Workforce Considerations, Training, and Diseases in the Middle East.

Evaluating and providing global health assistance, humanitarian aid, and medical missions to Middle Eastern countries can be rewarding and challenging. A broad spectrum of financial capabilities supports effective health care delivery and infrastructure. Middle East tension can make obtaining a visa difficult. Personal safety considerations may hinder efforts to develop and carry out clinical and educational programs. Several Middle East countries have sophisticated and modern health care systems. Medical education and specialty training compares with that of Western medicine. The Middle East has a proud heritage as the foundation of many fundamental and modern medical and surgical principles.

The role of nerve monitoring to predict postoperative recurrent laryngeal nerve function in thyroid and parathyroid surgery.

OBJECTIVES/HYPOTHESIS: To determine the role and efficacy of intraoperative recurrent laryngeal nerve (RLN) stimulation in the prediction of early and permanent postoperative nerve function in thyroid and parathyroid surgery. STUDY DESIGN: A retrospective review of thyroid and parathyroid surgeries was performed with calculation of sensitivity and specificity of the response of intraoperative stimulation for different pathological groups. METHODS: Normal electromyography (EMG) response with 0.5 mAmp stimulation was considered a positive stimulation response with postoperative function determined by laryngoscopy. No EMG response at >1-2 mAmps was considered a negative response. The rates of early and permanent paralysis, as well as sensitivity, specificity, and positive and negative predictive values for postoperative nerve function were calculated for separate pathological groups. RESULTS: The number of nerves at risk analyzed was 909. The overall early and permanent paralysis rates were 3.1% and 1.2%, respectively, with the highest rate being for Grave's disease cases. The overall sensitivity was 98.4%. The specificity was lower at 62.5% but acceptable in thyroid carcinoma and Grave's disease patients. The majority of nerves with a positive stimulation result and postoperative paralysis on laryngoscopy recovered function in 3 to 12 weeks, showing positive stimulation to be a good predictor of eventual recovery. CONCLUSIONS: Stimulation of the RLN during thyroid and parathyroid surgery is a useful tool in predicting postoperative RLN function. The sensitivity of stimulation is high, showing positive stimulation to be an excellent predictor of normal nerve function. Negative stimulation is more predictive of paralysis in cases of thyroid carcinoma and Grave's disease. LEVEL OF EVIDENCE: 2b.

Endothelial cell migration was impaired by irradiation-induced inhibition of SHP-2 in radiotherapy: an in vitro study.

The response of endothelial cells to radiation in the context of wound healing is not yet completely understood. In this study we investigated the mechanism involved in the wound healing process after low linear energy transfer (LET) radiation exposure. A scratch wound model on primary vascular endothelial cell monolayer was exposed to acute dose of 0.1, 2 or 10 Gy. The number of cells crossing the wound border and the wound closure percentage was measured. The expression of α(v)ß3 integrins, focal adhesion kinase (FAK) and phosphorylated FAK (tyr397) as well as SHP-2 phosphatase were assayed through immunoblotting, immunoprecipitation and optical imaging. Compared to the low dose irradiation, 2 and 10 Gy had remarkably inhibitory effects on cell motility and consequently the wound closure. Integrins α(v) and ß3 showed no irradiation-dose dependent variation. Contrast to the relatively constant level of FAK in all groups, the amount of phosphor-FAK tyr397 was higher with dose increasing. The protein and PCR analysis of SHP-2 revealed an opposite expression pattern to FAK tyr397. In conclusion, radiation-induced inhibition of cell migration could be attributed to the irradiative inhibition to SHP-2 phosphatase, and the subsequent accumulated phosphorylated FAK abrogated the contraction-extension cycle of cytoskeletons.

Direct intratumoral infusion of liposome encapsulated rhenium radionuclides for cancer therapy: effects of nonuniform intratumoral dose distribution.

