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Biomedical subjects

W R Lees

Publications and source records attributed to W R Lees.

At least 19 recordsLinked to original sources

Photodynamic therapy using meso tetra hydroxy phenyl chlorin (mTHPC) in early prostate cancer.

BACKGROUND AND OBJECTIVES: Prostate cancer is increasing in incidence, but current treatments including surgery and radiotherapy have significant side effects. This pilot study was designed to assess the potential of photodynamic therapy (PDT) using meso tetra hydroxy phenyl chlorin (mTHPC) for organ confined prostate cancer. STUDY DESIGN/PATIENTS AND METHODS: Six men with organ confined prostate cancer were photosensitised with mTHPC (0.15 mg/kg). Between 2 and 5 days later, red light (652 nm) was delivered to areas of biopsy proven cancer via fibres inserted through transperineal needles (50-100 J per site). RESULTS: After 8 of 10 PDT sessions, the prostate specific antigen (PSA) fell by up to 67%. Early MRI scans showed oedema and patchy necrosis, which resolved over 2 months. Biopsies of treated areas revealed necrosis and fibrosis at 1-2 months. CONCLUSIONS: PDT for primary prostate cancer appears safe and can reduce PSA levels. As this was a phase I study, no attempt was made to treat the whole prostate; this or targeted tumour ablation could be attempted in a phase II study with an increased number of fibres. This technique merits further investigation in early prostate cancer.

Aged↗

Diagnosing pancreatic cancer: the role of percutaneous biopsy and CT.

AIMS: To determine the sensitivity and complications of percutaneous biopsy of pancreatic masses, and whether typical computed tomography (CT) features of adenocarcinoma can reliably predict this diagnosis. MATERIALS AND METHODS: A 5 year retrospective analysis of percutaneous core biopsies of pancreatic masses and their CT features was undertaken. Data were retrieved from surgical/pathology databases; medical records and CT reports and images. RESULTS: Three hundred and three patients underwent 372 biopsies; 56 of 87 patients had repeat biopsies. Malignancy was diagnosed in 276 patients, with ductal adenocarcinoma in 259 (85%). Final sensitivity of percutaneous biopsy for diagnosing pancreatic neoplasms was 90%; for repeat biopsy it was 87%. Complications occurred in 17 (4.6%) patients, in three of whom the complications were major (1%): one abscess, one duodenal perforation, one large retroperitoneal bleed. CT features typical of ductal adenocarcinoma were: hypovascular pancreatic mass with bile and/or pancreatic duct dilatation. Atypical CT features were: isodense or hypervascular mass, calcification, non-dilated ducts, cystic change, and extensive lymphadenopathy. Defining typical CT features of adenocarcinoma as true-positives, CT had a sensitivity of 68%, specificity of 95%, positive predictive value (PPV) of 98%, and negative predictive value of 41% for diagnosing pancreatic adenocarcinoma. CONCLUSION: Final sensitivity of percutaneous biopsy for establishing the diagnosis was 90%. CT features typical of pancreatic adenocarcinoma had high specificity and PPV. On some occasions, especially in frail patients with co-morbidity, it might be reasonable to assume a diagnosis of pancreatic cancer if CT features are typical, and biopsy only if CT shows atypical features.

Adenocarcinoma↗

Diagnosis of duct disruption and assessment of pancreatic leak with dynamic secretin-stimulated MR cholangiopancreatography.

OBJECTIVE: The management of pancreatic duct disruption is complex and depends on several factors including the cause, morphology, and degree of disruption. ERCP can show duct disruption in as many as 75% of patients but is invasive and cannot detect disruption beyond an obstruction. We studied the role of secretin MR cholangiopancreatography in patients with suspected pancreatic duct disruption. CONCLUSION: Secretin MR cholangiopancreatography is a safe, noninvasive test that can provide additional useful information about duct integrity and facilitate management.

Adolescent↗

Radio-frequency ablation of colorectal liver metastases in 167 patients.

