A systematic review of outcomes after salvage abdominoperineal resection for persistent or recurrent anal squamous cell cancer.

AIM: Up to 30% of patients with squamous cell cancer of the anus (SCCA) will require a salvage abdominoperineal resection (APR) for either persistent or recurrent disease. The objective of this study was to assess cancer-related outcomes in patients with (i) persistent or (ii) recurrent SCCA. METHOD: Embase and MEDLINE were searched. Publications were included if they assessed overall survival (OS), disease-free survival (DFS) and locoregional recurrence or metastatic disease after salvage APR for persistent or recurrent SCCA. RESULTS: A total of 28 retrospective case series (study size ranged from nine to 111) met our inclusion criteria. The median time to salvage APR was 2.6 months [interquartile range (IQR) 2.6-5.0 months, six studies] for persistent disease and 27.6 months (IQR 15.0-32.7 months, five studies) for recurrent disease. The median 5-year OS from the time of salvage APR was 45.0% (IQR 32.0%-52.3%, 10 studies) for persistent disease and 51.0% (IQR 36.0%-60.9%, 11 studies) for recurrent disease. The median 5-year DFS following salvage APR was 44.0% (IQR 29.5%-53.0%, 10 studies) for all patients. Following salvage APR, the median locoregional recurrence rate was 23.5% (IQR 15.8%- 46.9%, 19 studies) and 9.0% (IQR 6.4%-13.3%, 16 studies) of patients developed metastatic disease after salvage APR. CONCLUSION: Our review characterizes the best evidence for outcomes following salvage APR for patients with persistent or recurrent SCCA. The evidence is limited by the quality of included studies, as many were single centre case series.

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer.

BACKGROUND: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. RESULTS: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first-line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. CONCLUSION: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer.

Time, space and technology in radiotherapy departments: how do these factors impact on patients' experiences of radiotherapy?

Radiation therapists (RTs) plan and deliver radiotherapy treatment for patients diagnosed with cancer. They need to communicate regularly with their patients and may have a role to play in reducing patient anxiety and distress. The objectives were to explore how the environment of radiotherapy departments supports or inhibits communication generally and information giving and supportive care provision in particular. An ethnographic approach was used to gather rich descriptive data through observations and interviews conducted in two Australian radiotherapy centres. Time, space and a technology driven culture was found to negatively affect the quality of interaction that occurred between RTs and their patients. This research has shown design/modification of spaces is needed in the radiotherapy environment to reflect a patient care centred culture and to enhance opportunities for RTs to provide supportive care for their patients.

Use of antimicrobials for animals in New Zealand, and in comparison with other countries.

AIM: To describe the use of antimicrobial drugs for food animals in New Zealand, based on sales data reported to government, changes over time, and in comparison with other countries and human use. METHODS: Data were sourced from official government and industry reports covering 26 European countries, Australia, Canada, New Zealand and the United States of America in 2012, the last year data were available for all countries. The data included antimicrobial sales, and animal and human populations. Antimicrobial use was estimated based on the amount of active ingredient sold, per standardised biomass (population correction unit). RESULTS: The estimated usage of antimicrobials for food animals in New Zealand for 2012 was 9.4 mg active ingredient/kg biomass. Total sales of antimicrobials between 2005-14 increased on average by 2.5% or 1.5 tonnes per year. Over the same time total animal biomass decreased by an estimated 4.3%, with the main decrease being in sheep (25%) and beef cattle (17%), while dairy cattle increased (28%). In the countries examined, the estimated usage of antimicrobials in food producing animals in 2012 varied from 3.8 to 341 mg active ingredient/kg biomass, in Norway and Italy, respectively, with use in New Zealand being the third lowest. Usage of antimicrobials for human health in New Zealand in 2012 was estimated at 121 mg active ingredient/kg biomass, being ranked sixteenth of the countries compared. Use in humans was 12.9 times the use in animals. CONCLUSIONS: New Zealand was the third lowest user of antimicrobials in animal production and used much less than in human medicine. This is the first report of baseline data which may be used by the New Zealand animal health industry to develop, and measure success in, approaches to maximise the life of antimicrobials for animal health and welfare. CLINICAL RELEVANCE: New Zealand veterinarians will soon have to make changes to adopt the World Health Organisation's global action plan to manage antimicrobial resistance. Having a benchmark of current antimicrobial use will inform priorities and allow measurement of the impact of future programmes.

First-line Palliative Chemotherapy for Colorectal Cancer: a Population-based Analysis of Delivery and Outcomes in a Single-payer Health System.

AIMS: Clinical practice guidelines recommend palliative chemotherapy for most patients with metastatic colorectal cancer. However, outcomes observed in the real world compared with patients enrolled in clinical trials have not been sufficiently described. The objective of this study was to evaluate the delivery and outcomes of first-line palliative chemotherapy administered to patients with colorectal cancer in routine clinical practice compared with clinical trials. MATERIALS AND METHODS: Using linked health administrative data, we carried out a retrospective population-level cohort study on patients diagnosed with colorectal cancer in Ontario, Canada from 2010 to 2019. Patient, disease and treatment characteristics were summarised. The primary outcome was median overall survival, stratified by treatment prescribed and age. Demographics and outcomes in this real-world population were compared with those from pivotal clinical trials. A multivariable Cox regression model reporting hazard ratios and 95% confidence intervals was used to determine factors associated with survival in patients receiving systemic treatment. RESULTS: We identified 70 987 patients with a new diagnosis of colorectal cancer, of which 4613 received first-line chemotherapy for unresectable locally advanced or metastatic disease and formed the study cohort. Fifty-eight per cent were male and the mean age was 63 years. Most had colon cancer (69%), at least one comorbidity (73%) and lived in an urban location (79%). Less than half (47%) had surgery after diagnosis. The most common regimen prescribed was folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) with bevacizumab or epidermal growth factor receptor inhibitors (EGFRi; n = 2784, 60%). Among all treated patients, the median overall survival was 17.1 months, with survival difference by regimen [median overall survival 18.3 for FOLFIRI with bevacizumab or EGFRi, 19.6 for folinic acid, 5-fluorouracil and oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (XELOX) with bevacizumab or EGFRi, 13.6 for FOLFIRI alone and 7.8 for 5-fluorouracil or capecitabine]. Patients aged >80 years were most likely to have received single-agent 5-fluorouracil or capecitabine, and had inferior overall survival compared with their younger counterparts. Compared with pivotal clinical trials, patients in the real world had inferior overall survival outcomes despite similar demographic characteristics (including age and sex). CONCLUSIONS: In this real-world population-based analysis of patients receiving first-line chemotherapy for unresectable locally advanced or metastatic colorectal cancer, survival outcomes were inferior to those reported in randomised trials despite similarities in age and sex. This information can be used when counselling patients in routine practice about expected outcomes.

Evaluation of weather-based rice yield models in India.

The objective of this study was to compare two different rice simulation models--standalone (Decision Support System for Agrotechnology Transfer [DSSAT]) and web based (SImulation Model for RIce-Weather relations [SIMRIW])--with agrometeorological data and agronomic parameters for estimation of rice crop production in southern semi-arid tropics of India. Studies were carried out on the BPT5204 rice variety to evaluate two crop simulation models. Long-term experiments were conducted in a research farm of Acharya N G Ranga Agricultural University (ANGRAU), Hyderabad, India. Initially, the results were obtained using 4 years (1994-1997) of data with weather parameters from a local weather station to evaluate DSSAT simulated results with observed values. Linear regression models used for the purpose showed a close relationship between DSSAT and observed yield. Subsequently, yield comparisons were also carried out with SIMRIW and DSSAT, and validated with actual observed values. Realizing the correlation coefficient values of SIMRIW simulation values in acceptable limits, further rice experiments in monsoon (Kharif) and post-monsoon (Rabi) agricultural seasons (2009, 2010 and 2011) were carried out with a location-specific distributed sensor network system. These proximal systems help to simulate dry weight, leaf area index and potential yield by the Java based SIMRIW on a daily/weekly/monthly/seasonal basis. These dynamic parameters are useful to the farming community for necessary decision making in a ubiquitous manner. However, SIMRIW requires fine tuning for better results/decision making.

Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction.

DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients.

Mixed-dictionary models and variational inference in task fMRI for shorter scans and better image quality.

The propensity of task-based functional magnetic resonance imaging (T-fMRI) to large physiological fluctuations, measurement noise, and imaging artifacts entail longer scans and higher temporal resolution (trading off spatial resolution) to alleviate the effects of degradation. This paper focuses on methods towards reducing scan times and enabling higher spatial resolution in T-fMRI. We propose a novel mixed-dictionary model combining (i) the task-based design matrix, (ii) a learned dictionary from resting-state fMRI, and (iii) an analytically-defined wavelet frame. For model fitting, we propose a novel adaptation of the inference framework relying on variational Bayesian expectation maximization with nested minorization. We leverage the mixed-dictionary model coupled with variational inference to enable 2×shorter scan times in T-fMRI, improving activation-map estimates towards the same quality as those resulting from longer scans. We also propose a scheme with potential to increase spatial resolution through temporally undersampled acquisition. Results on motor-task fMRI and gambling-task fMRI show that our framework leads to improved activation-map estimates over the state of the art.

Effectiveness of Trastuzumab in Routine Clinical Practice: A Population-based Study of Patients with HER-2-positive Oesophageal, Gastroesophageal and Gastric Cancer.

AIMS: In the pivotal Trastuzumab for Gastric Cancer (ToGA) trial, trastuzumab improved median survival in patients with advanced HER-2-positive gastric and gastroesophageal cancer from 11.1 to 13.8 months; however, its effectiveness in routine clinical practice has not been evaluated. Our objective was to evaluate the uptake and outcomes of trastuzumab in a population-based cohort of patients with oesophageal, gastroesophageal and gastric cancer in Ontario, Canada. MATERIALS AND METHODS: The Ontario Cancer Registry and linked treatment records were used to identify all patients with oesophageal, gastroesophageal and gastric cancer treated with trastuzumab during 2012-2017. Outcomes were analysed from the time of first trastuzumab cycle and included a primary outcome (survival) and secondary outcomes (uptake, delivery, 30-day hospital admission and 30-day mortality). Trends over the study period and survival were evaluated. RESULTS: In total, 476 patients with oesophageal, gastroesophageal and gastric cancer received trastuzumab during the study period. The mean age was 62 years, 78% (370/476) were male, and 65% (312/476) had gastric cancer. The annual number of patients receiving trastuzumab increased over the study period (53 in 2012 and 101 in 2017). The median number of cycles of trastuzumab delivered was six. Thirty-day hospital admission and mortality rates were 17% and 4%, respectively. The median overall survival was 282 days (9.3 months). CONCLUSIONS: The median survival of patients treated with trastuzumab for advanced oesophageal, gastroesophageal and gastric cancer in routine practice is substantially less than that observed in the pivotal clinical trial. Studies of comparative effectiveness using real-world data offer insight into outcomes achieved in routine practice.

Ion selectivity from local configurations of ligands in solutions and ion channels.

Probabilities of numbers of ligands proximal to an ion lead to simple, general formulae for the free energy of ion selectivity between different media. That free energy does not depend on the definition of an inner shell for ligand-counting, but other quantities of mechanistic interest do. If analysis is restricted to a specific coordination number, then two distinct probabilities are required to obtain the free energy in addition. The normalizations of those distributions produce partition function formulae for the free energy. Quasi-chemical theory introduces concepts of chemical equilibrium, then seeks the probability that is simplest to estimate, that of the most probable coordination number. Quasi-chemical theory establishes the utility of distributions of ligand-number, and sharpens our understanding of quasi-chemical calculations based on electronic structure methods. This development identifies contributions with clear physical interpretations, and shows that evaluation of those contributions can establish a mechanistic understanding of the selectivity in ion channels.