PURPOSE: Focused radiation therapy by direct intratumoral infusion of lipid nanoparticle (liposome)-carried beta-emitting radionuclides has shown promising results in animal model studies; however, little is known about the impact the intratumoral liposomal radionuclide distribution may have on tumor control. The primary objective of this work was to investigate the effects the intratumoral absorbed dose distributions from this cancer therapy modality have on tumor control and treatment planning by combining dosimetric and radiobiological modeling with in vivo imaging data. METHODS: 99mTc-encapsulated liposomes were intratumorally infused with a single injection location to human head and neck squamous cell carcinoma xenografts in nude rats. High resolution in vivo planar imaging was performed at various time points for quantifying intratumoral retention following infusion. The intratumoral liposomal radioactivity distribution was obtained from 1 mm resolution pinhole collimator SPECT imaging coregistered with CT imaging of excised tumors at 20 h postinfusion. Coregistered images were used for intratumoral dosimetric and radiobiological modeling at a voxel level following extrapolation to the therapeutic analogs, 186Re/ 18Re liposomes. Effective uniform dose (EUD) and tumor control probability (TCP) were used to assess therapy effectiveness and possible methods of improving upon tumor control with this radiation therapy modality. RESULTS: Dosimetric analysis showed that average tumor absorbed doses of 8.6 Gy/MBq (318.2 Gy/mCi) and 5.7 Gy/MBq (209.1 Gy/mCi) could be delivered with this protocol of radiation delivery for 186Re/188Re liposomes, respectively, and 37-92 MBq (1-2.5 mCi)/g tumor administered activity; however, large intratumoral absorbed dose heterogeneity, as seen in dose-volume histograms, resulted in insignificant values of EUD and TCP for achieving tumor control. It is indicated that the use of liposomes encapsulating radionuclides with higher energy beta emissions, dose escalation through increased specific activity, and increasing the number of direct tumor infusion sites improve tumor control. For larger tumors, the use of multiple infusion locations was modeled to be much more efficient, in terms of activity usage, at improving EUD and TCP to achieve a tumoricidal effect. CONCLUSIONS: Direct intratumoral infusion of beta-emitting radionuclide encapsulated liposomes shows promise for cancer therapy by achieving large focally delivered tumor doses. However, the results of this work also indicate that average tumor dose may underestimate tumoricidal effect due to substantial heterogeneity in intratumoral liposomal radionuclide distributions. The resulting intratumoral distribution of liposomes following infusion should be taken into account in treatment planning and evaluation in a clinical setting for an optimal cancer therapy.

Interventional therapy of head and neck cancer with lipid nanoparticle-carried rhenium 186 radionuclide.

PURPOSE: Minimally invasive interventional cancer therapy with drug-carrying lipid nanoparticles (ie, liposomes) via convection-enhanced delivery by an infusion pump can increase intratumoral drug concentration and retention while facilitating broad distribution throughout solid tumors. The authors investigated the utility of liposome-carrying beta-emitting radionuclides to treat head and neck cancer by direct intratumoral infusion in nude rats. MATERIALS AND METHODS: Four groups of nude rats were subcutaneously inoculated with human tongue cancer cells. After tumors reached an average size of 1.6 cm(3), the treatment group received an intratumoral infusion of liposomal rhenium-186 ((186)Re) (185 MBq [5 mCi]/cm(3) tumor). Three control groups were intratumorally infused with unlabeled liposomes, unencapsulated (186)Re-perrhenate, or unencapsulated intermediate (186)Re compound ((186)Re-N,N-bis[2-mercaptoethyl]-N',N'-diethyl-ethylenediamine [BMEDA]). In vivo distribution of (186)Re activity was measured by planar gamma-camera imaging. Tumor therapy and toxicity were assessed by tumor size, body weight, and hematology. RESULTS: Average tumor volume in the (186)Re-liposome group on posttreatment day 14 decreased to 87.7% +/- 20.1%, whereas tumor volumes increased to 395.0%-514.4% on average in the other three groups (P< .001 vs (186)Re-liposome). The (186)Re-liposomes provided much higher intratumoral retention of (186)Re activity, resulting in an average tumor radiation absorbed dose of 526.3 Gy +/- 93.3, whereas (186)Re-perrhenate and (186)Re-BMEDA groups had only 3.3 Gy +/- 1.2 and 13.4 Gy +/- 9.2 tumor doses, respectively. No systemic toxicity was observed. CONCLUSIONS: Liposomal (186)Re effectively treated head and neck cancer with minimal side effects after convection-enhanced interventional delivery. These results suggest the potential of liposomal (186)Re for clinical application in interventional therapy of cancer.

Intraoperative therapy with liposomal drug delivery: retention and distribution in human head and neck squamous cell carcinoma xenograft model.

