Lack of a small animal model of the human hepatitis C virus (HCV) has impeded development of antiviral therapies against this epidemic infection. By transplanting normal human hepatocytes into SCID mice carrying a plasminogen activator transgene (Alb-uPA), we generated mice with chimeric human livers. Homozygosity of Alb-uPA was associated with significantly higher levels of human hepatocyte engraftment, and these mice developed prolonged HCV infections with high viral titers after inoculation with infected human serum. Initial increases in total viral load were up to 1950-fold, with replication confirmed by detection of negative-strand viral RNA in transplanted livers. HCV viral proteins were localized to human hepatocyte nodules, and infection was serially passaged through three generations of mice confirming both synthesis and release of infectious viral particles. These chimeric mice represent the first murine model suitable for studying the human hepatitis C virus in vivo.

Gastric cancer with peritoneal carcinomatosis has an extremely poor prognosis, which may be improved with cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). We systematically reviewed the literature regarding the efficacy of CRS + HIPEC in these patients. Electronic databases were searched from 2000 to 2010. Following CRS + HIPEC, overall median survival was 7.9 months and improved to 15 months for patients with completeness of cytoreduction scores of 0/1, however with a 30-day mortality rate of 4.8%.

Breath tests are a simple and safe alternative to more invasive investigation strategies for many gastroenterological conditions. Both the hydrogen breath tests and the new 13C stable radioisotope breath tests are nonradioactive and safe in children and pregnancy. The range of diseases that can be identified include Helicobacter pylori infection, lactose and fructose intolerance, bacterial overgrowth, bile salt wastage, pancreatic insufficiency, liver dysfunction, and abnormal small bowel transit. In this review, the physiology supporting these tests and the principles of normal gas dynamics in the gut are briefly reviewed and then related to the test preparation and interpretation in two parts: 1) detection of H. pylori and 2) small bowel, pancreatic, and hepatobiliary disorders. A MEDLINE search reviewing all English language abstracts from 1966 to March, 2001 was performed, with an additional review of abstracts from major national meetings from 1997 to 2001. Using the information from this review, the performance characteristics of the various tests were detailed, and an attempt is made to provide some literature-based guidance regarding their indications and limitations. The interpretation of "flat" breath tests and the selective use of methane collection and colonic alkalinization are discussed. Breath tests are valuable tools that are, in general, underutilized in evaluating dyspepsia and functional bloating and diarrhea, as well as suspected malabsorption, including lactose intolerance.

SS for anal canal cancer was associated with significant morbidity. Long-term survival was achieved in 39% of patients. Comorbidities should guide patient selection, and R0 resection should be the goal.

Metabolomics, the newest of the "omics" sciences, has brought much excitement to the field of oncology as a potential new translational tool capable of bringing the molecular world of cancer care to the bedside. While still early in its development, metabolomics could alter the scope and role of surgery in the multidisciplinary treatment of cancer. This review examines potential roles of metabolomics in areas of early cancer detection, personalized therapeutics and tumorigenesis.

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Background:Metabolomics has shown promise in gastric cancer (GC) detection. This research sought to identify whether GC has a unique urinary metabolomic profile compared with benign gastric disease (BN) and healthy (HE) patients.Methods:Urine from 43 GC, 40 BN, and 40 matched HE patients was analysed using 1H nuclear magnetic resonance (1H-NMR) spectroscopy, generating 77 reproducible metabolites (QC-RSD <25%). Univariate and multivariate (MVA) statistics were employed. A parsimonious biomarker profile of GC vs HE was investigated using LASSO regularised logistic regression (LASSO-LR). Model performance was assessed using Receiver Operating Characteristic (ROC) curves.Results:GC displayed a clear discriminatory biomarker profile; the BN profile overlapped with GC and HE. LASSO-LR identified three discriminatory metabolites: 2-hydroxyisobutyrate, 3-indoxylsulfate, and alanine, which produced a discriminatory model with an area under the ROC of 0.95.Conclusions:GC patients have a distinct urinary metabolite profile. This study shows clinical potential for metabolic profiling for early GC diagnosis.

Colorectal cancers (CRCs) deficient in DNA mismatch repair (dMMR) contain abundant CD8+ tumor-infiltrating lymphocytes (TILs) responding to the abundant neoantigens from their unstable genomes. Priming of such tumor-targeted TILs first requires recruitment of CD8+ T cells into the tumors, implying that this is an essential prerequisite of successful dMMR anti-tumor immunity. We have discovered that selective recruitment and activation of systemic CD8+ T cells into dMMR CRCs strictly depend on overexpression of CCL5 and CXCL10 due to endogenous activation of cGAS/STING and type I IFN signaling by damaged DNA. TIL infiltration into orthotopic dMMR CRCs is neoantigen-independent and followed by induction of a resident memory-like phenotype key to the anti-tumor response. CCL5 and CXCL10 could be up-regulated by common chemotherapies in all CRCs, indicating that facilitating CD8+ T cell recruitment underlies their efficacy. Induction of CCL5 and CXCL10 thus represents a tractable therapeutic strategy to induce TIL recruitment into CRCs, where local priming can be maximized even in neoantigen-poor CRCs.