Rejection, Recurrence, or Something Else?

Since the introduction of liver transplant as treatment for end-stage liver disease, thousands of lives have been saved. To prevent organ rejection, immunosuppression is given chronically and hence, patients are at increased risk for opportunistic infections related to immunosuppression, especially within the first year after the transplant. However, opportunistic infections can occur years after the transplantation. Disseminated nocardiosis is one of these infections, and although the common presentation includes involvement of skin, lungs, and central nervous system. We present an uncommon presentation of nocardiosis in which cholestasis and elevated liver enzymes predominate, mimicking organ rejection and liver disease recurrence. Infectious etiologies, including opportunistic microorganisms, must always be ruled out in patients presenting elevation in liver enzymes and cholestasis after liver transplant as early diagnosis can prevent complications such as re-transplantation and even death.

Endoscopic surveillance of gastrointestinal premalignant lesions: current knowledge and future directions.

PURPOSE OF REVIEW: Provide an evidence-based resource for the surveillance of gastrointestinal premalignant lesions, focusing on the scientific articles reported recently. RECENT FINDINGS: No randomized controlled clinical trials exist to definitively support the efficacy of surveillance programs for Barrett's esophagus and gastric intestinal metaplasia. However, surveillance of these premalignant lesions is recommended by some of the leading organizations. To optimize the usefulness of surveillance programs, targeting high-risk patients might maximize its benefits. A Barrett's esophagus segment of at least 3 cm and evidence of intestinal metaplasia can help stratify those patients at highest risk for progression to esophageal adenocarcinoma. The location, extent, and severity of intestinal metaplasia are indicators of risk of developing gastric cancer. Patients with extensive intestinal metaplasia should be offered endoscopic surveillance. Quality in the baseline colonoscopy is crucial to decrease the risk of interval colorectal cancers. The importance of serrated polyps, as well as their surveillance intervals, is emphasized. SUMMARY: To optimize the usefulness of surveillance programs, targeting high-risk patients might maximize its benefits. Future research is needed to design more effective surveillance strategies. Recently, emerging imaging techniques hold promise for improving sensitivity of endoscopic surveillance of premalignant conditions in the gastrointestinal tract.

Approach to Familial Predisposition to Colorectal Cancer.

The traditional approach of one-size-fits-all for colorectal cancer has been replaced by personalized interventions to an individual's unique genetic, molecular, and environmental profile, seeking to identify high-risk individuals who would benefit from individualized screening and surveillance. This change in approach is due, in part, to emerging technologies, such as next-generation DNA sequencing.

Novel methylated DNA markers accurately discriminate Lynch syndrome associated colorectal neoplasia.

Aim: Acquired molecular changes in Lynch syndrome (LS) colorectal tumors have been largely unstudied. We identified methylated DNA markers (MDMs) for discrimination of colorectal neoplasia in LS and determined if these MDMs were comparably discriminant in sporadic patients. Patients & methods: For LS discovery, we evaluated DNA from 53 colorectal case and control tissues using next generation sequencing. For validation, blinded methylation-specific PCR assays to the selected MDMs were performed on 197 cases and controls. Results:OPLAH was the most discriminant MDM with areas under the receiver operating characteristic curve ≥0.97 for colorectal neoplasia in LS and sporadic tissues. ALKBH5, was uniquely hypermethylated in LS neoplasms. Conclusion: Highly discriminant MDMs for colorectal neoplasia in LS were identified with potential use in screening and surveillance.

Clinical and molecular features of young-onset colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression.

Association of NOD2 and IL23R with inflammatory bowel disease in Puerto Rico.

The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD) to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn's disease (CD) and ulcerative colitis (UC) in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn's disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10-6) and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10-4). The haplotype structure of both regions resembled that reported for European populations and "local" continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10-6). Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci.