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Background: Indocyanine green angiography (ICGA) reduces ischemic complications by assessing mastectomy flap perfusion intraoperatively. However, outcomes of ICGA can be surgeon-dependent due to its relative novelty. We aimed to determine whether patient outcomes improved with the adoption of ICGA over time., Methods: We conducted a single-institution retrospective study of mastectomy patients between March 2012 (date of ICGA introduction) and October 2016. We included patients who underwent immediate expander-based reconstruction with intraoperative ICGA, followed by second-stage permanent implant placement. Patients were chronologically sorted into 3 groups, of 45 patients each, based on the date of ICGA. Complications and reconstruction wait times (time between initial expander placement and subsequent final reconstruction) amongst the 3 groups were evaluated. Using the Cochran-Armitage test for trend, we tested the change in median adjusted expander fill volumes (expander fill volume in milliliter per gram of breast removed) over time., Results: We identified 135 patients. Rates of ischemic complications significantly decreased (Group 1, 36%; Group 2, 22%; Group 3, 11%; p = 0.03), despite significantly increasing median adjusted expander fill volumes (Group 1, 0.46 mL/g; Group 2, 0.63 mL/g; Group 3, 0.76 mL/g; p = 0.003) over time. The rates of unexpected returns to the operating room across the 3 groups were not significantly different. The median reconstruction wait time was significantly reduced in the later groups (Group 1, 146 days; Group 2, 122 days; Group 3, 87 days; p = 0.01)., Conclusions: Outcomes for mastectomy with immediate expander-based reconstruction were found to improve with increasing case volume after implementation of ICGA., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: The 21-gene recurrence score (RS) (Oncotype Dx, Genomic Health, Redwood City Ca) has not been validated in an older cohort with estrogen receptor (ER)-positive breast cancer. The objective of this study was to evaluate RS validity in a group of older women with ER-positive breast cancer., Methods: Utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database with available RS, we evaluated women with ER-positive breast cancer aged 18-69 and those 70 years of age and older from 2004 to 2014. We utilized multivariable logistic regression models to evaluate factors associated with RS testing as well as a high-risk categorization for those who underwent testing. Survival was analyzed using Kaplan Meier curves and Cox proportional hazard models., Results: We identified 363,876 women aged 18-69 years and 147,107 women aged 70 years and older. A smaller proportion of patients in the older group (8%) underwent RS testing than in the younger group (18%). Of the patients who underwent testing, distribution of RS was similar between groups. High-risk categorization independently predicted a higher likelihood of death for older patients (hazard ratio 1.47, 95% confidence interval 1.15-1.90). Among patients with high-risk RS, chemotherapy was associated with a decreased risk of death in the younger group, but not in the older group., Conclusion: Older women are less likely to receive RS testing, but when tested, older patients have a similar distribution of RS as compared to younger patients. While high-risk categorization in the older cohort was prognostic, chemotherapy was not associated with improved survival., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Nodal positivity is a predictor of poor survival following resection for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the impact of surgical resection on survival in patients with lymph node (LN) positive ICC., Methods: An augmented version of the Surveillance, Epidemiology, and End Results program database was utilized to identify patients with LN-positive ICC without distant metastases from 2000 to 2014. Patients were stratified by treatment: chemotherapy alone or surgical resection with/without chemotherapy. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models., Results: 169 patients who underwent treatment for LN-positive ICC were identified. 88% underwent surgical resection and 12% underwent chemotherapy alone. The median survival for patients who underwent surgical resection was not different from patients treated with chemotherapy alone (19 months 95% Confidence Interval (CI) 17-33 versus 20 months CI 10-27, p = 0.323). A cox-proportional hazard ratio model demonstrated that black race was associated with worse survival (p < 0.05), while surgical resection was not independently associated with survival., Conclusion: Surgical resection for patients with LN-positive ICC may not improve survival compared to chemotherapy alone. Pathologic LN evaluation should be performed prior to surgical resection, to improve patient selection and ensure receipt of optimal therapy., (Copyright © 2018. Published by Elsevier Ltd.)

Background: In KEYNOTE-010, pembrolizumab versus docetaxel improved overall survival (OS) in patients with programmed death-1 protein (PD)-L1-positive advanced non-small-cell lung cancer (NSCLC). A prespecified exploratory analysis compared outcomes in patients based on PD-L1 expression in archival versus newly collected tumor samples using recently updated survival data., Patients and Methods: PD-L1 was assessed centrally by immunohistochemistry (22C3 antibody) in archival or newly collected tumor samples. Patients received pembrolizumab 2 or 10 mg/kg Q3W or docetaxel 75 mg/m2 Q3W for 24 months or until progression/intolerable toxicity/other reason. Response was assessed by RECIST v1.1 every 9 weeks, survival every 2 months. Primary end points were OS and progression-free survival (PFS) in tumor proportion score (TPS) ≥50% and ≥1%; pembrolizumab doses were pooled in this analysis., Results: At date cut-off of 24 March 2017, median follow-up was 31 months (range 23-41) representing 18 additional months of follow-up from the primary analysis. Pembrolizumab versus docetaxel continued to improve OS in patients with previously treated, PD-L1-expressing advanced NSCLC; hazard ratio (HR) was 0.66 [95% confidence interval (CI): 0.57, 0.77]. Of 1033 patients analyzed, 455(44%) were enrolled based on archival samples and 578 (56%) on newly collected tumor samples. Approximately 40% of archival samples and 45% of newly collected tumor samples were PD-L1 TPS ≥50%. For TPS ≥50%, the OS HRs were 0.64 (95% CI: 0.45, 0.91) and 0.40 (95% CI: 0.28, 0.56) for archival and newly collected samples, respectively. In patients with TPS ≥1%, OS HRs were 0.74 (95% CI: 0.59, 0.93) and 0.59 (95% CI: 0.48, 0.73) for archival and newly collected samples, respectively. In TPS ≥50%, PFS HRs were similar across archival [0.63 (95% CI: 0.45, 0.89)] and newly collected samples [0.53 (95% CI: 0.38, 0.72)]. In patients with TPS ≥1%, PFS HRs were similar across archival [0.82 (95% CI: 0.66, 1.02)] and newly collected samples [0.83 (95% CI: 0.68, 1.02)]., Conclusion: Pembrolizumab continued to improve OS over docetaxel in intention to treat population and in subsets of patients with newly collected and archival samples., Trial Registration: ClinicalTrials.gov: NCT01905657., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and objectives: The incidence of incisional hernia (IH) after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is largely unknown. Methods: We conducted a retrospective study to identify patients who underwent CRS/HIPEC from 2001 to 2016. Patients were followed postoperatively for a minimum of two years. The primary outcome was the occurrence of an IH identified either on CT scan or physical examination. Univariate and multivariable logistic regression models were used to test associations with IH. Results: We identified 155 patients who underwent CRS/HIPEC; 26 patients (17%) were diagnosed with an IH at a median time of 245 days (Interquartile range [IQR] 175 - 331 days). On multivariable analysis, older age [50-64 vs. 18-49 years: hazard ratio (HR) = 0.08; 95% confidence interval (CI), 0.01 to 0.64)], female gender (HR  =  0.09; 95% CI, 0.01 to 0.75), and increased BMI (>30 vs. <25; HR  =  0.03; 95% CI, 0.01 to 0.37) were significant independent predictors of IH. Conclusions: The incidence of IH in this high-risk patient population treated with CRS/HIPEC is similar to that after other abdominal cancer operations. Nevertheless, the occurrence of IH is an important patient outcome, so alternative closure techniques for reducing IH should be studied in this patient population. Synopsis In a single-institutional study, the incidence of incisional hernia was 17% after cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy. Independent risk factors of incisional hernia were older age, female gender and obesity.