A noninferiority clinical trial comparing fluconazole and ketoconazole in combination with cephalexin for the treatment of dogs with Malassezia dermatitis.

This double-blinded noninferiority clinical trial evaluated the use of oral fluconazole for the treatment of Malassezia dermatitis in dogs by comparing it with use of an accepted therapeutic agent, ketoconazole. Dogs presenting with Malassezia dermatitis were treated with either fluconazole or ketoconazole in addition to cephalexin for concurrent bacterial dermatitis. Statistically significant improvements in cytologic yeast count, clinical signs associated with Malassezia dermatitis, and pruritus were seen with both antifungal treatments. There was no statistical difference between the treatments with regard to the magnitude of reduction in these parameters. These results suggest that fluconazole is at least as effective as ketoconazole for the treatment of dogs with Malassezia dermatitis.

R-fMRI reconstruction from k-t undersampled data using a subject-invariant dictionary model and VB-EM with nested minorization.

Higher spatial resolution in resting-state functional magnetic resonance imaging (R-fMRI) can give reliable information about the functional networks in the cerebral cortex. Typical methods can achieve higher spatial or temporal resolution by speeding up scans using either (i) complex pulse-sequence designs or (ii) k-space undersampling coupled with priors on the signal. We propose to undersample the R-fMRI acquisition in k-space and time to speedup scans in order to improve spatial resolution. We propose a novel model-based R-fMRI reconstruction framework using a robust, subject-invariant, spatially regularized dictionary prior on the signal. Furthermore, we propose a novel inference framework based on variational Bayesian expectation maximization with nested minorization (VB-EM-NM). Our inference framework allows us to provide an estimate of uncertainty of the reconstruction, unlike typical reconstruction methods. Empirical evaluation of (i) simulated R-fMRI reconstruction and (ii) functional-network estimates from brain R-fMRI reconstructions demonstrate that our framework improves over the state of the art, and, additionally, enables significantly higher spatial resolution.

An End-to-End Solution for Automatic Contouring of Tumor Region in Intraoperative Images of Breast Lumpectomy.

Breast-conserving surgery, also known as lumpectomy, is an early stage breast cancer treatment that aims to spare as much healthy breast tissue as possible. A risk associated with lumpectomy is the presence of cancer positive margins post operation. Surgical navigation has been shown to reduce cancer positive margins but requires manual segmentation of the tumor intraoperatively. In this paper, we propose an end-to-end solution for automatic contouring of breast tumor from intraoperative ultrasound images using two convolutional neural network architectures, the U-Net and residual U-Net. The networks are trained on annotated intraoperative breast ultrasound images and evaluated on the quality of predicted segmentations. This work brings us one step closer to providing surgeons with an automated surgical navigation system that helps reduce cancer-positive margins during lumpectomy.

Increased tumour dihydroceramide production after Photofrin-PDT alone and improved tumour response after the combination with the ceramide analogue LCL29. Evidence from mouse squamous cell carcinomas.

Photodynamic therapy (PDT) has been proven effective for treatment of several types of cancer. Photodynamic therapy alone, however, attains limited cures with some tumours and there is need for its improved efficacy in such cases. Sphingolipid (SL) analogues can promote tumour response in combination with anticancer drugs. In this study, we used mouse SCCVII squamous cell carcinoma tumours to determine the impact of Photofrin-PDT on the in vivo SL profile and the effect of LCL29, a C6-pyridinium ceramide, on PDT tumour response. Following PDT, the levels of dihydroceramides (DHceramides), in particular C20-DHceramide, were elevated in tumours. Similarly, increases in DHceramides, in addition to C20:1-ceramide, were found in PDT-treated SCCVII cells. These findings indicate the importance of the de novo ceramide pathway in Photofrin-PDT response not only in cells but also in vivo. Notably, co-exposure of SCCVII tumours to Photofrin-PDT and LCL29 led to enhanced tumour response compared with PDT alone. Thus, we show for the first time that Photofrin-PDT has a distinct signature effect on the SL profile in vitro and in vivo, and that the combined treatment advances PDT therapeutic gain, implying translational significance of the combination.

How membrane proteins travel across the mitochondrial intermembrane space.

A newly discovered family of small proteins in the yeast mitochondrial intermembrane space mediates import of hydrophobic proteins from the cytoplasm into the inner membrane. Loss of one of these chaperone-like proteins from human mitochondria results in a disease that causes deafness, muscle weakness and blindness.

Incremental clinical and economic burden of suspected respiratory infections due to multi-drug-resistant Pseudomonas aeruginosa in the United States.

BACKGROUND: Multi-drug resistant (MDR) Pseudomonas aeruginosa can negatively affect patients and hospitals. AIM: To evaluate excess mortality and cost burden among patients hospitalized with suspected respiratory infections due to MDR P. aeruginosa vs patients with non-MDR P. aeruginosa in 78 United States (US) hospitals. METHODS: This study analyzed electronically captured microbiological and outcomes data of patients hospitalized with non-duplicate P. aeruginosa isolates from respiratory sources collected ≥3 days after admission to identify hospital-onset MDR or non-MDR P. aeruginosa per the Centers for Disease Control and Prevention definition. The risk of multi-drug resistance was estimated on mortality, length of stay (LOS), cost, operation gain/loss, and 30-day readmission. A sensitivity analysis was conducted utilizing a cohort with pharmacy data available. FINDINGS: Of 523 MDR and 1381 non-MDR P. aeruginosa cases, unadjusted mortality was 23.7% vs 18.0% and multi-variable-adjusted mortality was 20.0% (95% confidence interval (CI): 14.3-27.2%) vs 15.5% (95% CI: 11.2-20.9%; P=0.026), the average adjusted excess LOS was 6.7 days (P<0.001); excess cost per case was US$22,370 higher (P=0.002) and operational loss per case was US$10,661 (P=0.024) greater, and the multi-variable adjusted readmission rate was 16.2% (95% CI: 11.2-22.9%) vs 11.1% (95% CI: 7.8-15.6%; P=0.006). The sensitivity analysis yielded similar results. CONCLUSIONS: Compared with suspected infections due to non-MDR P. aeruginosa, patients with MDR P. aeruginosa had higher risk of mortality, readmission, and longer LOS, as well as US$20,000 incremental cost and >US$10,000 incremental net loss per case after controlling for patient and hospital characteristics.

Mirror movements or functional tremor masking organic tremor.

BACKGROUND: Functional tremors can be diagnosed based on clinical and physiologic criteria such as entrainment, suggestibility, distractibility, variable nature with the associated clinical history of psychosomatic co-morbidities. The current case report highlights the underrecognized utility of neurophysiology in the correct diagnosis of tremors, providing useful clinical and neurophysiologic insights into clinical and physiological assessment of tremors. CASE REPORT: A 62-year-old woman with a past medical history of polio was referred by a movement disorders neurologist for evaluation of tremor with concerns of a likely functional etiology. On first assessment there were findings notable for a possible organic etiology, but upon subsequent evaluation the tremor was noted to be variable and entrainable, suggestive of a functional etiology. Neurophysiological tremor study could identify an underlying organic tremor (likely of multi-factorial etiology). Tremor entrainment with contralateral hand tapping could be mirror movements or functional movements, as the underlying organic tremor was not entrained. The amplitude of mirrored movement was commensurate with the tapping amplitude. DISCUSSION: Functional tremors may mask an underlying organic tremor. Additionally, motor overflow which may happen especially with large amplitude movements may masquerade as mirror movements, which can be difficult to differentiate from an entrained functional tremor. Objective physiology and refinement of the current clinical and physiologic tremor evaluation techniques may help identify an underlying organic etiology.

