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1.
Clin Oncol (R Coll Radiol) ; 36(5): 287-299, 2024 05.
Article in English | MEDLINE | ID: mdl-38395634

ABSTRACT

AIMS: The Scottish Medical Consortium recently approved first-line pembrolizumab monotherapy or in combination with chemotherapy for head and neck squamous cell carcinoma in the palliative setting, contrasting with the decision made by the National Institute for Health and Care Excellence, who approved monotherapy alone in England and Wales. The aim of this study was to provide real-world performance data for first-line pembrolizumab-containing treatments for head and neck squamous cell carcinoma in the palliative setting in Scotland. MATERIALS AND METHODS: We analysed the electronic records of patients who started pembrolizumab-containing treatment between 1 March 2020 and 30 September 2021. Outcomes included overall survival, progression-free survival (PFS), the duration of response and the disease control rate. Data were compared with the KEYNOTE-048 study and clinical factors were evaluated for association with survival. RESULTS: Our cohort included 91 patients (median follow-up 10.8 months). Patient characteristics were similar to those in the KEYNOTE-048 study, although our cohort had a higher proportion of patients with newly diagnosed, non-metastatic disease. For patients receiving monotherapy (n = 76), 12- and 24-month overall survival were 45% and 27%, respectively. For patients receiving pembrolizumab-chemotherapy (n = 15), 12-month overall survival was 60% (24-month overall survival had not yet been reached). Experiencing one or more immune-related adverse event (irAE; versus no irAEs), of any grade, was associated with favourable overall survival and PFS for patients receiving monotherapy in both univariable Log-rank analysis (median overall survival 17.4 months versus 8.6 months, respectively, P = 0.0033; median PFS 10.9 months versus 3.0 months, respectively, P < 0.0001) and multivariable analysis (Cox proportional hazards regression: overall survival hazard ratio 0.31, P = 0.0009; PFS hazard ratio 0.17, P < 0.0001). CONCLUSION: Our real-world data support the KEYNOTE-048 study findings and the value of combination treatment options. Additionally, our data show that irAEs of any grade, as reported in routine clinical records, are associated with better outcomes in this patient group, adding to the growing body of evidence showing that irAEs are generally a positive marker of programmed death-ligand 1 (PD-L1) inhibitor response.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Agents, Immunological , Head and Neck Neoplasms , Lung Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/drug therapy , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Head and Neck Neoplasms/drug therapy , United Kingdom , Lung Neoplasms/pathology , B7-H1 Antigen
2.
Clin Oncol (R Coll Radiol) ; 35(12): e699-e707, 2023 12.
Article in English | MEDLINE | ID: mdl-37798198

ABSTRACT

AIMS: The high negative predictive value of post-chemoradiation (CRT) positron emission tomography-computed tomography (PET-CT) is well established in head and neck squamous cell cancers (HNSCC). The positive predictive value (PPV) remains under scrutiny, with increasing evidence that it is affected by several factors. The aim of this study was to assess the PPV of post-treatment PET-CT for residual nodal disease when stratified by treatment modality and tumour human papillomavirus (HPV) status. MATERIALS AND METHODS: This was a retrospective cohort study in a tertiary oncology centre carried out between January 2013 and December 2019. Patients were radically treated with radiotherapy only/CRT for node-positive HNSCC. PET-CT nodal responses were categorised as complete, equivocal (EQR) or incomplete (ICR), and outcomes extracted from electronic records. RESULTS: In total, 480 patients were evaluated, all had a minimum potential follow-up of 2 years, with a median of 39.2 months. The PPV of 12-week PET-CT was significantly different between HPV-positive (22.5%) and HPV-unrelated (52.7%) disease, P < 0.001. It was also significantly different between the CRT (24.8%) and radiotherapy-only (51.1%) groups, P = 0.001. The PPV of an EQR was significantly less than an ICR, irrespective of HPV status and primary treatment modality. In HPV-positive disease, the PPV of an EQR was 9.0% for the CRT group compared with 21.4% for radiotherapy only, P = 0.278. The PPV in those who achieved an ICR was 34.2% in the CRT group, significantly lower than 70.0% in the radiotherapy-only group, P = 0.03. CONCLUSION: The PPV of 12-week PET-CT is significantly lower for HPV-positive compared with HPV-unrelated HNSCC. It is poorer in patients with HPV-positive disease treated with CRT compared with radiotherapy alone.


