E Shamil

Bio: E Shamil is an academic researcher from King's College London. The author has contributed to research in topics: Medicine & Metastasis. The author has an hindex of 4, co-authored 4 publications receiving 102 citations.

OrVil™-assisted anastomosis in laparoscopic upper gastrointestinal surgery: friend of the laparoscopic surgeon

Abstract: Background An increasing number of minimally invasive oesophagogastrectomies (MIOG) are being performed. However, the complexity of the surgical skills required and the steep learning curve have thus far confined the minimally invasive approach to selected tertiary centres. The oesophagogastric and the oesophagojejunal anastomosis can be challenging and often time-consuming. The recently developed transorally inserted anvil (OrVil™) is a technique aimed to simplify the anastomotic procedure. The aim of the study was to evaluate the safety, feasibility, and efficacy of OrVil™-assisted anastomosis during laparoscopic surgery in a tertiary upper-GI cancer centre.

The challenges of integrating molecular imaging into the optimization of cancer therapy

Abstract: We review novel, in vivo and tissue-based imaging technologies that monitor and optimize cancer therapeutics. Recent advances in cancer treatment centre around the development of targeted therapies and personalisation of treatment regimes to individual tumour characteristics. However, clinical outcomes have not improved as expected. Further development of the use of molecular imaging to predict or assess treatment response must address spatial heterogeneity of cancer within the body. A combination of different imaging modalities should be used to relate the effect of the drug to dosing regimen or effective drug concentration at the local site of action. Molecular imaging provides a functional and dynamic read-out of cancer therapeutics, from nanometre to whole body scale. At the whole body scale, an increase in the sensitivity and specificity of the imaging probe is required to localise (micro)metastatic foci and/or residual disease that are currently below the limit of detection. The use of image-guided endoscopic biopsy can produce tumour cells or tissues for nanoscopic analysis in a relatively patient-compliant manner, thereby linking clinical imaging to a more precise assessment of molecular mechanisms. This multimodality imaging approach (in combination with genetics/genomic information) could be used to bridge the gap between our knowledge of mechanisms underlying the processes of metastasis, tumour dormancy and routine clinical practice. Treatment regimes could therefore be individually tailored both at diagnosis and throughout treatment, through monitoring of drug pharmacodynamics providing an early read-out of response or resistance.

Imaging tumour heterogeneity of the consequences of a PKCα-substrate interaction in breast cancer patients.

Abstract: Breast cancer heterogeneity demands that prognostic models must be biologically driven and recent clinical evidence indicates that future prognostic signatures need evaluation in the context of early compared with late metastatic risk prediction. In pre-clinical studies, we and others have shown that various protein–protein interactions, pertaining to the actin microfilament-associated proteins, ezrin and cofilin, mediate breast cancer cell migration, a prerequisite for cancer metastasis. Moreover, as a direct substrate for protein kinase Cα, ezrin has been shown to be a determinant of cancer metastasis for a variety of tumour types, besides breast cancer; and has been described as a pivotal regulator of metastasis by linking the plasma membrane to the actin cytoskeleton. In the present article, we demonstrate that our tissue imaging-derived parameters that pertain to or are a consequence of the PKC–ezrin interaction can be used for breast cancer prognostication, with inter-cohort reproducibility. The application of fluorescence lifetime imaging microscopy (FLIM) in formalin-fixed paraffin-embedded patient samples to probe protein proximity within the typically

Molecular imaging for drug development

Abstract: In vivo molecular imaging has become a key technology for pathophysiological science and drug development. We are mostly utilizing PET(positron emission tomography) as a first-choice modality, because of its ultra-high sensitivity for molecules, adequate temporal and spatial resolution, and especially broad spectrum of target molecules. In vivo molecular imaging could bring the high-quality information about: 1. Molecular diagnosis for living patients with symptoms 2. Closer approach for etiology and differential diagnosis 3. Direct follow-up of key molecules as disease markers 4. Pharmacokinetics/Pharmacodynamics in primates/human 5. Dose finding information for individuals, corresponding to SNPs 6. Direct evidence for accumulation in non-target organs related to adverse effects 7. Drug effects with surrogate markers 8. Early decision of dropout substances (drug candidates) Here, the examples are shown as beta-amyloid imaging for Alzheimer's and mild cognitive impairment, serotonin transporter imaging for chronic fatigue, and dopaminergic components imaging for evaluation of drug for autistic spectrum disorder. In 2005, RIKEN and National Institute of Radiological Science were selected as the key centers for development of All-Japan research network to further promote mutual international and multi -disciplinary collaboration on in vivo molecular imaging.

Comparison of patterns and prognosis among distant metastatic breast cancer patients by age groups: a SEER population-based analysis

Abstract: To investigate the effects of age at diagnosis on metastatic breast cancer and patients’ prognosis, we collected patient data from the Surveillance, Epidemiology, and End Results (SEER) database. We finally identified 4932 eligible metastatic breast cancer patients diagnosed between 2010–2013, including 850 younger patients ( 69 years). The results revealed that in stage IV patients, elder patients were more likely to have lung metastasis (P < 0.001) and less likely to have only distant lymphatic spread (P = 0.004). Higher proportion of younger (34.9%) and middle-aged (36.2%) patients had multiple metastatic sites than elder patients (28.3%) (P < 0.001). In survival analysis, younger patients presented the best prognosis, while elder patients had the worst both in overall survival (χ2 = 121.9, P < 0.001) and breast cancer-specific survival (χ2 = 69.8, P < 0.001). Age at diagnosis was an independent prognostic factor for metastatic breast cancer patients. Moreover, patients with bone metastasis only had superior survival compared to other metastatic patients (P < 0.001). Brain metastasis only group and multiple sites metastasis group had the poorest prognosis (P < 0.05). We hope the results will provide insights into a better understanding of distant metastatic breast cancer.

Systematic review of anastomotic complications of esophagojejunostomy after laparoscopic total gastrectomy.

Abstract: AIM: To investigate the anastomotic complications of esophagojejunostomy (EJS) after laparoscopic total gastrectomy (LTG), we reviewed retrospective studies. METHODS: A literature search was conducted in PubMed for studies published from January 1, 1994 through January 31, 2015. The search terms included “laparoscopic,” “total gastrectomy,” and “gastric cancer.” First, we selected 16 non-randomized controlled trials (RCTs) comparing LTG with open total gastrectomy (OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system (NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0% (30 of 984 patients) among LTG procedures and 2.1% (31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG (odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I2 = 0%). Anastomotic stenosis related to EJS was reported in 72 (2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG (OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I2 = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar (1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the OrVilTM device was used (8.8%) compared with other procedures (1.0% to 3.6%). CONCLUSION: The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the OrVilTM device was used.