Quantification of pleural effusion from single area measurements on CT

The objective of this study was to determine if area measurements of pleural fluid on computed tomography (CT) reflect the actual pleural fluid volume (PEvol) as measured at autopsy, to establish a formula to estimate the volume of pleural effusion (PEest), and to test the accuracy and observer reliability of PEest.132 human cadavers, with pleural effusion were divided into phase 1 (n = 32) and phase 2 (n = 100). In phase 1, PEvol was compared to area measurements on axial (axA), sagittal (sagA), and coronal (corA) CT images. Linear regression analysis was used to create a formula to calculate PEest. In phase 2, intra-class correlation (ICC) was used to assess inter-reader reliability and determine the agreement between PEest and PEvol. PEvol correlated to a higher degree to axA (r s mean = 0.738; p < 0.001) than to sagA (r s mean = 0.679, p < 0.001) and corA (r s mean = 0.709; p < 0.001). PEest can be established with the following formula: axA × 0.1 = PEest. Mean difference between PEest and PEvol was less than 40 mL (ICC = 0.837-0.874; p < 0.001). Inter-reader reliability was higher between two experienced readers (ICC = 0.984-0.987; p < 0.001) than between an inexperienced reader and both experienced readers (ICC = 0.660-0.698; p < 0.001). Pleural effusions may be quantified in a rapid, reliable, and reasonably accurate fashion using single area measurements on CT.

Malignant nail tumors

Because of the large number of different tissues making up the distal phalanx of fingers and toes, a large variety of malignant tumors can be found in and around the nail apparatus. Bowen disease is probably the most frequent nail malignancy. It is usually seen as a verrucous plaque of the nail fold and nail bed in persons above the age of 40 years. It slowly grows over a period of years or even decades before degenerating to an invasive squamous cell carcinoma. The latter may also occur primarily often as a weeping onycholysis. The next most frequent nail malignancy is ungual melanoma. Those arising from the matrix are usually pigmented and often start with a longitudinal melanonychia whereas those originating from the nail bed remain amelanotic, are often nodular and mistaken for an ingrown nail in an elderly person. The treatment of choice for in situ and early invasive subungual melanomas is generous extirpation of the nail apparatus whereas distal amputation is only indicated for advanced melanomas. In addition to these frequent nail malignancies, nail-specific carcinomas, malignant vascular and osseous tumors, other sarcomas, nail involvement in malignant systemic disorders and metastases may occur. In most cases, they cannot be diagnosed accurately on clinical grounds. Therefore, a high degree of suspicion is necessary in all isolated or single-digit proliferations that do not respond to conservative treatment.

Novel prognostic markers revealed by a proteomic approach separating benign from malignant insulinomas.

The prognosis of pancreatic neuroendocrine tumors is related to size, histology and proliferation rate. However, this stratification needs to be refined further. We conducted a proteome study on insulinomas, a well-defined pancreatic neuroendocrine tumor entity, in order to identify proteins that can be used as biomarkers for malignancy. Based on a long follow-up, insulinomas were divided into those with metastases (malignant) and those without (benign). Microdissected cells from six benign and six malignant insulinomas were subjected to a procedure combining fluorescence dye saturation labeling with high-resolution two-dimensional gel electrophoresis. Differentially expressed proteins were identified using nano liquid chromatography-electrospray ionization/multi-stage mass spectrometry and validated by immunohistochemistry on tissue microarrays containing 62 insulinomas. Sixteen differentially regulated proteins were identified among 3000 protein spots. Immunohistochemical validation revealed that aldehyde dehydrogenase 1A1 and voltage-dependent anion-selective channel protein 1 showed significantly stronger expression in malignant insulinomas than in benign insulinomas, whereas tumor protein D52 (TPD52) binding protein was expressed less strongly in malignant insulinomas than in benign insulinomas. Using multivariate analysis, low TPD52 expression was identified as a strong independent prognostic factor for both recurrence-free and overall disease-related survival.

Towards the introduction of the 'Immunoscore' in the classification of malignant tumours.

The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) TNM staging system provides the most reliable guidelines for the routine prognostication and treatment of colorectal carcinoma. This traditional tumour staging summarizes data on tumour burden (T), the presence of cancer cells in draining and regional lymph nodes (N) and evidence for distant metastases (M). However, it is now recognized that the clinical outcome can vary significantly among patients within the same stage. The current classification provides limited prognostic information and does not predict response to therapy. Multiple ways to classify cancer and to distinguish different subtypes of colorectal cancer have been proposed, including morphology, cell origin, molecular pathways, mutation status and gene expression-based stratification. These parameters rely on tumour-cell characteristics. Extensive literature has investigated the host immune response against cancer and demonstrated the prognostic impact of the in situ immune cell infiltrate in tumours. A methodology named 'Immunoscore' has been defined to quantify the in situ immune infiltrate. In colorectal cancer, the Immunoscore may add to the significance of the current AJCC/UICC TNM classification, since it has been demonstrated to be a prognostic factor superior to the AJCC/UICC TNM classification. An international consortium has been initiated to validate and promote the Immunoscore in routine clinical settings. The results of this international consortium may result in the implementation of the Immunoscore as a new component for the classification of cancer, designated TNM-I (TNM-Immune).

Can in-vitro chemoresponse assays help find new treatment regimens for malignant gliomas?

Various in-vitro chemosensitivity and resistance assays (CSRAs) have been demonstrated to be helpful decision aids for non-neurological tumors. Here, we evaluated the performance characteristics of two CSRAs for glioblastoma (GB) cells. The chemoresponse of fresh GB cells from 30 patients was studied in vitro using the ATP tumor chemoresponse assay and the chemotherapy resistance assay (CTR-Test). Both assay platforms provided comparable results. Of seven different chemotherapeutic drugs and drug combinations tested in vitro, treosulfan plus cytarabine (TARA) was the most effective, followed by nimustine (ACNU) plus teniposide (VM26) and temozolomide (TMZ). Whereas ACNU/VM26 and TMZ have proven their clinical value for malignant gliomas in large randomized studies, TARA has not been successful in newly diagnosed gliomas. This seeming discrepancy between in vitro and clinical result might be explained by the pharmacological behavior of treosulfan. Our results show reasonable agreement between two cell-based CSRAs. They appear to confirm the clinical effectiveness of drugs used in GB treatment as long as pharmacological preconditions such as overcoming the blood-brain barrier are properly considered.

Implications of Imaging Criteria for the Management and Treatment of Intraductal Papillary Mucinous Neoplasms - Benign versus Malignant Findings

OBJECTIVES Evaluation of computed tomography (CT) and magnetic resonance imaging (MRI) for differentiation of pancreatic intraductal papillary mucinous neoplasm (IPMN) subtypes based on objective imaging criteria. METHODS Fifty-eight patients with 60 histologically confirmed IPMNs were included in this retrospective study. Eighty-three imaging studies (CT,n = 42; MRI,n = 41) were analysed by three independent blinded observers (O1-O3), using established imaging criteria to assess likelihood of malignancy (-5, very likely benign; 5, very likely malignant) and histological subtype (i.e., low-grade (LGD), moderate-grade (MGD), high-grade dysplasia (HGD), early invasive carcinoma (IPMC), solid carcinoma (CA) arising from IPMN). RESULTS Forty-one benign (LGD IPMN,n = 20; MGD IPMN,n = 21) and 19 malignant (HGD IPMN,n = 3; IPMC,n = 6; solid CA,n = 10) IPMNs located in the main duct (n = 6), branch duct (n = 37), or both (n = 17) were evaluated. Overall accuracy of differentiation between benign and malignant IPMNs was 86/92 % (CT/MRI). Exclusion of overtly malignant cases (solid CA) resulted in overall accuracy of 83/90 % (CT/MRI). The presence of mural nodules and ductal lesion size ≥30 mm were significant indicators of malignancy (p = 0.02 and p < 0.001, respectively). CONCLUSIONS Invasive IPMN can be identified with high confidence and sensitivity using CT and MRI. The diagnostic problem that remains is the accurate radiological differentiation of premalignant and non-invasive subtypes. KEY POINTS • CT and MRI can differentiate benign from malignant forms of IPMN. • Identifying (pre)malignant histological IPMN subtypes by CT and MRI is difficult. • Overall, diagnostic performance with MRI was slightly (not significantly) superior to CT.

Autophagy in malignant transformation and cancer progression.

Autophagy plays a key role in the maintenance of cellular homeostasis. In healthy cells, such a homeostatic activity constitutes a robust barrier against malignant transformation. Accordingly, many oncoproteins inhibit, and several oncosuppressor proteins promote, autophagy. Moreover, autophagy is required for optimal anticancer immunosurveillance. In neoplastic cells, however, autophagic responses constitute a means to cope with intracellular and environmental stress, thus favoring tumor progression. This implies that at least in some cases, oncogenesis proceeds along with a temporary inhibition of autophagy or a gain of molecular functions that antagonize its oncosuppressive activity. Here, we discuss the differential impact of autophagy on distinct phases of tumorigenesis and the implications of this concept for the use of autophagy modulators in cancer therapy.

Benign vs malignant inferolateral early repolarization: Focus on the T wave.