Subject(s)
Head and Neck Neoplasms , Papillomavirus Infections , Humans , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Predictive Value of Tests , Human Papillomavirus Viruses , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/radiotherapy , Retrospective Studies , Papillomavirus Infections/diagnostic imaging , Papillomavirus Infections/radiotherapy
3.
J Small Anim Pract ; 63(2): 142-146, 2022 02.
Article in English | MEDLINE | ID: mdl-33939184

ABSTRACT

OBJECTIVES: To describe the clinical findings, imaging findings and outcome in patients in which CT sinography was performed, and assess to what degree this technique adds information about the extent of a tract or increases the accuracy of diagnosis of foreign bodies on CT. MATERIALS AND METHODS: Retrospective review of medical records of 27 dogs and one cat with draining tracts that had CT sinography. Pre- and post-intravenous (IV) contrast CT series were compared with CT sinography in each patient. RESULTS: Median duration of clinical signs before referral was 85 days (range 2 to 1478 days). The most common reported clinical signs were swelling (14/28, 50%) and regional pain (5/28, 18%). CT sinography revealed a more extensive tract than post-IV contrast CT in 21% cases. On post-IV contrast CT, 31% of foreign bodies were detected compared to 23% on CT sinography. All four foreign bodies detected by CT were observed in the non-contrast images. Surgery was performed after CT in 22 (79%) cases. Thirteen (46%) draining tracts resolved after surgery, three (11%) resolved without surgery, six (21%) persisted or recurred after surgery, and six (21%) were lost to follow-up. CLINICAL SIGNIFICANCE: CT sinography provides limited additional information about the extent of draining tracts compared to pre- and post-IV contrast CT images and did not increase the number of foreign bodies identified.


Subject(s)
Dog Diseases , Foreign Bodies , Animals , Dog Diseases/diagnostic imaging , Dog Diseases/surgery , Dogs , Foreign Bodies/diagnostic imaging , Foreign Bodies/surgery , Foreign Bodies/veterinary , Recurrence , Retrospective Studies , Tomography, X-Ray Computed/veterinary
4.
Clin Oncol (R Coll Radiol) ; 32(10): 665-673, 2020 10.
Article in English | MEDLINE | ID: mdl-32561027

ABSTRACT

AIMS: To evaluate the implementation of 18-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) surveillance after (chemo)radiotherapy, to compare outcomes for those who achieved a complete (CR), equivocal (EQR) and incomplete (ICR) nodal response on 12-week PET-CT according to their human papillomavirus (HPV) status, and to assess the safety of ongoing surveillance beyond 12 weeks in the HPV-positive EQR group. MATERIALS AND METHODS: All patients with node-positive head and neck squamous cell carcinoma (HNSCC) treated with (chemo)radiotherapy between January 2013 and September 2017 were identified. PET-CT responses were classified as CR, ICR or EQR. Patient outcomes were obtained from electronic records. RESULTS: In total, 236 patients with a minimum of 2 years of follow-up were identified. The mean age was 59 years; 79.3% had N2 disease; 77.1% of patients had oropharyngeal cancer and 10.1% had squamous cell carcinoma of unknown primary, of whom 82.0% (169) were HPV positive; 78.0% received chemoradiotherapy. The median time from the end of radiotherapy to PET-CT was 91 days. Of the HPV-related HNSCC, 60.4% achieved CR, 29.0% EQR and 10.6% ICR. With a median follow-up of 41.7 months, there was no difference in survival between patients with HPV-related HNSCC achieving CR and EQR (median overall survival not reached for both, P = 0.67) despite the omission of immediate neck dissection in 98.0% of the EQR group. CONCLUSION: Patients with HPV-positive HNSCC who have achieved EQR have comparable survival outcomes to those who achieved a CR despite the omission of immediate neck dissections; this shows the safety of ongoing surveillance beyond 12 weeks in this group of patients.


Subject(s)
Chemoradiotherapy/methods , Head and Neck Neoplasms/pathology , Positron Emission Tomography Computed Tomography/methods , Squamous Cell Carcinoma of Head and Neck/pathology , Female , Fluorodeoxyglucose F18/metabolism , Head and Neck Neoplasms/diagnostic imaging , Head and Neck Neoplasms/therapy , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Squamous Cell Carcinoma of Head and Neck/diagnostic imaging , Squamous Cell Carcinoma of Head and Neck/therapy , Survival Rate
5.
J Small Anim Pract ; 61(6): 338-345, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32323304

ABSTRACT

OBJECTIVES: To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma. MATERIALS AND METHODS: Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded. Progression-free survival and overall survival time were calculated. RESULTS: Thirty dogs were included. Twenty-four of 29 dogs undergoing imaging of the thorax had lung and/or mediastinal involvement. The median overall survival time for dogs that were not euthanased within 3 days of diagnosis was 117 days (range 10 to 790). Three dogs underwent surgery; 13 received treatment with lomustine as a sole therapy - with partial responses documented on imaging in five of six dogs and 11 of 13 showing clinical improvement. CLINICAL SIGNIFICANCE: Histiocytic sarcoma should be considered as a differential diagnosis for miniature schnauzers with pulmonary masses. Although responses to treatment were common, they were usually short-lived because of the aggressive nature of the disease.


