Laparoscopic colectomy for cancer: Improved compliance with guidelines for chemotherapy and survival.

BACKGROUND: Laparoscopic surgery for colon cancer has been demonstrated in clinical trials to have short-term benefits when compared to the open surgical approach. Guidelines of the National Comprehensive Cancer Network recommend that patients with stage III or high-risk stage II colon cancer undergo adjuvant chemotherapy. We hypothesized that laparoscopic colectomy is associated with increased compliance to recommendations for chemotherapy, a lesser time to start of chemotherapy, and increased overall survival. METHODS: The National Cancer Data Base was queried to identify patients with stage III or high-risk stage II colon cancer (T4, positive margins, <12 lymph nodes, or high tumor grade) diagnosed 2010-2012. Patients were divided into laparoscopic colectomy and open colectomy groups. Intent-to-treat analysis was used with converted cases included in the laparoscopic colectomy group. Rates of receiving adjuvant chemotherapy, time from diagnosis and date of operation to start of chemotherapy, and overall survival were compared. RESULTS: A total of 48,257 patients were included for analysis; 18,801 patients underwent laparoscopic colectomy and 29,456 underwent open colectomy. Laparoscopic colectomy patients received adjuvant chemotherapy at a somewhat greater rate than open colectomy (66.2% vs 59.4%, P < .01). Among patients who received chemotherapy, mean time to start of chemotherapy after definitive resection was somewhat less for laparoscopic colectomy than open colectomy (48.7 vs 52.7 days, P < .01). Two-year overall survival was greater for laparoscopic colectomy than open colectomy (81.9% vs 73.2%, P < .01). CONCLUSION: Compared to open colectomy, laparoscopic colectomy is associated with somewhat greater rates of compliance with guidelines for adjuvant chemotherapy for stage III and high-risk stage II colon cancer, as well as a slightly lesser time to start of chemotherapy and improved overall survival.

A pilot study: portable out-of-center sleep testing as an early sleep apnea screening tool in acute ischemic stroke.

INTRODUCTION: Prompt diagnosis of obstructive sleep apnea (OSA) after acute ischemic stroke (AIS) is critical for optimal clinical outcomes, but in-laboratory conventional polysomnograms (PSG) are not routinely practical. Though portable out-of-center type III cardiopulmonary sleep studies (out-of-center cardiopulmonary sleep testing [OCST]) are widely available, these studies have not been validated in patients who have recently suffered from AIS. We hypothesized that OCST in patients with AIS would yield similar results when compared to conventional PSG. METHODS: Patients with AIS had simultaneous type III OCST and PSG studies performed within 72 hours from symptom onset. The accuracy of OCST was compared to PSG using: chi-square tests, receiver operatory characteristic curves, Bland-Altman plot, paired Student's t-test/Wilcoxon signed-rank test, and calculation of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: Twenty-one out of 23 subjects with AIS (age 61±9.4 years; 52% male; 58% African-American) successfully completed both studies (9% technical failure). Nearly all (95%) had Mallampati IV posterior oropharynx; the mean neck circumference was 16.8±1.6 in. and the mean body mass index (BMI) was 30±7 kg/m(2). The apnea hypopnea index (AHI) provided by OCST was similar to that provided by PSG (19.8±18.0 vs 22.0±22.7, respectively; P=0.49). On identifying subjects by OCST with an AHI ≥5 on PSG, OCST had the following parameters: sensitivity 100%, specificity 85.7%, PPV 93%, and NPV 100%. On identifying subjects with an AHI ≥15 on PSG, OCST parameters were as follows: sensitivity 100%, specificity 83.3%, PPV 81.8%, and NPV 100%. Bland-Altman plotting showed an overall diagnostic agreement between OCST and PSG modalities for an AHI cutoff >5, despite fine-grained differences in estimated AHIs. CONCLUSION: Compared with PSG, OCST provides similar diagnostic information when run simultaneously in AIS patients. OCST is a reliable screening tool for early diagnosis of OSA in AIS patients.

18F-fluorodeoxythymidine micro-positron-emission tomography versus 18F-fluorodeoxyglucose micro-positron-emission tomography for in vivo minimal residual disease imaging.

