Oral R115866 in the treatment of moderate to severe facial acne vulgaris: an exploratory study.

BACKGROUND: R115866 (Rambazole; Barrier Therapeutics NV, Geel, Belgium), a new-generation retinoic acid metabolism-blocking agent, is a nonretinoid compound enhancing intracellularly the endogenous levels of all-trans-retinoic acid by blocking its catabolism. By virtue of this property, and the proven positive effects of retinoids in the treatment of acne, R115866 could potentially be a useful drug for acne. OBJECTIVES: To explore the efficacy, safety and tolerability of systemic R115866 in male patients with moderate to severe facial acne vulgaris (at least 15 papules and/or pustules and at least two nodulocystic lesions). METHODS: In this exploratory trial, 17 patients were treated with oral R115866 1 mg once daily for 12 weeks, followed by a 4-week treatment-free period. RESULTS: At the end of treatment (week 12, n = 16) a mean reduction in inflammatory lesion count of 77.4% (P < 0.001), in noninflammatory lesion count of 58.3% (P < 0.001) and in total lesion count of 76.0% (P < 0.001) was observed as compared with baseline. All lesion counts were significantly reduced from week 4 onwards. Mild side-effects were reported occasionally. CONCLUSIONS: The current data indicate that treatment with oral R115866 1 mg once daily for 12 weeks in patients with moderate to severe facial acne vulgaris is efficacious and well tolerated and merits further investigation.

Comparison of automatic quantification software for the measurement of ventricular volume and ejection fraction in gated myocardial perfusion SPECT.

The aim of this study was to compare the performance of three different software packages for the calculation of ejection fraction (EF) and end diastolic volume (EDV) from gated myocardial single photon emission computed tomography studies. Two hundred patients undergoing gated stress myocardial perfusion scans were analysed retrospectively. Patients were grouped as follows: small heart (n=31), normal perfusion scan (n=71), and scan with perfusion defects (n=98). EF and EDV were calculated for each using QGS (Cedars Sinai, Los Angeles, CA), 4D-MSPECT (University of Michigan, Ann Arbor, MI), and ECT (Emory University, Atlanta, GA). Bland-Altman plots, repeated measures ANOVA, and linear regression analysis were used to compare methods. Correlation coefficients between the methods for both EF and EDV were high, greater than 0.9. However, Bland-Altman plots revealed a large standard deviation of the difference between methods, preventing the confident estimate of the value of one method from an observation of another. Despite good correlation, the variance between methods was high. These algorithms behave differently, produce widely variable results from one another, and should not be used interchangeably. It may prove prudent for laboratories to independently validate the software algorithm that is chosen against a 'gold standard' using their own population.

Impact of fluorine-18 fluorodeoxyglucose positron emission tomography on patient management: first year's experience in a clinical center.

PURPOSE: To measure the impact of whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET) on patient management during its first year of use in a community hospital. MATERIALS AND METHODS: First-year FDG-PET impact was determined from 463 referring physicians' evaluations of their patients' PET imaging results using two surveys. Survey 1 was given to all physicians referring patients to PET to discover whether PET changed patient management or had decision-making value in the patient's clinical algorithm. Survey 2 was given to one surgeon and one pulmonologist after therapy to determine how PET affected the surgical, chemotherapeutic, and/or radiotherapeutic treatment for the 53 cancer patients they referred. RESULTS: The 463 responses to survey 1 described 23 different PET indications. Lung (40%), head and neck (18%), and colorectal cancers (11%) were the three leading causes of referral. PET changed patient management/therapy in 45% of all patients referred and had inferential/decision-making value in another 44%. Overall, PET had some type of positive influence in 412 (89%) of the patients. Survey 2 provided a more detailed assessment of 53 referrals from two specialists. PET positively affected surgery in 31 patients (58%), prompted the addition of chemotherapy or radiation therapy in nine patients (17%), and eliminated chemotherapy or radiation therapy in four cases (8%). Overall, PET affected patient management/therapy in 70% of the cases and had some decision-making value in another 26%, for a combined PET impact on patient management of 96%. CONCLUSION: FDG-PET can be valuable for physicians in clinical practice. Its sensitivity and specificity in metabolic imaging, when combined with complementary anatomic imaging techniques, contribute significantly to the clinical treatment of cancer patients. In addition, the high accuracy of FDG-PET makes it a cost-effective radiologic procedure in the work-up of all suspected and/or recurrent cancer patients. Further research is needed to link this demonstrated impact on patient management to cost-effectiveness.

Sentinel node staging for cutaneous melanoma in a university-affiliated community care setting.

BACKGROUND: The feasibility of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) in settings other than high-volume specialized clinics has been questioned. We sought to determine the feasibility of SLND in a university-affiliated private teaching hospital. METHODS: A multidisciplinary sentinel node program was established to include surgeons, nuclear medicine physicians, and pathologists. Within this program, 79 patients with cutaneous melanoma underwent attempted SLND after cutaneous lymphoscintigraphy (CL), between January 1994 and December 1998. All sentinel nodes were examined by hematoxylin-eosin staining and determined whether negative for evidence metastatic disease by both S-100 and HMB 45 immunohistochemical staining. RESULTS: CL was successful in 77 (97%) of 79 patients. A total of 88 lymphatic basins were found to be at risk for metastatic disease by CL. SLND was not successful in the two patients who did not have a successful CL. Sentinel nodes were identified in all but three patients with the remaining 88 lymphatic basins (technical success, 97%). There was one false negative in this group of patients (approximately 1%). CONCLUSIONS: SLND is a highly accurate way of staging the regional node basin. Our technical success rates and false-negative rates indicate the feasibility of this approach in settings other than high-volume specialty clinics.

Current imaging and possible therapeutic management of glucagonoma tumors: a case report.

Glucagonomas, like other neuroendocrine tumors, express somatostatin receptors in more than 80% of cases. Unfortunately, because of the rarity of these tumors, the sensitivity and specificity of somatostatin analog (octreotide) imaging have not been established. Nonetheless, there have been limited reports in the literature supporting the use of indium In-111 DTPA N-terminal D-phenylalanine (D-PHE1) octreotide for glucagonoma imaging and may be most beneficial as an adjuvant to conventional imaging for tumor staging and therapeutic decision making. Current therapeutic applications of octreotide focus on stabilization of disease in tumors expressing somatostatin receptors, and tumor destruction, using beta-emitting isotopes. In this report, imaging of a glucagonoma with In-111 DTPA-D-PHE1 octreotide scintigraphy is described in a 51-year-old woman examined for a large palpable abdominal mass.

Imaging of non-small-cell lung cancer with indium-111 pentetreotide.

PURPOSE: Lung cancer is the leading cause of cancer deaths in the United States. Non-small-cell lung cancer (NSCLC) accounts for 75% to 85% of lung cancers. CT has been the standard anatomic study for localizing and staging NSCLC, although it is associated only with moderate accuracy. In-111 pentetreotide, a radiolabeled somatostatin analog largely used in the scintigraphic localization of neuroendocrine tumors, has been shown incidentally to identify NSCLC lesions. This observation is important in the workup for metastatic disease for neuroendocrine tumors, because presumed metastatic lesions may actually be second primary tumors of NSCLC. In-111 may also serve as a potentially useful adjunct to CT in the anatomic evaluation of NSCLC. The purpose of this study was to determine the likelihood of detecting and localizing NSCLC using In-111 pentetreotide scintigraphy. MATERIALS AND METHODS: Ten patients with known or possible NSCLC were examined using In-111 pentetreotide. Scans were compared with the patients' previously performed chest radiographs and CT scans. RESULTS: In-111 pentetreotide imaging correctly identified sites of tumor involvement as detected by chest CT and surgery in all 10 patients with NSCLC. CONCLUSION: This study demonstrates the uptake of In-111 pentetreotide by NSCLC. This important observation should be considered in the workup for metastatic disease of neuroendocrine tumors with In-111 pentetreotide, because NSCLC can be a source of false-positive findings. In-111 pentetreotide imaging may also serve as a potentially useful adjunct to CT for identifying obscured or equivocal lesions and as an aid in localizing tissue for biopsy.

1. Positron Emission Tomography of Thoracic Malignancies. Reduction of Myocardial Fluorodeoxyglucose Uptake Artifacts With a Carbohydrate Restricted Diet.

Purpose: To reduce the artifact caused by cardiac uptake of F-18 fluorodeoxyglucose (FDG); we investigated the change in myocardial FDG uptake after placing a group of patients on a carbohydrate-restricted diet.Methods: Case control study involving 130 whole body FDG PET scans. 73 scans were of patients on carbohydrate-restriction; the remaining 57 were without dietary restrictions. Dietary intake for the last meal prior to scanning was recorded for both groups. Coronal and axial images were assessed and scored based on myocardial FDG uptake the presence of associated image artifacts.Results: Of the 73 patients on the diet, 50 did not consume carbohydrates, while of the 57 patients without dietary restriction, 13 did not consume carbohydrates. Of the 67 patients from both groups who consumed carbohydrates prior to their PET scan, 17 (25.4%) had a clinically significant image artifact versus only 6 (9.5%) of the 63 patients who did not consume carbohydrates (P = 0.018) in their meals prior to scanning. The odds ratio was calculated to be 3.23 (confidence interval 1.09-10.00), indicating that the risk a clinically significant image artifact will occur is 3.23 times higher for patients who consume carbohydrates in their last meal prior to scanning.Conclusion: A substantial reduction in the prevalence of myocardial FDG uptake image artifacts among patients who did not consume carbohydrates was observed. A carbohydrate dietary restriction prior to scanning may play a significant role in increasing lesion detectability and in preventing false negative scans when imaging for thoracic neoplasm.

Preoperative lymphoscintigraphy in the evaluation of squamous cell cancer of the vulva.

PURPOSE: A pilot study was undertaken to determine the lymphatic drainage of vulvar cancer using cutaneous lymphoscintigraphy. METHODS: Six patients with biopsy-proved T1 squamous cell cancer of the vulva were studied using 0.4 to 0.6 mCi Tc-99m HSA. Planar imaging was performed after patients received intradermal injections of Tc-99m HSA in a total volume of 0.4 ml at four sites around the vulvar lesion. RESULTS: Tumor locations included two midline lesions and three anterior third lesions. One tumor was located in the midthird of the labia majora. There was no clinically suspicious inguinal adenopathy in any patient. Based on classic anatomic descriptions of cutaneous lymphatic drainage, all but one patient would have been predicted to have drainage to both inguinal nodal basins. Cutaneous lymphoscintigraphy was successful in all six patients. Unilateral drainage was shown in five of six patients. Only one patient had bilateral inguinal drainage, and her tumor was located in the left anterior third of the labia minora. CONCLUSIONS: Cutaneous lymphoscintigraphy with Tc-99m HSA is easily performed and may be potentially useful in defining lymphatic basins at risk in squamous cell cancer of the vulva.

Combined use of intraoperative lymphatic mapping and lymphoscintigraphy in the management of squamous cell cancer of the vulva.

BACKGROUND: The standard care of the patient with squamous cell cancer of the vulva is radical vulvectomy along with inguinal-femoral node dissection. We explored the feasibility of sentinel lymphadenectomy in patients with squamous cell cancer of the vulva. METHODS: Patients with biopsy proven squamous cell cancer of the vulva were studied with preoperative lymphoscintigraphy, intraoperative lymphatic mapping with isosulfan blue combined with intraoperative lymphoscintigraphy utilizing a hand-held gamma counter. RESULTS: Five patients with invasive squamous cell cancer were studied. Sentinel nodes were identified in six lymphatic basins. One lymphatic basins had two sentinel nodes. Six of seven sentinel nodes were blue and all retained radioactivity at a ratio of at least 3:1 above the background levels in the regional node basin. One patient was found to have metastatic tumor which was confined to a sentinel lymph node. There was minimal morbidity associated with the procedure. CONCLUSIONS: Lymphatic mapping is feasible in patients with squamous cell cancer of the vulva. These initial results suggests further study is warranted.

Lack of effect of particle size on the identification of the sentinel node in cutaneous malignancies.

BACKGROUND: Radiotracers have become a routine technical component of the new procedure of intraoperative lymphatic mapping and selective lymphadenectomy. Because different colloids have differing physicochemical properties, their distribution and uptake may be different. For this reason, the optimal colloid to identify and localize the sentinel node remains controversial. METHODS: Nineteen consecutive patients with cutaneous malignancies underwent diagnostic lymphoscintigraphy with 99mTc-labeled human serum albumin (99mTc-HSA) and preoperative lymphoscintigraphy with 99mTc-labeled sulfur colloid (99mTc-SC). The results of intraoperative lymphatic mapping and selective lymphadenectomy were reviewed. RESULTS: Intraoperative lymphatic mapping and selective node dissection were successful in 21 of 22 lymphatic basins (18 of 19 patients). There was excellent correlation between the "hot" marker placed on the skin surface when 99mTc-HSA was used compared with the use of 99mTc-SC. In 20 of 21 lymphatic basins the sentinel node both was "hot" and was stained with isosulfan blue. CONCLUSIONS: No discernible difference between the ability to localize in the sentinel node with these two radiocolloids was identified. For logistical reasons, 99mTC-SC appears to be the colloid of choice in intraoperative lymphatic mapping.

Multi-center sestamibi parathyroid imaging study in Hawaii.

Technetium-99m (99mTc) sestamibi (MIBI) was first used as a parathyroid imaging agent in Hawaii in 1991. The purpose of this study was to determine the sensitivity and positive predictive value of the MIBI scan in detecting abnormal parathyroid glands. A retrospective, multi-center study from 1992-1994 involving 33 patients in four hospitals showed the overall sensitivity of the MIBI scan for detecting hyperparathyroid disease was 90%. The positive predictive value was 93%. It was more sensitive in detecting adenomas (95%) than hyperplasia (45%). In conclusion, the MIBI scan can be helpful in detecting abnormal parathyroid glands and may be most useful prior to reoperations for persistent and recurrent hyperparathyroidism.