Subject(s)
Dog Diseases , Histiocytic Sarcoma/veterinary , Animals , Dogs , Lomustine , Retrospective Studies
6.
J Small Anim Pract ; 61(1): 24-31, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31592537

ABSTRACT

OBJECTIVES: To describe pre- and post-operative ultrasonographic and fluoroscopic findings, including any abnormalities, in cats treated for ureteral obstruction with a subcutaneous ureteral bypass system. METHODS: Retrospective review of imaging findings in cats with ureteral obstruction that had surgery to place the first version of the bypass system and at least one follow-up ultrasound or fluoroscopic study. Pre- and post-operative renal pelvic diameter on ultrasound, fluoroscopic appearance of the bypass system and any related abnormality were recorded. RESULTS: Eighty-one cats were included (47 unilateral, 34 bilateral bypass systems). Median preoperative renal pelvic diameter was 9 mm (range 3 to 28 mm) and median renal pelvic diameter at the first postoperative ultrasound was 3 mm (range 2 to 23 mm). The median number of postoperative imaging studies was two (range 1 to 8) and the median follow-up period after surgery was 205 days (range 1 to 1378 days). Bypass system abnormalities were identified postoperatively in 43 (53%) cats, including nephrostomy or cystostomy catheter blockage due to an undetermined cause or kinking of the catheter, nephrostomy or cystostomy catheter leakage, non-obstructive kinking of the catheter and loose nephrostomy pig-tail loop. Many abnormalities required repeat surgery, but others were managed conservatively. Fifty-four percent of obstructed ureters became patent after bypass placement, although the majority remained slightly dilated or had irregular margins compatible with chronic inflammation. CLINICAL SIGNIFICANCE: Bypass abnormalities, mainly tube blockage, occurred frequently in cats treated for ureteral obstruction. Ultrasonography and fluoroscopy were useful for postoperative examination, including documenting renewed ureteral patency and investigation of suspected abnormalities.


Subject(s)
Cat Diseases , Ureter , Ureteral Obstruction/veterinary , Animals , Cats , Fluoroscopy , Retrospective Studies , Stents , Ultrasonography
7.
Br J Oral Maxillofac Surg ; 57(10): 1119-1125, 2019 12.
Article in English | MEDLINE | ID: mdl-31672256

ABSTRACT

Radiotherapy-induced xerostomia (RIX) is a common and untreatable side effect of radiotherapy to the head and neck. Visco-ease™ mouth spray (Lamellar Biomedical Ltd), a new product that is made from lamellar body mimetics, reduces the viscosity of saliva ex vivo. The purpose of this study was to evaluate its safety and effectiveness in the treatment of RIX in 43 patients with cancer of the head and neck. They were randomised into the Visco-ease™ or placebo groups, and asked to complete the Groningen radiotherapy-induced xerostomia (GRIX) questionnaire each week. The primary endpoint was a change in GRIX score from baseline to end of treatment. There was no difference in scores between the two groups, and none of the patients had device-related serious adverse events. Visco-ease™ oral spray was safe and tolerable but no better than placebo in reducing RIX in this group of patients.


Subject(s)
Head and Neck Neoplasms , Oral Sprays , Radiation Injuries , Xerostomia , Double-Blind Method , Head and Neck Neoplasms/radiotherapy , Humans , Radiation Injuries/prevention & control , Saliva , Xerostomia/prevention & control
8.
J Small Anim Pract ; 59(12): 752-757, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30175457

ABSTRACT

OBJECTIVES: To identify CT features of canine hepatic masses that could be used to determine their divisional or lobar origin. MATERIALS AND METHODS: Preoperative, postcontrast CT images of 57 surgically resected hepatic masses were reviewed with respect to their size, position relative to the midline, gallbladder and portal vein, nearest recognisable hepatic lobar vein or portal vein and point of contact with the diaphragm and displacement of adjacent organs. RESULTS: The most prevalent histological diagnoses were hepatocellular carcinoma (n=26; 46%) and adenoma (n=10; 18%). Based on surgical assessment, it was observed that masses originated in the left hepatic division in 30 (53%) instances, central division in seven (12%) and right division in 20 (35%). All masses to the left of midline were left divisional, but only 18/30 (60%) masses to the right of midline were right divisional. Most (26/31; 84%) masses to the left of the gallbladder were left divisional and 84% (16/19) masses to the right of the gallbladder were right divisional. Half (10/20; 50%) of the right-divisional masses were medial, lateral or dorsal to the portal vein, but all other hepatic masses were ventral to the portal vein. A hepatic lobar vein or portal vein branch adjacent to the mass was observed in 53 (93%) instances; this feature correlated with surgical assessment of the affected division in 53 (93%) hepatic masses and the affected lobe in 32 (56%). CLINICAL SIGNIFICANCE: Combining CT features of hepatic masses appears to be an accurate method for determining their divisional or lobar origin.


