Radionuclide Imaging in Medullary Thyroid Carcinoma: Evaluation of Two New Radiopharmaceuticals

We assessed the uptake of two new radiopharmaceuticals, 131I meta-iodo-benzylguanidine (MIBG) and 99mTc(V) dimercaptosuccinic acid (DMSA), in patients with histologically proven medullary thyroid carcinoma (MTC). MIBG detected tumor in 40% of patients with known primary or recurrent tumor. 99m Tc(V) DMSA successfully demonstrated primary and recurrent tumor in 86% of patients imaged, with true negative results in 100% of patients imaged after successful surgical resection and a false-negative rate of 14%. We therefore suggest that 99m Tc(V) DMSA is the imaging agent of choice in patients with both primary and recurrent disease. 131I MIBG, with its high false-negative rate, has no place in tumor localization, but its potential role in therapy warrants further evaluation

5-Aminolevulinic acid-mediated fluorescence diagnosis of colon cancer: A histopathological comparison of fluorescent and non-fluorescent tumours

Background: 5-Aminolevulinic acid (5-ALA) selectively accumulates in cancer cells and is metabolised in the mitochondria to the fluorophore protoporphyrin IX. The GLiSten trial evaluated 5-ALA as a fluorescent probe for intraoperative detection of colon cancer and lymph node metastases. Only 13 of 40 cases showed fluorescence, suggesting a fundamental difference between fluorescent and non-fluorescent cancers. The aim of this study was to investigate whether differences in fluorescence were due to tumour cellularity, in particular T cell infiltration, which may be of prognostic significance. Method: Primary tumour tissue was available from 30 patients. The density of tumour cells, vascularity and stromal compartment size were quantified using digitally scanned tissue sections stained with haematoxylin and eosin. A set of 300 random points was superimposed onto each tumour image. The structure indicated by each point was then categorised as tumour, stroma, vessel or other. The proportions of tumour and vessel points gave the tumour cell density and vessel density respectively. The relative size of the stromal compartment was given by the tumour to stroma ratio. A tissue section was also stained for the T cell marker CD3 by immunohistochemistry. Percentage staining was quantified in three high-density fields using the Nuance imaging system. Results: We were unable to detect any difference between fluorescent and non-fluorescent cancers in terms of tumour cell density (difference in means 3.7%; P = 0.452), vessel density (difference in means 0.17%; P = 0.684), tumour-stroma ratio (difference in mean ratios 0.12; P = 0.934), or T cell count (difference in means 0.92%; P = 0.726). Furthermore, comparisons of the distributions of each variable demonstrated substantial overlap between the fluorescent and non-fluorescent cohorts. Conclusion: The results suggest that tumour and microenvironment structure do not differ between cancers that fluoresce with 5-ALA and those that do not. We therefore propose that the cellular metabolism of 5-ALA is a more likely explanation for differential fluorescence

FDG–PET in the prediction of survival of patients with cancer of the pancreas: a pilot study

Carcinoma of the pancreas is an aggressive tumour with an extremely poor prognosis. Recent studies have shown that chemotherapy can improve survival as well as quality of life. Since the prognosis is generally poor, the identification of early responders to chemotherapy is important to avoid unnecessary toxicity in patients who are not responding. Response assessment by conventional radiographic methods is problematical because treatment induces fibrosis and makes tumour measurements difficult. The aim of this pilot study was to assess 18-fluoro-deoxy-glucose positron emission tomography (FDG-PET) as an early marker of the benefit of chemotherapy. Eleven patients with histologically proven adenocarcinoma of the pancreas were treated with protracted venous infusional 5-fluorouracil (PVI 5-FU) alone or PVI 5-FU and mitomycin C (MMC). FDG-PET scans were performed prior to and at 1 month following the commencement of chemotherapy. FDG uptake was compared with the tumour dimensions measured on a computer tomographic (CT) scan. Patients were followed up for relapse, death and symptomatic response. Three of the 11 patients had no measurable FDG uptake prior to chemotherapy. Of the eight patients who had measurable uptake prior to treatment, seven had a reduction in uptake at 1 month. Six out of the 11 patients had no measurable FDG uptake at 1 month. The overall survival (OS) in these patients ranged from 124 to 1460 days, with a median of 318.5 days. This was superior in comparison to patients who had residual FDG uptake at 1 month (median survival 318.5 days vs 139 days;P = 0.034) and there was a trend to improved symptoms (84% [5/6] vs 20% [1/5];P = 0.13). There was no statistically significant correlation between best CT response and FDG uptake at 1 month. These results suggest that the absence of FDG uptake at 1 month following chemotherapy for carcinoma of the pancreas is an indicator of improved overall survival. This suggests that FDG-PET may be superior to response assessment by conventional radiographic methods and FDG-PET may have the potential to help make difficult treatment decisions in the management of pancreatic cancer. Larger prospective studies are required to confirm this finding. © 2000 Cancer Research Campaig

