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Find video protocols related to scientific articles indexed in Pubmed.
Increasing Disparities in the Age-Related Incidences of Colon and Rectal Cancers in the United States, 1975-2010.
JAMA Surg
PUBLISHED: 11-06-2014
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The overall incidence of colorectal cancer (CRC) has been decreasing since 1998 but there has been an apparent increase in the incidence of CRC in young adults.
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The role of systemic chemotherapy and multidisciplinary management in improving the overall survival of patients with metastatic squamous cell carcinoma of the anal canal.
Oncotarget
PUBLISHED: 10-01-2014
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Metastatic squamous cell carcinoma (SCCA) of the anal canal is a rare malignancy for which no standard treatment algorithm exists. To determine the best approach, all patients diagnosed with metastatic SCCA of the anal canal treated at a single institution were evaluated for choice of chemotherapy and treatment outcome. A retrospective study from January 2000 to May 2012 was conducted. Electronic medical records were reviewed for diagnosis of metastatic SCCA of the anal canal. All patients were treatment naïve for metastatic disease and completed all radiographic imaging at our institution. The purpose of this study was to evaluate outcomes among patients who received systemic chemotherapy and if appropriate were referred for multidisciplinary intervention (e.g., surgery, radiofrequency ablation, etc.). Seventy-seven patients fulfilled eligibility criteria. Forty-two patients (55%) received 5-fluorouracil (5-FU) + cisplatin (PF); 24 patients (31%) received carboplatin + paclitaxel (CP); 11 patients (14%) received an alternative regimen. After a median follow-up of 42 months, the median progression-free survival (PFS) for all patients was 7 months; the median overall survival (OS) was 22 months. Thirty-three patients (43%) underwent multidisciplinary management for metastatic disease resulting in a median PFS of 16 months (95% CI: 9·2 -22·8) and median OS of 53 months (95% CI: 28·3 - 77·6). Systemic chemotherapy provides durable survival for patients with surgically unresectable metastatic SCCA of the anal canal. Multidisciplinary management for select patients with metastatic disease effectively improves survival and should be considered whenever possible.
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Definitive Chemoradiation for Squamous Cell Carcinoma of the Rectum.
Am. J. Clin. Oncol.
PUBLISHED: 09-16-2014
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Squamous cell carcinoma (SCC) of the rectum is a rare disease with <80 cases reported in the English literature. We reviewed outcomes in patients with SCC of the rectum treated with definitive chemoradiation at a single institution.
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Failure of evidence-based cancer care in the United States: the association between rectal cancer treatment, cancer center volume, and geography.
Ann. Surg.
PUBLISHED: 09-10-2014
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This study examines recent adherence to recommended neoadjuvant chemoradiotherapy guidelines for patients with rectal cancer across geographic regions and institution volume and assesses trends over time.
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Adequacy of the National Quality Forum's Colon Cancer Adjuvant Chemotherapy Quality Metric: Is 4 Months Soon Enough?
Ann. Surg.
PUBLISHED: 09-01-2014
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To ascertain whether the National Quality Forum-endorsed time interval for adjuvant chemotherapy (AC) initiation optimizes patient outcome.
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Risk-Adjusted Pathologic Margin Positivity Rate As a Quality Indicator in Rectal Cancer Surgery.
J. Clin. Oncol.
PUBLISHED: 08-06-2014
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Margin positivity after rectal cancer resection is associated with poorer outcomes. We previously developed an instrument for calculating hospital risk-adjusted margin positivity rate (RAMP) that allows identification of performance-based outliers and may represent a rectal cancer surgery quality metric.
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Transforaminal versus interlaminar approaches to epidural steroid injections: a systematic review of comparative studies for lumbosacral radicular pain.
Pain Physician
PUBLISHED: 07-24-2014
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The superiority of transforaminal epidural steroid injections (TFESI) vs. interlaminar epidural steroid injections (ILESI) for treating unilateral lumbosacral radicular pain (LSRP) is unproven.
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The potential contributing effect of ketorolac and fluoxetine to a spinal epidural hematoma following a cervical interlaminar epidural steroid injection: a case report and narrative review.