The objective of this paper is to report our results from a prospective study of 167 patients with colorectal liver metastases treated with radio-frequency ablation (RFA). Three hundred fifty-four treatments were performed in 167 patients, 99 males, mean age 57 years (34-87). The mean number of metastases was 4.1 (1-27). The mean maximum diameter was 3.9 cm (1-12). Fifty-one (31%) had stable/treated extra-hepatic disease. Treatments were performed under general anaesthesia using US and CT guidance and single or cluster water-cooled electrodes (Valleylab, Boulder, CO). All patients had been rejected for or had refused surgical resection. Eighty percent received chemotherapy. Survival data were stratified by tumour burden at the time of first RFA. The mean number of RFA treatments was 2.1 (1-7). During a mean follow-up of 17 months (0-89), 72 developed new liver metastases and 71 developed progressive extra-hepatic disease. There were 14/354 (4%) major local complications and 22/354 (6%) minor local complications. For patients with < or =5 metastases, maximum diameter < or =5 cm and no extra-hepatic disease, the 5-year survival from the time of diagnosis was 30% and from the time of first thermal ablation was 26%. Given that the 5-year survival for operable patients is a median of 32%, our 5-year survival of 30% is promising.

Adult↗

Comparison of resection and radiofrequency ablation for treatment of solitary colorectal liver metastases.

BACKGROUND: Liver resection is the treatment of choice for patients with solitary colorectal liver metastases. In recent years, however, radiofrequency ablation has been used increasingly in the treatment of colorectal liver metastases. In the absence of randomized clinical trials, this study aimed to compare outcome in patients with solitary colorectal liver metastases treated by surgery or by radiofrequency ablation. METHODS: Solitary colorectal liver metastases were treated by radiofrequency destruction in 25 patients. The indications were extrahepatic disease in seven, vessel contiguity in nine and co-morbidity in nine patients. Outcome was compared with that of 20 patients who were treated by liver resection for solitary metastases and had no evidence of extrahepatic disease. Most patients in both groups also received systemic chemotherapy. RESULTS: Median survival after liver resection was 41 (range 0-97) months with a 3-year survival rate of 55.4 per cent. There was one postoperative death and morbidity was minimal. Median survival after radiofrequency ablation was 37 (range 9-67) months with a 3-year survival rate of 52.6 per cent. CONCLUSION: Survival after resection and radiofrequency ablation of solitary colorectal liver metastases was comparable. The latter is less invasive and requires either an overnight stay or day-case facilities only.

Adult↗

Radiofrequency ablation extends the scope of surgery in colorectal liver metastases.

AIMS: To assess outcome in patients treated by a multidisciplinary team, with a combination of liver resection and RF ablation. METHODS: Sixteen unselected patients (f=9; m=7) with colorectal liver metastases who were not suitable for surgery alone, were treated as follows: six had RF ablation at open laparotomy, three patients had synchronous ablation and resection while seven patients had RF ablation after liver resection. Standard liver resection techniques were used. RF was performed using internally cooled, single or cluster electrodes with a high power (200 W) generator. All patients were followed with regular contrast enhanced CT and survival noted. RESULTS: A total of 27 tumours with diameters 1.2-10 cm were treated. Two minor complications were recorded. 2/6 (33%) who had intraoperative RF had incomplete ablation due to large tumour size (6 and 10 cm respectively). Further RF ablation sessions were carried out successfully. 11/16 (69%) are alive at 2 years of whom 7 (44%) have no evidence of residual or recurrent liver disease. CONCLUSION: In our study, RF ablation extends the therapeutic envelope, is an effective local treatment of liver metastases and improves life expectancy.

Aged↗

Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP.

