Adjacent thoracic lymph node metastases originating from two separate primary cancers: case report

Reported is an unusual case of adjacent thoracic lymph nodes demonstrating metastases from two different primary malignancies. A 51 year-old woman with a previous history of bilateral breast cancer underwent a radical gastro-oesophagectomy for adenocarcinoma of the lower third of the oesophagus. The resection specimen demonstrated breast and oesophageal metastases in adjacent thoracic lymph nodes. Mechanisms for this phenomenon, including the known local immune suppression on lymphoid cells by oesophageal carcinoma cells, are discussed

Expression of multidrug resistance markers ABCB1 (MDR-1/P-gp) and ABCC1 (MRP-1) in renal cell carcinoma

Background: Renal cancer patients respond poorly to conventional chemotherapy, this unresponsiveness may be attributable to multidrug resistance (MDR). The mechanisms of MDR in renal cancer are not fully understood and the specific contribution of ABC transporter proteins which have been implicated in the chemoresistance of various cancers has not been fully defined in this disease. Methods: The aim of this prospective study was to analyse by immunohistochemistry the expression of two of these transporter efflux pumps, namely MDR-1/P-gp (ABCB1) and MRP-1 (ABCC1) in archival material from 113 renal carcinoma patients. Results: In the largest study of its kind, results presented here show 100% of cases stained positively for P-gp and MRP-1 protein expression. Conclusion: However, although these findings do not prove a causal role, the high frequency of tumours expressing these efflux pumps suggests that they may be important contributors to the chemoresistance of this tumour type

Management of cutaneous metastases using electrochemotherapy

Background. Cutaneous metastases may cause considerable discomfort as a consequence of ulceration, oozing, bleeding and pain. Electrochemotherapy has proven to be highly effective in the treatment of cutaneous metastases. Electrochemotherapy utilises pulses of electricity to increase the permeability of the cell membrane and thereby augment the effect of chemotherapy. For the drug bleomycin, the effect is enhanced several hundred-fold, enabling once-only treatment. The primary endpoint of this study is to evaluate the efficacy of electrochemotherapy as a palliative treatment. Methods. This phase II study is a collaboration between two centres, one in Denmark and the other in the UK. Patients with cutaneous metastases of any histology were included. Bleomycin was administered intratumourally or intravenously followed by application of electric pulses to the tumour site. Results. Fifty-two patients were included. Complete and partial response rate was 68% and 18%, respectively, for cutaneous metastases <3 cm and 8% and 23%, respectively, for cutaneous metastases >3 cm. Treatment was well-tolerated by patients, including the elderly, and no serious adverse events were observed. Conclusions. ECT is an efficient and safe treatment and clinicians should not hesitate to use it even in the elderly

Nonlinear changes in the activity of the oxygen-dependent demethylase system in Rhodococcus erythropolis cells in the presence of low and very low doses of formaldehyde

The effect of exogenous, highly diluted formaldehyde on the rate of demethylation/re-methylation of veratric acid by the bacteria Rhodococcus erythropolis was studied using electrophoretic and microscopic techniques. The activity of 4-O-demethylase, responsible for accumulation of vanillic acid, and the levels of veratric and vanillic acids were determined using capillary electrophoresis. Formaldehyde was serially diluted at 1:100 ratios, and the total number of iterations was 20. After incubation of the successive dilutions of formaldehyde with the bacteria, demethylase activity oscillated in a sinusoidal manner. It was established using capillary electrophoresis that methylation of vanillic acid to veratric acid occurred at a double rate, as shown by the doubled fluctuation in the concentration of veratrate. There were also changes in the NADH oxidase activity, which is associated with methylation processes. Microscopic observations revealed the presence of numerous enlarged vacuoles in bacterial cells during the accumulation of large amounts of vanillic acid, and their disappearance together with a decrease in 4-O-demethylase activity. The presented results give evidence for the ability of living cells to detect the presence of submolecular concentrations of biological effectors in their environment and provide a basis for a scientific explanation of the law of hormesis and the therapeutic effect of homeopathic dilutions

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

A qualitative study on healthcare professionals’ perceived barriers to insulin initiation in a multi-ethnic population

Background: Nationwide surveys have shown that the prevalence of diabetes rates in Malaysia have almost doubled in the past ten years; yet diabetes control remains poor and insulin therapy is underutilized. This study aimed to explore healthcare professionals’ views on barriers to starting insulin therapy in people with type 2 diabetes. Methods: Healthcare professionals consisting of general practitioners (n = 11), family medicine specialists (n = 10), medical officers (n = 8), government policy makers (n = 4), diabetes educators (n = 3) and endocrinologists (n = 2) were interviewed. A semi-structured topic guide was used to guide the interviews by trained facilitators. The interviews were transcribed verbatim and analysed using a thematic analysis approach. Results: Insulin initiation was found to be affected by patient, healthcare professional and system factors. Patients’ barriers include culture-specific barriers such as the religious purity of insulin, preferred use of complementary medication and perceived lethality of insulin therapy. Healthcare professionals’ barriers include negative attitudes towards insulin therapy and the ‘legacy effect’ of old insulin guidelines; whilst system barriers highlight the lack of resources, language and communication challenges. Conclusions: Tackling the issue of insulin initiation should not only happen during clinical consultations. It requires health education to emphasise the progressive nature of diabetes and the eventuality of insulin therapy at early stage of the illness. Healthcare professionals should be trained how to initiate insulin and communicate effectively with patients from various cultural and religious backgrounds

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty