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1.
NPJ Precis Oncol ; 6(1): 13, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-35233056

ABSTRACT

The NCI-MATCH was designed to characterize the efficacy of targeted therapies in histology-agnostic driver mutation-positive malignancies. Sub-protocols F and G were developed to evaluate the role of crizotinib in rare tumors that harbored either ALK or ROS1 rearrangements. Patients with malignancies that progressed following at least one prior systemic therapy were accrued to the NCI-MATCH for molecular profiling, and those with actionable ALK or ROS1 rearrangements were offered participation in sub-protocols F or G, respectively. There were five patients who enrolled on Arm F (ALK) and four patients on Arm G (ROS1). Few grade 3 or 4 toxicities were noted, including liver test abnormalities, and acute kidney injury. For sub-protocol F (ALK), the response rate was 50% (90% CI 9.8-90.2%) with one complete response among the 4 eligible patients. The median PFS was 3.8 months, and median OS was 4.3 months. For sub-protocol G (ROS1) the response rate was 25% (90% CI 1.3-75.1%). The median PFS was 4.3 months, and median OS 6.2 months. Data from 3 commercial vendors showed that the prevalence of ALK and ROS1 rearrangements in histologies other than non-small cell lung cancer and lymphoma was rare (0.1% and 0.4% respectively). We observed responses to crizotinib which met the primary endpoint for ALK fusions, albeit in a small number of patients. Despite the limited accrual, some of the patients with these oncogenic fusions can respond to crizotinib which may have a therapeutic role in this setting.

2.
Hernia ; 26(3): 953-957, 2022 06.
Article in English | MEDLINE | ID: mdl-33886018

ABSTRACT

PURPOSE: Visceral obesity rather than body mass index has been reported to be associated with a higher incidence of incisional hernias. The aim of this study was to examine the relationship between CT measured adipose tissue and muscle in primary and recurrent incisional hernia. METHODS: Patients with a 'Primary' or 'Recurrent incisional hernia' were obtained from a prospective cohort of patients who were being assessed for incisional hernia repair over a 2-year period. Computerised tomography (CT)-images were analysed using NIH Image-J software to quantify adipose tissue and skeletal muscle cross-sectional areas at the level of lumber vertebra 3/4 using standard Hounsfield units. To test inter-observer 'absolute agreement', each parameter was measured independently by two investigators and reliability analysis performed. RESULTS: Thirty-six patients were included in the study: 15 had a Primary while 21 had a Recurrent incisional hernia. Both groups had similar baseline characteristics. Reliability analysis for CT-measured areas showed very high interclass correlation coefficient (ICC) between observers. Patients in the recurrent group had significantly greater subcutaneous adipose tissue (SAT) [median = 321.9cm2 vs 230.9cm2, p = 0.04] and visceral adipose tissue (VAT) [median = 221.1cm2 vs 146.8cm2, p = 0.03] than those in the primary group. There was no difference in skeletal muscle areas for right [median = 2.8cm2 vs 2.9cm2] and left [median = 3.7cm2 vs 4.1cm2] rectus muscles between groups. CONCLUSION: Our study shows that patients with a recurrent incisional hernia have significantly more subcutaneous and visceral adipose tissue than those with a primary incisional hernia. Further studies in this area are required if we are to reduce the burden of recurrent hernia following repair of a primary incisional hernia.


Subject(s)
Hernia, Ventral , Incisional Hernia , Hernia, Ventral/surgery , Herniorrhaphy/methods , Humans , Incisional Hernia/etiology , Incisional Hernia/surgery , Intra-Abdominal Fat/diagnostic imaging , Prospective Studies , Reproducibility of Results
3.
Hernia ; 26(2): 489-493, 2022 04.
Article in English | MEDLINE | ID: mdl-34426878