Our objective was to quantify water volume using magnetic resonance cholangiopancreatography (MRCP) sequences and apply this to secretin-stimulated studies with the aim of quantifying pancreatic exocrine function. A commercially available single-shot MRCP sequence was used in conjunction with a body phased-array coil and a 1.5-T MR system. Signal intensity was measured in samples of water, pancreatic, duodenal juice, and secretin-stimulated pancreatic juice. A water phantom was made and MR calculated volumes compared with known water volumes within the phantom. Changes in small intestinal volume in response to secretin were measured in a group of 11 patients with no evidence of pancreatic disease. Changes in water volume were plotted over time. The pancreatic duct diameter before and after secretin was noted and filling defects were sought. All patients also underwent an axial breath-hold T1-weighted gradient-echo sequence and the pancreatic parenchyma was evaluated for size and signal intensity. There was no difference in the signal intensity of the different juice samples. There was excellent correlation between known and calculated MRCP volumes (chi(2)=0.99). All patients demonstrated normal duct morphology on MRCP and normal pancreatic parenchyma on T1-weighted imaging. The mean flow rate in the patient population was 8.1+/-2.5 ml/s over a median of 7 min (range 5-9 min). The MRCP sequence can be used to measure water volume. Sequential MRCP measurements following secretin permitted calculation of volume change and flow rate. This should prove useful as an indicator of pancreatic exocrine function.

Adolescent↗

Dynamic three-dimensional color Doppler ultrasound of human fetal intracardiac flow.

OBJECTIVES: To develop dynamic three-dimensional ultrasound techniques for prenatal imaging of the intracardiovascular flow as well as the cardiovascular structure to address difficulties in assessing the spatially complex hemodynamics and morphology of the fetal heart. METHODS: Gray-scale and color (velocity) Doppler echocardiography were performed on 12 fetuses to provide serial anatomical and rheological tomograms which were spatially registered in three dimensions. Using a second ultrasound machine simultaneously, spectral Doppler ultrasound was performed to record umbilical arterial waveforms, thus providing the temporal (fourth) dimension in terms of the cardiac cycle and facilitating removal of motion artifacts. RESULTS: Acquisitions were successful in eight of 15 attempts. Imaging of the flow of blood in four dimensions was achieved in six of the eight datasets. In one case with complex cardiac malformations, three-dimensional reconstructions at systole and diastole offered dynamic diagnostic views not appreciated on the cross-sectional images. CONCLUSIONS: Our novel technique has made possible the prenatal visualization of the spatial distribution and true direction of intracardiac flow of blood in four dimensions in the absence of motion artifacts. The technique suggests that diagnosis of cardiac malformations can be made on the basis of morphological and hemodynamic changes throughout the entire cardiac cycle, offering unique and significant information complementary to conventional techniques. Further work to integrate the several non-purpose-built machines into a single system will improve the rate of acquisition of data, and may provide a new means of imaging and modeling structure and hemodynamics, not only for the fetal heart but for many other moving body parts.

Coronary Circulation↗

Comparison of B-mode and conventional colour/power Doppler ultrasound, contrast-enhanced Doppler ultrasound and spiral CT in the diagnosis of focal lesions of the liver: Results of a multicentre study.

AIM: In patients with lesions of the liver we compared diagnoses based on different methods of ultrasound as well as spiral CT with the final diagnosis reached at the time of the patient's discharge from hospital. METHOD: From records of a prospective multicentre study including 90 liver lesions investigated with B-mode baseline and conventional colour/power Doppler ultrasound, contrast-enhanced colour/power Doppler ultrasound and spiral-CT, we evaluated only those where diagnoses for all modalities were available, and where the diagnosis at discharge comprising all clinical, laboratory and imaging data as well as histologic proof was at least "highly probable". RESULTS: 60 lesions met the inclusion criteria. 20 lesions were ultimately diagnosed as benign, and 40 as malignant. With respect to the diagnosis of malignancy, sensitivity was 92.5 % (37/40) with B-mode and unenhanced conventional colour/power Doppler US ultrasound, 97.5 % (39/40) with contrast-enhanced colour/ power Doppler ultrasound, and 100 % with CT; the corresponding specificities were 65 % (13/20), 85 % (17/20) and 80 % (16/20). 4 of 7 false positive, and 2 of 3 false negative results in the unenhanced technique were diagnosed correctly with contrast-enhanced Doppler ultrasound. CONCLUSION: Compared to conventional ultrasound, contrast-enhanced Doppler ultrasound improved the diagnostic accuracy in 10 % of the cases. Its accuracy in our study was equal to that of CT.

