The Intended Scope of the Second Amendment of the Bill of Rights

This paper addresses the much debated Second Amendment to the US Constitution. The Second Amendment reads: ”A well regulated Militia, being necessary to the security of a free State, the right of the people to keep and bear arms, shall not be infringed”. With a combination of a originalist approach a textualist approach, this work aims at answering what was the intended scope of the Second Amendment. Was it meant to protect the right of citzens to have arms for the collective purpose of serving the militia, or was it also intended to protect the individual right to own arms for self-defense? In the late 1780s, a debate over the ratification of the new Constitution took place. One of the discussed issues was allocation of military powers. With the new Constitution, the federal government would be given power to call forth militias, to organize, arm, and disciplin them. This created a fear among the people of the United States that the state militias might be ordered disarmed. As the state militias served as a security against standing armies and tyranny, they were considered necessary to the security of a free state. Antifederalists, opponents of the Constitution, demanded a Bill of Rights be added to the Constitutions which would include a security against disarmament. The Second Amendment has rarely been considered by the Supreme Court and only two cases exists in which the Court has directly questioned the scope of the Amendment. In United States v. Miller (1939), the Court found that the obvious purpose of the Second Amendment was to assure the continuation and effectiveness of the militia and that the Amendment must be applied with this in mind. Though the case has been used to support different views of the scope of the Amendment, the Court dismissed the defendants’ claim that the law at issue was unconstitutional because there was no connection to militia service. Though the precedential value of Miller is debatable, I believe the opinion of the Court was that there must be a militia connection for a person to invoke their right to arms. However, this is not what the Court found in District of Columbia v. Heller (2008). The Court in Heller found that the Second Amendment protects an individual right to keep handguns for the purpose of self-defense. A wide range of people has engaged in the debate over the Second Amendment and in this paper, interpretations by 3 important scholars of the 19th century are presented. The two most prominent interpretative theories which have emerged in the 20th century are also discussed - The Individual Right Theory and the Collective Right Theory. According to the Collective Rights Theory, the significance of the prefatory clause is to announce the only purpose of the Second Amendment. This purpose was to ensure that state militias would remain and that the people were granted the right to keep and bear arms to participate in a well regulated militia and, thus, the Second Amendment only protects this collective right. Those in support of the Individual Right Theory, however, interpret the Second Amendment as a codification of the pre-existing right to arms for self-defense and that the scope of the Amendment is not limited by the prefatory clause. I find that the Second Amendment was adopted only to secure that the federal government would not encroach on the people’s right to keep and bear arms for serving the militia. The Amendment must be read with its two phrases as a whole, and the fact that this was the only purpose stated in the prefatory clause must be considered. Had the framers intended to constitutionally protect the right to arms for self-defense, they