To date, the number of studies reporting use of NUC for prevention of HCC recurrence is limited to four studies, each with small case numbers (10–43) and short treatment duration (12–43 months), so that the results of each study are inconclusive (Table 1). As viral hepatocarcinogenesis progresses through multiple stages and is a multifactorial process, its progression takes years, often decades. Although the efficacy of LAM, ADV and ETV in the tertiary prevention of HCC recurrence is still unsatisfactory, more effective long-term HBV DNA suppression is likely to increase the survival

rate and Apoptosis Compound Library cost probably will significantly reduce the HCC recurrence. In addition, long-term studies will undoubtedly confirm that the effects of ETV or tenofovir in reducing HCC recurrence are similar to or better than those of LAM because of their superior potency, which ensures both lower levels of residual HBV DNA (in serum and liver) and correspondingly

much lower risk of drug resistance. Hence, we await with interest the results of long-term large-scale prospective surveys of clinical outcomes involving these better antiviral regimens. It is also expected that such observations will prove that tertiary prevention of HCC recurrence is possible in patients receiving curative physical treatments (surgical resection or ablation) for HCC. “
“We read with great interest the article by Kamo et al.[1] in which the authors showed that after hepatic ischemia-reperfusion Ku-0059436 price (I/R) injury, inflammasome activation mediated by apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) leads to interleukin-1β (IL-1β) production and subsequently promotes high mobility group box 1(HMGB1) induction, which triggers a Toll-like receptor 4 (TLR4)-driven inflammatory response. find more Consistent with their findings, we recently showed that ASC-mediated inflammasome activation plays an essential role in the initial inflammatory response after myocardial I/R injury.[2] Recently, it has been shown that inflammasome components such as ASC and NLR family pyrin domain containing 3 (NLRP3) can function independently of inflammasomes. Shigeoka et al.[3]

showed that mice deficient in NLRP3 but not ASC or caspase-1 had reduced renal I/R. Because the inflammasome is defined as a molecular platform that induces caspase-1 activation, they concluded that an NLRP3-dependent and inflammasome-independent pathway contributed to the development of I/R injury in the kidney. Similar to their findings, we observed that hepatic I/R injury was significantly ameliorated in mice deficient for NLRP3 but not ASC. This was inconsistent with the finding of Kamo et al.[1] Although the reason for this discrepancy is unclear, the differences between our study and Kamo et al.’s study are the hepatic I/R protocol used and the extent of injury. We subjected C57BL/6 wild-type mice to hepatic I/R with 60 minutes ischemia of the left lateral and median lobes (i.e.

This target level is based on early observations in haemophilia A that joint bleeds are less frequent in patients with moderate haemophilia than in those with

severe disease. PK calculations for FVIII are useful to design optimal dosing schedules to achieve this target [23, 24]. However, the clinical significance of maintaining a 1% trough level is widely debated, and such evidence that does exist is mainly applicable to FVIII deficiency [25]. Furthermore, baseline factor levels are not the only determinants of bleeding phenotype in haemophilia, and the severity and frequency of bleeding may be different for people with haemophilia with the same factor activity [26]. There is therefore a need to strike a balance

between clinical and PK endpoints in the evaluation of clinical efficacy Selleckchem Ensartinib in the real-life clinical setting, particularly in people with haemophilia B for whom limited disease-specific data exist. In people with haemophilia, bleeding frequency is considered a key clinical indicator of the efficacy of a treatment regimen. However, the causes of bleeding are multifactorial and bleeding frequency is dependent on multiple factors, such as physical activity (trauma), presence of target joints and the rest of the haemostatic system. As factor levels cannot always predict bleeding frequency, CT99021 supplier other methods of predicting bleeding risk have been developed, such as the Haemophilia Severity Score (HSS) [27], which includes the annual joint bleeding rate, annual factor consumption and World Federation of Hemophila (WFH) orthopaedic score in its assessment.

Vyas and colleagues examined clinical data for 178 haemophilia patients without inhibitors in a single US centre and documented the differing symptomatology of haemophilia patients [haemophilia A (n = 139), haemophilia B (n = 39)] see more using the HSS. They found widespread variability in the HSS values of patients with the same baseline factor activity, demonstrating the heterogeneity of haemophilia phenotype [28]. Data from a single-centre cohort study of 171 patients with severe haemophilia A and B in The Netherlands demonstrated the importance of clinical issues in determining phenotype. They found that age at first joint bleed was an indicator of bleeding pattern, as assessed by the Pettersson score, a radiologic classification of haemophilic arthropathy [29]. Subjects who experienced their first joint bleed at an early age had demonstrated consistently higher annual clotting factor consumption compared with those experiencing their first joint bleed later in life (P < 0.01; 95% confidence interval: −221 to −134 IU kg−1 year−1) [30]. Large variations in rates of clotting factor concentrate (CFC) consumption in patients with the same diagnosis are also widely observed.