ABSTRACT

BACKGROUND: Repair of a ventral hernia is increasingly being performed by a laparoscopic approach despite lack of good long term follow up data on outcomes. The aim of this study was to examine the long term performance of a polyester mesh and to assess its elastic properties in patients undergoing laparoscopic ventral hernia repair. METHODS: All patients being assessed for a ventral hernia repair between August 2011 and November 2013 were placed on a prospective database. Those undergoing laparoscopic repair with a polyester mesh were seen at clinic at one month and one year, while their electronic records were assessed at 34 months (range 24-48 months) and 104 months (range 92-116 months). In addition, CT scans of the abdomen and pelvis performed for any reason on these patients during the follow up period were reviewed by a consultant gastrointestinal radiologist. Mechanical failure testing of the mesh was also performed. RESULTS: Thirty-two of the 100 patients assessed for ventral hernia repair had a laparoscopic repair with a polyester mesh. Nineteen (59%) had CT scans performed during the follow-up period. No recurrence was recorded at 34 months, while three (9.4%) had a recurrence at 104 months. Two had central breakdown of the mesh at 81 and 90 months, while 1 presented acutely at 116 months after operation. Mesh had stretched across the defect by an average of 21% (range 5.7-40%) in nine patients. Mechanical testing showed that this mesh lost its elasticity at low forces ranging between 1.8 and 3.2 N/cm. CONCLUSION: This study shows that late recurrence is a problem following laparoscopic ventral hernia repair with polyester mesh. The mesh loses it elasticity at a low force. This combined with degradation of mesh seems the most likely cause of failure. This is unlikely to be a unique problem of polyester mesh and further long-term studies are required to better assess this operative approach to ventral hernia repair.


Subject(s)
Hernia, Ventral , Laparoscopy , Elasticity , Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Humans , Recurrence , Retrospective Studies , Surgical Mesh , Treatment Outcome
6.
Br J Radiol ; 93(1114): 20200463, 2020 Oct 01.
Article in English | MEDLINE | ID: mdl-32795181

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate if small group teaching in Radiology impacted Anatomy scores in the summative end of year examination. METHODS: Small group teaching in Radiology was incorporated into Anatomy of year one medical students during the academic years 2016/17 and 2017/18. Examination outcome for 2 years before and 1 year after the study period were compared.Question papers for end of year summative examinations were retrieved; questions relating to Anatomy were identified and anonymised scores for students were obtained. RESULTS: Student numbers ranged 238 to 290/year. Mean Anatomy scores ranged 62-74%, this compared with mean total exam score of 62-65%. No significant difference in Anatomy and Total examination scores for 2015, 2016 and 2019. Mean (SD) Anatomy scores were significantly higher than the Total examination scores for the study period of 2017 and 2018 [68.97 (17.32) vs 63.12 (11.51) and 73.77 (17.85) vs 64.99 (10.31) (p < 0.001)]. Combined Anatomy scores 2017 and 2018 were significantly higher than 2015 and 2016, difference of 5.50 (95% C.I. 3.31-7.70; p < 0.001). CONCLUSION: This is the first study to objectively demonstrate Radiology small group teaching significantly improved Anatomy scores for medical students in the summative end of year examination. ADVANCES IN KNOWLEDGE: No evidence in the literature that Radiology teaching improves examination outcomes for medical students.This is the first study to directly link Radiology teaching with improved Anatomy examination result.Small group teaching in Radiology is a feasible way to teach Anatomy.


Subject(s)
Anatomy/education , Education, Medical, Undergraduate , Educational Measurement , Radiology/education , Curriculum , Female , Humans , Male , Scotland , Young Adult
7.
Br J Radiol ; 93(1112): 20200380, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32463292