Subject(s)
Dog Diseases/diagnostic imaging , Liver Neoplasms/veterinary , Tomography, X-Ray Computed/veterinary , Adenoma/diagnostic imaging , Adenoma/veterinary , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/veterinary , Dogs , Liver/diagnostic imaging , Liver/pathology , Liver Diseases/diagnostic imaging , Liver Diseases/veterinary , Liver Neoplasms/diagnostic imaging
9.
Physiol Res ; 67(6): 935-943, 2018 12 18.
Article in English | MEDLINE | ID: mdl-29750887

ABSTRACT

The binding of high-mobility group box-1 (HMGB-1) to the membrane receptor for advanced glycation end-products (mRAGE) is a key early mediator of non-infectious inflammation and its triggers include ischaemia/hypoxia. The effects of acute hypoxia on soluble RAGE (sRAGE) are unknown. Fourteen healthy adults (50 % women; 26.6+/-3.8 years) were assessed at baseline normoxia (T0), followed by four time-points (T90, 95, 100 and 180 min) over three hours of continuous normobaric hypoxia (NH, 4,450 m equivalent) and again 60 min after return to normoxia (T240). A 5-min exercise step test was performed during NH at T90. Plasma concentrations of HMGB-1, sRAGE VCAM-1, ICAM-1, VEGF IL-8 and IL-13 were measured using venous blood. Arterial and tissue oxygen saturations were measured using pulse oximetry (SpO(2)) and near-infrared spectroscopy (StO(2)), respectively. NH led to a significant reduction in SpO(2), StO(2), sRAGE and VEGF, which was compounded by exercise, before increasing to baseline values with normoxic restoration (T240). NH-exercise led to a paired increase in HMGB-1. sRAGE inversely correlated with HMGB-1 (r=-0.32; p=0.006), heart rate (r=-0.43; p=0.004) but was not linked to SpO(2) or StO(2). In conclusion, short-term NH leads to a fall in sRAGE and VEGF concentrations with a transient rise post NH-exercise in HMGB-1.


Subject(s)
Alarmins/blood , Hypoxia/blood , Inflammation Mediators/blood , Oxygen Consumption/physiology , Adult , Biomarkers/blood , Female , HMGB1 Protein/blood , Humans , Hypoxia/diagnosis , Male , Prospective Studies , Receptor for Advanced Glycation End Products/blood , Vascular Endothelial Growth Factor A/blood , Young Adult
10.
Br J Oral Maxillofac Surg ; 56(4): 272-277, 2018 05.
Article in English | MEDLINE | ID: mdl-29576230

ABSTRACT

Depth of invasion is an important predictor of survival. A study by the International Consortium (ICOR) for Outcome Research proposed incorporation of it (together with the greatest surface dimension, or the anatomical criteria, or both) into the T stage. This has been adopted in part by the 8th edition of the Union for International Cancer Control (UICC) TNM 8 classification of malignant tumours for oral squamous cell carcinoma (SCC). Our aim was to verify depth of invasion as an independent prognostic factor, and to validate the staging by comparing it with that specified in the 7th edition (TNM 7) and the T-staging model proposed by the International Consortium. We retrospectively studied 449 patients who had had operations for a previously untreated primary oral cancer between 2006 and 2014 at a single centre, and analysed the independent predictive value of depth of invasion for both disease-specific and overall survival. It was an independent predictor of disease-specific survival as were sex, perineural invasion, and N stage. It was also an independent predictor of overall survival together with sex and N status. Staging in TNM 8 gave a better balance of distribution than that in TNM 7, but did not discriminate between prognosis in patients with T3 and T4 disease. The proposed International Consortium rules for T-staging gave an improved balance in distribution and hazard discrimination. The incorporation of depth of invasion into the T-staging rules for oral SCC improved prognostic accuracy and is likely to influence the selection of patients for adjuvant treatment. Our findings suggest that the TNM 8 staging lacks hazard discrimination in patients with locally-advanced disease because its T4 staging is restricted to anatomical criteria.


