Impact of Adjuvant Radiotherapy on Survival after Pancreatic Cancer Resection: An Appraisal of Data from the National Cancer Data Base

Purpose

The impact of adjuvant radiotherapy for pancreatic adenocarcinoma (PAC) remains controversial. We examined effects of adjuvant therapy on overall survival (OS) in PAC, using the National Cancer Data Base (NCDB).

Methods

Patients with resected PAC from 1998 to 2002 were queried from the NCDB. Factors associated with receipt of adjuvant chemotherapy (ChemoOnly) versus adjuvant chemoradiotherapy (ChemoRad) versus no adjuvant treatment (NoAdjuvant) were assessed. Cox proportional hazard modeling was used to examine effect of adjuvant therapy type on OS. Propensity scores (PS) were developed for each treatment arm and used to produce matched samples for analysis to minimize selection bias.

Results

From 1998 to 2002, a total of 11,526 patients underwent resection of PAC. Of these, 1,029 (8.9 %) received ChemoOnly, 5,292 (45.9 %) received ChemoRad, and 5,205 (45.2 %) received NoAdjuvant. On univariate analysis, factors associated with improved OS included: younger age, higher income, higher facility volume, lower tumor stage and grade, negative margins and nodes, and absence of adjuvant therapy. On multivariate analysis with matched PS, factors independently associated with improved OS included: younger age, higher income, higher facility volume, later year of diagnosis, smaller tumor size, lower tumor stage, and negative tumor margins and nodes. ChemoRad had the best OS (hazard ratio 0.70, 95 % confidence interval 0.61–0.80) in a PS matched comparison with ChemoOnly (hazard ratio 1.04, 95 % confidence interval 0.93–1.18) and NoAdjuvant (index).

Conclusions

Adjuvant chemotherapy with radiotherapy is associated with improved OS after PAC resection in a large population from the NCDB. On the basis of these analyses, radiotherapy should be a part of adjuvant therapy for PAC.     

Manual planimetric measurement of carotid plaque volume using three-dimensional ultrasound imaging

We investigated the utility of three manual planimetric methods to quantify carotid plaque volume. A single observer measured 15 individual plaques from 15 three-dimensional (3D) ultrasound (3D US) images of patients ten times each using three different planimetric approaches. Individual plaque volumes were measured (range: 32.6-597.1 mm3) using a standard planimetric approach (M1) whereby a plaque end was identified and sequential contours were measured. The same plaques were measured using a second approach (M2), whereby plaque ends were first identified and the 3D US image of the plaque was then subdivided into equal intervals. A third method (M3) was used to measure total plaque burden (range: 165.1-1080.0 mm3) in a region (+/- 1.5 cm) relative to the carotid bifurcation. M1 systematically underestimated individual plaque volume compared to M2 (V2 = V1 + 14.0 mm3, r = 0.99, p = 0.006) due to a difference in the mean plaque length measured. Coefficients of variance (CV) for M1 and M2 decrease with increasing plaque volume, with M2 results less than M1. Root mean square difference between experimental and theoretical CV for M2 was 3.2%. The standard deviation in the identification of the transverse location of the carotid bifurcation was 0.56 mm. CVs for plaque burden measured using M3 ranged from 1.2% to 7.6% and were less than CVs determined for individual plaque volumes of the same volume. The utility of M3 was demonstrated by measuring carotid plaque burden and volume change over a period of 3 months in three patients. In conclusion, M2 was determined to be a more superior measurement technique than M1 to measure individual plaque volume. Furthermore, we demonstrated the utility of M3 to quantify regional plaque burden and to quantify change in plaque volume.     

Effects of reduction in dose and discontinuation of hydrochlorothiazide in patients with controlled essential hypertension

We studied the effects of a reduction in dose of hydrochlorothiazide from 50 to 25 mg/d, and its discontinuation for up to 22 months in 36 well-controlled hypertensive patients. Hydrochlorothiazide was discontinued if the diastolic blood pressure remained less than or equal to 94 mm Hg after a 6-month period on the lower dose of hydrochlorothiazide. No other changes were made in medications or diet. Sitting systolic blood pressure rose from 135 +/- 15 mm Hg to 140 +/- 14 mm Hg on reduction of the hydrochlorothiazide dose and rose still further to 145 +/- 20 mm Hg on discontinuation. Even greater increases in standing blood pressure were observed. There were no significant effects on the diastolic blood pressure with reduction of dose or discontinuation of hydrochlorothiazide. A significant decrease in the serum uric acid and a rise in serum potassium occurred. There were no changes in serum glucose or lipids on reduction in the dose of hydrochlorothiazide; whereas, with discontinuation, the serum lipids and hemoglobin A1C fell significantly. These results suggest that the benefits of a reduced dose of hydrochlorothiazide may not be as great as considered heretofore.     