ABSTRACT

OBJECTIVE: Rising clinical demand and changes to Radiologists' job plans mean it is becoming ever more difficult for Radiologists to teach medical students.The aim of this study was to assess the current role of Radiologists in undergraduate medical education in Scotland. METHODS: Consultant Radiologists working across all 14 Scottish Health Boards were invited by email to participate in an anonymous short online survey. The survey ran for 6 weeks from November 2019. One reminder email was sent a week before the survey closed. RESULTS: 102 responses were recorded, representing 34% of the total whole time equivalent Radiologists in Scotland. All agreed Radiology should be taught to medical students. Over 70% (n = 73) taught medical students, most often during supporting professional activity time. 76 percent of Radiologists who did not teach expressed a desire to do so. The most common barrier to teaching was not having enough time in their job plan. Scottish Radiologists delivered a median of 10 h (IQR 0-22) a year of teaching to medical students. Thematic analysis of free comments revealed staffing/time constraints severely limiting ability to teach. CONCLUSION: This is the first national survey to assess the current role of Radiologists in teaching medical students. While most are teaching or want to teach, there is a large drop-off between current Scottish and previously reported UK median teaching hours. Engagement from Universities, Royal College of Radiologists and Health Boards is urgently needed to reverse this trend. ADVANCES IN KNOWLEDGE: This is the first national survey into the current role of Radiologists in undergraduate medical education. There is a large drop-off between current Scottish and previously reported UK median teaching hours.


Subject(s)
Education, Medical, Undergraduate/statistics & numerical data , Teaching/statistics & numerical data , Adult , Female , Humans , Male , Middle Aged , Radiologists/statistics & numerical data , Scotland , Surveys and Questionnaires , Time Factors
8.
Ann Oncol ; 30(11): 1821-1830, 2019 11 01.
Article in English | MEDLINE | ID: mdl-31504139

ABSTRACT

BACKGROUND: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) is a national precision medicine study incorporating centralized genomic testing to direct refractory cancer patients to molecularly targeted treatment subprotocols. This treatment subprotocol was designed to screen for potential signals of efficacy of ado-trastuzumab emtansine (T-DM1) in HER2-amplified histologies other than breast and gastroesophageal tumors. METHODS: Eligible patients had HER2 amplification at a copy number (CN) >7 based on targeted next-generation sequencing (NGS) with a custom Oncomine AmpliSeq™ (ThermoFisher Scientific) panel. Patients with prior trastuzumab, pertuzumab or T-DM1 treatment were excluded. Patients received T-DM1 at 3.6 mg/kg i.v. every 3 weeks until toxicity or disease progression. Tumor assessments occurred every three cycles. The primary end point was centrally assessed objective response rate (ORR). Exploratory end points included correlating response with HER2 CN by NGS. The impact of co-occurring genomic alterations and PTEN loss by immunohistochemistry were also assessed. RESULTS: Thirty-eight patients were enrolled and 36 included in efficacy analysis. Median prior therapies in the metastatic setting was 3 (range 0-9; unknown in one patient). Median HER2 CN was 17 (range 7-139). Partial responses were observed in two (5.6%) patients: one mucoepidermoid carcinoma of parotid gland and one parotid gland squamous cell cancer. Seventeen patients (47%) had stable disease including 8/10 (80%) with ovarian and uterine carcinomas, with median duration of 4.6 months. The 6-month progression-free survival rate was 23.6% [90% confidence interval 14.2% to 39.2%]. Common toxicities included fatigue, anemia, fever and thrombocytopenia with no new safety signals. There was a trend for tumor shrinkage with higher levels of gene CN as determined by the NGS assay. CONCLUSION: T-DM1 was well tolerated. While this subprotocol did not meet the primary end point for ORR in this heavily pre-treated diverse patient population, clinical activity was seen in salivary gland tumors warranting further study in this tumor type in dedicated trials.


Subject(s)
Ado-Trastuzumab Emtansine/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Biomarkers, Tumor/genetics , Neoplasms/drug therapy , Receptor, ErbB-2/genetics , Ado-Trastuzumab Emtansine/pharmacology , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Immunological/pharmacology , Drug Resistance, Neoplasm/genetics , Female , Gene Amplification , Humans , Middle Aged , National Cancer Institute (U.S.) , Neoplasms/genetics , Neoplasms/mortality , Neoplasms/pathology , Precision Medicine/methods , Progression-Free Survival , Receptor, ErbB-2/antagonists & inhibitors , United States/epidemiology
9.
Ann Oncol ; 28(2): 354-361, 2017 02 01.
Article in English | MEDLINE | ID: mdl-27998964

