,P 0.05) and AST(1253.9 ± 223.4 IU/L vs 621.9 ± 478.2 IU/L,P 0.05) in the MK615 group were significantly lower than the control group.Scattered single cell necrosis,loss of hepatocytes,and extensive inflammatory cell infiltration were observed in hepatic tissue samples collected from the control group.However,these findings were less pronounced in the group receiving MK615.At the end of the clinical study,serum ALT and AST levels were significantly decreased compared with pre-intake baseline levels from 103.5 ± 58.8 IU/L to 71.8 ± 39.3 IU/L(P 0.05) and from 93.5 ± 55.6 IU/L to 65.5 ± 34.8 IU/L(P 0.05),respectively.A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 26(45%) of the 58 patients,while 25(43%) patients exhibited similar AST level reductions.The chronic hepatitis C group exhibited significant ALT and AST level reductions from 93.4 ± 51.1 IU/L to 64.6 ± 35.1 IU/L(P 0.05) and from 94.2 ± 55.5 IU/L to 67.2 ± 35.6 IU/L(P 0.05),respectively.A reduction of ≥ 30% from the pre-study baseline ALT level was observed in 20(50%) of the 40 patients.ALT levels in both the combined ursodeoxycholic acid(UDCA) treatment and the UDCA uncombined groups were significantly lower after Misatol ME administration.MK615 protected hepatocytes from D-GalN-induced cytotoxicity in rats.Misatol ME decreased elevated ALT and AST levels in patients with liver disorders.CONCLUSION:These results suggest that MK615 and Misatol ME are promising hepatoprotective agents for patients with liver disorders.     

Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer

AIM:To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer. METHODS:One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman’s correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer. RESULTS:Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively). CONCLUSION:KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biom     

Patients ≥75 years with acute coronary syndrome but without critical epicardial coronary disease: prevalence, characteristics, and outcome

Objective Absence of significant epicardial coronary artery disease (CAD) in patients with acute onset of chest pain and elevation of myocardial necrosis markers is occasionally observed. The aim of this study was to analyse the clinical characteristics and outcome of such patients with advanced age. Methods We retrospectively analysed 4,311 patients with acute onset of chest pain plus necrosis marker elevation. Two hundred and seventy two patients without CAD on angiogram (6.3%) were identified. Out of them, 50 (1.2%) patients ≥ 75 years (Group I) were compared with (1) 222 acute coronary syndrome (ACS) patients without CAD on angiogram < 75 years (Group II), and (2) 610 consecutive patients ≥ 75 years with Non-ST-elevation Myocardial Infarction (NSTEMI) undergoing percutaneous coronary intervention (Group III). Results Group I compared to Group III patients made up for more females (64.0% vs. 49.2%; P < 0.0001), and had more severe anginal symptoms on presentation [Canadian Cardiovascular Society (CCS) class I/II, 26.0% vs. 49.8%; P = 0.02]. Group I patients also had lower troponin levels (0.62 ± 0.8 ng/mL vs. 27 ± 74 ng/mL; P < 0.02), lower leukocyte count (9.4 ± 3.13 × 10⁹ vs. 12 ± 5.1 × 10⁹; P = 0.001) and better preserved left ventricular function (56.7% ± 14.3% vs. 45% ± 11%; P < 0.0001). Event-free survival (cardiac death, myocardial infarction, recurrent angina, and re-hospitalisation) was more frequent in Group I and II patients compared to Group III patients (64.9%, 66.7%, and 41.6%, respectively; P < 0.0001). Conclusions ACS in patients ≥ 75 years without CAD is very infrequent, associated with a (1) similar outcome compared to ACS patients < 75 years without CAD, and (2) significant better outcome compared to NSTEMI patients ≥ 75 years.     

Donor preoperative oxygen delivery and post-extubation hypoxia impact donation after circulatory death hypoxic cholangiopathy

