Comparison of contrast-enhanced ultrasonography and MRI results obtained by expert and novice radiologists indicating short-term response after transarterial chemoembolisation for hepatocellular carcinoma.

AIM: To evaluate inter-reader agreement between novice and expert radiologists in assessing contrast-enhanced ultrasonography (CEUS) and magnetic resonance imaging (MRI) images for detecting viable tumours with different sizes after conventional transarterial chemoembolisation (cTACE). MATERIALS AND METHODS: This prospective study included patients who had less than five hepatomas and who underwent cTACE. Hepatomas with one or two feeding arteries were selected as target lesions. CEUS and MRI were performed within 1 week after cTACE to evaluate viable tumours. RESULTS: The expert group had higher kappa values in evaluating all tumour sizes via CEUS compared with MRI. The novice group had similar kappa values. In patients with tumours measuring ≤3 cm, the expert group had higher kappa values in reading CEUS compared with MRI images; however, in the novice group, the kappa value was lower in evaluating CEUS compared with MRI images. In patients with tumours measuring >3 cm, the expert and novice groups had good to excellent kappa values. The confidence level of the two groups in reading MRI images was high; however, the novice group had a lower confidence level. CONCLUSION: CEUS is a convenient, cost-effective, and easy to apply imaging tool that can help interventionists perform early detection of viable hepatocellular carcinoma post-TACE. It has a higher inter-rater agreement in interpreting CEUS images compared with MRI images among expert radiologists even when they are extremely familiar with post-cTACE MRI images. In novice radiologists, there may be a learning curve to achieve good consistency in CEUS interpretation.

Nuclear Vav3 is required for polycomb repression complex-1 activity in B-cell lymphoblastic leukemogenesis.

Acute B-cell lymphoblastic leukemia (B-ALL) results from oligo-clonal evolution of B-cell progenitors endowed with initiating and propagating leukemia properties. The activation of both the Rac guanine nucleotide exchange factor (Rac GEF) Vav3 and Rac GTPases is required for leukemogenesis mediated by the oncogenic fusion protein BCR-ABL. Vav3 expression becomes predominantly nuclear upon expression of BCR-ABL signature. In the nucleus, Vav3 interacts with BCR-ABL, Rac, and the polycomb repression complex (PRC) proteins Bmi1, Ring1b and Ezh2. The GEF activity of Vav3 is required for the proliferation, Bmi1-dependent B-cell progenitor self-renewal, nuclear Rac activation, protein interaction with Bmi1, mono-ubiquitination of H2A(K119) (H2AK119Ub) and repression of PRC-1 (PRC1) downstream target loci, of leukemic B-cell progenitors. Vav3 deficiency results in de-repression of negative regulators of cell proliferation and repression of oncogenic transcriptional factors. Mechanistically, we show that Vav3 prevents the Phlpp2-sensitive and Akt (S473)-dependent phosphorylation of Bmi1 on the regulatory residue S314 that, in turn, promotes the transcriptional factor reprogramming of leukemic B-cell progenitors. These results highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.

Peritoneal metastases from extra-abdominal cancer - A population-based study.

INTRODUCTION: Peritoneal metastases (PM) are predominantly seen as a manifestation of intra-abdominal malignancy such as colorectal or ovarian cancer. However, extra-abdominal primary cancer can also metastasise to the peritoneum. Population-based data on the incidence of PM from extra-abdominal cancer is lacking. This study aims to assess the patterns and survival of patients in Ireland with PM from extra-abdominal cancers. METHODS: The National Cancer Registry of Ireland database was interrogated to identify patients diagnosed with PM from extra-abdominal malignancy during the period 1994-2012. Patient demographics and tumour characteristics were analysed. RESULTS: 5791 patients were diagnosed with PM during the study period. Of these, 543 (9%) had an extra-abdominal primary malignancy. Breast (40.8%), lung (25.6%) and melanoma (9.3%) were the most common extra-abdominal cancers to develop PM. The majority of patients with peritoneal metastases of breast origin (75%) were diagnosed at a long interval (median interval 59.5 months; range = 1-485) from the diagnosis of the primary. The median survival from diagnosis of PM was 5.8 months compared with 22.6 months from diagnosis of stage IV disease without peritoneal involvement. Survival in patients with lung cancer and melanoma who developed PM was very poor and similar to that in patients with stage IV disease not involving the peritoneum. CONCLUSION: This is the first population-based study to report the incidence of PM secondary to extra-abdominal malignancy. The most common primary cancers were melanoma, breast and lung cancer. Metastatic disease to the peritoneum was uniformly associated with a poor prognosis.