6%, BOC: 59.4%, p>0.05). Ribavirin plasma concentration was not a predictive factor of RVR (1.87 ± 0.91 mg/L vs 1.96 selleckchem ± 0.72 mg/L, respectively in RVR and in non RVR patients, p=0.65). In multivariate analysis, only the Fibroscan® value was a predictive factor of SVR with a cutoff value below 20 KPa. Anemia (hemoglobin

level <12 g/dL) occured in 56 of the 66 patients (85%). A significant correlation (p=0.0006) was found between hemoglobin level and ribavirin plasma concentration. Anemia was more frequent when the ribavirin plasma concentration was above the cutoff value of 1.65 mg/L (p=0.04). The decrease of the creatinine clearance after 4 weeks of protease inhibitor was more important in patients treated with TPV (26.51 mL/min) than in patients treated by BOC (4.17 mL/min), p<0.05. The logistic regression Wnt inhibitor analysis showed a significant correlation between a high ribavirin concentration and a decrease of creatinine clearance (p=0.0157). Conclusion: In combination therapy with telaprevir or bocepre-vir, rapid or sustained virological response was not influenced by ribavirin plasma concentration. However, plasma ribavirin level was a predictive factor associated to anemia and kidney function impairment during therapy. Disclosures: Laurent Alric – Grant/Research Support: Roche, MSD, BMS, Gilead The following people have nothing to disclose: Marie Julia, Peggy Gandia, Mathieu Guivarch, Laura Coimet-Berger, Florence Abravanel, Delphine

Bonnet Background: Real life data of triple based therapy in patients with chronic hepatitis C are investigated in this multicentric survey of 11 clinical centers

of South Italy. This is a retrospective study analyzing data from 176 consecutive patients fol-lowed-up for a maximum of 12 weeks after the end of therapy (EOT). Patients and Methods: One hundred and twenty-five (70%) patients were treated with telaprevir and 51 (30%) with boceprevir. No differences were found in the two groups for the principal demographic characteristics. selleck The degree of liver fibrosis (LF) was done according to liver biopsy (LB) and/or transient elastography (TE). Patients with evidence of clinical signs of liver cirrhosis (LC) (ie. esophageal varices) did not undergo neither LB or TE. Fifthy-three/ 176 patients (30%) had liver cirrhosis. Sixteen patients (9%) were naïve and all the remaining were experienced patients: 92 non responders ( 52,84%); 63 relapsers (35,79%) and 5 drop-out (2,8%). Uni-variate and multivariate analysis were performed according to SPSS program. Results: The rate of rapid virological response (RVR) and EOT, analyzed on all patients were the following: 116 (68%) and 94 (75.8%). Ninety-seven patients have been followed-up for at least 12 weeks after the EOT and of these 61 (62.9%) achieved sustained virological response (SVR). The multivariate analysis for SVR, RVR is the only independent predictive factor of SVR irrespective of the degree of LF and the type of response to previous treatment.

12 We found that FGF17 and FGF18 stimulate replicative DNA synthesis in MF cells. A similar effect was evident on the DNA replication of endothelial cells that were isolated from human tumor-bearing livers (Fig. 6). Furthermore, all three FGFs induced tube formation of endothelial cells, which is a further necessary step in

neoangiogenesis. This suggests that FGF8 subfamily members favor the formation of new blood vessels in HCC directly and indirectly via the multiplication of vEGF-producing MFs. Here we show for the first time that FGF8, FGF17, and FGF18 have more or less equal potency in enhancing neoangiogenesis and the aggressive behavior of malignant hepatocytes. Accordingly, at least one of these FGFs was up-regulated in the majority of the investigated HCC cases. This implies that the FGF8 subfamily members are crucial components in autocrine and paracrine loops supporting the autonomous growth of advanced stages CB-839 research buy of hepatocarcinogenesis, as outlined in the following. In this study, we found pronounced overexpression of FGF18 in a subset of human HCC cases. The human FGF18 gene harbors T cell factor/lymphoid enhancer-binding factor binding sites in the promoter region. Accordingly, FGF18 transcription is under the control of the β-catenin T cell factor/lymphoid enhancer-binding

