Detection of interval distant metastases: clinical utility of integrated CT-PET imaging in patients with esophageal carcinoma after neoadjuvant therapy

BACKGROUND: The objective of the study was to determine the utility of integrated computed tomography / positron emission tomography (CT-PET) imaging for detecting interval distant metastases and assessing therapeutic response in patients with locally advanced, potentially resectable esophageal carcinoma after neoadjuvant therapy. METHODS: A retrospective study was performed of 88 patients with potentially resectable esophageal carcinoma who received neoadjuvant therapy before planned surgical resection. CT-PET before and after completion of neoadjuvant was used for evaluating therapeutic response; response criteria were based on qualitative and semiquantitative analyses. RESULTS: Neoadjuvant therapy comprised chemoradiotherapy in 85 patients, with prior induction chemotherapy in 39 patients. Fifty-five patients proceeded to esophagectomy. Repeat CT-PET was performed after induction chemotherapy (n = 23) and after completing chemoradiotherapy (n = 85). CT-PET identified the interval appearance of metastatic disease in 7 (8%) patients. For assessment of locoregional therapeutic response, CT-PET was unable to predict pathological response to neoadjuvant therapy in the primary tumor or locoregional lymph nodes. CT-PET had sensitivity, specificity, and positive and negative predictive values of 57%, 46%, 39%, and 64%, respectively, for detection of residual macroscopic malignancy within the primary tumor; and sensitivity, specificity, and positive and negative predictive values of 0%, 90%, 0%, and 69% for detection of residual malignancy within resected lymph nodes. CONCLUSIONS: CT-PET performed after neoadjuvant therapy in patients with potentially resectable esophageal carcinoma is important for detecting interval metastases that preclude surgical resection, but is of limited utility for assessing locoregional therapeutic response.     

Disentangling the relative influence of built and socioeconomic environments on walking: The contribution of areas homogenous along exposures of interest

The geography of small areas has important implications for studying the contextual determinants of health because of potential errors when measuring ecologic exposures and estimating their effects on health. In this paper, we present an approach for designing homogeneous zones optimising the spatial distribution of an area-level exposure, active living potential (ALP), based on data collected in Montreal, Canada. The objectives are to (1) assess and compare variation in walking behaviours between these purposefully designed zones and between standard administrative units, census tracts; and (2) disentangle the relative influence of ALP and area-level socioeconomic conditions on walking using the alternative geographies. Zones were designed by statistically classifying smallest census areas (disseminations areas) into seven categories of exposure similar along three indicators of ALP: population density, land use mix, and geographic accessibility to services. Mapping of categories resulted in the delineation of zones characterised by one of seven levels of ALP. A sample of 2716 adults aged ≥45 years was geocoded and cross-classified in 270 zones and 112 census tracts. Individuals reported on minutes and motives of walking and provided socioeconomic information. Data were analysed using cross-classified multilevel models. Variation in utilitarian walking was larger across the purposefully defined zones than across census tracts. Total walking varied significantly between census tracts only. Greater ALP was associated with more utilitarian walking but with less recreational walking. Higher socioeconomic position in census tracts was positively associated with total, utilitarian, and recreational walking. The soundness of standard administrative units for measuring ecologic exposure and their associations with health should be considered prior to conducting analyses. The added value of different approaches for understanding how place relates to health remains to be established and should be the focus of further investigations.     

Multimodality imaging evaluation of esophageal cancer: staging, therapy assessment, and complications

Esophageal cancer is among the leading causes of cancer-related deaths worldwide. The management of patients with esophageal cancer is determined to a large extent by patient performance status, location of the primary cancer, and stage of disease at presentation. Multimodality regimens combining neoadjuvant chemotherapy and/or radiotherapy followed by surgery have been increasingly used in suitable candidates with locally advanced cancer. There is substantial morbidity and mortality associated with this treatment strategy, which makes appropriate patient selection important. Endoscopic esophageal ultrasound is the optimal modality to evaluate the local extent of the primary tumor and diagnose locoregional nodal metastasis. Computed tomography is more useful in detecting distant nodal and systemic metastasis. Positron emission tomography/CT is increasingly being used in patient management and improves the accuracy of staging, particularly in the detection of distant nodal and systemic metastatic disease. In this article, we review the role of imaging in the staging, assessment of therapeutic response, and detection of recurrent disease, as well as the evaluation of therapeutic complications in patients with esophageal cancer.     