Contrast Media↗

Photodynamic therapy for cancer of the pancreas.

BACKGROUND: Few pancreatic cancers are suitable for surgery and few respond to chemoradiation. Photodynamic therapy produces local necrosis of tissue with light after prior administration of a photosensitising agent, and in experimental studies can be tolerated by the pancreas and surrounding normal tissue. AIMS: To undertake a phase I study of photodynamic therapy for cancer of the pancreas. PATIENTS: Sixteen patients with inoperable adenocarcinomas (2.5-6 cm in diameter) localised to the region of the head of the pancreas were studied. All presented with obstructive jaundice which was relieved by biliary stenting prior to further treatment. METHODS: Patients were photosensitised with 0.15 mg/kg meso-tetrahydroxyphenyl chlorin intravenously. Three days later, light was delivered to the cancer percutaneously using fibres positioned under computerised tomographic guidance. Three had subsequent chemotherapy. RESULTS: All patients had substantial tumour necrosis on scans after treatment. Fourteen of 16 left hospital within 10 days. Eleven had a Karnofsky performance status of 100 prior to treatment. In 10 it returned to 100 at one month. Two patients with tumour involving the gastroduodenal artery had significant gastrointestinal bleeds (controlled without surgery). Three patients developed duodenal obstruction during follow up that may have been related to treatment. There was no treatment related mortality. The median survival time after photodynamic therapy was 9.5 months (range 4-30). Seven of 16 patients (44%) were alive one year after photodynamic therapy. CONCLUSIONS: Photodynamic therapy can produce necrosis in pancreatic cancers with an acceptable morbidity although care is required for tumours invading the duodenal wall or involving the gastroduodenal artery. Further studies are indicated to assess its influence on the course of the disease, alone or in combination with chemoradiation.

Adenocarcinoma↗

Spiral CT pneumocolon: applications, status and limitations.

CT pneumocolon is a promising new technique in the diagnosis and management of colon pathology. CT pneumocolon can detect (sensitivity >95%) and stage (accuracy 79%) colorectal cancer and is very accurate in the differentiation of malignant from benign colonic pathologies. It has excellent detection rates for polyps >10 mm in diameter. Several studies using 3D virtual colonoscopy have already proven its high sensitivity and specificity in polyp detection making this technique robust as a screening tool. The combined results for virtual colonoscopy, from all centres, show a sensitivity of >85% in the detection of polyps 10 mm or greater in size, 70-80% for 5-9 mm polyps and an overall specificity of 90%. CT pneumocolon is a safe, non-invasive and cost-effective method for detecting colonic carcinomas and adenomas and correctly identifying which patients need further colonoscopy. The technique is quick, well tolerated and non-operator dependent. It can also image the proximal colon when distal stenoses prevent endoscopic and barium examination. CT pneumocolon is able to identify the features and complications of inflammatory bowel disease. Further research is warranted to fully assess its impact in terms of a screening tool, acceptability, availability and cost benefit.

Air↗

Online motion-gated dynamic three-dimensional echocardiography in the fetus--preliminary results.

The aim of this study was to visualise the fetal heart in dynamic three dimensions (4-D) during an ultrasound (US) scan (online), rather than after (offline). With special pairing and sequential setting to minimise interference between two scanners, umbilical arterial Doppler waveforms (UADWs) from one scanner were used as an online motion gating source to trigger simultaneous 3-D cardiac structural data acquisition by another. Of 25 data sets from 10 fetuses, 18 were acquired in 15 to 30 s per set with > or = 50% Doppler waveforms efficiently converted to triggering signals. Of 15 valid 4-D data sets, 10 were reconstructed in 2 to 20 min, compared to over 2 h previously reported (mainly for offline gating). Fine structures (including chordae tendinae and trabecular muscles) were depicted in six sets. The main problems in degrading 4-D images were extensive shadowing (6) from bony structures during rigid mechanical scanning, and random motion artefacts (6) from prolonged setting-up time with a complex combination of several systems. Integration of these systems is, therefore, recommended.

Artifacts↗

Conversion of umbilical arterial Doppler waveforms to cardiac cycle triggering signals: a preparatory study for online motion-gated three-dimensional fetal echocardiography.

To remove motion artefacts, a device was built to convert "noisy" umbilical arterial Doppler waveforms (UADWs) from an ultrasound (US) system into sharp ECG R-wave-like cardiac cycle triggering signals (CCTSs). These CCTSs were then used to gate a simultaneous (online) 3-D acquisition of sectional fetal echocardiograms from another US system. To test the conversion performance, a study was carried out in sheep fetal twins. Pulmonary arterial flow waveforms (PAFWs) from implanted probes were traced, in the meantime, to determine the reference cardiac cycle. Interference caused by running the two nonsynchronised US systems was controlled to three degrees (not-noticeable, moderate, and severe), together with high (> or = 40 cm/s) and low (< 40) flow velocities on UADWs. The conversion efficiency, assessed by the percentage of UADWs converted into CCTSs, was in the range of 83% to 100% for not-noticeable and moderate interference, and 0% to 71% for severe interference. The triggering accuracy, assessed by [(time lag mean between the onsets of PAFWs and corresponding CCTSs) -- (its 99% confidence level)] / the mean, was 90% to 96% for the not-noticeable interference high- and low-flow groups and for the moderate interference high-flow group; 19% to 93% for the moderate interference low-flow group; and from not obtainable up to 90% for the severe interference groups. The results show that UADWs can be used as a satisfactory online motion-gating source even in the presence of moderate interference. The major problems are from severe interference or moderate interference with low-flow velocity, which can be minimised/eliminated by the integration of the individual systems involved.

Animals↗

Multi-slice technology in computed tomography.

Multi-slice systems represent a considerable advance in CT and will assure the future of the technique for many years to come. This article describes this new technology, indicating its provenance and its position in the evolution of CT. While it does not seek to be a physics and engineering text, enough detail of these are given to allow an informed discussion of the many advantages and a few potential problems associated with the technology. A discussion of a number of applications and a brief consideration of contrast enhancement regimens and the possible need for their modification are presented.

Equipment Design↗

Neo-adjuvant therapy improves resectability rates for colorectal liver metastases.

PURPOSE: Liver resection improves survival in selected patients with colorectal liver metastases. However, the majority of patients with colorectal liver metastases have inoperable disease at presentation. Neo-adjuvant therapy (systemic or regional chemotherapy and interstitial laser therapy) used singly or in combination may convert a selected group of patients with irresectable liver metastases into an operable state. PATIENTS AND METHODS: We report a series of patients with initially inoperable multiple colorectal liver metastases who became operable after neo-adjuvant therapy. Operability was defined as unilateral disease limited to the liver. Twelve patients (7 female, 5 male, median age 57 years, range 38-69 years) with multiple inoperable colorectal liver metastases (8 synchronous, 4 metachronous) were initially treated with systemic chemotherapy (n = 7), hepatic arterial chemotherapy (n = 2) and chemotherapy plus interstitial laser therapy (n = 3). RESULTS: In all cases, a significant response was achieved which enabled subsequent liver resection to be undertaken. There was only one postoperative complication (8%) and no peri-operative deaths. 3 patients were operated on within the last 12 months and are still alive. Of the remainder, 1 died within 1 year with recurrent disease. The remaining patients have a median survival of 2.5 years, range 1.39-4 years. CONCLUSIONS: These results are similar to those reported for patients undergoing resection for operable metastases without neo-adjuvant therapy. Aggressive multimodality treatment of colorectal liver metastases in specialised centres may improve the resectability rates and survival in a selected group of patients.