Pain Physician
PUBLISHED: 05-23-2014
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Cervical interlaminar epidural steroid injections (ESIs) are commonly performed as one part of a multi-modal analgesic regimen in the management of upper extremity radicular pain. Spinal epidural hematoma (SEH) is a rare complication with a reported incidence ranging from 1.38 in 10,000 to 1 in 190,000 epidurals. Current American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians (ASIPP), and the International Spine Intervention Society (ISIS) recommendations are that non-steroidal anti-inflammatory drugs (NSAIDs) do not need to be withheld prior to epidural anesthesia. We report a case wherein intramuscular ketorolac and oral fluoxetine contributed to a SEH and tetraplegia following a cervical interlaminar (ESI). A 66 year-old woman with chronic renal insufficiency and neck pain radiating into her right upper extremity presented for evaluation and was deemed an appropriate CESI candidate. Cervical magnetic resonance imaging (MRI) revealed multi-level neuroforaminal stenosis and degenerative intervertebral discs. Utilizing a loss of resistance to saline technique, an 18-gauge Tuohy-type needle entered the epidural space at C6-7. After negative aspiration, 4 mL of saline with 80 mg of methyl-prednisolone was injected. Immediately thereafter, the patient reported significant spasmodic-type localized neck pain with no neurologic status changes. A decision was made to administer 30 mg intramuscular ketorolac as treatment for the spasmodic-type pain. En route home, she developed a sudden onset of acute tetraplegia. She was brought to the emergency department for evaluation including platelet and coagulation studies which were normal. MRI demonstrated an epidural hematoma extending from C5 to T7. She underwent a bilateral C5-T6 laminectomy with epidural hematoma evacuation and was discharged to an acute inpatient rehabilitation hospital. Chronic renal insufficiency, spinal stenosis, female gender, and increasing age have been identified as risk factors for SEH following epidural anesthesia. In the present case, it is postulated that after the spinal vascular system was penetrated, hemostasis was compromised by the combined antiplatelet effects of ketorolac, fluoxetine, fish oil, and vitamin E. Although generally well tolerated, the role of ketorolac, a potent anti-platelet medication used for pain relief in the peri-neuraxial intervention period, should be seriously scrutinized when other analgesic options are readily available. Although the increased risk of bleeding for the alternative medications are minimal, they are nevertheless well documented. Additionally, their additive impairment on hemostasis has not been well characterized. Withholding NSAIDs, fluoxetine, fish oil, and vitamin E in the peri-procedural period is relatively low risk and should be considered for all patients with multiple risk factors for SEH.
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Functional Deficits and Symptoms of Long-Term Survivors of Colorectal Cancer Treated by Multimodality Therapy Differ by Age at Diagnosis.
J. Gastrointest. Surg.
PUBLISHED: 05-21-2014
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With advances in multimodality therapy, colorectal cancer survivors are living longer. However, little is known about the quality of their long-term survival. We investigated the functional outcomes and symptoms among long-term survivors.
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Systematic review of educational interventions for ostomates.
Dis. Colon Rectum
PUBLISHED: 03-11-2014
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Stoma-related complications lead to increased hospital length of stay and readmissions. Although education of new ostomates is widely recommended, there is a lack of data regarding effective evidence-based educational interventions to prevent or decrease these complications.
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Association between travel distance and metastatic disease at diagnosis among patients with colon cancer.
J. Clin. Oncol.
PUBLISHED: 02-10-2014
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Health care access and advanced cancer stage are associated with oncologic outcomes for numerous common cancers. However, the impact of patient travel distance to health care on stage at diagnosis has not been well characterized.
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Postoperative chemotherapy use after neoadjuvant chemoradiotherapy for rectal cancer: Analysis of Surveillance, Epidemiology, and End Results-Medicare data, 1998-2007.
Cancer
PUBLISHED: 01-28-2014
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Neoadjuvant chemoradiotherapy followed by tumor resection and postoperative chemotherapy is the standard of care for patients with clinical stage II or III adenocarcinoma of the rectum. Significant variation exists in the receipt of postoperative chemotherapy after resection in this population. The objective of this study was to determine the demographic and clinicopathologic factors associated with the initiation of postoperative chemotherapy in elderly patients with rectal cancer and to identify potential targets for reducing treatment variation.
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Intraoperative radiation therapy for locally advanced primary and recurrent colorectal cancer: ten-year institutional experience.
J Surg Oncol
PUBLISHED: 01-14-2014
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We evaluated the role of intraoperative radiation therapy (IORT) during radical resection of locally advanced colorectal cancer (CRC).
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Identification of a novel, non-tetrahydroquinoline variant of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, with improved aqueous solubility.
Xenobiotica
PUBLISHED: 01-02-2014
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1. Elaborate studies of cholesteryl ester transfer protein (CETP) polymorphisms and genetic deficiency in humans suggest direct links between CETP, high-density lipoprotein cholesterol (HDL-c) levels and coronary heart diseases. The hypothesis that CETP inhibition by small molecule inhibitors raises HDL-c has been validated clinically with structurally-diverse CETP inhibitors such as torcetrapib, anacetrapib, dalcetrapib and evacetrapib. 2.?Despite promising phase 2 results with respect to HDL-c elevation, torcetrapib was discontinued in phase 3 trials due to increased mortality rates in the cardiovascular outcomes study. Emerging evidence for the adverse effects hints at off-target chemotype-specific cardiovascular toxicity, possibly related to the pressor effects of torcetrapib, since structurally diverse CETP inhibitors such as anacetrapib, evacetrapib and dalcetrapib are not associated with blood pressure increases in humans. Nonclinical follow-up studies showed that torcetrapib induces aldosterone biosynthesis and secretion in vivo and in vitro, an effect which is not observed with other CETP inhibitors in clinical development. 3.?As part of ongoing efforts to identify novel CETP inhibitors devoid of pressor effects, strategies were implemented towards the design of compounds, which lack the 1,2,3,4-tetrahydroquinoline (THQ) scaffold present in torcetrapib. In this article, we disclose results of structure-activity relationship studies for a series of novel non-THQ CETP inhibitors, which resulted in the identification of a novel isonipecotic acid derivative 10 (also referred to as PF-04445597) with vastly improved oral pharmacokinetic properties mainly as a result of improved aqueous solubility. This feature is attractive in that, it bypasses significant investments needed to develop compatible solubilizing formulation(s) for oral drug delivery of highly lipophilic and poorly soluble compounds; attributes, which are usually associated with small molecule CETP inhibitors. PF-04445597 was also devoid of aldosterone secretion in human H295R adrenal carcinoma cells.
