Semiautomated Measure of Abdominal Adiposity Using Computed Tomography Scan Analysis.

BACKGROUND: The obesity epidemic has prompted the need to better understand the impact of adipose tissue on human pathophysiology. However, accurate, efficient, and replicable models of quantifying adiposity have yet to be developed and clinically implemented. We propose a novel semiautomated radiologic method of measuring the visceral fat area (VFA) using computed tomography scan analysis. MATERIALS AND METHODS: We obtained a cohort of 100 patients with rectal adenocarcinoma, with a median age of 60.9 y (age range: 35-87 y) and an average body mass index of 28.8 kg/m2 ± 6.56 kg/m2. The semiautomated quantification method of adiposity was developed using a commercial imaging suite. The method was compared to two manual delineations performed using two different picture archiving communication systems. We quantified VFA, subcutaneous fat area (SFA), total fat area (TFA), and visceral-to-subcutaneous fat ratio (V/S ratio) on computed tomography axial slices that were at the L4-L5 intervertebral level. RESULTS: The semiautomated method was comparable to manual measurements for TFA, VFA, and SFA with intraclass correlation (ICC) of 0.99, 0.97, and 0.96, respectively. However, the ICC for the V/S ratio was only 0.44, which led to the identification of technical outliers that were identified using robust regression. After removal of these outliers, the ICC improved to 0.99 for TFA, VFA, and SFA and 0.97 for the V/S ratio. Measurements from the manual methodology highly correlated between the two picture archiving communication system platforms, with ICC of 0.98 for TFA, 0.98 for VFA, 0.96 for SFA, and 0.95 for the V/S ratio. CONCLUSIONS: This semiautomated method is able to generate precise and reproducible results. In the future, this method may be applied on a larger scale to facilitate risk stratification of patients using measures of abdominal adiposity.

The impact of pathologic nodal status on survival following neoadjuvant chemoradiation for locally advanced rectal cancer.

PURPOSE: For patients with locally advanced rectal cancer, the accuracy rates of preneoadjuvant therapy nodal staging and potential nodal downstaging make the prognostic significance of nodal status unclear. We therefore sought to review our experience in order to better understand the impact of clinical and pathologic nodal status upon patient outcomes. METHODS: 174 patients were identified as having undergone neoadjuvant chemoradiation and resection for rectal cancer. For analytic purposes, patients were grouped into four nodal categories (uN( 0)· pN( 0), uN( 0)· pN( +), uN (+) · pN( 0), and uN (+) · pN( +)). Univariate and multivariate analyses were performed. RESULTS: 104 men and 70 women of median age 60 years (29-85 years) were followed for a median of 31 months (1-121 months). Nodal staging was available for 129 patients, with a median of 8 lymph nodes (range 0-39) evaluated. Disease recurred in 3 of 41 (7%) uN (0) ·pN ( 0), 10 of 52 (20%) uN ( +)·pN ( 0), 7 of 18 (41%) uN ( 0)·pN ( +), and 6 of 17 (35%) uN ( +)·pN ( +) patients. Those patients having nodal downstaging (uN ( +)·pN ( 0)) experienced superior overall survival (p = 0.03). Only pathologic nodal status was a significant predictor of both disease-free and overall survival in multivariate modeling. Adjuvant chemotherapy did not impact disease-free or overall survival for patients with pN0. CONCLUSIONS: Pathologic nodal status may represent a superior predictor of survival for patients with local advanced rectal cancers. Our findings may have potential implications for the application of adjuvant therapy.

Causes of dissatisfaction after laparoscopic fundoplication: the impact of new symptoms, recurrent symptoms, and the patient experience.

