Utility of hybrid SPECT/CT in Sentinel Lymph Node mapping, and 18F FDG-PET/CT for treatment response evaluation in cancer patients.

The Sentinel Lymph Node Biopsy (SLNB) method is currently well established in the staging of clinically node-negative breast cancer. However, there is some debate concerning the reliability of this method following previous breast surgery. The SLNB method may also be a valuable tool in the staging of oesophageal cancer or cancer of the gastro-oesophageal junction (GOJ), though there are also indications that the method may be less reliable in more advanced cases. Moreover, the impact of a history of neoadjuvant treatment with either chemo-radiotherapy or chemotherapy alone on lymphatic drainage patterns from the oesophagus or GOJ is not well understood. Therefore, there exists a need to further investigate the SLNB method in this patient group. The addition of neoadjuvant therapy in patients with cancer of the oesophagus or GOJ has been shown to improve long-term survival when compared to surgery alone, but there is a need for better diagnostic tools to evaluate the clinical effects of neoadjuvant therapy in this patient group. This thesis had two main aims. The first aim was to evaluate the utility of hybrid SPECT/CT lymphoscintigraphy in patients with lesions of the breast, or lesions of the oesophagus or GOJ. The second aim was to evaluate the predictive value of 18F-FDG PET/CT in regard to histological response following neoadjuvant treatment in patients with cancer of the oesophagus or GOJ. Paper I: In this study including patients with benign breast lesions, and using SPECT/CT lymphoscintigraphy prior to, and six weeks following a diagnostic breast excision, with the non-operated breasts serving as a control group. We observed no statistically significant differences in reproducibility between the operated and non-operated breasts regarding SLN detection. Paper II: In this study including patients with cancer of the oesophagus/GOJ and using hybrid SPECT/CT lymphoscintigraphy. SPECT/CT yielded a high number of detected Sentinel Lymph Nodes. Another aim was to investigate the overall performance of the SLNB method in this patient group, however the accuracy of the Sentinel Lymph Node Biopsy method in the current patient population was poor. Paper III: In this study investigating the effect of neoadjuvant chemo-radiotherapy on tumour lymphatic drainage patterns in patients with cancer of the oesophagus or GOJ using sequential SPECT/CT lymphoscintigraphy before and following chemo-radiotherapy, but before surgery. The reproducibility of SLN detection was very poor. The SLNB method may be unreliable in patients with cancer of the oesophagus/GOJ with a history of previous neoadjuvant chemo-radiotherapy or chemotherapy. Neoadjuvant chemo-radiotherapy in fact appears to have a considerable impact on lymphatic drainage patterns from the oesophagus or GOJ regarding SLN detection. Paper IV: In this study including patients with cancer of the oesophagus/GOJ. randomised to either neoadjuvant chemo-radiotherapy or neoadjuvant chemotherapy and using consecutive 18F-FDG PET/CT examinations. Changes in PET parameters were studied in relation to post- operative histological response in the primary tumour. In particular, changes to the hitherto seldom-used Standardized Uptake Ratio (SUR) PET-parameter was of interest. When pooling the two treatment arms, there was found to be a statistically significant difference in reduction of SUR in patients with histological response compared to patients with little or no histological response. However, it was not possible to predict a complete histological response

Hur går fastighetsbolag tillväga vid värdering? – En undersökning av fem fastighetsbolag i Göteborg