The focus of this study is to investigate the retention and biodistribution of technetium-99m ((99m)Tc) labeled liposomes in a human head and neck squamous cell carcinoma (HNSCC) positive surgical margin animal xenograft model. Positive surgical margin (with margin<1mm) in HNSCC is associated with significant higher mortality and recurrence rate when compared to clear margin. An immediate intraoperative application of liposome-carried therapeutic agents may treat the residual disease intraoperatively and improve long term survival in these patients. To understand the feasibility of this intraoperative therapy in HNSCC, the in vivo behavior of liposomes after intraoperative administration of (99m)Tc-labeled liposomes using non-invasive nuclear imaging was investigated in an animal xenograft model. Neutral and cationic (99m)Tc-labeled liposomes of 100 nm, 1 microm and 2 microm in diameter (6 study groups with 4 rats per study group) were injected into a nude rat HNSCC positive surgical margin xenograft model. Intratumoral, locoregional, and systemic retention and distribution of the (99m)Tc-liposomes were determined using non-invasive nuclear imaging and post-mortem organ distribution. The (99m)Tc-liposomes demonstrated high locoregional retention rate of 55.9+/-3.7% to 72.9+/-2.4% at 44 h after intraoperative injection to allow significant radiation to the surgical cavity if therapeutic radionuclides were used. Overall, the cationic liposomes demonstrated higher intratumoral retention rate, and the neutral liposomes showed greater retention in the paratumoral cavity (p<0.05 respectively). In conclusion, intraoperative therapy with liposome carried radionuclide drug delivery system carries great potential in treating unresectable HNSCC, and further study using therapeutic radionuclide should be explored.

Real-time iterative monitoring of radiofrequency ablation tumor therapy with 15O-water PET imaging.

UNLABELLED: A method that provides real-time image-based monitoring of solid tumor therapy to ensure complete tumor eradication during image-guided interventional therapy would be a valuable tool. The short, 2-min half-life of (15)O makes it possible to perform repeated PET imaging at 20-min intervals at multiple time points before and after image-guided therapy. In this study, (15)O-water PET was evaluated as a tool to provide real-time feedback and iterative image guidance to rapidly monitor the intratumoral coverage of radiofrequency (RF) ablation therapy. METHODS: Tumor RF ablation therapy was performed on head and neck squamous cell carcinoma (SCC) xenograft tumors (length, approximately 23 mm) in 6 nude rats. The tumor in each animal was ablated with RF (1-cm active size ablation catheter, 70 degrees C for 5 min) twice in 2 separate tumor regions with a 20-min separation. The (15)O-water PET images were acquired before RF ablation and after the first RF and second RF ablations using a small-animal PET scanner. In each PET session, approximately 100 MBq of (15)O-water in 1.0 mL of saline were injected intravenously into each animal. List-mode PET images were acquired for 7 min starting 20 s before injection. PET images were reconstructed by 2-dimensional ordered-subset expectation maximization into single-frame images and dynamic images at 10 s/frame. PET images were displayed and analyzed with software. RESULTS: Pre-RF ablation images demonstrate that (15)O-water accumulates in tumors with (15)O activity reaching peak levels immediately after administration. After RF ablation, the ablated region had almost zero activity, whereas the unablated tumor tissue continued to have a high (15)O-water accumulation. Using image feedback, the RF probe was repositioned to a tumor region with residual (15)O-water uptake and then ablated. The second RF ablation in this new region of the tumor resulted in additional ablation of the solid tumor, with a corresponding decrease in activity on the (15)O-water PET image. CONCLUSION: (15)O-water PET clearly demonstrated the ablated tumor region, whereas the unablated tumor continued to show high (15)O-water accumulation. (15)O-water imaging shows promise as a tool for on-site, real-time monitoring of image-guided interventional cancer therapy.

Intraoperative 186Re-liposome radionuclide therapy in a head and neck squamous cell carcinoma xenograft positive surgical margin model.

