Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Active surveillance in clinically complete responders after neoadjuvant chemoradiotherapy for esophageal or junctional cancer.

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is standard of care for locally advanced esophageal cancer in many countries. After nCRT up to one third of all patients have a pathologically complete response in the resection specimen, posing an ethical imperative to reconsider the necessity of standard surgery in all operable patients after nCRT. An active surveillance strategy following nCRT, in which patients are subjected to frequent clinical investigations after the completion of neoadjuvant therapy, has been evaluated in other types of cancer with promising results. In esophageal cancer, both patients who are cured by neoadjuvant therapy alone as well as patients with subclinical disseminated disease at the time of completion of neoadjuvant therapy may benefit from such an organ sparing approach. Active surveillance is currently applied in selected patients with esophageal cancer who refuse surgery or are medically unfit for major surgery after completion of nCRT, but this strategy is not (yet) adopted as an alternative to standard surgery or definitive chemoradiation. The available literature is scarce, but suggests that long-term oncological outcomes after active surveillance are noninferior compared to standard surgical resection, providing justification for comparison of both treatments in a phase III trial. This review gives an overview of the current knowledge regarding active surveillance after completion of nCRT in esophageal cancer and outlines future research perspectives.

The G protein beta subunit is essential for multiple responses to chemoattractants in Dictyostelium.

Increasing evidence suggests that the beta gamma-subunit dimers of heterotrimeric G proteins play a pivotal role in transducing extracellular signals. The recent construction of G beta null mutants (g beta-) in Dictyostelium provides a unique opportunity to study the role of beta gamma dimers in signaling processes mediated by chemoattractant receptors. We have shown previously that g beta- cells fail to aggregate; in this study, we report the detailed characterization of these cells. The g beta- cells display normal motility but do not move towards chemattractants. The typical GTP-regulated high affinity chemoattractant-binding sites are lost in g beta- cells and membranes. The g beta- cells do not display chemoattractant-stimulated adenylyl cyclase or guanylyl cyclase activity. These results show that in vivo G beta links chemoattractant receptors to effectors and is therefore essential in many chemoattractant-mediated processes. In addition, we find that G beta is required for GTP gamma S stimulation of adenylyl cyclase activity, suggesting that the beta gamma-dimer activates the enzyme directly. Interestingly, the g beta- cells grow at the same rate as wild-type cells in axenic medium but grow more slowly on bacterial lawns and, therefore, may be defective in phagocytosis.

Neoadjuvant chemoradiotherapy for resectable oesophageal cancer.

At present, treatment of potentially curable oesophageal cancer includes neoadjuvant chemoradiotherapy followed by oesophagectomy. Alternatively, neoadjuvant chemotherapy is used. To date, strong evidence on the superiority of one modality over the other has not been provided. Currently, up to one-third of patients show a pathologically complete response after neoadjuvant chemoradiotherapy. To optimise the efficacy of neoadjuvant treatment for individual patients, prediction of response to neoadjuvant treatment is highly desired. Therefore, several clinical diagnostic modalities have been investigated for early response evaluation, of which positron emission tomography (PET) has been studied most extensively. To identify patients who might benefit from postponing or even omitting surgery, recent advances have been made in evaluating response after completion of neoadjuvant chemoradiotherapy. This review provides an overview of current evidence and recent advances in neoadjuvant chemoradiotherapy for oesophageal cancer and discusses the use of neoadjuvant chemotherapy compared to chemoradiotherapy. Moreover, clinical response evaluation to neoadjuvant chemoradiotherapy is reviewed.