Risk factors associated with anaphylaxis and other allergic-like events following receipt of 2009 monovalent AS03-adjuvanted pandemic influenza vaccine in Quebec,Canada

Introduction

In Quebec, Canada, receipt of the 2009 AS03-adjuvanted pandemic H1N1 vaccine was associated with increased risk of anaphylaxis and other allergic-like events (ALE), especially among women of childbearing age. In response to this safety signal, a case–control study was conducted to identify potential risk factors.

Methods

A total of 435 ALE (50 anaphylaxis) occurring <24 h following pandemic vaccination were compared to 849 age-gender matched controls randomly selected from the provincial Pandemic Influenza Vaccination Registry. More than 60 potential risk factors were evaluated through phone interviews and included demographic information, medical history, medication use or acute respiratory illnesses (ARI) concurrent with vaccination and other risk factors associated with general allergy. Odds ratios (ORs) with 95% confidence intervals were estimated with unconditional logistic regression.

Results

Factors associated with increased risk of anaphylaxis included concurrent ARI (18% cases vs. 4% controls, ORadj 7.67, 95%CI: 3.04–13.37), food allergy (26% cases vs. 4% controls, ORadj 3.84, 95%CI: 1.51–9.74) and vaccination during the first four weeks of the campaign (66% cases vs. 50% controls, ORadj 2.16, 95%CI: 1.10–4.25) whereas alcohol exposure (≥1 drink/week) was associated with reduced risk (29% cases vs. 42% controls, ORadj 0.26, 95%CI: 0.13–0.57). These factors were also significantly associated with any ALE but the strength of association was weaker. Allergy to components found in the vaccine (e.g., egg, thimerosal) was infrequent and did not significantly differ between cases and controls.

Conclusion

Increased anaphylaxis and other allergic-like events observed in association with AS03-adjuvanted pandemic H1N1 vaccine remain mostly unexplained despite extensive risk factor review. However, prior to mass vaccination with similar formulations this safety signal warrants further consideration and better understanding. In particular, the predominance among women of childbearing age may be a clue to underlying biological or hormonal influences on adverse immunological responses to vaccine.     

A systematic review of synthetic and biologic materials for abdominal wall reinforcement in contaminated fields

Background

Guidelines recommend the use of bioprosthetics for abdominal wall reinforcement in contaminated fields, but the evidence supporting the use of biologic over synthetic non-absorbable prosthetics for this indication is poor. Therefore, the objective was to perform a systematic review of outcomes after synthetic non-absorbable and biologic prosthetics for ventral hernia repair or prophylaxis in contaminated fields.

Methods

The systematic literature search identified all articles published up to 2013 that reported outcomes after abdominal wall reinforcement using synthetic non-absorbable or biologic prosthetics in contaminated fields. Studies were included if they included at least 10 cases (excluding inguinal and parastomal hernias). Quality assessment was performed using the MINORS instrument. The main outcomes measures were the incidence of wound infection and hernia at follow-up. Weighted pooled proportions were calculated using a random effects model.

Results

A total of 32 studies met the inclusion criteria and were included for synthesis. Mean sample size was 41.4 (range 10–190), and duration of follow-up was >1 year in 72 % of studies. Overall quality was low (mean 6.2, range 1–12). Pooled wound infection rates were 31.6 % (95 % CI 14.5–48.7) with biologic and 6.4 % (95 % CI 3.4–9.4) with synthetic non-absorbable prosthetics in clean-contaminated cases, with similar hernia rates. In contaminated and/or dirty fields, wound infection rates were similar, but pooled hernia rates were 27.2 % (95 % CI 9.5–44.9) with biologic and 3.2 % (95 % CI 0.0–11.0) with synthetic non-absorbable. Other outcomes were comparable.

Conclusions

The available evidence is limited, but does not support the superiority of biologic over synthetic non-absorbable prosthetics in contaminated fields.     

Boron-containing capsaicinoids

This study reports on the preparation of eight new boron-containing capsaicinoids bearing long aliphatic chains, as an expansion of our previous studies to include tertiary amide derivatives into our substrate scope. Our boron-moiety, a pinacolboronate ester (Bpin) fragment, has been incorporated in two locations: as an aryl substituent of the capsaicinoid produced by the reductive amination of veratraldehyde, or at the terminal end of an aliphatic substituent using an iridium catalyzed hydroboration reaction. We report that most compounds in our series show moderate antimicrobial and cytotoxic activity, surpassing activities noted in our previous study.

This study reports on the preparation of eight new boron-containing capsaicinoids bearing long aliphatic chains, and initial bioactivities are reported.