Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma

<p>Abstract</p> <p>Background and Aim</p> <p>PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC). However, the results published to date reported on studies with no more than 6 (mostly up to 4) PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14) settings of PDT, combined with biliary drainage, and (in some cases) with chemotherapy.</p> <p>Methods</p> <p>Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010.</p> <p>Results</p> <p>Ten patients (male/female = 5/5), mean age 68.8 years (range, 54 - 81 years) who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40%) bilateral metal stenting (JoStent SelfX^®) was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14). Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1^stline, GEMOX plus cetuximab as 2^ndline). The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1.</p> <p>Conclusion</p> <p>Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years.</p

Renal impairment after liver transplantation - a pilot trial of calcineurin inhibitor-free vs. calcineurin inhibitor sparing immunosuppression in patients with mildly impaired renal function after liver transplantation

<p>Abstract</p> <p>Objectives</p> <p>Chronic kidney disease is frequent in patients after orthotopic liver transplantation (OLT) and has impact on survival. Patients receiving calcineurin inhibitors (CNI) are at increased risk to develop impaired renal function. Early CNI reduction and concomitant use of mycophenolat mofetil (MMF) has been shown to improve renal function.</p> <p>Methods</p> <p>The aim of this trial was to compare dose-reduced CNI/MMF versus CNI-free MMF/prednisone-based treatment in stable patients after OLT with respect to glomerular filtration rate (GFR). 21 patients [GFR 44.9 ± 9.9 mL/min/1.73 m²measured by 99m-Tc-DTPA-clearance, serum creatinine (SCr) 1.5 ± 0.42 mg/dL] were randomized either to exchange CNI for 10 mg prednisone (group 1; n = 8) or to receive CNI at 25% of the initial dose (group 2; n = 13) each in combination with 1000 mg MMF b.i.d.</p> <p>Results</p> <p>At month 12 mean SCr (-0.3 ± 0.4 mg/dL, p = 0.031) and GFR improved (8.6 ± 13.1 mL/min/1.73 m², p = 0.015) in group 2 but remained unchanged in group 1. Main side effects were gastroinstestinal symptoms (14.3%) and infections (4.8%). Two biopsy proven, steroid-responsive rejections occurred. In group 1 mean diastolic blood pressure (BP) increased by 11 ± 22 mmHg (p = 0.03).</p> <p>Conclusions</p> <p>Reduced dose CNI in combination with MMF but not CNI-free-immunosuppression leads to improvement of GFR in patients with moderately elevated SCr levels after OLT. Addition of steroids resulted in increased diastolic blood pressure presumably counterbalancing the benefits of CNI withdrawal on renal function.</p

Cancer risk in HIV-infected individuals on HAART is largely attributed to oncogenic infections and state of immunocompetence

<p>Abstract</p> <p>Objectives</p> <p>To estimate the cancer risk of HIV-infected patients in the HAART era with respect to a general reference population and to determine risk factors for malignancy.</p> <p>Methods</p> <p>Long term (1996-2009) cancer incidence of the Bonn single centre HIV cohort was compared to the incidence of the reference population of Saarland using standardized incidence ratios (SIR). Poisson regression analysis was used to identify predictors of cancer risk.</p> <p>Results</p> <p>1,476 patients entered the cohort, enabling 8,772 person years of observation. 121 tumours in 114 patients, 7 in-situ and 114 invasive cancers, were identified. Malignancies associated with infectious agents such as Kaposi sarcoma (SIRs: male: 5,683; female: 277), non-Hodgkin lymphoma (SIRs male: 35; female: 18), anal cancer (SIRs male: 88; female: 115) as well a cervical carcinoma (SIR female: 4) and Hodgkin's disease (SIR male: 39) and liver cancer (SIR male: 18) were substantially more frequent in HIV-infected patients than in the general population (p < 0.001, each), whereas all other types of cancer were not increased. Poisson regression identified HAART (incidence rate ratio IRR (95% CI): 0.28 (0.19-0.41), p < 0.001), CD4 count (IRR per 100 cells/μl increase: 0.66 (0.57-0.76), p < 0.001), hepatitis B (IRR: 2.15 (1.10-4.20), p = 0.046) and age (IRR per 10 year increase: 1.23 (1.03 - 1.46), p = 0.023) as independent predictors for the occurrence of any type of cancer.</p> <p>Conclusions</p> <p>HAART and preserved CD4 cells preferentially reduce the risk of malignancies associated with oncogenic infections.</p