could have included it in the Amendment’s preamble together the militia purpose.Denna uppsats behandlar det omtvistade andra tillägget i den amerikanska konstitutionens rättighetsstadga. Det andra tillägget lyder: ”En väl reglerad milis, nödvändig för en fri stats säkerhet, folkets rätt att ha och bära vapen, skall inte kränkas” (egen översättning). Med hjälp av ursprungstolkning och texttolkning, är syftet med denna uppsats att besvara vad som var det andra tilläggets avsedda omfattning. Var det menat att skydda folkets rätt att ha vapen för det gemensamma syftet att delta i milisen, eller var det också avsett att skydda varje medborgares rätt till vapen för självförsvar? Genom den nya konstitutionen skulle den nybildade federala regeringen få makt att kalla in miliser, att organisera, beväpna och träna dem. Detta skapade en rädsla hos det amerikanska folket, som oroade sig att staternas miliser skulle kunna bli avväpnade. Eftersom staternas miliser fungerade som en säkerhet mot permanenta arméer och tyranni ansågs de nödvändiga för en fri stats säkerhet. För att anta rättighetsstadgan krävde därför Antifederalister, konstitutionens motståndare, att en rättighetsstadga lades till och att det i den fanns en säkerhet mot bland annat avväpning. Det andra tillägget har berörts av Högsta Domstolen väldigt sällan och det finns bara två rättsfall i vilka domstolen direkt har tolkat omfattningen av tillägget. I United States v. Miller (1939) ansåg domstolen att det uppenbara syftet med det andra tillägget var att säkerställa fortlevnaden och effektiviteten av milisen, samt att det andra tillägget måste tolkas i ljuset av detta. Även om fallet har använts både som argument för att tillägget är en individuell rättighet och att det är en gemensam rättighet, avvisade domstolen de anklagades påstående att lagen i fråga var oförenlig med konstitutionen eftersom det saknades militär koppling. Även om prejudikatvärdet av Miller är omdebatterat, tror jag att domstolen ansåg att det måste finnas en koppling till militärt syfte för att någon ska kunna åberopa rättigheten i andra tillägget. Detta var dock inte var domstolen kom fram till i District of Columbia v. Heller (2008). I Heller ansåg domstolen att det andra tillägget skyddar en individuell rätt att ha vapen i syfte att användas i självförsvar. Denna uppsats behandlar hur tre viktiga forskare under 18-talet, tolkade tillägget. De två teorier om hur det andra tillägget ska tolkas som har vuxit fram under 1900-talet diskuteras också. Enligt den gemensamma rättighetsteorin ska den inledande meningen i tillägget förstås som att den klargör det enda syftet med tillägget. Detta syfte var att säkerställa att statliga milisen skulle kvarstå och att folket skulle vara garanterade en rätt att ha vapen för att kunna delta i milisen. Därmed förespråkar anhängare av denna teori att den andra tillägget enbart syftade att skydda en gemensam rättighet. Å andra sidan menar de som förespråkar den individuella rättigshetsteorin att det andra tillägget kodifierade en redan existerande rättighet att ha vapen för självförsvar och att omfattningen av tillägget inte begränsas av den inledande meningen. Jag drar slutsatsen att det andra tillägget antogs enbart för att säkerställa att den federala regeringen inte skulle kränka folkets rätt att ha vapen för att kunna delta i milisstyrkorna. Tillägget måste läsas med dess två meningar som en helhet och det faktum att den inledande meningen enbart nämner ett syfte måste beaktas. Om skaparna av rättighetsstadgan hade avsett att skapa ett konstitutionellt skydd till rätten att ha vapen för självförsvar hade de kunnat inkludera detta syfte i tilläggets inledning, tillsammans med syftet att ha en välreglerad milis