ABSTRACT

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Pancreatic Ductal/drug therapy , Pancreatic Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Dasatinib/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Double-Blind Method , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Pancreatic Neoplasms/mortality , Pancreatic Neoplasms/pathology , Proportional Hazards Models , Treatment Outcome , Gemcitabine
10.
Hernia ; 18(5): 701-4, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25038894

ABSTRACT

PURPOSE: Mesh infection following incisional hernia repair has been reported at around 6-10 %. The aim of this study is to assess the outcome of patients following treatment for chronically infected mesh after repair of an abdominal wall hernia. METHODS: Data were gathered on all patients with chronically infected mesh following failed conservative management treated under the care of one surgeon between January 2004 and December 2010. This included patient demographics, reason for first operation, number of previous operations and the number of previous hernia repairs. In addition, the type of mesh removed was recorded as was the organism cultured from the wound. Patients were followed up in a clinic at 1 month, 3 months and 1 year after surgery. RESULTS: 15 patients had 18 operations under general anaesthesia for infected mesh (10 partial and 8 complete mesh excisions). The interval between the last mesh implantation or abdominal operation and re-operation for infection was a median of 17 months (range 7-49 months). All patients who had complete mesh removal had complete healing of their wound at 3 months compared with four in the partial excision group (P = 0.011). At a median follow-up of 19 months, only five in the complete and three in the partial excision group had complete wound healing (P = 0.184). CONCLUSION: The outcome of patients treated for chronic mesh infection is unsatisfactory with high risk of recurrent herniation and development of further chronic abdominal wall sepsis; therefore, every effort should be made to prevent this problem in the first instance.


Subject(s)
Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Surgical Mesh/microbiology , Abdominal Wall/surgery , Adult , Aged , Chronic Disease , Female , Hernia, Ventral/etiology , Humans , Male , Middle Aged , Prosthesis-Related Infections/etiology , Recurrence , Reoperation , Treatment Outcome
11.
Ann Oncol ; 24(12): 3061-5, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24146220

ABSTRACT

BACKGROUND: Current data suggest that chemotherapy combinations may be superior to single agents in biliary tract cancer. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan. PATIENTS AND METHODS: Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate organ function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m(2)) and irinotecan (100 mg/m(2)) on days 1 and 8 of a 21-day cycle. The primary objective was to evaluate the 5-month progression-free survival (PFS). Secondary objectives included overall response rate (ORR) and overall survival (OS). Mutational analyses of EGFR, KRAS and BRAF were carried out when feasible. RESULTS: Thirty-five patients received a median of 7 (0-30) cycles. The most common grade 3/4 toxic effects were neutropenia (10 patients, 29%), thrombocytopenia (10 patients, 29%), skin rash (13 patients, 37%) and dehydration (9 patients, 26%). Two patients had CR, 9 had partial response (PR), and 15 had SD for a disease-control rate of 74% (by RECIST) in 28 assessable patients. Two patients went on to have surgical resection. The 5-month PFS was 69%. The median PFS was 9.7 months and the median OS was 12.9 months. In 17 testable samples, no EGFR or BRAF mutations were identified; there were 7 KRAS mutations, with no difference in OS by KRAS status. CONCLUSIONS: This study showed encouraging efficacy of this regimen with good tolerability. Further study in this area is warranted. Clinical Trials Number: The trial was registered with the National Cancer Institute (www.clinicaltrials.gov identifier NCT00948935).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bile Duct Neoplasms/drug therapy , Cholangiocarcinoma/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/administration & dosage , Bile Duct Neoplasms/genetics , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Cholangiocarcinoma/genetics , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , DNA Mutational Analysis , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Irinotecan , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Staging , Panitumumab , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Treatment Outcome , ras Proteins/genetics , Gemcitabine
12.
Hernia ; 17(5): 669-72, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23563741