PURPOSE: Positive surgical margins in advanced head and neck squamous cell carcinoma (HNSCC) have a well-documented association with an increased risk of locoregional recurrence and significantly poorer survival. Traditionally, unresectable tumor is treated with postoperative radiotherapy and/or chemotherapy. However, these therapeutic options can delay treatment and increase toxicity. The potential value of intraoperative injection of liposomal therapeutic radionuclides as a locoregional, targeted therapy in unresectable advanced HNSCC was assessed in a nude rat xenograft positive surgical margin model. EXPERIMENTAL DESIGN: The therapeutic effects of beta-emission rhenium-186 (186Re) carried by liposomes into the tumor remnants in a nude rat squamous cell carcinoma xenograft model were studied. Following the partial resection of tumor xenografts, the animals were intratumorally injected with 186Re-labeled or unlabeled (control) neutrally charged or positively charged 100-nm-diameter liposomes. Tumor size, body weight, hematology, and toxicity were monitored for 35 days posttherapy. RESULTS: The neutral (n = 4) and cationic (n = 4) liposome control groups showed an increase in tumor growth of 288.0 +/- 37.3% and 292.2 +/- 133.7%, respectively, by day 15. The 186Re-neutral-liposome group (n = 8) and the 186Re-cationic-liposome group (n = 8) presented with an average final tumor volume of 25.6 +/- 21.8% and 28.5 +/- 32.2%, respectively, at the end of the study (day 35). All groups showed consistent increases in body weight. No significant systemic toxicity was observed in any of the animals. CONCLUSIONS: With excellent tumor suppression and minimal side-effect profile, the intraoperative use of liposomal therapeutic radionuclides may play a role in the management of positive surgical margins in advanced HNSCC.

Management of the unknown primary carcinoma: long-term follow-up on a negative PET scan and negative panendoscopy.

BACKGROUND: The unknown primary carcinoma in the head and neck has been estimated to represent up to 7% of all head and neck carcinomas. In an attempt to identify the occult primary tumor the evaluation of this patient population has included a complete head and neck examination, flexible fiberoptic endoscopy, and imaging with CT/MRI. More recently, positron emission tomography (PET) has been advocated as a tool to detect primary tumors. METHODS: A cohort of 31 patients with fine-needle aspiration biopsy-confirmed squamous cell carcinoma were prospectively entered into a diagnostic protocol to identify the occult primary tumor. The diagnostic protocol included a comprehensive head and neck examination (including flexible endoscopy) and CT and/or MRI. If the initial diagnostic evaluation failed to identify a primary tumor, the patients then underwent whole body PET imaging followed by staging endoscopy with biopsy of the at-risk occult tumor sites. The outcome measures included the accuracy of the PET to predict the presence of occult tumor at staging endoscopy and the accuracy of the negative PET and negative panendoscopy in predicting the subsequent development of a primary tumor in the upper aerodigestive tract during follow-up. RESULTS: The PET detected 9 occult primary tumors in the 31 patients (detection rate, 29%). Five occult primary tumors (2 base of tongue and 3 palatine tonsil) were detected during panendoscopy despite a negative PET. The combination of PET and panendoscopy detected 45.2% of the unknown primary tumors. Seventeen patients (N1, n = 7; N2a, n = 4; N2b, n = 2; N3, n = 4) had no primary tumor detected and were treated as an unknown primary carcinoma with primary neck dissection +/- radiation therapy +/- chemotherapy. In this series of 17 patients, there were 3 neck recurrences (17.6%). In addition, only 1 patient (5.8%) developed a primary tumor of the upper aerodigestive tract with a mean follow-up of 31.1 months (range, 21-60 months). CONCLUSION: A negative PET study in patients with an occult primary head and neck carcinoma does not preclude the need for panendoscopy with biopsy to detect the occult primary tumor. The risk of subsequent primary tumor appears to be low in the patients with a negative PET and a negative panendoscopy (<6%).

Setup and characterization of a human head and neck squamous cell carcinoma xenograft model in nude rats.

OBJECTIVE: To develop and characterize a new head and neck cancer animal model. STUDY DESIGN: A human head and neck squamous cell carcinoma (HNSCC) xenograft model in nude rats was established via subcutaneous inoculation of a human-origin HNSCC cell line, SCC-4. The tumor was evaluated for growth characteristics, pathologic features by hematoxylin-eosin (HE) staining, and immunohistochemistry of epidermal growth factor receptor (EGFR). 2-[18F] fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography (PET) imaging characteristics were studied too. RESULTS: A new HNSCC animal model was successfully established. Tumor sizes reached about 1 cm3 on day 15 after tumor cell inoculation. HE staining pathology has confirmed that this tumor is a typical SCC. EGFR immunohistochemistry demonstrated this tumor model to be strongly EGFR positive. 18F-FDG PET study has shown that 18F-FDG accumulated in tumors. CONCLUSIONS: This study has demonstrated that this tumor model is an appropriate HNSCC tumor model for animal studies on HNSCC.

