But the microbiota also contain numerous potential- ly opportunistic pathogens. Gut microbiota have long been known to be a key determinant of intesti- nal inflammation, and have very recently been shown to play a role in generating chronic inflam- mation of the liver. 45 They appear to cause the lat-
patients (5%) were assigned in the very early stage (0), 78 patients (35%) in the early stage (A), 78 (35%) in the in- termediate stage (B), 39 (17%) in the advanced (C) stagem and 18 (8%) in the terminal (D) stage. Survival curves (Ka- plan-Meier estimator) (Figure 1) were compared for PS 0 and 1 and the log-rank test demonstrated that these two levels were not statistically different (p = 0.203). Thus, patients with PS 1 were also accepted in the BCLC 0 (five patients), A (41 patients) and B (46 patients) stages, and six patients with PS 0 were furthermore classified in the BCLC C stage. One-quarter of patients (10/39, 26%) in the advanced stage category had a PS score of 2, and 44% (8/18) of patients in the terminal stage category had PS scores of 3 or 4. The treatment allocation among all patients is described in table 1. One hundred and seven pa- tients (48%) were treated according to the BCLC recom- mendations and 116 patients (52%) were not. Of the 116 patients treated differently from the algorithm, the majori- ty (74%) received a treatment recommended for other tu- mor stages, while the remaining 26% of patients (30/116) received a treatment not mentioned in the BCLC algo- rithm, such as TARE, external radiotherapy, or a combina- tion of sorafenib and TACE.
Acute pancreatitis is a constant management challenge, especially with peripancreatic collection that are one of the most common complications; after the first surgical attempts that had high mortality, there had to be a new approach based in decades of acquired knowledge in physiopathology added to the development of endoscopic intervention techniques and the evolution of endoscopic devices help to establish less invasive and conservative management. This review allows us to know the last advances in the management of acute pancreatitis, pancreatic pseudocyst and walled off necrosis, determined the right time for the management to become more invasive, even considering surgery at a final stage. It also reviews the different types of drainage of peripancreatic collections and the accessories currently in use.
At inclusion patients were evaluated for the follow- ing variables: demographic information (age, sex, race), date of initial diagnosis of HCC, methods of diagnosis (CT, MRI, histology), context leading to the diagnosis of HCC (finding in a surveillance pro- gram, new symptoms, laboratory results, incidental radiological finding), risk factors for HCC and co- morbidities (cirrhosis, smoking, alcohol consumption, diabetes, elevated BMI), tumor burden, Child-Pugh stage and its variables (albumin, bilirubin, pro- thrombin time, ascites, encephalopathy), Barcelona Clinic Liver Cancer (BCLC) classification, Model of End-Stage Liver Disease (MELD) score, α-fetoprotein (AFP) level, socio-economic parameters (achieved education, professional occupation, type of health insurance). The diagnosis of cirrhosis was based on histology and/or indirect clinical signs such as the presence of varices or ascites. With regard to the causeof liver disease multiple etiologies were
with a moderate success, but merged with renewed strength during the last decade of the same century, due to the technologic advances in virology and in the use of viruses as vectors for gene transfer. The aim of the onco- lytic virotherapy is to achieve a strong cytolytic effect highly restricted to transformed cells. Several kinds of vi- ruses have been used for oncolytic virotherapy. The first viruses reported were human wild-type adenoviruses for the treatment of cervical cancer. Oncolytic viruses can be divided in two categories: wild-type oncolytic viruses (myxomavirus, reovirus, herpesvirus, parvovirus, etc.) and genetically modified, particularly, adenoviruses with ge- netic modifications for conditioned replication, by tissue- specific promoter activities controlling viral functions, or «arming» an adenoviral vector with cytotoxic genes.