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Stakeholder engagement for comparative effectiveness research in cancer care: experience of the DEcIDE Cancer Consortium.
J Comp Eff Res
PUBLISHED: 11-19-2013
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Stakeholder input is a critical component of comparative effectiveness research. To ensure that the research activities of the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network, supported by the Agency for Healthcare Research and Quality, translate into the greatest impact for everyday practice and policy-making in cancer, we were tasked with soliciting stakeholder input regarding priority areas in cancer-related comparative effectiveness research for the DEcIDE Cancer Consortium. Given the increasing emphasis on stakeholder engagement in research, many investigators are facing a similar task, yet there is limited literature to guide such efforts, particularly in cancer care. To help fill this gap, we present our approach to operationalizing stakeholder engagement and discuss it in the context of other recent developments in the area. We describe challenges encountered in convening stakeholders from multiple vantage points to prioritize topics and strategies used to mitigate these barriers. We offer several recommendations regarding how to best solicit stakeholder input to inform comparative effectiveness research in cancer care. These recommendations can inform other initiatives currently facing the challenges of engaging stakeholders in priority setting for cancer.
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Phantom Limb Pain: A Systematic Neuroanatomical-Based Review of Pharmacologic Treatment.
Pain Med
PUBLISHED: 11-13-2013
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Review the current evidence-based pharmacotherapy for phantom limb pain (PLP) in the context of the current understanding of the pathophysiology of this condition.
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Impact of Ileostomy-Related Complications on the Multidisciplinary Treatment of Rectal Cancer.
Ann. Surg. Oncol.
PUBLISHED: 10-02-2013
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Radical resection is the primary treatment for rectal cancer. When anastomosis is possible, a temporary ileostomy is used to decrease morbidity from a poorly healed anastomosis. However, ileostomies are associated with complications, dehydration, and need for a second operation. We sought to evaluate the impact of ileostomy-related complications on the treatment of rectal cancer.
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Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 08-07-2013
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The goal of this phase 1 trial was to determine the maximum tolerated dose (MTD) of concurrent capecitabine, bevacizumab, and erlotinib with preoperative radiation therapy for rectal cancer.
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Improving the AJCC/TNM staging for adenocarcinomas of the appendix: the prognostic impact of histological grade.
Ann. Surg.
PUBLISHED: 08-02-2013
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Though histological grade is known to have a major prognostic impact in metastatic mucinous appendiceal adenocarcinomas, the prognostic impact of grade in localized disease, and the validity of the American Joint Committee on Cancer AJCC Staging Manual 7th editions decision to combine moderately and poorly differentiated mucinous adenocarcinomas into a single mucinous high-grade category, is not known.
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Long-term Intrathecal Baclofen: Outcomes after Greater than 10 Years of Treatment.
PM R
PUBLISHED: 07-19-2013
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No study has reported outcomes of intrathecal baclofen (ITB) therapy for spasticity in a cohort of patients who have received this treatment for least 10 years. This study explored long term outcomes of ITB for spasticity management.
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A novel risk-adjusted nomogram for rectal cancer surgery outcomes.
JAMA Surg
PUBLISHED: 06-28-2013
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The circumferential resection margin is the primary determinant of local recurrence and a major factor in survival in rectal cancer. Neither chemotherapy nor chemoradiation compensates for a margin positive for cancer.
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Acute pain control challenges with buprenorphine/naloxone therapy in a patient with compartment syndrome secondary to McArdles disease: a case report and review.
Pain Med
PUBLISHED: 05-03-2013
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We report the first case of non-iatrogentic exertional rhabdomyolysis leading to acute compartment syndrome in a patient with McArdles disease. We describe considerations of concurrent buprenorphine/naloxone therapy during episodes of severe acute pain.
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Long-term results of weekly/daily cisplatin-based chemoradiation for locally advanced squamous cell carcinoma of the anal canal.
Cancer
PUBLISHED: 05-02-2013
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Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based chemoradiation was evaluated for patients with locally advanced squamous cell carcinoma (SCC) of the anal canal treated at a single institution over a 20-year period.
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An individualized conditional survival calculator for patients with rectal cancer.
Dis. Colon Rectum
PUBLISHED: 04-12-2013
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Conditional survival estimates account for time survived since diagnosis to provide prognostic information for long-term cancer survivors. For rectal cancer, stage-related treatment (eg, neoadjuvant radiotherapy) affects pathologic stage and therefore stage-associated survival estimates.
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Comprehensive geriatric assessment of risk factors associated with adverse outcomes and resource utilization in cancer patients undergoing abdominal surgery.
J Surg Oncol
PUBLISHED: 04-01-2013
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The purpose of this prospective study was to identify risk factors for adverse outcomes or increased resource utilization after abdominal cancer surgery in geriatric patients.