Aktieägaravtalets civilrättsliga verkningar - särskilt om avtalade avståenden från rätt till tvångsinlösen och hembudsinlösen

Aktieägaravtal är vanligt förekommande i svenska aktiebolag och fungerar som ett kompletterande styrinstrument för bolagets ägare. Genom att ingå avtal kan aktieägare frångå reglerna i aktiebolagslagen2 och bolagsordningen. Avgörande för om avtalet får den effekt som parterna avser är dock vilka rättsliga verkningar gällande rätt tillmäter aktieägaravtalet. Utgångspunkten är att aktieägaravtal inte medför aktiebolagsrättsliga verkningar, om inte lag föreskriver annat. Detta följer av den aktiebolagsrättsliga separationsprincipen, en princip som bygger på att avtalsrätten och aktiebolagsrätten utgör två inbördes autonoma rättsområden. Aktieägaravtal kan t.ex. innehålla föreskrifter om att parterna avsäger sig sin rätt till tvångsinlösen eller hembudsinlösen. Huruvida den aktiebolagsrättsliga separationsprincipen kan tillämpas för att bedöma vilka rättsliga verkningar sådana avtal medför är beroende av principens tillämpningsomfång. Enligt Nerep är principen tillämplig så snart ett aktieägaravtal tar sikte på någon regel i ABL medan Arvidsson anser att principen enbart är tillämplig på rättsfrågor som rör bolagets inre rättsförhållande, dvs. relationen mellan å ena sidan bolaget och å andra sidan bolagets aktörer. I arbetet tar jag ställning för Arvidssons uppfattning eftersom denna bygger på en rättslig analys och denna syn har flera fördelar. Eftersom rätten till inlösen inte berör bolagets inre rättsförhållande saknar den aktiebolagsrättsliga separationsprincipen all betydelse för frågan om vilka verkningar avtalade avstående från rätt till inlösen har. Bedömningen av sådana avtals rättsliga verkningar får istället ske utifrån den avtalsrättsliga distinktionen mellan tvingande och dispositivt. Inlösenrättigheter är obligationsrättsliga rättigheter även om rättigheterna i fråga kommer till uttryck i ABL. NJA 2011 s. 429 visar dock att det finns möjlighet att företa en analog tillämpning av den aktiebolagsrättsliga separationsprincipen. Det kan dock endast ske om syftet med de ifrågavarande reglerna motiverar det. I arbetet finner jag att aktieägare har en begränsad möjlighet att i aktieägaravtal avstå från rätten till tvångsinlösen. Genom NJA 2011 s. 429 har Högsta domstolen konstaterat att sådana avtal inte ska beaktas i en tvångsinlösenprocess. Däremot tycks det råda större frihet för aktieägare att förfoga över den rätten till inlösen som följer av ett hembudsförbehåll i bolagsordningen. Aktieägaravtal i vilka parterna avstår från sin rätt till hembudsinlösen torde vara obligationsrättsligt bindande och även bindande i en aktiebolagsrättslig kontext. Förutsatt att förvärvaren är avtalspart, kan rätten till hembudsinlösen därför elimineras helt genom aktieägaravtal. Aktieägaravtal kan t.ex. innehålla föreskrifter om att parterna avsäger sig sin rätt till tvångsinlösen eller hembudsinlösen. Huruvida den aktiebolagsrättsliga separationsprincipen kan tillämpas för att bedöma vilka rättsliga verkningar sådana avtal medför är beroende av principens tillämpningsomfång. Enligt Nerep är principen tillämplig så snart ett aktieägaravtal tar sikte på någon regel i ABL medan Arvidsson anser att principen enbart är tillämplig på rättsfrågor som rör bolagets inre rättsförhållande, dvs. relationen mellan å ena sidan bolaget och å andra sidan bolagets aktörer. I arbetet tar jag ställning för Arvidssons uppfattning eftersom denna bygger på en rättslig analys och denna syn har flera fördelar. Eftersom rätten till inlösen inte berör bolagets inre rättsförhållande saknar den aktiebolagsrättsliga separationsprincipen all betydelse för frågan om vilka verkningar avtalade avstående från rätt till inlösen har. Bedömningen av sådana avtals rättsliga verkningar får istället ske utifrån den avtalsrättsliga distinktionen mellan tvingande och dispositivt. Inlösenrättigheter är obligationsrättsliga rättigheter även om rättigheterna i fråga kommer till uttryck i ABL. NJA 2011 s. 429, det s.k. Mineralmålet, visar dock att det finns möjlighet att företa en analog tillämpning av den aktiebolagsrättsliga separationsprincipen. Det kan dock endast ske om syftet med de ifrågavarande reglerna motiverar det. I arbetet finner jag att aktieägare har en begränsad möjlighet att i aktieägaravtal avstå från rätten till tvångsinlösen. Genom Mineralmålet har Högsta domstolen konstaterat att sådana avtal inte ska beaktas i en tvångsinlösenprocess. Däremot tycks det råda större frihet för aktieägare att förfoga över den rätten till inlösen som följer av ett hembudsförbehåll i bolagsordningen. Aktieägaravtal i vilka parterna avstår från sin rätt till hembudsinlösen torde vara obligationsrättsligt bindande och även bindande i en aktiebolagsrättslig kontext. Förutsatt att förvärvaren är avtalspart, kan rätten till hembudsinlösen elimineras helt.Shareholder agreements are often used as a governing instrument in Swedish limited