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BACKGROUND AND OBJECTIVES: The impact of perioperative blood transfusion (PBT) on outcomes for pancreatic ductal adenocarcinoma (PDAC) patients given multimodality therapy (MMT) remains undefined. We sought to evaluate the association of PBT with survival after PDAC resection. METHODS: Pancreatectomy patients (July 2011-December 2017) who received MMT were abstracted from a prospective database. Overall survival (OS) was compared by PBT within 30 days, 24 h (24HR-BT), or 24 h until 30 days (Postop-BT). RESULTS: Most (76.6%) of 312 MMT patients underwent neoadjuvant therapy (NT). Eighty-nine patients (28.5%) received PBT; 58 (18.6%) 24HR-BT, and 31 (9.9%) Postop-BT. Compared with surgery-first, NT patients received more 24HR-BTs (22.2% vs. 6.8%, p = 0.003) and PBTs overall (32.6% vs. 15.1%, p = 0.004). Overall median OS was 45 months. The association of PBT with shorter median OS appeared limited to first 24-h transfusions (34 months 24HR-BT vs. 48 months Postop-BT vs. 53 months no-PBT, p = 0.009) and was dose-dependent, with a median OS of 52 months for 0 units 24HR-BT, 35 months for 1 unit, and 25 months for ≥2 units (p = 0.004). Independent predictors of OS included node-positivity (hazard ratio [HR]: 1.93, p < 0.001), perineural invasion (HR: 1.64, p = 0.050), postoperative pancreatic fistula (HR: 1.94, p = 0.018), and 24HR-BT (HR: 1.75, p = 0.001). CONCLUSIONS: Transfusions given within 24 h are associated with dose-dependent decreases in survival after pancreatectomy for PDAC.

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BACKGROUND: Recovery after CRS-HIPEC influenced by several factors, including pain and opioid consumption. We hypothesized that 4Q-TAP blocks provide not inferior quality of recovery compared with TEA after CRS-HIPEC. We conducted a randomized, controlled trial to determine whether 4-quadrant transversus abdominis plane (4Q-TAP) block analgesia was noninferior to thoracic epidural (TEA) among patients who underwent cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS HIPEC). METHODS: Patients 18 years or older who underwent a CRS-HIPEC surgery were randomly assigned to have either TEA or 4Q-TAP blocks. The primary outcome of this study was the change in quality of recovery 2 days after surgery. Secondary outcomes included quality of recovery on Days 1, 3, 5, 7, 10, and 30 postoperatively, opioid consumption, pain intensity, length of stay, and postoperative complications. Analyses were performed on a per-protocol basis. RESULTS: Sixty-eight patients were included in the analysis. The difference between 4Q-TAP and TEA in the mean QoR-15 change from surgery at postoperative Days 1, 2, and 3 was 0.80 (P = 0.004), -4.5 (P = 0.134), and 3.4 (P = 0.003), respectively. All differences through postoperative day 30 were significantly within the noninferiority boundary of -10 except at postoperative Day 2 (P = 0.134). Length of stay, opioid-related adverse events, and frequency and grade of complications were not significantly different between TEA and 4Q-TAP patients. CONCLUSIONS: Despite the significantly higher use of opioids after CRS-HIPEC in patients with 4Q-TAP blocks, their short-term quality of recovery was not inferior to those treated with TEA. Patients undergoing CRS-HIPEC can be effectively managed with 4Q-TAP blocks.

