Myocardial Metastases on 6-[18F] fluoro-L-DOPA PET/CT: A Retrospective Analysis of 116 Serotonin Producing Neuroendocrine Tumour Patients

Purpose

This study evaluates the prevalence of cardiac metastases in patients with serotonin producing neuroendocrine tumours (NET), examined with ¹⁸F-FDOPA PET/CT, and the relationship of these metastases to the presence of carcinoid heart disease (CHD) based on echocardiography.

Background

CHD occurs in patients with serotonin producing NET. The diagnostic method of choice remains echocardiography. The precise prevalence of cardiac metastases is unknown given the limitations of standard technologies. Nuclear medicine modalities have the potential to visualize metastases of NET.

Methods

All patients who underwent ¹⁸F-FDOPA PET/CT because of serotonin producing NET between November 2009 and May 2012 were retrospectively analyzed. The presence of cardiac metastasis was defined as myocardial tracer accumulation higher than the surrounding physiological myocardial uptake. Laboratory tests and transthoracic echocardiography (TTE) results were digitally collected.

Results

116 patients (62 male) underwent ¹⁸F-FDOPA PET/CT, mean age was 61±13 years. TTE was performed in 79 patients. Cardiac metastases were present in 15 patients, of which 10 patients also underwent TTE. One patient had both cardiac metastasis (only on ¹⁸F-FDOPA PET/CT) and echocardiographic signs of CHD. There were no differences in echocardiographic parameters for CHD between patients with and without cardiac metastases. TTE in none of the 79 patients showed cardiac metastases.

Conclusion

The prevalence of cardiac metastases detected with ¹⁸F-FDOPA PET/CT in this study is 13%. ¹⁸F-FDOPA PET/CT can visualize cardiac metastases in serotonin producing NET patients. There appears to be no relationship between the presence of cardiac metastases and TTE parameters of CHD.     

18F-2-deoxy-2-fluoro-D-glucose positron emission tomography, computed tomography, and magnetic resonance imaging for the detection of experimental colorectal liver metastases

During the treatment of colorectal liver metastases, evaluation of treatment efficacy is of the utmost importance for decision making. The aim of the present study was to explore the ability of preclinical imaging modalities to detect experimental liver metastases. Nine male Wag/Rij rats underwent a laparotomy with intraportal injection of CC531 tumor cells. On days 7, 10, and 14 after tumor induction, sequential positron emission tomography (PET), computed tomography (CT), and magnetic resonance imaging (MRI) scans were acquired of each rat. At each time point, three rats were euthanized and the metastases in the liver were documented histologically. Topographically, the liver was divided into eight segments and the image findings were compared on a segment-by-segment basis with the histopathologic findings. Sixty-four liver segments were analyzed, 20 of which contained tumor deposits. The overall sensitivity of PET, CT, and MRI was 30%, 25%, and 20%, respectively. For the detection of tumors with a histologic diameter exceeding 1 mm (n = 8), the sensitivity of PET, CT, and MRI was 63%, 38%, and 38%, respectively. The overall specificity of PET, CT, and MRI was 98%, 100%, and 93%, respectively. This study showed encouraging detectability and sensitivity for preclinical imaging of small liver tumors and provides valuable information on the imaging techniques for designing future protocols.     

Incidentally discovered adrenal tumors: a lesson from observation of 1,444 patients

This study was aimed at summarizing our experience in the management of 1,444 patients with incidentally found adrenal tumors observed at a single endocrinological centre. Hormonal determinations were performed in all patients at the beginning of the observation period to detect subclinical adrenal hyperfunction. The imaging phenotype on CT and MRI was analyzed for defining the malignant potential of the tumors. Based on the results of these examinations we diagnosed among our cohort probably benign masses in 87%, malignant tumors in 10% (adrenal carcinoma - 9%), and metastases in 3%. Subclinical hyperfunction was diagnosed in 8%; the most frequent was the pre-Cushing's syndrome. A subgroup of 480 patients (33%) was submitted to surgery because of oncological or endocrinological indications. The patients not qualified for surgery were carefully controlled by imaging and hormonal examinations. Malignancy is the most serious risk in the group of patients with incidentally discovered adrenal tumors.     

Can Microwave Ablation be an Alternative to Resection for the Treatment of Neuroendocrine Liver Metastases?

