Biomedical subjects

Y Shyr

Publications and source records attributed to Y Shyr.

At least 55 records · Page 3Linked to original sources

PubMed2000

Early post-prostatectomy pelvic floor biofeedback.

PURPOSE: We determined whether biofeedback enhanced pelvic floor exercises begun 6 weeks after radical prostatectomy improve the early recovery of continence. MATERIALS AND METHODS: We randomized 30 patients who underwent radical retropubic prostatectomy into a group that received 5 biofeedback sessions and a control group. RESULTS: Overall 87% of patients were pad-free at 6 months with similar results in the treatment and control groups (86% versus 88%). There was no statistically significant difference in pad test results or voiding diary records in the 2 groups. CONCLUSIONS: A treatment program of biofeedback enhanced pelvic floor exercises begun 6 weeks after radical retropubic prostatectomy did not significantly affect continence in this study.

Biofeedback, Psychology↗

PubMed1999

National survey on prophylactic cranial irradiation: differences in practice patterns between medical and radiation oncologists.

PURPOSE: Prophylactic cranial irradiation (PCI) in the treatment of small cell lung cancer (SCLC) patients remains controversial in the oncology community because of its potential for long-term toxicity and unproven survival benefit in randomized trials. A national survey of 9176 oncologists was conducted to characterize the use of PCI with regard to physician demographics, patient characteristics, and oncologists' beliefs. METHODS: Data was collected via a questionnaire letter survey. Biographical data, treatment patterns, and clinical impressions were analyzed by the generalized linear model and generalized estimating equations method. RESULTS: There were 1231 responders overall (13.4% of those surveyed), including 628 (51%) radiation oncologists (RO), 587 (48%) medical oncologists (MO), 8 (0.6%) surgical oncologists, and 8 (0.6%) from other oncology subspecialties. Of respondents, 74% overall recommend PCI in limited-stage patients, including 65% of MO and 82% RO (p = 0.001). Of responders who recommend PCI in limited-stage patients, 67% do so only after complete response to initial therapy. Only 30% of respondents recommend PCI for extensive-stage SCLC patients (p = 0.001), and 94% of these recommend PCI only when those patients have a complete response after initial therapy. Interestingly, 38% of responding MO feel that PCI improves survival of limited-stage patients, but only 11% believe PCI improves quality of life. Of the RO, 48% believe PCI improves survival in limited-stage SCLC, and 36% feel PCI improves quality of life (p < 0.05 and p < 0.01, respectively). MO responders believe PCI causes late neurological sequelae more often than do RO responders (95% vs. 84%, p < 0.05), with impaired memory (37%), chronic fatigue (19%), and loss of motivation (13%) as most commonly seen side effects. Only 1.5% overall, however, routinely obtain neuropsychiatric testing in PCI patients, and 42% overall never obtain them. CONCLUSION: Results confirm that oncologic subspecialists have statistically significant differences in opinion regarding the use of PCI. However, these differences may not translate into large differences in clinical practice. Most oncologists continue to recommend PCI in limited-stage SCLC patients, despite many believing PCI may not provide a survival advantage nor improve quality of life.

Brain Neoplasms↗

PubMed1999

The utility of exercise testing after cardiac transplantation in older patients.

BACKGROUND: The criteria for cardiac transplantation recipient selection, including the appropriate recipient upper age limit, continue to expand with an increasing number of recipients greater than 60 years of age. While others have reported their transplant experience in older recipients in terms of quality of life assessment, we have examined the role of exercise cardiopulmonary testing post-transplantation in older cardiac transplant recipients. METHODS: We reviewed inpatient and outpatient charts of 28 patients 60 years of age or older who underwent orthotopic heart transplantation at Vanderbilt University Medical Center. RESULTS: In this population, perioperative mortality of 7.1% and Kaplan-Meier survival at 1 and 5 years of 89 and 77%, respectively, were similar to the institutional 1-year (89%) and 5-year (75%) survival among younger adult transplant recipients. Exercise cardiopulmonary testing results were available in 22/25 patients surviving greater than 1 year. Both peak oxygen consumption and percentage of maximum VO2 were significantly greater among patients reporting NYHA Class 1 or 2 functional status, in comparison with those NYHA Class 3 or greater. CONCLUSION: Following cardiac transplantation, survival of patients greater than 60 years of age is equivalent to that of younger patients at our institution. Exercise testing provides an objective measure of performance and correlates with subjective status following heart transplantation. Most patients demonstrate good functional status, with minimal symptoms and good exercise capacity. These results, although retrospective, suggest that cardiac transplantation remains a reasonable therapeutic option for patients greater than 60 years of age with end-stage cardiomyopathy.

Aged↗

PubMed1999

ACE I/D gene polymorphism predicts renal damage in congenital uropathies.

We investigated angiotensin converting enzyme gene (ACE I/D) polymorphism as a risk for progressive renal damage in congenital uropathies. The ACE I/D genotype was determined in 196 Caucasian patients with congenital uropathies and 163 individuals with no clinical or sonographic evidence of any urological malformations. The study group included patients with ureteropelvic junction obstruction (n=49), primary obstructive megaureter (n=19), primary vesicoureteral reflux (VUR) (n=67), and posterior urethral valves (n=27). Thirty-four patients were excluded because of additional diseases or insufficient follow-up. There was no difference in the ACE I/D distribution between children with uropathies and normal controls (II 16%, ID 56%. DD 28% vs. II 26%, ID 50%, DD 24%). Renal lesions were found in 99 of 162 children by ultrasonography, intravenous pyelography, and nuclear scans. In these children there was significant over-representation of the DD genotype (II 11%, ID 53%, DD 36%) compared with normals (P<0.005, X2=14.9) or with patients with uropathies but no renal lesions (II 23%, ID 62%, DD 15%, P<0.005, X2=14.9). Because ACE I/D has been linked with progressive deterioration of renal function, we evaluated a subset of patients with initially normal kidneys who developed radiographic renal lesions (n=28). Among these patients there was an even greater over-representation of the DD genotype (II 0%, ID 43%, DD 57%, P<0.001, X2=22.6) compared with patients with uropathies but no radiographic lesions. Multivariate analysis revealed that the DD genotype is a risk factor for parenchymal destruction, which was independent of time of diagnosis, surgical intervention, or urinary tract infection. This finding was particularly relevant in patients with VUR who constituted the majority with initially normal kidneys who developed radiographic damage (22/28). Indeed, the odds ratio of developing parenchymal damage with VUR was significantly increased if the individual had the DD genotype (4.2, 95% confidence interval 1.4-13.0). In conclusion the ACE I/D gene polymorphism is a risk factor for renal parenchymal damage in patients with congenital urological abnormalities and appears particularly relevant in children with VUR, where it is an independent predisposing factor.

Adolescent↗

PubMed1999

Laparoscopic cholecystectomy in children: lessons learned from the first 100 patients.

BACKGROUND/PURPOSE: Laparoscopic cholecystectomy is a very common operation in adults but is relatively infrequently required in children. A retrospective review of 100 consecutive infants and children undergoing laparoscopic cholecystectomies from 1990 to 1998 was performed to see what lessons have been learned from this relatively large population of pediatric patients. RESULTS: The patients ranged in age from 25 to 230 months, with a mean of 105 months. Only 19 patients had hemolytic disease as the etiology for their cholelithiasis. Two patients had biliary dyskinesia. Seventy-eight patients underwent an elective operation. Twenty-two children required urgent hospitalization because of complications from their cholelithiasis: acute cholecystitis (n = 7), jaundice and pain (n = 6), gallstone pancreatitis (n = 5), acute biliary colic (n = 4). All 6 patients who presented with jaundice underwent endoscopic retrograde cholangiopancreatography (ERCP) before their laparoscopic cholecystectomy. Two patients required laparoscopic choledochal exploration. The operating time and postoperative hospitalization were significantly longer (P = .0005) in the complicated group when compared with the elective patients. No significant complications such as the need for reoperation, injury to the choledocuhus or to other viscera, bile leak, or retained choledocholithiasis occurred. CONCLUSIONS: Laparoscopic cholecystectomy is a safe, effective procedure in children for removal of the gallbladder. The exact role of routine cholangiography and ERCP remains unclear.

Child↗

PubMed1999

Intradialytic serial vascular access flow measurements.