The endoscopic management of Zenker diverticulum: CO2 laser versus endoscopic stapling.

OBJECTIVE: The purpose of this project was to analyze the endoscopic management of Zenker diverticulum (ZD) using both the CO2 laser and endoscopic stapling techniques. This study compares the two techniques in terms of diverticulum size, onset to oral intake, hospital stay, resolution of symptoms (dysphagia and regurgitation), and complications. STUDY DESIGN: A retrospective consecutive case series was performed at an academic medical center. METHODS: Forty patients underwent an attempted endoscopic resection of the ZD using either the CO2 laser or the endoscopic stapling technique. The two techniques were compared on a variety of parameters, including diverticulum size, hospital stay, onset to oral intake, resolution of symptoms, and complications. Symptom scores were obtained before and after surgery with a patient self-reported scoring report (scale 0-3 for both dysphagia and regurgitation with 0 indicating asymptomatic and 3 severe symptoms). RESULTS: Forty patients underwent an attempted endoscopic management of ZD. Five patients (12.5%) failed endoscopic exposure (four converted to open, one observed). Sixteen patients underwent CO2 laser management and 19 underwent endoscopic stapling. The mean diverticulum size (3.8 cm CO2 laser versus 4.4 cm stapling) was not significantly different for the two groups. Both groups demonstrated a significant decrease in preoperative versus postoperative dysphagia and regurgitation symptoms scores, respectively, CO2 laser dysphagia scores decreasing from 2.75 to 1.38 and the regurgitation score dropping from 1.51 to 0.68, whereas endoscopic stapling dysphagia score decreased from 2.74 to 1.21 and the regurgitation score dropped from 1.37 to 0.53. Overall, 86% of patients demonstrated an onset of liquid intake on postoperative day 1 and the average length of stay was 3.4 days in the CO2 laser group and 1.5 days in the endoscopic stapling (P < .0015). Complications included dental trauma in four patients (two CO2 laser and two stapling) and subcutaneous air in three patients (all three CO2 laser). There were no cases of mediastinitis, recurrent laryngeal nerve injury, fistula, or perioperative death. CONCLUSIONS: The endoscopic management of ZD is a safe and effective technique. The endoscopic stapling technique appears to have an improved efficacy and safety when compared with the CO2 laser technique. The two techniques are compared and contrasted.

The role of positron emission tomography scans in the management of the N-positive neck in head and neck squamous cell carcinoma after chemoradiotherapy.

OBJECTIVE: The objective of this study was to determine the sensitivity, specificity, and predictive value of 18-fluorodeoxyglucose positron emission tomography (PET) in predicting residual cervical metastatic disease in patients with N-positive necks undergoing curative radiotherapy and chemoradiotherapy for squamous cell carcinoma (SCC) of the upper aerodigestive tract. METHODS: The authors studied a prospective case series of patients (2003-2005) of patients undergoing radiotherapy and chemoradiotherapy for advanced head and neck SSC. Study entry criteria included N-positive neck disease, a complete response to treatment at the primary tumor site, posttreatment PET scan (8-12 weeks after completion of treatment), followed by salvage neck dissection. The posttreatment PET scan neck findings were correlated to the salvage neck dissection pathology report. The sensitivity, specificity, and predictive values of the PET scan to predict residual cervical metastatic disease after curative chemoradiotherapy were calculated. RESULTS: Twenty-one neck dissections (pretreatment N1 = 5, N2a = 2, N2b = 8, N3 = 6) were entered into the protocol. Four (19.0%) of the 21 neck specimens were positive for residual cervical metastatic disease, whereas the remaining 17 (80.9%) specimens demonstrated no residual carcinoma. The overall sensitivity and specificity were 75.0% and 64.7%, respectively. The positive predictive value was 33% and the negative predictive value was 91.7%. CONCLUSIONS: Although the role of posttreatment neck dissection remains controversial, the surgeon must rely on clinical examination and imaging studies. Our practice has been to perform planned staged neck dissections on all N2 and N3 necks, as well as N1 necks with an incomplete response to treatment. Based on this small prospective study, it appears that PET imaging lacks adequate sensitivity and specificity to reliably predict the presence of residual cervical metastatic disease after completion of chemoradiotherapy. With a negative predictive value of 91.7%, however, a negative PET scan appears to be a reliable predictor of the absence of residual tumor.