Background: Intrahepatic cholangiocarcinoma (ICC) is a rare and aggressive disease with an increasing incidence in the United States, and there is no level 1 evidence to help guide treatment decisions. We sought to determine national trends in surgical and medical management of patients with resected ICC, and more specifically, the role of lymphadenectomy (LAD) and utilization of chemotherapy., Methods: An augmented version of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) cancer database registry was used to identify all surgically resected ICC patients from 2000 to 2014. We evaluated the incidence and adequacy of LAD, and receipt of chemotherapy over time. Next, multivariable logistic regressions were performed to determine the predictors of LAD and receipt of chemotherapy. Overall survival (OS) was evaluated using Kaplan-Meier and Cox proportional hazard models., Results: We identified 1,263 patients who underwent resection for ICC. Lymph nodes (LNs) were removed in 49% of patients, however, only 10% of patients received adequate LAD by the American Joint Committee on Cancer (AJCC) criteria (≥6 nodes). LN metastases were found in 29% of patients who underwent nodal evaluation. Chemotherapy was administered to 40% of patients, was utilized more frequently over time (P<0.05), and was associated with improved survival in node positive patients (P<0.05). Patients who did not have LNs evaluated were significantly less likely to receive chemotherapy than those who did. Lastly, OS for the entire cohort improved over time (P<0.05)., Conclusions: After analyzing the treatment and outcomes of resectable ICC, we concluded: (I) LN evaluation at the time of surgical resection remains inadequate; (II) utilization of chemotherapy has increased over time; (III) the lack of LAD likely results in under-staging and underutilization of chemotherapy; and (IV) despite less than ideal surgical and medical therapy median OS continues to improve., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Background: Predictive biomarkers of patients likely to benefit from anti-programmed death 1 inhibitor therapy have clinical relevance. We examined whether line of therapy or tumour programmed death ligand 1 (PD-L1) expression affects the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced melanoma., Methods: Of 834 patients enrolled in the randomised, open-label phase III KEYNOTE-006 study, 833 were included in this analysis. Patients were randomly assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24 months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease progression/intolerable toxicity. This analysis evaluated progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Data cut-off: 03 November 2016., Results: Of the patients, 60.3% were male, 65.9% were treatment naive and 80.6% had PD-L1-positive tumours (median follow-up was 33.9 months). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in treatment-naive (PFS 31.0% versus 14.6%; OS 58.0% versus 44.7%) and previously treated patients (PFS 25.7% versus 11.3%; OS 49.2% versus 37.9%). Twenty-four-month survival rates were higher with pembrolizumab than with ipilimumab in patients with PD-L1-positive tumours (PFS 33.2% versus 13.1%; OS 58.4% versus 45.0%) and similar in PD-L1-negative tumours (PFS 14.9% versus NR [no data at 24 months for a PFS estimate]; OS 43.6% versus 31.8%). Safety of pembrolizumab by subgroup was consistent with previous reports., Conclusions: Findings support pembrolizumab monotherapy as standard of care in patients with advanced melanoma, regardless of first- or second-line therapy or PD-L1 status. CLINICALTRIALS., Gov Identifier: NCT01866319., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The 21-gene recurrence score (RS) is a RT-PCR assay estimating risk of distant recurrence in estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2) breast cancer (BC). Studies validating RS are limited to women. Our objective was to assess RS distribution and factors associated with high-risk RS in male BC., Methods: Using the Surveillance, Epidemiology, and End Results database, we identified men and women with ER+/HER2- BC from 2010 to 2013. Patients were categorized into risk groups using the traditional and the Trial Assigning Individualized Options for Treatment (TAILORx) cutoffs. Multivariable logistic regression determined factors associated with testing and high-risk TAILORx RS., Results: We identified 1388 men and 154,196 women with ER+/HER2- BC. Twenty-five percent of men and 30% of women had RS testing. Mean age of tested men was 63; most were white (81%), had grade I or II tumors (67%), and had stage I or II (95%) BC. Factors associated with increased RS testing were younger age, recent year of diagnosis, lymph node negativity, and lower-stage tumors (p ≤ 0.05). By TAILORx, 21% of men had high-risk RS compared with 14% of tested women. Men with grade III and PR negative tumors were more likely to have a high-risk RS (p ≤ 0.05). Chemotherapy utilization was correlated with RS., Conclusions: Using a large population-based dataset, we found that compared with women, men were significantly more likely to have high-risk RS. Grade III and PR-negative BC were significantly associated with high-risk RS. Higher RS in men correlated with increased chemotherapy utilization.

Study Objective: The purpose of this study was to compare the efficacy of bilateral ultrasound guided thoracic paravertebral catheters to a thoracic epidural after open pancreatic surgery., Design: This was a prospective non-blinded randomized controlled trial., Setting: Academic hospital operating room, postoperative recovery area, and ward., Patients: 53 patients aged 18 and above who had open pancreatic surgery., Interventions: Patients received either bilateral thoracic paravertebral block at T8 with an infusion of 0.2% ropivacaine or thoracic epidural analgesia at T7/8 with an infusion of 0.125% bupivacaine with hydromorphone 6 μg/mL., Measurements: Pain scores, opioid use, length of recovery room and hospital stay, adverse events, and incidence of nausea and vomiting., Main Results: There was no difference in baseline demographics between the two groups. There were no significant differences in pain scores between the two groups in each of the first five days after surgery. There was no difference in length of stay nor nausea and vomiting. There was significantly less modality related adverse events in the paravertebral group compared to the epidural group (p = 0.02)., Conclusions: The use of thoracic paravertebral catheters provided comparable analgesia and less modality related adverse events when compared to a thoracic epidural in patients undergoing open pancreaticoduodenectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: In the United States, the overall survival rates for gastric adenocarcinoma have remained low, with surgical resection as the only therapy for many patients. Given the advances in multimodality treatment and the development of guidelines recommending adequate lymph node evaluation, the authors determined whether overall survival rates for patients with gastric adenocarcinoma have increased in the United States., Methods: The study used the Surveillance Epidemiology and End Results (SEER) database to examine overall survival for patients with the diagnosis of gastric adenocarcinoma between 1988 and 2013. The study cohort was divided into five periods: 1988-1992, 1993-1997, 1998-2002, 2003-2007, and 2008-2013. Kaplan-Meier methods and Cox proportional hazards modeling were used to determine the effect that year of diagnosis had on overall survival., Results: The diagnosis was determined for 13,470 patients between 1988 and 2013. The use of radiation therapy and the proportion of patients who had at least 15 lymph nodes evaluated significantly increased during the study period. Unadjusted Kaplan-Meier estimates demonstrated significantly better survival rates for the patients with a diagnosis of gastric cancer in the later periods (2003-2007 and 2008-2013) than for those in the three earlier periods. In our Cox proportional hazards model, recent period was associated with a significantly lower hazard of 5-year mortality., Conclusion: This analysis demonstrated for the first time that gastric cancer survival rates have significantly improved in the United States during the past 2 decades. This observation likely reflects improved adherence to cancer treatment guidelines, including adequate lymph node evaluation and delivery of adjuvant treatment more consistently.

The Mars Science Laboratory Mast camera and Descent Imager investigations were designed, built, and operated by Malin Space Science Systems of San Diego, CA. They share common electronics and focal plane designs but have different optics. There are two Mastcams of dissimilar focal length. The Mastcam-34 has an f/8, 34 mm focal length lens, and the M-100 an f/10, 100 mm focal length lens. The M-34 field of view is about 20° × 15° with an instantaneous field of view (IFOV) of 218 μrad; the M-100 field of view (FOV) is 6.8° × 5.1° with an IFOV of 74 μrad. The M-34 can focus from 0.5 m to infinity, and the M-100 from ~1.6 m to infinity. All three cameras can acquire color images through a Bayer color filter array, and the Mastcams can also acquire images through seven science filters. Images are ≤1600 pixels wide by 1200 pixels tall. The Mastcams, mounted on the ~2 m tall Remote Sensing Mast, have a 360° azimuth and ~180° elevation field of regard. Mars Descent Imager is fixed-mounted to the bottom left front side of the rover at ~66 cm above the surface. Its fixed focus lens is in focus from ~2 m to infinity, but out of focus at 66 cm. The f/3 lens has a FOV of ~70° by 52° across and along the direction of motion, with an IFOV of 0.76 mrad. All cameras can acquire video at 4 frames/second for full frames or 720p HD at 6 fps. Images can be processed using lossy Joint Photographic Experts Group and predictive lossless compression.