BACKGROUND Inferolateral early repolarization (ER) is highly prevalent and is associated with idiopathic ventricular fibrillation (VF). OBJECTIVE The purpose of this study was to evaluate the potential role of T-wave parameters to differentiate between malignant and benign ER. METHODS We compared the ECGs of patients with ER and VF (n = 92) with control subjects with asymptomatic ER (n = 247). We assessed J-wave amplitude, QTc interval, T-wave/R-wave (T/R) ratio in leads II and V5, and presence of low-amplitude T waves (T-wave amplitude <0.1 mV and <10% of R-wave amplitude in lead I, II, or V4-V6). RESULTS Compared to controls, the VF group had longer QTc intervals (388 ms vs 377 ms, P = .001), higher J-wave amplitudes (0.23 mV vs 0.17 mV, P <.001), higher prevalence of low-amplitude T waves (29% vs 3%, P <.001), and lower T/R ratio (0.18 vs 0.30, P <.001). Logistic regression analysis demonstrated that QTc interval (odds ratio [OR] per 10 ms: 1.15, 95% confidence interval [CI} 1.02-1.30), maximal J-wave amplitude (OR per 0.1 mV: 1.68, 95% CI 1.23-2.31), lower T/R ratio (OR per 0.1 unit: 0.62, 95% CI 0.47-0.81), presence of low-amplitude T waves (OR 3.53, 95% CI 1.26-9.88). and presence of J waves in the inferior leads (OR 2.58, 95% CI 1.18-5.65) were associated with malignant ER. CONCLUSION Patients with malignant ER have a higher prevalence of low-amplitude T waves, lower T/R ratio (lead II or V5), and longer QTc interval. The combination of these parameters with J-wave amplitude and distribution of J waves may allow for improved identification of malignant ER.

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

BACKGROUND The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. OBJECTIVES We evaluated the clinical effect of SLNB in patients with thick melanoma. METHODS We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. RESULTS 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). CONCLUSIONS Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

A retrospective study of 1- versus 2-cm excision margins for cutaneous malignant melanomas thicker than 2 mm.

BACKGROUND Most guidelines recommend at least 2-cm excision margin for melanomas thicker than 2 mm. OBJECTIVE We evaluated whether 1- or 2-cm excision margins for melanoma (>2 mm) result in different outcomes. METHODS This is a retrospective cohort study on patients with melanomas (>2 mm) who underwent tumor excision with 1-cm (228 patients) or 2-cm (97 patients) margins to investigate presence of local recurrences, locoregional and distant metastases, and disease-free and overall survival. RESULTS In all, 325 patients with mean age of 61.84 years and Breslow thickness of 4.36 mm were considered for the study with a median follow-up of 1852 days (1995-2012). There was no significant difference in the frequency of locoregional and distant metastasis between the 2 groups (P = .311 and .571). The survival analysis showed no differences for disease-free (P = .800; hazard ratio 0.948; 95% confidence interval 0.627-1.433) and overall (P = .951; hazard ratio 1.018; 95% confidence interval 0.575-1.803) survival. LIMITATIONS The study was not prospectively randomized. CONCLUSIONS Our study did not show any significant differences in important outcome parameters such as local or distant metastases and overall survival. A prospective study testing 1- versus 2-cm excision margin is warranted.

Positron emission mammography in the diagnosis of breast cancer. Is maximum PEM uptake value a valuable threshold for malignant breast cancer detection?

AIM To evaluate the diagnostic value (sensitivity, specificity) of positron emission mammography (PEM) in a single site non-interventional study using the maximum PEM uptake value (PUVmax). PATIENTS, METHODS In a singlesite, non-interventional study, 108 patients (107 women, 1 man) with a total of 151 suspected lesions were scanned with a PEM Flex Solo II (Naviscan) at 90 min p.i. with 3.5 MBq 18F-FDG per kg of body weight. In this ROI(region of interest)-based analysis, maximum PEM uptake value (PUV) was determined in lesions, tumours (PUVmaxtumour), benign lesions (PUVmaxnormal breast) and also in healthy tissues on the contralateral side (PUVmaxcontralateral breast). These values were compared and contrasted. In addition, the ratios of PUVmaxtumour / PUVmaxcontralateral breast and PUVmaxnormal breast / PUVmaxcontralateral breast were compared. The image data were interpreted independently by two experienced nuclear medicine physicians and compared with histology in cases of suspected carcinoma. RESULTS Based on a criteria of PUV>1.9, 31 out of 151 lesions in the patient cohort were found to be malignant (21%). A mean PUVmaxtumour of 3.78 ± 2.47 was identified in malignant tumours, while a mean PUVmaxnormal breast of 1.17 ± 0.37 was reported in the glandular tissue of the healthy breast, with the difference being statistically significant (p < 0.001). Similarly, the mean ratio between tumour and healthy glandular tissue in breast cancer patients (3.15 ± 1.58) was found to be significantly higher than the ratio for benign lesions (1.17 ± 0.41, p < 0.001). CONCLUSION PEM is capable of differentiating breast tumours from benign lesions with 100% sensitivity along with a high specificity of 96%, when a threshold of PUVmax >1.9 is applied.