Subject(s)
Carcinoma, Squamous Cell/pathology , Mouth Neoplasms/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/classification , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/mortality , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Mouth Neoplasms/classification , Mouth Neoplasms/diagnosis , Mouth Neoplasms/mortality , Neoplasm Invasiveness/pathology , Neoplasm Staging/standards , Prognosis , Survival Analysis , Young Adult
11.
J Small Anim Pract ; 2018 Mar 25.
Article in English | MEDLINE | ID: mdl-29577303

ABSTRACT

Pneumocystis carinii pneumonia is a rare disease in dogs. It is primarily reported in cavalier King Charles spaniels and miniature dachshunds with suspected underlying immunodeficiency. This case series reports the findings in five dogs (four cavalier King Charles spaniels and one Bedlington terrier) with confirmed P. carinii pneumonia. Thoracic (CT) revealed ground glass opacity of the pulmonary parenchyma with a diffuse or multifocal distribution. The severity of this pattern was variable. Less consistent imaging findings included parenchymal bands, bronchial dilation and signs consistent with pulmonary hypertension. Four dogs recovered well with treatment and there was resolution of CT abnormalities in all dogs with follow-up.

12.
J Small Anim Pract ; 59(1): 32-37, 2018 01.
Article in English | MEDLINE | ID: mdl-29105088

ABSTRACT

OBJECTIVE: To assess the utility of abdominal ultrasonography in the diagnostic work-up of dogs with diarrhoea. METHODS: Retrospective cross-sectional study based on a referral population of dogs with diarrhoea. Associations between the clinical signs, use of abdominal ultrasonography, results of abdominal ultrasonography and subsequent work-up were examined. The utility of abdominal ultrasonography was scored as high, moderate, none or counterproductive based on review of medical records. RESULTS: Medical records of 269 dogs were reviewed, of which 149 (55%) had abdominal ultrasonography. The most frequent result was no ultrasonographic abnormalities affecting the intestine in 65 (44%) dogs. Ultrasonography results were associated with subsequent work-up as follows: (1) no detected abnormalities and dietary trial; (2) focal thickening of the intestinal wall, loss of intestinal wall layers or enlarged abdominal lymph nodes and ultrasound-guided fine-needle aspirates; (3) diffuse thickening of the intestinal wall or hyperechoic striations in the small intestinal mucosa and endoscopy; and (4) small intestinal foreign body and coeliotomy. Abdominal ultrasonography was considered to be diagnostic without further testing in only four (3%) dogs: two had a portosystemic shunt identified ultrasonographically, one had a linear foreign body and one had a perforated pyloric ulcer. Abdominal ultrasonography had moderate utility in 56 (38%) dogs and no utility in 79 (53%) dogs. Abdominal ultrasonography was considered counterproductive in 10 (7%) dogs because results were either falsely negative or falsely positive. CLINICAL SIGNIFICANCE: These results should prompt clinicians to reconsider routine use of abdominal ultrasonography in dogs with diarrhoea.


Subject(s)
Abdomen/diagnostic imaging , Diarrhea/veterinary , Dog Diseases/diagnostic imaging , Ultrasonography/veterinary , Animals , Cross-Sectional Studies , Diarrhea/diagnostic imaging , Dogs , Female , Intestinal Diseases/diagnostic imaging , Intestinal Diseases/veterinary , Male , Retrospective Studies
13.
J Small Anim Pract ; 58(4): 211-218, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28276120

ABSTRACT

OBJECTIVES: To describe clinical and imaging findings in dogs with confirmed gastrointestinal ulceration, to compare findings in dogs with perforated and non-perforated ulcers and to estimate the sensitivities of radiography, ultrasonography and computed tomography (CT) for gastrointestinal ulceration and perforation. METHODS: Retrospective review of medical records of 82 dogs that had a macroscopic ulcer in the gastric or intestinal mucosa diagnosed directly at endoscopy, surgery or necropsy and had survey radiography, ultrasonography or a CT scan of the abdomen during the same period of hospitalisation. RESULTS: The most frequent clinical signs were vomiting in 88% dogs, haematemesis in 32%, melaena in 31% and weight loss in 7%. The most frequent imaging findings in dogs with non-perforated ulcers were gastrointestinal mural lesion in 56%, mucosal defect compatible with an ulcer in 44% and peritoneal fluid in 21%. In dogs with perforated ulcers the most frequent imaging findings were peritoneal fluid in 83%, gastrointestinal mural lesion in 48%, peritoneal gas in 31% and mucosal defect compatible with an ulcer in 29%. Sensitivities of radiography, ultrasonography and CT were 30, 65 and 67% in dogs with non-perforated ulcers and 79, 86 and 93% in dogs with perforated ulcers, respectively. CLINICAL SIGNIFICANCE: In dogs with non-perforated ulcers, survey radiography was usually negative whereas ultrasonography and CT frequently enabled detection of the site of the ulcer; in dogs with perforated ulcers, radiography was frequently positive for peritoneal gas and CT was a sensitive modality for both the ulcer and signs of perforation.


