Taned Chitapanarux

Randomized controlled trial of live lactobacillus acidophilus plus bifidobacterium bifidum in prophylaxis of diarrhea during radiotherapy in cervical cancer patients

BackgroundRadiation-induced diarrhea is frequently observed during pelvic radiotherapy. This study was performed to determine the ability of a probiotic containing live lactobacillus acidophilus plus bifidobacterium bifidum to reduce the incidence of radiation-induced diarrhea in locally advanced cervical cancer patients.MethodsPatients who were undergoing pelvic radiotherapy concurrent with weekly cisplatin were randomly assigned to a study drug or placebo, in a double-blind study. Diarrhea was graded weekly according the Common Toxicity Criteria (CTC) system. Stool consistency and white and red blood cell count in stool were also assessed. The primary endpoint was to reduce the incidence of diarrhea, defined by a CTC grade 2 or more, and the need for anti-diarrheal medication.ResultsA total of 63 patients were enrolled. Grade 2 -3 diarrhea was observed in 45% of the placebo group (n = 31) and 9% of the study drug group (n = 32) (p = 0.002). Anti-diarrheal medication use was significantly reduced in the placebo group (p = 0.03). The patients in the study drug group had a significantly improved stool consistency (p < 0.001).ConclusionsLive lactobacillus acidophilus plus bifidobacterium bifidum reduced the incidence of radiation-induced diarrhea and the need for anti-diarrheal medication and had a significant benefits on stool consistency.

Open-labeled pilot study of cysteine-rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients.

Background and Aims:  Glutathione (GSH) depletion contributes to liver injury and development of steatohepatitis. Undenatured cysteine‐rich whey protein isolate has been clinically proven to raise GSH in several patient groups. The aim of this study was to evaluate the effect of oral supplementation with whey protein on patients with nonalcoholic steatohepatitis (NASH).

Clinicopathologic Study of Hepatic Penicillium marneffei in Northern Thailand

CONTEXT Penicillium marneffei, an opportunistic fungus, is endemic in Southeast Asia, especially in human immunodeficiency virus-infected individuals living in northern Thailand. OBJECTIVE We present the results of a clinicopathologic study of hepatic penicilliosis among human immunodeficiency virus/acquired immunodeficiency syndrome patients. DESIGN A search of liver biopsies in one institution from 1998 to 1999 identified 30 cases of penicilliosis. RESULTS Histologically, hepatic lesions could be classified into 1 of 3 patterns: diffuse, granulomatous, and mixed. The diffuse pattern showed a diffuse infiltration of foamy macrophages that contained numerous P marneffei. The granulomatous pattern showed a formation of multiple granulomata with various degrees of inflammatory cell infiltration. The mixed pattern showed features intermediate between the diffuse and granulomatous patterns. Liver function tests of the 3 pathologic pattern groups were evaluated, but there were no statistically significant differences in aspartate aminotransferase, alanine aminotransferase, or alkaline phosphatase levels among the various histologic groups. CONCLUSION To our knowledge, this is the largest series to date that documents the liver pathology that results from this pathogen. We hypothesize that the histologic patterns seen on biopsy reflect the level of the hosts immunity. Hence, in addition to a diagnosis of penicilliosis, a liver biopsy may also provide an assessment of the hosts immune status, whereas liver function tests do not.

Risk Factors for the Development of Hepatocellular Carcinoma in Thailand.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. The incidence of HCC is on the rise in Thailand, where it has become the most common malignancy in males and the third most common in females. Here, we review some of the risk factors that have contributed to this increase in HCC incidence in the Thai population. Hepatitis B virus (HBV) is the main etiologic risk factor for HCC, followed by hepatitis C virus (HCV). Patients with HBV genotype C have a higher positive rate of hepatitis B early antigen (HBeAg) and progress to cirrhosis and HCC earlier than genotype B. For HCV patients, 16% developed HCC associated cirrhosis by year 5 after diagnosis, and the cumulative risk for death from HCC at year 10 was 60%. Dietary exposure to the fungal hepatocarcinogen aflatoxin B1 has been shown to interact synergistically with HBV infection to increase the risk of early onset HCC. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. In recent years, obesity and metabolic syndrome have markedly increased the incidence of HCC and are important causes of HCC in some resource-rich regions.