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BACKGROUND: Administration of dexamethasone to mitigate postoperative nausea and vomiting has been suggested to improve short- and long-term outcomes after pancreatic ductal adenocarcinoma (PDAC) resection. This study aimed primarily to evaluate these hypotheses in a contemporary patient cohort treated with multimodality therapy. METHODS: The clinicopathologic and perioperative characteristics of consecutive resected PDAC patients (July 2011 to October 2018) were analyzed from a prospectively maintained database. Intraoperative administration of dexamethasone (4-10 mg) was retrospectively abstracted from the electronic medical record. RESULTS: The majority of 373 patients (59.8%) received intraoperative dexamethasone. Most of these patients underwent neoadjuvant therapy (75.3%), were potentially resectable at presentation (69.7%), and underwent pancreaticoduodenectomy (79.9%). Women were more likely to receive dexamethasone than men (69.9 vs 30.1%; p < 0.001). The cohorts were otherwise clinically similar. Intraoperative dexamethasone was not associated with differences in postoperative major complications (PMCs) (21.1 vs 19.3%; p = 0.68), postoperative pancreatic fistulas (6.3 vs 6.7%; p = 0.88), or composite infectious complications (28.7 vs 24.7%; p = 0.39). Dexamethasone was not associated with any improvement in median recurrence-free survival (RFS) (17 vs 17 months; p = 0.99) or overall survival (OS) (46 vs 43 months; p = 0.90). After adjustment for clinical factors including margin status, clinical classification, tumor size, and dexamethasone, the only factors independently associated with OS were pathologic node-positivity (hazard ratio [HR], 1.80, 95% confidence interval [CI], 1.32-2.47), perineural invasion (HR, 2.02; 95% CI, 1.23-3.31), multimodality therapy (HR, 0.30; 95% CI, 0.13-0.70), and PMCs (HR, 1.64; 95% CI, 1.17-2.29) (all p < 0.006). CONCLUSIONS: Dexamethasone failed to demonstrate any protective advantage in terms of mitigating short-term PMCs or infectious complications, or to confer any long-term survival benefit. Tumor biology, multimodality therapy, and PMCs remain the main prognostic factors after PDAC resection.

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Liquid water on Mars might be created by deliquescence of hygroscopic salts or by permafrost melts, both potentially forming saturated brines. Freezing point depression allows these heavy brines to remain liquid in the near-surface environment for extended periods, perhaps as eutectic solutions, at the lowest temperatures and highest salt concentrations where ices and precipitates do not form. Perchlorate and chlorate salts and iron sulfate form brines with low eutectic temperatures and may persist under Mars near-surface conditions, but are chemically harsh at high concentrations and were expected to be incompatible with life, while brines of common sulfate salts on Mars may be more suitable for microbial growth. Microbial growth in saturated brines also may be relevant beyond Mars, to the oceans of Ceres, Enceladus, Europa and Pluto. We have previously shown strong growth of salinotolerant bacteria in media containing 2 M MgSO4 heptahydrate (~50% w/v) at 25 °C. Here we extend those observations to bacterial isolates from Basque Lake, BC and Hot Lake, WA, that grow well in saturated MgSO4 medium (67%) at 25 °C and in 50% MgSO4 medium at 4 °C (56% would be saturated). Psychrotolerant, salinotolerant microbes isolated from Basque Lake soils included Halomonas and Marinococcus, which were identified by 16S rRNA gene sequencing and characterized phenetically. Eutectic liquid medium constituted by 43% MgSO4 at -4 °C supported copious growth of these psychrotolerant Halomonas isolates, among others. Bacterial isolates also grew well at the eutectic for K chlorate (3% at -3 °C). Survival and growth in eutectic solutions increases the possibility that microbes contaminating spacecraft pose a contamination risk to Mars. The cold brines of sulfate and (per)chlorate salts that may form at times on Mars through deliquescence or permafrost melt have now been demonstrated to be suitable microbial habitats, should appropriate nutrients be available and dormant cells become vegetative.

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We enumerate the broad range of anesthetic considerations that affect the outcome of patients undergoing laparoscopic liver resection. Key elements for excellent outcomes after laparoscopic liver resection are careful patient selection and risk stratification, appropriate monitoring, techniques to reduce blood loss and transfusion, and active recovery management. Although some of these key elements are the same for open liver operation, there are specific anesthetic considerations of which both the surgical and anesthesia teams must be aware to achieve optimal patient outcomes after laparoscopic liver resection. While unique advantages of laparoscopic liver resection typically include decreased intraoperative bleeding, transfusion requirements, and a lower incidence of postoperative ascites, specific challenges include management of the complicated interplay between low-volume anesthesia and increased intraabdominal pressure due to pneumoperitoneum, with additional considerations regarding circulatory support to treat acute blood loss with need for emergent conversion in some cases. This article will address in detail the preoperative, intraoperative, and postoperative anesthetic considerations for patients undergoing laparoscopic liver resection that both the surgical and anesthesia team should be aware of to optimize outcomes.

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OBJECTIVES: The objective of this study is to evaluate postoperative complications and inflammatory profiles when using a total intravenous anesthesia (TIVA) or volatile gas-opioid (VO) based anesthesia in patients undergoing pancreatic cancer surgery. METHODS: Design, retrospective propensity score matched cohort; Setting, major academic cancer hospital; Patients, all patients who had pancreatic surgery between November 2011 and August 2014 were retrospectively reviewed. Propensity score matched patient pairs were formed. A total of 134 patients were included for analysis with 67 matched pairs; Interventions, Patients were categorized according to type of anesthetic used (TIVA or VO). Patients in the TIVA group received preoperative celecoxib, tramadol, and pregabalin in addition to intraoperative TIVA with propofol, lidocaine, ketamine, and dexmedetomidine. The VO-group received a volatile-opioid based anesthetic; Measurements, demographic, perioperative clinical data, platelet lymphocyte ratios, and neutrophil lymphocyte ratios were collected. Complications were graded and collected prospectively and later reviewed retrospectively. RESULTS: Patients receiving TIVA were more likely to have no complication or a lower grade complication than the VO-group (P = 0.014). There were no differences in LOS or postoperative inflammatory profiles noted between the TIVA and VO groups. CONCLUSIONS: In this retrospective matched analysis of patients undergoing pancreatic cancer surgery, TIVA was associated with lower grade postoperative complications. Length of hospital stay (LOS) and postoperative inflammatory profiles were not significantly different.

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BACKGROUND: Colorectal cancer patients require care across different disciplines. Integration of multidisciplinary care is critical to accomplish excellent oncologic results. We hypothesized that the establishment of a dedicated colorectal cancer center (CRCC) around specialty-trained surgeons will lead to increased multidisciplinary management and improved outcomes in colorectal cancer patients. METHODS: We analyzed data from three periods: a baseline group, a period after the recruitment of specialty-trained surgeons, and a period after the creation of a dedicated multidisciplinary cancer center. Data analyzed included surrogate markers of surgical oncologic care, multidisciplinary integration, and oncologic outcomes. RESULTS: Recruitment of specialized surgeons led to improvements in surgical oncologic care; the establishment of the CRCC resulted in further improvements in surgical oncologic care and multidisciplinary integration. CONCLUSION: Our study suggests that although the recruitment of specialty-trained surgeons in a high volume center leads to improvement in surgical oncologic care, it is the establishment of a multidisciplinary center around the surgeons that leads to integrated care and improvements in oncologic outcomes.

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BACKGROUND: Colorectal cancer staging criteria do not rely on examination of neuronal tissue. The authors previously demonstrated that perineural invasion is an independent prognostic factor of outcomes in colorectal cancer. For the current study, they hypothesized that neurogenesis occurs in colorectal cancer and portends an aggressive tumor phenotype. METHODS: In total, samples from 236 patients with colorectal cancer were used to create a tissue array and database. Tissue array slides were immunostained for protein gene product 9.5 (PGP9.5) to identify nerve tissue. The correlation between markers of neurogenesis and oncologic outcomes was determined. The effect of colorectal cancer cells on stimulating neurogenesis in vitro was evaluated using a dorsal root ganglia coculture model. RESULTS: Patients whose tumors exhibited high degrees of neurogenesis had 50% reductions in 5-year overall survival and disease-free survival compared with patients whose tumors contained no detectable neurogenesis (P = .002 and P = .006, respectively). Patients with stage II disease and high degrees of neurogenesis had greater reductions in 5-year overall survival and disease-free survival compared with lymph node-negative patients with no neurogenesis (P = .002 and P = .008, respectively). Patients with stage II disease and high degrees of neurogenesis had lower 5-year overall survival and disease-free survival compared with patients who had stage III disease with no neurogenesis (P = .01 and P = .008, respectively). Colorectal cancer cells stimulated neurogenesis and exhibited evidence of neuroepithelial interactions between nerves and tumor cells in vitro. CONCLUSIONS: Neurogenesis in colorectal cancer appeared to play a critical role in colorectal cancer progression. Furthermore, the current results indicated that neurogenesis functions as an independent predictor of outcomes and may play a role in therapy stratification for patients with lymph node-negative disease.