companies. By entering such agreements, the company’s shareholders can agree on rules that deviate from the rules of the Swedish Companies Act1 (SCA) or the Article of Association. However, whether the agreement will have the impact that the parties desire depends on what legal effects shareholder agreements are given under Swedish law. According to the separation principle in company law, explicit legal support in statutory law is necessary in order for a shareholder agreement to have company law effects. This principle is founded upon the idea that contract law and company law are two mutually autonomous areas of law. Shareholders may, for example, agree to refrain from their rights in chapter 22 SCA or their post-transfer acquisition right. Whether the separation principle can be adapted to assess the legal effects of such an agreement depends on how far the principle’s appliance scope reaches. According to Nerep, the principle applies whenever a shareholder agreement regulated a norm or right stated in SCA, regardless of the actual characteristics of the norm or right. Meanwhile, Arvidsson claims that the principle is only applicable when the question at hand relates to the internal legal relations of the company. Since the view presented by Arvidsson is based on a thourough legal analysis and because it leads to desired results, I agree with Arvidsson’s perception of the scope of the separations principle. In accordance with Arvidsson’s view, the separation principle of company law is not applicable on agreements among shareholders to refrain from their acquisition rights. This follows from the fact that such rights are not related to the internal legal relations of the company, i.e. between the company in its capacity as a legal entity on the one hand and its actors and bodies on the other. The legal effects of such shareholder agreements must thus instead be assessed on the distinction between mandatory and optional, since acquisition rights are contractual rights. However, it follows from the case NJA 2011 s. 429 that the separation principle may be applied analogically if motivated by the purpose of the rights or norms at hand. In this paper, I find that shareholders’ power to refrain from their acquisition rights under chapter 22 SCA is limited. The Swedish Supreme Court have concluded that such agreements should be ignored in an acquisition procedure. Meanwhile, shareholders have a greater liberty to refrain from their post-transfer acquisition rights. Agreements in which shareholders refrain from such rights are legally binding between the parties and should be considered even in a company context. Given that the acquirer is a party to the agreement, the post-transfer acquisition right can thus be eliminated altogether through shareholder agreements. Shareholders may, for example, agree to refrain from their rights in chapter 22 SCA or their post-transfer acquisition right. Whether the separation principle can be adapted to assess the legal effects of such an agreement depends on how far the principle’s appliance scope reaches. According to Nerep, the principle applies whenever a shareholder agreement deals with a norm or right that is stated in SCA, regardless of the actual characteristics of the norm or right. Meanwhile, Arvidsson claims that the principle is only applicable when the question at hand relates the internal legal relations of the company. Since the view presented by Arvidsson is based on a thourough legal analysis and because it leads to desired results, I agree with Arvidsson’s perception of the scope of the separations principle. In accordance with Arvidsson’s view, the separation principle of company law is not applicable on agreements among shareholders to refrain from their acquisition rights. This follows from the fact that such rights are not related to the internal legal relations of the company, i.e. between the company in its capacity as a legal entity on the one hand its actors and bodies on the other. The legal effects of such shareholder agreements must thus instead be assessed on the distinction between mandatory and optional, since acquisition rights are contractual rights. However, it follows from the case NJA 2011 s. 429 that the separation principle may be applied analogically if motivated by the purpose of the rights or norms at hand. In this paper, I find that shareholders’ power to refrain from their right to compulsory cession of shares under chapter 22 SCA is limited. The Swedish Supreme Court have concluded that such agreements should not be considered in an acquisition procedure. Meanwhile, shareholders have a greater liberty to refrain from their post-transfer acquisition rights. Agreements in which shareholders refrain from such rights are legally binding between the parties and should be considered even in a company context. Given that the acquirer is a party to the agreement, the post-transfer acquisition right can thus be eliminated altogether