Hemodialysis vascular access failure represents a major source of morbidity and mortality in chronic hemodialysis (CHD) patients. Serial vascular access blood flow (VABF) measurements are being used as a screening method at an increasing rate. There are limited data on the changes in VABF throughout the hemodialysis session, which may potentially affect the validity of VABF measurement. This study is performed to evaluate the trend in VABF during a given hemodialysis session by serial VABF measurements, along with potential factors that may affect VABF. Thirty-two CHD patients had serial VABF measurements performed during a hemodialysis session. Each patient had three serial VABF measurements during a hemodiaysis treatment (within 30, 90, and 150 minutes from the start of hemodialysis). Mean arterial blood pressure (MAP), ultrafiltration rate, and patient symptoms were recorded simultaneously. The mean VABF was 1,344 +/- 486 mL/min within 30 minutes of hemodialysis and decreased to 1,308 +/- 532 and 1,250 +/- 552 mL/min after 90 and 150 minutes, respectively. This trend was statistically significant (P = 0.03). There was a strong correlation between VABF measurements and MAP, which was more pronounced after 90 minutes of initiation of hemodialysis (r = 0.68; P < 0.001). Using multivariate analysis, it can be predicted that after 90 minutes of hemodialysis, each 10% decrease in MAP would result in an expected decrease of 8% in VABF. There was no effect of type of vascular access, baseline VABF, or amount of ultrafiltration on VABF changes. In conclusion, VABF measurements can be performed up to 2 to 2(1/2) hours from the start of hemodialysis in the majority of patients. The major determinant of VABF changes is MAP. In a subset of patients with a decrease MAP greater than 15%, it is advisable to perform VABF measurement either at the first 90 minutes of hemodialysis or postpone it to another treatment session, when MAP is more stable.

Adult↗

PubMed1999

Immunohistologic evaluation of mechanisms mediating hyperacute lung rejection, and the effect of treatment with K76-COOH, FUT-175, and anti-Gal column immunoadsorption.

Although most investigators agree that lung dysfunction occurs rapidly in various pig-to-primate hyperacute lung rejection (HALR) models, the basic mechanisms mediating this phenomenon remain in question. Here we describe an immunohistochemical method for assessment of mechanisms driving HALR. Using an established model wherein piglet lungs are perfused ex vivo with human blood, six experimental groups (K76 COOH; FUT-175; K76 with FUT; anti-alpha-Gal column adsorption; column with FUT; and column with K76) and two control groups (unmodified human blood; autologous pig blood) were studied. Each lung was biopsied serially during perfusion, and assessed using an immunohistochemical technique, with vWF staining as an internal control to quantitate binding of human IgM, IgG, C3, C5b-9, properdin, and C1q. The effect of each treatment and subsequent lung perfusion on IgG and IgM anti-alpha-Gal titers(by ELISA) and on pig endothelial cell cytotoxicity were correlated with histologic findings. We found that [1] the classical complement activation pathway was activated, as has been shown for other pig organs in primate or human blood environments [2]; alternative complement pathway activation is also seen, which has not been described for other organs in pig-to-primate models, but only in the context of classical pathway activation; and [3] anti-Gal column absorption, pharmacologic inhibition of complement, or combination therapy each was associated with histologic evidence of partial protection, consistent with what would be predicted for each intervention. Further, immunohistologic differences correlated with physiologic outcomes [8] and with antibody assay results, and revealed that treatments used were incompletely effective. Our data suggest that more complete inhibition of antibody- and complement-driven pathways than was achieved in these experiments will be necessary to prevent the antibody and complement-mediated facets of hyperacute lung rejection. This immunohistologic technique may also help us identify additional pathogenic mechanisms important to eventual clinical application of pig-to-human lung xenografts.

Acute Disease↗

PubMed1999

Measurement of the delivery of dialysis in acute renal failure.

BACKGROUND: Recent studies in patients with acute renal failure (ARF) have shown a relationship between the delivered dose of dialysis and patient survival. However, there is currently no consensus on the appropriate method to measure the dose of dialysis in ARF patients. In this study, the dose of dialysis was measured by blood- and dialysate-based kinetic methods in a group of ARF patients who required intermittent hemodialysis. METHODS: Treatments were performed using a Fresenius 2008E volumetric hemodialysis machine with the ability to fractionally collect the spent dialysate. Single-, double-pool, and equilibrated Kt/V were determined from the pre-, immediate post-, and 30-minute post-blood urea nitrogen (BUN) measurements. The solute reduction index was determined from the collected dialysate, as well as the single- and double-pool Kt/V. RESULTS: Forty-six treatments in 28 consecutive patients were analyzed. The mean prescribed Kt/V (1.11 +/- 0.32) was significantly greater than the delivered dose estimated by single-pool (0.96 +/- 0.33), equilibrated (0.84 +/- 0.28), and double-pool (0.84 +/- 0.30) Kt/V (compared with prescribed, each P < 0.001). There was no statistical difference between the equilibrated and double-pool Kt/V (P = NS). The solute removal index, as determined from the dialysate, corresponded to a Kt/V of 0.56 +/- 0.27 and was significantly lower than the single-pool and double-pool Kt/V (each P < 0.001). CONCLUSION: Blood-based kinetics used to estimate the dose of dialysis in ARF patients on intermittent hemodialysis provide internally consistent results. However, when compared with dialysate-side kinetics, blood-based kinetics substantially overestimated the amount of solute (urea) removal.