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BACKGROUND: Minimally invasive surgery (MIS) for colorectal resection has been shown to improve short-term outcomes compared with open surgery in patients with colorectal cancer. Currently, there is a paucity of data demonstrating similar efficacy between MIS and open colorectal resection in the elderly population. We hypothesized that minimally invasive surgery provides improved short-term outcomes in elderly patients with colorectal cancer. METHODS: A review of 242 consecutive elderly (≥ 65 y of age) patients who underwent either open or MIS colorectal resection for adenocarcinoma at one institution was conducted. Short-term and oncologic outcomes were analyzed. Continuous variables were analyzed by the Mann-Whitney U test. Categorical variables were compared by χ(2) tests. Survival was compared by the Kaplan-Meier method using the log rank test for comparison. RESULTS: Of the 242 elderly patients with colorectal cancer (median American Society of Anesthesiology score (ASA) scores of 3), 80% (n = 195) of patients underwent open and 20% (n = 47) had MIS colorectal cancer resections. Patients undergoing MIS had a faster return of bowel function, decreased days to nasogastric tube removal, decreased days to flatus and bowel movement, and quicker advancement to clear liquid and regular diets. The overall length of hospital stay in the MIS group was decreased by 40% as well as a trend towards a 50% decrease in SICU stay. Additionally, there was 66% decrease in cardiac complications in the MIS group. When evaluating for oncologic adequacy as measured by number of lymph nodes and surgical resection margins, MIS surgery offered equivalent results as open resection. Furthermore, there was no significant difference in overall survival for MIS versus open colorectal surgery. CONCLUSION: Minimally invasive colorectal cancer resection leads to improved short-term outcomes as demonstrated by decreased length of hospital stay and faster return of bowel function. Additionally, there appears to be no difference in oncologic outcomes in the elderly. On the basis of our data, age alone should not be a contra-indication to laparoscopic colorectal cancer resection.

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BACKGROUND: The impact of obesity on development of postoperative complications after gastrointestinal surgery remains controversial. This may be due to the fact that obesity has been calculated by body mass index, a measure that does not account for fat distribution. We hypothesized that waist circumference, a measure of central obesity, would better predict complications after high-risk gastrointestinal procedures. METHODS: Retrospective review of an institutional cancer database identified consecutive cases of men undergoing elective rectal resections. Waist circumference was calculated from preoperative imaging. RESULTS: From 2002 to 2009, 152 patients with mean age 65.2 ± 0.75 years and body mass index 28.0 ± 0.43 kg/m(2) underwent elective resection of rectal adenoma or carcinoma. Increasing body mass index was not significantly associated with risk of postoperative complications including infection, dehiscence, and reoperation. Greater waist circumference independently predicted increased risk of superficial infections (OR 1.98, 95% CI 1.19-3.30, p < 0.008) and a significantly greater risk of having one or more postoperative complications (OR 1.56, 95% CI 1.04-2.34, p < 0.034). CONCLUSIONS: Waist circumference, a measure of central obesity, is a better predictor of short-term complications than body mass index and can be used to identify patients who may benefit from more aggressive infection control and prevention.

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BACKGROUND: Over 70,000,000 American adults are overweight, and obesity accounts for $147 billion annually in medical expenses. Since measuring obesity by body mass index (BMI) fails to account for fat distribution and quantity, recent work has explored quantitative measures of visceral fat area (VFA) and subcutaneous fat area (SFA) obtained from CT imaging. However, use of CT to quantify adipose tissue has not been evaluated in colorectal cancer (CRC) patients and the optimal anatomic location for measuring VFA and SFA has yet to be determined. We measured VFA and SFA at three different anatomic locations to determine which location was optimal in CRC patients. METHODS: A database of patients undergoing CRC surgery from 2002 to 2009 was reviewed to identify patients with preoperative CT imaging. Quantitative measurements of both VFA and SFA were calculated at the level of L4-L5, L2-L3, and mid-waist. RESULTS: A total of 244 colorectal cancer patients had preoperative imaging available and 99% were men. VFA and SFA quantified by CT at the levels of L2-L3, L4-L5, and mid-waist were all significant independent predictors for medical complications of obesity including diabetes (HR 1.04 -1.06) and hypertension (HR 1.04-1.09) on multivariate analysis. The location used for imaging did not affect predictive power. Additionally, waist circumference was also a significant independent predictor of diabetes (HR 1.56) and hypertension (HR 1.70). CONCLUSIONS: Quantitative measures of obesity from CT imaging in CRC patients correlated significantly with medical conditions known to be associated with obesity. This indicates that direct measurement of adiposity is valid in colorectal cancer patients.