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Quantified pathologic response assessed as residual tumor burden is a predictor of recurrence-free survival in patients with rectal cancer who undergo resection after neoadjuvant chemoradiotherapy.
Cancer
PUBLISHED: 03-29-2013
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The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer.
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Race does not impact pancreatic cancer treatment and survival in an equal access federal health care system.
Ann. Surg. Oncol.
PUBLISHED: 03-27-2013
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Black patients with pancreatic adenocarcinoma (PDAC) have been reported to undergo surgical resection less frequently and to have a shorter overall survival duration than white patients. We sought to determine whether disparities in clinical management and overall survival exist between black and white patients with PDAC treated in an equal access health care system.
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Assessing the utility of cancer-registry-processed cause of death in calculating cancer-specific survival.
Cancer
PUBLISHED: 02-13-2013
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Cancer registries use algorithms to process cause of death (COD) data from death certificates, but uncertainties remain regarding the accuracy and utility of those data in calculating cancer-specific survival (CSS). Because it is impractical to reconfirm the COD through meticulous review of the primary medical records, the observed cancer deaths could be compared with the number of attributed deaths, as estimated by using a relative survival (RS) approach, to determine utility in CSS estimation.
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The Cost-Effectiveness of Neoadjuvant Chemoradiation is Superior to a Surgery-First Approach in the Treatment of Pancreatic Head Adenocarcinoma.
Ann. Surg. Oncol.
PUBLISHED: 02-10-2013
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In treating pancreatic cancer, there is no clearly defined optimal sequence of chemotherapy, radiation therapy and surgery. Therefore, cost-effectiveness should be considered. The objective of this study was to compare cost and outcomes between a surgery-first approach versus neoadjuvant chemoradiation followed by surgery for resectable pancreatic head cancer.
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Metformin use and improved response to therapy in rectal cancer.
Cancer Med
PUBLISHED: 02-03-2013
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Locally advanced rectal cancer is commonly treated with chemoradiation prior to total mesorectal excision (TME). Studies suggest that metformin may be an effective chemopreventive agent in this disease as well as a possible adjunct to current therapy. In this study, we examined the effect of metformin use on pathologic complete response (pCR) rates and outcomes in rectal cancer. The charts of 482 patients with locally advanced rectal adenocarcinoma treated from 1996 to 2009 with chemoradiation and TME were reviewed. Median radiation dose was 50.4 Gy (range 19.8-63). Nearly, all patients were treated with concurrent 5-fluorouracil-based chemotherapy (98%) followed by adjuvant chemotherapy (81.3%). Patients were categorized as nondiabetic (422), diabetic not taking metformin (40), or diabetic taking metformin (20). No significant differences between groups were found in clinical tumor classification, nodal classification, tumor distance from the anal verge or circumferential extent, pretreatment carcinoembryonic antigen level, or pathologic differentiation. pCR rates were 16.6% for nondiabetics, 7.5% for diabetics not using metformin, and 35% for diabetics taking metformin, with metformin users having significantly higher pCR rates than either nondiabetics (P = 0.03) or diabetics not using metformin (P = 0.007). Metformin use was significantly associated with pCR rate on univariate (P = 0.05) and multivariate (P = 0.01) analyses. Furthermore, patients taking metformin had significantly increased disease-free (P = 0.013) and overall survival (P = 0.008) compared with other diabetic patients. Metformin use is associated with significantly higher pCR rates as well as improved survival. These promising data warrant further prospective study.
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Comparative analysis of lymph node metastases in patients with ypT0-2 rectal cancers after neoadjuvant chemoradiotherapy.
Dis. Colon Rectum
PUBLISHED: 01-11-2013
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Neoadjuvant chemoradiotherapy before total mesorectal excision for rectal cancer is associated with improved local tumor control, primary tumor regression, and pathologic downstaging. Therefore, tumor response in the bowel wall has been proposed to be used to identify patients for organ-preserving strategies.
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The role of minimally invasive surgery and outcomes in colorectal cancer.
Perm J
PUBLISHED: 11-08-2011
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For some time now, there has been significant interest in understanding and defining the role of minimally invasive surgery in colorectal cancer. Laparoscopic surgery has been shown to have similar or better outcomes compared with open surgery. Recently, prospective randomized trials have demonstrated oncologic outcomes of laparoscopic colon surgery equivalent to those for open surgery. However, the technical challenges of performing laparoscopic resection of rectal cancers and the uncertainty of the oncologic quality of the surgical resection have hindered the growth of minimally invasive rectal surgery. Robotic rectal surgery has recently emerged as an attractive alternative to laparoscopic surgery because it allows for superior visualization within a narrow pelvic field and more precise dissection. Studies of robotic rectal resection have suggested similar or potentially improved short-term oncologic outcomes when compared with laparoscopic rectal resection. Ongoing randomized studies will provide additional insight into the role of laparoscopic and minimally invasive robotic surgery for rectal cancer.
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A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease.
Ann. Surg. Oncol.
PUBLISHED: 07-15-2011
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Because of its rarity, adenocarcinoma of the small intestine is frequently compared to adenocarcinoma of the colon, although the validity of this comparison is not known.