Automatic registration of multi-modal microscopy images for integrative analysis of prostate tissue sections

Background Prostate cancer is one of the leading causes of cancer related deaths. For diagnosis, predicting the outcome of the disease, and for assessing potential new biomarkers, pathologists and researchers routinely analyze histological samples. Morphological and molecular information may be integrated by aligning microscopic histological images in a multiplex fashion. This process is usually time-consuming and results in intra- and inter-user variability. The aim of this study is to investigate the feasibility of using modern image analysis methods for automated alignment of microscopic images from differently stained adjacent paraffin sections from prostatic tissue specimens. Methods Tissue samples, obtained from biopsy or radical prostatectomy, were sectioned and stained with either hematoxylin & eosin (H&E), immunohistochemistry for p63 and AMACR or Time Resolved Fluorescence (TRF) for androgen receptor (AR). Image pairs were aligned allowing for translation, rotation and scaling. The registration was performed automatically by first detecting landmarks in both images, using the scale invariant image transform (SIFT), followed by the well-known RANSAC protocol for finding point correspondences and finally aligned by Procrustes fit. The Registration results were evaluated using both visual and quantitative criteria as defined in the text. Results Three experiments were carried out. First, images of consecutive tissue sections stained with H&E and p63/AMACR were successfully aligned in 85 of 88 cases (96.6%). The failures occurred in 3 out of 13 cores with highly aggressive cancer (Gleason score ≥ 8). Second, TRF and H&E image pairs were aligned correctly in 103 out of 106 cases (97%). The third experiment considered the alignment of image pairs with the same staining (H&E) coming from a stack of 4 sections. The success rate for alignment dropped from 93.8% in adjacent sections to 22% for sections furthest away. Conclusions The proposed method is both reliable and fast and therefore well suited for automatic segmentation and analysis of specific areas of interest, combining morphological information with protein expression data from three consecutive tissue sections. Finally, the performance of the algorithm seems to be largely unaffected by the Gleason grade of the prostate tissue samples examined, at least up to Gleason score 7

miR-145 suppress the androgen receptor in prostate cancer cells and correlates to prostate cancer prognosis.

Androgen signalling through the androgen receptor (AR) is essential for prostate cancer initiation, progression and transformation to the lethal castration-resistant state. The aim of this study was to characterize the mechanisms by which miR-145 deregulation contribute to prostate cancer progression. The miR-145 levels, measured by quantitative reverse transcription-polymerase chain reaction, were found to inversely correlate with occurrence of metastases, survival and androgen deprivation therapy response in a well-characterized prostate cancer cohort. Introduction of ectopic miR-145 in prostate cancer cells generated an inhibitory effect on the AR at both transcript and protein levels as well as its activity and downstream targets prostate-specific antigen (PSA), kallikrein-related peptidase 2 and TMPRSS2. The regulation was shown to be mediated by direct binding using Ago2-specific immunoprecipitation, but there was also indication of synergetic AR activation. These findings were verified in clinical prostate specimens by demonstrating inverse correlations between miR-145 and AR expression as well as serum PSA levels. In addition, miR-145 was found to regulate androgen-dependent cell growth in vitro. Our findings put forward novel possibilities of therapeutic intervention, as miR-145 potentially could decrease both the stem cells and the AR expressing bulk of the tumour and hence reduce the transformation to the deadly castration-resistant form of prostate cancer

Cystatin C Is Downregulated in Prostate Cancer and Modulates Invasion of Prostate Cancer Cells via MAPK/Erk and Androgen Receptor Pathways

Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (rs2 = −0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis

Preclinical evaluation of (111)In-DTPA-INCA-X anti-Ku70/Ku80 monoclonal antibody in prostate cancer.