An 18 year population-based study on site of origin and outcome of patients with peritoneal malignancy in Ireland.

Peritoneal malignancy (PM) is predominantly metastatic spread from advanced gastrointestinal or gynaecological cancer. PM is generally considered incurable and therefore has rarely been the focus of novel therapeutic strategies. This study assessed patterns and survival outcomes for patients with PM in Ireland. The National Cancer Registry Ireland database was interrogated to identify patients diagnosed with PM during the period 1994-2012. Patient and tumour characteristics were retrieved and survival outcomes calculated. 5791 patients were diagnosed during the study period. Median age at diagnosis was 68 years; females accounted for 62%. The incidence increased annually from 228 in 1994 to 401 in 2012. Primary PM accounted for 3% of cases. Colorectal (22%), ovarian (16%) and gastric (13%) cancers accounted for the majority of cases of secondary PM. Almost 75% of patients had PM at initial presentation. Almost 40% of patients (n = 2274) underwent surgical intervention, while 44% (n = 2560) had tumour directed chemotherapy. The median survival (MS) in patients with secondary PM was 6.6 months, and did not improve significantly during the study period. Outcomes were best in patients with ovarian cancer (MS 15.9 months) and colorectal cancer (MS 14.3 months) and worst in patients with lung (MS 2.4 months) and pancreas (MS 1.9 months) cancers. This is the first population-based study from Ireland to report the incidence and outcomes for PM. PM is more common than previously reported and survival remains poor. These findings highlight the need for greater clinician awareness and the need to focus on new therapeutic approaches to improve patient outcomes.

Application of peripherally inserted central catheter in acute myeloid leukaemia patients undergoing induction chemotherapy.

Increasingly, peripherally inserted central catheters (PICC) are applied in patients with haematological malignancies. The feasibility and safety of PICC for induction chemotherapy in acute myeloid leukaemia (AML) remain unclear. Medical records of 89 newly diagnosed adult de novo AML patients, who achieved complete remission, were retrospectively reviewed (PICC group, n = 43; intravenous [IV] line group, n = 46). Patients' clinical characteristics and the number of blind punctures for blood sampling were compared between these two groups, and risk factors associated with bacteraemia were identified by univariate analysis. Patients in the PICC group experienced significantly fewer blind punctures than those in the IV line group (3.3 ± 3.6 vs. 14.4 ± 6.0; p = .000); 20.9% of PICC patients had bacteraemia, compared with 23.9% in the IV line group (p = .803). Most patients (76.7%) removed their PICC because treatment was completed. PICC increased the quality of life in AML patients undergoing chemotherapy induction by reducing the number of blind blood punctures required. Bacteraemia in PICC patients was comparable to that in IV line patients. PICC is, therefore, a feasible and safe central venous device for use in AML patients.

Mentored experience of establishing a national peritoneal malignancy programme - Experience of first 50 operative cases.

BACKGROUND: Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) are considered standard of care for pseudomyxoma peritonei (PMP) and selected patients with colorectal peritoneal metastases (CPM) or peritoneal mesothelioma. A National Peritoneal Malignancy programme was established in Ireland (population of 4.5 million) in May 2013 with mentoring and support from the Peritoneal Malignancy Institute, Basingstoke UK. This study reviews the operative and oncological outcomes for the first 50 patients who underwent CRS and HIPEC in Ireland. METHODS: This is a retrospective review of all patients referred, and of the subset who underwent CRS and HIPEC, for peritoneal malignancy in Ireland between May 2013 and November 2015. RESULTS: During the study period, 130 patients were referred and 50 patients were selected for CRS and HIPEC. Three patients were found to have unresectable disease at laparotomy. Of the remaining 47 patients, eight had major tumour debulking. In total, 39 underwent complete cytoreduction and 45 received HIPEC. After a median follow-up of 12.7 months, 12 patients had developed further metastatic disease. The rates of complete cytoreduction, major complication (Clavien-Dindo III/IV) and operative mortality were 83%, 0% and 0%, respectively. 32% of patients experienced grade I/II complications. CONCLUSIONS: We report the successful establishment of a national peritoneal malignancy programme. Mentoring from an experienced centre may have shortened the known learning curve evident by our encouraging outcomes. The follow-up period is short, however our early results are comparable with internationally reported figures.