OBJECTIVES/HYPOTHESIS: The early detection of persistent/recurrent disease of head and neck squamous cell carcinoma (HNSCC) after treatment can be challenging. The currently used radioisotope (18)F-fluorodeoxyglucose (FDG) is a nonspecific tracer for cancer cells as it detects all metabolically active cells including inflammation. (18)F-fluorodeoxythymidine (FLT) is a radioactive tracer for rapidly proliferating cells, and therefore is more specific for detecting cancer. Our aim was to compare FLT and FDG microPET (positron-emission tomography) to the gold standard in vivo bioluminescence imaging for serial assessment of neoplastic growth in a minimal residual disease in vivo model. STUDY DESIGN: Prospective outcomes research. METHODS: In order to mimic the postsurgical environment of HNSCC patients FaDu cells transfected with a luciferase-expressing retrovirus were inoculated into the skin flap of Balb/c nu/nu mice. Three days later before tumors formed, mice were randomized into (18)F-FLT or (18) F-FDG groups, and microPET imaging was performed on days 3, 6, 10, 18, and 24 after tumor cell inoculation. RESULTS: (18)F-FLT detected tumors as early as day 3 even before tumors were palpable, whereas (18)F-FDG only detected palpable tumors. The average overall normalized radioactivity in the FLT group was significantly higher than the FDG group (P = .025). CONCLUSIONS: (18)F-FLT identified tumor cells before tumors were palpable and can potentially be used for early detection of persistence/recurrence of HNSCC. In addition, this radioisotope can be used to monitor adjuvant therapy with novel targeted therapeutics in preclinical models of persistent disease.

High Sensitivity C - Reactive Protein is Associated with Diastolic Dysfunction in Young African Americans without Clinically Evident Cardiac Disease.

BACKGROUND: Diastolic dysfunction (DD) is associated with myocardial fibrosis mediated by inflammation. Higher levels of inflammation found in African Americans (AAs) may predict DD among asymptomatic individuals. We tested the hypothesis that high sensitivity C-reactive protein (hs-CRP), a biomarker of inflammation, is associated with DD in asymptomatic AAs. METHODS: We prospectively recruited 107 asymptomatic AAs without any history of cardiac, renal or inflammatory diseases or alcoholism. We measured hs-CRP and B-type Natriuretic peptide (BNP) levels and estimated left ventricular end diastolic pressure (LVEDP), mass and systolic function with echocardiography. Multivariate logistic regression analysis was used to define whether hs-CRP is an independent predictor of LVEDP. RESULTS: Among 107 subjects: the mean age was 48±10 yrs, 58 (54%) were men, 59 (55%) had diabetes (DM), 48 (45%) had hypertension (HTN), the mean BMI was 30.5±4.8 and the mean ejection fraction was 63.1±5.8%. DD was present in 56(52%) subjects, 38 (36%) of whom also had a high LVEDP. On multivariate analysis, hs-CRP was independently associated with DD [odds ratio 3.36 (95% CI= 1.07 - 10.5, p = 0.04]. There was a 61% and 133% increase in the prevalence of any DD and DD with high LVEDP, respectively, between the lowest and the highest hs-CRP quartiles. CONCLUSION: Diastolic dysfunction is prevalent among asymptomatic African Americans and it is independently associated with elevated level of hs-CRP, an inflammation marker.

Human papillomavirus in metastatic lymph nodes from unknown primary head and neck squamous cell carcinoma.

OBJECTIVE: Determine human papillomavirus (HPV) incidence in unknown primary squamous cell carcinomas (SCCa) of the head and neck and assess if HPV status influenced survival. STUDY DESIGN: Historical cohort study. SETTING: Tertiary care center. SUBJECTS: Patients with unknown primary SCCa despite a complete workup who underwent neck dissection or excisional biopsy and postoperative comprehensive ± chemoradiotherapy between 2002 and 2009. METHODS: HPV fluorescence in situ hybridization (FISH) and p16(INK4a) immunohistochemistry (p16 IHC) were performed. Results were compared with survival, age, race, gender, tobacco use, alcohol use, and nodal stage. RESULTS: Twenty-five patients met the inclusion criteria, of whom 88% were >10 pack year tobacco users. Twenty-eight percent were HPV-positive defined by both p16+ and FISH+. Five-year overall survival was 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .35). Similarly, 5-year disease-free survival rates were 66.7% in HPV-positive and 48.5% in HPV-negative patients (P = .54). All 3 HPV-positive nonsmokers were survivors, but this was not significant because of the small sample size (P > .05). No other characteristics were associated with survival (P > .05). CONCLUSION: Twenty-eight percent of metastatic lymph nodes from occult primary tumors were HPV positive. There was no survival difference associated with HPV status. Most of the HPV-positive patients in this study were tobacco users who had similar survival to HPV-negative patients, so caution should be used in interpreting HPV status in these patients.