The association of rectal equivalent dose in 2 Gy fractions (EQD2) to late rectal toxicity in locally advanced cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University.

Purpose To evaluate association between equivalent dose in 2 Gy (EQD2) to rectal point dose and gastrointestinal toxicity from whole pelvic radiotherapy (WPRT) and intracavitary brachytherapy (ICBT) in cervical cancer patients who were evaluated by rectosigmoidoscopy in Faculty of Medicine, Chiang Mai University. Materials and Methods Retrospective study was designed for the patients with locally advanced cervical cancer, treated by radical radiotherapy from 2004 to 2009 and were evaluated by rectosigmoidoscopy. The cumulative doses of WPRT and ICBT to the maximally rectal point were calculated to the EQD2 and evaluated the association of toxicities. Results Thirty-nine patients were evaluated for late rectal toxicity. The mean cumulative dose in term of EQD2 to rectum was 64.2 Gy. Grade 1 toxicities were the most common findings. According to endoscopic exam, the most common toxicities were congested mucosa (36 patients) and telangiectasia (32 patients). In evaluation between rectal dose in EQD2 and toxicities, no association of cumulative rectal dose to rectal toxicity, except the association of cumulative rectal dose in EQD2 >65 Gy to late effects of normal tissue (LENT-SOMA) scale ≥ grade 2 (p = 0.022; odds ratio, 5.312; 95% confidence interval, 1.269-22.244). Conclusion The cumulative rectal dose in EQD2 >65 Gy have association with ≥ grade 2 LENT-SOMA scale.

Intestinal myofibroblasts produce nitric oxide in response to combinatorial cytokine stimulation

Inflammatory bowel disease (IBD) patients display elevated levels of intraluminal nitric oxide (NO). NO can react with other molecules to form toxic compounds, which has led to the idea that NO may be an important mediator of IBD. However, the cellular source of NO and how its production is regulated in the intestine are unclear. In this study we aimed to determine if intestinal myofibroblasts produce NO in response to the IBD‐associated cytokines IL‐1β, TNFα, and IFNγ. Intestinal myofibroblasts were isolated from mice and found to express inducible nitric oxide synthase (iNOS) mRNA, but not endothelial NOS or neuronal NOS. Individual treatment of myofibroblasts with IL‐1β, TNFα, or IFNγ had no effect on NO production, but stimulation with combinations of these cytokines synergistically increased iNOS mRNA and protein expression. Treatment with TNFα or IFNγ increased cell surface expression of IFNγRI or TNFRII, respectively, suggesting that these cytokines act in concert to prime NO production by myofibroblasts. Impairment of NF‐κB activity with a small molecule inhibitor was sufficient to prevent increased expression of IFNγRI or TNFRII, and inhibition of Akt, JAK/STAT, or NF‐κB blocked nearly all NO production induced by combinatorial cytokine treatment. These data indicate that intestinal myofibroblasts require stimulation by multiple cytokines to produce NO and that these cytokines act through a novel pathway involving reciprocal cytokine receptor regulation and signaling by Akt, JAK/STAT, and NF‐κB. J. Cell. Physiol. 228: 572–580, 2013.

A phase II study of oxaliplatin with 5-FU/folinic acid and concomitant radiotherapy as a preoperative treatment in patients with locally advanced rectal cancer.

Objective: To evaluate the activity and safety of adding oxaliplatin to a standard chemoradiotherapy schema, including 5-fluorouracil (5-FU)/folinic acid (FA), in locally-advanced rectal cancer (LARC). Methods: Two cycles of oxaliplatin 130 mg/m2 plus FA 20 mg/m2 bolus for 5 days and 5-FU 350 mg/m2 continuous infusion for 5 days were given during week 1 and 4 of pelvic radiotherapy 46 Gy. Patients with a T3/4 and/or node-positive rectal tumour were eligible. Surgery was performed 4–6 weeks after radiotherapy. The primary endpoint was to determine the rate of pathological response. Secondary endpoints were to assess the rate of clinical response and the safety profile. Results: Between March 2005 and January 2009, a total of 35 patients were enrolled. The pathological down-staging rate was 79% with a pathological complete response rate of 17%. The overall clinical response rate (assessed by computed tomography or transrectal ultrasound) was 77%. Grade 3 diarrhoea and Grade 3 neutropaenia were reported in 14% and 11% of the patients, respectively. Eleven patients did not undergo surgery: four of them refused the operation, and seven patients were inoperable due to disease progression. In 24 patients who had surgery, a sphincter-preserving procedure could be performed in 29%. At the median follow-up time of 28.1 months, 25 patients (71%) survived with no evidence of disease. Conclusion: The promising results in terms of pathological response, and the associated good safety profile of a regimen of oxaliplatin plus 5-FU/FA with concomitant radiotherapy, suggest that the regimen could be used in LARC.

