Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics.

The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPINUC), DNA methylation and cancer-specific protein biomarkers. Our system allows for high-resolution detection of six active and repressive histone modifications and their ratios and combinatorial patterns on millions of individual nucleosomes by single-molecule imaging. In addition, our system provides sensitive and quantitative data on plasma proteins, including detection of non-secreted tumor-specific proteins, such as mutant p53. EPINUC analysis of a cohort of 63 colorectal cancer, 10 pancreatic cancer and 33 healthy plasma samples detected cancer with high accuracy and sensitivity, even at early stages. Finally, combining EPINUC with direct single-molecule DNA sequencing revealed the tissue of origin of colorectal, pancreatic, lung and breast tumors. EPINUC provides multilayered information of potential clinical relevance from limited (<1 ml) liquid biopsy material.

"Vanishing liver metastases"-A real challenge for liver surgeons.

Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.

Small for size liver remnant following resection: prevention and management.

In the latest decades an important change was registered in liver surgery, however the management of liver cirrhosis or small size hepatic remnant still remains a challenge. Currently post-hepatectomy liver failure (PLF) is the major cause of death after liver resection often associated with sepsis and ischemia-reperfusion injury (IRI). ''Small-for-size'' syndrome (SFSS) and PFL have similar mechanism presenting reduction of liver mass and portal hyper flow beyond a certain threshold. Few methods are described to prevent both syndromes, in the preoperative, perioperative and postoperative stages. Additionally to portal vein embolization (PVE), radiological examinations (mainly CT and/or MRI), and more recently 3D computed tomography are fundamental to quantify the liver volume (LV) at a preoperative stage. During surgery, in order to limit parenchymal damage and optimize regenerative capacity, some hepatoprotective measures may be employed, among them: intermittent portal clamping and hypothermic liver preservation. Regarding the treatment, since PLF is a quite complex disease, it is required a multi-disciplinary approach, where it management must be undertaken in conjunction with critical care, hepatology, microbiology and radiology services. The size of the liver cannot be considered the main variable in the development of liver dysfunction after extended hepatectomies. Additional characteristics should be taken into account, such as: the future liver remnant; the portal blood flow and pressure and the exploration of the potential effects of regeneration preconditioning are all promising strategies that could help to expand the indications and increase the safety of liver surgery.

Complications after percutaneous ablation of liver tumors: a systematic review.

BACKGROUND: Although ablation therapy has been accepted as a promising and safe technique for treatment of unrespectable hepatic tumors, investigation of its complications has been limited. A physician who performs ablation treatment of hepatic malignancies should be aware of the broad spectrum of complications. Proper management is possible only if the physician Performing ablation understands the broad spectrum of complications encountered after ablation. OBJECTIVES: TO SYSTEMATICALLY REVIEW THE COMPLICATIONS AFTER DIFFERENT ABLATION MODALITIES: Radiofrequency ablation (RFA), microwave ablation (MWA) and Nano knife for the treatment of liver tumors and analyze possible risk factors that precipitate these complications. SEARCH METHODS: WE PERFORMED ELECTRONIC SEARCHES IN THE FOLLOWING DATABASES: MEDLINE, EMBASE and COCHARNE. Current trials were identified through the Internet (from January 1, 2000 to January 1, 2014). We included only studies who specific mentioned complications after liver ablation therapy (RFA/MWA/Nano knife). MAIN RESULTS: A total of 2,588 publications were identified, after detailed examination only 32 publications were included in the review. The included studies involved 15,744 participants. According to the type of technique, 13,044 and 2,700 patients were included for RFA and MWA. Analysis showed a pooled mortality of 0.15% for RFA, and 0.23% for MWA. CONCLUSIONS: This systematic review gathers information from controlled clinical trials and observational studies which are vulnerable to different types of bias, never the less RFA and MWA can be considered safe techniques for the treatment of liver tumors.

[Laparoscopic colon and rectal surgery--after ten years and 350 operations].

BACKGROUND: Within a decade since laparoscopy was used in cholecystectomy it has become the preferred approach in many abdominal procedures. Laparoscopic colon and rectal surgery has not yet been adopted by the majority of surgeons, due to technical complexity and reservation regarding its oncological safety. As data and experience accumulate, this attitude is gradually changing. We present our experience with laparoscopic surgery of the large bowel over the last ten years. AIM: To assess the short and intermediate term results after laparoscopic colon and rectal surgery, and to summarize the long term results after curative colectomy for malignancy. METHODS: Data regarding all patients undergoing laparoscopic colon and rectal surgery was prospectively entered into a computerized database, including demographics, surgical technique and perioperative course. Follow-up information was gathered at outpatient clinic visits, and using telephone interviews in selected cases. Data analysis was performed using a statistical software package. RESULTS: Over a period of ten years, 350 various laparoscopic colon and rectal procedures were performed, for both benign and malignant conditions. Sixty percent of the operations were for treatment of colorectal cancer. In 14.5% of cases conversion to open laparotomy was required. Post-operative complications included surgical site infection in 17.4%, anastomotic leak in 6.9%, and a mortality rate of 2.8%. Long term follow-up revealed cancer recurrence locally in 2.3% and systemically in 8.2%. Five year survival was 56% after resection of colorectal cancer regardless of the stage, and 63% after resection with curative intent. CONCLUSIONS: The laparoscopic approach to large bowel surgery enables short and long term results comparable with those achieved by open technique, regarding perioperative complication rate and long term oncologic outcome. The advantages of laparoscopy, related to reduced abdominal wall trauma, justify the adoption of this technique as a legitimate alternative to the open approach.