Mechanistically based blood proteomic markers in the TGF-ß pathway stratify risk of hepatocellular cancer in patients with cirrhosis.

Hepatocellular carcinoma (HCC) is the third leading cause of death from cancer worldwide but is often diagnosed at an advanced incurable stage. Yet, despite the urgent need for blood-based biomarkers for early detection, few studies capture ongoing biology to identify risk-stratifying biomarkers. We address this gap using the TGF-ß pathway because of its biological role in liver disease and cancer, established through rigorous animal models and human studies. Using machine learning methods with blood levels of 108 proteomic markers in the TGF-ß family, we found a pattern that differentiates HCC from non-HCC in a cohort of 216 patients with cirrhosis, which we refer to as TGF-ß based Protein Markers for Early Detection of HCC (TPEARLE) comprising 31 markers. Notably, 20 of the patients with cirrhosis alone presented an HCC-like pattern, suggesting that they may be a group with as yet undetected HCC or at high risk for developing HCC. In addition, we found two other biologically relevant markers, Myostatin and Pyruvate Kinase M2 (PKM2), which were significantly associated with HCC. We tested these for risk stratification of HCC in multivariable models adjusted for demographic and clinical variables, as well as batch and site. These markers reflect ongoing biology in the liver. They potentially indicate the presence of HCC early in its evolution and before it is manifest as a detectable lesion, thereby providing a set of markers that may be able to stratify risk for HCC.

Short-term outcomes using magnetic sphincter augmentation versus Nissen fundoplication for medically resistant gastroesophageal reflux disease.

BACKGROUND: In 2012 the United States Food and Drug Administration approved implantation of a magnetic sphincter to augment the native reflux barrier based on single-series data. We sought to compare our initial experience with magnetic sphincter augmentation (MSA) with laparoscopic Nissen fundoplication (LNF). METHODS: A retrospective case-control study was performed of consecutive patients undergoing either procedure who had chronic gastrointestinal esophageal disease (GERD) and a hiatal hernia of less than 3 cm. RESULTS: Sixty-six patients underwent operations (34 MSA and 32 LNF). The groups were similar in reflux characteristics and hernia size. Operative time was longer for LNF (118 vs 73 min) and resulted in 1 return to the operating room and 1 readmission. Preoperative symptoms were abolished in both groups. At 6 months or longer postoperatively, scores on the Gastroesophageal Reflux Disease Health Related Quality of Life scale improved from 20.6 to 5.0 for MSA vs 22.8 to 5.1 for LNF. Postoperative DeMeester scores (14.2 vs 5.1, p=0.0001) and the percentage of time pH was less than 4 (4.6 vs 1.1; p=0.0001) were normalized in both groups but statistically different. MSA resulted in improved gassy and bloated feelings (1.32 vs 2.36; p=0.59) and enabled belching in 67% compared with none of the LNFs. CONCLUSIONS: MSA results in similar objective control of GERD, symptom resolution, and improved quality of life compared with LNF. MSA seems to restore a more physiologic sphincter that allows physiologic reflux, facilitates belching, and creates less bloating and flatulence. This device has the potential to allow individualized treatment of patients with GERD and increase the surgical treatment of GERD.

One-year clinical outcomes, midterm survival, and predictors of mortality after carotid stenting in elderly patients.

BACKGROUND: It has been demonstrated recently that carotid stenting can be performed safely in patients > or =80 years of age. However, it is uncertain whether these patients will derive benefit because longevity after revascularization is an important consideration. This study was conducted to determine survival and predictors of mortality of selected elderly patients after stenting. METHODS AND RESULTS: One hundred forty-two consecutive elderly patients who were non-high risk for stenting underwent 153 procedures. Patients had either symptomatic stenosis > or =50% or asymptomatic stenosis > or =70%. Demographics and in-hospital outcomes were entered into a database; subsequent outcomes and mortality data were obtained retrospectively. Mean+/-SD age was 83.3+/-3.1 years. Symptomatic patients accounted for 28%. Overall survival at 3 years was 76% (85% at 2 years). At 1 year, 1 fatal stroke had occurred, with 97% of survivors (n=114) free of neurological events (neurological status was undetermined in the remaining 3%). Predictors of mortality were remote (> or =6 months) transient ischemic attack or cerebrovascular accident, smoking history, and creatinine clearance (hemoglobin level showed a strong trend toward achieving significance); for the asymptomatic subgroup, predictors of mortality were smoking history, previous carotid endarterectomy, hemoglobin level, and increasing age. In particular, symptom status and sex were not independent predictors of mortality. CONCLUSIONS: This study demonstrates that in selected elderly patients, a high proportion (85%) survived 2 years and >75% survived 3 years after stenting. Carotid stenting may be considered a revascularization option in such patients. Better selection of patients using the predictors of mortality may help to reduce unwarranted procedures and to optimize survival likelihood.