ABSTRACT

CASES: Two cases of desmoid-type fibromatosis developing after laparoscopic hernia repair are described: one in a young male 3 years after laparoscopic umbilical hernia repair and the other in a young female 1 year after laparoscopic incisional hernia repair. FINDINGS: The male patient presented with a slowly enlarging non-tender firm abdominal wall mass; the female patient had similar findings. Excision biopsy in the male and core biopsy in the female were consistent with fibromatosis. TREATMENT: The young male patient underwent resection of the fibromatosis, and the female patient has been managed conservatively. RELEVANCE TO CURRENT KNOWLEDGE: These are the first documented cases of fibromatosis developing after laparoscopic hernia surgery. Whilst the safety of hernia meshes has been assessed in animal studies, it may be that more detailed study of intraperitoneal placement of these meshes is required.


Subject(s)
Fibromatosis, Abdominal , Hernia, Ventral/surgery , Herniorrhaphy/adverse effects , Laparoscopy/adverse effects , Postoperative Complications , Abdominal Wall/pathology , Abdominal Wall/physiopathology , Abdominal Wall/surgery , Adult , Biopsy , Female , Fibromatosis, Abdominal/etiology , Fibromatosis, Abdominal/pathology , Fibromatosis, Abdominal/physiopathology , Fibromatosis, Abdominal/surgery , Hernia, Ventral/physiopathology , Herniorrhaphy/instrumentation , Herniorrhaphy/methods , Humans , Laparoscopy/instrumentation , Laparoscopy/methods , Magnetic Resonance Imaging/methods , Male , Postoperative Complications/pathology , Postoperative Complications/physiopathology , Postoperative Complications/surgery , Surgical Mesh/adverse effects , Treatment Outcome , Ultrasonography/methods
13.
Clin Radiol ; 68(8): 776-9, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23587476

ABSTRACT

AIMS: To ascertain prospectively the health service cost of vertebroplasty in a cohort of consecutive patients with spinal metastases. MATERIALS AND METHODS: Percutaneous vertebroplasty was performed under conscious sedation and local anaesthetic in the Interventional Suite with fluoroscopic guidance. Data were collected prospectively on standard forms. Quality of life questionnaires (EQ-5D) were filled out pre-, 6 weeks, and at 6 months post-vertebroplasty. RESULTS: The majority of the procedures were performed on an outpatient basis (8/11). The median duration of the procedure was 60 min (range 40-80 min) with a further 60 min spent in the recovery room (range 10-230 min). Personnel involved included a consultant radiologist, a radiology registrar, four nurses, and two radiographers. The average cost of vertebroplasty per patient, including consumables, capital equipment, hotel/clinic costs, and staffing, was £2213.25 (95% CI £729.95). The mean EQ-5D utility scores increased from 0.421 pre-treatment to 0.5979 post-treatment (p = 0.047). The visual analogue scale (VAS) of perceived health improved from a mean of 41.88 to 63.75 (p = 0.00537). CONCLUSION: Health service costs for percutaneous vertebroplasty in patients with spinal metastases is significantly lower than previously estimated and is in keeping with that of other palliative radiological procedures.


Subject(s)
Health Care Costs , Spinal Neoplasms/secondary , Spinal Neoplasms/surgery , Vertebroplasty/economics , Ambulatory Care/economics , Anesthesia, Local/economics , Conscious Sedation/economics , Cost-Benefit Analysis , Humans , Length of Stay/statistics & numerical data , Prospective Studies , Quality-Adjusted Life Years , Radiography, Interventional/economics , Surveys and Questionnaires , Time Factors , United Kingdom
14.
Surgeon ; 10(6): 309-13, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22123434