AIM: To evaluate donation after circulatory death(DCD) orthotopic liver transplant outcomes [hypoxic cholangiopathy(HC) and patient/graft survival] and donor risk-conditions.METHODS: From 2003-2013, 45 DCD donor transplants were performed. Predonation physiologic data from UNOS Donor Net included preoperative systolic and diastolic blood pressure, heart rate, p H, SpO_2, PaO_2, FiO_2, and hemoglobin. Mean arterial bloodpressure was computed from the systolic and diastolic blood pressures. Donor preoperative arterial O_2 content was computed as [hemoglobin(gm/d L) × 1.37(m L O_2/gm) × SpO_2%) +(0.003 × PaO_2)]. The amount of preoperative donor red blood cell transfusions given and vasopressor use during the intensive care unit stay were documented. Donors who were transfused ≥ 1 unit of red-cells or received ≥ 2 vasopressors in the preoperative period were categorized as the red-cell/multi-pressor group. Following withdrawal of life support, donor ischemia time was computed as the number-of-minutes from onset of diastolic blood pressure 60 mm Hg until aortic cross clamping. Donor hypoxemia time was the number-of-minutes from onset of pulse oximetry 80% until clamping. Donor hypoxia score was(ischemia time + hypoxemia time) ÷ donor preoperative hemoglobin.RESULTS: The 1, 3, and 5 year graft and patient survival rates were 83%, 77%, 60%; and 92%, 84%, and 72%, respectively. HC occurred in 49% with 16% requiring retransplant. HC occurred in donors with increased age(33.0 ± 10.6 years vs 25.6 ± 8.4 years, P = 0.014), less preoperative multiple vasopressors or red-cell transfusion(9.5% vs 54.6%, P = 0.002), lower preoperative hemoglobin(10.7 ± 2.2 gm/d L vs 12.3 ± 2.1 gm/d L, P = 0.017), lower preoperative arterial oxygen content(14.8 ± 2.8 m L O_2/100 m L blood vs 16.8 ± 3.3 m L O_2/100 m L blood, P = 0.049), greater hypoxia score 2.0(69.6% vs 25.0%, P = 0.006), and increased preoperative mean arterial pressure(92.7 ± 16.2 mm Hg vs 83.8 ± 18.5 mm Hg, P = 0.10). HC was independently associated with age, multi-pressor/redcell transfusion status, arterial oxygen content, hypoxia score, and mean arterial pressure(r~2 = 0.6197). The transplantation rate was greater for the later period with more liberal donor selection [era 2(7.1/year)], compared to our early experience [era 1(2.5/year)]. HC occurred in 63.0% during era 2 and in 29.4% during era 1(P = 0.03). Era 2 donors had longer times for extubation-to-asystole(14.4 ± 4.7 m vs 9.3 ± 4.5 m, P = 0.001), ischemia(13.9 ± 5.9 m vs 9.7 ± 5.6 m, P = 0.03), and hypoxemia(16.0 ± 5.1 m vs 11.1 ± 6.7 m, P = 0.013) and a higher hypoxia score 2.0 rate(73.1% vs 28.6%, P = 0.006).CONCLUSION: Easily measured donor indices, including a hypoxia score, provide an objective measure of DCD liver transplantation risk for recipient HC. Donor selection criteria influence HC rates.     

Value of α-fetoprotein in association with clinicopathological features of hepatocellular carcinoma

AIM:To explore the relationship between α-fetoprotein(AFP) and various clinicopathological variables and different staging system of hepatocellular carcinoma(HCC) thoroughly.METHODS:A retrospective cohort study of consecutive patients diagnosed with HCC between January 2008 and December 2009 in West China Hospital was enrolled in our study.The association of serum AFP values with the HCC clinicopathological features was analysed by univariate and multivariate analysis,such as status of hepatitis B virus(HBV) infection,tumor size,tumor number,vascular invasion and degree of tumor differentiation.Also,patients were divided into four groups at the time of enrollment according to different cutoff values for serum value of AFP(≤ 20 μg/L,21-400 μg/L,401-800 μg/L,and ≥ 801 μg/L),to compare the positive rate of patient among four groups stratified by various clinicopathological variables.And the correlation of different kinds of tumor staging systems,such as TNM,Barcelona Clinic Liver Cancer(BCLC) staging classification and China staging,were compared with the serum concentration of AFP.RESULTS:A total of 2304 HCC patients were enrolled in this study totally;the mean serum level of AFP was 555.3 ± 546.6 μg/L.AFP levels were within the normal range(< 20 μg/L) in 27.4%(n = 631) of all the cases.81.4%(n = 1875) patients were infected with HBV,and those patients had much higher serum AFP level compared with non-HBV infection ones(573.9 ± 547.7 μg/L vs 398.4 ± 522.3 μg/L,P < 0.001).The AFP level in tumors ≥ 10 cm(808.4 ± 529.2 μg/L) was significantly higher(P < 0.001) than those with tumor size 5-10 cm(499.5 ± 536.4 μg/L) and with tumor size ≤ 5 cm(444.9 ± 514.2 μg/L).AFP levels increased significantly in patients with vascular invasion(694.1 ± 546.9 μg/L vs 502.1 ± 543.1 μg/L,P < 0.001).Patients with low tumor cell differentiation(559.2 ± 545.7 μg/L) had the significantly(P = 0.007) highest AFP level compared with high differentiation(207.3 ± 420.8 μg/L) and intermediate differe     