The aim of this investigation was to assess the Ku70/Ku80 complex as a potential target for antibody imaging of prostate cancer. We evaluated the in vivo and ex vivo tumor targeting and biodistribution of the (111)In-labeled human internalizing antibody, INCA-X ((111)In-DTPA-INCA-X antibody), in NMRI-nude mice bearing human PC-3, PC-3M-Lu2 or DU145 xenografts. DTPA-conjugated, non-labeled antibody was pre-administered at different time-points followed by a single intravenous injection of (111)In-DTPA-INCA-X. At 48, 72 and 96 h post-injection, tissues were harvested, and the antibody distribution was determined by measuring radioactivity. Preclinical SPECT/CT imaging of mice with and without the predose was performed at 48 hours post-injection of labeled DTPA-INCA-X. Biodistribution of the labeled antibody showed enriched activity in tumor, spleen and liver. Animals pre-administered with DTPA-INCA-X showed increased tumor uptake and blood content of (111)In-DTPA-INCA-X with reduced splenic and liver uptake. The in vitro and in vivo data presented show that the (111)In-labeled INCA-X antibody is internalized into prostate cancer cells and by pre-administering non-labeled DTPA-INCA-X, we were able to significantly reduce the off target binding and increase the (111)In-DTPA-INCA-X mAb uptake in PC-3, PC-3M-Lu2 and DU145 xenografts. The results are encouraging and identifying the Ku70/Ku80 antigen as a target is worth further investigation for functional imaging of prostate cancer

Plasma enterolactone and risk of prostate cancer in middle-aged Swedish men

Enterolactone (ENL) is formed in the human gut after consumption of lignans, has estrogenic properties, and has been associated with risk of prostate cancer. We examined the association between plasma ENL levels and prostate cancer in a nested case-control study within the population-based Malmo Diet and Cancer cohort. We also examined the association between plasma ENL and dietary and lifestyle factors. The study population consisted of 1010 cases occurring during a mean follow-up of 14.6 years, and 1817 controls matched on age and study entry date. We used national registers (95%) and hospital records (5%) to ascertain cases. Diet was estimated by a modified diet history method. Plasma ENL concentrations were determined by a time-resolved fluoroimmunoassay. Odds ratios were calculated by unconditional logistic regression. There were no significant associations between plasma ENL and incidence of all prostate cancer (odds ratio 0.99 [95% confidence interval 0.77-1.280] for the highest ENL quintile versus lowest, p for trend 0.66). However, in certain subgroups of men, including men with abdominal obesity (p for interaction = 0.012), we observed associations between high ENL levels and lower odds of high-risk prostate cancer. Plasma ENL was positively associated with consumption of high-fibre bread, fruit, tea, and coffee; with age, and with height, while it was negatively associated with smoking and waist circumference; however, although significant, all associations were rather weak (r ae |0.14|). ENL concentration was not consistently associated with lower prostate cancer risk, although it was weakly associated with a healthy lifestyle.Peer reviewe

Expression of STAT3 in Prostate Cancer Metastases

STAT3 and its upstream activator IL6R have been implicated in the progression of prostate cancer and are possible future therapeutic targets. We analyzed 223 metastatic samples from rapid autopsies of 71 patients who had died of castration-resistant prostate cancer (CRPC) to study protein and gene expression of pSTAT3 and IL6R. Immunohistochemical analysis revealed that 95% of metastases were positive for pSTAT3 and IL6R, with varying expression levels. Bone metastases showed significantly higher expression of both pSTAT3 and IL6R in comparison to lymph node and visceral metastases. STAT3 mRNA levels were significantly higher in bone than in lymph node and visceral metastases, whereas no significant difference in IL6R mRNA expression was observed. Our study strongly supports the suggested view of targeting STAT3 as a therapeutic option in patients with metastatic CRPC. Patient summary We studied the levels of two proteins (pSTAT3 and IL6R) in metastases from patients who died from castration-resistant prostate cancer. We found high levels of pSTAT3and IL6R in bone metastases, suggesting that these proteins could be used as targets for new anticancer drugs

Quality of life with pharmacological treatment in patients with benign prostatic enlargement: results from the Evolution European Prospective Multicenter Multi-National Registry Study.

