Medical Library

Perforated appendicitis masquerading as acute pancreatitis in a morbidly obese patient.

Diagnosis and treatment of common conditions in morbidly obese patients still pose a challenge to physicians and surgeons. Sometimes too much reliance is put on investigations that can lead to a misdiagnosis. This case demonstrates an obese woman admitted under the medical team with a presumed diagnosis of pneumonia, who was later found to have an acute abdomen and raised amylase, which led to an assumed diagnosis of pancreatitis. She died within 24 h of admission and post mortem confirmed the cause of death as systemic sepsis due to perforated appendicitis, with no evidence of pancreatitis. Significantly elevated serum amylase level may occur in non-pancreatitic acute abdomen.

Forster MJ, Akoh JA.

Level 03, Derriford Hospital, Plymouth PL6 8DH, United Kingdom. iacob.akoh@phnt.swest.nhs.uk.

Herbal compound 861 regulates mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells.

AIM: To identify the role of herbal compound 861 (Cpd 861) in the regulation of mRNA expression of collagen synthesis- and degradation-related genes in human hepatic stellate cells (HSCs). METHODS: mRNA levels of collagen types I and III, matrix metalloproteinase 1 (MMP-1), matrix metalloproteinase 2 (MMP-2), membrane type-1 matrix metalloproteinase (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and transforming growth factor beta1 (TGF-beta1) in cultured-activated HSCs treated with Cpd 861 or interferon-gamma (IFN-gamma) were determined by real-time PCR. RESULTS: Both Cpd 861 and IFN-gamma reduced the mRNA levels of collagen type III, MMP-2 and TGF-beta1. Moreover, Cpd 861 significantly enhanced the MMP-1 mRNA levels while down-regulated the TIMP-1 mRNA expression, increasing the ratio of MMP-1 to TIMP-1 to (6.3 + 0.3)- fold compared to the control group. CONCLUSION: The anti-fibrosis function of Cpd 861 may be mediated by both decreased interstitial collagen sythesis by inhibiting the transcription of collagen type III and TGF-beta1 and increased degradation of these collagens by up-regulating MMP-1 and down-regulating TIMP-1 mRNA levels.

Wang L, Wang BE, Wang J, Xiao PG, Tan XH.

Beijing Genomic Institute, Beijing 101300, China. tanxh@genomics.org.cn.

Cyclooxygenase 2 polymorphism and colorectal cancer: -765G>C variant modifies risk associated with smoking and body mass index.

AIM: To explore whether cyclooxygenase 2 (COX-2) -765G>C polymorphism is associated with susceptibility of colorectal cancer (CRC) and to evaluate the risk of colorectal cancer in relation to environmental exposures and polymorphism. METHODS: We conducted a case-control study of 137 patients with colorectal cancer and 199 cancer-free controls in northeast China. Multivariate logistic regression analysis was performed to calculate the adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: The -765G>C polymorphism was not independently associated with CRC risk. However, risk associated with the polymorphism differed by smoking and body mass index (BMI). Smoking and BMI associated risks were stronger among those with -765GG genotype, showing that smokers had a 2.682-fold greater risk of CRC than nonsmokers (51/43 vs 68/126, P = 0.006). Compared to those with a normal body mass index (BMI 18.5-22.9), those with overweight (BMI 23-24.9) had a 3.909-fold higher risk of CRC (OR = 3.909, 95% CI = 2.081-7.344; P < 0.001), while those with obesity (BMI > 25) had a 2.031- fold higher risk of CRC (OR = 1.107, 95% CI = 1.107-3.726; P = 0.022). CONCLUSION: Although COX-2 -765G>C polymorphism is not associated with an increased risk of CRC, -765GG genotype appears to be related to an increased risk in the presence of smoking and higher BMI.

Xing LL, Wang ZN, Jiang L, Zhang Y, Xu YY, Li J, Luo Y, Zhang X.

Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. josieon826@yahoo.com.cn.

Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B.

AIM: To evaluate the efficacy of short-term overlap lamivudine therapy with adefovir in patients with lamivudine-resistant and naive chronic hepatitis B, we compared patients receiving overlap therapy with those receiving adefovir alone. METHODS: Eighty patients who had received lamivudine treatment for various periods and had a lamivudine-resistant liver function abnormality were enrolled. Forty of these patients received adefovir treatment combined with lamivudine treatment for >= 2 mo, while the other 40 received adefovir alone. We assessed the levels of hepatitis B virus (HBV) DNA at 0, 12 and 48 wk and serum alanine aminotransferase (ALT) levels after 0, 12, 24 and 48 wk of adefovir treatment in each group. RESULTS: We found serum ALT became normalized in 72 (87.5%) of the 80 patients, and HBV DNA decreased by >= 2 log(10) copies/mL in 60 (75%) of the 80 patients at the end of a 48-wk treatment. HBV DNA levels were not significantly different between the groups. The improvements in serum ALT were also not significantly different between the two groups. CONCLUSION: These findings suggest short-term overlap lamivudine treatment results in no better virological and biological outcomes than non-overlap adefovir monotherapy.