A systematic review of the role of re-laparoscopy in the management of complications following laparoscopic colorectal surgery.

The benefits of laparoscopic versus open surgery for patients with both benign and malignant colorectal disease have been well established. Re-laparoscopy in patients who develop complications following laparoscopic colorectal surgery has recently been reported by some groups and the aim of this systematic review was to summarise this literature. A literature search of PubMed, Medline and EMBASE identified a total of 11 studies that reported laparoscopic re-intervention for complications in 187 patients following laparoscopic colorectal surgery. The majority of these patients required re-intervention in the immediate postoperative period (i.e. less than seven days). Anastomotic leakage was the commonest complication requiring re-laparoscopy reported (n = 139). Other complications included postoperative hernia (n = 12), bleeding (n = 9), adhesions (n = 7), small bowel obstruction (n = 4), colonic ischaemia (n = 4), bowel and ureteric injury (n = 3 respectively) and colocutaneous fistula (n = 1). Ninety-seven percent of patients (n = 182) who underwent re-laparoscopy had their complications successfully managed by re-laparoscopy, maintaining the benefits of the laparoscopic approach and avoiding a laparotomy. We conclude that re-laparoscopy for managing complications following laparoscopic colorectal surgery appears to be safe and effective in highly selected patients.

Neoadjuvant therapy does not affect lymph node ratio in rectal cancer.

AIMS: Recently, lymph-node ratio (LNR) has emerged as a prognostic tool in staging rectal cancer. Studies to date have demonstrated threshold values above and below which survival is differentially altered. Neoadjuvant therapy significantly reduces the number of lymph node retrieved. The aim of the present study was to determine the effect of neoadjuvant therapy on LNR and its prognostic properties. METHODS: Consecutive patients who underwent curative rectal cancer resections in a single institution from 2007 to 2010 were reviewed. LNR was stratified into five subgroups of 0, 0.01-0.17, 0.18-0.41, 0.42-0.69 and 0.7-1.0 based on a previous study. The effect of neoadjuvant therapy on lymph node retrieval, LNR, locoregional (LR) and systemic recurrence (SR), disease-free (DFS) and overall survival (OS) was compared between patients who did (Neoadjuvant) and did not (Surgery Alone) receive neoadjuvant therapy. RESULTS: Neoadjuvant and Surgery Alone groups were comparable in gender, age and tumour stage. The number of lymph nodes retrieved were significantly lower in the Neoadjuvant group (p < 0.01). However, LNR remained similar in both groups (p = 0.36). There was no statistical difference in the DFS and OS between the Neoadjuvant and Surgery Alone groups at the various LNR cut off values in patients with AJCC Stage 3 tumours. CONCLUSIONS: LNR ratio remains unaltered despite reduced lymph node retrieval after neoadjuvant therapy in rectal cancer. LNR may therefore be a more reliable prognostic indicator in this subgroup of patients.

Androgen metabolism in prostate cancer: from molecular mechanisms to clinical consequences.

Despite our most vigorous efforts, prostate cancer remains the second leading cause of cancer death in men. Understanding the intricacies of androgen metabolism is vital to finding therapeutic targets, particularly with progression of advanced prostate cancer after initial hormone therapy, where adrenal precursors are involved. Such is the case with castration-resistant prostate cancer, where adrenal androgens, for example, dehydroepiandrosterone, are a source for intratumoural synthesis of dihydrotestosterone. As prostate cancer progresses, androgen metabolism changes due to altered expression of steroidogenic enzymes and mutations in the components of the steroidogenic machinery. These alterations sustain disease and allow progression; mechanistically, they may also enable development of hormone therapy resistance. With the development of the newer agents, abiraterone acetate and enzalutamide, efforts have been made to better define the basis for response and resistance. This work can be carried out in cell lines, animal models, as well as with ex vivo analysis of tissues obtained from patients. Efforts to further elucidate the finer details of the steroidogenic pathway are necessary to move toward a curative paradigm for patients with localised disease at high risk for recurrence.