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BACKGROUND: Obesity increases the risk of wound infections following surgery for colon cancer. Considerably less data is available, however, regarding the impact of obesity on infections and wound complications after resection for rectal cancer. Additionally, the impact of minimally invasive surgery (MIS) on complications in rectal surgery remains unclear. We hypothesized that obesity is associated with prolonged operative time and more infectious complications in obese patients undergoing both MIS and open surgery for rectal cancer. MATERIALS AND METHODS: Review of retrospective surgical database. RESULTS: One hundred fifty patients underwent surgery for rectal cancer from 2002 to 2009. Open cases accounted for 72% (n = 108) and MIS for 28% (n = 42) of cases. BMI did not correlate with increased operative time in open rectal surgery, but in MIS patients, operative time increased from a median of 254 min in the lowest quartile of BMI to 333 min in the highest quartile (P < 0.004). Superficial wound infections in open rectal surgery increased from 17% to 52% with increasing BMI (P < 0.005). The increased rate of wound complications persisted in the MIS group. Rate of superficial wound infections and subsequent open packing in the MIS group increased from 0% in the lowest BMI quartile to 33% in the highest quartile (P < 0.029 and P < 0.007, respectively). CONCLUSIONS: Elevated BMI is associated with increased wound complications in both minimally invasive and open rectal surgery. This trend may be related to prolonged operative time in obese patients, particularly in MIS. Our observations suggest that more aggressive techniques to prevent infection are warranted in obese patients undergoing rectal surgery.

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BACKGROUND: Minimally invasive surgery (MIS) for colorectal cancer offers improved short-term outcomes compared with open surgery. However, there is concern that MIS is more difficult in obese patients and may be associated with worse oncologic outcomes while failing to preserve short-term benefits. We hypothesized that obese patients undergoing surgery for colorectal cancer (CRC) would benefit from MIS. METHODS: Retrospective database review. RESULTS: Database review identified 155 obese patients undergoing resections for CRC from 2002-2009. Open cases accounted for 73% (N = 113) and MIS for 27% (N = 42). Conversion from MIS to open surgery occurred in 26% of cases. Obese patients had a nonsignificantly decreased rate of wound infection after MIS (21%) versus open surgery (28%, P < 0.645), while the incidence of other complications did not differ by surgical approach. The MIS cohort demonstrated faster return of bowel function and returned home a median of 2 days faster group than in the open surgery group (P < 0.003). From an oncologic standpoint, MIS was at least equivalent to open surgery as median number of lymph nodes extracted (20 versus 15, P < 0.073) and proportion of margin negative resections (97% versus 98%, P < 0.654) did not significantly differ between the two groups. CONCLUSIONS: Minimally invasive surgery for CRC is safe and effective in obese patients since bowel function recovers rapidly, and hospital stay is significantly reduced while the quality of oncologic care is maintained.

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BACKGROUND: Despite significant advantages to patients, less than 5% of all colorectal surgeries for cancer are performed laparoscopically. A minimally invasive colorectal cancer program was created in our Veterans' Affairs hospital with the intent of increasing access and improving quality of patient care while maintaining patient safety and oncologic standards. METHODS: Sixty consecutive laparoscopic colorectal cancer resections and 60 age-matched open resections were identified. Our prospective database was queried for demographic, clinical outcomes, and oncologic data. RESULTS: Patients undergoing laparoscopic resections experienced a shorter hospital stay and a quicker return of bowel function. Both groups had similar intraoperative blood loss and surgical times. Laparoscopic resections achieved equivalent lymph node retrieval and resection completeness compared with open resections. Laparoscopic resections resulted in fewer wounds and fewer complications requiring reoperation. CONCLUSIONS: Establishment of a minimally invasive colorectal cancer program in a Veterans Affairs Medical Center leads to increased access to laparoscopic colorectal resections and improved patient care while maintaining patient safety.

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PURPOSE: Perineural invasion (PNI) is associated with decreased survival in several malignancies, but its significance in colorectal cancer (CRC) remains to be clearly defined. We evaluated PNI as a potential prognostic indicator in CRC, focusing on its significance in node-negative patients. PATIENTS AND METHODS: We identified 269 consecutive patients who had CRC resected at our institution. Tumors were re-reviewed for PNI by a pathologist blinded to the patients' outcomes. Overall and disease-free survivals were determined using the Kaplan-Meier method, with differences determined by multivariate analysis using the Cox multiple hazards model. Results were compared using the log-rank test. RESULTS: PNI was identified in less than 0.5% of the initial pathology reports. On rereview, 22% of tumors in our series were found to be PNI positive. The 5-year disease-free survival rate was four-fold greater for patients with PNI-negative tumors versus those with PNI-positive tumors (65% v 16%, respectively; P < .0001). The 5-year overall survival rate was 72% for PNI-negative tumors versus 25% for PNI-positive tumors. On multivariate analysis, PNI was an independent prognostic factor for both cancer-specific overall and disease-free survival. In a subset analysis comparing patients with node-negative disease with patients with stage III disease, the 5-year disease-free survival rate was 56% for stage III patients versus 29% for patients with node-negative, PNI-positive tumors (P = .0002). Similar results were seen for overall survival. CONCLUSION: PNI is grossly underreported in CRC and could serve as an independent prognostic factor of outcomes in these patients. PNI should be considered when stratifying CRC patients for adjuvant treatment.

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BACKGROUND: Angiocidin, first identified as a tumor-associated thrombospondin-1 (TSP-1) receptor, is a key mediator of tumor progression. TSP-1, an extracellular protein produced by stromal cells, up-regulates gelatinases and tumor cell invasion in epithelial malignancies. The authors recently developed 2 angiocidin-inhibitory peptides that block angiocidin-TSP-1 binding. They hypothesized that angiocidin mediates increased gelatinase expression and tumor cell invasion in sarcomas through its interaction with TSP-1. METHODS: Angiocidin, TSP-1, and gelatinase expression was evaluated in low-grade and high-grade sarcoma specimens. The authors established 3 distinct cell lines from a patient with an extraskeletal osteosarcoma: EXOS-N (normal mesenchymal), EXOS-P (primary osteosarcoma), and EXOS-M (lung metastasis). Each was evaluated for angiocidin, gelatinase, and gelatinase inhibitor (tissue inhibitors of metalloproteinase) expression and for invasive capacity. Their responsiveness to TSP-1 was determined. The role of angiocidin in up-regulating gelatinase expression and invasion was studied using the authors' angiocidin-inhibitory peptides. RESULTS: Expression of angiocidin, TSP-1, and gelatinases correlated with tumor grade. Angiocidin expression, gelatinase activity, and invasiveness in the EXOS cell lines correlated with phenotype; EXOS-N cells did not express angiocidin or gelatinases and were not invasive; EXOS-M cells were 5 times more invasive than EXOS-P cells and exhibited greater angiocidin and gelatinase expression. EXOS cell gelatinase activity and invasiveness increased 4- to 5-fold in response to TSP-1. Inhibition of angiocidin with the authors' inhibitory peptides blocked TSP-1-promoted increases in gelatinase activity and tumor cell invasion. CONCLUSIONS: Angiocidin promotes gelatinase up-regulation and tumor cell invasion in sarcomas. Angiocidin-inhibitory peptides are potent inhibitors of sarcoma cell invasion in vitro, suggesting a potential therapeutic role for these peptides in the treatment of sarcomas.

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Perineural invasion (PNI) is the process of neoplastic invasion of nerves and is an under-recognized route of metastatic spread. It is emerging as an important pathologic feature of many malignancies, including those of the pancreas, colon and rectum, prostate, head and neck, biliary tract, and stomach. For many of these malignancies, PNI is a marker of poor outcome and a harbinger of decreased survival. PNI is a distinct pathologic entity that can be observed in the absence of lymphatic or vascular invasion. It can be a source of distant tumor spread well beyond the extent of any local invasion; and, for some tumors, PNI may be the sole route of metastatic spread. Despite increasing recognition of this metastatic process, there has been little progress in the understanding of molecular mechanisms behind PNI and, to date, no targeted treatment modalities aimed at this pathologic entity. The objectives of this review were to lay out a clear definition of PNI to highlight its significance in those malignancies in which it has been studied best. The authors also summarized current theories on the molecular mediators and pathogenesis of PNI and introduced current research models that are leading to advancements in the understanding of this metastatic process.