ABSTRACT

AIMS: To analyse the outcome of patients with gastrointestinal stromal tumour (GIST) who receive imatinib therapy and undergo subsequent resection of focally progressive disease. METHODS: We reviewed the records of all cases of GIST discussed at the West of Scotland Sarcoma regional multi-disciplinary team meeting between January 2002 and December 2009 inclusive. We analysed all patients who had undergone surgery for progressive disease on imatinib therapy. Focally progressive disease was diagnosed on computated tomography (CT) and positron-emission tomography-CT and was defined by a GIST lesion initially responsive to imatinib therapy but then underwent growth with evidence of metabolic activity. All procedures were undertaken in a university teaching hospital by a single surgeon. RESULTS: Nine patients were identified who underwent ten resections of focally progressive GIST. Six had previously undergone resection of their primary tumour while three had presented with un-resectable disease. Nine operations were for resection of a solitary progression while one operation was for three foci of progression. Five patients underwent liver resection which was confined to the segments were there was focal progression of GIST; of these one patient had multiple liver metastases and portal hypertension with a mass at the porta hepatis. The absolute survival for patients after resection was 18.4±13.7 months (mean±standard deviation), with progression free survival of 14.1±13.5 months equating to 56% at 1-year. Four patients had been switched from imatinib to sunitinib, for further multi-focal progression. CONCLUSIONS: Surgical resection of focally progressive GIST may prolong survival and a second or third resection is a feasible option in selected patients.


Subject(s)
Benzamides/therapeutic use , Digestive System Surgical Procedures/methods , Drug Resistance, Neoplasm , Gastrointestinal Stromal Tumors/surgery , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Antineoplastic Agents/therapeutic use , Disease-Free Survival , Female , Follow-Up Studies , Gastrointestinal Stromal Tumors/drug therapy , Humans , Imatinib Mesylate , Male , Middle Aged , Retrospective Studies , Treatment Outcome
15.
Clin Radiol ; 66(12): 1193-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21968026

ABSTRACT

AIM: To assess patient outcome in a consecutive series of patients with myeloma and spinal metastases who underwent percutaneous vertebroplasty. MATERIALS AND METHODS: Data were gathered prospectively on all patients undergoing percutaneous vertebroplasty between June 2001 and June 2010. Outcome measures included visual analogue pain scores (VAS) and Roland-Morris Questionnaire (RMQ) in patients treated since 2005 as well as complications and long-term outcome in all patients. RESULTS: One hundred and twenty-eight patients underwent percutaneous vertebroplasty for myeloma (n=41) or spinal metastases (n=87) over a 9 year period. VAS scores fell from 7.75 ± 1.88 pre-vertebroplasty to 4.77 ± 2.69 post-vertebroplasty (p=0.001). RDQ scores improved from 18.55 ± 4.79 to 13.5 ± 6.96 (p=0.001). Complications were recorded in three patients: cement extension to vena cava (n=1), local haematoma (n=1), and loss of sensation over T1 dermatome (n=1). The Kaplan-Meier estimate of 5 year survival post-vertebroplasty was 40% for patients with myeloma and 25% for those with metastases. CONCLUSION: This large prospective study demonstrates percutaneous vertebroplasty reduces pain and improves disability in patients from intractable pain from myeloma or spinal metastases and now forms an important part of the multimodality treatment for these patients.


Subject(s)
Bone Cements/therapeutic use , Multiple Myeloma/pathology , Pain, Intractable/etiology , Polymethyl Methacrylate/therapeutic use , Spinal Neoplasms/secondary , Vertebroplasty/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/surgery , Pain Measurement , Prospective Studies , Radiography , Spinal Neoplasms/complications , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/surgery , Surveys and Questionnaires , Treatment Outcome
16.
Br J Surg ; 98(4): 596-9, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21656724