BACKGROUND: Although laparoscopic fundoplication effectively alleviates gastroesophageal reflux disease (GERD) in the great majority of patients, some patients remain dissatisfied after the operation. This study was undertaken to report the outcomes of these patients and to determine the causes of dissatisfaction after laparoscopic fundoplication. METHODS: All patients undergoing laparoscopic fundoplication in the authors' series from 1992 to 2010 were evaluated for frequency and severity of symptoms before and after laparoscopic fundoplication, and their experiences were graded from "very satisfying" to "very unsatisfying." Objective outcomes were determined by endoscopy, barium swallow, and pH monitoring. Primary complaints were derived from postoperative surveys. Median data are reported. RESULTS: Of the 1,063 patients undergoing laparoscopic fundoplication, 101 patients reported dissatisfaction after the procedure. The follow-up period was 33 months. The dissatisfied patients (n = 101) were more likely than the satisfied patients to have postoperative complications (9 vs 4 %; p < 0.05) and to have undergone a prior fundoplication (22 vs 11 %; p < 0.05). For the dissatisfied patients, heartburn decreased in frequency and severity after fundoplication (p < 0.05) but remained notable. Also for the dissatisfied patients, new symptoms (gas bloat/dysphagia) were the most prominent postoperative complaint (59 %), followed by symptom recurrence (23 %), symptom persistence (4 %), and the overall experience (14 %). Primary complaints of new symptoms were most common within the first year of follow-up assessment and less frequent thereafter. Primary complaints of recurrent symptoms generally occurred more than 1 year after fundoplication. CONCLUSIONS: Dissatisfaction is uncommon after laparoscopic fundoplication. New symptoms, such as dysphagia and gas/bloating, are primary causes of dissatisfaction despite general reflux alleviation among these patients. New symptoms occur sooner after fundoplication than recurrent symptoms and may become less common with time.

Delayed presentation of complete pancreatic ductal transection in children: management of two cases without resection.

Pancreatic ductal injuries in children are rare, and ductal transections presenting in a delayed or subacute fashion are seldom reported. We describe two cases of traumatic pancreatic ductal transection secondary to physical abuse, both of which presented late to medical care. Both were managed successfully without pancreatic resection. Judicious application of non-resectional management can yield favorable outcomes in this subset of pediatric patients.

Surgical shunting versus transjugular intrahepatic portasystemic shunting for bleeding varices resulting from portal hypertension and cirrhosis: a meta-analysis.

Surgical shunting was the mainstay in treating portal hypertension for years. Recently, transjugular intrahepatic portasystemic shunting (TIPS) has replaced surgical shunting, first as a "bridge" to transplantation and ultimately as first-line therapy for bleeding varices. This study was undertaken to examine evidence from trials comparing TIPS with surgical shunting to reassess the role of surgery in treating portal hypertension. The National Library of Medicine and the National Institutes of Health were searched for clinical trials comparing surgical shunting with TIPS. Meta-analysis using the fixed effects model was undertaken with end points of 30-day and 1- and 2-year survival and shunt failure (inability to complete shunt, irreversible shunt occlusion, major rehemorrhage, unanticipated liver transplantation, death). Three prospective randomized trials and one retrospective case-controlled study were identified. Analysis was limited to patients of Child Classes A or B. Significantly better 2-year survival (OR 2.5 [1.2-5.2]) and significantly less frequent shunt failure (OR 0.3 [0.1-0.9]) were seen in patients undergoing surgical shunting compared with TIPS. Meta-analysis promotes surgical shunting relative to TIPS because of improved survival and less frequent shunt failure. Surgical shunting should be accepted as first-line therapy for bleeding varices resulting from portal hypertension.

Surgery residency training programmes have greater impact on outcomes after pancreaticoduodenectomy than hospital volume or surgeon frequency.

BACKGROUND: Hospital volume of pancreaticoduodenectomy (PD) and surgeon frequency of PD have been shown to impact outcomes. The impact of surgery residency training programmes after PD is unknown. This study was undertaken to determine the impact of surgery training programmes on outcomes after PD, as well as their importance relative to hospital volume and surgeon frequency of PD. METHODS: The State of Florida Agency for Healthcare Administration Database was queried for patients undergoing PD during 2002-2007. Measures of outcome were compared for patients undergoing PD at centres with vs. without surgery residency training programmes. RESULTS: A total of 2345 PDs were identified, of which 1478 (63%) were undertaken at training centres and 867 (37%) were performed at non-training centres. Patients undergoing PD at training centres had shorter lengths of stay, lower hospital charges and lower in-hospital mortality. Relative to surgeon frequency of PD, training centres had a greater favourable impact on hospital length of stay, hospital charges and in-hospital mortality (P < 0.001 for each, ancova). Relative to hospital volume of PDs undertaken, training centres had a greater impact on hospital charges (P < 0.001, ancova). CONCLUSIONS: Surgery residency training programmes have a favourable effect on outcomes following PD and their impact on outcome is greater than the impact of hospital volume or surgeon frequency of PD.

Survival after pancreaticoduodenectomy is not improved by extending resections to achieve negative margins.