factor complex, as shown recently by our group and others.16, 27 In human HCC, the wnt/wingless signaling selleckchem cascade often is activated by mutations in AXIN1, AXIN2, or the gene coding for β-catenin [catenin (cadherin-associated protein) β1] (CTNNB1) and/or through epigenetic silencing of wnt antagonists, such as the secreted frizzled-related protein.9, 10, 13 These disturbances in the wnt signaling cascade may contribute to the observed up-regulation of FGF18 in human HCC. Here we found that the withdrawal of serum or oxygen is a potent inducer of all FGF8 subfamily members in HCC-1.2, HepG2, and Hep3B cells. These regimens simulate the conditions in rapidly expanding HCC with an inadequate blood supply. Generally, such conditions alter signaling cascades and gene expression learn more patterns of the affected cells

and lead to increased neoangiogenesis and glycolysis and decreased mitochondrial respiration. In our experiments, serum deprivation clearly elevated the phosphorylation of GSK3β at serine 9 in the hepatocarcinoma cells, and this may lead to reduced phosphorylation and degradation of β-catenin and increase the probability of β-catenin entering the nucleus and activating the transcription of FGF18. The molecular mechanisms underlying the induction of FGF8 and FGF17 by serum withdrawal are still unclear. In comparison with serum withdrawal, hypoxia is a more specific stimulus transduced by members of several transcription factor families, including the hypoxia inducible factor (HIF), aryl hydrocarbon receptor (AHR), E twenty-six (ETS), and metal-responsive transcription factor (MTF) families.

12 We found that FGF17 and FGF18 stimulate replicative DNA synthesis in MF cells. A similar effect was evident on the DNA replication of endothelial cells that were isolated from human tumor-bearing livers (Fig. 6). Furthermore, all three FGFs induced tube formation of endothelial cells, which is a further necessary step in

neoangiogenesis. This suggests that FGF8 subfamily members favor the formation of new blood vessels in HCC directly and indirectly via the multiplication of vEGF-producing MFs. Here we show for the first time that FGF8, FGF17, and FGF18 have more or less equal potency in enhancing neoangiogenesis and the aggressive behavior of malignant hepatocytes. Accordingly, at least one of these FGFs was up-regulated in the majority of the investigated HCC cases. This implies that the FGF8 subfamily members are crucial components in autocrine and paracrine loops supporting the autonomous growth of advanced stages Selleckchem Deforolimus of hepatocarcinogenesis, as outlined in the following. In this study, we found pronounced overexpression of FGF18 in a subset of human HCC cases. The human FGF18 gene harbors T cell factor/lymphoid enhancer-binding factor binding sites in the promoter region. Accordingly, FGF18 transcription is under the control of the β-catenin T cell factor/lymphoid enhancer-binding

factor complex, as shown recently by our group and others.16, 27 In human HCC, the wnt/wingless signaling http://www.selleckchem.com/products/i-bet-762.html cascade often is activated by mutations in AXIN1, AXIN2, or the gene coding for β-catenin [catenin (cadherin-associated protein) β1] (CTNNB1) and/or through epigenetic silencing of wnt antagonists, such as the secreted frizzled-related protein.9, 10, 13 These disturbances in the wnt signaling cascade may contribute to the observed up-regulation of FGF18 in human HCC. Here we found that the withdrawal of serum or oxygen is a potent inducer of all FGF8 subfamily members in HCC-1.2, HepG2, and Hep3B cells. These regimens simulate the conditions in rapidly expanding HCC with an inadequate blood supply. Generally, such conditions alter signaling cascades and gene expression selleck patterns of the affected cells

and lead to increased neoangiogenesis and glycolysis and decreased mitochondrial respiration. In our experiments, serum deprivation clearly elevated the phosphorylation of GSK3β at serine 9 in the hepatocarcinoma cells, and this may lead to reduced phosphorylation and degradation of β-catenin and increase the probability of β-catenin entering the nucleus and activating the transcription of FGF18. The molecular mechanisms underlying the induction of FGF8 and FGF17 by serum withdrawal are still unclear. In comparison with serum withdrawal, hypoxia is a more specific stimulus transduced by members of several transcription factor families, including the hypoxia inducible factor (HIF), aryl hydrocarbon receptor (AHR), E twenty-six (ETS), and metal-responsive transcription factor (MTF) families.