Short-term western diet aggravates non-alcoholic fatty liver disease (NAFLD) with portal hypertension in TGR(mREN2)27 rats

Non-alcoholic fatty liver disease (NAFLD) is gaining in importance and is linked to obesity. Especially, the development of fibrosis and portal hypertension in NAFLD patients requires treatment. Transgenic TGR(mREN2)27 rats overexpressing mouse renin spontaneously develop NAFLD with portal hypertension but without obesity. This study investigated the additional role of obesity in this model on the development of portal hypertension and fibrosis. Obesity was induced in twelve-week old TGR(mREN2)27 rats after receiving Western diet (WD) for two or four weeks. Liver fibrosis was assessed using standard techniques. Hepatic expression of transforming growth factor-β1 (TGF-β1), collagen type Iα1, α-smooth muscle actin, and the macrophage markers Emr1, as well as the chemoattractant Ccl2, interleukin-1β (IL1β) and tumor necrosis factor-α (TNFα) were analyzed. Assessment of portal and systemic hemodynamics was performed using the colored microsphere technique. As expected, WD induced obesity and liver fibrosis as confirmed by Sirius Red and Oil Red O staining. The expression of the monocyte-macrophage markers, Emr1, Ccl2, IL1β and TNFα were increased during feeding of WD, indicating infiltration of macrophages into the liver, even though this increase was statistically not significant for the EGF module-containing mucin-like receptor (Emr1) mRNA expression levels. Of note, portal pressure increased with the duration of WD compared to animals that received a normal chow. Besides obesity, WD feeding increased systemic vascular resistance reflecting systemic endothelial and splanchnic vascular dysfunction. We conclude that transgenic TGR(mREN2)27 rats are a suitable model to investigate NAFLD development with liver fibrosis and portal hypertension. Tendency towards elevated expression of Emr1 is associated with macrophage activity point to a significant role of macrophages in NAFLD pathogenesis, probably due to a shift of the renin-angiotensin system towards a higher activation of the classical pathway. The hepatic injury induced by WD in TGR(mREN2)27 rats is suitable to evaluate different stages of fibrosis and portal hypertension in NAFLD with obesity

Progression of liver fibrosis in HIV/HCV genotype 1 co-infected patients is related to the T allele of the rsI2979860 polymorphism of the IL28B gene

<p>Abstract</p> <p>Objective</p> <p>HIV/HCV co-infection is characterised by accelerated progression of liver disease. Recently, the rsl2979860 C/T polymorphism in the <it>IL28B </it>gene has been linked to progression towards cirrhosis in HCV mono-infected patients and to treatment response of HCV-infection in HIV/HCV co-infected patients. Our aim was to clarify by non-invasive techniques if this polymorphism affects fibrosis progression in HIV/HCV co-infection.</p> <p>Methods</p> <p>In a cross-sectional design, liver stiffness (transient elastography), surrogate markers of liver fibrosis (APRI and FIB-4 scores) and rsl2979860 genotypes were analysed in 84 HCV/H1V co-infected patients. <it>IL28B </it>genotypes were determined by real-time PCR using a light cycler. In 56 HIV/HCV co-infected patients we also studied progression of fibrosis in relation to rsl2979860 C/T genotypes over two years.</p> <p>Results</p> <p>82% of the patients were on HAART (74% without detectable HI viremia) and 67% were haemophiliacs, respectively. HCV genotype 1 was present in 62%. Cross-sectional median liver stiffness was 7.4 kPa and correlated with APRI and FIB-4 scores (r = 0.6 each, p < 0.001). Frequencies of <it>IL28B </it>genotypes were: CC 50%, CT 43% and TT 7%. In the cross-sectional analysis liver stiffness values were not different between the various <it>IL28B</it>-genotypes. Upon follow-up under HAART carriers of a C allele did not show further progression, while liver stiffness significantly increased in HIV/HCV co-infected patients with the T allele (p = 0.047).</p> <p>Conclusion</p> <p>Although progression of liver fibrosis was low under HAART in our cohort, progression was more pronounced in HIV/HCV genotype 1 co-infected patients with the T allele.</p

