Single stage management of suspected gallbladder cancer guided by intraoperative frozen section analysis: A retrospective cohort study.

BACKGROUND: The management of radiologically suspected gallbladder cancers (GBC) that lack definitive radiological features usually involves performing a first-stage routine laparoscopic cholecystectomy, followed by an open second-stage liver resection (segments IVB and V) and hilar lymphadenectomy (extended cholecystectomy) if subsequent formal histology confirms a malignancy. Performing a cholecystectomy with an intraoperative frozen section to guide the need for conversion to an extended cholecystectomy as a single-stage procedure has multiple benefits compared to a two-stage approach. However, the safety and efficacy of this approach have not yet been evaluated in a tertiary setting. METHODS: A retrospective cohort study was performed using a database of all consecutive patients with suspected GBC who had been referred to our tertiary unit. Following routine cholecystectomy, depending on the operative findings, the gallbladder specimen was removed and sent for frozen-section analysis. If malignancy was confirmed, the depth of tumour invasion was evaluated, followed by simultaneous extended cholecystectomy, when appropriate. The sensitivity and specificity of frozen section analysis for the diagnosis of GBC were measured using formal histopathology as a reference standard. RESULTS: A total of 37 consecutive cholecystectomies were performed. In nine cases, GBC was confirmed by intraoperative frozen section analysis, three of which had standard cholecystectomy only as their frozen section showed adenocarcinoma to be T1a or below (n=2) or were undetermined (n=1). In the remaining six cases, malignant invasion beyond the muscularis propria (T1b or above) was confirmed; thus, a synchronous extended cholecystectomy was performed. The sensitivity (95% CI 66.4%-100%) and specificity (95% CI 87.7%-100%) for identifying GBC using frozen section analysis were both 100%. The net cost of the single-stage pathway in comparison to the two-stage pathway resulted in overall savings of £3894. CONCLUSION: Intraoperative frozen section analysis is a reliable tool for guiding the use of a safe, single-stage approach for the management of GBC in radiologically equivocal cases. In addition to its lower costs compared to a conventional two-stage procedure, intraoperative analysis also affords the benefit of a single hospital admission and single administration of general anaesthesia, thus greatly enhancing the patient's experience and relieving the burden on waiting lists.

Pancreaticoduodenectomy with right hemicolectomy for advanced malignancy: a single UK hepatopancreaticobiliary centre experience.

AIM: Locally advanced intestinal neoplasms including colon cancer may require radical en bloc pancreaticoduodenectomy and right hemicolectomy (PD-RC) to achieve curative, margin-negative resection, but the safety and benefit of this uncommon procedure has not been established. The Association of Coloproctology of Great Britain and Ireland IMPACT initiative has also highlighted a lack of awareness about current services available within the UK for patients with advanced colorectal cancer and concerns about low-volume centres managing complex cases. Thus, we aimed to review the feasibility, safety and long-term outcomes of this procedure at a single high-volume hepatopancreaticobiliary surgery unit in the UK. METHOD: A retrospective cohort study was performed using a database of all consecutive patients with intestinal cancer who had been referred to our regional advanced multidisciplinary team and undergone PD-RC in a 7-year period (2013-2020). Clinico-pathological and outcome data were reviewed. RESULTS: Ten patients (mean age 54 ± 13, 8/10 men) were identified. Final histology revealed the primary tumour sites were colon (n = 7) and duodenum (n = 3). R0 resection was achieved in all cases. The major complication rate (Clavien-Dindo ≥ 3) was 10% (1/10) with no deaths within 90 days of surgery. The Kaplan-Meier estimated 5-year overall survival was 83.3% (95% CI 58.3%-100%). Univariate survival analysis identified perineural invasion and extra-colonic origin as predictors of poor survival (log-rank P < 0.05). CONCLUSION: En bloc PD-RC for locally advanced intestinal cancer can be performed safely with a high proportion of margin-negative resections and resultant long-term survival in carefully selected patients.

MTL-CEBPA, a Small Activating RNA Therapeutic Upregulating C/EBP-α, in Patients with Advanced Liver Cancer: A First-in-Human, Multicenter, Open-Label, Phase I Trial.

PURPOSE: Transcription factor C/EBP-α (CCAAT/enhancer-binding protein alpha) acts as a master regulator of hepatic and myeloid functions and multiple oncogenic processes. MTL-CEBPA is a first-in-class small activating RNA oligonucleotide drug that upregulates C/EBP-α. PATIENTS AND METHODS: We conducted a phase I, open-label, dose-escalation trial of MTL-CEBPA in adults with advanced hepatocellular carcinoma (HCC) with cirrhosis, or resulting from nonalcoholic steatohepatitis or with liver metastases. Patients received intravenous MTL-CEBPA once a week for 3 weeks followed by a rest period of 1 week per treatment cycle in the dose-escalation phase (3+3 design). RESULTS: Thirty-eight participants have been treated across six dose levels (28-160 mg/m2) and three dosing schedules. Thirty-four patients were evaluable for safety endpoints at 28 days. MTL-CEBPA treatment-related adverse events were not associated with dose, and no maximum dose was reached across the three schedules evaluated. Grade 3 treatment-related adverse events occurred in nine (24%) patients. In 24 patients with HCC evaluable for efficacy, an objective tumor response was achieved in one patient [4%; partial response (PR) for over 2 years] and stable disease (SD) in 12 (50%). After discontinuation of MTL-CEBPA, seven patients were treated with tyrosine kinase inhibitors (TKIs); three patients had a complete response with one further PR and two with SD. CONCLUSIONS: MTL-CEBPA is the first saRNA in clinical trials and demonstrates an acceptable safety profile and potential synergistic efficacy with TKIs in HCC. These encouraging phase I data validate targeting of C/EBP-α and have prompted MTL-CEBPA + sorafenib combination studies in HCC.

Tumor infiltration in the medial resection margin predicts survival after pancreaticoduodenectomy for pancreatic ductal adenocarcinoma.

BACKGROUND: Microscopic tumor involvement (R1) in different surgical resection margins after pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) has been debated. METHODS: Clinico-pathological data for 258 patients who underwent PD between 2001 and 2010 were retrieved from a prospective database. The rates of R1 resection in the circumferential resection margin (pancreatic transection, medial, posterior, and anterior surfaces) and their prognostic influence on survival were assessed. RESULTS: For PDAC, the R1 rate was 57.1% (48/84) for any margin, 31.0% (26/84) for anterior surface, 42.9% (36/84) for posterior surface, 29.8% (25/84) for medial margin, and 7.1% (3/84) for pancreatic transection margin. Overall and disease-free survival for R1 resections were significantly worse than those for R0 resection (17.2 vs. 28.7 months, P = 0.007 and 12.3 vs. 21.0 months, P = 0.019, respectively). For individual margins, only medial positivity had a significant impact on survival (13.8 vs. 28.0 months, P < 0.001), as opposed to involvement in the anterior (19.7 vs. 23.3 months, P = 0.187) or posterior margin (17.5 vs. 24.2 months, P = 0.104). Multivariate analysis demonstrated R0 medial margin was an independent prognostic factor (P = 0.002, HR = 0.381; 95% CI 0.207-0.701). CONCLUSION: The medial surgical resection margin is the most important after PD for PDAC, and an R1 resection here predicts poor survival.

Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma.

BACKGROUND: Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets. METHODS: DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment. RESULTS: DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained. CONCLUSIONS: We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.

Liver resection with bipolar radiofrequency device: Habib 4X.

BACKGROUND: Intraoperative blood loss has been shown to be an important factor correlating with morbidity and mortality in liver surgery. In spite of the technological advances in hepatic parenchymal transection devices, bleeding remains the single most important complication of liver surgery. The role of radiofrequency (RF) in liver surgery has been expanded from tumour ablation to major hepatic resections in the last decade. Habib 4X, a new bipolar RF device designed specifically for liver resection is described here. METHODS: Habib 4X is a bipolar, handheld, disposable RF device and consists of two pairs of opposing electrodes which is introduced perpendicularly into the liver, along the intended transection line. It produces controlled RF energy between the electrodes and the heat produced seals even major biliary and blood vessels and enables resection of the liver parenchyma with a scalpel without blood loss or biliary leak. RESULTS: Three hundred and eleven patients underwent 384 liver resections from January 2002 to October 2007 with this device. There were 109 major resections and none of the patients had vascular inflow occlusion (Pringle's manoeuvre). Mean intraoperative blood loss was 305 ml (range 0-4300) ml, with less than 5% (n=18) rate of transfusion. CONCLUSION: Habib 4X is an additional device for hepatobiliary surgeons to perform liver resections with minimal blood loss and low morbidity and mortality rates.

Repeat hepatic resection using a radiofrequency-assisted technique.

BACKGROUND: Repeat hepatic resection for recurrent primary or secondary liver cancer is performed due to advances in resection techniques and evidence of survival benefit. This paper presents the safety and efficacy of repeat radiofrequency-assisted hepatic resection to highlight the utility of the technique. METHODS: 264 consecutive hepatic resections performed on 218 patients were identified. The subset of patients with recurrent disease (n = 24) suitable for repeat hepatic resection had their records reviewed. RESULTS: Including initial (n = 24), second (n = 24) and third hepatic resection (n = 6), a total of 54 hepatic resections were performed in 24 patients. Non-anatomical resection in the form of metastasectomy was the most common procedure. There were no post-operative deaths. Four patients (17%) had complications after their second resection and 1 (17%) after the third resection. There were no cases of bile leak or liver failure. The proportion of repeat hepatic resection for recurrent disease was high: 50% of recurrences were suitable for further resection after initial resection and 43% after second resection. CONCLUSION: Radiofrequency-assisted repeat hepatic resection is a safe procedure and may increase the proportion of patients who can be considered for a curative repeat hepatic resection.

Prevalence of radiographic osteoarthritis--it all depends on your point of view.

OBJECTIVES: Knee pain and disability in older people may occur in the apparent absence of radiographic osteoarthritis. However, the view chosen to define radiographic osteoarthritis may be critical. We have investigated the prevalence and compartmental distribution of radiographic osteoarthritis in people with knee pain using different combinations of three separate radiographic views. METHODS: We performed a population-based study of 819 adults aged 50 yr and over with knee pain (part of the Clinical Assessment Study - Knee [CAS(K)]). Three radiographic views were obtained: weight-bearing posteroanterior (PA) semiflexed/metatarsophalangeal view; supine skyline; and supine lateral. RESULTS: Complete data for all three views were available on 777 subjects. The distribution of compartmental radiographic osteoarthritis was 314 (40%) combined tibiofemoral/patellofemoral, 186 (24%) isolated patellofemoral, 31 (4%) isolated tibiofemoral and 246 (32%) normal. Hence, the overall prevalence of radiographic osteoarthritis was 531/777 (68.3%) in this symptomatic population. Using a PA view alone (reflecting tibiofemoral osteoarthritis only) would identify 56.7% of the 531, whilst the addition of a skyline or lateral view increased this to 87.0%. When using both skyline and lateral views in addition to the PA view, 98.7% cases of radiographic osteoarthritis were identified. In addition to prevalence, compartmental distribution altered markedly when different combinations of views were used. CONCLUSIONS: Multiple views detect more radiographic osteoarthritis than single views alone. When different combinations of views are used, the prevalence and compartmental distribution of osteoarthritis changes and this may alter the accepted relationship, or lack of it, between symptoms and radiographic change.

An exceptionally bright flare from SGR 1806-20 and the origins of short-duration gamma-ray bursts.

Soft-gamma-ray repeaters (SGRs) are galactic X-ray stars that emit numerous short-duration (about 0.1 s) bursts of hard X-rays during sporadic active periods. They are thought to be magnetars: strongly magnetized neutron stars with emissions powered by the dissipation of magnetic energy. Here we report the detection of a long (380 s) giant flare from SGR 1806-20, which was much more luminous than any previous transient event observed in our Galaxy. (In the first 0.2 s, the flare released as much energy as the Sun radiates in a quarter of a million years.) Its power can be explained by a catastrophic instability involving global crust failure and magnetic reconnection on a magnetar, with possible large-scale untwisting of magnetic field lines outside the star. From a great distance this event would appear to be a short-duration, hard-spectrum cosmic gamma-ray burst. At least a significant fraction of the mysterious short-duration gamma-ray bursts may therefore come from extragalactic magnetars.

Comparative bronchial vasoconstrictive efficacy of inhaled glucocorticosteroids.

The vasoconstrictive efficacies of glucocorticosteroids (GS) are usually compared by the McKenzie skin-blanching test and taken as an index of relative potency. The rationale for the present study was to transpose the McKenzie test to the airway and to compare the airway vascular effects of three inhaled GS: beclomethasone dipropionate (BDP), fluticasone propionate (FP) and budesonide (BUD), in healthy subjects and patients with mild stable asthma. A soluble, inert gas-uptake method was used to measure airway blood flow (Qaw). Baseline mean+/-SD Qaw normalised for anatomical dead space was 53.1+/-1.4 microL x min(-1) x mL(-1) in healthy subjects (n=10) and 67.8+/-3 microL x min(-1) x mL(-1) in asthmatics (n=10). All GS caused a transient decrease in Qaw. The magnitude of the vasoconstriction was greater in asthmatics. The relative vasoconstrictive effect of BDP, FP and BUD was 1, 1.9, and 2.7, respectively, in asthmatics and 1, 3.3 and 3.0, respectively, in healthy subjects, as assessed by the dose required to decrease Qaw by 20%, from the baseline, 30-min postdrug inhalation. Therefore, measuring airway blood flow may be a useful, site-specific parameter to assess the tissue bioavailability and vasoconstrictive efficacy of inhaled glucocorticosteroids.

A regional audit of the prevention and treatment of corticosteroid-induced osteoporosis in patients with rheumatic diseases in the West Midlands.

BACKGROUND: Audit is an important tool in clinical governance. Combining resources from across a region may facilitate data collection and allow variation in practice between individual units to be analysed. This audit is the first such regional audit to be carried out in rheumatology in the West Midlands and the organization and value of regional audit is discussed. This audit assessed the prevention and management of corticosteroid-induced osteoporosis (CIOP). METHODS: Adult patients attending rheumatology follow-up clinics in 10 units, during a 2-week period were assessed using the 1998 National Osteoporosis Society (NOS) guidance on the prevention and management of CIOP. The audit standard adopted was that 80% of eligible patients should be on appropriate therapy. RESULTS: Data was collected on 1766 (95.2%) of 1855 patients during the audit period. Two hundred and thirty-five (13.3%) were currently being prescribed or about to commence >or=7.5 mg daily of oral prednisolone for >or=6 months. Dual X-ray absorptiometry scans were performed in 102 patients (43.4%). Of these, 53 (52%) had a T score of -1.5 or below at the hip or spine. Of the 235 patients, 202 (86%) were receiving osteoporosis treatment. One hundred and forty-eight patients (63%) were receiving appropriate osteoporosis medication according to the NOS 1998 guidelines and 87 (37%) were inappropriately treated. Of these, 71 (81.6%) were under-treated and 16 (18.4%) were over-treated. CONCLUSIONS: Overall, the Region failed to meet the audit standard. The audit highlighted a number of differences and potential problems in the West Midlands with regard to CIOP which are currently being addressed by individual units and the West Midlands Rheumatology Services and Training Committee (WMRSTC). The Committee plan to re-audit in 2 yr.

Elevated tissue expression of hyaluronic acid and hyaluronidase validates the HA-HAase urine test for bladder cancer.

PURPOSE: We examined the expression of 2 bladder tumor markers, hyaluronic acid (HA) and hyaluronidase (HAase), in bladder tissues and correlated tissue staining with the inferences of the HA-HAase urine test, which detects bladder cancer. MATERIALS AND METHODS: A biotinylated HA binding protein and an antiHYAL1 antibody were used to localize HA and HYAL1 type HAase, respectively, in 83 bladder tissues. Immunoblot analysis was performed using an antiHYAL1 antibody to detect HYAL1. RESULTS: A total of 12 normal bladder tissues showed no (66%) to 1+ (34%) HA staining and 0 (83%) to 1+ (17%) HYAL1 staining. The staining intensity of HA and HYAL1 increased in 71 bladder tumor specimens on chi-square analysis (p <0.001). Grade 1 tumors demonstrated 1+ (50%) to 2+ (50%) staining for HA and 1+ to 3+ staining for HYAL1 (37%, 37% and 26%, respectively). Grades 2 and 3 tumors showed 2+ to 3+ HA (94%) and HYAL1 (79%) staining. HA was expressed in tumor associated stroma and in tumor cells, whereas only tumor cells expressed HYAL1. In bladder tumor tissues HYAL1 expression was confirmed by immunoblot analysis. In 33 of the 34 patients (97%) with bladder cancer from whom urine and tumor tissue specimens were obtained at the same time 2+ to 3+ staining of HA and/or HYAL1 in 12 and 21, respectively, constituted a positive HA-HAase urine test (kappa = 0.945). CONCLUSIONS: To our knowledge this is the first report of HA localization in bladder tissues and of HYAL1 in any normal or tumor tissue. A close correlation of elevated HA and HYAL1 levels in tumor tissues with a positive HA-HAase urine test indicates that in patients with bladder cancer tumor associated HA and HYAL1 are secreted in urine, causing the HA-HAase test to be positive.

[Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers]. / Hyaluronsäure und Hyaluronidase. Zwei neue Blasenkarzinommarker.

The heterogeneity of bladder cancer concerning progress of recurrence is an essential characteristic of this disease. Hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are intricately associated with bladder cancer angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine. In 513 urine specimens (261 bladder cancer patients, 252 patients without bladder cancer) and 83 bladder tissue specimens (71 bladder tumors, 12 normal bladder tissues), the accuracy of HA and HAase as tumor markers was studied. Elevated urinary HA levels (> or = 500 ng/ml), indicating a positive HA test, suggest the presence of bladder cancer regardless of tumor grade. Elevated urinary HAase levels (> or = 10 mU/mg) indicate high-grade (G2/G3) bladder cancer. The combined HA-HAase urine test showed 91% sensitivity and 84% specificity to detect bladder cancer. The HA-HAase test is equally sensitive for monitoring tumor recurrence. Immunohistochemistry (IHC) staining of HA and HAase in the G1 and G2/G3 bladder cancer specimens was significantly (p < 0.001) higher than in normal bladder tissue. HA and HAase appear to be useful markers in the diagnosis of bladder cancer. When compared with other noninvasive tests, the HA-HAase urine test may be less expensive and more accurate.

Rubella virus glycoprotein interaction with the endoplasmic reticulum calreticulin and calnexin.

Very little is known about the cellular factors that are required for the maturation of rubella virus glycoproteins (E2 and E1) in the endoplasmic reticulum of the infected cell. In the present study, we established the interaction of the ER chaperone proteins, calreticulin and calnexin, with the RV E1 and E2 proteins in cells stably expressing the viral proteins. The interaction between E2 and calnexin was significantly higher than with calreticulin. In pulse-chase experiments, the half-life of the E2-calnexin was >45 min, whereas the half-life of the calreticulin-E2 interaction was approximately 10 min. Tunicamycin and castanospermine treatments altered the mobilities of intracellular E1 and E2, due to either lack of oligosaccharide ligand addition or trimming of terminal glucose residues, respectively. Further, the drug treatments resulted in a loss of E1 and E2 interaction with calreticulin or calnexin, thereby demonstrating that the interaction is through monoglucosylated forms of RV proteins. These studies suggest that the interaction of RV glycoproteins with the ER chaperone proteins is essential for their maturation in the endoplasmic reticulum.

Collaboration and practice patterns among urologists and gynecologists in the treatment of urinary incontinence and pelvic floor prolapse: a survey of the International Continence Society members.

Both urologists and gynecologists are involved in the care of women with urinary incontinence (UI) and pelvic floor prolapse (PFP). This study was designed to examine the differences among urologists and gynecologists who treat UI and PFP, and to characterize the collaboration between them. A 14-question survey was mailed to the International Continence Society (ICS) members who are urologists or gynecologists. Questions dealt with professional training, type of practice, volume of UI and PFP procedures, preferred procedures for various types of UI and PFP, and the type and extent of collaboration. Of the 666 urologists and gynecologists to whom the questionnaire was sent, 229 responded (34.4% response rate). Among them, 63.7% were urologists and 36.2% were gynecologists. Collaboration in the operating room was reported by 140 responders (50.7%) and was significantly correlated with the specialty, and with the country of practice, with P values of 0.004, and 0.004, respectively. Collaboration in the operating room was reported mainly in procedures for the correction of vaginal vault prolapse or enterocele, and hysterectomy. It was not statistically correlated with the time dedicated to UI and PFP, the volume of surgeries performed, UI and PFP fellowship training, university hospital affiliation, and years in practice. Reasons for not collaborating in the operating room included familiarity with all or most of the anti-incontinence and pelvic floor reconstruction procedures (44.5%), unavailability of the other professional (6.1%), and reimbursement problems (3.1%). While urologists and gynecologists do collaborate extensively in clinical research and diagnosis of challenging cases, surgical collaboration is limited to procedures traditionally performed by gynecologists. Future training programs exposing trainees to both fields of expertise may enable better ground for collaboration and improved care for women with UI and PFP.

Identification of trauma patients at risk of thoracic aortic tear by mechanism of injury.