Acute Kidney Injury↗

PubMed1999

Association of morbidity with markers of nutrition and inflammation in chronic hemodialysis patients: a prospective study.

BACKGROUND: Numerous studies suggest a strong association between nutrition and clinical outcome in chronic hemodialysis (CHD) patients. Nevertheless, the pathophysiological link between malnutrition and morbidity remains to be clarified. In addition, recent evidence suggests that nutritional indices may reflect an inflammatory response, as well as protein-calorie malnutrition. In this study, we prospectively assessed the relative importance of markers of nutritional status and inflammatory response as determinants of hospitalization in CHD patients. METHODS: The study consisted of serial measurements of concentrations of serum albumin, creatinine, transferrin, prealbumin, C-reactive protein (CRP), and reactance values by bio-electrical impedance analysis (BIA) as an indirect measure of lean body mass every 3 months over a period of 15 months in 73 CHD patients. Outcome was determined by hospitalizations over the subsequent three months following each collection of data. RESULTS: Patients who required hospitalization in the three months following each of the measurement sets had significantly different values for all parameters than patients who were not hospitalized. Thus, serum albumin (3.93 +/- 0.39 vs. 3.74 +/- 0.39 g/dl), serum creatinine (11.0 +/- 3.7 vs. 9.1 +/- 3.5 mg/dl), serum transferrin (181 +/- 35 vs. 170 +/- 34 mg/dl), serum prealbumin (33.6 +/- 9.2 vs. 30.0 +/- 10.1 mg/dl), and reactance (50.4 +/- 15.6 vs. 43.0 +/- 13.0 ohms) were higher for patients not hospitalized, whereas CRP (0.78 +/- 0.89 vs. 2.25 +/- 2.72 mg/dl) was lower in patients who were not hospitalized. All differences were statistically significant (P < 0.05 for all parameters). When multivariate analysis was performed, serum CRP and reactance values were the only statistically significant predictors of hospitalization (P < 0.05 for both). When a serum CRP concentration of 0.12 mg/dl was considered as a reference range (relative risk 1.0), the relative risk for hospitalization was 7% higher (relative risk = 1.07) for a CRP concentration of 0.92 mg/dl and was 30% (relative risk = 1.30) higher for a CRP concentration of 3.4 mg/dl. When a reactance value of 70 ohms was considered as a reference range with a relative risk of 1.0, the relative risk of hospitalization increased to 1.09 for a reactance value of 43 ohms and further increased to 1.14 for a reactance value of 31 ohms. CONCLUSIONS: The results of this study strongly indicate that both nutritional status and inflammatory response are independent predictors of hospitalization in CHD patients. CRP and reactance values by BIA are reliable indicators of hospitalization. Visceral proteins such as serum albumin, prealbumin, and transferrin are influenced by inflammation when predicting hospitalization. When short-term clinical outcomes such as hospitalizations are considered, markers of both inflammation and nutrition should be evaluated.

Aged↗

PubMed1999

Cognitive performance at school age of very low birth weight infants with bronchopulmonary dysplasia.

The hypothesis was that bronchopulmonary dysplasia (BPD) adversely affects cognitive performance at school age. This prospective cohort study examined three groups of children at 8 to 10 years of age. Group 1 (n = 311) consisted of very low birth weight (VLBW) infants without BPD and Group 2 (n = 95) consisted of VLBW infants with BPD. Group 3 (n = 188) consisted of term infants without BPD. Regression analysis determined the effect of BPD on eight performance measures while controlling for possible confounding variables. Children in Group 3 had the best performance and children in Group 2 had the poorest performance on all measures. These differences were significant (p = .0001) for the Full Scale IQ, Performance IQ, and reading and math grades and ages. Children in Groups 3 and 1 performed better than children in Group 2 for the Verbal IQ (p = .0001) and the Developmental Test of Visual-Motor Integration (p = .0012), but for these two measures there was no significant difference between children in Groups 3 and 1. Thus, poorer performance was found in VLBW infants with a history of BPD.

Achievement↗

PubMed1999

Reamed intramedullary nailing of the femur: 551 cases.

BACKGROUND: The care of the patient with the fractured femur entails a multiple surgical team approach. Healing of the fracture and expediency in the operating room are both important. We sought to determine the results of the treatment of fractures of the femoral shaft with interlocking femoral nails inserted with closed techniques, and to compare the outcomes of fractures nailed by using a fracture table with those stabilized with the leg draped free on a radiolucent table. METHODS: Eight hundred eighty-two consecutive patients with fractures of the femoral shaft treated with a first-generation intramedullary nail at the authors' institution during the years 1986 to 1996 were identified. Five hundred fifty-one fractures in 515 patients met the inclusion criteria. RESULTS: Treatment with an intramedullary nail led to a union rate of 98.9%. There were six infections, all occurring in closed fractures. Thirty-eight percent of the fractures had hardware removed, most commonly because of pain. One nail and 13 locking bolts broke. Four hundred eighteen fractures had adequate radiographs available to assess fracture alignment. No fracture healed with more than 10 degrees of angulation in either plane. Forty-four fractures healed with more than 5 degrees of angulation. A distal third fracture was found to be associated with an increased incidence of malalignment. There were no differences in outcomes between fractures stabilized with or without a fracture table. CONCLUSION: Reamed intramedullary nailing of femoral shaft fractures results in a low rate of nonunion, malunion, infection, and hardware failure. There is no difference in the outcomes of fractures treated with and without the use of a fracture table. This is particularly useful in the patient with multiple injuries for whom transfer to a fracture table may not be time effective.

Adolescent↗

PubMed1999

Risk factors for hospitalization in well-dialyzed chronic hemodialysis patients.

BACKGROUND/AIMS: Hemodialysis (HD) patients are hospitalized more frequently than patients with other chronic diseases, averaging 11.5 hospital days/patient/year. Hospital costs attributable to renal failure in the US exceed $2 billion per year. The present healthcare climate continues to force dialysis providers to focus on these issues in order to optimize patient care while limiting cost. METHODS: We used a novel method for analyzing hospitalization risk, a multiple-event Cox proportional hazards model, to identify factors that influenced hospitalization in a HD unit population over a two-year period. This model allows individual patients to contribute multiple failure events to the model while controlling for the serial dependency of events. RESULTS: 178 HD patients were retrospectively examined. There were 381 hospitalizations during the study period, averaging out to 1.9 hospitalizations and 10.5 hospital days/patient-year. Substance abuse and diabetes conveyed the largest risks for hospitalization (diabetes RR: 2.09; substance abuse RR: 2.24) in the study cohort, exposing the necessity for examining practice patterns and behavioral interventions as means for improving HD patient care. CONCLUSION: Despite the small numbers of patients in this single-center HD population, the model achieved adequate statistical power. Therefore, it has the potential to serve as a continuous quality improvement (CQI) tool in particular HD patient sub-groups, or in individual HD units.

Female↗

PubMed1999

Pyloric ratio: efficacy in the diagnosis of hypertrophic pyloric stenosis.

We sought to define a weight independent, highly sensitive and specific measurement to diagnose hypertrophic pyloric stenosis. A retrospective review of 87 children was performed. We determined the pyloric ratio (wall thickness/pyloric diameter) and its relationship to weight and compared it to standard criteria. The average pyloric ratios in normal children and in those with hypertrophic pyloric stenosis were 0.205 and 0.325, respectively (P < 0.001). A pyloric ratio of 0.27 yielded a sensitivity and specificity of 96% and 94%, respectively. The pyloric ratio maintained a linear relationship to weight in normal patients and those with hypertrophic pyloric stenosis. We conclude the pyloric ratio can be a highly sensitive, specific, and weight independent indicator of hypertrophic pyloric stenosis.

Female↗

PubMed1999

Esophagitis in combined modality therapy for locally advanced non-small cell lung cancer.

Within the last 10 to 15 years, several randomized trials have validated the importance of chemotherapy in the treatment of locally advanced non-small cell lung cancer and have shown that combined modality therapy improves survival compared with radiotherapy alone. Esophagitis appears to be the primary toxicity, with an increased incidence in combined modality trials. Esophagitis is an inflammatory response of the esophageal mucosa. Treatment with chemotherapy or radiotherapy destroys rapidly dividing cells, such as those in the basal epithelial cell layer. Cell death decreases the renewal rate of the basal epithelium, causing mucosal atrophy, ulceration, and initiation of the inflammatory response. Synergy between chemotherapy and radiotherapy may increase the severity and extent of esophagitis observed with combined modality therapy. Based on Radiation Therapy Oncology Group criteria, the incidence of >/=grade 3 esophagitis following radiation therapy alone or combined modality therapy ranges from less than 5% to 53%. Four sequential, multi-institutional phase I or II studies were conducted during the last 5 years to explore the use of paclitaxel in combined modality therapy for patients with non-small cell lung cancer. In the three phase II trials, esophagitis was the main toxicity, with incidences ranging from 17% to 26% using Radiation Therapy Oncology Group criteria. A multivariate analysis identified a statistically significant correlation between esophageal toxicity and both response to therapy and performance status. Other factors, including gender, age, histology, survival, and length of esophagus within the primary and boost radiation field, were not significantly correlated with esophageal toxicity.

Adult↗

PubMed1999

Acute pancreatitis after cardiac transplantation and other cardiac procedures: case-control analysis in 24,631 patients.

Previous series have identified an increased risk of developing acute postoperative pancreatitis in heart transplant recipients and other cardiac surgical patients, and some suggest that mortality is significantly increased when pancreatitis occurs in the transplant setting. We conducted a retrospective case-control analysis of adult patients undergoing orthotopic heart transplant or other cardiac procedures from April 1985 through June 1996 at our medical center. Specific risk factors for outcome were assessed including low cardiac output, intra-aortic balloon pump usage, exogenous calcium repletion, immunosuppression, cytomegalovirus infection, cholelithiasis, prior pancreatitis, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores. There was a 30-fold increase in the incidence of pancreatitis in the heart transplant group [12 of 394 (3%) vs 27 of 24,237 (0.1%); P < 0.01]. Compared with the nontransplant cardiopulmonary bypass patients, the transplant patients experienced a statistically significant increased incidence of immunosuppression and three or more risk factors. Transplant patients with pancreatitis demonstrated a significant increase in APACHE II scores and the incidence of three or more risk factors compared with their transplant control group. Patients undergoing nontransplant cardiac procedures and developing pancreatitis had significantly increased cross-clamp times, incidence of low cardiac output, APACHE II scores, and incidence of three or more risk factors compared with their nontransplant cohort. In conclusion, there is a significant increase in the incidence of pancreatitis after orthotopic heart transplant compared with other cardiac procedures. Analysis demonstrates the additive effect of multiple individual risk factors. Immunosuppression confers significant additional risk for pancreatitis in the orthotopic heart transplant patient.

APACHE↗

PubMed1999

Optimal interpretation of FDG PET in the diagnosis, staging and management of pancreatic carcinoma.