Sperm quality before treatment in patients with early stage Hodgkin’s lymphoma enrolled in EORTC-GELA Lymphoma Group trials

Background

Although widely recommended, cryopreservation of sperm is sometimes not performed for patients with Hodgkin’s lymphoma because of presumed poor sperm quality related to the disease. We investigated sperm quality and factors determining it in untreated patients with early stage Hodgkin’s lymphoma.

Design and Methods

Of 2362 males who participated in EORTC H6–H9 trials, 474 (20%) had data available. Sperm quality was defined according to World Health Organization guidelines. Determining factors were studied by logistic regression analysis.

Results

The median sperm concentration was 40×10⁶/mL (range, 0–345×10⁶/mL) and the median motility 50% (range, 0–90%). Sperm quality was good (concentration ≥20×10⁶/mL and motility ≥50%), intermediate (concentration ≥5×10⁶/mL) and poor (concentration <5×10⁶/mL but >0) in 41%, 49% and 7% of patients, respectively. Three percent of the patients were azoospermic. No relation was found between sperm quality and age or clinical stage of the Hodgkin’s lymphoma, but B-symptoms and elevated erythrocyte sedimentation rate predicted poor sperm quality. The odds ratios for the association of poor sperm quality with the variables examined were: presence of B-symptoms, 2.77 (95% CI, 1.50–5.12; p=0.001); erythrocyte sedimentation rate of 50 mm/h or greater, 2.35 (95% CI, 1.24–4.43; p=0.009); fever, 3.22 (95% CI, 1.41–7.33; p=0.005), and night sweats, 3.78 (95% CI, 1.97–7.26; p<0.001). There was no relation between sperm quality and pre-treatment follicle stimulating hormone level.

Conclusions

In this large study of males with Hodgkin’s lymphoma, 90% had good or intermediate sperm quality. Three percent were azoospermic. There was an association between sperm quality and the presence or absence of B-symptoms, in particular fever and night sweats. With modern fertilization techniques, in most patients with early-stage Hodgkin’s lymphoma sperm quality before treatment is good enough for future fatherhood.     

Prognosis of patients with gastric cancer and solitary lymph node metastasis

AIM:To investigate the relationship of solitary lymph node metastasis(SLNM)and age with patient survival in gastric cancer(GC).METHODS:The medical records databases of China’s Beijing Cancer Hospital at the Peking University School of Oncology and Shanghai Tenth People’s Hospital affiliated to Tongji University were searched retrospectively to identify patients with histologically proven GC and SLNM who underwent surgical resection between October 2003 and December 2012.Patients with distant metastasis or gastric stump carcinoma following resection for benign disease were excluded from the analysis.In total,936 patients with GC+SLNM were selected for analysis and the recorded parameters of clinicopathological disease and follow-up(range:13-2925 d)were collected.The Kaplan-Meier method was used to stratify patients by age(≤50 years-old,n=198;50-64 years-old,n=321;≥65 years-old,n=446)and by metastatic lymph node ratio[MLR<0.04(1/25),n=180;0.04-0.06(1/25-1/15),n=687;≥0.06(1/15),n=98]for 5-year survival analysis.The significance of intergroup differences between the survival curves was assessed by a log-rank test. RESULTS:The 5-year survival rate of the entire GC+SLNM patient population was 49.9%.Stratification analysis showed significant differences in survival time(post-operative days)according to age:≤50 yearsold:950.7±79.0 vs 50-64 years-old:1697.8±65.9 vs≥65 years-old:1996.2±57.6,all P<0.05.In addition,younger age(≤50 years-old)correlated significantly with mean survival time(r=0.367,P<0.001).Stratification analysis also indicated an inverse relationship between increasing MLR and shorter survival time:<0.04:52.8%and 0.04-0.06:51.1%vs≥0.06:40.5%,P<0.05.The patients with the shortest survival times and rates were younger and had a high MLR(≥0.06):≤50 years-old:496.4±133.0 and 0.0%vs 50-65 years-old:1180.9±201.8 and 21.4%vs≥65 years-old:1538.4±72.4 and 37.3%,all P<0.05.The same significant trend in shorter survival times and rates for younger patients was seen with     