Three‐day versus five‐day somatostatin infusion combination with endoscopic variceal ligation in the prevention of early rebleeding following acute variceal hemorrhage: A randomized controlled trial

Combined pharmacological and endoscopic therapy is recommended for initial treatment of acute variceal bleeding (AVB). The optimal duration of therapy with a vasoactive agent is not well established. The aim of this study was to compare the efficacy and safety of 3‐day and 5‐day somatostatin treatment in the prevention of early rebleeding after endoscopic variceal ligation (EVL).

Inducible NOS mediates CNP-induced relaxation of intestinal myofibroblasts

Contraction of intestinal myofibroblasts (IMF) contributes to the development of strictures and fistulas seen in inflammatory bowel disease, but the mechanisms that regulate tension within these cells are poorly understood. In this study we investigated the role of nitric oxide (NO) signaling in C-type natriuretic peptide (CNP)-induced relaxation of IMF. We found that treatment with ODQ, a soluble guanylyl cyclase (sGC) inhibitor, or N(G)-nitro-L-arginine (L-NNA) or N(G)-monomethyl-L-arginine (L-NMMA), inhibitors of NO production, all impaired the relaxation of human and mouse IMF in response to CNP. ODQ, L-NNA, and L-NMMA also prevented CNP-induced elevations in cGMP concentrations, and L-NNA or L-NMMA blocked CNP-induced decreases in myosin light phosphorylation. IMF isolated from transgenic mice deficient in inducible nitric oxide synthase (iNOS) had reduced relaxation responses to CNP compared with IMF from control mice and were insensitive to the effects of ODQ, L-NNA, and L-NMMA on CNP treatment. Together these data indicate that stimulation of sGC though NO produced by iNOS activation is required for maximal CNP-induced relaxation in IMF.

M2005 Nitric Oxide Disturbance and Chronic Liver Disease

In the setting of end-stage liver disease (ESLD), In-Vivo balance between proand anticoagulants has not been completely clear. Guidelines on prevention of Venous thromboembolism (VTE) fail to address patients with coagulopathy from ESLD. Risk of VTE still exists in hospitalized patients with ESLD despite elevated INR. We investigated the perceived risk of VTE in patients with ESLD among house-staff and weather this was reflected in clinical practice. Methods: We first distributed a questionnaire in 2006 among medicine housestaff in our tertiary medical center to evaluate their practices of VTE prophylaxis in ESRD and then distributed the same questionnaire in 2009. No housestaff was involved in both surveys. Housestaff with <3 months in medicine wards were excluded. Investigators were blinded to the data until all responses were obtained. Results: Among 244 housestaff, 223(91%) returned the questionnaire. Only 11/223(7%) housestaff believed that risk of VTE among hospitalized patients with ESLD and elevated INR is lower than those with normal liver function. Hundred and ninety of 223(85%) followed guidelines for VTE prophylaxis, and 155(70%) applied them to patients with ESLD. Subcutaneous heparin was the most commonly used agent(190;85%) for patients with normal INR. But as INR increased due to ESLD, the use of heparin decreased correspondingly (Figure). This pattern of practice persisted in both 2006 and 2009. Majority of the participants (198/223;89%), felt that patient compliance to intermittent compression devices (ICD) was inadequate. Conclusions: Although compliance with ICDs is perceived as inadequate and subcutaneous heparin is the cost-effective and preferred mode for VTE prophylaxis, ICD use increased with the rise in INR values. This phenomenon may be due to fear of a perceived increase in risk of bleeding in ESLD. Despite awareness of risk of VTE in patients with ESLD and elevated INR, no strides have been made in translating this into clinical practice due to lack of clear guidelines and fear of bleeding risk. Prospective studies to determine the risk of VTE in hospitalized patients with ESLD are warranted to enhance current guidelines for VTE prophylaxis