Objective: Surgical resection of neuroendocrine tumor liver metastases has been proven to improve survival, but the benefit of microwave ablation as an alternative or adjunct to surgery has yet to be assessed. Our hypothesis is that ablation is equal to surgery in terms of local recurrence and survival.Methods: We conducted a retrospective analysis including all patients treated with microwave ablation and/or surgical resection for neuroendocrine liver metastases in our institution between 2008 and 2017.Results: A total of 47 patients and 68 treatments were analyzed, including 34 liver resections, 20 ablations, and 14 combined procedures. A total of 130 individual metastases were treated with ablation, representing a median of 4 per session (range 1–30). While no major complications occurred after ablation, we observed 11 minor and 3 major complications after open surgical resection (P = .0135). Length of stay was significantly shorter after ablation (P = .0008). The majority of patients (33/47, 70.2%) underwent curative procedures, 14 patients underwent (29.8%) debulking procedures. There was no difference in local recurrence rate between tumors treated with ablation or resection. Liver-only disease progression was detected in 29% of the patients and overall progression was detected in 66% of the patients. The mean survival was not significantly different between patients treated with ablation only versus resection with or without ablation (P = .1570). Overall survival was mean 75.3 months (6 to 374 months).Conclusion: Depending on the extent of the liver metastases, microwave ablation might be a safe alternative or addition to resection for neuroendocrine tumor liver metastases with low morbidity and high local efficiency.Abbreviations: CT = computed tomography; MWA = microwave ablation; NET = neuroendocrine tumor; PET = positron emission tomography; RFA = radiofrequency ablation; RFS = recurrence-free survival; SMWA = stereotactic microwave ablation     

Comparative Oncology: Evaluation of 2-Deoxy-2-[18F]fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) for the Staging of Dogs with Malignant Tumors

Introduction

2-Deoxy-2-[18F]fluoro-D-glucose PET/CT is a well-established imaging method for staging, restaging and therapy-control in human medicine. In veterinary medicine, this imaging method could prove to be an attractive and innovative alternative to conventional imaging in order to improve staging and restaging. The aim of this study was both to evaluate the effectiveness of this image-guided method in canine patients with spontaneously occurring cancer as well as to illustrate the dog as a well-suited animal model for comparative oncology.

Methods

Ten dogs with various malignant tumors were included in the study and underwent a whole body FDG PET/CT. One patient has a second PET-CT 5 months after the first study. Patients were diagnosed with histiocytic sarcoma (n = 1), malignant lymphoma (n = 2), mammary carcinoma (n = 4), sertoli cell tumor (n = 1), gastrointestinal stromal tumor (GIST) (n = 1) and lung tumor (n = 1). PET/CT data were analyzed with the help of a 5-point scale in consideration of the patients’ medical histories.

Results

In seven of the ten dogs, the treatment protocol and prognosis were significantly changed due to the results of FDG PET/CT. In the patients with lymphoma (n = 2) tumor extent could be defined on PET/CT because of increased FDG uptake in multiple lymph nodes. This led to the recommendation for a therapeutic polychemotherapy as a treatment. In one of the dogs with mammary carcinoma (n = 4) and in the patient with the lung tumor (n = 1), surgery was cancelled due to the discovery of multiple metastasis. Consequently no treatment was recommended.

Conclusion

FDG PET/CT offers additional information in canine patients with malignant disease with a potential improvement of staging and restaging. The encouraging data of this clinical study highlights the possibility to further improve innovative diagnostic and staging methods with regard to comparative oncology. In the future, performing PET/CT not only for staging but also in therapy control could offer a significant improvement in the management of dogs with malignant tumors.     

Incidental Findings on Brain Magnetic Resonance Imaging (MRI) in Pediatric Endocrine Patients