Differentiation between intramedullary spinal ependymoma and astrocytoma: comparative MRI analysis.

AIM: To investigate magnetic resonance imaging (MRI) findings that could be used to differentiate intramedullary spinal ependymoma from astrocytoma, and to determine predictors for this differentiation. MATERIALS AND METHODS: MRI images of 43 consecutive patients with pathologically proven intramedullary spinal ependymoma (n = 24) and astrocytoma (n = 19) were comparatively evaluated with regard to size, location, margin, signal intensity, contrast enhancement, presence of syringohydromyelia, tumoural cyst, non-tumoural cyst, and haemorrhage. MRI findings and demographic data were compared between the two tumour groups using univariate and multivariate logistic regression analyses. RESULTS: In patients with ependymoma, older age and a larger solid component were more often observed than in astrocytoma. Central location, presence of enhancement, diffuse enhancement, syringohydromyelia, haemorrhage, and cap sign were more frequently observed in ependymoma. However, multivariate analysis revealed that syringohydromyelia was the only variable able to independently differentiate ependymoma from astrocytoma, with an odds ratio of 62.9 (95% CI: 4.38-903.22; p = 0.002). CONCLUSION: Among the various findings, the presence of syringohydromyelia is the main factor distinguishing ependymoma from astrocytoma.

Circulating fibrocytes and Crohn's disease.

BACKGROUND: Despite advances in medical therapy, there remains no effective preventive or non-surgical therapeutic option for fibrostenotic Crohn's disease (CD). Symptomatic recurrences are common, necessitating reintervention. Intestinal fibroblasts mediate stricture formation, but their exact source is unclear. Recent evidence indicates that circulating fibrocytes drive fibrosis through differentiation into fibroblasts and the production of extracellular matrix proteins. The aim of this review is to describe current understanding of the pathophysiology underlying fibrosis in CD, the cellular and molecular biology of fibrocytes and their role in CD. METHODS: The electronic literature (January 1972 to December 2012) on 'circulating fibrocytes' and 'Crohn's fibrosis' was reviewed. RESULTS: Circulating fibrocytes appear universally involved in organ fibrosis. A complex array of cytokines, chemokines and growth factors regulate fibrocyte biology, and these are associated with fibrogenesis in CD. The cytokines transforming growth factor ß1, connective tissue growth factor and interleukin 13, overexpressed in the strictured Crohn's intestine, promote fibrocyte generation and/or differentiation. CONCLUSION: Levels of circulating fibrocytes are raised in conditions marked by exaggerated fibrosis. These and other observations prompt a characterization of fibrocyte activity in CD with a view to investigating a pathogenic role.

Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated ß1/ß2-integrin trafficking.

Krüppel-like factor 5 regulates pluripotent stem cell self-renewal, but its role in somatic stem cells is unknown. Here we show that Krüppel-like factor 5-deficient haematopoietic stem cells and progenitors fail to engraft after transplantation. This haematopoietic stem cell and progenitor defect is associated with impaired bone marrow homing and lodging and decreased retention in bone marrow, and with decreased adhesion to fibronectin and expression of membrane-bound ß1/ß2-integrins. In vivo-inducible gain-of-function of Krüppel-like factor 5 in haematopoietic stem cells increases haematopoietic stem cell and progenitor adhesion. The expression of Rab5 family members, mediators of ß1/ß2-integrin recycling in the early endosome, is decreased in Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Krüppel-like factor 5 binds directly to the promoter of Rab5a/b, and overexpression of Rab5b rescues the expression of activated ß1/ß2-integrins, adhesion and bone marrow homing of Klf5(Δ/Δ) haematopoietic stem cells and progenitors. Altogether, these data indicate that Krüppel-like factor 5 is indispensable for adhesion, homing, lodging and retention of haematopoietic stem cells and progenitors in the bone marrow through Rab5-dependent post-translational regulation of ß1/ß2 integrins.

Screening for cytotoxic activity of ovotransferrin and its enzyme hydrolysates.