OBJECTIVE: This study was undertaken to determine the survival benefit of extending resections to obtain microscopically negative margins after positive intraoperative frozen sections. SUMMARY BACKGROUND DATA: The impact of residual microscopic disease after pancreaticoduodenectomy is currently a point of controversy. It is, however, generally believed that microscopically positive margins negatively impact survival and this may be improved by ultimately achieving negative margins. METHODS: Since 1995, patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma have been prospectively followed. Margin status has been codified as macro/microscopically negative (R0) or macroscopically negative/microscopically positive (R1). The impact of margin status on survival was evaluated utilizing survival curve analysis. Data are presented as median, mean +/- SD where appropriate. RESULTS: For pancreatic adenocarcinoma, 202 patients underwent pancreaticoduodenectomy. R0 resections were achieved in 158 patients, 17 of whom required extended resections to achieve complete tumor extirpation after an initially positive intraoperative frozen section (R1 --> R0). R1 resections were undertaken in 44 patients. Median survival for patients undergoing R0 resections was 21 months, 26 +/- 23.4 months versus 13 months, 17 +/- 21.0 months for patients undergoing R1 resections (P = 0.02). Median survival for patients undergoing R1 --> R0 resections was 11 months, 16 +/- 17.3, (P = 0.001). Margin status had a significant correlation with "N" stage and AJCC stage but not "T" stage. CONCLUSION: Survival after pancreaticoduodenectomy is not improved by extending pancreatic resections to achieve negative margins after initially positive intraoperative frozen sections. Tumor-specific factors beyond the presence of disease at a surgical margin are responsible for the abbreviated survival seen in patients undergoing R1 resections.

Pancreaticoduodenectomy for suspected periampullary cancers: the mimes of malignancy.

BACKGROUND: Pancreaticoduodenectomies are often undertaken with suspicion of malignancy. We undertook this study to determine if and how unnecessary pancreaticoduodenectomies can be avoided. METHODS: Data from patients undergoing pancreaticoduodenectomy were prospectively collected. Operative indications, including presenting symptoms and results with imaging, with or without biopsy, were reviewed. RESULTS: From 1996 through to 2007, 551 patients underwent pancreaticoduodenectomy at our institution. Chronic pancreatitis was the operative indication in 3% of patients; premalignant/malignant lesions were present in 86% of patients. Eleven per cent of patients underwent 'unnecessary' pancreaticoduodenectomies with presumptive diagnoses of cancer but were without premalignant/malignant disease on final report by Pathology [pancreatitis in 63%, serous cystadenomas (<4 cm) in 14%]. Of the unnecessary resections, 20% had histories and imaging sufficient to diagnose pancreatitis, 18% had inaccurate preoperative brushings/biopsies 'documenting' cancer, 11% had clear misinterpretations of their imaging studies and 7% had inadequate preoperative evaluations. However, 45% had signs/symptoms of cancer with a pancreatic head mass/biliary stricture. CONCLUSION: Only a small minority of patients undergoing pancreaticoduodenectomy for suspicion of periampullary cancer do so unnecessarily. Preoperative review of biopsies, better considerations of pancreatitis and careful evaluation of imaging, particularly for cystic masses, will decrease unnecessary pancreaticoduodenectomies.

Survival and variceal rehemorrhage after shunting support small-diameter prosthetic H-graft portacaval shunt.

This study was undertaken to report variceal rebleeding and survival after small-diameter prosthetic H-graft portacaval shunts (HGPCS) and to compare actual to predicted survival after shunting. Since 1987 we have prospectively followed patients after undergoing HGPCS to treat bleeding varices failing/not amenable to sclerotherapy/banding. One hundred and seventy patients underwent shunting. Cirrhosis was because of alcohol in 56%, hepatitis in 12%, both in 11%, and other causes in 21%. Child class was A for 10%, B for 28%, and C for 62%. Thirty-three patients died by 6 months, 54 by 24 months, 87 by 60 months, and 112 by 10 years, generally because of liver failure. Fifty-one patients are alive at a median of 48.3 months, 76 months +/- 57.8 (mean +/- SD). Variceal rehemorrhage was documented in 3 (2%) patients. By child class, 5-year/10-year survival rates were as follows: A 66.7/33.3%, B 48.6/15.6%, and C 29.2/7.0%. Actual survival was superior to predicted survival (Model for End-Stage Liver Disease [MELD]), (p < 0.001). Variceal rehemorrhage in patients undergoing small-diameter prosthetic H-graft portacaval shunting was very uncommon. Actual survival was superior to predicted survival (MELD). Long-term survival paralleled degree of hepatic function, although long-term survival was possible even with very advanced cirrhosis. Application of HGPCS is encouraged.