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Is the 1-cm rule of distal bowel resection margin in rectal cancer based on clinical evidence? A systematic review.
Ann. Surg. Oncol.
PUBLISHED: 06-07-2011
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Distal intramural spread is present within 1 cm from visible tumor in a substantial proportion of patients. Therefore, ? 1 cm of distal bowel clearance is recommended as minimally acceptable. However, clinical results are contradictory in answering the question of whether this rule is valid. The aim of this review was to evaluate whether in patients undergoing anterior resection, a distal bowel gross margin of <1 cm jeopardizes oncologic safety.
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Species independence in brain tissue binding using brain homogenates.
Drug Metab. Dispos.
PUBLISHED: 04-07-2011
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Species independence of brain tissue binding was assessed with a large number of structurally diverse compounds using equilibrium dialysis with brain homogenates of seven species and strains (Wistar Han rat, Sprague-Dawley rat, CD-1 mouse, Hartley guinea pig, beagle dog, cynomolgus monkey, and human). The results showed that the fractions unbound of the seven species and strains were strongly correlated with correlation coefficients ranging from 0.93 to 0.99. The cross-species/strain correlations were not significantly different from the interassay correlation with the same species. The linear correlation between Wistar Han and other species had a slope close to 1 and an intercept near 0. Based on orthogonal statistical analysis, no correction is needed for extrapolation of fraction unbound from Wistar Han rat to the other species or strains. Hence, brain tissue binding of Wistar Han rat can be used to obtain binding of other species and strains in drug discovery.
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Gastric adenocarcinoma in young patients: a population-based appraisal.
Ann. Surg. Oncol.
PUBLISHED: 03-22-2011
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Although international studies of young gastric cancer patients have mainly reported favorable survival outcomes compared with older patients, US-based experiences have shown a wider spectrum of outcomes. We examined the impact of young age (under 45 years) on the presentation and survival outcomes of gastric adenocarcinoma.
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Extraction of tacit knowledge from large ADME data sets via pairwise analysis.
Bioorg. Med. Chem.
PUBLISHED: 03-10-2011
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Pharmaceutical companies routinely collect data across multiple projects for common ADME endpoints. Although at the time of collection the data is intended for use in decision making within a specific project, knowledge can be gained by data mining the entire cross-project data set for patterns of structure-activity relationships (SAR) that may be applied to any project. One such data mining method is pairwise analysis. This method has the advantage of being able to identify small structural changes that lead to significant changes in activity. In this paper, we describe the process for full pairwise analysis of our high-throughput ADME assays routinely used for compound discovery efforts at Pfizer (microsomal clearance, passive membrane permeability, P-gp efflux, and lipophilicity). We also describe multiple strategies for the application of these transforms in a prospective manner during compound design. Finally, a detailed analysis of the activity patterns in pairs of compounds that share the same molecular transformation reveals multiple types of transforms from an SAR perspective. These include bioisosteres, additives, multiplicatives, and a type we call switches as they act to either turn on or turn off an activity.
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Number of lymph nodes examined and prognosis among pathologically lymph node-negative patients after preoperative chemoradiation therapy for rectal adenocarcinoma.
Cancer
PUBLISHED: 02-15-2011
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Preoperative chemoradiation for rectal cancer can decrease the number of evaluable lymph nodes. Hence, the prognostic role of lymph node evaluation in patients with rectal cancer who receive preoperative chemoradiation is unclear. The authors of this report evaluated the prognostic impact of the number of lymph nodes examined in patients with rectal cancer who had negative lymph nodes based on the pathologic extent of disease (ypN0) after they received preoperative chemoradiation.
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Multidisciplinary approach to recurrent/unresectable rectal cancer: how to prepare for the extent of resection.
Surg. Oncol. Clin. N. Am.
PUBLISHED: 10-02-2010
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Local recurrence from rectal cancer is a complex problem that should be managed by a multidisciplinary team. Pelvic re-irradiation and intraoperative radiation should be considered in the management of these patients. Long-term survival can be achieved in patients who undergo radical surgery with negative margins of resections. The morbidity of these procedures is high and at times may compromise quality of life. Palliative surgical procedures can be considered; however, in some cases, palliative resections may not be better than nonsurgical palliation.
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Identification and characterization of dual inhibitors for phospholipid transfer protein and microsomal triglyceride transfer protein.
J. Pharmacol. Exp. Ther.
PUBLISHED: 08-30-2010
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Phospholipid transfer protein (PLTP) plays an important role in atherogenesis and lipoprotein metabolism. PLTP exerts its functions intracellularly and extracellularly. Both PLTP and microsomal triglyceride transfer protein (MTP) have been shown to regulate the secretion of apolipoprotein B (apoB) in hepatocytes. We have previously reported the characterization of inhibitors that selectively inhibit PLTP activity and reduce apoB secretion in hepatocytes. In the present study, we identified more compounds that inhibit both PLTP and MTP activity to various extents. These dual inhibitors are structurally different from the PLTP-selective inhibitors. In human hepatoma cell lines, dual inhibitors seem to be more effective in reducing apoB secretion than selective PLTP or MTP inhibitors. Furthermore, the dual inhibitors markedly reduced triglyceride secretion from hepatocytes. In the absence of PLTP, the dual inhibitors can further reduce apoB secretion, whereas selective PLTP inhibitors had no effect. We conclude that MTP and PLTP may work coordinately in the process of hepatic apoB assembly and secretion. To avoid liver toxicity mediated by MTP inhibition, selective PLTP inhibitors should be pursued.