Narrow band imaging for the detection of gastric intestinal metaplasia and dysplasia during surveillance endoscopy

Background: Surveillance of premalignant gastric lesions relies mainly on random biopsy sampling. Narrow band imaging (NBI) may enhance the accuracy of endoscopic surveillance of intestinal metaplasia (IM) and dysplasia. We aimed to compare the yield of NBI to white light endoscopy (WLE) in the surveillance of patients with IM and dysplasia. Methods: Patients with previously identified gastric IM or dysplasia underwent a surveillance endoscopy. Both WLE and NBI were performed in all patients during a single procedure. The sensitivity of WLE and NBI for the detection of premalignant lesions was calculated by correlating endoscopic findings to histological diagnosis. Results: Forty-three patients (28 males and 15 females, mean age 59 years) were included. IM was diagnosed in 27 patients; 20 were detected by NBI and WLE, four solely by NBI and three by random biopsies only. Dysplasia was detected in seven patients by WLE and NBI and in two patients by random biopsies only. Sixty-eight endoscopically detected lesions contained IM: 47 were detected by WLE and NBI, 21 by NBI only. Nine endoscopically detected lesions demonstrated dysplasia: eight were detected by WLE and NBI, one was detected by NBI only. The sensitivity, specificity, positive and negative predictive values for detection of premalignant lesions were 71, 58, 65 and 65% for NBI and 51, 67, 62 and 55% for WLE, respectively. Conclusions: NBI increases the diagnostic yield for detection of advanced premalignant gastric lesions compared to routine WLE

Appropriateness of treatment recommendations for PPI in hospital discharge letters

International audienc

Endoscopic sclerotherapy compared with no specific treatment for the primary prevention of bleeding from esophageal varices. A randomized controlled multicentre trial [ISRCTN03215899]

BACKGROUND: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. METHODS: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs. RESULTS: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk. CONCLUSION: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding

Effects of common haplotypes of the ileal sodium dependent bile acid transporter gene on the development of sporadic and familial colorectal cancer: A case control study

<p>Abstract</p> <p>Background</p> <p>The genetics of sporadic and non-syndromic familial colorectal cancer (CRC) is not well defined. However, genetic factors that promote the development of precursor lesions, i.e. adenomas, might also predispose to CRC. Recently, an association of colorectal adenoma with two variants (c.507C>T;p.L169L and c.511G>T;p.A171S) of the ileal sodium dependent bile acid transporter gene (<it>SLC10A2</it>) has been reported. Here, we reconstructed haplotypes of the <it>SLC10A2 </it>gene locus and tested for association with non-syndromic familial and sporadic CRC compared to 'hyper-normal' controls who displayed no colorectal polyps on screening colonoscopy.</p> <p>Methods</p> <p>We included 150 patients with sporadic CRC, 93 patients with familial CRC but exclusion of familial adenomatous polyposis and Lynch's syndrome, and 204 'hyper-normal' controls. Haplotype-tagging <it>SLC10A2 </it>gene variants were identified in the Hapmap database and genotyped using PCR-based 5' exonuclease assays with fluorescent dye-labelled probes. Haplotypes were reconstructed using the PHASE algorithm. Association testing was performed with both SNPs and reconstructed haplotypes.</p> <p>Results</p> <p>Minor allele frequencies of all <it>SLC10A2 </it>polymorphisms are within previously reported ranges, and no deviations from Hardy-Weinberg equilibrium are observed. However, we found no association with any of the <it>SLC10A2 </it>haplotypes with sporadic or familial CRC in our samples (all P values > 0.05).</p> <p>Conclusion</p> <p>Common variants of the <it>SLC10A2 </it>gene are not associated with sporadic or familial CRC. Hence, albeit this gene might be associated with early stages of colorectal neoplasia, it appears not to represent a major risk factor for progression to CRC.</p