Item does not contain fulltext Background Lower urinary tract symptoms due to benign prostate enlargement (LUTS/BPE) can lead to significant disturbances to health-related quality of life (HRQoL) and psychological well-being. The aim of this study was to evaluate the effect of pharmacological treatment of LUTS/BPE on disease specific and generic QOL measures. Methods Evolution was a European prospective, multicenter multi-national, observational registry collecting real-life clinical data over 2 years on the management of LUTS/BPE in primary and secondary care. This study investigated disease-specific QOL using questionnaires such as IPSS Q8, BPH Impact Index (BII) and generic QOL using questionnaires like EuroQOL Five Dimension (EQ5D) which encompassed EQ5D VAS and EQ5D health index. Results The registry enrolled 1838 BPE patients and 1246 patients were evaluable at the end of 24 months. Nearly 70% of patients in the study were previously treated with medical therapy and 17% of these had already discontinued medical treatment previously for various reasons with lack of efficacy being the most common. The mean time since diagnosis of LUTS in the previously treated group was 4.7 years (0-26 years). Medical management produced statistically significant improvement in QOL (disease specific and generic) in previously untreated patients and an insignificant change in generic QOL in previously treated patients. Conclusions After 5-years from the onset of symptoms, LUTS/BPE patients previously treated with medication had significantly impaired QOL in patients in a manner comparable to other chronic diseases. Earlier intervention with minimally invasive surgical techniques (MIT) should be considered in LUTS/BPE patients that do not show a significant improvement in QOL with medical therapy

Effects of radiation therapy on tissue and serum concentrations of tumour associated trypsin inhibitor and their prognostic significance in rectal cancer patients

<p>Abstract</p> <p>Background</p> <p>We have previously demonstrated that elevated concentrations of tumour-associated trypsin inhibitor (TATI) in both tumour tissue (t-TATI) and in serum (s-TATI) are associated with a poor prognosis in colorectal cancer patients. It was also found that s-TATI concentrations were lower in patients with rectal cancer compared to patients with colon cancer. In this study, we investigated the effects of neoadjuvant radiotherapy (RT) on concentrations of t-TATI and s-TATI in patients with rectal cancer.</p> <p>Methods</p> <p>TATI was analysed in serum, normal mucosa and tumour tissue collected at various time points in 53 rectal cancer patients enrolled in a case-control study where 12 patients received surgery alone, 20 patients 5 × 5 Gy (short-term) preoperative RT and 21 patients 25 × 2 Gy (long-term) preoperative RT. T-TATI was analysed by immunohistochemistry and s-TATI was determined by an immunofluorometric assay. Mann-Whitney U test and Wilcoxon Z (Z) test were used to assess t-TATI and s-TATI concentrations in relation to RT. Spearman's correlation (R) test was used to explore the associations between t-TATI, s-TATI and clinicopathological parameters. Overall survival (OS) according to high and low t-TATI and s-TATI concentrations was estimated by classification and regression tree analysis, Kaplan-Meier analysis and the log rank test.</p> <p>Results</p> <p>RT did not affect concentrations of t-TATI or s-TATI. In patients receiving short-term but not long-term RT, s-TATI concentrations were significantly higher 4 weeks post surgery than in serum drawn prior to surgery (Z = -3.366, P < 0.001). T-TATI expression correlated with male gender (R = 0.406, P = 0.008). High t-TATI expression in surgical specimens was associated with a significantly shorter OS (P = 0.045). S-TATI concentrations in serum drawn at all time points were associated with an impaired OS (P = 0.035 before RT, P = 0.001 prior to surgery, P = 0.043 post surgery). At all time points, s-TATI correlated with higher age (P < 0.001-0.021) and with increased s-creatinine concentrations assessed prior to surgery (P = 0.041).</p> <p>Conclusions</p> <p>The results presented here further validate the utility of t-TATI and s-TATI as prognostic biomarkers in patients with rectal cancer, independent of neoadjuvant RT.</p