A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

In Dictyostelium discoideum extracellular cyclic AMP (cAMP), as shown by previous studies, induces a transient accumulation of intracellular cyclic guanosine-5'-monophosphate (cGMP), which peaks at 10 s and recovers basal levels at 30 s after stimulation, even with persistent cAMP stimulation. Additional investigations have shown that the cAMP-mediated cGMP response is built up from surface cAMP receptor-mediated activation of guanylyl cyclase and hydrolysis of cGMP by phosphodiesterase. The regulation of these activities was measured in detail on a seconds time-scale, demonstrating complex adaptation of the receptor, allosteric activation of cGMP-phosphodiesterase by cGMP, and potent inhibition of guanylyl cyclase by Ca2+. In this paper we present a computer model that combines all experimental data on the cGMP response. The model is used to investigate the contribution of each structural and regulatory component in the final cGMP response. Four models for the activation and adaptation of the receptor are compared with experimental observations. Only one model describes the magnitude and kinetics of the response accurately. The effect of Ca2+ on the cGMP response is simulated by changing the Ca2+ concentrations outside the cell (Ca2+ influx) and in stores (IP3-mediated release) and changing phospholipase C activity. The simulations show that Ca2+ mainly determines the magnitude of the cGMP accumulation; simulations are in good agreement with experiments on the effect of Ca2+ in electropermeabilized cells. Finally, when cGMP-phosphodiesterase activity is deleted from the model, the simulated cGMP response is elevated and prolonged, which is in close agreement with the experimental observations in mutant stmF that lacks this enzyme activity. We conclude that the computer model provides a good description of the observed response, suggesting that the main structural and regulatory components have been identified.

[Organ-sparing treatment in oesophagus cancer: feasible and safe?] / Orgaansparende behandeling bij slokdarmcarcinoom.

In many countries, neoadjuvant chemoradiotherapy (nCRT) plus surgery is standard treatment for resectable oesophageal cancer. After nCRT, up to 30% of all patients have no residual disease in the resection specimen. Consequently, an active surveillance approach, in which patients undergo frequent clinical investigations after nCRT instead of standard oesophagectomy, is increasingly applied in selected patients. Here, we describe outcomes for three patients who underwent active surveillance. A 63-year old woman was considered unfit for surgery after nCRT. Four years after completion of nCRT, she still had no signs of disease recurrence. The second patient, a 57-year old woman, refused surgery when no residual disease was detectable after nCRT. One year following treatment, she developed a vertebral metastasis, in the absence of locoregional disease. The third patient concerned a 66-year old man with a clinically complete response after nCRT, who also refused surgery. During active surveillance, he developed a locoregional regrowth and underwent a radical oesophagectomy.

The use of bisphosphonates in the treatment of osteoporosis.

The efficacy of bisphosphonates in the treatment of conditions characterized by increased osteoclastic bone resorption has been established. Recent evidence indicates that these compounds are also effective in the treatment of patients with osteoporosis. Two main protocols have been tried. One is based on the intermittent administration of the bisphosphonate, which is expected to decrease bone resorption, and give a drug-free period during which bone formation may proceed at a normal rate, leading to a positive calcium balance. The other argues that the resetting of the equilibrium in a cyclical process is, as a rule, incomplete and continuous low-grade suppression of resorption will result in a continuing positive bone balance. Intermittent administration of the first generation bisphosphonate, etidronate, for up to three years increases trabecular bone density, stabilizes it after two years, and appears to reduce the rate of new vertebral fractures in women with postmenopausal osteoporosis. Longer follow-up studies are needed before this beneficial effect is unequivocally established. Continuous administration of the second-generation bisphosphonate, pamidronate, increases spinal bone density in patients with osteoporosis linearly for up to four years, and is associated with a low rate of new vertebral fractures. These results need to be confirmed in controlled studies involving more patients. There are indications that pamidronate given continuously can prevent glucocorticoid-induced bone loss. There is no information about the effects of bisphosphonates on non-vertebral fractures. There are limited data about the use of bisphosphonates in the prevention of postmenopausal bone loss. Extensive studies on efficacy and safety are needed before this treatment is offered as an alternative to hormone replacement therapy.

Somatostatin receptor scintigraphy in the initial staging of low-grade non-Hodgkin's lymphomas.

UNLABELLED: In this prospective study, somatostatin receptor (SS-R) scintigraphy was compared with conventional staging procedures for the initial staging of patients with low-grade non-Hodgkin's lymphoma (NHL). METHODS: Fifty consecutive untreated patients with low-grade NHL underwent SS-R scintigraphy as part of their initial staging. Planar images were obtained 24 and 48 h after intravenous injection of 220 MBq (111)In-pentetreotide. SPECT images of the upper abdomen were obtained from all patients. SS-R scans were evaluated blindly without knowledge of the results of the conventional staging methods. SS-R scintigraphy findings were compared with the results of physical and radiologic examinations. RESULTS: SS-R scintigraphy findings were positive in 42 of 50 patients (84%). In 10 patients (20%), the SS-R scan revealed new lesions that had not been revealed by conventional staging procedures. These 10 patients were all upgraded to a higher stage. Consequently, the treatment plan would have been altered in 5 patients (10%). However, in 19 patients (38%), lesions apparent after conventional staging methods were missed by SS-R scintigraphy. The sensitivity of SS-R scintigraphy varied from 62% for supradiaphragmatic lesions to 44% for infradiaphragmatic lesions. The specificity of SS-R scintigraphy was high (98%-100%). In comparison with CT scanning and sonography, SS-R scintigraphy is inferior for the visualization of NHL lesions in the thorax and abdomen. CONCLUSION: Although SS-R scintigraphy findings are positive in a large proportion of patients with low-grade NHL, in most patients only part of the lesions can be visualized. Because of the limited sensitivity, we recommend SS-R scintigraphy for initial staging of patients with low-grade NHL only in selected conditions and not for the general work-up.

Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background.

The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements.

Preclinical and initial clinical evaluation of 111In-labeled nonsulfated CCK8 analog: a peptide for CCK-B receptor-targeted scintigraphy and radionuclide therapy.

UNLABELLED: The presence of cholecystokinin (CCK)-B (gastrin) receptors has been shown in more than 90% of medullary thyroid cancers (MTCs) and in a high percentage of small cell lung cancers, stromal ovarium cancers and several other tumor types. METHODS: The aim of this study was to evaluate in vitro and in vivo whether 111In-labeled CCK-B receptor-specific CCK8 analog [D-Asp26,Nle28,31]CCK26-33 (D-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2) is suitable for CCK-B receptor scintigraphy based on the finding that unlabeled nonsulfated diethylenetriamine pentaacidic acid [DTPA0]CCK8 and tetraazacyclododecanetetraacetic acid [DOTA0]CCK8 analogs show high and specific binding for CCK-B receptors in human tumors. Fifty percent inhibitory concentrations were in the low nanomolar range. RESULTS: In vitro, [111In-DOTA0]CCK8 showed specific internalization in CCK-B receptor-positive rat pancreatic tumor cells AR42J. Internalization of the analog appeared to be time and temperature dependent and receptor specific. From the data obtained with [111In-DOTA0]CCK8 and (125I)I-gastrin, the latter being a specific ligand for the CCK-B receptor, the rat pancreatic cell line CA20948 also appeared to be CCK-B receptor positive. This provides an in vitro and in vivo rat tumor model because this cell line can be grown to solid tumors in Lewis rats. In vivo biodistribution experiments in CA20948 tumor-bearing Lewis rats showed rapid clearance of [111In-DOTA0]CCK8, and specific uptake was found in the CCK-B receptor-expressing stomach and tumor. Furthermore, comparing [111In-DOTA0]CCK8 with the radioiodinated nonsulfated CCK10 analog (D-Tyr-Gly-Asp-Tyr-Nle-Gly-Trp-Nle-Asp-Phe-NH2), both ligands having high affinity for the CCK-B receptor, tumor-to-blood ratios were significantly higher for [111In-DOTA0]CCK8 than for 125I-CCK10, analogous to the findings with radioiodinated and 111In-labeled octreotide. The study in humans with [111In-DTPA0]CCK8 showed receptor-specific uptake in the CCK-B receptor-positive stomach and in metastases in the neck region up to 48 h after injection. CONCLUSION: [111In-DOTA0]CCK8 is most promising for scintigraphy and, after coupling to therapeutic radionuclides, for radionuclide therapy of human CCK-B receptor-positive tumors such as MTC and small cell lung cancer.

Safety of dobutamine-atropine stress myocardial perfusion scintigraphy.

UNLABELLED: Dobutamine stress testing is increasingly used for the diagnosis and functional evaluation of coronary artery disease. However, the relationship between myocardial perfusion abnormalities and complications of the test has not been studied. METHODS: We studied the hemodynamic profile, safety and feasibility of dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion SPECT imaging (with 201TI, 99mTc-MIBI or tetrofosmin) in a consecutive series of 1076 patients (age = 59 +/- 11 yr, 50% with previous myocardial infarction) referred for evaluation of myocardial ischemia. RESULTS: No infarction or death occurred during the test. The test was considered feasible (achievement of 85% of the target heart rate or an ischemic endpoint) in 1005 patients (94%). Hypotension (systolic blood pressure drop > or = 40 mm Hg) occurred in 37 patients (3.4%). Independent predictors were higher baseline systolic blood pressure (p < 0.0001), number of ischemic segments (p < 0.05) and age (p < 0.05). Supraventricular tachyarrhythmias occurred in 48 patients (4.4%). Independent predictors were fixed perfusion defect (infarction) score (p < 0.005) and age (p < 0.05). Ventricular tachycardia occurred in 41 patients (3.8%). Independent predictors were infarction score (p < 0.01) and male gender (p < 0.05). All arrhythmias terminated spontaneously or after metoprolol administration. CONCLUSION: Dobutamine-atropine myocardial perfusion scintigraphy is a feasible method for the evaluation of coronary artery disease with a safety profile and feasibility comparable to those reported for dobutamine stress echocardiography. Patients with more severe fixed perfusion abnormalities are at a higher risk of developing tachyarrhythmias during the test.

Relationship between preoperative viability and postoperative improvement in LVEF and heart failure symptoms.

UNLABELLED: The presence of myocardial viability is predictive of improvement in regional left ventricular (LV) function after revascularization. Studies on predicting improvement in global LV function are scarce, and the amount of viable myocardium needed for improvement in LV ejection fraction (LVEF) after revascularization is unknown. Moreover, whether the presence of viability is associated with relief of heart failure symptoms after revascularization is uncertain. Hence, the aims were to define the extent of viable myocardium needed for improvement in LVEF and to determine whether preoperative viability testing can predict improvement in heart failure symptoms. METHODS: Patients (n = 47) with ischemic cardiomyopathy (mean LVEF +/- SD, 30% +/- 6%) undergoing surgical revascularization were studied with 18F-FDG SPECT to assess viability. Regional and global function were measured before and 3-6 mo after revascularization. Heart failure symptoms were graded according to the New York Heart Association (NYHA) criteria, before and 3-6 mo after revascularization. RESULTS: The number of viable segments per patient was directly related to the improvement in LVEF after revascularization (r = 0.79, P < 0.01). Receiver operating characteristic curve analysis revealed that the cutoff level of four viable segments (representing 31% of the left ventricle) yielded the highest sensitivity and specificity (86% and 92%, respectively) for predicting improvement in LVEF. Furthermore, the presence of four or more viable segments predicted improvement in heart failure symptoms after revascularization, with positive and negative predictive values of 76% and 71%, respectively. CONCLUSION: The presence of substantial viability (four or more viable segments, 31% of the left ventricle) on FDG SPECT is predictive of improvement in LVEF and heart failure symptoms postoperatively.

Dobutamine stress echocardiography and technetium-99m-tetrofosmin/fluorine 18-fluorodeoxyglucose single-photon emission computed tomography and influence of resting ejection fraction to assess myocardial viability in patients with severe left ventricular dysfunction and healed myocardial infarction.

The purpose of this study was to compare 2 different techniques--dobutamine-atropine stress echocardiography (DSE) and dual-isotope simultaneous acquisition (technetium-99-m-tetrofosmin/fluorine 18-fluorodeoxyglucose) single-photon emission computed tomography (DISA-SPECT)--for assessment of viable myocardium. One hundred ten patients (mean age 55 +/- 9 years) with left ventricular (LV) dysfunction (mean LV ejection fraction 27 +/- 13%) underwent both DISA-SPECT and DSE. A 16-segment scoring model was adopted for both techniques. Four types of wall motion during DSE were assessed: (1) biphasic, improvement at low dose (10 microg/kg/min) with worsening at high dose; (2) worsening, deterioration without initial improvement; (3) sustained, persistent or late improvement; and (4) no change. Viability criteria were biphasic, worsening, and sustained improvement with DSE. Viability criteria with DISA-SPECT were normal perfusion and metabolism (normal), concordantly mildly reduced perfusion and metabolism (subendocardial scar), or severely reduced perfusion and increased metabolism (mismatch). Myocardium was considered nonviable with DSE in case of unchanged wall motion, or moderate reduction or absence in both technetium-99m-tetrofosmin perfusion and fluorodeoxyglucose uptake with DISA-SPECT. Of 1,756 of 1,760 analyzable LV segments, 1,373 (78%) had severe wall motion abnormalities at baseline (severe hypokinesia, akinesia, or dyskinesia). Of these abnormal segments, 282 (21%) were considered viable during DSE (63 [5%] with biphasic response, 47 [3%] with ischemia, and 172 [13%]) with sustained improvement, whereas 1,091 (79%) were considered nonviable. With DISA-SPECT, 396 (29%) segments were considered viable (312 [23%] with matched perfusion/metabolism and 84 [6%] with mismatch), whereas 977 segments (71%) were considered nonviable. Both techniques showed agreement for viability in 201 segments and 896 were concordantly classified as nonviable. Disagreement was present in 276 segments of which 195 (71%) were nonviable with DSE and viable with DISA-SPECT. Overall agreement between the 2 techniques was 81% (kappa 0.46) in a subgroup of patients with an ejection fraction <25% 78% (kappa 0.39). Thus, DSE and DISA-SPECT show good agreement for assessing viable myocardium not influenced by resting ejection fraction. DSE underestimated the amount of viable tissue compared with DISA-SPECT.

Safety, hemodynamic profile, and feasibility of dobutamine stress technetium myocardial perfusion single-photon emission CT imaging for evaluation of coronary artery disease in the elderly.

OBJECTIVES: Cardiovascular disease is the leading cause of morbidity and mortality in the elderly. The evaluation of coronary artery disease by exercise stress testing is frequently limited by the patient's inability to exercise. Although pharmacologic stress testing with dobutamine is an alternative, the safety of dobutamine myocardial perfusion scintigraphy in the elderly has not been previously studied. PATIENTS AND METHODS: We studied the safety and feasibility of dobutamine (up to 40 microg/kg/min)-atropine (up to 1 mg) stress myocardial perfusion scintigraphy using technetium single-photon emission CT imaging in 227 patients > or = 70 years old (mean +/- SD age, 75 +/- 4 years). A control group of 227 patients < 70 years old (mean age, 55 +/- 11 years; matched for gender, prevalence of previous infarction, beta-blocker therapy, and severity of resting perfusion abnormalities) was studied to assess age-related differences in the safety and the hemodynamic response. A feasible test was defined as the achievement of the target heart rate and/or an ischemic end point (angina, ST-segment depression, or reversible perfusion abnormalities). RESULTS: No myocardial infarction or death occurred during the test. The target heart rate was achieved more frequently in the elderly patients (87% vs 79%; p < 0.05). The elderly patients had a higher prevalence of supraventricular tachycardia (7% vs 1%; p < 0.005) and premature ventricular contraction (74% vs 32%; p < 0.005) during the test, as compared to the younger patients. There was a trend to a higher prevalence of ventricular tachycardia (5% vs 2%) and atrial fibrillation (3% vs 0.4%) in the elderly patients. Arrhythmias were terminated spontaneously by termination of dobutamine infusion or by administration of metoprolol. Independent predictors of supraventricular tachyarrhythmias and ventricular tachycardia were older age (p < 0.001; chi(2), 9.8) and myocardial perfusion defect score at rest (p < 0.01; chi(2), 6.8) respectively, by using a multivariate analysis of clinical and stress test variables. Elderly patients had a higher prevalence of systolic BP drop > 20 mm Hg during the test (37% vs 12%; p < 0.05). The test was terminated due to hypotension in 2% of the elderly patients and in 1% of the control group. Age was the most powerful predictor of hypotension (p < 0.005; chi(2), 10.3). The test was considered feasible in 216 elderly patients (95%) and in 209 patients of the control group (92%). CONCLUSION: Dobutamine-atropine stress myocardial perfusion scintigraphy is a highly feasible method for the evaluation of coronary artery disease in the elderly. Elderly patients have a higher risk for developing hypotension and supraventricular tachyarrhythmias during a dobutamine stress test. However, dobutamine-induced hypotension is often asymptomatic and rarely necessitates the termination of the test.

Accuracy of dobutamine tetrofosmin myocardial perfusion imaging for the noninvasive diagnosis of transplant coronary artery stenosis.

BACKGROUND: Exercise stress myocardial perfusion scintigraphy has been used for the diagnosis of transplant coronary artery stenosis (TCAS) in cardiac allograft recipients. However, the role of pharmacologic stress myocardial perfusion imaging has not been evaluated. Aim of the study is to assess the accuracy of dobutamine stress 99m technetium tetrofosmin myocardial perfusion imaging for the diagnosis of TCAS in heart transplant recipients. PATIENTS AND METHODS: We studied 50 patients (age 56 +/- 8 year, 45 men) at a mean of 6.4 +/- 2.8 years after cardiac transplant with dobutamine (up to 40 ìg/kg/min) stress 99m technetium tetrofosmin SPECT. Resting images were acquired 24 hours after the stress study. Significant TCAS was defined as > or =50% luminal diameter stenosis by coronary angiography. RESULTS: Significant TCAS was detected in 30 patients (60%). Myocardial perfusion abnormalities (reversible and/or fixed defects) were detected in 27 of the 30 patients with and in 9 of the 20 patients without significant TCAS (sensitivity = 90%, CI 82-98, specificity = 55% CI 41-69, positive predictive value = 75%, CI 63-87, negative predictive value = 79%, CI 67-90 and accuracy = 76%, CI 64-88). Patients with multivessel TCAS had a larger stress perfusion defect score (5.6 +/- 3.1 vs 3.2 +/- 2.4, p < 0.05) compared to patients with single vessel TCAS. Among patients with abnormal perfusion who had no significant TCAS, 2 had lesions <50%, 2 had luminal irregularities and 5 had no abnormalities at angiography. Therefore specificity was 62% (8/13) in patients without any detectable angiographic abnormalities. CONCLUSIONS: Dobutamine stress tetrofosmin myocardial perfusion imaging is a highly sensitive method for the detection of TCAS in recipients of cardiac allografts. The high negative predictive value of the test indicates that patients who demonstrate normal perfusion by this method may be excluded from further invasive studies.

The diagnostic utility of somatostatin receptor scintigraphy in oncology.

Somatostatin receptor scintigraphy (SRS) with the diethylenetriaminopentaacetic-acid-conjugated somatostatin analogue [111In-DTPA-D-Phe1] octreotide, also known as 111In-pentetreotide, is a new non-invasive modality for the evaluation of tumours that express receptors for somatostatin. These receptors are present on neuroendocrine and other tumours, including lymphomas and some breast cancers. In oncology SRS is a promising diagnostic tool for localizing primary tumours, staging, control and follow-up after therapy, and for identification of patients who may benefit from therapy with unlabelled octreotide or, in the future, with radiolabelled octreotide. In the past few years many small and large studies investigating various aspects of SRS have been reported. In this review the value of SRS in the management of individual tumour types is explored. For many tumours the best sensitivity in lesion detection is only achieved by very careful imaging after the administration of at least 200 MBq 111In-pentetreotide. On the basis of the current experience the main value of SRS in oncology is in the staging and evaluation of gastroenteropancreatic tumours, paragangliomas, small-cell lung cancer and lymphomas. Promising areas for SRS are the evaluation of breast cancer, non-medullary thyroid cancer and melanoma, and initial results with targeted radionuclide therapy using radiolabelled octreotide have been reported.

The role of radioactive somatostatin and its analogues in the control of tumor growth.

Peptide receptor scintigraphy with the radioactive somatostatin analogue [111In-DTPA-D-Phe1]octreotide is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localized. This technique is currently used to assess the possibility of peptide receptor radionuclide therapy with repeated administration of high doses of [111In-DTPA-D-Phe1]octreotide. 111In emits Auger and conversion electrons, having a tissue penetration of 0.02-10 microns and 200-500 microns, respectively. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with [111In-DTPA-D-Phe1]octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase-I trial. There were no major clinical side effects after up to 2 years of treatment, except that in a few patients a transient decline in platelet counts and lymphocyte subsets occurred. Promising beneficial effects on clinical symptoms, hormone production, and tumor proliferation were found. Of the 21 patients who received a cumulative dose of more than 20 GBq, eight showed stabilization of disease and six others a reduction in tumor size. There is a tendency towards better results in patients whose tumors have a higher accumulation of the radioligand. Peptide receptor radionuclide therapy is also feasible with 111In as the radionuclide. Theoretically, depending on the homogeneity of distribution of tumor cells expressing peptide receptors and the size of the tumor, beta-emitting radionuclides, e.g., 90Y, labeled to DOTA-chelated peptides may be more effective than 111In for peptide receptor radionuclide therapy. The first peptide receptor radionuclide therapy trials with [90Y-DOTA-Tyr3]octreotide started recently.

Bone mineral density in ambulant, non-steroid treated female patients with rheumatoid arthritis.

Bone mass measurements were performed in a group of 30 ambulant, non-steroid treated female patients with rheumatoid arthritis (RA) of relatively short duration (mean 4.9 years). The bone mineral density (BMD) of the lumbar spine and femoral neck was assessed by dual-energy x-ray absorptiometry (DEXA), and related to parameters of disease activity and severity. Lumbar BMD was within the range of normal while femoral BMD was decreased compared to age-matched controls. BMD values, expressed as the percentage of age-matched healthy controls (BMD%), were positively related to the body mass index and negatively related to the number of swollen joints, the erythrocyte sedimentation rate and the platelet count. No relation was found between the lumbar and femoral bone mass on the one hand and disease duration, number of disease modifying anti-rheumatic drugs ever used, Ritchie articular index, C-reactive protein, functional ability or radiological scores on the other. It is concluded that in ambulant non-steroid treated female RA patients lumbar bone mass as measured with DEXA is within the range of normal, while femoral bone mass is slightly reduced. Both lumbar and femoral bone mass are related to the body mass index and parameters of disease activity.

Automatic region of interest determination in dual photon absorptiometry of the lumbar spine.

In a heuristic approach, the authors developed an algorithm for automatic region-of-interest (ROI) determination in bone mineral density (BMD) measurements of the lumbar spine. First, the algorithm detects the boundaries of the spine utilizing simple smoothing and gradient operators followed by a dynamic programming technique. Second, it selects L2, L3, and L4 from the spine by examining the BMD values along lines that are orthogonal to the local direction of the spine. The algorithm was tested in studies of a spine phantom, normal subjects (30), and patients (94). In all but two patient studies of severely affected spines the contours were detected correctly. The ROI determination was performed satisfactorily in all studies of the phantom, normals, and patients that had no spinal fractures. The coefficient of variation (CV) in the phantom studies was equal to 0.7%. In duplicate studies of 15 normal subjects and nine patients, the CV was equal to 1.0 and 2.7%, respectively. Compared to manual determination of the ROI, the precision of BMD measurements was clearly improved by the automatic procedure.

Usefulness of F-18-fluorodeoxyglucose positron emission tomography to confirm suspected pancreatic cancer: a meta-analysis.

INTRODUCTION: Pancreatic cancer is among the five most lethal malignancies in the world. Unfortunately, many malignant tumors go undetected by the current primary diagnostic tools. (18)FDG-PET and (18)FDG-PET/CT might be useful to confirm suspected pancreatic cancer. METHODS: A meta-analysis was performed using all major search engines. Methodological quality of included studies was assessed as well as quality of the PET-protocol. The following pooled estimates served as primary outcome measures: sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy. RESULTS: Thirty-five studies were included. Pooled estimates for (18)FDG-PET were: sensitivity 90%, specificity 76%, PPV 90%, NPV 76% and accuracy 86%. Pooled estimates for (18)FDG-PET/CT were: sensitivity 90%, specificity 76%, PPV 89%, NPV 78% and accuracy 86%. The pooled sensitivity and specificity for (18)FDG-PET to differentiate between pancreatic cancer and chronic pancreatitis were 90% and 84%, respectively. CONCLUSION: Both (18)FDG-PET and (18)FDG-PET/CT offer no benefit over the current primary diagnostic tools in diagnosing pancreatic cancer. However, the (18)FDG-PET/CT systems are still improving. We should investigate the sensitivity and specificity of these new systems while reevaluating the tradeoff between false positive and false negative results. Yet, (18)FDG-PET/CT may have a role in the staging of pancreatic cancer, in survival prediction, and may add to other diagnostic information, like histology.