Results: A total of 24 cases were identified, 14 (63%) from re nal cell carcinoma; 12 were men (85%), with a mean age of 53 y. The diagnoses were made a median of 8 y (3–20) after the initial tumor. All where asymptomatic save for one, which manifested as hemosuccus pancreaticus. 11 presented as the only GDC-0068 supplier metastatic site, 1 with lung metastases, 1 with multiple metastasic sites

and 1 to the remaining kidney. Size was from 1.2–4 cm, 10 in the body/tail, 3 in the head (none jaundized) and 1 with multiple tumors. All hypoechoic, well demarcated and homogeneous by EUS. FNA was positive in 11 of 12 at first pass. None had a Karnovsky score lower than 90 or clinically advanced. Few had FU to establish final condition Conclusion: Metastases to the pancreas are rare, and most are from renal

cell carcinoma; interestingly, the great majority are asymptomatic and do not seem to produce systemic effects, so most patients seem well when diagnosed. Key Word(s): 1. Pancreas; 2. EUS; 3. Endosonography; 4. Metastases; Presenting Author: GUOYING WANG Additional Authors: GUOLI DAI Corresponding Author: GUOYING WANG Affiliations: learn more Liver Transplantation Center, the third affiliated hospital of sun yat-sen university; Indiana University-Purdue University Objective: Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular defense against oxidative stress and inflammation and is also involved in regulating liver regeneration. The aim of the study is to evaluate whether Nrf2 mediates hepatic repair response during cholestasis. Methods: Wild-type and Nrf2-null mice were subjected to bile duct ligation (BDL) or sham operation. find more Various assessments

were performed at 5, 10, 15, 25, and 40 days following surgery. Significant genotype-dependent differences in liver injury, cell proliferation, and collagen deposition were not seen over the time course of the study, in line with several reports. Results: Nrf2-null mice exhibited a more prominent network of septual tissue containing laminin and α fetal protein expressing cells at 15 days after injury, suggesting a stronger repair response, than their wild-type litter mates. In the livers of both genotypes of mice, cytokeratin 19 (CK19), a marker of bipotent liver epithelial progenitors and immature biliary epithelial cells, were expressed in the epithelial cells of newly formed bile ducts and a population of hepatocytic-appearing cells in parenchyma. Notably, Nrf2-null mice showed higher hepatic protein expression of CK19 at 5 days following BDL, indicating earlier onset of the activation of CK19+ progenitor cells, than wild-types. CD133, a marker of liver progenitors, were found to be expressed by newly generated bile duct epithelial cells and a population of hepatocytic-appearing parenchymal cells in the livers of the two genotypes of mice.

Our results also suggest that blocking any portion of this axis will attenuate liver injury and neutrophil infiltration. However, our research cannot exclude the possibility that HMGB1 directly induces IL-17A production independent of IL-23. In addition to HMGB1, other DAMPs (such as DNA and cyclophilin A) have been reported to participate in activating the innate immune response.7, 21, 22 Except for TLR4, other receptors for HMGB1 may also stimulate the release of inflammatory http://www.selleckchem.com/products/Vorinostat-saha.html cytokines and should be further investigated. Macrophages can quickly respond

to endogenous stimulating factors after tissue injury.35 However, the role of macrophages in the acetaminophen-induced liver injury is controversial. Hepatic macrophages have been demonstrated to play a pathogenic role through their secretion of proinflammatory factors, such as tumor necrosis factor alpha (TNF-α), IL-1β, and NO.36 However, hepatic macrophages have also been reported to play a protective role through their secretion of regulatory factors, such as IL-10.37 This controversy stems from the effects of compounds used to inactivate (GdCl3) and deplete macrophages (clodronate/liposome).

Macrophages are heterogeneous and plastic, and at least two major macrophage populations exist, including classically activated macrophages (M1) and alternatively activated macrophages (M2).35 An induced macrophage (IM) population that differs from resident hepatic macrophages has been reported in acetaminophen-induced liver injury. IMs are formed from Anti-infection Compound Library circulating monocytes infiltrating the liver after acetaminophen treatment and exhibit phenotypes of alternatively activated macrophages. The absence of IMs delays the recovery of liver injury.38 However, resident hepatic macrophages isolated from normal livers have enhanced mRNA