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Prognostic value of lymph node evaluation in small bowel adenocarcinoma: analysis of the surveillance, epidemiology, and end results database.
Cancer
PUBLISHED: 08-16-2010
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The presence of distant metastases and the completeness of resection are important prognostic factors in patients with small bowel adenocarcinoma (SBA); however, the influence of lymph node metastasis on patient outcome has not been well characterized. The objective of the current study was to evaluate the impact of the number of positive and negative lymph nodes on survival after curative resection.
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Long-term survival and recurrence outcomes following surgery for distal rectal cancer.
Ann. Surg. Oncol.
PUBLISHED: 06-15-2010
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Treatment of distal rectal cancer remains clinically challenging and includes proctectomy and coloanal anastomosis (CAA) or abdominoperineal resection (APR). The purpose of this study is to evaluate operative and pathologic factors associated with long-term survival and local recurrence outcomes in patients treated for distal rectal cancer.
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Renal clearance in drug discovery and development: molecular descriptors, drug transporters and disease state.
Expert Opin Drug Metab Toxicol
PUBLISHED: 05-04-2010
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Kidney plays a key role in the elimination of xenobiotics and metabolic products from the body, where renal clearance is determined by glomerular filtration, tubular secretion and reabsorption processes. The proximal tubule of the nephron is equipped with multi-specificity uptake and efflux transporters for the secretion of a broad range of xenobiotics, while the compound physicochemical space drives the tubular reabsorption. Due to involvement of transporters, renal clearance is possibly associated with renal drug-drug interactions (DDIs) in clinical situations. Nevertheless, renal insufficiency in diseased population is associated with altered transporter activity and evidently affects the pharmacokinetics of both renally and non-renally cleared compounds. Thus, early information on renal clearance is critical for successful development of compounds in certain chemical space.
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Conditional survival estimates improve over 5 years for melanoma survivors with node-positive disease.
Ann. Surg. Oncol.
PUBLISHED: 04-06-2010
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Conditional survival estimates provide useful prognostic information for cancer survivors. The objective of this study was to determine conditional survival estimates for melanoma patients with substages of stage III disease.
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Prognostic value of quality of life and pain in patients with locally recurrent rectal cancer.
Ann. Surg. Oncol.
PUBLISHED: 03-23-2010
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Care of patients with locally recurrent rectal cancer (LRRC) requires careful patient selection. While curative resection offers survival benefits, significant trade-offs exist for the patient. Knowledge of patient-reported outcomes will help inform treatment decisions.
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Assessment of in silico models for fraction of unbound drug in human liver microsomes.
Expert Opin Drug Metab Toxicol
PUBLISHED: 03-18-2010
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Fraction of unbound drug in human liver microsome (fu(mic)) incubation media is an important parameter for accurate assessment of hepatic intrinsic clearance and drug-drug interactions. In recent years, there have been considerable advances in understanding structure-microsomal binding relationships.
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Conditional survival estimates improve over time for patients with advanced melanoma: results from a population-based analysis.
Cancer
PUBLISHED: 02-27-2010
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Conditional survival (CS) has emerged as a clinically relevant measure of prognosis for cancer survivors. The objective of this analysis was to provide melanoma-specific CS estimates to help clinicians promote more informed patient decision making.
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Population-based study of contralateral prophylactic mastectomy and survival outcomes of breast cancer patients.
J. Natl. Cancer Inst.
PUBLISHED: 02-25-2010
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Despite increased demand for contralateral prophylactic mastectomy (CPM), the survival benefit of this procedure remains uncertain.
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Surgical strategies for synchronous colorectal liver metastases in 156 consecutive patients: classic, combined or reverse strategy?
J. Am. Coll. Surg.
PUBLISHED: 02-06-2010
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An increasing number of patients with synchronous colorectal liver metastases (CLM) are candidates for resection. The optimal treatment sequence in these patients has not been defined.
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Midsacral amputation for en bloc resection of chordoma.
Neurosurgery
PUBLISHED: 02-04-2010
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En bloc resection, with adequate surgical margins, of primary malignant bone tumors of the sacrum is associated with long term disease control and potential cure. Resection of sacral tumors is difficult due to the proximity of neurovascular and visceral structures, and complete, or even partial, sacrectomy often results in functional loss for the patient.
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Primary peritoneal cancer after bilateral salpingo-oophorectomy in two patients with Lynch syndrome.
Obstet Gynecol
PUBLISHED: 01-23-2010
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Women with Lynch syndrome or hereditary nonpolyposis colorectal carcinoma (HNPCC) have a 40-60% lifetime risk of endometrial cancer and a 7-12% lifetime risk of ovarian cancer. Risk-reducing surgery, including hysterectomy and bilateral salpingo-oophorectomy (BSO), is currently recommended once child bearing is complete. We describe two cases of primary peritoneal cancer after BSO in women with Lynch syndrome or HNPCC.