The aim of this study was to investigate the cytotoxic activities of ovotransferrin (OTF) from egg white and its enzyme hydrolysates (OTH). The OTF was hydrolyzed at 45°C for 3 h using neutrase, alcalase, acid (0.03 N HCl, pH 2.5), protamex, protex 6L, flavorzyme, α-chymotrypsin, trypsin, and collupulin MG. The enzyme to substrate ratio was 1:25 (wt/wt) in all experiments. Using the 3-(4,5-dimethylthizol-2-yl)-2,5-diphenylatetetrazolium bromide (MTT) assay, the cytotoxicity of OTF and OTH was evaluated in human cancer cell lines of various tissue origins, including the lung (A549 and SK-MES-1), stomach (AGS), breast (MCF-7), larynx (Hep-2), cervix (HeLa), and liver (HepG2). The growth of all cancer cell lines was inhibited by both OTF and OTH in a dose-dependent manner. In particular, OTF displayed relatively high cytotoxicity (≤60% inhibition effects) at 40 mg/mL. At lower concentrations (≤5 mg/mL), however, OTF- and OTH-mediated cytotoxic effects were not significant in all cancer cell lines tested. The MCF-7 cells were the least sensitive to all treatments among all cancer cell lines tested. The OTH-trypsin and OTH-neutrase showed a potent cytotoxicity (over 90% cytotoxicity) to HeLa cells at the 10 mg/mL level. The OTH-trypsin, OTH-protamex, OTH-protex 6L, and OTH-collupulin MG caused 95, 96, 86, and 87% growth inhibition, respectively, in AGS cells. These results indicated there are possibilities that OTF and OTH can be used as natural growth inhibitors of human cancer cell lines.

Distinct features between longitudinally extensive transverse myelitis presenting with and without anti-aquaporin 4 antibodies.

OBJECTIVES: Longitudinally extensive transverse myelitis (LETM) with spinal cord lesions spanning three or more vertebral segments is a key feature of neuromyelitis optica (NMO). However, the role of anti-aquaporin 4 (anti-AQP4) antibody, a sensitive biomarker of NMO, in the conversion of LETM to NMO remains uncertain. METHODS: Thirty first-ever LETM patients were retrospectively analysed and divided into two groups according to the presence of anti-AQP4 antibodies. RESULTS: Eighteen (60%) patients presented with anti-AQP4 antibodies. Fifteen (83.33%) anti-AQP4 (+) LETM patients converted to NMO, while only three of 12 (25%, p = 0.002) anti-AQP4 (-) LETM patients progressed to NMO, over a mean follow-up period of 5.63 years. Seven (38.89%) anti-AQP4 (+) and one (8.33%) anti-AQP4 (-) LETM patients received interferon-ß1a treatment, respectively. Anti-AQP4 (+) LETM patients demonstrated a higher immunogamma globulin (IgG) index (0.68 ± 0.43 versus 0.47 ± 0.19, p = 0.018), annual relapse rate (0.72 ± 0.31 versus 0.42 ± 0.17, p = 0.01) and Kurtzke Expanded Disability Status Scale (4.28 ± 2.22 versus 2.67 ± 2.26, p = 0.031), than anti-AQP4 (-) LETM patients. In spinal magnetic resonance imaging (MRIs), more than half (58.33%) of the anti-AQP4 (+) LETM patients were observed to have central grey matter-predominant involvement in the axial view, while peripheral white matter-predominant involvement (51.85%) was the most common pattern observed in the anti-AQP4 (-) LETM patients. CONCLUSION: Anti-AQP4 (+) LETM demonstrated a high conversion rate to NMO (83.33%), suggesting that anti-AQP4 (+) LETM may represent an early, isolated syndrome of NMO spectrum disorder. The greater number of patients receiving interferon-ß treatment in anti-AQP4 (+) LETM may contribute to its high annual relapse rate.

ATXN8 -62 G/A promoter polymorphism and risk of Taiwanese Parkinson's disease.