High-fibre diet and Lactobacillus paracasei B21060 in symptomatic uncomplicated diverticular disease

AIM:To investigate in symptomatic uncomplicated diverticular disease the efficacy of symbiotics associated with a high-fibre diet on abdominal symptoms.METHODS:This study was a multicentre,6-mo randomized,controlled,parallel-group intervention with a preceding 4-wk washout period.Consecutive outpatients with symptomatic uncomplicated diverticular disease,aged 40-80 years,evaluated in 4 Gastroenter-ology Units,were enrolled.Symptomatic uncomplicated diverticular disease patients were randomized to two treatment arms A or B.Treatment A(n = 24 patients) received 1 symbiotic sachet Flortec(Lactobacillus paracasei B21060) once daily plus high-fibre diet for 6 mo.Treatment B(n = 21 patients) received high-fibre diet alone for 6 mo.The primary endpoint was regression of abdominal symptoms and change of symptom severity after 3 and 6 mo of treatment.RESULTS:In group A,the proportion of patients with abdominal pain 24 h decreased from 100% at baseline to 35% and 25% after 3 and 6 mo,respectively(P 0.001).In group B the proportion of patients with this symptom decreased from 90.5% at baseline to 61.9% and 38.1% after 3 and 6 mo,respectively(P = 0.001).Symptom improvement became statistically significant at 3 and 6 mo in group A and B,respectively.The proportion of patients with abdominal pain 24 h decreased from 60% to 20% then 5% after 3 and 6 mo,respectively in group A(P 0.001) and from 33.3% to 9.5% at both 3 and 6 mo in group B(P = 0.03).In group A the proportion of patients with abdominal bloating significantly decreased from 95% to 60% after 3 mo,and remained stable(65%) at 6-mo follow-up(P = 0.005) while in group B,no significant changes in abdominal bloating was observed(P = 0.11).After 6 mo of treatment,the mean visual analogic scale(VAS) values of both short-lasting abdominal pain(VAS,mean ± SD,group A:4.6 ± 2.1 vs 2.2 ± 0.8,P = 0.02;group B:4.6 ± 2.9 vs 2.0 ± 1.9,P = 0.03) and abdominal bloating(VAS,mean ± SD,group A:5.3 ± 2.2 vs 3.0 ± 1.7,P = 0.005;group B:5.3 ± 3.2 vs 2.3 ± 1.9,P = 0.006) decreased in both groups,whilst the VAS values of prolonged abdominal pain decreased in the Flortec group,but remained unchanged in the high-fibre diet group(VAS,mean ± SD,group A:6.5 ± 1.5 vs 4.5 ± 2.1,P = 0.052;group B:4.5 ± 3.8 vs 5.5 ± 3.5).CONCLUSION:A high-fibre diet is effective in relievingabdominal symptoms in symptomatic uncomplicated diverticular disease.This treatment may be implemented by combining the high-fibre diet with Flortec.     

Relationship between methylation and colonic inflammation in inflammatory bowel disease

AIM:To investigate the relationship between the methylation status in the SLIT2 and TGFB2 promoters and colonic inflammation in inflammatory bowel disease patients.METHODS:We evaluated the methylation status of 2genes(SLIT2 and TGFB2)in 226 biopsies taken from62 colonoscopies of 38 patients(29 ulcerative colitis and 9 Crohn’s colitis)using methylation-specific melting curve analysis.The relationships between methylation status and clinical,biological,endoscopic and histological activities were evaluated.Twenty-three of the 38patients had a second colonoscopy and were included in a longitudinal analysis.Numerical results were given as the means±SD of the sample and range,except when specified.Student t analysis,U Mann Whitney and ANOVA factor were used to compare the means.Qualitative results were based on theχ2 test.RESULTS:SLIT2 methylation was more frequent in samples with endoscopic activity than with endoscopic remission(55%vs 18%,P<0.001).SLIT2 methylation was also higher in samples with acute inflammation(56.5%)than in samples with chronic(24%)or absent inflammation(15%)(P<0.001).For TGFB2methylation,the correlation was only significant with endoscopic activity.Methylation was higher in the distal colon for both genes(P<0.001 for SLIT2 and P=0.022for TGFB2).In the multivariate analysis,only inflammation status(and not disease duration or extension)was independently associated with SLIT2 methylation[OR=6.6(95%CI:1.65-27.36),P=0.009].In the longitudinal analysis,the maintenance of endoscopic remission was protective for methylation.CONCLUSION:Endoscopic and histological inflammation are predictive for SLIT2 methylation.