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Physicochemical space for optimum oral bioavailability: contribution of human intestinal absorption and first-pass elimination.
J. Med. Chem.
PUBLISHED: 01-15-2010
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Oral bioavailability (F) is a product of fraction absorbed (Fa), fraction escaping gut-wall elimination (Fg), and fraction escaping hepatic elimination (Fh). In this study, using a database comprised of Fa, Fg, Fh, and F values for 309 drugs in humans, an analysis of the interrelation of physicochemical properties and the individual parameters was carried out in order to define the physicochemical space for optimum human oral bioavailability. Trend analysis clearly indicated molecular weight (MW), ionization state, lipophilicity, polar descriptors, and free rotatable bonds (RB) influence bioavailability. These trends were due to a combination of effects of the properties on Fa and first-pass elimination (Fg and Fh). Higher MW significantly impacted Fa, while Fg and Fh decreased with increasing lipophilicity. Parabolic trends were observed for bioavailability with polar descriptors. Interestingly, RB has a negative effect on all three parameters, leading to its pronounced effect on bioavailability. In conclusion, physicochemical properties influence bioavailability with typically opposing effects on Fa and first-pass elimination. This analysis may provide a rational judgment on the physicochemical space to optimize oral bioavailability.
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Blood-brain barrier disruption in humans is independently associated with increased matrix metalloproteinase-9.
Stroke
PUBLISHED: 12-24-2009
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Matrix metalloproteinases (MMP) may play a role in blood-brain barrier (BBB) disruption after ischemic stroke. We hypothesized that plasma concentrations of MMP-9 are associated with a marker of BBB disruption in patients evaluated for acute stroke.
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Pharmacologic inhibition of phospholipid transfer protein activity reduces apolipoprotein-B secretion from hepatocytes.
J. Pharmacol. Exp. Ther.
PUBLISHED: 11-20-2009
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Phospholipid transfer protein (PLTP) plays an important role in atherogenesis, and its function goes well beyond that of transferring phospholipids between lipoprotein particles. Previous studies showed that genetic deficiency of PLTP in mice causes a substantially impaired hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins. To understand whether the impaired apoB secretion is a direct result from lack of PLTP activity, in this study, we further investigated the function of PLTP in apoB secretion by using PLTP inhibitors. We identified a series of compounds containing a 3-benzazepine core structure that inhibit PLTP activity. Compound A, the most potent inhibitor, was characterized further and had little cross-reactivity with microsomal triglyceride transfer protein. Compound A reduced apoB secretion in human hepatoma cell lines and mouse primary hepatocytes. Furthermore, we confirmed that the reduction of apoB secretion mediated by compound A is PLTP-dependent, because the PLTP inhibitor had no effect on apoB secretion from PLTP-deficient hepatocytes. These studies provided evidence that PLTP activity regulates apoB secretion and pharmacologic inhibition of PLTP may be a new therapy for dyslipidemia by reducing apoB secretion.
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Practical application of a calculator for conditional survival in colon cancer.
J. Clin. Oncol.
PUBLISHED: 10-05-2009
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Conditional survival (CS) estimates provide important prognostic information for clinicians and patients who have survived a period after diagnosis. In this study we performed a contemporary evaluation of conditional survival among colon cancer patients and created a browser-based tool for real-time determination of conditional survival expectancies.
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Lymph node status after neoadjuvant radiotherapy for rectal cancer is a biologic predictor of outcome.
Cancer
PUBLISHED: 08-13-2009
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Lymph node (LN) status after surgery for rectal cancer is affected by preoperative radiotherapy. The purpose of this study was to perform a population-based evaluation of the impact of pathologic LN status (ypN) after neoadjuvant radiotherapy on survival.
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A twenty-year experience with adenocarcinoma of the anal canal.
Dis. Colon Rectum
PUBLISHED: 07-21-2009
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Adenocarcinoma of the anal canal is a rare malignancy with limited data regarding treatment and outcomes. The purpose of this study is to evaluate disease control and survival outcomes in patients with adenocarcinoma of the anal canal.
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Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy.
J. Clin. Oncol.
PUBLISHED: 05-26-2009
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Fluorouracil/leucovorin as the sole therapy for metastatic colorectal cancer (CRC) provides an overall survival of 8 to 12 months. With an increase in surgical resections of metastatic disease and development of new chemotherapies, indirect evidence suggests that outcomes for patients are improving in the general population, although the incremental gain has not yet been quantified.
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Hyperfractionated accelerated radiotherapy for rectal cancer in patients with prior pelvic irradiation.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 02-04-2009
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To retrospectively determine rates of toxicity, freedom from local progression, and survival in rectal cancer patients treated with reirradiation.
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Management and outcomes of anorectal infection in the cancer patient.
Ann. Surg. Oncol.
PUBLISHED: 01-21-2009
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The objective of this retrospective cohort study is to examine the presentation and outcomes for a contemporary series of cancer patients with anorectal infection. In addition, we seek to identify factors which are associated with surgical intervention.
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Phase II trial of neoadjuvant bevacizumab, capecitabine, and radiotherapy for locally advanced rectal cancer.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-21-2009
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We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer.