Syftet med denna uppsats är att beskriva vilka värderingsmodeller som fastighetsbolag i Göteborg använder sig av vid värdering av hyreshus, samt beskriva hur dessa används. Påverkande faktorer kommer också att beskrivas. 1980-talets överhettade ekonomi ledde under början av 90-talet till att den svenska ekonomin kraschade. Många fastighetsbolag var överbelånade och gick därför i konkurs. Krisen som uppstod på fastighetsmarknaden ledde till att fastighetsbolagen fick sig en tankeställare och började omvärdera sitt sätt att värdera fastigheter. Det finns i vårt teorikapitel huvudsakligen tre metoder för fastighetsvärdering. Nuvärdesmetoden är benämning på de värderingsmetoder där användaren diskonterar framtida överskott eller nyttor till den tidpunkt då fastigheten önskas värderas. Ortsprismetoden bygger på en jämförelse mellan fastigheten som skall värderas och ett urval av jämförbara fasigheter. En fördel med denna metod är att den tar hänsyn till trender på marknaden som inte beaktats i kassaflödena. Produktionskostnadsmetoden bygger på att värderaren ser på vad kostnaden skulle bli för att uppföra en likadan byggnad. Metoden är särskilt användbar då värderaren önskar värdera ett objekt med speciella egenskaper. Det är viljan att minimera riskerna som gör att fastighetsbolagen använder sig av värderingsmetoder. Samtliga de företag som intervjuats bygger sina värderingar på fastighetens driftsnetto. Tre av de fem fastighetsbolagen nuvärdesberäknar kassaflödena, medan de andra två upprättar något som liknar en budget. Vi tror att företagets ägarstruktur påverkar valet av värderingsmodell. De tre fastighetsbolag som använder sig av de teoretiskt mest avancerade metoderna vid fastighetsvärdering är också de företag som har störst skyldighet att visa upp för sina ägare hur företaget arbetar med värdering av fastigheter. Fyra av de fem fastighetsbolagen vi har intervjuat tar hänsyn till risken genom att justera kassaflödena, medan det femte hanterar risken genom att använda sig av olika diskonteringsräntor

Comparison of Regularized Reconstruction and Ordered Subset Expectation Maximization Reconstruction in the Diagnostics of Prostate Cancer Using Digital Time-of-Flight 68Ga-PSMA-11 PET/CT Imaging

In prostate cancer, the early detection of distant spread has been shown to be of importance. Prostate-specific membrane antigen (PSMA)-binding radionuclides in positron emission tomography (PET) is a promising method for precise disease staging. PET diagnostics depend on image reconstruction techniques, and ordered subset expectation maximization (OSEM) is the established standard. Block sequential regularized expectation maximization (BSREM) is a more recent reconstruction algorithm and may produce fewer equivocal findings and better lesion detection. Methods: 68Ga PSMA-11 PET/CT scans of patients with de novo or suspected recurrent prostate cancer were retrospectively reformatted using both the OSEM and BSREM algorithms. The lesions were counted and categorized by three radiologists. The intra-class correlation (ICC) and Cohen’s kappa for the inter-rater reliability were calculated. Results: Sixty-one patients were reviewed. BSREM identified slightly fewer lesions overall and fewer equivocal findings. ICC was excellent with regards to definitive lymph nodes and bone metastasis identification and poor with regards to equivocal metastasis irrespective of the reconstruction algorithm. The median Cohen’s kappa were 0.66, 0.74, 0.61 and 0.43 for OSEM and 0.61, 0.63, 0.66 and 0.53 for BSREM, with respect to the tumor, local lymph nodes, metastatic lymph nodes and bone metastasis detection, respectively. Conclusions: BSREM in the setting of 68Ga PMSA PET staging or restaging is comparable to OSEM

Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies

The utility of anthracycline antineoplastic agents in the clinic is compromised by the risk of cardiotoxicity. It has been calculated that approximately 10% of patients treated with doxorubicin or its derivatives will develop cardiac complications up to 10 years after the cessation of chemotherapy. Oxidative stress has been established as the primary cause of cardiotoxicity. However, interventions reducing oxidative stress have not been successful at reducing the incidence of cardiotoxicity in patients treated with doxorubicin. New insights into the cardiomyocyte response to oxidative stress demonstrate that underlying differences between in vitro and in vivo toxicities may modulate the response to superoxide radicals and related compounds. This has led to potentially new uses for pre-existing drugs and new avenues of exploration to find better pharmacotherapies and interventions for the prevention of cardiotoxicity. However, much work still must be done to validate the clinical utility of these new approaches and proposed mechanisms. In this review, the authors have reviewed the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin-induced cardiotoxicity and propose potential pharmacological interventions and treatment options to prevent or reverse this specific type of heart failure. (C) 2012 Elsevier Ltd. All rights reserved

Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies

AbstractThe utility of anthracycline antineoplastic agents in the clinic is compromised by the risk of cardiotoxicity. It has been calculated that approximately 10% of patients treated with doxorubicin or its derivatives will develop cardiac complications up to 10years after the cessation of chemotherapy. Oxidative stress has been established as the primary cause of cardiotoxicity. However, interventions reducing oxidative stress have not been successful at reducing the incidence of cardiotoxicity in patients treated with doxorubicin. New insights into the cardiomyocyte response to oxidative stress demonstrate that underlying differences between in vitro and in vivo toxicities may modulate the response to superoxide radicals and related compounds. This has led to potentially new uses for pre-existing drugs and new avenues of exploration to find better pharmacotherapies and interventions for the prevention of cardiotoxicity. However, much work still must be done to validate the clinical utility of these new approaches and proposed mechanisms. In this review, the authors have reviewed the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin-induced cardiotoxicity and propose potential pharmacological interventions and treatment options to prevent or reverse this specific type of heart failure

“Sentinel lymph node imaging with sequential SPECT/CT lymphoscintigraphy before and after neoadjuvant chemoradiotherapy in patients with cancer of the oesophagus or gastro-oesophageal junction – a pilot study”

Abstract Background In current best practise, curatively intended treatment for oesophageal cancer usually consists of neoadjuvant chemo-radiotherapy (nCRT) or perioperative chemotherapy, and oesophagectomy. Sentinel Lymph Node Biopsy (SLNB) has the potential to identify patients without lymph node metastases and thus improve the staging accuracy and influence treatment. The impact of neoadjuvant treatment on the lymphatic drainage of oesophageal cancers and subsequently the SLNB procedure in this tumour type has previously not been well studied. Purpose To evaluate changes in lymphatic drainage patterns of the tumour in patients with cancer of the oesophagus or gastro-oesophageal junction (GOJ) using Sentinel Lymph Node (SLN) hybrid SPECT/CT lymphoscintigraphy before and after nCRT. Methods Patients with clinical stage T2-T3, any N-stage, M0 cancer of the oesophagus or GOJ underwent endoscopically guided peri−/intratumoral injection of radio-colloid followed by hybrid SPECT/CT lymphoscintigraphy prior to, and once again following, nCRT. SPECT/CT images were evaluated to number and location of SLNs and compared between the two examinations. Results Ten patients were included in this pilot trial. SPECT/CT lymphoscintigraphy was performed in twenty procedures. The same Sentinel Lymph Node station before and after nCRT was observed in one single patient. In two patients, no SLN was detected before nCRT. In three patients no SLN was detected following nCRT. In four patients, the SLN stations were not the same station at baseline compared to follow-up examination. Conclusions The reproducibility SLN detection in patients with cancer of the oesophagus/GOJ following nCRT was very poor. nCRT appears to alter lymphatic drainage patterns and thus may affect detection of SLNs and potentially also the accuracy of an SLNB in these patients. On the basis of these initial results, we abort further patient recruitment in our institution. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR). Identifier ACTRN12618001433291. Date registered: 27/08/2018. Retrospectively registered

Fatty acid synthase as a novel target for meningioma therapy

High levels of fatty acid synthase (FAS) expression have been reported in hormone receptor-positive tumors, including prostate, breast, and ovarian cancers, and its inhibition reduces tumor growth in vitro and in vivo. Similar to other hormone receptor-positive tumor types, meningiomas are progesterone receptor- and estrogen receptor-immunoreactive brain tumors. To define the role of FAS in human meningioma growth control, we first analyzed the FAS expression using a tissue microarray containing 38 meningiomas and showed increased FAS expression in 70% of atypical WHO grade II and anaplastic WHO grade III meningiomas compared with 10% of benign WHO grade I tumors. We next confirmed this finding by real-time PCR and Western blotting. Second, we demonstrated that treatment with the FAS inhibitor, cerulenin (Cer), significantly decreased meningioma cell survival in vitro. Third, we showed that Cer treatment reduced FAS expression by modulating Akt phosphorylation (activation). Fourth, we demonstrated that Cer treatment of mice bearing meningioma xenografts resulted in significantly reduced tumor volumes associated with increased meningioma cell death. Collectively, our data suggest that the increased FAS expression in human meningiomas represents a novel therapeutic target for the treatment of unresectable or malignant meningioma