expression of IL-1β and TNF-α after stimulation with DAMPs in vitro.24 Thus, selleck chemicals these studies demonstrate that hepatic resident macrophages are classically activated macrophages, which are prone to generating proinflammatory cytokines during acetaminophen-induced liver injury. In our study, macrophages also produced IL-23 after HMGB1 stimulation. γδ T cells were also able to produce IL-17A rapidly in response to DAMPs,18 and naïve γδ T cells produced IL-17 in response to IL-23 in the absence of TCR engagement,39 which was enhanced by the addition of IL-1β.40 In this study, IL-17 was dramatically elevated after acetaminophen treatment. Although NK and NKT cells are the dominant innate immune cells in murine liver,41 they did not produce IL-17A, which was confirmed by depleting NK and NKT cells with mAb (Fig. 3D). In our study, hepatic CD4+ T cells were not the major source of IL-17A, and CD4+ T cell depletion did not influence IL-17A production (Fig. 3C). Surprisingly, deletion of γδ T cells significantly reduced IL-17A production.

6D). To further determine the correlation of HNF4α and miR-134 in HCC, we examined their expression profiles in the DEN-induced HCC rat model (n = 4 at each indicated PKC inhibitor timepoint). In agreement with our previous study,[8] HNF4α expression decreased gradually after DEN administration. Interestingly, the transcript level of miR-134 (pri-miR134) was also suppressed in the process of hepatocarcinogenesis (Fig. 7A). A striking positive correlation between HNF4α and pri-miR-134 levels was observed in DEN-treated rat liver (Fig. 7B). We then analyzed the

association of HNF4α and pri-miR-134 expression in human HCC samples (n = 71). As compared with their surrounding noncancerous tissues, 63% (45/71) and 70% (50/71) of the HCC tissues showed lower levels of HNF4α and pri-miR-134, respectively Selleck Tamoxifen (Fig. 7C). Reduced pri-miR-134 expression was more frequent in HCCs with lower HNF4α levels relative to those with

intermediate and high HNF4α levels (89% versus 38%; Fig. 7D). The correlation was particularly apparent in HCC subjects with alpha-fetoprotein (AFP) levels over 1,000 μg/L (r = 0.6241, P = 0.0003, n = 29; Fig. 7E). The clinicopathological significance of pri-miR-134 levels in the above 71 patients with HCC was further analyzed. The median value of pri-miR-134 levels in HCC tissues was chosen as the cutoff point; 49.3% of HCCs (35/71) had low-level expression of pri-miR-134, and 50.7% of HCCs (36/71) had high-level expression of pri-miR-134 (Table 1). The low-level expression of pri-miR-134 in HCCs was associated with more aggressive pathological features, including liver cirrhosis (P = 0.0127), high levels of AFP (P = 0.0142), large tumor size (P = 0.0271), advanced tumor stage (P = 0.0051), presence of tumor microsatellites (P = 0.0434), and absence of tumor encapsulation (P = 0.0013) (Table 1). HNF4α is a transcription factor that plays a key role in hepatocyte differentiation

and in the maintenance of hepatic function. It is well established that the miRNAs at the DLK1-DIO3 imprinting locus are critical for the differentiation of stem cells and for the development of the mouse embryo.[14, 15, 32] The DLK1-DIO3 miRNA cluster is up-regulated in c-MET mouse liver tumors and in this website a subgroup of HCC patients[26]; however, the expression status and function of this miRNA cluster in human HCC are largely unknown. In the current study, we demonstrated that the HNF4α-regulated miR-379-656 cluster in the DLK1-DIO3 region is suppressed in the majority of HCC tumor tissues. Experiments in cultured HCC cells confirmed a suppressive effect of the miR-379-656 cluster on malignant phenotypes. The DLK1-DIO3 imprinted locus contains three paternally expressed protein-coding genes and several maternally expressed noncoding RNA genes (MEGs).

6D). To further determine the correlation of HNF4α and miR-134 in HCC, we examined their expression profiles in the DEN-induced HCC rat model (n = 4 at each indicated Aloxistatin ic50 timepoint). In agreement with our previous study,[8] HNF4α expression decreased gradually after DEN administration. Interestingly, the transcript level of miR-134 (pri-miR134) was also suppressed in the process of hepatocarcinogenesis (Fig. 7A). A striking positive correlation between HNF4α and pri-miR-134 levels was observed in DEN-treated rat liver (Fig. 7B). We then analyzed the

association of HNF4α and pri-miR-134 expression in human HCC samples (n = 71). As compared with their surrounding noncancerous tissues, 63% (45/71) and 70% (50/71) of the HCC tissues showed lower levels of HNF4α and pri-miR-134, respectively U0126 mouse (Fig. 7C). Reduced pri-miR-134 expression was more frequent in HCCs with lower HNF4α levels relative to those with