Potential use of drug carried-liposomes for cancer therapy via direct intratumoral injection.

Liposomes have recognized advantages as nano-particle drug carriers for tumor therapy. In this study, the pharmacokinetics and distribution of intratumorally administered liposomes were investigated as drug carriers for treating solid tumors via direct intratumoral administration. 99mTc-liposomes were administered intratumorally to nude rats bearing human head and neck squamous cell carcinoma xenografts. Planar gamma camera images were analyzed to evaluate the local retention of the intratumorally administered liposomes. Co-registered pinhole micro-single photon emission computed tomography (SPECT)/computed tomography (CT) images were acquired of the whole animal as well as the dissected tumors to determine intratumoral distribution of the 99mTc-liposomes. For 99mTc-liposomes, there was an initial retention of 47.4 +/- 11.0% (n = 4) in tumors and surrounding tissues. At 20 h, 39.2 +/- 10.6% (n = 4) of 99mTc-activity still remained in the tumor. In contrast, only 18.7 +/- 3.3% (n = 3) of the intratumoral 99mTc-activity remained for unencapsulated 99mTc-complex at 20 h. Pinhole micro-SPECT images demonstrated that 99mTc-liposomes also have a superior intratumoral 99mTc-activity diffusion compared with unencapsulated 99mTc-complex. Higher intratumoral retention of 99mTc-liposomes accompanied by an improved intratumoral diffusion suggests that intratumorally administered liposomal drugs are potentially promising agents for solid tumor local therapy.

Risk factors for the development of hypothyroidism after hemithyroidectomy.

OBJECTIVES: To assess the incidence of hypothyroidism after hemithyroidectomy and to identify risk factors for the development of hypothyroidism. DESIGN: Retrospective analysis. SETTING: A tertiary care academic medical center. PATIENTS: The study included 90 patients who underwent a hemithyroidectomy from 1999 to 2004. MAIN OUTCOME MEASURES: Hypothyroidism was defined as a serum thyrotropin level greater than 6.0 mIU/L at least 8 weeks after hemithyroidectomy. All patients were analyzed for age, sex, surgical indications, preoperative and postoperative thyrotropin levels, weight of resected specimen, final pathologic analysis, and length of follow-up. Multivariate analysis was performed to identify multiple risk factors for the development of hypothyroidism. RESULTS: The final pathologic analysis demonstrated 49 follicular adenomas, 17 cases of Hashimoto thyroiditis, 10 multinodular goiters, and 14 other abnormalities. The overall incidence of the development of hypothyroidism after hemithyroidectomy was 27% (24 of 90 patients). When the groups were broken down by pathologic diagnosis, the incidence of hypothyroidism developing during follow-up among the Hashimoto thyroiditis and multinodular goiter groups was 59% and 50%, respectively. Also, the patients who developed hypothyroidism were noted to have statistically significant higher preoperative serum thyrotropin levels (3.15 mIU/L vs 1.95 mIU/L; P<.001) than those who remained euthyroid. There was no relationship between age, sex, or weight of the resected tissue and the subsequent risk of hypothyroidism. CONCLUSIONS: The overall incidence of posthemithyroidectomy hypothyroidism was 27%, and the majority of cases developed in the first 6 to 12 months after surgery. Risk factors for the development of hypothyroidism include pathologic diagnosis (Hashimoto thyroiditis and multinodular goiter) as well as a high-normal serum thyrotropin level. Routine monitoring of serum thyrotropin levels should be performed in all patients who undergo a hemithyroidectomy.

Positron emission tomography in the management of unknown primary head and neck carcinoma.