Metabolomics is a powerful high-throughput approach that relies on state of the art analytical methods, such as nuclear magnetic resonance (NMR), to identify meta- bolic signatures or biomarkers associated with homeo- stasis perturbations . Metabolomic strategies play an increasingly important role in clinical and observational studies, in the hope that they will offer new perspectives not only in understanding the processes of disease devel- opment, but also for identification of diagnostic/prog- nostic markers and targeted healthcare . Indeed, several recent studies have leveraged metabolite profiling to provide new insights into pathological processes pertaining to cancer, heart disease, or diabetes melli- tus [9–15]. Although a number of metabolomic-based approaches have been applied to HCC, they have either been largely based on traditional case–control designs, high risk patient groups (e.g. hepatitis infection, cirrhosis, or other chronic liver diseases), non-Western populations where traditional HCC risk factors predominate, or on tumor tissues [16–31]. However, there is currently very lit- tle information derived from prospective settings where biological samples have been collected prior to disease diagnosis [32–34].
A subgroup analysis was conducted by publication year, country, methodology, clinical features, and study quality. However, subject size was the only possible source of het- erogeneity found (whether the number of patients in both HCC and LC groups were ³ 40 or not). For GPC3, in the subgroup that had a larger sample size was 66.5%, while the heterogeneity in another subgroup was 77.2%. The present meta-analysis did not include any RCTs. Other covariates were also potential sources of heteroge- neity, such as the differences in operating protocol, enrollment period, pathological grades and tumor burden.
diagnosing bone metastasis from HCC has increased with improved HCC patient prognosis, and because radiation therapy can palliate symptoms, radiolo- gists should take care not to miss base metastasis at an early stage when the initial symptoms appear. Al- though HCC should be included in the differential diagnosis of osteolytic, hypervascular lesions, bone metastasis from renal cell carcinoma, thyroid gland cancer, parotid gland cancer, and pheochromocyto- ma may show similar imaging findings. 15
tions regarding the effectiveness of serum AFP as a screening test. Since elevated serum AFP levels are not observed solely in HCC patients, we speculated that there might be limitations in increasing the PPV; however, when we applied different cutoff val- ues according to each individual’s hepatitis status, PPV could be raised without sacrificing sensitivity. In this study, we demonstrated that such an ap- proach is especially effective in individuals that are not HBsAg(+) or anti-HCV(+). The benefits of this approach will be mostly in the reduction of medical costs and the decrease in false positive screening re- sults in individuals with little reason to suspect HCC.
PPARc participates in the antiproliferative effect evoked by cannabinoids. It has been recently described that the cannabinoid WIN induces apoptosis through PPARg in HepG2 cells. 18 Moreover, in previous studies, we demon- strated that cannabinoids induce apoptosis and autophagy in HCC cells and in xenograft tumor models. To investigate the role of PPARg in the anti-proliferative response exerted by THC or JWH-015, HCC cells were incubated with increasing doses of both cannabinoids for 48 h in the presence of the PPARg-selective antagonist GW9669 and cell viability was measured by MTT. Pharmacological inhibition of PPARg caused a shift of the dose–response curve to the right, thus increasing the IC50 dose in HepG2 and in HUH-7 cells (Figure 5a). Moreover, when HepG2 cells or HuH-7 cells were transfected with PPARg siRNA, the inhibitory effect of cannabinoids on cell viability was reduced (Figure 5b). As PPARg agonists have been evaluated as potential anti- tumoral agents, we decided to test the possible synergic effect between cannabinoids and the PPARg agonist Troglitazone (TRO) in combinatorial treatment. In agreement with the results obtained by other groups, 16,29–33 we observed that TRO treatment produced a dose-dependent reduction in cell viability that reached a value of 50% when 40 mM concentrations were used (Figure 5c). We therefore selected submaximal doses of Troglitazone (20 mM), THC (2 mM) and JWH-015 (2 mM) to evaluate whether the combined administration of PPAR ligands and cannabinoids enhanced their ability to reduce cell viability. In line with this possibility, combined treatment with low doses of TRO and THC or JWH-015 reduced the viability of HepG2 cells (Figure 5d).
The extraction of total RNA was operated in line with the instructions on the Trizol reagent (Invitrogen Life Technologies, Carlsbad, CA, USA), and the RNA extract was determined for its purity and concentration by a Nan- oDrop2000 spectrophotometer (Thermo Scientific, Willmington, DE, USA). The primer sequences for PCR were designed by using Primer 5.0 software based on the gene sequences published in the Genbank and were syn- thesized by Sangon Biotech (Shanghai) Co. Ltd (Table 1). The PCR reaction system was prepared according to in- structions on the ABI PRISM 7500 real-time PCR System (ABI). And the conditions for real-time PCR were as fol- lows: pre-denaturation for 10 s at 95 °C and 40 cycles of 5 s at 94 °C, 5 s at 60 °C, and 10 s at 72 °C. With GAPDH as the internal reference gene, each gene of each sample had 3 replicates and the dissolution curve was used to evaluate the reliability of PCR. CT value (the inflection point of
Results of this study showed that curcumin in both doses significantly blocked the elevation of AFP concen- tration found in TAA group. Curcumin groups also signif- icantly blocked the elevation in ALT and AST activities in TAA group. Cur high-dose group significantly blocked se- rum albumin concentration reduction found in TAA group. Histopathological examination of liver sections showed marked improvement in both curcumin groups than TAA group, with more improvement in Cur high- dose group. These results show that curcumin in both doses help in protection against HCC induced by TAA in rats. Correlation studies also showed significant correla- tions between LC3-II gene expression levels as a marker of autophagy and each of AFP concentration (r = - 0.445, P < 0.05), ALT activity (r = - 0.571, P <0.05), and AST ac- tivity (r = - 0.579, P < 0.05).
After preliminary analyses, 180 days from HCC diagno- sis until LT was selected as our time-point for statistical analysis, to compare short wait times with longer wait times (Table 1). This not only allowed for nearly equal groups of comparison, but also seemed most relevant in light of the recent UNOS policy change. These two groups had similar patient demographics and etiologies for underlying liver disease. The group waiting less than 180 days had lower MELD at LT, larger average tumor size, but had no difference in overall or recurrence-free surviv- al rates over five years of follow-up (Figure 3).
He died of loss of a large volume of blood and was subsequently subjected to an autopsy. A tissue spe- cimen subjected to hematoxylin and eosin staining showed that portal vein thrombosis was consistent with poorly-differentiated HCC (Figure 2A). By Elas- tica van Gieson staining, it was shown that HCC raised intra-luminally with no extra-luminal inva- sion (Figure 2B). The HCC was found from the por- tal vein trunk to the portal vein branches and upper mesenteric vein. The HCC had only a few tumor ves- sels, which were compressed by fibromatous change originating from HCC formation (Figure 2C). As for immunohistochemical examinations, HCC was nega- tive for AFP (Figure 3A), and was positive for c-kit (Figure 3B). Tumor nodules in the whole liver parenchyma were not found pathologically (data not shown).
In Mexico, the medical community is not fully aware of HCC surveillance in high-risk patients. In addition, treatment options are not completely re- cognized. A pitfall to these circumstances is that HCC is diagnosed in advanced stage where curative treatments are not feasible. As it is shown in table 1, AJCC02 staging 3 represented 55.3% of cases and 21.3% were stage 4. BCLC staging showed ad- vance disease as well since 51.1% of patients were on D stage, suggesting null curative options and few choices of palliative treatments. This is in con- cordance with previous reports in Mexico, as in the study of Mondragon where it was found that tumor median size was 8 cm, same as our series, never- theless he did not describe staging in any classifica- tion system. 8 On the other hand, Meza and
Liver cirrhosis was confirmed by histological analysis and/or based on clinical-laboratory parameters such asas- cites, hepatic encephalopathy, portal hypertension (splenomegaly, esophageal varices, thrombocytopenia), and ultrasonographic signs suggestive of liver cirrhosis. Excessive alcohol consumption as a causeof cirrhosis was defined as ethanol consumption > 40 g/day in women and > 60 g/day in men for more than 5 years. Patients with liv- er cirrhosis were evaluated using the Child-Turcotte- Pugh and MELD scores.