ABSTRACT

BACKGROUND: Up to one-third of patients with an inguinal hernia have no symptoms from the hernia. The aim of this study was to determine the long-term outcome of patients with a painless inguinal hernia randomized to observation or operation. METHODS: Some 160 men aged 55 years or more with a painless inguinal hernia were randomized to observation or operation between 2001 and 2003. All were invited to attend a research clinic at 6 and 12 months, and 5 years after randomization. Those unable to attend for clinical review were sent a questionnaire based on the clinical review pro forma. RESULTS: After a median follow-up of 7.5 (range 6.2-8.2) years, 42 men had died (19 in the observation and 23 in the operation group); 46 of the 80 men randomized to observation had conversion to operation. The estimated conversion rate (using the Kaplan-Meier method) for the observation group was 16 (95 per cent confidence interval 9 to 26) per cent at 1 year, 54 (42 to 66) per cent 5 years and 72 (59 to 84) per cent at 7.5 years. The main reason for conversion was pain in 33 men, and two presented with an acute hernia. Sixteen men developed a new primary contralateral inguinal hernia and three had recurrent hernias. There have been 90 inguinal hernia repairs in the 80 patients randomized to surgery compared with 56 in those randomized to observation. CONCLUSION: Most patients with a painless inguinal hernia develop symptoms over time. Surgical repair is recommended for medically fit patients with a painless inguinal hernia.


Subject(s)
Hernia, Inguinal/surgery , Watchful Waiting , Aged , Aged, 80 and over , Cross-Over Studies , Follow-Up Studies , Hernia, Inguinal/mortality , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pain/etiology , Recurrence , Treatment Outcome
17.
Br J Cancer ; 104(12): 1862-8, 2011 Jun 07.
Article in English | MEDLINE | ID: mdl-21610706

ABSTRACT

BACKGROUND: This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo. METHODS: A total of 33 patients with retinoblastoma protein-positive advanced solid tumours or non-Hodgkin's lymphoma refractory to standard therapy or for which no therapy was available received PD 0332991 once daily (QD) for 14 days followed by 7 days off treatment (21-day cycles; Schedule 2/1). RESULTS: Six patients had DLTs (18%; four receiving 200 mg QD; two receiving 225 mg QD); the MTD was 200 mg QD. Treatment-related, non-haematological adverse events occurred in 29 patients (88%) during cycle 1 and 27 patients (82%) thereafter. Adverse events were generally mild-moderate. Of 31 evaluable patients, one with testicular cancer achieved a partial response; nine had stable disease (≥10 cycles in three cases). PD 0332991 was slowly absorbed (mean T(max) 4.2 h) and eliminated (mean half-life 26.7 h). Volume of distribution was large (mean 3241 l) with dose-proportional exposure. Using a maximum effective concentration model, neutropenia was proportional to exposure. CONCLUSION: PD 0332991 was generally well tolerated, with DLTs related mainly to myelosuppression. The MTD, 200 mg QD, is recommended for phase II study.


Subject(s)
Cyclin-Dependent Kinases/antagonists & inhibitors , Neoplasms/drug therapy , Piperazines/administration & dosage , Pyridines/administration & dosage , Adult , Aged , Drug Administration Schedule , Female , Humans , Lymphoma, Non-Hodgkin/drug therapy , Male , Maximum Tolerated Dose , Middle Aged , Piperazines/adverse effects , Piperazines/pharmacokinetics , Pyridines/adverse effects , Pyridines/pharmacokinetics , Retinoblastoma Protein/analysis
18.
Colorectal Dis ; 13(5): 583-7, 2011 May.
Article in English | MEDLINE | ID: mdl-20163424

ABSTRACT

AIM: C-reactive protein (CRP) may be useful in predicting postoperative complications [1]. We investigated the sensitivity and specificity of postoperative CRP for infective complications after elective colorectal surgery. METHOD: One hundred and sixty consecutive patients (72 years old; interquartile range, 63-79) undergoing elective resection for colorectal cancer treated between September 2003 and October 2006 were studied. Details of the postoperative course were prospectively entered into a database. Of the 160 patients, 10 had incomplete CRP data and were excluded from further analysis. RESULTS: Infective complications occurred in 21%, with an overall complication rate of 29%. Infective complications occurred as follows: respiratory (10), wound (9), urinary tract (2) and central line infection (1), anastomotic leakage (5), intra-abdominal abscess (3) and septicaemia of unknown origin (2). There were three postoperative deaths. The positive predictive value for infection of CRP > 145 mg/l on postoperative day 4 was 61%. The negative predictive value of CRP < 145 mg/l on postoperative day 4 for an infective complication was 96%. CONCLUSION: A CRP > 145 mg/l on day 4 has high specificity and sensitivity for infective complications following elective colorectal resection.