Guidelines regarding the prevention, detection, and management of surgical site infections (SSIs) have been published previously by a variety of organizations. The American College of Surgeons (ACS)/Surgical Infection Society (SIS) Surgical Site Infection (SSI) Guidelines 2016 Update is intended to update these guidelines based on the current literature and to provide a concise summary of relevant topics.

Manual Chart Review (MCR) is an important but labor-intensive task for clinical research and quality improvement. In this study, aiming to accelerate the process of extracting postoperative outcomes from medical charts, we developed an automated postoperative complications detection application by using structured electronic health record (EHR) data. We applied several machine learning methods to the detection of commonly occurring complications, including three subtypes of surgical site infection, pneumonia, urinary tract infection, sepsis, and septic shock. Particularly, we applied one single-task and five multi-task learning methods and compared their detection performance. The models demonstrated high detection performance, which ensures the feasibility of accelerating MCR. Specifically, one of the multi-task learning methods, propensity weighted observations (PWO) demonstrated the highest detection performance, with single-task learning being a close second.

O-GlcNAc glycosylation (or O-GlcNAcylation) is a dynamic, inducible posttranslational modification found on proteins associated with neurodegenerative diseases such as α-synuclein, amyloid precursor protein, and tau. Deletion of the O-GlcNAc transferase (ogt) gene responsible for the modification causes early postnatal lethality in mice, complicating efforts to study O-GlcNAcylation in mature neurons and to understand its roles in disease. Here, we report that forebrain-specific loss of OGT in adult mice leads to progressive neurodegeneration, including widespread neuronal cell death, neuroinflammation, increased production of hyperphosphorylated tau and amyloidogenic Aβ-peptides, and memory deficits. Furthermore, we show that human cortical brain tissue from Alzheimer's disease patients has significantly reduced levels of OGT protein expression compared with cortical tissue from control individuals. Together, these studies indicate that O-GlcNAcylation regulates pathways critical for the maintenance of neuronal health and suggest that dysfunctional O-GlcNAc signaling may be an important contributor to neurodegenerative diseases., Competing Interests: The authors declare no conflict of interest.

Background: The survival rates after pancreatectomy for elderly patients with adenocarcinoma of the pancreas remain poor. Elderly patients have increased perioperative mortality rates, higher morbidity rates, and higher rates of continued inpatient nursing care after pancreatectomy. The objective of the current study was to evaluate the outcomes of surgical resection versus chemotherapy (with or without radiotherapy) for elderly patients with potentially resectable adenocarcinoma of the pancreas., Methods: Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data for 2000 through 2010, the authors examined the relationship between patient characteristics and receipt of surgery using multivariate logistic regression. The patient cohort was restricted to patients with American Joint Committee on Cancer stage I and stage II disease and Charlson Comorbidity index of ≤2. The association between treatment (surgery or chemotherapy without surgery) and hazard of death was evaluated using Kaplan-Meier Cox proportional hazards modeling., Results: The authors identified 2629 patients with pancreatic adenocarcinoma who underwent either surgery (pancreatectomy) or chemotherapy without surgery. Younger patient age and smaller tumor size were found to be significantly associated with receipt of surgery. For the overall cohort, the median survival rate was significantly longer for those patients treated with surgery compared with those who received chemotherapy (15 months vs 10 months). However, the absolute survival benefit attenuated as the cohort became older., Conclusions: The survival benefit associated with surgical resection compared with chemotherapy was very small for certain subgroups of patients (those aged ≥80 years and those with lymph node metastases). The results of the current study indicate that although surgery is associated with a survival benefit in the elderly, chemotherapy should be considered as a legitimate therapeutic alternative. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:3378-3385. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

The post-translational modification of serine or threonine residues of proteins with a single N-acetylglucosamine monosaccharide (O-GlcNAcylation) is essential for cell survival and function. However, relatively few O-GlcNAc modification sites have been mapped due to the difficulty of enriching and detecting O-GlcNAcylated peptides from complex samples. Here we describe an improved approach to quantitatively label and enrich O-GlcNAcylated proteins for site identification. Chemoenzymatic labelling followed by copper(i)-catalysed azide-alkyne cycloaddition (CuAAC) installs a new mass spectrometry (MS)-compatible linker designed for facile purification of O-GlcNAcylated proteins from cell lysates. The linker also allows subsequent quantitative release of O-GlcNAcylated proteins for downstream MS analysis. We validate the approach by unambiguously identifying several established O-GlcNAc sites on the proteins α-crystallin and O-GlcNAc transferase (OGT), as well as discovering new, previously unreported sites on OGT. Notably, these novel sites on OGT lie in key functional domains of the protein, underscoring how this site identification method may reveal important biological insights into protein activity and regulation.

Objective: The Milan criteria for the selection of patients with hepatocellular carcinoma (HCC) for liver transplantation were originally based on the findings of contrast-enhanced CT examinations. Studies have shown improvement in HCC detection of using contrast-enhanced MRI instead of CT, but they have provided little information on the potential downstream effect on patient management that might result from discrepant imaging findings. We sought to assess the effect of discrepant imaging findings on patient eligibility to undergo liver transplantation., Materials and Methods: From 2006 to 2013, patients with a diagnosis of HCC who underwent both MDCT and MRI examinations within a 40-day period were studied retrospectively. All examinations were independently reviewed by two abdominal radiologists who recorded the number, diameter, and location of each lesion. Secondary confirmation of the lesions was made on the basis of histopathologic findings, diffusion restriction on DWI, increased T2 signal intensity, lesion growth, presence of fat, uptake of ethiodized oil, or a combination of these findings., Results: Sixty-four patients (48 men and 16 women; mean age, 62 years) met the criteria for inclusion in the study. Of the 129 lesions identified by MRI, only 102 of these lesions (79%) were identified by MDCT. This discrepancy led to a difference in the Milan criteria scoring for nine patients (14%). There was no statistically significant difference in the mean (± SD) greatest lesion diameter measured using the two modalities, with measurements of 3.52 ± 2.8 cm and 3.46 ± 2.8 cm noted on MDCT and MRI, respectively (p = 0.8). Lesions missed on MDCT studies tended to be smaller, with a mean diameter of 2.7 cm. Of the 129 lesions identified by MRI, 112 (87%) had available histopathologic findings or other confirmatory diagnostic evidence., Conclusion: MDCT missed one-fifth of the HCC lesions detected by MRI. Had MDCT been the only imaging examination performed, failure to identify these lesions would have led to a different management plan for 14% of patients.

