Ido Nachmany

Hepatectomy for Noncolorectal Non-Neuroendocrine Metastatic Cancer: A Multi-Institutional Analysis

BACKGROUND Although hepatic metastasectomy is well established for colorectal and neuroendocrine cancer, the approach to hepatic metastases from other sites is not well defined. We sought to examine the management of noncolorectal non-neuroendocrine liver metastases. STUDY DESIGN A retrospective review from 4 major liver centers identified patients who underwent liver resection for noncolorectal non-neuroendocrine metastases between 1990 and 2009. The Kaplan-Meier method was used to analyze survival, and Cox regression models were used to examine prognostic variables. RESULTS There were 420 patients available for analysis. Breast cancer (n = 115; 27%) was the most common primary malignancy, followed by sarcoma (n = 98; 23%), and genitourinary cancers (n = 92; 22%). Crude postoperative morbidity and mortality rates were 20% and 2%, respectively. Overall median survival was 49 months, and 1, 3, and 5-year Kaplan-Meier survival rates were 73%, 50%, and 31%. Survival was not significantly different between the various primary tumor types. Recurrent disease was found after hepatectomy in 66% of patients. In multivariable models, lymphovascular invasion (p = 0.05) and metastases ≥5 cm (p = 0.04) were independent predictors of poorer survival. Median survival was shorter for resections performed between 1990 and 1999 (n = 101, 32 months) when compared with resections between 2000 and 2009 (n = 319, 66 months; p = 0.003). CONCLUSIONS Hepatic metastasectomy for noncolorectal non-neuroendocrine cancers is safe and feasible in selected patients. Lymphovascular invasion and metastases ≥5 cm were found to be associated with poorer survival. Patients undergoing metastasectomy in more recent years appear to be surviving longer, however, the reasons for this are not conclusively determined.

Pancreatic cancer: Surgery is a feasible therapeutic option for elderly patients

BackgroundCompromised physiological reserve, comorbidities, and the natural history of pancreatic cancer may deny pancreatic resection from elderly patients. We evaluated outcomes of elderly patients amenable to pancreatic surgery.MethodsThe medical records of all patients who underwent pancreatic resection at our institution (1995-2007) were retrospectively reviewed. Patient, tumor, and outcomes characteristics in elderly patients aged ≥ 70 years were compared to a younger cohort (<70y).ResultsOf 460 patients who had surgery for pancreatic neoplasm, 166 (36%) aged ≥ 70y. Compared to patients < 70y (n = 294), elderly patients had more associated comorbidities; 72% vs. 43% (p = 0.01) and a higher rate of malignant pathologies; 73% vs. 59% (p = 0.002). Operative time and blood products consumption were comparable; however, elderly patients had more post-operative complications (41% vs. 29%; p = 0.01), longer hospital stay (26.2 vs. 19.7 days; p < 0.0001), and a higher incidence of peri-operative mortality (5.4% vs. 1.4%; p = 0.01). Multivariable analysis identified age ≥ 70y as an independent predictor of shorter disease-specific survival (DSS) among patients who had surgery for pancreatic adenocarcinoma (n = 224). Median DSS for patients aged ≥ 70y vs. < 70y were 15 months (SE: 1.6) vs. 20 months (SE: 3.4), respectively (p = 0.05). One, two, and 5-Y DSS rates for the cohort of elderly patients were 58%, 36% and 23%, respectively.ConclusionsProperly selected elderly patients can undergo pancreatic resection with acceptable post-operative morbidity and mortality rates. Long term survival is achievable even in the presence of adenocarcinoma and therefore surgery should be seriously considered in these patients.

Resection of colorectal liver metastases in the elderly—Is it justified?

Liver resection of colorectal liver metastasis (CRLM) may necessitate large metabolic and physiologic reserve. As the population ages, resection of CRLM is increasingly required in the elderly. We assessed the safety and efficacy of these operations.

Augmented expression of RUNX1 deregulates the global gene expression of U87 glioblastoma multiforme cells and inhibits tumor growth in mice

Glioblastoma multiforme is the most common and aggressive primary brain tumor in adults. A mesenchymal phenotype was associated with tumor aggressiveness and poor prognosis in glioblastoma multiforme patients. Recently, the transcription factor RUNX1 was suggested as a driver of the glioblastoma multiforme mesenchymal gene expression signature; however, its independent role in this process is yet to be described. Here, we assessed the role of RUNX1 in U87 glioblastoma multiforme cells in correspondence to its mediated transcriptome and genome-wide occupancy pattern. Overexpression of RUNX1 led to diminished tumor growth in nude and severe combined immunodeficiency mouse xenograft tumor model. At the molecular level, RUNX1 occupied thousands of genomic regions and regulated the expression of hundreds of target genes, both directly and indirectly. RUNX1 occupied genomic regions that corresponded to genes that were shown to play a role in brain tumor progression and angiogenesis and upon overexpression led to a substantial down-regulation of their expression level. When overexpressed in U87 glioblastoma multiforme cells, RUNX1 down-regulated key pathways in glioblastoma multiforme progression including epithelial to mesenchymal transition, MTORC1 signaling, hypoxia-induced signaling, and TNFa signaling via NFkB. Moreover, master regulators of the glioblastoma multiforme mesenchymal phenotype including CEBPb, ZNF238, and FOSL2 were directly regulated by RUNX1. The data suggest a central role for RUNX1 as master regulator of gene expression in the U87 glioblastoma multiforme cell line and mark RUNX1 as a potential target for novel future therapies for glioblastoma multiforme.

Management of endoscopic retrograde cholangiopancreatography-related perforations: Experience of a tertiary center.

Background. Endoscopic retrograde cholangiopancreatography–induced perforation (EP) is a rare but severe complication. We describe the risk factors, management, and outcome of ERCP‐induced perforations in a tertiary center. Methods. This is a case‐control study. All EP cases between March 2004 and February 2015 were compared to a control group without perforation. Data on patients, procedures, presentation, perforation type, radiologic findings, management, and outcome were assessed. Results. Of 6,934 endoscopic retrograde cholangiopancreatographies, 37 patients (0.53%) had EP. Independent risk factors included failure of cannulation, a procedure described as “difficult,” performing a precut and resection of a periampullary adenoma. Perforation was diagnosed during the procedure in 7 patients (19%). Median interval for diagnosis was 11 hours (range: 0–201 hours), with 84% diagnosed within 30 hours. The periampullary region was the most common EP site (51%). Twenty‐nine patients (78%) were managed conservatively and 8 (22%) were operated. Three patients failed conservative management and required delayed operation. Failure of conservative management had a detrimental effect on morbidity and duration of stay. All patients who required operative intervention had perforation of either the duodenal free wall or the periampullary region. Conclusion. Clear risk factors can be used to raise suspicion of EP. Early diagnosis and management are critical for better outcome. This is especially important when operative intervention is indicated. Nonetheless, the majority of patients may be managed conservatively.