Subject(s)
C-Reactive Protein/metabolism , Colectomy/adverse effects , Infections/etiology , Infections/metabolism , Aged , Biomarkers/metabolism , Female , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/metabolism , Predictive Value of Tests , Sensitivity and Specificity
19.
Clin Radiol ; 66(1): 63-72, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21147301

ABSTRACT

AIM: To establish the efficacy and complications associated with vertebroplasty in spinal metastases and myeloma. MATERIALS AND METHODS: A literature search was performed from inception to April 2010. Thirty relevant studies were identified. Only one was a randomized, controlled trial and seven were prospective studies. Nine hundred and eighty-seven patients aged between 45 and 72 years were included in this systematic review. RESULTS: Most studies report performing the procedure under local anaesthetic and continuous fluoroscopic screening, and only two centres reported treating more than four vertebrae per session. Five deaths were attributable to vertebroplasty, with a further 19 patients suffering a serious complication related to the procedure. There is some evidence to suggest that the complication rate may be related to the higher cement volume used, although the data are not robust enough for meta-analysis. Pain reduction ranged between 47-87%, similar to the results for osteoporosis. There was no correlation between pain reduction and cement volume. CONCLUSION: This systematic review reveals the paucity of good-quality, robust data available on the subject of percutaneous vertebroplasty in malignancy. It also highlights the apparent high risk of serious complication (2%). Further research into the subject is required in this group of patients.


Subject(s)
Multiple Myeloma/surgery , Spinal Neoplasms/surgery , Vertebroplasty/methods , Aged , Humans , Middle Aged , Multiple Myeloma/diagnostic imaging , Multiple Myeloma/secondary , Palliative Care , Radiography , Randomized Controlled Trials as Topic , Spinal Neoplasms/diagnostic imaging , Spinal Neoplasms/secondary , Treatment Outcome , Vertebroplasty/adverse effects
20.
Surgeon ; 8(1): 9-14, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20222397

ABSTRACT

BACKGROUND: Perioperative haemodynamic changes are well recognised sequelae of adrenalectomy for phaeochromocytomas. The aim of this study was to compare haemodynamic changes in patients undergoing laparoscopic adrenalectomy (LA) for phaeochromocytomas and other adrenal tumours. METHOD: Patients were identified from a prospective database (Jan 1999-Feb 2008). All patients were managed by a multi-disciplinary team. Haemodynamic variables were: pulse, blood pressure and the requirement of antihypertensive or vasopressor therapies in the perioperative period. RESULTS: Over the nine-year period, 34 consecutive patients underwent laparoscopic phaeochromocytoma resection (one patient had delayed contralateral LA) and 104 consecutive patients underwent LA for other tumours (two patients had delayed contralateral LA). 5 out of 35 resections in the phaeochromocytoma group experienced severe hypertension (systolic blood pressure (SBP) >200 mm Hg) compared to two out of 106 resections in the non phaeochromocytoma group (p=0.010). No patient in either group had a transient or persistent (>10 min) SBP >220 mm Hg. Intraoperative antihypertensive use was significantly increased in the phaeochromocytoma group (p<0.005). There were no significant differences between groups for persistent hypotension (SBP <80 mm Hg), heart rate >120/min and recovery room haemodynamic parameters. CONCLUSION: LA for phaeochromocytoma can be accomplished with low perioperative haemodynamic complications when compared to LA for other adrenal tumours.


Subject(s)
Adrenal Gland Neoplasms/physiopathology , Adrenalectomy/methods , Hemodynamics/physiology , Laparoscopy , Pheochromocytoma/physiopathology , Adrenal Gland Neoplasms/pathology , Adrenal Gland Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pheochromocytoma/pathology , Pheochromocytoma/surgery , Preoperative Period , Prognosis , Retrospective Studies , Young Adult
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