intermediate and high HNF4α levels (89% versus 38%; Fig. 7D). The correlation was particularly apparent in HCC subjects with alpha-fetoprotein (AFP) levels over 1,000 μg/L (r = 0.6241, P = 0.0003, n = 29; Fig. 7E). The clinicopathological significance of pri-miR-134 levels in the above 71 patients with HCC was further analyzed. The median value of pri-miR-134 levels in HCC tissues was chosen as the cutoff point; 49.3% of HCCs (35/71) had low-level expression of pri-miR-134, and 50.7% of HCCs (36/71) had high-level expression of pri-miR-134 (Table 1). The low-level expression of pri-miR-134 in HCCs was associated with more aggressive pathological features, including liver cirrhosis (P = 0.0127), high levels of AFP (P = 0.0142), large tumor size (P = 0.0271), advanced tumor stage (P = 0.0051), presence of tumor microsatellites (P = 0.0434), and absence of tumor encapsulation (P = 0.0013) (Table 1). HNF4α is a transcription factor that plays a key role in hepatocyte differentiation

and in the maintenance of hepatic function. It is well established that the miRNAs at the DLK1-DIO3 imprinting locus are critical for the differentiation of stem cells and for the development of the mouse embryo.[14, 15, 32] The DLK1-DIO3 miRNA cluster is up-regulated in c-MET mouse liver tumors and in this website a subgroup of HCC patients[26]; however, the expression status and function of this miRNA cluster in human HCC are largely unknown. In the current study, we demonstrated that the HNF4α-regulated miR-379-656 cluster in the DLK1-DIO3 region is suppressed in the majority of HCC tumor tissues. Experiments in cultured HCC cells confirmed a suppressive effect of the miR-379-656 cluster on malignant phenotypes. The DLK1-DIO3 imprinted locus contains three paternally expressed protein-coding genes and several maternally expressed noncoding RNA genes (MEGs).

The final category involves traumatic bowel erosions. When the entire colon is affected, toxic megacolon may result. Patients with NE present with fever in most cases, right lower quadrant pain in 13% to 92%

of cases,39,52–54 diarrhea in 38% to 94%,52,53 nausea and vomiting in 27% to 75%.49,53,54 They may be tachycardic, tachypneic, and diaphoretic find more with signs of dehydration and sepsis. According to a retrospective analysis, malabsorption of D-xylose, as a measure of the functional integrity of the mucosa, is an independent predictor of NE as it correlates with the risk of invasive infection independent of the degree of myelosuppression.55 It also correlates with the type of induction therapy. Gross bleeding occurs in 36% to 65% of patients35,52 due to the combination of mucosal damage and thrombocytopenia. Septicemia may occur in 73% of patients with about half of these cases being polymicrobial.49 Occasionally, NE may present with sepsis alone, without any GI symptoms.56 Physical findings include a right-lower-quadrant mass or fullness,38 abdominal distension in 50% to 58% of patients,53,54 and diffuse tenderness in 63%.53 The absolute Palbociclib supplier neutrophil count is uniformly low with a median duration before diagnosis of 32 days57 and a median neutrophil count of 200.36 Gram-negative bacteria are the most frequently

indentified pathogens.36,48 There may be an increase in total bilirubin, primarily the direct fraction, of unclear significance.38 Plain films are abnormal in 50% to 100% of cases39,58 with a lack of bowel gas in the right lower quadrant and distension of the small bowel. Also seen may be a right lower quadrant soft tissue mass representing fluid-filled, atonic, dilated cecum and ascending colon,59 occasionally progressing selleck inhibitor to bowel obstruction.40,60 Ultrasound is a modality often preferred by pediatricians since

it is convenient, inexpensive, avoids ionizing radiation, and does not involve contrast.37 It will show homogeneous echogenic thickening of the bowel wall or the target sign in 79% of evaluated patients.36,61,62 The degree of bowel wall thickening detected by ultrasonography correlated with the need for surgery, the duration of diarrhea,36 and the outcome of patients: 60% of patients with mural thickness greater than 10 mm die from this complication.63 CT scan, the modality preferred by many physicians, may show non-specific ileus, diffuse bowel wall thickening, phlegmon, extraluminal collections, mesenteric stranding, pericecal inflammation, or pneumatosis intestinalis.64–66 The thickened cecum is usually isodense compared to surrounding normal bowel but may have hypodense areas presumably from edema, hemorrhage, or necrosis.