Curcumin inhibits carcinogen and nicotine-induced Mammalian target of rapamycin pathway activation in head and neck squamous cell carcinoma.

Curcumin appears to be a safe, bioactive food compound that is a potential chemopreventive for patients at a high risk for head and neck squamous cell carcinoma (HNSCC). Identification and validation of intermediate endpoints is an important step in evaluating chemopreventive agents. AKT/MTOR pathway biomarkers are intrinsic to the carcinogenic process as well as the mechanism of intervention with curcumin. Antiproliferative effects of curcumin were assayed in 9 HNSCC and a keratinocyte cell line. Nicotine, a genotoxic alkaloid involved in tobacco addiction, forms DNA adducts and has been implicated in upper aerodigestive tract cancer promotion. The antiproliferative effects of curcumin were associated with inhibition of the AKT/MTOR pathway in presence and absence of nicotine, which also induced this pathway. Curcumin was highly effective at suppressing growth of SCC40 xenografts and its activity is associated with modulation of MTOR's downstream target pS6. Curcumin at 15 mg significantly increased survival (286 ± 37 vs. 350 days) in the 4NQO carcinogenic model survival study. A major cause of lethal progression of HNSCC is local regional migration and invasion of malignant cells, and curcumin significantly inhibited cancer cell migration and invasion in vitro and in vivo where downregulation of pS6 was associated with a significant decrease in MMP-9. This is the first study to demonstrate that curcumin inhibits the adverse effects of nicotine by blocking nicotine-induced activation of the AKT/MTOR pathway in HNSCC, which retards cell migration. These studies indicate that inhibiting the AKT/MTOR pathway with curcumin may be useful as an oral chemopreventive agent.

Thigh grafts contribute significantly to patients' time on dialysis.

BACKGROUND AND OBJECTIVES: Thigh grafts are placed in hemodialysis patients who have exhausted all arm access sites. The goal of this study was to compare the survival, complication rates, and overall contribution of thigh grafts with arm grafts and fistulas in patients with at least one functional thigh graft during their dialysis history. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal review of a prospectively acquired clinical database included 85 thigh graft recipients. The rates of survival, thrombosis, infection, and other complications were determined for a total of 268 fistulas, arm grafts, and thigh grafts placed in these patients. RESULTS: In this patient subset, thigh graft primary failure rate was lower than arm grafts and fistulas (3 versus 13 and 61%, respectively). Excluding primary failures, thigh grafts survived longer than both arm grafts and mature fistulas (53 versus 14 and 32%, at 3 years; 47 versus 3 and 11% at 5 years). Thigh grafts had a lower thrombosis rate than arm grafts (0.543 versus 1.457/patient-year) but similar rates of loss as a result of infection and surgical revision. In patients with previous arm accesses, thigh grafts contributed 51% of total dialysis time compared with 38 and 11% for arm grafts and fistulas. CONCLUSIONS: Thigh grafts provide long-term, thrombosis- and infection-free dialysis access for patients with exhausted arm access sites. The decision for thigh graft placement should, therefore, be made as soon as there is evidence for unavailability of arm access sites so that catheter use can be minimized.

Electrocardiographic abnormalities in patients with acute burn injuries.

OBJECTIVE: To determine the incidence and types of electrocardiographic (ECG) abnormalities in patients admitted with acute burn injuries and correlate them with the degree and the extent of burn injuries. METHODS: Retrospective analysis of 192 patients admitted to the burn unit was performed. Thirty-four patients met the inclusion criteria of having a 12-lead ECG performed on admission and at least one more time during their stay. RESULTS: There were 26 men and 8 women. The average age of patients was 53.4 +/- 17.5 years. The average degree of burn was 2.4 +/- 0.6 and the average body surface area (BSA) involved was 12.8 +/- 11.8%. There were 18 patients (53%) with ECG abnormalities. Five patients had sinus tachycardia, including two with premature atrial complexes (PACs) and one with ST-T abnormality. Three patients had premature ventricular complexes (PVCs), including one with a paced atrial rhythm and one with a prolonged QT interval. Right bundle branch block was present in two patients, and low voltage QRS was present in one. Atrial fibrillation was present in two patients, including one with ST-T abnormality due to digitalis effect. Four patients had a prolonged QT interval as the sole abnormality. One patient had left ventricular hypertrophy, an old inferior myocardial infarct, PACs, and non-specific ST-T wave abnormality. CONCLUSIONS: In patients with acute burn injuries sinus tachycardia and a prolonged QT interval were the most common ECG abnormalities. There was no correlation between the extent of burn injuries and observed ECG abnormalities. No patient had a life threatening arrhythmia, and all patients had a good outcome.