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Sacral insufficiency fractures after preoperative chemoradiation for rectal cancer: incidence, risk factors, and clinical course.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 01-13-2009
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Sacral insufficiency (SI) fractures can occur as a late side effect of pelvic radiation therapy. Our goal was to determine the incidence, risk factors, and clinical course of SI fractures in patients treated with preoperative chemoradiation for rectal cancer.
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Association between adherence to National Comprehensive Cancer Network treatment guidelines and improved survival in patients with colon cancer.
Cancer
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The objective of the current study was to examine the impact of adherence to guidelines on stage-specific survival outcomes in patients with stage III and high-risk stage II colon cancer. The National Comprehensive Cancer Network (NCCN) has established working, expert consensus, and evidence-based guidelines for organ-specific cancer care, including care of patients with colon cancer.
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Intraoperative radiotherapy in colorectal cancer: systematic review and meta-analysis of techniques, long-term outcomes, and complications.
Surg Oncol
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The precise contribution of IORT to the management of locally advanced and recurrent colorectal cancer (CRC) remains uncertain. We performed a systematic review and meta-analysis to assess the value of IORT in this setting.
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Neuroendocrine tumors of the colon and rectum: prognostic relevance and comparative performance of current staging systems.
Ann. Surg. Oncol.
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With increasing interest in neuroendocrine tumors (NETs), three staging systems for NETs of the colon and rectum have been published. Their prognostic relevance has not been examined and compared in an independent clinical database.
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Digital subtraction angiography does not reliably prevent paraplegia associated with lumbar transforaminal epidural steroid injection.
Pain Physician
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Digital subtraction angiography (DSA) has been touted as a radiologic adjunct to interventional neuraxial procedures where it is imperative to identify vascular compromise during the injection. Transforaminal epidural steroid injections (TFESI) are commonly performed interventions for treating acute and chronic radicular spine pain. We present a case of instantaneous and irreversible paraplegia following lumbar TFESI wherein a local anesthetic test dose, as well as DSA, were used as adjuncts to fluoroscopy. An 80-year-old man with severe lumbar spinal stenosis and chronic L5 radiculopathic pain was evaluated at a university pain management center seeking symptomatic pain relief. Two prior lumbar interlaminar epidural steroid injections (LESI) provided only transient pain relief, and a decision was made to perform right-sided L5-S1 TFESI. A 5-inch, 22-gauge Quincke-type spinal needle with a curved tip was used. Foraminal placement of the needle tip was confirmed with anteroposterior, oblique, and lateral views on fluoroscopy. Aspiration did not reveal any blood or cerebrospinal fluid. Digital subtraction angiography was performed twice to confirm the absence of intravascular contrast medium spread. Subsequently, a 0.5 mL of 1% lidocaine test dose was performed without any changes in neurological status. Two minutes later, a mixture of one mL of 1% lidocaine with 80 mg triamcinolone acetonide was injected. Immediately following the completion of the injection, the patient reported extreme bilateral lower extremity pain. He became diaphoretic, followed by marked weakness in his bilateral lower extremities and numbness up to his lower abdomen. The patient was transferred to the emergency department for evaluation. Magnetic resonance imaging (MRI) of the lumbar and thoracic spine was completed 5 hours postinjection. It showed a small high T2 signal focus in the thoracic spinal cord at the T7-T8 level. The patient was admitted to the critical care unit for neurological observation and treatment with intravenous methylprednisolone. Follow-up MRI revealed a hyper-intense T2 and short-tau inversion recovery signal in the central portion of the spinal cord beginning at the level of the T6 superior endplate and extending caudally to the T9-T10 level with accompanying development of mild spinal cord expansion. The patient was diagnosed with paraplegia from acute spinal cord infarction. At discharge to an acute inpatient rehabilitation program, the patient had persistent bilateral lower extremity paralysis, and incontinence of bowel and bladder functions. In the present patient, DSA performed twice and an anesthetic test dose did not prevent a catastrophic spinal cord infarction and resulting paraplegia. DSA use is clearly not foolproof and may not be sufficient to identify potentially life-or-limb threatening consequences of lumbar TFESI. We believe that this report should open further discussion regarding adding the possibility of these catastrophic events in the informed consent process for lumbar TFESIs, as it has for cervical TFESI. Utilizing blunt needles or larger bevel needles in place of sharp, cutting needles may minimize the chances of this event occurring. Considering eliminating use of particulate steroids for TFESI should be evaluated, although the use of nonparticulate agents remains controversial due to the perception that their respective duration of action is less than that of particulate steroids.
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Multimodality salvage of recurrent disease after local excision for rectal cancer.
Dis. Colon Rectum
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Local excision, alone or in combination with chemoradiation, is increasingly considered for rectal cancer. Higher risks of disease recurrence have been demonstrated after local excision.
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Morbidity of staged proctectomy after hepatectomy for colorectal cancer: a matched case-control analysis.
Ann. Surg. Oncol.
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Proctectomy after hepatectomy, or the reverse approach, is an alternative to traditional sequencing for advanced liver metastases with asymptomatic colorectal primary tumors. We sought to evaluate the surgical morbidity of proctectomy for colorectal cancer after previous liver surgery.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.