Objective: To explore incidental findings on brain magnetic resonance imaging (MRI) studies of pediatric patients referred due to endocrine disorders.Methods: A retrospective, observational study conducted in a tertiary referral center. The neuroimaging database of 17,445 brain MRI studies of 11,011 pediatric patients were searched for cases with endocrine referrals and without medical history of malignancy, genetic syndromes, and/or neurologic comorbidities. This database was linked to the pediatric neurosurgical database. Clinical data were retrieved from medical files.Results: In total, 524 patients (50.2% males, mean age 8.5 ± 3.5 years) were referred to brain MRI due to growth disturbances (n = 313), pubertal disorders (n = 183), prolactin hypersecretion (n = 18), central diabetes insipidus (n = 8), and obesity (n = 1). Incidental findings were found in 128 (24.4%) cases. Chiari type 1 malformation was more prevalent in patients with growth disturbances (P<.001). Small pituitary cysts were observed in 20 (3.8%) patients, and pineal cysts in 25 (4.8%) patients, mostly girls (68%, P<.001). White matter lesions were diagnosed in 30 (5.7%) patients, none with clinical evidence of neurologic disease. Brain asymmetry without clinical significance and developmental venous anomalies were observed in 14 (2.7%) and 8 (1.5%) patients, respectively. Twelve patients were diagnosed with intracranial tumors, and 5 required surgical intervention for a histopathologic diagnosis of juvenile pilocytic astrocytoma (n = 3), choroid plexus papilloma (n = 1), or inconclusive (n = 1). The rest were managed conservatively.Conclusion: Incidental findings on brain MRIs of pediatric patients referred by endocrinologists are common and raise dilemmas. The spectrum ranges from structural disruptions to tumors. Decision-making is individualized and patient-centered.     

Gastroenteropancreatic neuroendocrine tumors: standardizing therapy monitoring with 68Ga-DOTATOC PET/CT using the example of somatostatin receptor radionuclide therapy

The purpose of this study was to standardize therapy monitoring of hepatic metastases from gastroenteropancreatic neuroendocrine tumors (GEP-NETs) during the course of somatostatin receptor radionuclide therapy (SRRT). In 21 consecutive patients with nonresectable hepatic metastases of GEP-NETs, chromogranin A (CgA) and 68Ga-DOTATOC PET/CT were compared before and after the last SRRT. On 68Ga-DOTATOC PET/CT, the maximum standard uptake values (SUVmax) of normal liver and hepatic metastases were calculated. In addition, the volumes of hepatic metastases (volume of interest [VOI]) were measured using four cut-offs to separate normal liver tissue from metastases (SUVmax of the normal liver plus 10% [VOIliver+10%], 20% [VOIliver+20%], 30% [VOIliver+30%] and SUV = 10 [VOI10SUV]). The SUVmax of the normal liver was below 10 (7.2 ± 1.3) in all patients and without significant changes. Overall therapy changes (Δ) per patient (mean [95% CI]) were statistically significant with p < .01 for ΔCgA = -43 (-69 to -17), ΔSUVmax = -22 (-29 to-14), and ΔVOI10SUV = -53 (-68 to -38)% and significant with p < .05 for ΔVOIliver+10% = -29 (-55 to -3)%, ΔVOIliver+20% = -32 (-62 to -2) and ΔVOIliver+30% = -37 (-66 to -8). Correlations were found only between ΔCgA and ΔVOI10SUV (r = .595; p < .01), ΔSUVmax and ΔVOI10SUV (0.629, p < .01), and SUVmax and ΔSUVmax (r = -.446; p < .05). 68Ga-DOTATOC PET/CT allows volumetric therapy monitoring via an SUV-based cut-off separating hepatic metastases from normal liver tissue (10 SUV recommended).     

慢性心力衰竭患者B型利钠肽、C反应蛋白浓度变化的临床意义及丹参酮ⅡA磺酸钠注射液的治疗作用

目的:观察慢性心力衰竭患者外周血B型利钠肽(BNP)、C反应蛋白(CRP)浓度的变化,探讨丹参酮ⅡA磺酸钠注射液增加心肌供血,改善心功能的机制.方法:采用美国BIOSITE公司的trige分析仪检测外周血BNP的浓度,免疫浊度法测定CRP的浓度,研究正常对照组(20人),心脏病心功能正常组(33人),慢性心力衰竭组(61人)BNP、CRP浓度变化与慢性心衰患者心功能的相关性.并将CHF患者分为治疗组(33人)和对照组(28人),两组在同等的抗心衰治疗基础上,治疗组加用丹参酮ⅡA磺酸钠注射液60毫克,1个疗程(15天)结束后评定治疗前后两组的疗效及血浆BNP、CRP水平的变化.结果:与正常对照组和心脏病心功能正常组相比较,慢性心衰组BNP、CRP浓度均明显升高.治疗后慢性心力衰竭治疗组总有效率87.9%,对照组总有效率75%(P＜0.05).结论:慢性心力衰竭患者存在非特异炎症反应,血浆BNP、CRP水平与患者心功能密切相关.丹参酮ⅡA磺酸钠注射液可改善CHF患者的心功能,其机制可能是通过增加心肌供血,抑制炎症反应而实现的.     

Prospective comparative study of ultrasound, CT-scan, scintigraphy and laboratory tests to detect hepatic metastases.

The conventional methods of CT scan (CT), ultrasound (US), scintigraphy (SC), and laboratory tests (LDH, AP, 5-Nt) were prospectively compared in 135 patients with gastrointestinal carcinoma to define the most useful test to detect hepatic metastases. Thirty-six patients (26.7%) had hepatic metastases at laparotomy. Sensitivities were low: 46% for SC, 58% for US, 68% for CT and 63% for LDH. Accuracies ranged from 62% (LDH) to 78% (SC). No significant differences were found. Accurate and efficient detection of hepatic metastases is hampered by the relatively low sensitivity, specificity and accuracy of conventional imaging and laboratory tests.     

Radioimmunoscintigraphy using monoclonal antibodies to CEA, CA 19-9 and CA 125

131I labelled F (ab')2 fragments of monoclonal antibodies against CA 19-9 and CEA ("radioimmunococktail" IMACIS 1) were used in a prospective study (n = 60 patients) and in a retrospective study (n = 32 patients) for the detection of colorectal carcinomas (n = 67) and other gastrointestinal CEA/CA 19-9-producing tumors (n = 32). Sensitivity was 82% and specificity 90%. Immunoscintigraphy proved useful and complementary to CT scan and sonography, especially in the diagnosis of pelvic recurrences and intra-abdominal metastases. In addition, monoclonal antibody OC 125 (IMACIS 2) was used for the detection of ovarian carcinomas (n = 10) and other CA 125 producing tumors. Immunoscintigraphy was positive in all patients (n = 18) suggesting that this radioimmunological approach could be of use in the staging, therapeutic control and earlier diagnosis of recurrent epithelial ovarian carcinoma.     

Accuracy of [18F]FDG PET/MRI for the Detection of Liver Metastases

Background

The aim of this study was to compare the diagnostic accuracy of [¹⁸F]FDG-PET/MRI with PET/CT for the detection of liver metastases.

Methods

32 patients with solid malignancies underwent [¹⁸F]FDG-PET/CT and subsequent PET/MRI of the liver. Two readers assessed both datasets regarding lesion characterization (benign, indeterminate, malignant), conspicuity and diagnostic confidence. An imaging follow-up (mean interval: 185±92 days) and/-or histopathological specimen served as standards of reference. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for both modalities. Accuracy was determined by calculating the area under the receiver operating characteristic (ROC) curve. Values of conspicuity and diagnostic confidence were compared using Wilcoxon-signed-rank test.

Results

The standard of reference revealed 113 liver lesions in 26 patients (malignant: n = 45; benign: n = 68). For PET/MRI a higher accuracy (PET/CT: 82.4%; PET/MRI: 96.1%; p<0.001) as well as sensitivity (67.8% vs. 92.2%, p<0.01) and NPV (82.0% vs. 95.1%, p<0.05) were observed. PET/MRI offered higher lesion conspicuity (PET/CT: 2.0±1.1 [median: 2; range 0–3]; PET/MRI: 2.8±0.5 [median: 3; range 0–3]; p<0.001) and diagnostic confidence (PET/CT: 2.0±0.8 [median: 2; range: 1–3]; PET/MRI 2.6±0.6 [median: 3; range: 1–3]; p<0.001). Furthermore, PET/MRI enabled the detection of additional PET-negative metastases (reader 1: 10; reader 2: 12).

Conclusions

PET/MRI offers higher diagnostic accuracy compared to PET/CT for the detection of liver metastases.     

