Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery.

Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

Best Practices for Robotic Surgery Programs.

BACKGROUND AND OBJECTIVES: Robotic surgical programs are increasing in number. Efficient methods by which to monitor and evaluate robotic surgery teams are needed. METHODS: Best practices for an academic university medical center were created and instituted in 2009 and continue to the present. These practices have led to programmatic development that has resulted in a process that effectively monitors leadership team members; attending, resident, fellow, and staff training; credentialing; safety metrics; efficiency; and case volume recommendations. RESULTS: Guidelines for hospitals and robotic directors that can be applied to one's own robotic surgical services are included with examples of management of all aspects of a multispecialty robotic surgery program. CONCLUSION: The use of these best practices will ensure a robotic surgery program that is successful and well positioned for a safe and productive environment for current clinical practice.

Comparison of SPECT/CT and planar MIBI in terms of operating time and cost in the surgical management of primary hyperparathyroidism.

We conducted a retrospective study to compare operating times and costs in patients who underwent guided parathyroidectomies with either (1) technetium-99m ((99m)Tc) multiplex ion-beam imaging (MIBI) parathyroid scintigraphy with single-photon emission computed tomography/computed tomography (SPECT/CT) fusion images or (2) sestamibi dual-phase (99m)Tc MIBI planar parathyroid scintigraphy alone preoperatively. Our study population was made up of the first 24 patients at our facility who had undergone SPECT/CT parathyroid imaging with technetium-99m ((99m)Tc) MIBI and a group of 24 patients who had undergone MIBI planar imaging alone. Patient demographics, preoperative laboratory test results, operating times, and hospital charges were analyzed. We found that less operating time was required for the planar MIBI group than in the SPECT/CT group (mean: 135 vs. 158 min), although the difference was not statistically significant. Likewise, the total cost of treatment was lower in the planar MIBI group (mean: $10,035 vs. $11,592); the difference was statistically significant by one measure (p × 0.02, Wilcoxon rank sum test) but not by another (p × 0.06, Student t test). Although SPECT/CT is efficient for patients with small and difficult-to-localize adenomas, it has yet to demonstrate greater efficacy or cost-effectiveness than planar MIBI for routine parathyroidectomy in patients with primary hyperparathyroidism when an easily identifiable parathyroid adenoma is localized.

The Cost of Hospice Services in Terminally Ill Patients With Head and Neck Cancer.

IMPORTANCE: Hospice care has been suggested as a way to preserve dignity and to lower costs at the end of life, which may be particularly important for patients with head and neck cancer because this disease is associated with considerable morbidity and a high mortality risk. OBJECTIVES: To use data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to estimate monthly costs of all services used during the last months of life by patients with oral cavity and pharyngeal cancers and to determine whether those who used hospice services had lower costs. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of SEER-Medicare data (January 1, 1995, to December 31, 2007). The setting was all participating SEER hospitals that treated patients with oral cavity or pharyngeal cancer. Participants were 65 years and older who were diagnosed as having oral cavity (n = 4205) or pharyngeal (n = 3178) cancer between January 1, 1995, and December 31, 2005, who subsequently died between January 1, 1995, and December 31, 2007. EXPOSURE: Use of hospice services before death. MAIN OUTCOMES AND MEASURES: Hospice use was identified through Medicare claims. The primary outcome was all-cause Medicare expenditures, inflated to 2009 US dollars. We used a propensity score analysis to estimate the difference in the mean costs to Medicare in the last month of life between patients who used hospice services and patients who did not use hospice services. RESULTS: Most patients (63.4% [1018 of 1605] with oral cavity cancer and 57.8% [644 of 1114] with pharyngeal cancer) who enrolled in hospice did so within 30 days of death. Patients who received hospice care had $7035 (95% CI, $6040-$8160) lower costs in the last month of life for oral cavity cancer and $7430 (95% CI, $6340-$9100) lower costs in the last month of life for pharyngeal cancer. These cost savings were greater in the last month of life when patients enrolled in hospice more than 30 days before death. CONCLUSIONS AND RELEVANCE: Encouraging hospice admissions for patients with oral cavity and pharyngeal cancers provides not only compassionate, dignified care at the end of life but also an opportunity for substantial savings in health care costs.

Determinants of Medicare Costs for Elderly Patients With Oral Cavity and Pharyngeal Cancers.

IMPORTANCE: In the United States, nearly 8400 patients die each year from oral cavity and pharynx cancers, most of whom are 65 years and older; however, the costs attributable to these cancers are not well described. OBJECTIVE: To identify the primary determinants of cost in patients with oral and pharyngeal cancer. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cohort analysis of data from Medicare and Surveillance, Epidemiology, and End Results hospitals (January 1, 1995, through December 31, 2005), we studied patients 66 years and older with newly diagnosed oral cavity (n = 6724) and pharyngeal (n = 3987) cancers. MAIN OUTCOMES AND MEASURES: Five-year cumulative costs, defined as Medicare Parts A and B payments, were estimated using inverse probability weighting. Linear regression analysis with inverse probability weighting was used in multivariate analyses of costs to estimate the effects of covariates on cumulative costs. RESULTS: In multivariate analyses, costs were significantly increased by demographics, comorbidities, and treatment selection. Compared with white patients, African Americans accumulated $11,450 (95% CI, $1320-$22,299) and $25,093 (95% CI, $14,917-$34,985) more in costs for oral cavity and pharyngeal cancers, respectively. The presence of 1 or 2 comorbidities increased the mean 5-year cumulative costs by $13,342 (95% CI, $6248-$19,186) and $14,139 (95% CI, $6009-$22,217) for patients with oral cavity and pharyngeal cancers, respectively. For 3 or more comorbidities, the mean 5-year cumulative costs increased by $22,196 (95% CI, $15,319-$28,614) and $27,799 (95% CI, $19,139-$36,702) for patients with oral cavity and pharyngeal cancers, respectively. Patients who received chemotherapy accumulated a mean of $26,919 (95% CI, $18,309-$35,056) and $37,407 (95% CI, $29,971-$44,644) more in costs by 5 years for oral cavity and pharyngeal cancers, respectively. CONCLUSIONS AND RELEVANCE: Oral and pharyngeal cancer is burdensome to elderly patients from a Medicare cost perspective. Several factors were associated with 5-year costs, including some modifiable factors that may be potential targets for interventions to reduce overall costs.

Public awareness of human papillomavirus as a causative factor for oropharyngeal cancer.

OBJECTIVE: To assess the public's awareness of human papillomavirus (HPV) as a causative factor for oropharyngeal cancer. STUDY DESIGN: Twenty-three-item survey. SETTING: Local shopping malls and Maxwell Air Force Base in 2012. METHODS: Respondents were randomly chosen to participate in 23-item survey at various local shopping malls and at Maxwell Air Force Base in 2012. The χ(2) test was used in statistical analysis. RESULTS: The majority of respondents (n = 319) were civilians; 158 were military officer trainees (MOTs). All MOTs had a bachelor's degree or higher, while 37% of civilian respondents had a bachelor's degree or higher. Most MOTs (82%) were aware of oropharyngeal cancer, and 53% of civilians had not heard of oropharyngeal cancer (P < .0001). Most respondents (73% civilian and 91% military) were aware of the association between HPV and cervical cancer. Conversely, 75% of civilian population and 49% of MOTs were not aware of the association between HPV and oropharyngeal cancer (P < .0001). The majority of respondents (61% military and 81% civilian) did not know that both sexes were eligible for HPV vaccine (P < .0001). CONCLUSIONS: Most respondents were aware that HPV is a causative agent of cervical cancer. However, the majority were not aware of the association between oropharyngeal cancer and HPV. Furthermore, many respondents were not aware that HPV equally affects males and females and that the vaccine is available for both sexes. This underscores the need to educate the public on the availability of HPV vaccine and the association between HPV and oropharyngeal cancer.

Imaging, genetic testing, and biomarker assessment of follicular cell-derived thyroid cancer.

Thyroid carcinoma is the most common endocrine malignancy worldwide, and its incidence continues to increase. As such the approach to a recently identified thyroid nodule is important to understand. The relevant imaging, examination, and need for fine-needle aspiration biopsy (FNA) are discussed. In approximately 25% of nodules, the diagnosis cannot be established with FNA-based cytology, and surgical excision is necessary for definitive diagnosis. Recent advances in genetic and molecular testing may increase the diagnostic accuracy of FNA in managing thyroid nodules.

Attributable costs of differentiated thyroid cancer in the elderly Medicare population.

BACKGROUND: Little is known about costs associated with differentiated thyroid cancer (DTC) and follow-up care. This study used data from the Surveillance Epidemiology and End Results (SEER) database to examine cumulative costs attributable to disease stage and treatment options of DTC in elderly patients over 5 years. METHODS: We identified 2,823 patients aged >65 years with DTC and 5,646 noncancer comparison cases from SEER Medicare data between 1995 and 2005. Cumulative costs were obtained by estimating average costs/patient in each month up to 60 months after diagnosis. We performed multivariate analyses of costs by fitting each monthly cost to linear models, controlling for demographics and comorbidities. Marginal effects of covariates were obtained by summing coefficients over 60 months. RESULTS: Cumulative costs were $17,669/patient the first year and $48,989/patient 5 years after diagnosis. Regional disease was associated with higher costs at 1 year ($9,578) and 5 years ($8,902). Distant disease was associated with 1-year costs of $28,447 and 5-year costs of $20,103. Patients undergoing surgery and radiation had a decrease in cost of $722 at 5 years. CONCLUSION: DTC in the elderly is associated with significant economic burden largely attributable to patient demographics, stage of disease, and treatment modalities.

Outcomes of thyroid cancer in African Americans.

CONTEXT: Thyroid cancer, the most common endocrine cancer, is on the rise. It is less common in the African American (AA) population in the United States. Few studies have looked at outcome disparities for different patient populations, particularly those involving race. OBJECTIVE: Using data from the SEER registry, we sought to determine whether five-year survival differed significantly between AA and White patients and, whether differences were due to patient or disease characteristics. DESIGN: Retrospective cohort analysis. Univariate comparisons were made using Student-t tests for continuous variables, chi-square tests for categorical variables. Survivor functions were estimated using Kaplan-Meier curves, and comparisons were made by log rank tests. SETTING AND PATIENTS: 26,902 patients (25,210 White and 1,692 AA) were diagnosed with thyroid cancer between 1992 and 2006. MAIN OUTCOME MEASURE(S): Five-year survival defined as time from diagnosis to death from cancer within five years. RESULTS: AA had a significantly lower rate of five-year survival compared to Whites (96.5% vs 97.4%, P = .006). AA patients were 2.3 times more likely to be diagnosed with anaplastic disease (Risk ratio [RRI = 2.33 (95% CI: 1.52-3.58), P = .0001), and were also nearly 80% more likely to be diagnosed with follicular disease (RR = 1.78 [95% CI: 1.59-1.99], P < .0001). They were nearly twice as likely to have larger tumors (> or = 4 cm) than White patients (RR = 1.94 [95% CI: 1.78-2.12], P < .0001). CONCLUSIONS: AA had poorer survival from thyroid cancer relative to White patients; this difference may be explained by differences in disease characteristics such as a relatively higher rate of anaplastic thyroid cancer, follicular cancer and larger tumors at presentation.

A novel facile method of labeling octreotide with (18)F-fluorine.

UNLABELLED: Several methods have been developed to label peptides with (18)F. However, in general these are laborious and require a multistep synthesis. We present a facile method based on the chelation of (18)F-aluminum fluoride (Al(18)F) by 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The method is characterized by the labeling of NOTA-octreotide (NOTA-d-Phe-cyclo[Cys-Phe-d-Trp-Lys-Thr-Cys]-Throl (MH(+) 1305) [IMP466]) with (18)F. METHODS: Octreotide was conjugated with the NOTA chelate and labeled with (18)F in a 2-step, 1-pot method. The labeling procedure was optimized with regard to the labeling buffer, peptide, and aluminum concentration. Radiochemical yield, specific activity, in vitro stability, and receptor affinity were determined. Biodistribution of (18)F-IMP466 was studied in AR42J tumor-bearing mice and compared with that of (68)Ga-labeled IMP466. In addition, small-animal PET/CT images were acquired. RESULTS: IMP466 was labeled with Al(18)F in a single step with 50% yield. The labeled product was purified by high-performance liquid chromatography to remove unbound Al(18)F and unlabeled peptide. The radiolabeling, including purification, was performed in 45 min. The specific activity was 45,000 GBq/mmol, and the peptide was stable in serum for 4 h at 37 degrees C. Labeling was performed at pH 4.1 in sodium citrate, sodium acetate, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, and 2-(N-morpholino)ethanesulfonic acid buffer and was optimal in sodium acetate buffer. The apparent 50% inhibitory concentration of the (19)F-labeled IMP466 determined on AR42J cells was 3.6 nM. Biodistribution studies at 2 h after injection showed a high tumor uptake of (18)F-IMP466 (28.3 +/- 5.2 percentage injected dose per gram [%ID/g]; tumor-to-blood ratio, 300 +/- 90), which could be blocked by an excess of unlabeled peptide (8.6 +/- 0.7 %ID/g), indicating that the accumulation in the tumor was receptor-mediated. Biodistribution of (68)Ga-IMP466 was similar to that of (18)F-IMP466. (18)F-IMP466 was stable in vivo, because bone uptake was only 0.4 +/- 0.2 %ID/g, whereas free Al(18)F accumulated rapidly in the bone (36.9 +/- 5.0 %ID/g at 2 h after injection). Small-animal PET/CT scans showed excellent tumor delineation and high preferential accumulation in the tumor. CONCLUSION: NOTA-octreotide could be labeled rapidly and efficiently with (18)F using a 2-step, 1-pot method. The compound was stable in vivo and showed rapid accretion in somatostatin receptor subtype 2-expressing AR42J tumors in nude mice. This method can be used to label other NOTA-conjugated compounds with (18)F.

Percutaneous dilation tracheotomy versus surgical tracheotomy: our experience.

BACKGROUND: Percutaneous dilation tracheotomy (PDT) is becoming a popular alternative to surgical tracheotomy. In our department, we recently adopted the use of the PDT in intensive care unit patients. Here, we compare the results of the use of these 2 techniques on 150 patients, all performed by the same surgeon. We discuss the pros and cons of PDT and present our experience with the technique compared with surgical tracheotomy (ST). MATERIALS AND METHODS: A prospective study of 75 PDTs and a retrospective study of 75 surgical tracheotomies (ST) were performed at the Department of Otolaryngology-Head and Neck Surgery, Rambam Medical Center, Haifa, Israel. Age, sex, duration of intubation before surgery, time interval between the decision to perform and the performance of tracheotomy, and cost were compared. RESULTS: One hundred fifty tracheotomies were reviewed. The indication for tracheotomy in both groups was prolonged mechanical ventilation. Seven patients were found unsuitable for PDT and underwent ST. Complications included 3 cases of mild postoperative hemorrhage in the ST group, and 1 case of subcutaneous emphysema, 1 case of stomal cellulitis and 2 cases of mild postoperative hemorrhage in the PDT group. The average waiting interval was between 2 to 5 days for ST and 1 to 24 hours for PDT. The intraoperative time for ST was 20 minutes; for PDT, 5 minutes. The cost was 565 dollars for ST and 274 dollars for PDT. CONCLUSIONS: PTD provides an easy, less expensive, and convenient alternative to ST and should be added to the otolaryngologists' armamentarium of surgical airway procedures. The procedure is advantageous for the patient. Complication rates of both techniques are similar and low; however, PDT is a blind technique of obtaining a surgical airway and therefore holds more potential for serious complications. It is our conclusion that this technique is suitable for many, but not all, critical care patients and that the procedure should be performed only by surgeons who are capable of urgently obtaining a surgical airway or exploring the neck should the PDT fail.

An assessment of polymorphonuclear leukocyte rigidity in HIV-infected individuals after immune recovery.

PURPOSE: To determine whether polymorphonuclear leukocytes (PMNs) remain rigid after immune reconstitution in human immunodeficiency virus (HIV)-infected individuals with a history of severe immunosuppression. METHODS: PMN rigidity was measured in vitro in three groups: (1) HIV-infected individuals with a history of CD4+ T-lymphocyte counts of less than 50/microL, but with current counts of more than 200/microL attributable to potent antiretroviral therapy (group 1); (2) HIV-infected individuals whose CD4+ T-lymphocyte counts had always been more than 200/microL (group 2); and (3) HIV-negative control subjects. Rigidity was determined with a cell transit analyzer (containing a micropore filter with 30 identical, 8-microm diameter pores), representing a simple in vitro model of a capillary bed. A longer PMN pore transit time reflects increased PMN rigidity. RESULTS: PMN transit time (median) in group 1 (n = 11) was 3.34 ms, in group 2 (n = 9) was 3.19 ms, and in control subjects (n = 15) was 2.66 ms. PMN rigidity was significantly greater in groups 1 (P = 0.014) and 2 (P = 0.046) than in control subjects (Wilcoxon rank-sum test). A significant difference was not identified between groups 1 and 2 (P = 0.518). CONCLUSIONS: The increased PMN rigidity known to occur in severely immunosuppressed HIV-infected individuals persists after immune reconstitution. Furthermore, PMN rigidity is increased in those HIV-infected individuals who do not have a history of severe immunosuppression. Because PMN rigidity can alter microvascular blood flow, HIV-infected individuals may remain at risk for retinal vascular damage in the era of potent antiretroviral therapy.