OBJECTIVE: We sought to identify potential measurable on-scene information that would assist clinicians in the identification of patients at risk for thoracic aortic tear (AT) after vehicular trauma. METHODS: Data were prospectively collected at the scene of 295 motor vehicle crashes from 1995 to 1999. There were 34 cases (12%) with AT. Scene data consisted of vehicle maximal crush, maximal intrusion into the occupant compartment, change in velocity (Delta V) and principal direction of force. Thoracic aortic injuries were confirmed radiographically or at autopsy. Crash factors were analyzed for correlation with AT by logistic regression. RESULTS: Delta V > or = 20 mph and near-side impact were the factors having the strongest correlation with thoracic aortic injury. Delta V > or = 20 mph (n = 32 with AT) had an odds ratio = 6.4, (p < 0.01). Near impact (n = 20 with AT) had an odds ratio = 2.3, (p < 0.05) and intrusion > or = 15 inches had an odds ratio = 3.2, p < 0.05. The sensitivity, specificity, and accuracy of the presence of near impact, Delta V > or = 20 mph, or both, were 100%, 34%, and 64%. The positive and negative predictive values were 16% and 100%, respectively. There was no relationship of AT to use of seat belts or airbags. CONCLUSION: Thoracic aortic injury after vehicular collision can be reliably excluded if near-impact, Delta V > or = 20 mph, or intrusion > or = 15 inches are not present. Mechanism of injury in the form of crash scene information may aid clinicians in identifying individuals at risk for thoracic aortic tear after vehicular trauma.

MR imaging and localized proton spectroscopy of the precentral gyrus in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In the search for a diagnostic test for amyotrophic lateral sclerosis (ALS), especially upper motor neuron (UMN) involvement, MR imaging and proton spectroscopy techniques have each received attention, but their findings have not been correlated. The purpose of this study was to identify relationships among the results of current techniques, taking into account the severity of clinical UMN disease, so that objective measures of the pathogenesis of ALS may be established. METHODS: Eighteen subjects with clinically diagnosed ALS and 12 healthy volunteers underwent MR imaging of the brain and localized proton MR spectroscopy. Water-suppressed spectra from the left precentral gyrus and from the left cuneus gyrus were analyzed with the LCModel method, yielding concentrations for N-acetyl (NA), total creatine (Cr), choline (Cho), glutamate (Glu), glutamine (Gin), and myo-inositol (Ins) metabolic substrates. Signal intensities of the precentral gyrus on T2-weighted images were assessed qualitatively in a blinded fashion. RESULTS: For the precentral gyrus, mean Cho (1.3 mM) and Ins (3.25 mM) for the ALS group were significantly increased. After adjustment for Cr covariance, mean Glu (5.08 mM) and NA (6.31 mM) were decreased. For the cuneus gyrus, no difference in metabolite concentrations between groups was observed. Trend analysis of the precentral gyrus metabolite concentrations revealed significant increases in Cho and Ins and decreases in NA and Glu with respect to the severity of clinical UMN signs. Metabolic changes were greater in the subset of ALS patients with precentral gyrus signal changes on imaging, and significantly increased Ins was associated with cortical hypointensity on fast spin-echo images. CONCLUSION: Mean metabolite concentrations determined from precentral gyrus spectra reflect clinical and pathologic changes that occur in ALS. Imaging findings, while related to the spectral and clinical results, are not specific to ALS.

Deferred treatment of localized prostate cancer in the elderly: the impact of the age and stage at the time of diagnosis on the treatment decision.

OBJECTIVE: To assess the clinical behaviour of clinically localized prostate cancer in elderly patients monitored until progression, and the impact of clinical variables, i.e. clinical stage, Gleason score, the dynamics of prostate specific antigen (PSA) and age, on the natural history of the disease. PATIENTS AND METHODS: Between February 1991 and January 1998, 54 patients (mean age 76.4 years, median 77 at the time of diagnosis) with clinically localized prostate cancer who elected for watchful waiting were identified. They were monitored regularly and treatment deferred until progression. Progression was defined as local stage progression (as assessed on a digital rectal examination), biochemical progression or metastasis. All patients who progressed were offered either radiation therapy or hormonal treatment. Each clinical variable was assessed by univariate and multivariate analysis to predict disease progression. The mean follow-up was 47 months. RESULTS: Of the 54 patients, 28 (52%) progressed; 10 had biochemical, 11 local and four biochemical and local progression, and three developed metastasis. All the patients who progressed elected to receive hormonal treatment. The mean time to progression was 35 months. Gleason score ( 6), age ( 75 years) and serum PSA level ( 10 ng/mL) were statistically significant predictors of disease progression (P = 0.04, < 0.001 and 0.02, respectively). The clinical stage at the time of diagnosis had a borderline effect on disease progression (P = 0.06). On multivariate analysis, Gleason score and PSA level were statistically significant predictors of disease progression. CONCLUSION: These results suggest that the treatment of prostate cancer should not be deferred in patients aged > 75 years with a good performance status when the biopsy has a Gleason score >/= 6 and the serum PSA level is >/= 10 ng/mL.