Diagnostic and therapeutic difficulties in MEN 1 syndrome

MEN 1 syndrome (Multiple Endocrine Neoplasia type 1) is a rare endocrine disorder characterized by the association of tumors in several endocrine glands, mainly in parathyroids, gut and pituitary. At our institution in the years 1982-2004 we have followed 26 patients with MEN 1 syndrome belonging to 19 families. The diagnosis of MEN 1 was based on Gubbio Consensus (JCEM 86: 5658-5671, 2001). Mean age at the diagnosis of MEN 1 was 35 years. Primary hyperparathyroidism was the most frequent pathology, which was diagnosed in 25 of 26 patients (96%). Gut endocrine tumors were found in 20 patients (77%), while pituitary tumors in 18 (70%). Non-functioning gut tumors were most frequent (n=9), followed by insulinoma (n=7) and gastrinoma (n=4). Prolactinoma was the most frequent pituitary tumor found in 12 patients (67%). Three patients died during the observation period - all of them of generalized gut endocrine tumor (gastrinoma in 2 cases and foregut carcinoid in one case). The management of MEN 1 is not easy and careful analysis of clinical picture is necessary in each individual case. Several important observations can be made on the basis of own experience and the literature: 1. In each sporadic pathology, which may be a part of MEN 1, one should consider. the possibility of MEN 1. The individual MEN 1 abnormalities are often diagnosed after 40 and later 2. MEN 1 tumor are usually multiple thus necessitating a different therapeutic approach (more radical surgery) 3. The most valuable screening tests are: Ca++, PP, CgA and prolactin 4. Endoscopic ultrasound is the most specific method for the localization of pancreatic endocrine tumors. 5. The results of surgical treatment of MEN 1 tumors are worse than that of sporadic tumors. 6. Prognosis in MEN 1 is determined by the behaviour of gut neuroendocrine tumor 7. No genotype/phenotype correlation in MEN 1 syndrome was found so far. In summary, it should be underlined that MEN 1 syndrome is an endocrine disorder, in which early diagnosis and optimal treatment may significantly improve the prognosis.     

The challenge of CT and MRI imaging of obese individuals who present to the emergency department: a national survey

The objective of this study was to estimate the availability of large weight capacity computed tomography (CT) and magnetic resonance imaging (MRI) equipment in US hospitals with emergency departments (EDs) and to evaluate animal facilities as alternate sources of imaging. We conducted a telephone survey of radiology technicians from a random sample of all the US hospitals with EDs (n = 262) and all 136 primary hospitals of academic EDs, 145 zoos, and 28 veterinary schools. We measured the prevalence of large weight capacity (>450 lb) CT and MRI, stratified by hospital characteristics. Response rates were 94-100% across samples. Nationally, 10% (95% confidence interval, 7-15) of hospitals with EDs had large weight capacity CT and 8% (95% confidence interval, 5-13) had large weight capacity MRI. In academic hospitals, access to large capacity equipment was better for CT (28%), but similar for MRI (10%) (P < 0.001 and 0.51, respectively). Few rural (5%) and critical-access hospitals (3%) had large capacity CT. In addition, 34% of trauma centers, 23% of stroke centers, and 21% of bariatric surgery centers of excellence had large capacity CT. Only two zoos (1%) had CT scanners; both would not image human patients. Among veterinary schools, 16 (57%) had large weight capacity CT equipment, but only 4 (14%) would consider imaging human patients. Further, 23 (82%) veterinary schools reported policies that specifically prohibited imaging humans. For patients who weigh >450 lb, access to emergent CT and MRI is limited, even at academic and bariatric surgery centers. Animal facilities are not a viable alternative for diagnostic imaging of human patients.     

Diagnosis of Coronary Heart Diseases Using Gene Expression Profiling; Stable Coronary Artery Disease,Cardiac Ischemia with and without Myocardial Necrosis

Cardiovascular disease (including coronary artery disease and myocardial infarction) is one of the leading causes of death in Europe, and is influenced by both environmental and genetic factors. With the recent advances in genomic tools and technologies there is potential to predict and diagnose heart disease using molecular data from analysis of blood cells. We analyzed gene expression data from blood samples taken from normal people (n = 21), non-significant coronary artery disease (n = 93), patients with unstable angina (n = 16), stable coronary artery disease (n = 14) and myocardial infarction (MI; n = 207). We used a feature selection approach to identify a set of gene expression variables which successfully differentiate different cardiovascular diseases. The initial features were discovered by fitting a linear model for each probe set across all arrays of normal individuals and patients with myocardial infarction. Three different feature optimisation algorithms were devised which identified two discriminating sets of genes, one using MI and normal controls (total genes = 6) and another one using MI and unstable angina patients (total genes = 7). In all our classification approaches we used a non-parametric k-nearest neighbour (KNN) classification method (k = 3). The results proved the diagnostic robustness of the final feature sets in discriminating patients with myocardial infarction from healthy controls. Interestingly it also showed efficacy in discriminating myocardial infarction patients from patients with clinical symptoms of cardiac ischemia but no myocardial necrosis or stable coronary artery disease, despite the influence of batch effects and different microarray gene chips and platforms.     