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Once diagnosed, prognosis is poor with a 5-year survival rate of less than 5%. Exposure to carcinogenic heterocyclic amines (HCAs) derived from cooked meat has been shown to be positively associated with pancreatic cancer risk. To evaluate the processes that determine the carcinogenic potential of HCAs for human pancreas, 14-carbon labeled 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), a putative human carcinogenic HCA found in well-done cooked meat, was administered at a dietary relevant dose to human volunteers diagnosed with pancreatic cancer undergoing partial pancreatectomy and healthy control volunteers. After (14)C-MeIQx exposure, blood and urine were collected for pharmacokinetic and metabolite analysis. MeIQx-DNA adducts levels were quantified by accelerator mass spectrometry from pancreatic tissue excised during surgery from the cancer patient group. Pharmacokinetic analysis of plasma revealed a rapid distribution of MeIQx with a plasma elimination half-life of approximately 3.5 h in 50% of the cancer patients and all of the control volunteers. In 2 of the 4 cancer patients, very low levels of MeIQx were detected in plasma and urine suggesting low absorption from the gut into the plasma. Urinary metabolite analysis revealed five MeIQx metabolites with 2-amino-3-methylimidazo[4,5-f]quinoxaline-8-carboxylic acid being the most abundant accounting for 25%-50% of the recovered 14-carbon/mL urine. There was no discernible difference in metabolite levels between the cancer patient volunteers and the control group. MeIQx-DNA adduct analysis of pancreas and duodenum tissue revealed adduct levels indistinguishable from background levels. Although other meat-derived HCA mutagens have been shown to bind DNA in pancreatic tissue, indicating that exposure to HCAs from cooked meat cannot be discounted as a risk factor for pancreatic cancer, the results from this current study show that exposure to a single dietary dose of MeIQx does not readily form measurable DNA adducts under the conditions of the experiment.

Background: Adequate lymph node evaluation (LNE) is recommended for surgically treated pancreatic adenocarcinoma because studies have shown an association between improved survival and adequate LNE. This study aimed to understand the mechanism of this association and determine whether LNE is a valuable quality metric., Methods: Using the linked Surveillance Epidemiology End Results Medicare database, we identified patients with surgically treated pancreatic adenocarcinoma from 2000 to 2010. Adequate LNE was defined as evaluation of ≥15 nodes. Survival was determined using Kaplan-Meier and Cox proportional hazards., Results: We identified 2629 patients who underwent resection for pancreatic adenocarcinoma. Overall, 33 % had adequate LNE. Adequate LNE was significantly associated with receipt of postoperative chemotherapy. A significant decrease in hazard of death was associated with adequate LNE (HR 0.86, p < 0.05). Receipt of postoperative chemotherapy was also significantly associated with decreased hazard of death (HR 0.77, p < 0.05). On unadjusted analysis, the survival benefit associated with adequate LNE was lost when stratified by receipt of postoperative chemotherapy., Conclusion: The survival benefit associated with LNE is in part derived from the fact that patients who receive adequate LNE are also more likely to receive chemotherapy. Thus, the use of lymph node counts has limitations as a quality metric.

Background: Increased lymph node evaluation has been associated with improved survival rates in patients with pancreatic cancer. We sought to evaluate the trends and factors associated with lymph node examination over time and the effects on survival., Methods: Using the Surveillance, Epidemiology and End Results database, we conducted an analysis of adults with adenocarcinoma of the pancreas who underwent surgical resection. Using the Cochrane Armitage test for trend and logistic regression we identified factors associated with lymph node evaluation. Kaplan-Meier and Cox proportional hazards modeling were used to examine survival., Results: We identified 4831 patients who underwent surgical resection from 1990 to 2010. The proportion of patients with 15 or more lymph nodes evaluated increased from 16% to 42% (p < 0.05) and the median number of lymph nodes examined increased from 7 to 15 nodes (p < 0.05) during the study period. Overall, 56% of patients had lymph node metastases; this proportion significantly increased during the study period. Factors that were independently associated with less than 15 lymph nodes evaluated included male gender, receipt of pre-operative radiation therapy, early year of diagnosis, older age, and missing information on tumor grade and size (p < 0.05). Survival rates significantly improved when 15 or more lymph nodes were examined., Conclusion: We observed a significant increase in the number of lymph nodes evaluated with pancreas cancer resection over time. Lymph node evaluation was significantly associated with patient, tumor, and treatment characteristics. Our results suggest that adequate lymph node evaluation is associated with improved survival., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Pancreatitis-an inflammation of pancreas-is a severe and costly disease. Although many risk factors for pancreatitis are known, many pancreatitis cases, especially in elderly women, are of unknown etiology., Methods: Risk factors for acute pancreatitis (AP) and chronic pancreatitis (CP) were assessed in a prospective cohort (n = 36,436 women, aged ≥ 65 years). Exposures were self-reported at baseline. Pancreatitis was ascertained by linkage to Medicare claims (1986-2004) categorized by a physician as follows: "AP", one AP episode (n = 511) or "CP", 2+ AP or 1+ CP episodes (n = 149)., Results: Multivariable odds ratios (ORs) and 95% confidence intervals for AP and CP were calculated using multinomial logistic regression. Alcohol use was not associated with AP or CP. Heavy smoking (40+ vs. 0 pack-years) was associated with a twofold increased OR for CP. For body mass index greater than or equal to 30 versus less than 25 kg/m(2), the ORs were 1.35 (1.07-1.70) for AP (P trend = .009) and 0.59 (0.37-0.94) for CP (P trend = .01). ORs for AP and CP were increased for hormone replacement therapy use, heart disease, and hypertension. There were positive significant associations between protein and total fat intake for CP and AP., Conclusions: We identified factors associated with AP and CP that may be specific to older women., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The benefit and timing of radiation therapy (RT) for patients undergoing a resection for pancreatic adenocarcinoma remains unclear. This study identifies trends in the use of radiation over a 10-year period and factors associated with the use of pre-operative radiation, in particular., Methods: The Surveillance, Epidemiology and End Results registry was used to identify patients aged ≥18 years with pancreatic adenocarcinoma who underwent a surgical resection between 2000 and 2010. Logistic regression was used to identify time trends and factors associated with the use of pre-operative radiation., Results: The overall use of radiation decreased with time among the 8474 patients who met the inclusion criteria. However, the use of pre-operative radiation increased from 1.8% to 3.9% (P ≤ 0.05). Factors significantly associated with receipt of pre-operative radiation were younger age, treatment in more recent years and having an advanced T-stage tumour. The 5-year hazard of death was significantly less for those who received pre-operative radiation versus surgery alone [hazard ratio (HR) 0.64, 95% confidence interval (CI) 0.55-0.74] and for those who received post-operative radiation versus surgery alone (HR 0.69, 95% CI 0.65-0.73)., Discussion: The use of pre-operative radiation significantly increased during the study period. However, the overall use of pre-operative radiation therapy remains low in spite of the potential benefits., (© 2015 International Hepato-Pancreato-Biliary Association.)

Introduction: Sorafenib is the only drug approved by the Food and Drug Administration for metastatic hepatocellular carcinoma (HCC). Triptolide, a diterpene triepoxide, exhibits antineoplastic properties in multiple tumor cell types. In this study, we examined the effects of these agents and their combination on HCC in vitro and in vivo models., Methods: HuH-7 and PLC/PRF/5 cells were treated with triptolide (50 nM), sorafenib (1.25 or 2.5 μM), or a combination of both. Cell viability assay (CCK-8), caspase 3&7 activation, and nuclear factor κB assays were performed. For in vivo studies, 40 mice were implanted with subcutaneous HuH7 tumors and divided into four treatment groups (n = 10); saline control, sorafenib 10 mg/kg PO daily (S), Minnelide (a prodrug of triptolide) 0.21 mg/kg intraperitoneally7 daily (M), and combination of both (C). Tumor volumes were assessed weekly., Results: The combination of triptolide and sorafenib was superior to either drug alone in inducing apoptosis and decreasing viability, whereas triptolide alone was sufficient to decrease nuclear factor κB activity. After 2 weeks of treatment, tumor growth inhibition rates were S = 59%, M = 84%, and C = 93%, whereas tumor volumes in control animals increased by 9-fold. When crossed over to combination treatment, control mice tumor growth volumes plateaued over the following 4 weeks., Conclusion: The combination of sorafenib and triptolide is superior to single drug treatment in increasing cell death and apoptosis in vitro. Combining sorafenib with Minnelide inhibited tumor growth with greater efficacy than single-agent treatments. Importantly, in vivo combination treatment allowed for using a lesser dose of sorafenib (10 mg/kg), which is less than 10% of currently prescribed dose for HCC patients. Therefore, combination treatment could have translational potential in the management of HCC., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objectives: Neoadjuvant chemoradiotherapy (CRT) is a viable treatment strategy for patients with pancreatic cancer. This study was conducted to evaluate the Virginia Mason Protocol (5-fluorouracil, cisplatin, interferon-α and radiation) given in the neoadjuvant setting for the treatment of locally advanced pancreatic cancer., Methods: A Phase II pilot study evaluating interferon-based neoadjuvant CRT in patients with locally advanced pancreatic cancer was performed., Results: A total of 23 patients were enrolled. The mean age of the patients was 58.6 years. Of the 23 patients, seven (30.4%) completed all treatments. In the remaining 16 (69.6%) patients, treatment was interrupted as a result of toxicity. The most commonly reported effects of toxicity were leucopoenia/cytopoenia (n = 19, 82.6%) and gastrointestinal effects (n = 19, 82.6%). Surgical resection was successful in seven (30.4%) patients. Margins were negative in six (85.7%) of these seven patients. Positive lymph nodes were identified in three (42.9%) of seven patients. Overall survival was 11.5 months. Surgery provided improved survival (22.6 months) compared with CRT alone (8.8 months). Disease-free survival in resected patients was 17.2 months., Conclusions: Interferon-based neoadjuvant CRT may allow for resection of locally advanced pancreatic cancer, but with significant toxicity. In the absence of surgical resection, survival remains dismal., (© 2013 International Hepato-Pancreato-Biliary Association.)

Background: Neo-adjuvant chemo-radiotherapy has been proposed to improve resectability of locally-advanced pancreatic cancer (LAPC). However, the ability of neo-adjuvant therapy to induce radiological tumour regression has not been reported., Methods: Pre- and post-treatment computed tomography (CT) scans of patients undergoing neo-adjuvant chemo-radiotherapy for LAPC were reviewed. LAPC was sub-classified into borderline resectable disease [≤ 180° involvement of the superior mesenteric artery (SMA); short-segment encasement/abutment of the common hepatic artery; or tumour-associated deformity, abutment or short-segment occlusion of the superior mesenteric vein (SMV)/ portal vein (PV) that was amenable to vascular resection and reconstruction] and locally advanced un-resectable pancreatic cancer (vascular involvement more than that described for borderline resectable pancreatic cancer). The radiological response and surgical resection rates were assessed., Results: Sixteen patients received neo-adjuvant therapy for LAPC during 2005-2008. Regression of major vascular involvement, i.e. un-encasement or regression of abutment of any involved vessels was not observed in any patient. Pre- and post-treatment tumour densities were not statistically different. Fifty per cent of patients with borderline resectable disease and none of the patients with locally advanced un-resectable pancreatic cancer eventually underwent surgical resection., Conclusion: Neo-adjuvant treatment does not induce radiological tumour regression of LAPC with major vascular involvement. Patient selection for neo-adjuvant trial enrollment should remain focused on borderline disease which may have a potential for surgical resection., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: Stapled pancreatic transection is widely used although pancreatic fistula remains a common post-surgical complication., Methods: We performed a meta-analysis of existing data regarding pancreatic fistula following stapled pancreatic transection, comparing bare metal staples to reinforced staple loads., Results: We identified ten manuscripts between 2007 and 2009 reporting outcomes following stapled division of the pancreas (five retrospective reviews, five prospective case series). A total of 483 stapled pancreatic resections are included in this meta-analysis. Of these, 234(48 %) were reinforced (REINF) and 249 (52 %) were bare staples (STPL). Out of 483 cases, there were a total of 100 documented pancreatic leaks (21 %). Sixty-one leaks were reported out of 249 STPL divisions (24 %), while 39 leaks were reported following REINF division (17 %). The overall relative risk of developing a pancreatic fistula following distal pancreatectomy was not significantly different comparing STPL to REINF when all studies were combined (RR 1.00, 95% CI 0.65-1.53). We further evaluated the data stratifying by study design (prospective or retrospective) and found that prospective studies reported a significantly higher risk of pancreatic fistula with STPL compared to REINF technique (RR 14.45, 95 % CI 3.15-66.21)., Conclusion: Reinforced staples may be a preferred method of pancreatic stump closure following distal pancreatectomy.

Introduction: The timing of surgical resection for stage IV colon cancer with liver metastasis and the safety of simultaneous colon and liver resection remains controversial. The purpose of our study was to evaluate short-term outcomes after combined colon and liver resection (CCLR) versus colon resection (CR) or liver resection alone (LR) using a population database., Methods: The National Inpatient Sample was used to select patients who had surgery for colon cancer from 2002 to 2006. We evaluated for in-hospital morbidity, mortality, and prolonged length of stay (PLOS). Our analysis was done using design-weighted unadjusted analysis and logistic regression., Results: We identified 361,096 patients during our study period (CCLR 3,625; CR 322,286; LR 35,185). CCLR was not associated with an increased risk of complications (odds ratio (OR) 1.12; 95% confidence interval (CI) 0.94-1.33; P=0.21) or PLOS (OR 1.19; 95% CI 0.99-1.4; P=0.06) compared with CR. In-hospital mortality occurred in 3.5% of patients who underwent CCLR and was not significantly associated with mortality compared with CR alone (OR 1.17; 95% CI 0.79-1.74; P=0.43). Liver lobectomy with CR was associated with a PLOS and a trend toward increased morbidity and mortality. Significant predictors of complications, mortality, and PLOS included: age>70 years, male gender, nonprivate health insurance, and Elixhauser score>1., Conclusions: CCLR with limited liver resection can be performed with similar morbidity and mortality to colectomy alone. For patients who require hepatic lobectomy, however, strong consideration should be given to a staged approach.

Background and Objectives: Given the lack of population-based data in the literature, we sought to (1) identify predictors of appendiceal carcinoid tumor nodal metastasis to distinguish which patients would most likely benefit from hemicolectomy and (2) compare survival after hemicolectomy versus appendectomy alone., Methods: Using the Surveillance Epidemiology and End Results Database (1988-2005), we identified patients with appendiceal carcinoid tumors who underwent resection. We identified risk factors for nodal metastasis using logistic regression models and used the Kaplan-Meier method to compare adjusted overall and cancer-specific survival after right hemicolectomy versus appendectomy alone., Results: 576 patients met our inclusion criteria. We found that tumor size (>2.0 cm) and tumor histology (pure carcinoid tumors) were significant predictors of lymph node metastasis. After stratifying by tumor size, we did not detect a significant difference in survival between patients who underwent hemicolectomy and those that underwent appendectomy alone (log-rank, P > 0.10)., Conclusions: Tumor size and histology are significant predictors of appendiceal carcinoid tumor nodal metastasis and therefore may be helpful to identify which patients would most likely benefit from a hemicolectomy. However, our population-based study did not demonstrate a significant difference in adjusted survival rates between hemicolectomy versus appendectomy alone.