In-stent stenosis: potential role of increased oxidative stress and glutathione-linked detoxification mechanisms.

This study was designed to determine whether red-cell oxidative stress status and antioxidant enzyme levels can serve as markers in patients predisposed to in-stent stenosis. Blood was collected from patient groups undergoing coronary angiography for chest pain evaluation, namely, group A (without coronary artery disease), group B (previous coronary stents without in-stent stenosis), and group C (previous coronary stents with in-stent stenosis). Thiobarbituric acid reactive substances (measure of lipid peroxidation), glutathione-linked detoxification enzymes, catalase, and superoxide dismutase were determined. Compared with group A, patients in group C showed increased lipid peroxidation products and glutathione-S-transferase but decreased glutathione peroxidase and glutathione reductase activities. Results in group B patients were intermediate between those of groups A and C with significant decreases in glutathione peroxidase versus controls. In-stent stenosis is associated with significant increase in lipid peroxidation and attenuated glutathione-linked detoxification enzymes, consistent with oxidative stress.

Survival trends in elderly patients with glioblastoma multiforme: resective surgery, radiation, and chemotherapy.

BACKGROUND: It is appropriate to investigate and to determine survival trends following glioblastoma multiforme treatment using resective surgery, radiation therapy, and/or chemotherapy in patients aged 59 years and higher. METHODS: We retrospectively reviewed 30 elderly patients (> or =59 years old) who were treated for histopathologically confirmed glioblastoma multiforme at our tertiary care institution from 1990 through 2002. All patients were treated with steroids. In addition, 22 patients underwent resective surgery (RS), 17 patients underwent radiation therapy (RT), and 10 patients underwent chemotherapy (C). Many patients underwent these treatments in various combinations: 6 underwent biopsy only, 7 RS only, 6 RS+RT only, and 9 RS+RT+C. For each case, pre-treatment Karnofsky performance scores (KPS), tumor location, presenting symptoms and signs, associated surgical morbidity, and pre-existing medical conditions were also recorded. Patients were categorized into one of four treatment subgroups: Biopsy only, RS only, RS+RT, and RT+RS+C. For each of these subgroups, pretreatment KPS and post-treatment survival were compared. RESULTS: Post-treatment survival following biopsy only was 3.2 +/- 0.8 months (mean +/- SE); RS 2.2 +/- 0.5; RS+RT 5.5 +/- 1.2; RS+RT+C 13.6 +/- 2.1. A longer survival trend was noted for the RS+RT versus RS group (two-tailed unpaired t test, p = 0.02;), as well as the RS+RT+C group, which showed consistently higher survival in comparison to most of the other groups (p = 0.0021, 0.00039, 0.013 vs. the biopsy only, RS only, and RS+RT groups, respectively). No significant difference was found in KPS, comparing all individual groups versus each other (p > or = 0.06). Remarkably, 6 patients survived over 14 months (range, 14.1-22.7 months), all of which received RS+RT+C. CONCLUSIONS: This study suggests a significant improvement in elderly patients treated with the combination of resective surgery, radiation therapy, and chemotherapy, rather than either treatment alone or other combination. This significant improvement does not appear to be biased by pretreatment KPS, as mean KPS values did not significantly differ between any of these groups. However, a greater number of patients in each group must be considered to achieve the power to make more definitive treatment guidelines.

Quantification of the advantages of the extended frontal approach to skull base.

This anatomic study evaluated the extent that a fronto-orbital osteotomy (FOO) added to a bilateral frontal craniotomy widened the exposure to the midline compartment of the anterior, middle, and posterior cranial fossae. The goal was to determine if osteotomy would significantly increase angles for two targets: the foramen magnum (FM) and anterior clinoid process (ACP). Stepwise dissections were performed on five cadaveric heads. A bilateral frontal craniotomy was made, followed by FOO. After the ethmoids were removed, the planum sphenoidale was drilled to enter the sphenoid sinus. Further drilling exposed the anterior clivus, which was drilled down to FM. Excellent exposure of the basilar artery, vertebral artery, and brain stem was achieved. With and without FOO, angles of exposure were measured for two targets: the ACP and FM. The angle of exposure after FOO increased markedly with an average gain of 76% for the ACP and of 80% for FM. Compared with a conventional bifrontal craniotomy, the addition of FOO increased the surgical exposure and minimized frontal lobe retraction for accessing lesions of the anterior, middle, and posterior cranial fossae.

Outcomes of coronary artery bypass grafting in patients with a history of illicit drug use.

To date, no studies have been conducted on the effects of illicit drug use in patients with ischemic heart disease treated with coronary artery bypass grafting. Our retrospective study suggests that current illicit drug use is a significant predictor of cardiovascular complications in the first 6 months after coronary artery bypass grafting.

A randomized controlled trial of blood flow and stenosis surveillance of hemodialysis grafts.

BACKGROUND: It is widely accepted that hemodialysis graft surveillance combined with correction of stenosis reduces thrombosis and prolongs graft survival. Nevertheless, few randomized controlled trials have evaluated this approach. METHODS: In this randomized controlled trial, 101 patients were assigned to control, flow (Qa), or stenosis groups, and were followed for up to 28 months. All patients had monthly Qa measured by ultrasound dilution and quarterly percent stenosis measured by duplex ultrasound. Referral for angiography was based on the following criteria: (1) control group (N = 34), clinical criteria; (2) flow group (N = 32), Qa <600 mL/min or clinical criteria; and (3) stenosis group (N = 35), stenosis>50% or clinical criteria. Stenosis >or=50% during angiography was corrected by preemptive percutaneous transluminal angioplasty (PTA). RESULTS: The preemptive PTA rate in the control group (0.22/patient year) was two thirds the rate in the flow group (0.34/patient year), and was highest in the stenosis group (0.65/patient year, P < 0.01). The percentage of grafts that thrombosed was similar in the control (47%) and flow groups (53%), but reduced in the stenosis group (29%, P = 0.10). Two-year graft survival was similar in the control (62%), flow (60%), and stenosis groups (64%) (P = 0.89). CONCLUSION: Qa and stenosis surveillance were not associated with improved graft survival, although thrombosis was reduced in the stenosis group. The most important factors in this result may be that monthly Qa and quarterly stenosis measurements were not accurate or timely indicators of risk of thrombosis or progressive stenosis. This study does not support the concept that Qa or stenosis surveillance are superior to aggressive clinical monitoring.

Association between blood pressure, ultrafiltration, and hemodialysis graft thrombosis: a multivariable logistic regression analysis.

Although a low blood flow (Q(a)) is the most important cause of graft thrombosis, several studies have shown that Q(a) measurements do not accurately predict thrombosis. This suggests that additional variables may influence thrombosis. Identification of such variables may be essential to designing surveillance protocols that accurately predict thrombosis. In this nested case-control study, we prospectively followed 105 patients for up to 2.5 years in order to test the association of a number of variables with thrombosis. These included Q(a) (monthly by ultrasound dilution), percentage stenosis (quarterly by duplex ultrasound), mean arterial pressure (MAP), percentage ultrafiltration (%UF) during dialysis (%UF = 100[liters]/[kilogram of weight]), and other variables that defined patient and graft characteristics. Patients were divided into patent (n = 53) and thrombosed groups (n = 52), and MAP and %UF from seven consecutive dialysis sessions were analyzed. In the thrombosed group, the last session was the final session before thrombosis. A multivariable logistic regression model showed that Q(a), MAP (the predialysis average of seven sessions), and %UF (from the last session) were independently associated with thrombosis, whereas all other variables were not. The model yielded the following odds ratios for thrombosis: for a single Q(a) value (reduction of 1,000 mL/min), 12.0 (P < 0.01); for %UF (increase of 4%), 5.3 (P < 0.01); for MAP (reduction of 30 mm Hg), 4.1 (P = 0.02); and for percentage decrease in Q(a) (> or =20% versus <20%), 2.4 (P = 0.12). We conclude that in addition to Q(a), both %UF at the last session before thrombosis and average predialysis MAP from seven sessions are independently associated with thrombosis. These results help explain why Q(a) alone does not accurately predict thrombosis. A prospective study is needed to determine whether %UF at each session and a moving average MAP from seven sessions improve the prediction of thrombosis. However, it should be recognized that a large %UF is a preterminal event that likely provides too short a warning for intervention before thrombosis.