Subject(s)
Dog Diseases/diagnostic imaging , Intestinal Diseases/veterinary , Stomach Ulcer/veterinary , Ulcer/veterinary , Animals , Dogs , Female , Intestinal Diseases/diagnostic imaging , Male , Radiography, Abdominal/veterinary , Retrospective Studies , Sensitivity and Specificity , Stomach Ulcer/diagnostic imaging , Tomography, X-Ray Computed/veterinary , Ulcer/diagnostic imaging , Ultrasonography/veterinary
14.
Methods Enzymol ; 587: 21-42, 2017.
Article in English | MEDLINE | ID: mdl-28253957

ABSTRACT

Autophagy relies on the sequential, hierarchical association of proteins with phagophores, and forming autophagosomes to allow completion of the process. Additionally, the trafficking of the unique transmembrane autophagy-related protein ATG9 is vital for autophagy progression. In this chapter, we discuss methods to monitor autophagosome number using confocal microscopy, by following the association of different autophagosomal markers with the phagophore and completed autophagosome. We also discuss methods to monitor the trafficking of ATG9 in mammalian cells under starvation conditions.


Subject(s)
Autophagosomes/ultrastructure , Microscopy, Confocal/methods , Animals , Autophagy-Related Proteins/analysis , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Fluorescent Antibody Technique, Indirect/methods , HEK293 Cells , Humans , Mammals , Membrane Proteins/analysis , Membrane Proteins/genetics , Membrane Proteins/metabolism , Molecular Imaging/methods , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Vesicular Transport Proteins/analysis , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
15.
Clin Oncol (R Coll Radiol) ; 29(1): 60-67, 2017 01.
Article in English | MEDLINE | ID: mdl-27780693

ABSTRACT

AIMS: To carry out statistical validation of a newly developed magnetic resonance imaging (MRI) auto-contouring software tool for gross tumour volume (GTV) delineation in head and neck tumours to assist in radiotherapy planning. MATERIALS AND METHODS: Axial MRI baseline scans were obtained for 10 oropharyngeal and laryngeal cancer patients. GTV was present on 102 axial slices and auto-contoured using the modified fuzzy c-means clustering integrated with the level set method (FCLSM). Peer-reviewed (C-gold) manual contours were used as the reference standard to validate auto-contoured GTVs (C-auto) and mean manual contours (C-manual) from two expert clinicians (C1 and C2). Multiple geometric metrics, including the Dice similarity coefficient (DSC), were used for quantitative validation. A DSC≥0.7 was deemed acceptable. Inter- and intra-variabilities among the manual contours were also validated. The two-dimensional contours were then reconstructed in three dimensions for GTV volume calculation, comparison and three-dimensional visualisation. RESULTS: The mean DSC between C-gold and C-auto was 0.79. The mean DSC between C-gold and C-manual was 0.79 and that between C1 and C2 was 0.80. The average time for GTV auto-contouring per patient was 8 min (range 6-13 min; mean 45 s per axial slice) compared with 15 min (range 6-23 min; mean 88 s per axial slice) for C1. The average volume concordance between C-gold and C-auto volumes was 86.51% compared with 74.16% between C-gold and C-manual. The average volume concordance between C1 and C2 volumes was 86.82%. CONCLUSIONS: This newly designed MRI-based auto-contouring software tool shows initial acceptable results in GTV delineation of oropharyngeal and laryngeal tumours using FCLSM. This auto-contouring software tool may help reduce inter- and intra-variability and can assist clinical oncologists with time-consuming, complex radiotherapy planning.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Magnetic Resonance Imaging/methods , Radiotherapy Planning, Computer-Assisted/methods , Software , Aged , Female , Humans , Middle Aged , Observer Variation
16.
Aliment Pharmacol Ther ; 44(10): 1030-1038, 2016 11.
Article in English | MEDLINE | ID: mdl-27666418