Nam SW, Bae SH, Lee SW, Kim YS, Kang SB, Choi JY, Cho SH, Yoon SK, Han JY, Yang JM, Lee YS.

Division of Gastroenterology and Hepatology, Department of Internal medicine, Medical College of the Catholic University of Korea, Daejeon St. Mary’s Hospital, #62 Daeheung-dong, Chung-gu, Daejeon, Republic of Korea. drswnam@hanmail.net.

Model for end-stage liver disease score versus Child score in predicting the outcome of surgical procedures in patients with cirrhosis.

AIM: To determine factors affecting the outcome of patients with cirrhosis undergoing surgery and to compare the capacities of the Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) score to predict that outcome. METHODS: We reviewed the charts of 195 patients with cirrhosis who underwent surgery at two teaching hospitals over a five-year period. The combined endpoint of death or hepatic decompensation was considered to be the primary endpoint. RESULTS: Patients who reached the endpoint had a higher MELD score, a higher CTP score and were more likely to have undergone an urgent procedure. Among patients undergoing elective surgical procedures, no statistically significant difference was noted in the mean MELD (12.8 +/- 3.9 vs 12.6 +/- 4.7, P = 0.9) or in the mean CTP (7.6 +/- 1.2 vs 7.7 +/- 1.7, P = 0.8) between patients who reached the endpoint and those who did not. Both mean scores were higher in the patients reaching the endpoint in the case of urgent procedures (MELD: 22.4 +/- 8.7 vs 15.2 +/- 6.4, P = 0.0007; CTP: 9.9 +/- 1.8 vs 8.5 +/- 1.8, P = 0.008). The performances of the MELD and CTP scores in predicting the outcome of urgent surgery were only fair, without a significant difference between them (AUC = 0.755 +/- 0.066 for MELD vs AUC = 0.696 +/- 0.070 for CTP, P = 0.3). CONCLUSION: The CTP and MELD scores performed equally, but only fairly in predicting the outcome of urgent surgical procedures. Larger studies are needed to better define the factors capable of predicting the outcome of elective surgical procedures in patients with cirrhosis.

Hoteit MA, Ghazale AH, Bain AJ, Rosenberg ES, Easley KA, Anania FA, Rutherford RE.

Emory University School of Medicine, Division of Digestive Diseases, 615 Michael Street, Suite 201, Atlanta, GA 30322, United States. fanania@emory.edu.

Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection.

AIM: To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis (S. stercoralis) hyperinfection. METHODS: Over a period of 23 years (1984-2006), we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively. RESULTS: Twenty-four (96%) of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 (HTLV-1) infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 (92%) patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative (Endoscopic severity score: 4.86 +/- 2.47 vs 2.71 +/- 1.38, P < 0.05). CONCLUSION: Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.

Kishimoto K, Hokama A, Hirata T, Ihama Y, Nakamoto M, Kinjo N, Kinjo F, Fujita J.

Department of Medicine and Therapeutics (First Department of Internal Medicine), Control and Prevention of Infectious Disease, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan. hokama-a@med.u-ryukyu.ac.jp.

Aberrant activation of nuclear factor of activated T cell 2 in lamina propria mononuclear cells in ulcerative colitis.

AIM: To investigate the role of nuclear factor of activated T cell 2 (NFAT2), the major NFAT protein in peripheral T cells, in sustained T cell activation and intractable inflammation in human ulcerative colitis (UC). METHODS: We used two-dimensional gel-electrophoresis, immunohistochemistry, double immunohistochemical staining, and confocal microscopy to inspect the expression of NFAT2 in 107, 15, 48 and 5 cases of UC, Crohn\’s disease (CD), non-specific colitis, and 5 healthy individuals, respectively. RESULTS: Up-regulation with profound nucleo-translocation/activation of NFAT2 of lamina propria mononuclear cells (LPMC) of colonic mucosa was found specifically in the affected colonic mucosa from patients with UC, as compared to CD or NC (P < 0.001, Kruskal-Wallis test). Nucleo-translocation/activation of NFAT2 primarily occurred in CD8+T, but was less prominent in CD4+ T cells or CD20+B cells. It was strongly associated with the disease activity, including endoscopic stage (tau = 0.2145, P = 0.0281) and histologic grade (tau = 0.4167, P < 0.001). CONCLUSION: We disclose for the first time the nucleo-translocation/activatin of NFAT2 in lamina propria mononuclear cells in ulcerative colitis. Activation of NFAT2 was specific for ulcerative colitis and highly associated with disease activity. Since activation of NFAT2 is implicated in an auto-regulatory positive feedback loop of sustained T-cell activation and NFAT proteins play key roles in the calcium/calcineurin signaling pathways, our results not only provide new insights into the mechanism for sustained intractable inflammation, but also suggest the calcium-calcineurin/NFAT pathway as a new therapeutic target for ulcerative colitis.

Shih TC, Hsieh SY, Hsieh YY, Chen TC, Yeh CY, Lin CJ, Lin DY, Chiu CT.

Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, No. 5, Fu-Hsin Road, Taoyuan 333, Taiwan. siming.shia@msa.hinet.net.

Genome-wide differences in hepatitis C- vs alcoholism-associated hepatocellular carcinoma.

AIM: To look at a comprehensive picture of etiology-dependent gene abnormalities in hepatocellular carcinoma in Western Europe. METHODS: With a liver-oriented microarray, transcript levels were compared in nodules and cirrhosis from a training set of patients with hepatocellular carcinoma (alcoholism, 12; hepatitis C, 10) and 5 controls. Loose or tight selection of informative transcripts with an abnormal abundance was statistically valid and the tightly selected transcripts were next quantified by qRTPCR in the nodules from our training set (12 + 10) and a test set (6 + 7). RESULTS: A selection of 475 transcripts pointed to significant gene over-representation on chromosome 8 (alcoholism) or -2 (hepatitis C) and ontology indicated a predominant inflammatory response (alcoholism) or changes in cell cycle regulation, transcription factors and interferon responsiveness (hepatitis C). A stringent selection of 23 transcripts whose differences between etiologies were significant in nodules but not in cirrhotic tissue indicated that the above dysregulations take place in tumor but not in the surrounding cirrhosis. These 23 transcripts separated our test set according to etiologies. The inflammation-associated transcripts pointed to limited alterations of free iron metabolism in alcoholic vs hepatitis C tumors. CONCLUSION: Etiology-specific abnormalities (chromo-some preference; differences in transcriptomes and related functions) have been identified in hepatocellular carcinoma driven by alcoholism or hepatitis C. This may open novel avenues for differential therapies in this disease.

Derambure C, Coulouarn C, Caillot F, Daveau R, Hiron M, Scotte M, Francois A, Duclos C, Goria O, Gueudin M, Cavard C, Terris B, Daveau M, Salier JP.

Inserm Unite 519, Faculte de Medecine-Pharmacie, 22 Bvd Gambetta, Rouen cedex 76183, France. celine.derambure1@univ-rouen.fr.

DNA methylation in hepatocellular carcinoma.

As for many other tumors, development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSG). In the last decades, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In HCC, aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

Tischoff I, Tannapfe A.

Institute of Pathology, Ruhr-University of Bochum, Burkle-de-la-Camp-Platz 1, Bochum 44789, Germany. iris.tischoff@rub.de.

Molecular mechanism underlying the functional loss of cyclindependent kinase inhibitors p16 and p27 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common human cancers, and its incidence is still increasing in many countries. The prognosis of HCC patients remains poor, and identification of useful molecular prognostic markers is required. Many recent studies have shown that functional alterations of cell-cycle regulators can be observed in HCC. Among the various types of cell-cycle regulators, p16 and p27 are frequently inactivated in HCC and are considered to be potent tumor suppressors. p16, a G1-specific cell-cycle inhibitor that prevents the association of cyclindependent kinase (CDK) 4 and CDK6 with cyclin D1, is frequently inactivated in HCC via CpG methylation of its promoter region. p16 may be involved in the early steps of hepatocarcinogenesis, since p16 gene methylation has been detected in subsets of pre-neoplastic liver cirrhosis patients. p27, a negative regulator of the G1-S phase transition through inhibition of the kinase activities of Cdk2/cyclin A and Cdk2/cyclin E complexes, is now considered to be an adverse prognostic factor in HCC. In some cases of HCC with increased cell proliferation, p27 is overexpressed but inactivated by sequestration into cyclin D1-CDK4-containing complexes. Since loss of p16 is closely related to functional inactivation of p27 in HCC, investigating both p16 and p27 may be useful for precise prognostic predictions in individuals with HCC.

Matsuda Y.

Department of Medical Technology, Niigata University Graduate School of Health Sciences, Asahimachi-dori 2-746, Niigata 9518518, Japan. yasunobu@med.niigata-u.ac.jp.