Influence of anatomic correction for transposition of the great arteries on myocardial perfusion: Radionuclide imaging with technetium-99m 2-methoxy isobutyl isonitrile

AbstractObjectives. We sought to determine the incidence of late perfusion defects attributable to coronary artery mobilization in patients undergoing anatomic correction for complete transposition of the great arteries.Background. Anatomic correction (arterial switch procedure) is currently the surgical treatment of choice for complete transposition. From its conception, there has been concern about the impact on myocardial perfusion of the coronary artery mobilization and reimplantation involved in the correction. Previous studies have demonstrated myocardial perfusion defects in patients after correction, although a causal relation between coronary mobilization, and perfusion abnormality has not been established.Methods. In a case-comparison study designed to test this hypothesis, 29 children underwent imaging with technetium-99m 2-methoxy isobutyl isonitrile (technetium-99m mibi). Ten had undergone anatomic correction (arterial switch group; interval from operation 6.9 ± 1.42 years [range 4.9 to 9.1]); 9 had required noncoronary open heart surgery for other cardiac lesions (postbypass group; interval from operation 5.6 ± 3.6 years [range 1.0 to 13.25]); and 10 had had no surgical procedure (control group). The latter group comprised children with atrial or ventricular septal defects who required a radionuclide study for shunt calculation. Planar studies were performed in all 29 children, and additional tomographic acquisition was achieved in 25. To assess reversibility of perfusion defects both an exercise and a rest planar study were performed in the arterial switch group.Results. Perfusion abnormalities were observed in seven of the nine children in the postbypass group and in all 10 children in the arterial switch group. The frequency of perfusion defects in these two groups was similar, with at least 25% of the tomographic segments reported being abnormal. The control group had significantly fewer defects than the other two groups (p = 0.02), with only 8% of the tomographic segments judged to be abnormal. In all except one patient in the arterial switch group, the segments reported as abnormal on the planar exercise study were either abnormal or equivocal on the rest study, indicating a fixed abnormality.Conclusions. Although the precise etiology of these perfusion abnormalities cannot be defined from this study, these data suggest that their origin is related more to the insult of open heart surgery itself than to the coronary manipulation involved in the arterial switch procedure. The functional importance requires further study

First shark from the late Devonian (Frasnian) gogo formation, Western Australia sheds new light on the development of tessellated calcified cartilage

Background: Living gnathostomes (jawed vertebrates) comprise two divisions, Chondrichthyes (cartilaginous fishes, including euchondrichthyans with prismatic calcified cartilage, and extinct stem chondrichthyans) and Osteichthyes (bony fishes including tetrapods). Most of the early chondrichthyan (‘shark’) record is based upon isolated teeth, spines, and scales, with the oldest articulated sharks that exhibit major diagnostic characters of the group—prismatic calcified cartilage and pelvic claspers in males—being from the latest Devonian, c. 360 Mya. This paucity of information about early chondrichthyan anatomy is mainly due to their lack of endoskeletal bone and consequent low preservation potential. Methodology/Principal Findings: Here we present new data from the first well-preserved chondrichthyan fossil from the early Late Devonian (ca. 380–384 Mya) Gogo Formation Lägerstatte of Western Australia. The specimen is the first Devonian shark body fossil to be acid-prepared, revealing the endoskeletal elements as three-dimensional undistorted units: Meckel’s cartilages, nasal, ceratohyal, basibranchial and possible epibranchial cartilages, plus left and right scapulocoracoids, as well as teeth and scales. This unique specimen is assigned to Gogoselachus lynnbeazleyae n. gen. n. sp.Conclusions/Significance: The Meckel’s cartilages show a jaw articulation surface dominated by an expansive cotylus, and a small mandibular knob, an unusual condition for chondrichthyans. The scapulocoracoid of the new specimen shows evidence of two pectoral fin basal articulation facets, differing from the standard condition for early gnathostomes which have either one or three articulations. The tooth structure is intermediate between the ‘primitive’ ctenacanthiform and symmoriiform condition, and more derived forms with a euselachian-type base. Of special interest is the highly distinctive type of calcified cartilage forming the endoskeleton, comprising multiple layers of nonprismatic subpolygonal tesserae separated by a cellular matrix, interpreted as a transitional step toward the tessellated prismatic calcified cartilage that is recognized as the main diagnostic character of the chondrichthyans

Double-outlet right ventricle: Morphologic demonstration using nuclear magnetic resonance imaging

Sixteen patients with double-outlet right ventricle, aged 1 week to 29 years (median 5 months), were studied with a 1.5 tesla nuclear magnetic resonance (NMR) imaging scanner. Two-dimensional echocardiography was performed in all patients. Thirteen patients underwent angiography, including nine who underwent subsequent surgical correction. Three patients underwent postmortem examination.Small children and infants were scanned inside a 32 cm diameter proton head coil. Multiple 5 mm thick sections separated by 0.5 mm and gated to the patient's electrocardiogram were acquired with a spin-echo sequence and an echo time of 30 ms. A combination of standard and oblique imaging planes was used. Imaging times were <90 min. The NMR images were technically unsuitable in one patient because of excessive motion artifact.In the remaining patients, the diagnosis of double outlet right ventricle was confirmed and correlated with surgical and postmortern findings. The NMR images were particularly valuable in demonstrating the interrelations between the great arteries and the anatomy of the outlet septum and the spatial relations between the ventricular septal defect and the great arteries. Although the atrioventricular (AV) valves were not consistently demonstrated, NMR imaging in two patients identified abnormalities of the mitral valve that were not seen with two-dimensional echocardiography. In one patient who had a superoinferior arrangement of the ventricles, NMR imaging was the most useful imaging technique for demonstrating the anatomy.In patients with double-outlet right ventricle, NMR imaging can provide clinically relevant and accurate morphologic information that may contribute to future improvement in patient management

Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer

Background: Photodynamic Therapy (PDT) is an attractive modality for treating solid cancers. This study evaluates the efficacy of Hypericin-PDT as a cytotoxic therapy in colorectal cancer (CRC), using 2D cell cultures and 3D multicellular tumour spheroids. Methods: Spheroids were generated through forced-floating and agitation-based techniques. 2D and spheroid models of HT29 and HCT116 CRC cells were incubated with Hypericin (0–200 nM) for 16 h. Cultures were irradiated with light (1 J/cm²) and cytotoxicity assessed using Propidium Iodide fluorescence. Expression of ABCG2 protein was assessed by immunoassays in 2D and spheroid cultures. The effect of ABCG2 inhibition, using 10 μM Ko143, on cytotoxicity following Hypericin-PDT was evaluated. Results: Hypericin-PDT produced a significant reduction in HT29 (p < 0.0001) and HCT116 (p < 0.0001) cell viability in 2D cultures, with negligible non-phototoxicity. Spheroids were more resistant than 2D cultures to Hypericin-PDT (HT29: p = 0.003, HCT116: p = 0.006) and had a greater expression of ABCG2. Inhibition of ABCG2 in spheroids with Ko143 resulted in an enhanced Hypericin-PDT effect compared to Hypericin-PDT alone (HT29: p = 0.04, HCT116: p = 0.01). Conclusions: Hypericin-PDT has reduced efficacy in CRC spheroids as compared to 2D cultures, which may be attributable through upregulation in ABCG2. The clinical efficacy of Hypericin-PDT may be enhanced by ABCG2 inhibition

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

Body odor quality predicts behavioral attractiveness in humans

Growing effort is being made to understand how different attractive physical traits co-vary within individuals, partly because this might indicate an underlying index of genetic quality. In humans, attention has focused on potential markers of quality such as facial attractiveness, axillary odor quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here we extend this approach to include visually-assessed kinesic cues (nonverbal behavior linked to movement) which are statistically independent of structural physical traits. The utility of such kinesic cues in mate assessment is controversial, particularly during everyday conversational contexts, as they could be unreliable and susceptible to deception. However, we show here that the attractiveness of nonverbal behavior, in 20 male participants, is predicted by perceived quality of their axillary body odor. This finding indicates covariation between two desirable traits in different sensory modalities. Depending on two different rating contexts (either a simple attractiveness rating or a rating for long-term partners by 10 female raters not using hormonal contraception), we also found significant relationships between perceived attractiveness of nonverbal behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary odor pleasantness was the single attribute that consistently predicted attractiveness of nonverbal behavior. Our results demonstrate that nonverbal kinesic cues could reliably reveal mate quality, at least in males, and could corroborate and contribute to mate assessment based on other physical traits