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BACKGROUND: A dedicated colorectal cancer (CRC) center was created in a Veterans Affairs Medical Center with the intent of improving quality of patient care and multidisciplinary cooperation. METHODS: Retrospective and prospective databases before and after creation of the CRC center, respectively, were created. Patients entered in each database included those requiring surgical intervention for CRC treatment. Statistical analyses included Fisher's exact, chi-square, and unpaired Student t tests as well as analysis of variance. RESULTS: The overall quality of care of CRC patients has improved as evidenced by a larger percentage of complete, margin-negative resections (P <.05) as well as an increase in the number of lymph nodes excised at surgery (P <.0001). Furthermore, a multidisciplinary approach is clearly beneficial as evidenced by the increased number of CRC patients receiving appropriate multidisciplinary therapy (P <.0001). CONCLUSIONS: A dedicated CRC center has significantly improved quality of care for CRC patients.

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BACKGROUND: Thoracic aortic aneurysmal diseases are characterized by degeneration of elastin within the aortic wall. Although proteinases, such as matrix metalloproteinase, appear to contribute to elastin degradation, little is known about the role of elastic fiber assembly in such diseases. Fibulin-5 is an extracellular protein that is expressed in the vascular basement membrane and regulates elastic fiber assembly by microfibril machinery. In this study, we examined whether thoracic aortic dissection (TAD) is associated with abnormal fibulin-5 expression. METHODS: Intraoperative aortic samples were obtained from 21 patients with proximal aortic dissection. Control aortic tissue was obtained from 11 organ donors, heart transplant recipients, and patients undergoing coronary artery bypass. An in vitro culture of vascular smooth muscle cells was obtained from 2 TAD patients and 1 control subject. To evaluate elastin expression, we stained tissue sections with Verhoeff-Van Gieson stain. Fibulin-5 messenger RNA (mRNA) expression was determined by quantitative real-time reverse-transcriptase-polymerase chain reaction. RESULTS: Aortic fibulin-5 mRNA and elastin content were decreased in TAD patients, compared with controls (P=.001 and P=.02, respectively). Decreased fibulin-5 expression strongly correlated with decreased amounts and fragmentation of elastin in aortic samples from patients with TAD (r=0.83, P < .0001 and F=20.7, P < .0001 respectively). The fibulin-5 mRNA in aortic vascular smooth muscle cells collected from TAD demonstrated a 38% decrease in expression, compared with the control. CONCLUSIONS: Patients with proximal aortic dissection exhibited significantly decreased expression of aortic fibulin-5. Decreased fibulin-5 may contribute to the pathogenesis of aortic dissection by impairing elastic fiber assembly.

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BACKGROUND: Abnormal matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) expression contributes to the development of abdominal aortic aneurysms. Recent data suggest that MMP-2 and MMP-9 may also play a role in thoracic aortic disease. We sought to determine (1) whether ascending aortic aneurysms are associated with increased MMP expression and (2) whether aortic inflammation and MMP expression differ between patients with congenital bicuspid aortic valves (BAVs) and those with trileaflet aortic valves (TAVs). MATERIALS AND METHODS: Samples of ascending aortic aneurysms were obtained from 29 patients; 14 patients had BAVs and 15 had TAVs. Control ascending aorta was obtained from 14 organ donors or heart transplant recipients. Aortic histology and immunohistochemistry were performed to evaluate elastin degradation, inflammatory changes, and MMP-2 and MMP-9 expression. Aortic levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured using ELISA. RESULTS: Aneurysms in the TAV patients exhibited marked inflammation, high CD68 expression, diminished elastin content, increased MMP-9 expression, and normal MMP-2 levels. In contrast, BAV aneurysms were characterized by a relative lack of inflammation, preservation of elastin content, normal MMP-9 levels, and elevated MMP-2 expression. TIMP-1 and TIMP-2 levels were not significantly different among the three groups. CONCLUSIONS: Ascending aortic aneurysms exhibited increased MMP expression. The pattern of MMP expression and the degree of inflammation, however, differed between aneurysms associated with BAVs and those with TAVs. Variations in the molecular mechanisms underlying different types of thoracic aortic aneurysms warrant further investigation.

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