OBJECTIVE: To assess the role of positron emission tomography (PET) in the management of unknown primary carcinoma of the head and neck region. DESIGN AND SETTING: Prospective case series at an academic medical center. PATIENTS: Twenty-six patients with an open excisional biopsy or a fine-needle aspiration biopsy finding that confirmed squamous cell carcinoma of the cervical lymph nodes and no visible primary tumor (as determined by results of a comprehensive physical examination and computed tomography and/or magnetic resonance imaging) underwent PET. The standard evaluation consisted of a comprehensive head and neck examination that included fiberoptic laryngoscopy/nasopharyngoscopy, computed tomography and/or magnetic resonance imaging, and PET followed by panendoscopy with selected biopsies and tonsillectomy. MAIN OUTCOME MEASURES: Sensitivity, specificity, and positive and negative predictive values of PET to detect an occult primary tumor. RESULTS: The PET detected 8 occult primary tumors in 26 patients (detection rate, 30.8%). Four occult primary tumors (2 at the base of the tongue and 2 in the tonsil) were detected during routine panendoscopy with negative PET findings. The sensitivity of PET was 66.0%, with a specificity of 92.9%. The positive predictive value was 88.8%, and the negative predictive value was 76.5%. CONCLUSIONS: Positron emission tomography can be a valuable tool to identify a subset of patients with an occult primary tumor in the head and neck region. In addition, it can be used to screen for primary tumors below the clavicle. Early identification of the primary tumor may allow for more accurate tumor staging and targeted radiotherapy to minimize adverse effects and complications. A normal PET finding, however, does not eliminate the need for a careful panendoscopy with directed biopsies and tonsillectomy.

Theoretical study of the influence of a heterogeneous activity distribution on intratumoral absorbed dose distribution.

Radioimmunotherapy of hematopoeitic cancers and micrometastases has been shown to have significant therapeutic benefit. The treatment of solid tumors with radionuclide therapy has been less successful. Previous investigations of intratumoral activity distribution and studies on intratumoral drug delivery suggest that a probable reason for the disappointing results in solid tumor treatment is nonuniform intratumoral distribution coupled with restricted intratumoral drug penetrance, thus inhibiting antineoplastic agents from reaching the tumor's center. This paper describes a nonuniform intratumoral activity distribution identified by limited radiolabeled tracer diffusion from tumor surface to tumor center. This activity was simulated using techniques that allowed the absorbed dose distributions to be estimated using different intratumoral diffusion capabilities and calculated for tumors of varying diameters. The influences of these absorbed dose distributions on solid tumor radionuclide therapy are also discussed. The absorbed dose distribution was calculated using the dose point kernel method that provided for the application of a three-dimensional (3D) convolution between a dose rate kernel function and an activity distribution function. These functions were incorporated into 3D matrices with voxels measuring 0.10 x 0.10 x 0.10 mm3. At this point fast Fourier transform (FFT) and multiplication in frequency domain followed by inverse FFT (iFFT) were used to effect this phase of the dose calculation process. The absorbed dose distribution for tumors of 1, 3, 5, 10, and 15 mm in diameter were studied. Using the therapeutic radionuclides of 131I, 186Re, 188Re, and 90Y, the total average dose, center dose, and surface dose for each of the different tumor diameters were reported. The absorbed dose in the nearby normal tissue was also evaluated. When the tumor diameters exceed 15 mm, a much lower tumor center dose is delivered compared with tumors between 3 and 5 mm in diameter. Based on these findings, the use of higher beta-energy radionuclides, such as 188Re and 90Y is more effective in delivering a higher absorbed dose to the tumor center at tumor diameters around 10 mm.

Computed tomography-generated templates: a new approach to frontal sinus osteoplastic flap surgery.

BACKGROUND: The aim of this study was to present a new technique for frontal sinus template creation used in osteoplastic flap surgery, obviating the need for the traditional 6-ft Caldwell radiograph. METHODS: Seventeen human cadaver skulls were studied prospectively. Using digital addition algorithms of sequential coronal computed tomography (CT) images of the frontal sinus to create a composite image, an image is printed to 1 cm = 1 cm scale. A frontal sinus template was created using this processed image and compared with a control 6-ft Caldwell radiograph. RESULTS: The mean variance between corresponding vertical points on the templates was 0.71 mm (95% confidence interval, 0.56-0.87 mm). The mean variance between horizontal points was 1.11 mm (95% confidence interval, 0.97-1.28 mm). The mean difference in width was 2.46 mm. The plain film templates were always wider than the CT-generated templates. CONCLUSION: The CT-generated frontal sinus templates are virtually identical to the Caldwell radiograph-derived templates. They may obviate the need for additional imaging and minimize the potential errors commonly associated with 6-ft Caldwell templates.