Proton beam therapy for hepatocellular carcinoma: a retrospective review of 162 patients.

PURPOSE: We present results of patients with hepatocellular carcinoma (HCC) treated with proton beam therapy. EXPERIMENTAL DESIGN: We reviewed 162 patients having 192 HCCs treated from November 1985 to July 1998 by proton beam therapy with or without transarterial embolization and percutaneous ethanol injection. The patients in the present series were considered unsuitable for surgery for various reasons, including hepatic dysfunction, multiple tumors, recurrence after surgical resection, and concomitant illnesses. The median total dose of proton irradiation was 72 Gy in 16 fractions over 29 days. RESULTS: The overall survival rate for all of the 162 patients was 23.5% at 5 years. The local control rate at 5 years was 86.9% for all 192 tumors among the 162 patients. The degree of impairment of hepatic functions attributable to coexisting liver cirrhosis and the number of tumors in the liver significantly affected patient survival. For 50 patients having least impaired hepatic functions and a solitary tumor, the survival rate at 5 years was 53.5%. The patients had very few acute reactions to treatments and a few late sequelae during and after the treatments. CONCLUSIONS: Proton beam therapy for patients with HCC is effective, safe, well tolerable, and repeatable. It is the useful treatment mode for either cure or palliation for patients with HCC irrespective of tumor size, tumor location in the liver, insufficient feeding of the tumor with arteries, presence of vascular invasion, impaired hepatic functions, and coexisting intercurrent diseases.     

Clinical significance of tumor microsatellite instability and immunohistochemistry for mismatch repair deficiency in colorectal cancers

Referrals to genetics services are becoming increasingly common for patients who are diagnosed with early-onset colorectal cancer (CRC) or patients who have a family history of CRC. Microsatellite instability (MSI) testing and immunohistochemical analysis (IHC) of the patient’s tumor tissue, which assess indirectly the cellular status of DNA mismatch repair, have proven important tools for geneticists and genetic counselors to determine whether or not these individuals may be at risk for an inherited cancer syndrome, Lynch syndrome (a subset of hereditary nonpolyposis colorectal cancer). The application of tumor MSI/ IHC also extends to the group of providers involved in the diagnosis and management of CRC, demonstrating the growing clinical applicability of MSI/IHC testing. This review discusses the clinical utility of MSI/IHC analysis, including its benefits and limitations, and addresses some of the current debates surrounding testing.     

Environmental risk factors and colorectal neoplasia: Recent developments

The vast majority of new cases of colorectal cancer, the second most common cause of death in men and women in the United States, are attributable to environmental rather than genetic causes. Recent research has clarified inconsistencies in the literature and has explored new pathways through which risk factors may act. This review discusses newly published, selected interesting and important findings in colorectal cancer etiology; these include postmenopausal hormone use, nonsteroidal anti-inflammatory drug use, obesity, physical activity, diet, and other confirmed epidemiologic associations. This research provides insight into mechanisms and offers opportunities for prevention.     

Promises and pitfalls of untargeted metabolomics

Metabolomics is one of the newer omics fields, and has enabled researchers to complement genomic and protein level analysis of disease with both semi-quantitative and quantitative metabolite levels, which are the chemical mediators that constitute a given phenotype. Over more than a decade, methodologies have advanced for both targeted (quantification of specific analytes) as well as untargeted metabolomics (biomarker discovery and global metabolite profiling). Untargeted metabolomics is especially useful when there is no a priori metabolic hypothesis. Liquid chromatography coupled to mass spectrometry (LC-MS) has been the preferred choice for untargeted metabolomics, given the versatility in metabolite coverage and sensitivity of these instruments. Resolving and profiling many hundreds to thousands of metabolites with varying chemical properties in a biological sample presents unique challenges, or pitfalls. In this review, we address the various obstacles and corrective measures available in four major aspects associated with an untargeted metabolomics experiment: (1) experimental design, (2) pre-analytical (sample collection and preparation), (3) analytical (chromatography and detection), and (4) post-analytical (data processing).