ABSTRACT

BACKGROUND: Since 1970, there has been a 400% increase in liver-related deaths due to the increasing prevalence of chronic liver disease in the United Kingdom (UK). The 2013 UK National Confidential Enquiry into Patient Outcome and Death report found that only 47% of patients who died from alcohol-related liver disease received 'good care' during their hospital stay. AIM: To develop a 'care bundle' for patients with decompensated cirrhosis, aiming to ensure that evidence-based treatments are delivered within the first 24 h of hospital admission. METHODS: This work gives practical advice about how to implement the bundle and examines its effects on patient care at three National Health Service Hospital Trusts in the UK by collecting data on patient care before and after introduction of the bundle. RESULTS: Data were collected on 228 patients across three centres (59% male, median age 53 years). Alcohol-related liver disease was the aetiology of chronic liver disease in 85% of patients. The overall mortality rate during hospital admission was 15%. The audits demonstrated improvements in patient care for patients with a completed care bundle who were significantly more likely to have a diagnostic ascitic performed within the first 24 h (P = 0.020), have an accurate alcohol history documented (P < 0.0001) and be given antibiotics as prophylaxis against infection following a variceal haemorrhage (P = 0.0096). In Newcastle, the bundle completion rate increased from 25% to 90% during the review periods. CONCLUSIONS: The introduction of a care bundle was associated with increased rates of diagnostic paracentesis and antibiotic prophylaxis with variceal haemorrhage in patients with decompensated cirrhosis.


Subject(s)
Hospitalization/statistics & numerical data , Liver Cirrhosis, Alcoholic/therapy , Patient Care Bundles , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Esophageal and Gastric Varices/drug therapy , Esophageal and Gastric Varices/epidemiology , Female , Gastrointestinal Hemorrhage/drug therapy , Gastrointestinal Hemorrhage/epidemiology , Humans , Liver Cirrhosis, Alcoholic/diagnosis , Liver Cirrhosis, Alcoholic/drug therapy , Liver Cirrhosis, Alcoholic/epidemiology , Male , Middle Aged , Paracentesis , United Kingdom
17.
Br J Anaesth ; 117(3): 387-94, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27543534

ABSTRACT

BACKGROUND: Posterior variants of abdominal wall block include the quadratus lumborum type I, quadratus lumborum type II and quadratus lumborum transmuscular blocks. Our objectives were to compare the spread of injectate and nerve involvement, after conducting blocks using ultrasound guidance in soft embalmed cadavers. METHODS: After randomization, an experienced anaesthetist conducted three quadratus lumborum 1, three quadratus lumborum 2 and four transmuscular blocks on the left or right sides of five cadavers. All cadavers were placed in the lateral position and the quadratus lumborum muscle seen using a 3-9 MHz ultrasound probe placed in the flank. For each block, a 20 ml mixture of 17.75 ml water, 2 mls latex and 0.25 ml India ink was injected. The lumbar region and abdominal flank were dissected 72 h later. RESULTS: We conducted 10 blocks. Two quadratus lumborum 1 and two quadratus lumborum 2 blocks were associated with spread of dye within the TAP plane. One quadratus lumborum 1 block spread to the deep muscles of the back and one quadratus lumborum 2 block dispersed within the subcutaneous tissue surrounding the abdominal flank. All transmuscular quadratus lumborum blocks spread consistently to L1 and L3 nerve roots and within psoas major and quadratus lumborum muscles. CONCLUSIONS: Consistent spread to lumbar nerve roots was achieved using the transmuscular approach through the quadratus lumborum.


Subject(s)
Abdominal Wall/innervation , Nerve Block , Cadaver , Coloring Agents , Humans
18.
J Small Anim Pract ; 57(10): 561-567, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27467170

ABSTRACT

OBJECTIVES: To estimate the prevalence of subclinical abnormalities reported in thoracic (CT) scans of cats and to investigate associations between respiratory signs and CT signs. METHODS: Retrospective review of signalment, indications, respiratory signs and reported CT findings in a series of cats. Associations between patient variables, respiratory signs and CT signs were analysed using multi-variable regression methods. RESULTS: Records of 352 consecutive cats were reviewed. Abnormalities affecting thoracic structures were reported in CT scans of 138/179 (77%) cats that did not have respiratory signs; the most prevalent CT findings were pulmonary collapse (41%), evidence of bronchial disease (24%) and space-occupying lesions (21%). Dyspnoea, cough and tachypnoea were associated with space-occupying lesions. Dyspnoea was also associated with pulmonary consolidation and atelectasis. Increasing body weight was associated with pulmonary atelectasis and increasing age was associated with evidence of bronchial disease. CLINICAL SIGNIFICANCE: Abnormalities were commonly detected in thoracic CT scans of cats that did not show respiratory signs. The most prevalent abnormality - pulmonary atelectasis - is probably a temporary effect of sedation or anaesthesia. A high prevalence of subclinical abnormalities and limited correlations between clinical signs and CT findings will complicate diagnosis.