UNLABELLED: This study had two purposes: to optimize the semiquantitative interpretation of 18F-fluorodeoxyglucose (FDG) PET scans in the diagnosis of pancreatic carcinoma by analyzing different cutoff levels for the standardized uptake value (SUV), with and without correction for serum glucose level (SUV(gluc)); and to evaluate the usefulness of FDG PET when used in addition to CT for the staging and management of patients with pancreatic cancer. METHODS: Sixty-five patients who presented with suspected pancreatic carcinoma underwent whole-body FDG PET in addition to CT imaging. The PET images were analyzed visually and semiquantitatively using the SUV and SUV(gluc). The final diagnosis was obtained by pathologic (n = 56) or clinical and radiologic follow-up (n = 9). The performance of CT and PET at different cutoff levels of SUV was determined, and the impact of FDG PET in addition to CT on patient management was reviewed retrospectively. RESULTS: Fifty-two patients had proven pancreatic carcinoma, whereas 13 had benign lesions, including chronic pancreatitis (n = 10), benign biliary stricture (n = 1), pancreatic complex cyst (n = 1) and no pancreatic pathology (n = 1). Areas under receiver operating characteristic curves were not significantly different for SUV and SUV(gluc). Using a cutoff level of 3.0 for the SUV, FDG PET had higher sensitivity and specificity than CT in correctly diagnosing pancreatic carcinoma (92% and 85% versus 65% and 61%). There were 2 false-positive PET (chronic pancreatitis, also false-positive with CT) and 4 false-negative PET (all with true-positive CT, abnormal but nondiagnostic) examinations. There were 5 false-positive CT (4 chronic pancreatitis and 1 pancreatic cyst) and 18 false-negative CT (all with true-positive FDG PET scans) examinations. FDG PET clarified indeterminate hepatic lesions or identified additional distant metastases (or both) in 7 patients compared with CT. Overall, FDG PET altered the management of 28 of 65 patients (43%). CONCLUSION: FDG PET is more accurate than CT in the detection of primary tumors and in the clarification and identification of hepatic and distant metastases. The optimal cutoff value of FDG uptake to differentiate benign from malignant pancreatic lesions was 2.0. Correction for serum glucose did not significantly improve the accuracy of FDG PET. Although FDG PET cannot replace CT in defining local tumor extension, the application of FDG PET in addition to CT alters the management in up to 43% of patients with suspected pancreatic cancer.

Adenocarcinoma↗

PubMed1999

Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis.

Mouse mammary tumor virus-transforming growth factor alpha (MMTV-TGF alpha) and MMTV-TGF alpha/neu transgenic mice develop mammary tumors after a long latency and therefore provide useful model systems for breast cancer with its recognized activation of receptor tyrosine kinase signaling. We used these mice to study the antitumor effect of L-744,832 (FTI), a potent and selective inhibitor of farnesyl-protein transferase, and hence of Ras function. A total of 55 mice were assigned randomly to treatment with FTI or vehicle, and one-half of the mice were crossed over after initial treatment to the opposite group. L-744,832 induced reversible regression of mammary tumors that was paralleled by a decrease in serum levels of TGF alpha secreted by the tumor cells. There was no difference in response to treatment with FTI between MMTV-TGF alpha mice, in which tumorigenesis was accelerated by multiparity or the chemical carcinogen 7,12-dimethylbenzanthracene, and MMTV-TGF alpha/neu mice. The tumor histological type had no impact on FTI sensitivity. For mechanistic analyses, tumor excision biopsies were obtained from 12 mice before and after treatment with L-744,832. In these samples, tumor regression was paralleled biochemically by inhibition of mitogen-activated protein kinase activity and biologically by an increase in G1-phase and decrease in S-phase fractions, as well as induction of apoptosis. These results suggest that the potential clinical use of FTI could be expanded to include cancers harboring activated receptor tyrosine kinases as well as those containing activated Ras.

Alkyl and Aryl Transferases↗

PubMed1998

Antioxidants reduce cyclooxygenase-2 expression, prostaglandin production, and proliferation in colorectal cancer cells.

Increased expression of cyclooxygenase (COX) and overproduction of prostaglandins (PGs) have been implicated in the development and progression of colorectal cancer (CRC). Recent observations suggest that reactive oxygen intermediates play a role in tumor cell growth regulation and expression of the inducible COX, COX-2. We therefore evaluated the effects of various antioxidants on COX expression and cellular growth in the human CRC cell line HCA-7. The antioxidants pyrrolidinedithiocarbamate (PDTC), N-acetylcysteine, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), and U74006 decreased PG production, intracellular redox status, and cellular growth in a concentration-dependent manner. The decrease in cellular growth was associated with the induction of apoptosis. Unlike the selective COX inhibitors 1-[(4-methylsulfonyl)phenyl]-3-trifluoromethyl-5-[(4-fluoro)phenyl]pyraz ole (SC 58125) and (2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS 398) that inhibit COX-2 catalytic activity, these antioxidants decreased COX-2 expression at the transcriptional level. Combined treatment of HCA-7 cells with PDTC and SC 58125 resulted in an additive decrease in PG levels and anchorage-dependent and -independent growth. Furthermore, whereas antioxidants or SC 58125 reduced tumor growth in vivo, coadministration of PDTC and SC 58125 resulted in actual tumor regression. These results suggest that combined therapy with NSAIDs and antioxidants might be useful in the prevention and/or treatment of CRC.

Animals↗