Fluorescent-tilmanocept for tumor margin analysis in the mouse model

Background

Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment.

Materials and methods

[^99mTc]- cyanine 7 (Cy7)-tilmanocept was synthesized and in vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0 nmol of [^99mTc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2 h after injection, the tumor, muscle, and blood were assayed for radioactivity to calculate percent-injected dose. Digital images of the tumors after immunohistochemical staining for DC were analyzed to determine DC density.

Results

In vitro binding demonstrated subnanomolar affinity of [^99mTc]-Cy7-tilmanocept to DC (K_A = 0.31 ± 0.11 nM). After administration of [^99mTc]-Cy7-tilmanocept, fluorescence imaging showed a 5.5-fold increase in tumor signal as compared with preinjection images and a 3.3-fold difference in fluorescence activity when comparing the tumor with the surgical bed after tumor excision. Immunohistochemical staining analysis demonstrated that DC density positively correlated with tumor percent of injected dose per gram (r = 0.672, P = 0.03), and higher DC density was observed at the periphery versus center of the tumor (186 ± 54 K versus 64 ± 16 K arbitrary units, P = 0.001).

Conclusions

[^99mTc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.     

Genetic Biomarkers in Epilepsy

The identification of valid biomarkers for outcome prediction of diseases and improvement of drug response, as well as avoidance of side effects is an emerging field of interest in medicine. The concept of individualized therapy is becoming increasingly important in the treatment of patients with epilepsy, as predictive markers for disease prognosis and treatment outcome are still limited. Currently, the clinical decision process for selection of an antiepileptic drug (AED) is predominately based on the patient’s epileptic syndrome and side effect profiles of the AEDs, but not on effectiveness data. Although standard dosages of AEDs are used, supplemented, in part, by therapeutic monitoring, the response of an individual patient to a specific AED is generally unpredictable, and the standard care of patients in antiepileptic treatment is more or less based on trial and error. Therefore, there is an urgent need for valid predictive biomarkers to guide patient-tailored individualized treatment strategies in epilepsy, a research area that is still in its infancy. This review focuses on genomic factors as part of an individual concept for AED therapy summarizing examples that influence the prognosis of the disease and the response to AEDs, including side effects.     

Continuous Absorbable Intradermal Sutures Yield Better Cosmetic Results than Nonabsorbable Interrupted Sutures in Open Appendectomy Wounds: A Prospective,Randomized Trial

Background

Acute appendicitis is the most common reason for abdominal surgery in young adults and children. Open appendectomy is still the treatment often chosen because it is simple, safe, and effective. Our aim was to study whether cosmetic results of appendectomy wounds are better after using continuous absorbable intradermal (A) sutures compared with wound closure with interrupted nonabsorbable (NA) sutures.

Methods

A total of 206 adult patients with clinically suspected appendicitis were allocated to the study and prospectively randomized into two wound-closure groups: the interrupted NA suture group and the A suture group. Of these, 193 patients with sufficient data were invited to the outpatient clinic for cosmetic analysis. Cosmetic results were evaluated after a median of 14 months. For subjective scar assessment, the Vancouver scar scale, the patient and observer scar assessment scale (POSAS), and a visual analog scale (VAS) were used. Objective evaluation was carried out by measuring surface area, average width, and estimated concentration change (ECC) of hemoglobin and melanin in the scar using spectrocutometry. For statistical analyses we used the Mann–Whitney test and Student’s t test.

Results

Both objective and subjective analyses showed better cosmetic results for absorbable intradermal suturing. The difference between the two groups was statistically significant as regards POSAS in both patient (p = 0.032) and observer scales (p = 0.001), and VAS (p = 0.002). Scar surface area was significantly smaller in group A than in group NA (p = 0.002). ECC measurements showed higher values for melanin in group NA than in group A (p = 0.034).

Conclusion

Continuous intradermal absorbable suturing yields a better cosmetic result than interrupted nonabsorbable suturing in lower abdominal transverse appendectomy.