Background: Given the underrepresentation of older persons in cancer trials, the association between increasing age and receipt of recommended gastric cancer care in the United States was examined., Materials and Methods: Using the 1998-2006 SEER database, 8637 Medicare-eligible patients, aged ≥ 65 years who underwent gastrectomy for nonmetastatic gastric adenocarcinoma were identified. Multivariate analyses was used to assess the effect of increasing age on receipt of recommended gastric cancer care (adequate lymph node evaluation [≥ 15 lymph nodes] and adjuvant radiation therapy for AJCC Ib-IVM0) and cancer-specific mortality controlling for covariates., Results: While 61% of gastric cancer operations were performed in patients ≥ 65 years, less than 30% received adequate lymphadenectomy or adjuvant radiation therapy. Older patients were less likely to receive adequate nodal evaluation and adjuvant radiotherapy (P < 0.0001). These findings persisted on multivariate analyses. Older age was also associated with worse cancer-specific mortality. Because an age-tumor location interaction for cancer mortality (P = 0.047) was observed, stratified analyses were performed which showed that the adverse effect of older age on cancer-specific mortality was augmented in proximal gastric cancers., Conclusions: This population-based study showed significant age-based variations in gastric cancer care. These results should encourage assessment of generalizability of gastric cancer trials to this expanding population of elderly in the era of comparative effectiveness research.

Background: Although surgical studies have reported inconsistent associations between increased body mass index (BMI) and operative outcomes, the accuracy of BMI for measuring obesity has been questioned in previous epidemiologic studies. Simultaneously, BMI has known comorbidities, which may mediate the effect of BMI if included in multivariable models. We sought to examine the effect of BMI on operative outcomes after adjusting for preoperative factors., Methods: We identified 8858 patients who underwent major thoracic, abdominal, and pelvic surgery for solid organ tumors in American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) centers from 2005 to 2007. We used multivariable analyses to assess the effect of BMI on short-term operative outcomes after controlling for covariates., Results: Increased BMI was not associated with worse short-term operative outcomes in our bivariable analyses. However, patients with BMI > or = 35 had higher American Society of Anesthesiologists scores, longer operative times, and an increased number of postoperative complications (P < 0.0001). After adjusting for pre- and intraoperative factors, BMI did not predict any short-term operative outcome except for an increased total number of complications in BMI > or = 35. These results persisted after removing potential mediators from the multivariable analysis., Conclusions: In ACS NSQIP, BMI has minimal association with short-term operative outcomes after major cancer surgery. Although these findings may suggest a lack of association between obesity and cancer surgery outcomes, it confirms the previously examined limitations of BMI. Because of the rising incidence of obesity in the United States and its challenging effect on surgeon's practice, ACS NSQIP should consider exploring alternative measures of general and abdominal obesity.

Background: The projected increase in older persons in the United States, their underrepresentation in clinical trials, and the rarity of extremity soft tissue sarcomas (ESTS) limit our understanding of ESTS care in the elderly. We explored the extent of older age (> or =65 years) on patterns of ESTS care in NCI-sponsored population-based dataset., Materials and Methods: Using the 1991-2006 Surveillance Epidemiology and End Results registries, we identified 2586 Medicare aged persons > or =65 years with ESTS. We compared demographics, tumors, and treatments by age category. Multivariable analyses were used to examine the effect of older age on ESTS care and survival, adjusting for covariates., Results: More than 30% of adult ESTS were diagnosed in patients older than 65 years. A significant trend was observed between increasing age and decreased use of sarcoma-directed surgery and delivery of radiotherapy after limb-sparing surgery for high-grade or T2 tumors. Limb amputation rates did not vary by age. However, both African-American (odds ratio [OR] 1.85, 95% confidence interval [95% CI] 1.05-3.27, P = .0341) and Hispanic races (OR 2.17, 95% CI 1.27-3.70, P = .0044) predicted higher rates of limb amputation than whites. Although our multivariable analyses showed that decreased use of sarcoma-directed surgery was only limited to age 85 + years, it also showed that older age predicted poorer cancer-specific mortality following sarcoma-directed surgery (P < .0001)., Conclusions: In this US population-based study, the decreased use of sarcoma-directed surgery in the elderly was only limited to those older than 85 years. The association between older age and increased cancer-related mortality deserves future investigation to carefully examine potential effects of undertreatment.

Purpose: Although mucinous adenocarcinomas represent 6% to 19% of all colorectal adenocarcinomas, little is known about the genome-wide alterations associated with this malignancy. We have sought to characterize both the gene expression profiles of mucinous adenocarcinomas and their clinicopathologic features., Methods: Tumors from 171 patients with primary colorectal cancer were profiled using the Affymetrix HG-U133Plus 2.0 GeneChip with characterization of clinicopathologic data. Gene ontology software was used to identify altered biologic pathways., Results: Twenty (11.7%) mucinous adenocarcinomas and 151 (89.3%) nonmucinous adenocarcinomas were identified. Mucinous adenocarcinomas were more likely to be diagnosed with lymph node (LN) metastases (75% vs 51%, P = .04) and at a more advanced stage (85% vs 54%, P = .006) but long-term survival (5-y survival 58.9% vs 58.7%, P = NS) was similar. Mucinous adenocarcinomas displayed 182 upregulated and 135 downregulated genes. The most upregulated genes included those involved in cellular differentiation and mucin metabolism (eg, AQP3 + 4.6, MUC5AC +4.2, MUC2 + 2.8). Altered biologic pathways included those associated with mucin substrate metabolism (P = .002 and .02), amino acid metabolism (P = .02), and the mitogen-activated protein kinase cascade (P = .02)., Discussion: Using gene expression profiling of mucinous adenocarcinomas, we have identified the differential upregulation of genes involved in differentiation and mucin metabolism, as well as specific biologic pathways. These findings suggest that mucinous adenocarcinomas represent a genetically distinct variant of colorectal adencarcinoma and have implications for the development of targeted therapies.

Background: Evolving evidence suggests that, in selected patients with tumour category 1 (T1) extremity soft tissue sarcoma (ESTS), surgery alone offers satisfactory results without decreasing survival. This study assessed the effect of sarcoma treatments on survival outcomes of T1 ESTS in a population-based data set., Methods: Using the Surveillance, Epidemiology, and End Results database, 1618 patients with primary ESTS underwent limb-sparing surgery. Multivariable analysis was used to assess the impact of radiotherapy on overall survival (OS) and sarcoma-specific survival (SSS), adjusting for co-variables., Results: Some 803 patients (49.6 per cent) underwent surgery alone for T1 ESTS. Radiotherapy in patients with low- and high-grade tumours did not result in any significant difference in OS or SSS. When stratified by grade, multivariable analysis showed that adjuvant radiotherapy was not an independent predictor of SSS (hazard ratio (HR) 1.05; P = 0.906) or OS (HR 0.89; P = 0.695) in low-grade tumours. Neither was radiotherapy a significant predictor of SSS (HR 0.87; P = 0.608) or OS (HR 0.67; P = 0.071) in high-grade tumours., Conclusion: This population-based appraisal validated previous evidence supporting a role for surgery alone in the treatment of T1 ESTS. Future policies should be tailored to offer patients minimal yet effective therapy, rather than maximum tolerated therapy., (Copyright 2010 British Journal of Surgery Society Ltd.)

Objective: To examine the association between older age and short-term outcomes after major oncologic resections., Summary Background Data: The effect of older age on outcomes from major cancer surgery remains conflicting because of limitations in measuring coexisting comorbidities. Given the critical role of surgery, older patients and their surgeons often question decisions regarding major cancer surgery., Methods: We identified 8781 patients who underwent elective or emergent major thoracic, abdominal, or pelvic resections for neoplasms in the 2005 to 2007 American College of Surgeons National Surgical Quality Improvement Program database. Pre, intra-, and postoperative characteristics were compared by age groups. Multivariable techniques were used to predict adjusted short-term operative outcomes., Results: Older patients were more likely to have preoperative comorbidities and to receive intraoperative blood transfusions, but at the same time have shorter operative times. Increased age was also associated with higher operative mortality (4.83% for >or=75 years vs. 1.09% for ages 40-55 years), a greater frequency of major complications, and more prolonged hospital stays-all of which persisted after multivariable adjustments. Despite its strong association with 30-day operative mortality, the impact of older age was comparable to other preoperative risk-factors predictive of short-term operative outcomes., Conclusions: The present study, which is one of the largest multihospital studies, showed that older age is independently associated with worse short-term outcomes after major oncologic resections. However, the effect of age was not prohibitively worse, and is comparable to the effects of other preoperative risk factors. These findings support the use of risk-based treatment decision-making in older patients.

Background: Pancreatobiliary access following Roux-en-Y gastric bypass (RYGBP) is challenging. We reviewed 32 cases of surgical gastrostomy for complex transgastric upper gastrointestinal endoscopy., Methods: Retrospective review of prospectively collected database of patients with history of RYGBP that had surgical gastrostomy for pancreatobiliary and duodenal access at a single institution from 2004-2008. Indication for procedure, surgical findings, successful cannulation, and complications are reported., Results: Thirty patients (25 female), with age ranging from 27 to 72, underwent 32 procedures. The indications to access the gastric remnant were sphincter of Oddi dysfunction (13), pancreatitis (six), common bile duct stone/obstruction (five), cholangitis (three), pancreatic mass evaluation (two), gastrointestinal bleed (two), and cystic duct leak after cholecystectomy (one). Mean operative time was 200 min (98-338) and estimated blood loss (mean) 85 cc (10-500). Laparoscopic gastrostomy was attempted in 28 cases with one conversion to open (3.6%). Four planned open procedures were also performed. All 30 patients underwent successful endoscopy and 28 had an endoscopic retrograde cholangiopancreatography, all with successful cannulation of the pancreatobiliary tree (100%)., Conclusions: Surgical gastrostomy is an effective means to gain access to the upper GI tract and pancreatobiliary tree following RYGBP. This technique should be considered when traditional endoscopic approaches are impossible.

Background: Guidelines for the current National Comprehensive Cancer Network recommend radical cholecystectomy, including hepatic resection and portal lymph node (LN) dissection, for patients with early stage gallbladder (GB) cancer. We sought to determine the survival benefit conferred by adequate LN evaluation., Methods: We used the surveillance, epidemiology and end results (SEER) neoplasm registry to identify patients who had an operation for GB cancer between 1988 and 2004. Patients were classified by stage of disease, operative procedure performed (cholecystectomy alone or radical resection), number of LNs evaluated (0, 1, >1), and receipt of radiation (RT). We included patients with T1B, T2, and T3 neoplasms who were LN positive or negative. Patients with T4 neoplasms and those with metastatic disease were excluded. Multivariate analysis included adjustment for age, race, sex, neoplasm grade, stage, operation performed, receipt of RT, and neoplasm registry., Results: We identified 4,614 patients who underwent operative treatment for stage 1-2B GB (including T1B-T3 and LN positive or negative) cancer between 1988 and 2004. Of 4,614 patients, 9.6% (442) had radical resection, whereas 90.4% (4,172) had cholecystectomy alone. Among patients undergoing radical resection, 56% had LNs evaluated as compared with 28% of patients after cholecystectomy. For patients with T1B and T2 neoplasms who underwent radical resection, pathologic evaluation of at least 1 LN was associated with a significant improvement in median overall survival (OS) compared with those who had no LN evaluated (123 months vs 22 months; P < .0001). Radical resection with no LN evaluation provided similar OS compared with cholecystectomy alone (22 months vs 23 months; P = NS). For patients with T3 neoplasms, radical resection, including pathologic evaluation of at least 1 LN, was also associated with improved OS compared with radical resection with no LN evaluation (12 months vs 7 months; P = .0014). Again, individuals who had radical resection without LN evaluation had similar OS compared with those who had cholecystectomy alone (7 months vs 6 months; P = NS). Individuals who had radical resection with LN evaluation were more likely to receive RT than those who had radical resection without LN evaluation (33.1% vs 19.1%; P = .002). In multivariate analysis (including adjustment for RT), however, LN evaluation was still associated with a decrease in mortality compared with no LN evaluated (HR = 0.611; 95% CI = 0.484, 0.770). The pathologic evaluation of additional LN (>1) did not provide any additional benefit compared with the evaluation of a single node (HR = 0.795; 95% CI = 0.571, 1.107). Radical resection alone (without LN evaluation) did not provide any benefit over cholecystectomy alone (HR = 1.098; 95% CI = 0.971, 1.241)., Conclusion: LN evaluation is a critical component of radical resection for GB cancer. In the absence of LN evaluation, radical resection provides no benefit over cholecystectomy alone.

Background: Radical resection is recommended for selected patients with gallbladder (GB) cancer. We sought to determine whether radical resection improves survival for patients with early-stage cancer and to evaluate surgeon compliance with current treatment recommendations., Patients and Methods: Patients with stage 0, I, or II GB cancer who underwent surgical resection were identified from the Surveillance, Epidemiology, and End Results (SEER) tumor registry from 1988 through 2004. Patients were classified by surgical procedure performed (simple vs. radical resection) and adjuvant treatment given (radiation therapy [RT] vs. no RT). Unadjusted and adjusted overall survival (OS) and cancer-specific survival (CSS) were compared., Results: Of the 4,631 patients who underwent surgery for early-stage GB cancer from 1988 through 2004, 4,188 (90.4%) underwent cholecystectomy alone and 443 (9.6%) underwent radical surgery including hepatic resection. The proportion of patients having radical surgery for T1b, T2, and T3 cancers was 4.5%, 5.6%, and 16.3%, respectively. For patients with T1b/T2 cancer, radical resection was associated with significant improvement in adjusted CSS (p = 0.01) and OS (p = 0.03). For patients with T3 cancers, we noted no improvement in CSS or OS. Survival for patients with node-positive disease (stage 2b) was universally poor and not improved by radical resection. For all patients who underwent radical resection, node negativity, female sex, age <70, low grade, and RT predicted improved CSS and OS., Conclusions: Despite a significant survival advantage for patients with T1b/T2 GB cancer who undergo radical resection, this treatment is significantly underutilized. Ensuring delivery of recommended surgical treatment is vital to improving outcomes for patients with this disease.

Background: Pancreatic cancer cells express different mutations that increase the aggressiveness and confer resistance to conventional chemotherapy and radiotherapy. Molecules that selectively bind and inhibit these mutations are effective in other solid tumors and are now emerging as a complementary therapy in pancreatic cancer. The objective of this review is to describe the effect of drugs that inhibit specific mutations present in pancreatic cancer with special emphasis on clinical trials., Data Sources: We reviewed the English-language literature (MedLine) addressing the role of drugs that target mutations present in pancreatic cancer. Both preclinical and clinical studies were included., Conclusions: Preclinical evidence supports the combination of conventional approved therapies plus drugs that block epidermal growth factor receptor and vascular growth endothelial factor or induce apoptosis. However, most of the current clinical evidence is limited to small phase I trials evaluating the toxicity and safety of these regimens. The results of additional randomized trials that are still undergoing will clarify the role of these drugs in pancreatic cancer.

Background and Purpose: The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery., Methods: Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak., Results: Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181., Conclusions: Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.