Conventional predictors of survival poorly predict and significantly underpredict survival after H-graft portacaval shunts.

OBJECTIVE: This study was undertaken to evaluate the ability to predict survival after 8 mm prosthetic H-graft portacaval shunts (HGPCS). METHODS: Since 1988, 170 patients have been prospectively followed after HGPCS. Using preshunt data, predictors of survival after shunting [MELD Score, Emory Score, Child Pugh Score, Discriminant Function (DF), and Child Class] were determined and related to actual survival. RESULTS: Child Class was: (a) 10%, (b) 28%, and (c) 62%. Actual 5- and 10-year survival by Child Class was: (a) 67% and 33%, (b) 49% and 16%, (c) 29% and 7%. Survival correlated with all predictors of survival (p < 0.01 for each). Actual survival was better than predicted by MELD (p < 0.001). By Multiple Variable Regression Analysis--Computed Model, explained variation in survival was greatest for Child Class (18%), followed by MELD (14%), with DF, Emory Score, and Child Pugh Score not significantly contributing. CONCLUSIONS: After HGPCS, actual survival is better than predicted by MELD. Child Class explains only a minor variation in survival, although it better explains survival than MELD, Emory Score, Child Pugh Score, or DF. Conventional predictors of survival poorly and underpredict survival after HGPCS and should be used with caution.

Can pancreatic cancer behavior be predicted based on computed tomography measurements of fat and muscle mass?

Many studies purport that obesity, and specifically visceral fat, impact survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. However, these studies involve crude measures of obesity [eg, body mass index (BMI)] or visceral fat [eg, linear measurements on computed tomographic (CT) scans]. Some studies purport that weight loss and muscle wasting (ie, sarcopenia) presage poor survival in these patients. This study was undertaken to accurately measure and reexamine the impact of visceral fat, subcutaneous fat, and sarcopenia on pancreatic cancer. MATERIALS AND METHODS: CT scans of 100 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were reviewed using specialized software to precisely determine the cross-sectional area (CSA) of subcutaneous fat, visceral fat, and psoas muscles at the level of L5 vertebra. In addition, linear measurements of subcutaneous fat and visceral fat were undertaken. Measures of cancer progression included tumor (T) status, nodal (N) status, American Joint Committee on Cancer stage, and overall survival after resection. Regression analysis was utilized, with and without standardization of all measurements to body size. Median data are presented. RESULTS: The median patient age was 67 years, with a BMI of 24 kg/m2. Cancer stage was IIB for 60% of patients. BMI, CSA of visceral fat, CSA for subcutaneous fat, CSA for psoas muscles, and linear measurements of visceral and subcutaneous fat were not significantly related to any measures of cancer progression or survival. Standardization to body size did not demonstrate any relationships with cancer progression or survival. CONCLUSIONS: Precise and reproducible measures of visceral fat, subcutaneous fat, and muscle mass, even when standardized to body size, do not predict cancer progression or survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma. Pancreatic cancer biology and behavior is too complex to predict with a CT scanner. The main focus of pancreatic cancer research should continue to be at the molecular, genetic, and immunologic levels.

The Tumor Suppressive Effects of HPP1 Are Mediated Through JAK-STAT-Interferon Signaling Pathways.

HPP1, a novel tumor suppressive epidermal growth factor (EGF)-like ligand, mediates its effects through signal transducer and activators of transcription (STAT) activation. We previously demonstrated the importance of STAT1 activation for HPP1 function; however the contribution of STAT2 remains unclear. We sought to delineate the components of JAK-STAT-interferon (IFN) signaling specifically associated with HPP1s biological effects. Using stable HPP1-HCT116 transfectants, expression analyses were performed by polymerase chain reaction (PCR)/western blotting while expression knockdowns were achieved using siRNA. Growth parameters evaluated included proliferation, cell cycle distribution, and anchorage-independent growth. STAT dimerization, translocation, and DNA binding were examined by reporter assays, fluorescent microscopy, and chromatin immunoprecipitation (ChIP), respectively. Forced expression of HPP1 in colon cancer cell lines results in the upregulation of total and activated levels of STAT2. We have also determined that JAK1 and JAK2 are activated in response to HPP1 overexpression, and are necessary for subsequent STAT activation. Overexpression of HPP1 was associated with significant increases in STAT1:STAT1 (p=0.007) and STAT1:STAT2 (p=0.036) dimer formation, as well as subsequent nuclear translocation. By ChIP, binding of activated STAT1 and STAT2 to the interferon-signaling regulatory element promoter sites of the selected genes, protein kinase RNA-activated (PKR), IFI44, and OAS1 was demonstrated. STAT2 knockdown resulted in partial abrogation of HPP1s growth suppressive activity with increased proliferation (p<0.0001), reduced G1/G0 phase cell cycle fraction, and a restoration of growth potential in soft agar (p<0.01). Presumably as a consequence of upregulation of IFN signaling elements, HPP1 overexpression resulted in an acquisition of exogenous IFN sensitivity. Physiologic doses of IFN-α resulted in a significant reduction in proliferation (p<0.001) and increase in G1/G0 cell cycle arrest in HPP1 transfectants. STAT2 is necessary for HPP1-associated growth suppression, and mediates these effects through activation of IFN-α pathways. Given the interest in therapeutic targeting of oncogenic erbB proteins, further understanding of HPP1s role as a tumor suppressive EGF-like ligand is warranted.

The interplay between histone deacetylases and c-Myc in the transcriptional suppression of HPP1 in colon cancer.

HPP1 (hyperplastic polyposis protein 1), a tumor suppressor gene, is downregulated by promoter hypermethylation in a number of tumor types including colon cancer. c-Myc is also known to play a role in the suppression of HPP1 expression via binding to a promoter region cognate E-box site. The contribution of histone deacetylation as an additional epigenetic mechanism and its potential interplay with c-Myc in the transcriptional regulation of HPP1 are unknown. We have shown that the treatment of the HPP1-non-expressing colon cancer cell lines, HCT116 and DLD-1 with HDAC inhibitors results in re-expression of HPP1. RNAi-mediated knockdown of c-Myc as well as of HDAC2 and HDAC3 in HCT116 and of HDAC1 and HDAC3 in DLD-1 also resulted in significant re-expression of HPP1. Co-immunoprecipitation (IP), chromatin IP (ChIP), and sequential ChIP experiments demonstrated binding of c-Myc to the HPP1 promoter with recruitment of and direct interaction with HDAC3. In summary, we have demonstrated that c-Myc contributes to the epigenetic regulation of HPP1 via the dominant recruitment of HDAC3. Our findings may lead to a greater biologic understanding for the application of targeted use of HDAC inhibitors for anti-cancer therapy.

Outcomes after transjugular intrahepatic portosystemic stent shunt: a "bridge" to nowhere.

BACKGROUND: Transjugular intrahepatic portosystemic stent shunt (TIPS) has become the modality of choice for complicated portal decompression. This study was undertaken to determine outcomes after TIPS and the usefulness of TIPS as a "bridge" to transplantation. METHODS: Patients undergoing TIPS from 2001 to 2010 at a teaching hospital with a transplant program were studied. The median data are presented. RESULTS: TIPS was undertaken in 256 patients. TIPS decreased portal vein-inferior vena cava (IVC) gradients from 17 to 5 mm Hg (P < .001). Reinterventions were undertaken in 54 patients (21%). Survival after TIPS was 26 months; liver transplantation was undertaken in 35 (14%) patients. CONCLUSIONS: TIPS effectively decompresses portal hypertension but leads to frequent reinterventions and short survival. After TIPS, liver transplantation is uncommonly undertaken. TIPS is a "bridge" to transplantation that is seldom "crossed," and TIPS continues to be plagued by frequent reinterventions. Outcomes after TIPS and the infrequency of transplantation after TIPS make it difficult to recommend on merit.

Quantitative measures of visceral adiposity and body mass index in predicting rectal cancer outcomes after neoadjuvant chemoradiation.