Agreement between husband and wife reports of domestic violence: evidence from poor refugee communities in Lebanon

BACKGROUND: This paper compares husband and wife reports of wife beating using household survey data collected from poor Palestinian refugee communities in Lebanon. METHODS: The analyses are based on a matched data file of 417 currently married couples, drawn from a unique multi-purpose living conditions sample survey of about 3600 Palestinian refugee households interviewed in the spring and summer of 1999. Four outcomes (ever beaten, last year beating, beating during pregnancy, and injuries caused by beating) were analysed using Kappa statistics and per cent agreement. Logistic regression was used to analyse discordant reporting of wife beating during the year preceding the survey. RESULTS: Husband and wives' reports of the four different outcomes are in 'good' agreement as judged by Kappa coefficients, ranging from 0.62 for 'beaten during pregnancy' to 0.69 for 'injuries resulting from beating'. Prevalence estimates of domestic violence are also remarkably similar. However, findings from a multivariate logistic regression model on agreement regarding 'last year beating' show that only age of men was a significant predictor of agreement, controlling for education level, marital duration, region of residence, household size, health status, and consanguinity. CONCLUSIONS: Our findings show that men's self-reports of their violent behaviour against their wives are fairly congruent with those of their spouses, implying that the perpetrators, men, can be 'trusted' in providing basic information on 'beating histories' in epidemiological and demographic population-based investigations in contexts similar to ours. However, care should be taken in studies of young men's current beating behaviour using only their self-reports.     

Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications

BACKGROUND: Integrated computed tomography-positron emission tomography imaging with coregistration of anatomic and functional imaging data may improve the accuracy of malignant pleural mesothelioma staging. We evaluate the use of integrated computed tomography-positron emission tomography in patients with malignant pleural mesothelioma who are being considered for extrapleural pneumonectomy. METHODS: Twenty-nine patients with malignant pleural mesothelioma who were judged to be candidates for extrapleural pneumonectomy after clinical and conventional radiologic evaluation underwent whole-body integrated computed tomography-positron emission tomography and pathologic staging. Two reviewers blinded to the results of clinical and pathologic staging retrospectively evaluated computed tomography, positron emission tomography, and coregistered computed tomography-positron emission tomography images. Staging was performed according to the International Mesothelioma Interest Group TNM staging system. Histopathology and/or results of further radiologic evaluation or follow-up served as the reference standard. RESULTS: Integrated computed tomography-positron emission tomography provided additional information in 11 of 29 patients that precluded extrapleural pneumonectomy. The overall tumor stage was correctly classified in 21 of 29 patients. The tumor stage was correctly determined in 15 of 24 patients, 6 of whom had T4 (nonresectable) disease. The node stage was accurately determined in 6 of 17 patients. Extrathoracic metastases not identified by routine clinical and conventional radiologic evaluation were detected in 7 of 29 patients and were found to be diffuse (n = 2) or solitary (n = 5). CONCLUSIONS: Integrated computed tomography-positron emission tomography increases the accuracy of malignant pleural mesothelioma staging and is important in determining the appropriate therapy in patients being considered for extrapleural pneumonectomy.     

Pigmented villonodular synovitis (PVNS) of the knee joint: magnetic resonance imaging (MRI) using standard and dynamic paramagnetic contrast media. Report of 52 cases surgically and histologically controlled

PURPOSE: Pigmented villonodular synovitis (PVNS) is a rare proliferative disorder of the synovial membrane, exhibiting benign behaviour from a biological point of view. This kind of synovial hyperplasia leads to the formation of villi and nodules characterized by deposit of intracellular haemosiderin. It primarily involves young adults, the peak age being between the second and fourth decade of life. It may appear either in a diffuse or a localized (nodular) form. The joint most affected is the knee and diffuse PVNS is the most common form. Diagnostic imaging techniques, particularly MRI, allow lesion identification, suggesting a diagnosis. However, such diagnosis can be confirmed only on histology as the final diagnosis of PVNS, and therefore the possibility of differential diagnosis with other haemorrhagic and chronic hyperplastic synovites, is based on the detection of intracellular haemosiderin components. The aim of this study is to evaluate the usefulness of MRI, which might be completed with the intravenous injection of contrast medium, in the characterization of such pathological picture. MATERIALS AND METHODS: From January 1999 to December 2002, we evaluated 52 patients presenting knee swelling, pain and functional impairment. Only 19 patients had a history of trauma. All patients underwent MRI using a dedicated 0.2 T unit or a whole-body' 1.5 T unit. In 30 cases the baseline examination was completed with intravenous injection of contrast medium, followed by dynamic 3D-SPGR sequences at 45, 90, 135 and 225 seconds from the initial injection. These dynamic sequences were then processed by means of early and late subtractions, evaluating the regions of interest (ROI) positioned in the areas with higher post-contrast enhancement. Thirty-eight patients had been previously submitted to Ultrasonography (US), whereas twenty-five patients to Computed Tomography (TC). Later, all patients underwent surgery. Only two patients required an arthrotomy. We then retrospectively evaluated the imaging findings obtained, comparing them with the histological data. Patients affected by autoimmune and systemic inflammatory disorders were excluded from this study. RESULTS: The suspected diagnosis of PVNS was confirmed in 44/52 patients examined. CT examination allowed to detect the presence of a synovial proliferation with densitometric values ranging from 55 to 75 Hounsfield Units (HU) in all cases. In 11 cases, US examination revealed the presence of nodular hyperechoic structures surrounded by anechoic areas, with no differentiation between diffuse and nodular forms. Baseline MRI images showed no differential features among the various histological forms detected. In fact, the nodular structures demonstrated intermediate-to-low intensity signal in all sequences performed. Contrast enhanced MRI showed the presence of areas of inhomogeneous signal due to the increased intensity signal of hypervascular areas. The analysis of vascular dynamics demonstrated a characteristic exponential intensity/time curve both in diffuse and localized forms. DISCUSSION: The definition of pigmented villonodular synovitis was first employed by Jaffé in 1941 to describe the benign proliferative inflammatory nature of such pathology, characterized by a thickened and hyperplastic synovia organized into villi and nodules, leading to deposition of intracellular haemosiderin pigments. Presently, Authors prefer to include in hemorrhagic synovites all chronic and haemorragic synovial disorders, regardless of the aetiopathogenesis (rheumatoid arthritis, arthropathy secondary to haemorrhagic diathesis, chronic articular traumatism, haemangioma, synovial sarcoma). PVNS involves young adults, with no gender preference; it affects the knee joint in 66-80% of cases, with no typical symptomatology. The absolute absence of any characteristic feature makes a correct differential diagnosis difficult. So far, the only possibility to diagnose PVNS is based on the histological examination: presence of intracellular and subsynovial haemosiderin pigments, predominance of nodular structures as compared to villi, presence of macrophage multinucleate cells, production of collagen, mitotic cellular elements. Therefore, the possibility of characterizing PVNS using MRI is based on detection of a higher number of nodules as compared to villi, as the presence of haemosiderin is always characterized by low signal intensity on T2-weighted images, both intra- and extracellularly. New information on MRI semeiotics has come from the use of post-contrast enhanced dynamic sequences which are able to provide semi-quantitative data on CM velocity distribution within the hyperplastic areas. However, in our experience, dynamic-enhanced MRI did not provide any differential feature between PVNS and the other chronic hemorrhagic forms. Any inflammatory pathology leads to an increased capillary permeability with progressive deposit of CM in the area of interest. In all cases examined, the maximum deposit of contrast medium was observed in the extracellular phase, with a delayed wash-out. CONCLUSIONS: PVNS of the knee presents a difficult differential diagnosis. In many cases, only MRI is able to identify the presence of haemosiderin precipitates within the nodules characterizing the lesion. The use of standard and dynamic contrast media seems unable to provide additional diagnostic information. Thus, the diagnosis still pertains to histology.     

Relaxant effects of selective phosphodiesterase inhibitors on U46619 precontracted human intralobar pulmonary arteries and role of potassium channels

We examined the influence of K+ channel antagonists on the vasorelaxation induced by theophylline (non selective PDEI), siguazodan (PDE3I), rolipram (PDE4I) and zaprinast (PDE5I) in human intralobar pulmonary arteries. All PDEI tested induced a concentration-dependent relaxation with theophylline being significantly (p < 0.05) more efficient and rolipram more potent than PDE5I and PDE3I (Emax values, expressed as a percentage of maximal relaxation by papaverine 10(-4)M, were 92% +/- 2%, 84% +/- 8%, 90% +/- 4% and 99% +/- 1%, and pD2 values were 7.30 +/- 0.35, 6.14 +/- 0.25, 5.86 +/- 0.17, and 4.85 +/- 0.47 for rolipram, siguazodan, zaprinast and theophylline, respectively). 4-Aminopyridine (4-AP, Kv, voltage dependent channel blocker, 1 mM) induced a significant increase (+17% p < 0.05) of U46619-induced vasoconstriction whereas the other K+-channels blockers, glibenclamide (KATP channels, 1 microM) charybdotoxin (predominant BKCa, large conductance Ca2+-sensitive K+ channels, 0.1 microM) and apamine (SKCa, small conductance, 0.3 microM) were without effect. The concentration response curves (CRC) for rolipram were significantly shifted to the right by glibenclamide (1 microM), charybdotoxin (0.1 microM) and 4-AP (1 mM). The CRC for siguazodan was significantly displaced to the right by 4-AP. None of the potassium channel blockers displaced the CRC for zaprinast and theophylline. Apamine was without effect on the CRC for all the PDEI used in this study. (1) PDE3, 4 and 5 are functionally present in human intralobar pulmonary arteries; (2) the vasoconstriction induced by U46619 is downregulated by 4-aminopyridine sensitive-K+ channels; (3) the relaxant effects of rolipram (PDE4I) are partly mediated through KATP, BKCa, and Kv potassium channels and those of siguazodan (PDE3I) by Kv potassium channels.