treatment for small hepatocellular carcinomas. PEI in- duces local tumor necrosis as a result of cellular de- hydration, protein denaturation, and chemical occlusion of tumor vessels. The major advantages of ethanol ablation are its low cost and low rate of com- plications. Ethanol injection remains a widely used and effective option for patients waiting for LT. The main limitation of this technique is the presence of fi- brous septa inside the lesion, which limits the sprea- ding of ethanol; most of the times, multiple sessions are needed to achieve a complete response.
A few days after starting the treatment with sorafenib, the patient developed an increase in liver test levels, raised temperature (up to 38.5 °C) and increased blood pressure. The most significant findings of the laboratory tests were: (a) alkaline phosphatase, (b) 223 UI/L, (c) SGOT (AST) 414 UI/L, (d) SGPT (ALT) 670 UI/L, (e) bilirubinemia within the normal range, (f) lactate dehydrogenase 314 U/L and (g) elevated C-reactive protein (265 mg/L). A further abdominal ultrasound scan did not reveal any obstructive liver-biliary pathology. These symptoms were interpreted as drug-induced hepatitis, with the consequent suspension of the antineoplastic treatment, which was later restarted in June 2014 at a 50% dose with good tolerance. Once normal values in the liver tests were achieved, the dose of sorafenib was progressively increased without reaching the maximum recommended dose. Examinations of the thorax, abdomen and pelvis were carried out using a scanner (09-2014). These showed signs of progression in the primary lesion with portal vein thrombosis, signs of peritoneal car- cinomatosis and regional lymph node enlargements, ascites and the previously detected secondary bone lesion in the right femur. October 2014 lab tests showed AFP:7865 ng/dl, plasma albumin 2,65 gr/dl, SGOT (AST) 78 U/L, SGPT (ALT) 81 U/L and FA 254 U/L with normal levels of total and direct bilirubin. A scan of the abdomen and pelvis revealed an increase in deep vein thrombosis and the appearance of signs of portal hypertension; therefore, a decision was made to suspend chemotherapy and keep the patient exclusively in palliative care. The patient died at the end of January 2015.
Hepatocellularcarcinoma is a common malignancy affecting approximately one million people around the world every year. The incidence is low in the occiden- tal world and high in locations such as Southeast Asia and sub-Saharan Africa. Hepatocellularcarcinoma primarily affects old people, reaching its highest preva- lence among those aged 65 to 69 years old. Chronic in- fection by the hepatitis B virus is the most common causeof this disease. Other important causes are cir- rhosis, chronic viral hepatitis (hepatitis C virus, and hepatitis B plus D viruses), alcohol abuse, obesity, hemochromatosis, alfa 1 -antitripsin deficiency, and tox- ins similar to aflatoxin. In most cases, hepatocellularcarcinoma is asymptomatic and has a low life expect- ancy. This article presents a review of the most impor- tant epidemiological, diagnostic and treatment data about this disease.
was indeed 48 months (C.I. 29-66) for patients with low (≤ 130 AU/mL) SCCA-IgM and 26 months (C.I. 22-30) for those with high SCCA- IgM (> 130 AU/mL). At multivariate analysis tu- mour size and SCCA-IgM levels were identified as the only independent predictors of survival. In addition, SCCA-IgM levels correlated with overall response to treatment (including surgery, TACE, percutaneous ablation), with a median time to progression of 14 months in patients with low SCCA-IgM, vs. 6 months in those with high SCCA-IgM levels. Additional studies however are required to confirm these preliminary data and to better assess the behaviour of this oncomarker in relation to different methodologies of HCC treatment.