Background: The effectiveness of prophylactic antibiotics in the prevention of surgical site infection (SSI) after elective colorectal surgery is dependent on many factors, including the body mass index (BMI) of the patient. In this study, the association of BMI and type of antibiotic prophylaxis with SSI was evaluated in patients undergoing elective colorectal surgery., Method: A post-hoc analysis was performed using data obtained from a multicenter randomized, double-blind study of 1,002 patients undergoing elective colorectal surgery who received prophylactic administration of ertapenem (1 g) or cefotetan (2 g). Among 650 evaluable patients, the effect of BMI and type of antibiotic prophylaxis on SSI rates was assessed four weeks after surgery. Mechanical bowel preparation was standardized, and no patient received oral antibiotics; intravenous antibiotics were not repeated during or after surgery., Results: The majority of patients had a BMI between 18.5 and 39.9 kg/m2. Regardless of the type of prophylaxis, SSI rates were significantly higher in patients with a BMI > or = 30 kg/m2 than in those with a BMI < 30 kg/m2. However, failure, defined as SSI, was significantly less common after ertapenem than after cefotetan prophylaxis at both BMI < 30 kg/m2 (12.7% vs. 26.4%, respectively; difference -13.7; 95% confidence interval [CI] -21.0, -6.5) and BMI > or = 30 kg/m2 (26.7% vs. 41.9%, respectively; difference -15.3; 95% CI -28.2, -2.0). The most prevalent type of SSI was superficial incisional infection, which was more common with both treatments in patients with a BMI > or = 30 kg/m2; however, the incidence of superficial SSI was lower after ertapenem than cefotetan prophylaxis., Conclusion: In patients undergoing elective colorectal surgery, the incidence of SSI, specifically superficial incisional SSI, was higher in patients with a BMI > or = 30 kg/m2, regardless of the prophylactic antibiotic given. Ertapenem prophylaxis was more effective than cefotetan in the prevention of SSI at any BMI.

Physicians must consider multiple factors when determining the most appropriate preoperative imaging strategy for gastric cancer. Health care resources are not unlimited, and the use of multiple expensive imaging techniques that do not alter treatment decisions is not recommended. With this in mind, EGD and CT scan alone should form the basis for preoperative evaluation, with further imaging considered only in selected cases. Based on the reviewed literature, we do not recommend routine surveillance imaging after curative surgery for gastric cancer. We agree with current NCCN guidelines that recommend history and physical examination every 4 to 6 months for 3 years, followed by yearly examinations. Imaging studies and endoscopy should be selectively performed in symptomatic patients.

Introduction: Down-regulation of apoptosis genes has been implicated in the development and progression of malignant melanoma. We used cDNA microarray to evaluate pro-apoptotic gene expression comparing normal skin to melanoma (thin and thick), nodal disease and distant metastases., Methods: Twenty-eight specimens including skin (n = 1), thin melanoma (n = 6), thick melanoma (n = 7), nodal disease (n = 6), and distant metastases (n = 8), were harvested at the time of resection from 16 individuals. RNA was isolated and microarray analysis utilizing the Affymetrix GeneChip (54,000 genetic elements, U133A+B... levels) was performed. Mean level of expression was calculated for each gene within a sample group. Expression profiles were then compared between tissue groups. Student's t-test was used to determine variance in expression between groups., Results: We reviewed the expression of 54,000 genetic elements, of which 2,015 were found to have significantly altered expression. This represents 1,602 genes. Twenty-two pro-apoptotic genes were found to be down-regulated when compared to normal skin. Overall reduction was evaluated comparing normal skin to metastases with a range of 3.31-64.04-fold-decrease. When comparing the tissue types sequentially, the greatest fold-decrease in gene expression occurred when comparing skin to all melanomas (thin and thick) (p = 0.011). Subset analysis comparing normal skin to thin melanoma or thick melanoma, revealed the greatest component of overall reduction at the transition from thin to thick lesions (p = 0.003)., Conclusion: Sequential down-regulation of pro-apoptotic genes is associated with the progression of malignant melanoma. The greatest fold-decrease occurs in the transformation from thin to thick lesions.

Background: Cytoreductive therapy for metastatic carcinoid provides symptomatic relief and improvement in overall survival. We evaluated whether CgA and 5HIAA could predict symptomatic relief and control of disease progression after cytoreductive surgery., Methods: We retrospectively reviewed 70 patients who underwent cytoreductive surgery for neuroendocrine hepatic metastases between 1996 and 2005. Twenty-two patients had pre and post-operative CgA and/or 5HIAA levels measured. Reduction of biomarkers following cytoreduction was correlated with patient symptoms and progression of disease following surgery., Results: Our study consisted of 14 males and 8 females with a mean age of 55 (+/-12 years). Median follow-up was 18 months (range 5-64 months). Six patients (26.1%) had complete (R0) cytoreduction, while 4 (17.4%) and 13 (56.5%) had microscopic (R1) and gross (R2) disease remaining. All patients reported improvements in their symptoms, with 12 (54.5%) reporting complete resolution (CR) and 10 (45.5%) reporting partial resolution (PR). Reduction of CgA of >or= 80% was highly predictive of complete resolution of symptoms (P = 0.007) and stabilization of disease (P = 0.034). Reduction of 5HIAA levels of >or= 80% (or normalization) was predictive of symptomatic relief, but not progression of disease (P = 0.026 and P = 0.725). Five of six patients who had R0 resections had CR and were free of disease at last follow-up (median 24.5 months, range: 11-48, P = 0.002)., Conclusions: We conclude that >or= 80% reduction in CgA level following cytoreductive surgery for carcinoid tumors is predictive of subsequent symptom relief and disease control. Substantial reduction in CgA is associated with improved patient outcomes, even after incomplete cytoreduction.

Background: Complicated intra-abdominal infections are a common problem in surgical practice. This study compared the effectiveness of ertapenem (1 g qd) and piperacillin/tazobactam (3.375 g q6h) in the treatment of these infections., Methods: This was a multicenter, double-blinded, randomized study conducted in patients with complicated intra-abdominal infections. Of the 535 patients screened, 500 were stratified on the basis of disease severity (Acute Physiology and Chronic Health Evaluation [APACHE] II score < or =10 or >10), then randomized (1:1) to 4-14 days of treatment with one of the regimens and six weeks of followup. Nearly all patients (N = 494) were treated. The primary endpoint was the proportion of microbiologically evaluable patients with a favorable clinical response (cure) at two weeks. Non-inferiority of ertapenem was based on a difference in response rate of <15 percentage points compared with piperacillin/tazobactam (lower bound of the 95% CI > -15)., Results: Of the 494 treated patients, 231 were microbiologically evaluable, with 123 and 108 patients in the ertapenem and piperacillin/tazobactam groups, respectively. Statistically similar cure rates were observed in the ertapenem (82.1%) and piperacillin/tazobactam (81.7%) groups (difference 0.3 [95% CI: -9.6, 10.5]). The pathogens isolated most frequently were Escherichia coli, Bacteroides fragilis, and Bacteroides thetaiotamicron, typical isolates associated with intra-abdominal infections. There were no statistical differences between the groups in serious drug-related clinical adverse events, drug-related clinical adverse experiences leading to study discontinuation, or mortality., Conclusions: Ertapenem was non-inferior to piperacillin/tazobactam in the cure of intra-abdominal infections caused by susceptible pathogens. Both study drugs generally were well tolerated.

Background: The type of mechanical bowel preparation (MBP) used before elective colorectal surgery remains controversial., Methods: This post hoc analysis of a prospective randomized controlled antibiotic prophylaxis trial (ertapenem vs. cefotetan) evaluated the effect of polyethylene glycol (PEG) and sodium phosphate (SP) MBPs on the rates of postoperative surgical site infections (SSI)., Results: Good to excellent MBPs were observed in 281 of 303 (93%) evaluable patients for the PEG and 336 of 367 (92%) for the SP types. A higher rate of SSI was observed in the PEG (34%) than SP (24%) group (difference, 10%; 95% confidence interval, 3.4-17.2). The MBP type was a significant risk factor for SSI, with SP favored over PEG (odds ratio, .6; 95% confidence interval, .43-.85) in univariate analysis; multivariate analysis favored SP, but was not significant (odds ratio, .69; 95% confidence interval, .46-1.02). SSI was lowest with SP and ertapenem (19%) and highest with PEG and cefotetan (44%)., Conclusions: SP, coupled with ertapenem antibiotic prophylaxis, may improve outcomes and reduce SSIs in patients undergoing elective colorectal surgery when compared with PEG coupled with cefotetan antibiotic prophylaxis.