BACKGROUND AND PURPOSE: We recently reported a novel -62 G/A polymorphism within ataxin 8 (ATXN8) gene promoter region, with -62 G displaying significantly higher luciferase activity compared with -62 A. Phenotypic variability in spinocerebellar ataxia type 8 (SCA8) has been suggested, and large SCA8 repeats were found in patients with Parkinson's disease (PD). We aimed to investigate the association of ATXN8 -62 G/A polymorphism with the risk of Taiwanese PD, and identify the trans-acting factor modulating the ATXN8 promoter activity. METHODS: A case-control study in a cohort of 569 PD cases and 547 ethnically matched controls was conducted by polymerase chain reaction (PCR) and restriction enzyme analysis. The trans-acting factor binding to the ATXN8 promoter was examined by chromatin immunoprecipitation (ChIP)-PCR assay, cDNA co-transfection and luciferase reporter assay. RESULTS: When genotype distribution was calculated by comparing the rare AA genotype with the GG + GA genotypes (recessive model), a significant difference was found (P = 0.035, 1 df). Individuals carrying AA genotype exhibited a decreased risk of developing PD (odds ratio: 0.73; 95% CI: 0.55-0.98, P = 0.035). After stratification by age, individuals over 60 years of age carrying AA genotype demonstrated a further decrease in the risk of developing PD (odds ratio: 0.64; 95% CI: 0.43-0.96, P = 0.030). ChIP-PCR and cDNA over-expression revealed that CCAAT/enhancer-binding protein alpha binds to the ATXN8 proximal promoter to upregulate ATXN8 expression in neuroblastoma SK-N-SH cells. CONCLUSIONS: Our data suggest that ATXN8 -62 G/A polymorphism plays a role in Taiwanese PD susceptibility.

The surgical significance of residual mucosal abnormalities in rectal cancer following neoadjuvant chemoradiotherapy.

BACKGROUND: Local excision of rectal cancer after neoadjuvant chemoradiotherapy (CRT) has been proposed as an alternative to radical surgery in selected patients. However, little is known about the significance of the morphological and histological features of residual tumour. METHODS: Patients who had undergone CRT at the authors' institution between 1997 and 2010 were identified. Multiple features were assessed as putative markers of pathological response. These included: gross residual disease, diameter of residual mucosal abnormalities, tumour differentiation, presence of lymphovascular/perineural invasion and lymph node ratio. RESULTS: Data from 220 of 276 patients were suitable for analysis. Diameter of residual mucosal abnormalities correlated strongly with pathological tumour category after CRT (ypT) (P < 0·001). Forty of 42 tumours downstaged to ypT0/1 had residual mucosal abnormalities of 2·99 cm or less after CRT. Importantly, 19 of 31 patients with a complete pathological response had evidence of a residual mucosal abnormality consistent with an incomplete clinical response. The ypT category was associated with both pathological node status after CRT (P < 0·001) and lymph node ratio (P < 0·001). Positive nodes were found in only one of 42 patients downstaged to ypT0/1. The risk of nodal metastases was associated with poor differentiation (P = 0·027) and lymphovascular invasion (P < 0·001). CONCLUSION: In this series, the majority of patients with a complete pathological response did not have a complete clinical response. In tumours downstaged to ypT0/1 after CRT, residual mucosal abnormalities were predominantly small and had a 2 per cent risk of positive nodes, thus potentially facilitating transanal excision. The presence of adverse histological characteristics risk stratified tumours for nodal metastases.

MicroRNA-21 and PDCD4 expression in colorectal cancer.

INTRODUCTION: MiRNAs regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. Studies have shown that miR-21 exerts its oncogenic activity by targeting the PDCD4 tumour suppressor 3'-UTR. However, the mechanism of this regulation is poorly understood. In colorectal cancer, loss of PDCD4 has been reported in association with increased tumour aggressiveness and poor prognosis. The purpose of this study was to delineate the interaction between PDCD4 and its oncogenic modulator miR-21 in colorectal cancer. METHODS: A cohort of 48 colorectal tumours, 61 normal tissues and 7 polyps were profiled for miR-21 and PDCD4 gene expression. A subset of 48 specimens (31 tumours and 17 normal tissues) were analysed for PDCD4 protein expression by immunohistochemistry. RESULTS: A significant inverse relationship between miR-21 and PDCD4 gene expression (p < 0.001) was identified by RT-qPCR. In addition, significant reduction of PDCD4 (p < 0.001) expression and reciprocal upregulation of miR-21 (p = 0.005) in a progressive manner from tumour-polyp-normal mucosae was identified. Analysis of protein expression by IHC revealed loss of PDCD4 staining in tumour tissue. Patients with disease recurrence had higher levels of miR-21. CONCLUSION: This study demonstrates the inverse relationship between miR-21 and PDCD4, thus suggesting that miR-21 post-transcriptionally modulates PDCD4 via mRNA degradation. Pharmacological manipulation of the miR-21/PDCD4 axis could represent a novel therapeutic strategy in the treatment of colorectal cancer.