Subject(s)
Cat Diseases/diagnostic imaging , Respiration Disorders/veterinary , Tomography, X-Ray Computed/veterinary , Animals , Cat Diseases/epidemiology , Cats , Female , Male , Prevalence , Respiration Disorders/diagnostic imaging , Respiration Disorders/epidemiology , Retrospective Studies
19.
Chest ; 149(3)Mar. 2016. tab
Article in English | BIGG - GRADE guidelines | ID: biblio-964628

ABSTRACT

BACKGROUND: Endobronchial ultrasound (EBUS) was introduced in the last decade, enabling real-time guidance of transbronchial needle aspiration (TBNA) of mediastinal and hilar structures and parabronchial lung masses. The many publications produced about EBUS-TBNA have led to a better understanding of the performance characteristics of this procedure. The goal of this document was to examine the current literature on the technical aspects of EBUS-TBNA as they relate to patient, technology, and proceduralist factors to provide evidence-based and expert guidance to clinicians. METHODS: Rigorous methodology has been applied to provide a trustworthy evidence-based guideline and expert panel report. A group of approved panelists developed key clinical questions by using the PICO (population, intervention, comparator, and outcome) format that addressed specific topics on the technical aspects of EBUS-TBNA. MEDLINE (via PubMed) and the Cochrane Library were systematically searched for relevant literature, which was supplemented by manual searches. References were screened for inclusion, and well-recognized document evaluation tools were used to assess the quality of included studies, to extract meaningful data, and to grade the level of evidence to support each recommendation or suggestion. RESULTS: Our systematic review and critical analysis of the literature on 15 PICO questions related to the technical aspects of EBUS-TBNA resulted in 12 tatements: 7 evidence-based graded recommendations and 5 ungraded consensus-based statements. Three questions did not have sufficient evidence to generate a statement. CONCLUSIONS: Evidence on the technical aspects of EBUS-TBNA varies in strength but is satisfactory in certain areas to guide clinicians on the best conditions to perform EBUS-guided tissue sampling. Additional research is needed to enhance our knowledge regarding the optimal performance of this effective procedure.(AU)


Subject(s)
Humans , Conscious Sedation , Carcinoma, Non-Small-Cell Lung/pathology , Deep Sedation , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Lung Neoplasms/pathology , Sarcoidosis/pathology , Bronchoscopy/methods , Simulation Training , GRADE Approach , Lymphatic Diseases/pathology , Mediastinal Neoplasms/pathology
20.
Aliment Pharmacol Ther ; 43(8): 910-923, 2016 04.
Article in English | MEDLINE | ID: mdl-26892328

ABSTRACT

BACKGROUND: Infliximab and adalimumab have established roles in inflammatory bowel disease (IBD) therapy. UK regulators mandate reassessment after 12 months' anti-TNF therapy for IBD, with consideration of treatment withdrawal. There is a need for more data to establish the relapse rates following treatment cessation. AIM: To establish outcomes following anti-TNF withdrawal for sustained remission using new data from a large UK cohort, and assimilation of all available literature for systematic review and meta-analysis. METHODS: A retrospective observational study was performed on 166 patients with IBD (146 with Crohn's disease (CD) and 20 with ulcerative colitis [UC) and IBD unclassified (IBDU)] withdrawn from anti-TNF for sustained remission. Meta-analysis was undertaken of all published studies incorporating 11 further cohorts totalling 746 patients (624 CD, 122 UC). RESULTS: Relapse rates in the UK cohort were 36% by 1 year and 56% by 2 years for CD, and 42% by 1 year and 47% by 2 years for UC/IBDU. Increased relapse risk in CD was associated with age at diagnosis [hazard ratio (HR) 2.78 for age <22 years], white cell count (HR 3.22 for >5.25 × 109 /L) and faecal calprotectin (HR 2.95 for >50 µg/g) at drug withdrawal. Neither continued immunomodulators nor endoscopic remission were predictors. In the meta-analysis, estimated 1-year relapse rates were 39% and 35% for CD and UC/IBDU respectively. Retreatment with anti-TNF was successful in 88% for CD and 76% UC/IBDU. CONCLUSIONS: Assimilation of all available data reveals remarkable homogeneity. Approximately one-third of patients with IBD flare within 12 months of withdrawal of anti-TNF therapy for sustained remission.


Subject(s)
Colitis, Ulcerative/drug therapy , Crohn Disease/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab/administration & dosage , Adult , Feces/chemistry , Female , Humans , Immunologic Factors/therapeutic use , Infliximab/administration & dosage , Male , Proportional Hazards Models , Recurrence , Retrospective Studies , Time Factors
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