BACKGROUND: The association between body mass index as a measure of obesity and rectal cancer outcomes has been inconsistent. Radiologic measures of visceral adiposity using CT scans have not been well characterized among rectal cancer patients. The objective of this study was to examine quantitative radiologic measures of visceral obesity compared with body mass index in predicting patient outcomes among patients undergoing neoadjuvant chemoradiation and resection for locally advanced rectal cancers. STUDY DESIGN: We identified 99 rectal adenocarcinoma patients treated with neoadjuvant chemoradiation and surgical resection. Visceral and subcutaneous fat areas, as well as perinephric fat thickness (PNF), were recorded and categorized as obese (body mass index ≥30, visceral fat area to subcutaneous fat area ratio [V/S] ≥0.4, or median PNF). The Kaplan-Meier method, log-rank test, and Cox proportional hazards models evaluated overall and disease-free survival differences by adiposity. RESULTS: Viscerally obese rectal cancer patients (V/S >0.4 or PNF) were more likely to be older, male, and have pre-existing obesity-related conditions (eg, diabetes, hypertension, and/or hypercholesterolemia). Elevated V/S or PNF was associated with shorter disease-free survival (p = 0.02) or overall survival time (p = 0.047), respectively. Among patients with well to moderately differentiated tumors, visceral obesity was associated with poorer disease-free survival (V/S >0.4: adjusted hazard ratio = 5.0; 95% CI, 1.2-22.0). CONCLUSIONS: Visceral fat area to subcutaneous fat area ratio and PNF were strongly associated with key preoperative metabolic comorbidities, and body mass index was not. Findings suggests that elevated visceral adiposity was associated with an increased risk of recurrence, which was most evident among patients with well to moderately differentiated tumors and those with incomplete response to neoadjuvant chemoradiation treatment. Quantitative measures of visceral adiposity warrant large-scale prospective evaluation.

Targeting early deaths following pancreaticoduodenectomy to improve survival.

INTRODUCTION: There is increasing focus on disease-specific outcomes. This study was undertaken to analyze early mortality after pancreaticoduodenectomy as part of a strategy to improve long-term outcome. METHODS: One thousand thirty-one patients who underwent pancreaticoduodenectomy from 1992 to 2010 were studied. Median data are reported. RESULTS: Fifty-eight (5.6%) patients died within 90 days after pancreaticoduodenectomy. All patients had at least one significant comorbidity, commonly cardiorespiratory in nature (76%). Sixty percent of patients had depressed serum albumin levels, and 43% were jaundiced. The American Society of Anesthesiologists class was: 17% class II, 72% class III, and 10% class IV. Seventy-four percent had malignant disease. Twenty-two percent of patients underwent a major vascular resection at the time of pancreaticoduodenectomy. Causes of death were vascular/bleeding related (26%), cardiorespiratory causes (17%), multiorgan failure (12%), leak/perforation (10%), cancer progression (9%), infection (7%), or indeterminate (19%). CONCLUSIONS: Death within 90 days after pancreaticoduodenectomy is uncommon, occurs in relatively older deconditioned patients, and is generally not causally related to underlying malignancy. Early death is generally associated with vascular or bleeding complications. Strategies to minimize early death should focus on careful patient selection and prompt recognition and management of herald bleeding or vascular thrombosis, as it can often result in perioperative death following pancreaticoduodenectomy.

Complementary strand microRNAs mediate acquisition of metastatic potential in colonic adenocarcinoma.

BACKGROUND: Altered expression of specific microRNAs (miRNA) is known to occur during colorectal carcinogenesis. However, little is known about the genome-wide alterations in miRNA expression during the neoplastic progression of primary colorectal cancers. METHODS: Using a miRNA array platform, we evaluated the expression of 668 miRNA in primary colonic adenocarcinomas. Biological functions of selected miRNA were evaluated with in vitro invasion assays. RESULTS: RNA was extracted for miRNA analysis from 65 primary colon cancers. We identified a seven-miRNA expression signature that differentiated stage I and stage IV primary colon cancers. We then demonstrated this signature was able to discriminate between stage II and III primary colon cancers. Six differentially expressed miRNA were downregulated in association with the development of metastases, and all 7 miRNA were complementary strand miRNA. We transfected HCT-116, a highly invasive colon cancer cell line, with corresponding downregulated miRNA and demonstrated that overexpression of three miRNA (miR200c*, miR143*, and miR424*) significantly abrogated invasive potential. CONCLUSION: We have identified a seven-miRNA signature that is associated with metastatic potential in the primary tumor. Forced overexpression of three downregulated miRNA resulted in attenuation of in vitro invasion, suggesting direct tumor suppressive function and further supporting the biological importance of complementary strand miRNA.