Adult↗

Novel technique for three-dimensional visualisation and quantification of deformable, moving soft-tissue body parts.

BACKGROUND: Three-dimensional (3D) imaging of delicate, moving soft-tissue body parts is very difficult. Our understanding of the muscles that control lip movements is based largely on histological and cadaveric studies, which provide scant information about dynamic morphology. Our aim was to develop an innovative scanning technique for the imaging and reconstruction of dynamic orofacial morphology by use of 3D and four-dimensional (4D, ie, 3D plus time) ultrasonography. METHODS: Four volunteers (including one patient) underwent ultrasonography with 3D/4D imaging systems. To avoid deformation of the delicate orofacial structures, a water bath with an acoustic window was devised. The orofacial part was immersed in the bath throughout scanning, and a timer was used to synchronize lip movements with the 4D scan. FINDINGS: 4D views showed the functional differences in superficial and deep muscle groups of the lips, and clearly showed the changes occurring with movement of the lips and mouth. In the patient, a pathological layer and its extension corresponding to surface malformation were clearly identified. INTERPRETATION: We have developed a prototype device that has made possible 3D and 4D examination of orofacial anatomy and function. With further refinement of the device and improvement in 4D acquisition timing, this technique may offer a new way of dynamically imaging and quantifying many soft-tissue parts in 3D without deforming structure or disturbing function.

Adult↗

Survival after percutaneous, image-guided, thermal ablation of hepatic metastases from colorectal cancer.

PURPOSE: One-year, two-year, three-year, and four-year survival rates and median survival time for patients with inoperable liver metastases from colorectal cancer is 32, 10, and 3 percent and 7.4 to 11 months, respectively. Systemic chemotherapy produces a modest improvement to 48, 21, and 3 percent and 12 months, respectively. Regional chemotherapy produces a further improvement to 64, 25, and 5 percent and 15 to 17 months, respectively. For those with operable disease, hepatic resection survival rates are 90, 62, 48, and 40 percent, respectively, and survival time is 33 months. Thermal ablation is effective in producing necrosis in liver metastases. We report the impact on survival in 69 patients treated from 1993 to 1997, with follow-up to 1998. METHODS: Sixty-nine patients, 50 male, mean age 60 (range, 33-87) years were treated. Liver resection was not feasible because of disease extent in the liver, extrahepatic disease or concurrent medical conditions. The average number of liver metastases was 2.9 (range, 1-16), the mean maximal diameter was 3.9 (range, 1-8) cm, and the mean initial total liver tumor volume was 47 (range, 1-371) ml. Eighteen (26 percent) had undergone previous hepatic resection. Sixty-two of 67 (93 percent) received chemotherapy at some stage. Twenty (29 percent) had extrahepatic disease. RESULTS: One-year, two-year, three-year, and four-year survival rates and median survival time from liver metastasis diagnosis was 90, 60, 34, and 22 percent and 27 months, respectively. Forty of 69 (58 percent) developed new liver metastases, and 23 of 69 (33 percent) developed new extrahepatic disease. Of a subgroup of 24 patients with less than four metastases, <5 cm diameter, treated after January 1995, the median survival time was 33 months from first thermal ablation vs. 15 months for the remainder (P = 0.0004). Major morbidity occurred in 3.2 percent, minor morbidity occurred in 12 percent, and there was one periprocedural death. CONCLUSIONS: Thermal ablation therapy improves survival in patients with inoperable but limited liver metastases. This is an improvement on the natural history of the disease and published chemotherapy results. Recent and ongoing technical refinements, not reflected in these results, are expected to further improve survival.

Adult↗