Stereotactic radiotherapy for liver oligometastases

The liver is the first metastatic site in 15–25% of colorectal cancer patients and one of the first metastatic sites for lung and breast cancer patients.A computed tomography (CT ) scan with contrast medium is a standard procedure for assessing liver lesions but magnetic resonance imaging (MRI) characterizes small lesions better thanks to its high soft-tissue contrast. Positron emission tomography with computed tomography (PET-CT ) plays a complementary role in the diagnosis of liver metastases. Triphasic (arterial, venous and time-delayed) acquisition of contrast-medium CT images is the first step in treatment planning. Since the liver exhibits a relatively wide mobility due to respiratory movements and bowel filling, appropriate techniques are needed for target identification and motion management. Contouring requires precise recognition of target lesion edges. Information from contrast MRI and/or PET-CT is crucial as they best visualize metastatic disease in the parenchyma. Even though different fractionation schedules were reported, doses and fractionation schedules for liver stereotactic radiotherapy (SRT ) have not yet been established. The best local control rates were obtained with BED₁₀ values over 100 Gy. Local control rates from most retrospective studies, which were limited by short follow-ups and included different primary tumors with intrinsic heterogeneity, ranged from 60% to 90% at 1 and 2 years. The most common SRT-related toxicities are increases in liver enzymes, hyperbilirubinemia and hypoalbuminemia. Overall, late toxicity is mild even in long-term follow-ups.     

Fine needle aspiration cytology of cutaneous and subcutaneous metastatic deposits from epithelial malignancies. An analysis of 146 cases

OBJECTIVE: To analyze cases suggestive of cutaneous/subcutaneous metastatic deposits from a known carcinoma or as the first manifestation of an unknown carcinoma using fine needle aspiration cytology (FNAC). STUDY DESIGN: The study group consisted of 146 patients (86 males and 60 females) ranging in age from 34 to 82 years. In 135 cases there was a previous history of carcinoma, and in these cases FNAC showed the tumor to be similar to the carcinoma that had been treated by surgery and/or radiotherapy. In 11 patients no tumor had been found previously, and the site of the unknown primary was suggested by immunostaining. Aspirations were performed using a 22-gauge needle. The material was collected in 30% ethyl alcohol, and filter preparations and cell blocks were made. RESULTS: The size of metastatic nodules ranged from 1.5 to 2 cm. The sites of metastases were on the chest wall (n = 35), back (n = 8), abdomen (including umbilicus) (n = 46), head and neck (n = 35), upper extremity (n = 12), lower extremity ((n = 6), penile skin (n = 1) and vulva (n = 3). The sites of known primary carcinomas were breast (n = 39), lung (n = 35), gastrointestinal tract (n = 38), endometrium (n = 2), cervix (n = 3), urinary tract (n = 4), prostate (n = 3), hand (n = 1), scalp (n = 1), tongue (n = 1), brain (n = 1), ear (n = 3) and ovary (n = 4). The sites of primary carcinomas unknown at the time of aspiration and found after FNAC were the gastrointestinal tract (n = 3), lung (n = 2), prostate (n = 1), breast (n = 3), liver (n = 1) and kidney (n = 1). No false negatives or positives were observed, and no second primary tumors were found. Cytologic preparations were sufficient for diagnosis and typing in tumors with a known primary tumor. Immunostaining was helpful in establishing a diagnosis of carcinoma and in determining the likely primary site in tumors with unknown primaries. CONCLUSION: Cutaneous and subcutaneous metastatic deposits from previously known carcinomas can be diagnosed rapidly and accurately utilizing FNAC. A combination of FNAC and immunostaining may also help define the site of an unknown primary.     

Myocardial hypertrophy of normotensive Wistar-Kyoto rats

In our studies with spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats, we observed normotensive WKY rats with cardiac hypertrophy determined by a greater left ventricular (LV) mass (LVM)-to-body weight (BW) ratio (LVM/BW) than that of normotensive Wistar rats. Thus we compared the following parameters in SHR, WKY, and Wistar rats: LVM/BW, cell capacitance as index of total surface area of the myocytes, length, width, and cross-sectional area of cardiac myocytes, LV collagen volume fraction, and myocardial stiffness. The LVM/BW of WKY (2.41 +/- 0.03 mg/g, n = 41) was intermediate between SHR (2.82 +/- 0.04 mg/g, n = 47) and Wistar rats (1.98 +/- 0.04 mg/g, n = 28). A positive correlation between blood pressure and LVM was found in SHR, whereas no such relationship was observed in WKY or Wistar rats. Cell capacitance and cross-sectional area were not significantly different in SHR and WKY rats; these values were significantly higher than those of Wistar rats. The cell length was smaller but the width was similar in WKY compared with SHR. Papillary muscles isolated from the LV of WKY and SHR were stiffer than those from Wistar rats. Consistently, a greater level of myocardial fibrosis was detected in WKY and SHR compared with Wistar rats. These findings demonstrate blood pressure-independent cardiac hypertrophy in normotensive WKY rats.     