Uncovering the truth about covered stents: is there a difference between covered versus uncovered stents with transjugular intrahepatic portosystemic shunts?

INTRODUCTION: Polytetrafluoroethylene (PTFE)-covered transjugular intrahepatic portosystemic shunt (TIPS) stents purportedly provide superior patency. This study was undertaken to determine whether covered stents provide better long-term patency and outcomes after TIPSs. METHODS: Patients with portal hypertension undergoing TIPS at a large teaching hospital from 2001 to 2010 were studied. Median data are presented. RESULTS: Two hundred forty-six patients underwent TIPS; 70 received uncovered stents, and 176 received covered stents. Patients who received uncovered stents had more severely impaired liver function (41% were Child class C cirrhotics). The follow-up was longer with uncovered stents (48 vs 24 months, P < .01). Reinterventions for stenosis were undertaken in 33% with uncovered stents versus 19% with covered stents (P = .01). Shunt dysfunction occurred in 57% with uncovered stents versus 21% covered (P = .05). A deterioration of hepatic function occurred in 31% with uncovered stents versus 30% with covered (P = .32). Survival with uncovered stents was 31 months versus 33 months with covered stents (P = .55, Kaplan-Meier). CONCLUSIONS: Covered stents may improve patency but do not mitigate postshunt hepatic dysfunction and do not improve survival.

H-graft portacaval shunts versus TIPS: ten-year follow-up of a randomized trial with comparison to predicted survivals.

OBJECTIVE: To report long-term outcome of patients undergoing prosthetic 8-mm H-graft portacaval shunts (HGPCS) or TIPS and to compare actual with predicted survival data. METHODS: A randomized trial comparing TIPS to HGPCS for bleeding varices began in 1993. Predicted survival was determined using MELD (Model for End-stage Liver Disease). RESULTS: Patients undergoing TIPS (N = 66) or HGPCS (N = 66) were very similar by Child's class and MELD scores and predicted survival. After TIPS (P = 0.01) and HGPCS (P = 0.001), actual survival was superior to predicted survival. Through 24 months, actual survival after HGPCS was superior to actual survival after TIPS (P = 0.04). Compared with TIPS, survival was superior after HGPCS for patients of Child's class A and B (P = 0.07) and with MELD scores less than 13 (P = 0.04) with follow-up at 5 to 10 years. Shunt failure was less following HGPCS (P < 0.01). CONCLUSIONS: Predicted survival data for patients undergoing TIPS or HGPCS confirms an unbiased randomization. Actual survival following TIPS or HGPCS was superior to predicted survival. Shunt failure favored HGPCS, as did survival after shunting, particularly for the first few years after shunting and for patients of Child's class A or B or with MELD scores less than 13. This trial irrefutably establishes a role for surgical shunting, particularly HGPCS.

Post-shunt resource consumption favors small-diameter prosthetic H-graft portacaval shunt over TIPS for patients with poor hepatic reserve.

OBJECTIVE: To define the role of surgical shunting for patients with poor hepatic reserve (Child's class C) in the era of TIPS. SUMMARY BACKGROUND DATA: Most physicians prefer TIPS to surgical shunting for patients with poor hepatic reserve because of anticipated poor long-term survival. METHODS: Sixty-two patients of Child's class C with bleeding varices not amenable to endoscopic sclerotherapy or banding were prospectively randomized to undergo TIPS or 8-mm prosthetic H-graft portacaval shunt (HGPCS) from 1993 to 1999. Resource consumption and survival after shunting were determined. RESULTS: Twenty-nine patients underwent TIPS and 33 underwent HGPCS. After HGPCS, survival at 3 years was favorable but not statistically superior. TIPS was more often associated with shunt stenoses/occlusions, recurrent hemorrhage, shunt revisions, and shunt failure. Long-term follow-up documented that after HGPCS, patients required fewer hospital and ICU days and fewer units of RBCs transfused. After HGPCS, cost of care was less, as was the median cost of care per day of survival. CONCLUSIONS: For Child's class C patients undergoing HGPCS or TIPS, long-term survival is similar, though favoring HGPCS. Similarly, measures of resource consumption and cost of care following hospital discharge favor HGPCS. HGPCS should be preferentially applied for acceptable patients without access to convenient capable post-shunt care or without definitive plans for imminent transplantation.