Relationship between radiological characteristics and combined 1p and 19q deletion in World Health Organization grade III oligodendroglial tumours.

OBJECTIVE: The radiological characteristics of World Health Organization grade III oligodendroglial tumours in relation to chromosome 1p and 19q deletions were analysed. METHODS: 56 patients recently diagnosed with anaplastic oligodendroglioma (AO, n=49) or anaplastic oligoastrocytoma (AOA, n=7) were studied. Their preoperative magnetic resonance images were examined. Deletions of chromosome 1p and 19q were determined using the fluorescence in situ hybridisation method. Both 1p and 19q chromosomes had deletions (1p19q codeletion) in 39 patients (36 AO and 3 AOA). RESULTS: Tumors associated with the 1p19q codeletion were predominantly located in the frontal lobe (p=0.044). The magnetic resonance image characteristics of indistinct tumour borders (p=0.005 on T1, p=0.036 on T2) and a heterogeneous intratumoural signal intensity (p=0.033 on T1, p=0.041 on T2) were significantly correlated with the 1p19q codeletion. Analysis of patient survival showed those with the 1p19q-co-deleted tumours survived significantly longer than those lacking the 1p19q codeletion (p=0.042). The presence of a heterogeneous signal intensity in T2-weighted images, a characteristic significantly related to the 1p19q codeletion, indicated a favourable prognosis for patients' survival (HR; 0.125, 95% CI, 0.016 to 0.963, p=0.046) based on multivariate analysis. CONCLUSION: A relationship between radiological characteristics and molecular signatures in AO/AOAs was shown. It is believed that radiological characteristics have prognostic value as a surrogate marker for molecular characteristics.

Surgery for oesophageal cancer at Galway University Hospital 1993-2008.

BACKGROUND: Surgical volume and outcome remain controversial in the management of oesophageal cancer. AIMS: To assess the outcome of oesophagectomy for cancer at Galway University Hospital (GUH). METHODS: Between 1994 and 2008, patients who underwent oesophagectomy were analysed. RESULTS: During the study period, 126 oesophagectomies were performed for cancer. The average surgeon volume was 9 cases per year. The 30-day and overall in-hospital mortality rates were 6.3 and 7.9%, respectively. Restructuring of our critical care services has led to a reduction in 30-day mortality from 8.2 to 5.1%. The use of neoadjuvant chemoradiotherapy has increased from 17 to 35% during the study period. In patients who underwent resection, the 3 and 5-year overall survival rates were 45 and 29%, respectively. CONCLUSIONS: Operative morbidity and mortality at GUH are comparable with worldwide outcomes. Improved resources and national restructuring of cancer services have significantly improved the quality of care and outcomes of patients.

Sustained weight loss and improvement of quality of life after laparoscopic adjustable gastric banding for morbid obesity: a single surgeon experience in Ireland.

BACKGROUND: Although substantial weight loss is the primary outcome following bariatric surgery, changes in obesity-related morbidity and quality of life (QoL) are equally important. This study reports on weight loss, QoL and health outcomes following laparoscopic adjustable gastric banding (LAGB). METHODS: Bariatric analysis and reporting outcome system questionnaire survey was carried out on patients who had LAGB. Patients' body weight, body mass index, QoL and co-morbidities were recorded. RESULTS: Twenty-three of 26 patients answered the questionnaire (response rate of 92%). Fifteen patients (60%) achieved over 50% excess weight loss. Twenty-two patients (84.6%) reported improvement in QoL. Co-morbidities in 18 patients (75%) resolved or improved. One patient had postoperative aspiration pneumonia and no other morbidity was recorded. CONCLUSIONS: Laparoscopic adjustable gastric banding is a safe and feasible method of bariatric surgery. It can achieve satisfactory weight loss with significant improvement in QoL and co-morbidity provided patients undergo thorough preoperative preparation and rigorous postoperative follow-up.