Imaging of stress injuries to bone. Radiography, scintigraphy, and MR imaging.

Although conventional radiographs continue to be used as a primary method for the diagnosis of stress fractures, the limitations of radiography in early detection have been increasingly recognized. Advanced imaging techniques, including radionuclide methods, and more recently, MR imaging, have increasingly been employed in the assessment of stress fractures, and have provided valuable insights into the spectrum of stress-related changes to bone. This article reviews the diagnostic methods available to the clinician for detection of stress injuries to bone.

Blinded reading of radiographs increases the frequency of errors in vertebral fracture detection.

We examined the effect of blinding X-rays to film sequence and patient identity on vertebral fracture detection. A sample of 50 postmenopausal women with low bone density and two sets of spine X-rays 3.6 years apart was selected; based on prior morphometric studies, about half of the women had experienced new fractures after the initial film. New morphometric and semiquantitative radiologist readings were each performed twice: blinded and unblinded. For morphometry, incident fractures were defined as vertebral height decreases of more than 15% compared with the initial film. The incidence was slightly higher when blinded versus unblinded (5.6 vs. 5.3% of all vertebrae for morphometry, and 9.7 vs. 8.7% for the radiologist), but these differences were not significant. The error rate was investigated by examining the frequency of "fracture reversals"-vertebrae identified as fractured on the initial film but not on the later film. Agreement between blinded and unblinded readings was generally greater than 80% for fractures but less than 10% for "fracture reversals," suggesting that reversals are not true events but random errors. The number of reversals was higher when the radiologist was blinded (2.1% of all vertebrae vs. 0.8% when unblinded; p = 0.07). The number of vertebrae with increases greater than 15% in size over time was also greater when morphometry readings were blinded versus unblinded: 0.8 versus 0% (p < 0.05). Although these errors are small, they are similar in magnitude to the annual fracture incidence in many populations. These data show that blinding X-rays to sequence offers no advantages, increases the frequency of errors, and may inflate incidence rates. We conclude that the assessment of X-rays for vertebral fractures in clinical trials should not be performed with the evaluator blinded to the sequence of the X-rays.

The effects of ice on blood flow and bone metabolism in knees.

The effects of an ice wrap, applied to a knee for 20 minutes, on blood flow and bone metabolism were measured using triple-phase technetium bone scans. Twenty-one subjects between 29 and 63 years of age were studied. A commercially available ice wrap was applied to one knee 20 minutes before scanning, while an identical wrap left at room temperature was applied to the opposite knee to act as a control. Scans of the knees were obtained at the completion of cooling, and the images were quantified by computer image analysis for each knee at each phase of the scan. Percentage of decrease in blood flow and subsequent bone uptake of technetium for the iced knee as compared with the opposite knee were calculated. All iced knees demonstrated decreased arterial and soft tissue blood flow as well as decreased bone uptake, which is a reflection of changes in both bone blood flow and metabolism. The average decrease was 38.4% +/- 4.97 in arterial blood flow, 25.8% +/- 2.04 in soft tissue blood flow, and 19.3% +/- 2.0 (standard error of the mean in each) in bone uptake. This "ice effect" was not related to age, sex, knee circumference, or skin temperature after cooling. By decreasing blood flow and cell metabolism, ice theoretically can limit hemorrhage and cell death in the setting of acute traumatic injury. This study thus provides a scientific rationale for the use of ice as tested for such injuries to a large joint, whether in the soft tissues or bones.

Heat-damaged red cell scan for intraoperative localization of the accessory spleen.

Destruction of platelets by the reticuloendothelial system in immune thrombocytopenia purpura (ITP) is enhanced by platelet-associated IgG. Relapse after splenectomy may result from IgG produced in the accessory spleen. These structures may be located at any site between Gerota's fascia and the left ovary or testicle as well as adjacent to the spleen. The heat-damaged red cell scan (HDRCS) has been demonstrated to be an accurate method for identifying accessory spleens. HDRCS using semi-in vitro labeling of the patient's red blood cells with technetium 99m pertechnetate delineated accessory splenic tissue as the etiology of post-splenectomy relapse three times in two patients 3 to 9 months postoperatively. A labeled intraabdominal probe and HDRCS were subsequently used by the surgical team for identification and excision of the accessory spleen. Four additional patients underwent splenectomy for ITP between 1989 and 1992; heat-damaged red blood cells were injected after the major splenic tissue was removed. Accessory spleens were identified in two patients. All patients were discharged within 6 days, without perioperative complications. Two patients currently require steroids. The techniques of intraoperative HDRCS allow rapid localization and removal of the accessory spleen at the time of laparotomy. Evidence of growth of accessory splenic tissue postsplenectomy was demonstrated.