Emerging technologies in therapeutic ultrasound: Thermal ablation to gene delivery

Ultrasound is used today in medicine as a modality for diagnostic imaging. Recently, there have been numerous reports on the application of thermal and nonthermal ultrasound energy for treating various diseases. In addition to thermal ablation of tumors, non-thermal ultrasound combined with drugs and genes have led to much excitement especially for cancer treatment, vascular diseases, and regenerative medicine. Ultrasound energy can enhance the effects of thrombolytic agents such as urokinase for treatment of stroke and acute myocardial infarction. New ultrasound technologies have resulted in advanced devices such as a) ultrasound catheters, b) Non-invasive methods as high intensity focused ultrasound (HIFU) in conjunction with MRI and CT is already being applied in the clinical field, c) Chemical activation of drugs by ultrasound energy for treatment of tumors is another new field recently termed “Sonodynamic Thew”, and d) Combination of genes and microbubble have induced great hopes for ideal gene therapy (sonoporation). Various examples of ultrasound combined modalities are under investigation which could lead to revolutionary therapy.     

Pancreastatin-like immunoreactivity in human carcinoid disease

Pancreastatin-like immunoreactivity has been demonstrated in human carcinoid tumors by immunohistochemistry and radioimmunoassay, employing antisera raised to a synthetic C-terminal fragment of porcine pancreastatin. Immunohistochemistry revealed intense immunoreactivity in all tumors. By radioimmunoassay, high concentrations of pancreastatin-like immunoreactivity were measured in carcinoid tumors arising from the fore-gut (mean +/- S.D. and range: 369 +/- 955 and 9.4-3670 pmol g-1, respectively, n = 14), mid-gut (mean +/- S.D. and range: 1354 +/- 1538 and 337-3978 pmol g-1, respectively, n = 5) and in metastases associated with mid-gut tumors (mean +/- S.D. and range: 684 +/- 739 and 31-2255 pmol g-1, respectively, n = 7), compared to corresponding normal tissues (less than 1.4 pmol g-1). Individuals with hepatic metastases and carcinoid syndrome had elevated circulating levels of pancreastatin-like immunoreactivity (mean +/- S.D. and range: 770 +/- 1249 and 42-4120 pmol l-1; n = 12), significantly above the normal, fasting range (mean +/- S.D. and range: 14.9 +/- 7.5 and 4-37.5 pmol l-1, respectively, n = 42). However, patients with non-metastatic carcinoid tumors (n = 4), who had been clinically cured after primary tumor resection, had plasma levels within the normal range. Chromatographic analysis of extracts of primary lung and ileal tumors, hepatic metastases from ileal tumors and plasma from individuals with carcinoid syndrome revealed molecular heterogeneity of pancreastatin-like immunoreactivity.     

Emerging technologies in therapeutic ultrasound: Thermal ablation to gene delivery

Ultrasound is used today in medicine as a modality for diagnostic imaging. Recently, there have been numerous reports on the application of thermal and nonthermal ultrasound energy for treating various diseases. In addition to thermal ablation of tumors, non-thermal ultrasound combined with drugs and genes have led to much excitement especially for cancer treatment, vascular diseases, and regenerative medicine. Ultrasound energy can enhance the effects of thrombolytic agents such as urokinase for treatment of stroke and acute myocardial infarction. New ultrasound technologies have resulted in advanced devices such as a) ultrasound catheters, b) Non-invasive methods as high intensity focused ultrasound (HIFU) in conjunction with MRI and CT is already being applied in the clinical field, c) Chemical activation of drugs by ultrasound energy for treatment of tumors is another new field recently termed "Sonodynamic Therapy", and d) Combination of genes and microbubble have induced great hopes for ideal gene therapy (sonoporation). Various examples of ultrasound combined modalities are under investigation which could lead to revolutionary therapy.