Regulation by copper of the expression of plastocyanin and cytochrome c552 in Chlamydomonas reinhardi.

Plastocyanin and cytochrome c552 are interchangeable electron carriers in the photosynthetic electron transfer chains of some cyanobacteria and green algae (P. M. Wood, Eur. J. Biochem. 87:9-19, 1978; G. Sandmann et al., Arch. Microbiol. 134:23-27, 1983). Chlamydomonas reinhardi cells respond to the availability of copper in the medium and accordingly accumulate either plastocyanin (if copper is available) or cytochrome c552 (if copper is not available). The response occurs in both heterotrophically and phototrophically grown cells. We have studied the molecular level at which this response occurs. No immunoreactive polypeptide is detectable under conditions where the mature protein is not spectroscopically detectable. Both plastocyanin and cytochrome c552 appear to be translated (in vitro) from polyadenylated mRNA as precursors of higher molecular weight. RNA was isolated from cells grown either under conditions favorable for the accumulation of plastocyanin (medium with Cu2+) or for the accumulation of cytochrome c552 (without Cu2+ added to the medium). Translatable mRNA for preapoplastocyanin was detected in both RNA preparations, although mature plastocyanin was detected in C. reinhardi cells only when copper was added to the culture. Translatable mRNA for preapocytochrome, on the other hand, was detected only in cells grown under conditions where cytochrome c552 accumulates (i.e., in the absence of copper). We conclude that copper-mediated regulation of plastocyanin and cytochrome c552 accumulation is effected at different levels, the former at the level of stable protein and the latter at the level of stable mRNA.

Testing a method for quantifying the output of implantable middle ear hearing devices.

This report describes tests of a standard practice for quantifying the performance of implantable middle ear hearing devices (also known as implantable hearing aids). The standard and these tests were initiated by the Food and Drug Administration of the United States Government. The tests involved measurements on two hearing devices, one commercially available and the other home built, that were implanted into ears removed from human cadavers. The tests were conducted to investigate the utility of the practice and its outcome measures: the equivalent ear canal sound pressure transfer function that relates electrically driven middle ear velocities to the equivalent sound pressure needed to produce those velocities, and the maximum effective ear canal sound pressure. The practice calls for measurements in cadaveric ears in order to account for the varied anatomy and function of different human middle ears.

Evaluation of 18F-fluorothymidine positron emission tomography ([18F]FLT-PET/CT) methodology in assessing early response to chemotherapy in patients with gastro-oesophageal cancer.

BACKGROUND: 3'-Deoxy-3'-[18F]fluorothymidine ([18F]FLT) PET has limited utility in abdominal imaging due to high physiological hepatic uptake of a tracer. We evaluated [18F]FLT-PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (KSF) to improve tumour visualisation in patients with locally advanced and metastatic gastro-oesophageal cancer and as a marker of early response to chemotherapy. Dynamic [18F]FLT-PET/CT data were collected before and 3 weeks post first cycle of chemotherapy. Changes in tumour [18F]FLT-PET/CT variables were determined. Response was determined on contrast-enhanced CT after three cycles of therapy using RECIST 1.1. RESULTS: Ten patients were included. Following application of the KSF, visual distinction of all oesophageal and/or gastric tumours was observed in [18F]FLT-PET images. Among the nine patients available for response evaluation (RECIST 1.1), three patients had responded (partial response) and six patients were non-responders (stable disease). There was a significant association between Ki-67 and all baseline [18F]FLT-PET parameters. Area under the curve (AUC) from 0 to 1 min was associated with treatment response. CONCLUSIONS: The results of this study indicate that application of the KSF allowed accurate visualisation of both primary and metastatic lesions following imaging with the proliferation marker, [18F]FLT-PET/CT. However, [18F]FLT-PET uptake parameters did not correlate with response. Instead, we observe significant changes in tracer delivery following chemotherapy suggesting that further [18F]FLT-PET/CT studies in this tumour type should be undertaken with caution.