Biomedical subjects

J K Wright

Publications and source records attributed to J K Wright.

At least 19 recordsLinked to original sources

PubMed2001

Effect of dopamine infusion on hemodynamics after hepatic denervation.

BACKGROUND: . The effects of dopamine (DA) on systemic hemodynamics are better understood than its effects on hepatic hemodynamics, especially after liver denervation occurring during liver transplantation. Therefore, a porcine model was used to study DA's effects on hemodynamics after hepatic denervation. MATERIALS AND METHODS: Fifteen pigs underwent laparotomy for catheter and flow probe placement. The experimental group (n = 7) also underwent hepatic denervation. After 1 week, all pigs underwent DA infusion at increasing doses (3-30 mcg/kg/min) while measuring hepatic parameters [portal vein flow (PVF), hepatic artery flow (HAF), total hepatic blood flow (THBF = HAF + PVF), portal and hepatic vein pressures] and systemic parameters [heart rate (HR), mean arterial pressure (MAP)]. RESULTS: There was a significant increase in HAF from baseline to the 30 mcg/kg/min DA infusion rate (within-subjects P < 0.01), but the differences between the two groups were not significant. PVF and THBF showed large effects (increases) with denervation, but the increase in flow with DA infusion was not present after denervation. Perihepatic pressures were unchanged by denervation or DA. Heart rate differed significantly between the control and denervated animals at baseline, 3, 6, 12 (all P < 0.05), and 30 mcg/kg/min DA (P = 0.10). Control vs denervation MAP at baseline was 100 +/- 4 vs 98 +/- 4 Torr and at 30 mcg/kg/min it was 110 +/- 3 vs 101 +/- 5 mm Hg. CONCLUSIONS: Hepatic flows tended to be higher after denervation. HAF showed similar increases with DA in both control and denervation groups. Increases in PVF and THBF with DA infusion were not present after denervation. HR was significantly decreased and MAP tended to be lower after denervation. The HR and MAP response to DA was similar in both groups. Therefore, both denervation and DA infusion have an effect on systemic and hepatic hemodynamics.

Animals↗

PubMed2000

Effect of dopamine infusion (3-30 microg/kg/min) on hepatic hemodynamics.

BACKGROUND: While dopamine produces well-characterized dose-dependent effects on systemic hemodynamics, there is a paucity of information regarding its effects on hepatic hemodynamics. Infusion rates above 10 microg/kg/min are reported to produce significant vasoconstriction and impair organ perfusion. Therefore, donors are sometimes considered unsuitable when higher doses of dopamine are in use. The aim of this study was to determine the effect of increasing doses of dopamine on hepatic hemodynamics in a nonanesthetized swine model. MATERIALS AND METHODS: Sixteen pigs were instrumented with indwelling catheters in a peripheral artery, peripheral vein, portal vein, and hepatic vein and flow probes around the portal vein and hepatic artery. After recovery, the following variables were measured 10 +/- 1 days postinstrumentation: hepatic arterial flow (HAF), portal venous flow (PVF), mean systemic arterial pressure (MAP), central venous pressure (CVP), portal venous pressure (PVP), hepatic venous pressure (HVP), heart rate (HR). Recordings were obtained at baseline and subsequently when dopamine was infused at rates of 3, 6, 12, 15, 21, and 30 microg/kg/min increasing at 1-h intervals. RESULTS: HAF and PVF increased linearly over the entire infusion range, to 69 and 13% over baseline, respectively (P < 0.001, P < 0.05). Total hepatic blood flow rose 23% over baseline at the 30 microg/kg/min dosage (P < 0.01). MAP increased linearly 13% over the range 12 to 30 microg/kg/min (P < 0.001). CVP, HVP, and PVP did not change significantly. HR decreased from 12 to 15 microg/kg/min (P < 0.01), then increased from 15 to 30 microg/kg/min (P < 0.05). CONCLUSION: These data show that dopamine infused at dosages of 3-30 microg/kg/min augments HAF, PVF, and THBF and that this effect is linear. These results suggest high-dose dopamine infusion does not disqualify a potential donor liver for transplantation.

Animals↗

PubMed2000

Prostaglandins potentiate U-46619-induced pulmonary microvascular dysfunction.

The induction of cyclooxygenase is an important event in the pathophysiology of acute lung injury. The purpose of this study was to examine the synergistic effects of various cyclooxygenase products (PGE(2), PGI(2), PGF(2alpha)) on thromboxane A(2) (TxA(2))-mediated pulmonary microvascular dysfunction. The lungs of Sprague-Dawley rats were perfused ex vivo with Krebs-Henseleit buffer containing indomethacin and PGE(2) (5 x 10(-8) to 1 x 10(-7) M), PGF(2alpha) (7 x 10(-9) to 5 x 10(-6) M), or PGI(2) (5 x 10(-8) to 2 x 10(-5) M). The TxA(2)-receptor agonist U-46619 (7 x 10(-8) M) was then added to the perfusate, and then the capillary filtration coefficient (K(f)), pulmonary arterial pressure (Ppa), and total pulmonary vascular resistance (RT) were determined. The K(f) of lungs perfused with U-46619 was twice that of lungs perfused with buffer alone (P = 0.05). The presence of PGE(2), PGF(2alpha), and PGI(2) within the perfusate of lungs exposed to U-46619 caused 118, 65, and 68% increases in K(f), respectively, over that of lungs perfused with U-46619 alone (P < 0.03). The RT of lungs perfused with PGE(2) + U-46619 was approximately 30% greater than that of lungs exposed to either U-46619 (P < 0.02) or PGE(2) (P < 0.01) alone. When paired measurements of RT taken before and then 15 min after the addition of U-46619 were compared, PGI(2) was found to attenuate U-46619-induced increases in RT (P < 0.01). These data suggest that PGE(2), PGI(2), and PGF(2alpha) potentiate the effects of TxA(2)-receptor activation on pulmonary microvascular permeability.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

Effect of diabetes mellitus on endotoxin-induced lung injury.

OBJECTIVE: To examine the effects of diabetes mellitus on lipopolysaccharide (LPS)-induced pulmonary edema and alveolar neutrophil recruitment and activation. HYPOTHESIS: Zucker diabetic fatty rats are resistant to the effects of intratracheal LPS on the extravasation of plasma proteins into the lungs. DESIGN: Zucker diabetic fatty (ZDF) rats (genotype fa/fa) were used as a model of diabetes mellitus, while their normoglycemic heterozygous littermates served as controls. Lipopolysaccharide (Escherichia coli 0111: B4; 100-200 microg) or vehicle (0.25 mL of isotonic sodium chloride solution) was instilled into the airways of ZDF and control rats. Four hours later, pulmonary microvascular dysfunction was assessed by measuring the extravasation of Evans blue dye into the lung. Lipopolysaccharide-induced neutrophil recruitment was assessed by counting the number of neutrophils within the bronchoalveolar lavage fluid and measuring their expression of CD11b/CD18 by fluorescence-activated cell analysis sorting. RESULTS: The LPS (200 microg) induced a 32% increase in Evans blue dye extravasation into the lungs of controls (P = .008) but had no such effect in diabetic animals. Pulmonary extravasation of Evans blue dye in controls was greater than that of ZDF rats both at baseline (P = .002) and in response to 200 microg of LPS (P<.001). The LPS upregulated neutrophil CD11b/CD18 expression in diabetic and nondiabetic groups and induced a greater than 50-fold increase in the number of neutrophils within the airways of both control and diabetic groups (P<.001). CONCLUSION: Despite the recruitment of a large number of neutrophils into the lung, the LPS-induced change in pulmonary microvascular permeability in diabetic animals is substantially less than that of nondiabetic controls.

Animals↗

PubMed1999

Nitric oxide and thromboxane A2-mediated pulmonary microvascular dysfunction.

OBJECTIVES: To examine whether the lung releases nitric oxide (NO) in response to thromboxane A2 and to examine the local release of NO as a protective compensatory mechanism by which the lung responds to the proinflammatory and vasoactive effects of thromboxane A2. DESIGN: The lungs of anesthetized Sprague-Dawley rats were perfused in vitro with Krebs-Henseleit buffer that contained an inhibitor of NO synthase (nitroglycerinenitro-L-arginine methyl ester [L-NAME]) (10(-4) mol/L), an NO donor (sodium nitroprusside) (10(-8) mol/L), or perfusate alone. Following equilibration, the thromboxane A2 receptor agonist 9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F2alpha(U-46619) (7.1 X 10(-8) mol/L) was added to the perfusate. Fifteen minutes later, the capillary filtration coefficient, pulmonary arterial pressure, and vascular resistance were measured. Pulmonary NO release was assessed by quantitating the release of cyclic guanosine monophosphate into the perfusate. RESULTS: The capillary filtration coefficient of lungs exposed to U-46619 was 3.5 times greater than that of lungs perfused with buffer alone (P<.05). The addition of sodium nitroprusside reduced the increase in capillary filtration coefficient associated with U-46619 by 50% (P<.05) whereas L-NAME had no effect. The addition of U-46619 to the perfused lung caused a 3.0+/-0.4 mm Hg increase in pulmonary artery pressure (P<.01) with a corresponding rise in total vascular resistance (P<.05). This effect was exacerbated by L-NAME (P<.05) and inhibited by sodium nitroprusside (P<.05). Exposure of the isolated lungs to U-46619 caused a 4-fold increase in cyclic guanosine monophosphate levels within the perfusate. CONCLUSION: These data are consistent with the hypothesis that NO release may be an important protective mechanism by which the lung responds to thromboxane A2.

Animals↗

PubMed1999

The effect of nutritional and hormonal supplementation on protein synthesis immediately after liver transplantation.

We have previously shown that immediately after liver transplantation (LT) the porcine recipient exhibits elevated plasma glucagon, increased fractional synthetic rate (FSR) of fibrinogen, and decreased FSR of fixed or structural liver proteins. The purpose of this study was to evaluate the effect of nutritional and hormonal supplementation on these observations 24 h after LT. Two groups of nine pigs were studied 1 day after LT using radioisotopic and arteriovenous difference techniques. A control group underwent LT with saline infusion and a supplemented group underwent LT with infusion of glucose, amino acids (6 and 1.06 mg/kg. min, respectively), and intraportal insulin (0.6 mU/kg. min) and glucagon (1.3 ng/kg. min). Primed constant infusions of [3H]leucine were used to determine leucine flux, an estimate of whole body protein breakdown, and fractional synthetic rates (FSR). The following changes were noted with supplementation: elevated plasma insulin (6 +/- 1 versus 29 +/- 4 microU/ml, control versus supplemented, respectively, P < 0.05), decreased glucagon to normal levels (323 +/- 65 versus 102 +/- 12 pg/ml, P < 0.05), decreased fibrinogen FSR (108 +/- 15 versus 70 +/- 6%/day, P < 0.025), and increased fixed liver protein FSR (8 +/- 1 versus 13 +/- 2%/day, P < 0.05, respectively). Albumin FSR was unaltered by supplementation (8 +/- 2 versus 6 +/- 1%/day, respectively). Nutritional and hormonal supplementation immediately after LT restored the measured protein synthesis in the allograft to near normal levels 1 day after transplantation.

Amino Acids↗

PubMed1999

Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. METHODS: In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. RESULTS: During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child's classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. CONCLUSIONS: TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Abdominal Pain↗

PubMed1999

18Fluorodeoxyglucose-positron emission tomography in the management of patients with suspected pancreatic cancer.

OBJECTIVE: To assess the accuracy and clinical impact of 18fluorodeoxyglucose-positron emission tomography (18FDG-PET) on the management of patients with suspected primary or recurrent pancreatic adenocarcinoma, and to assess the utility of 18FDG-PET in grading tumor response to neoadjuvant chemoradiation. SUMMARY BACKGROUND DATA: The diagnosis, staging, and treatment of pancreatic cancer remain difficult. Small primary tumors and hepatic metastases are often not well visualized by computed tomographic scanning (CT), resulting in a high incidence of nontherapeutic celiotomy and the frequent need for "blind resection." In addition, the distinction between local recurrence and nonspecific postoperative changes after resection can be difficult to ascertain on standard anatomic imaging. 18FDG-PET is a new imaging technique that takes advantage of increased glucose metabolism by tumor cells and may improve the diagnostic accuracy of preoperative studies for pancreatic adenocarcinoma. METHODS: Eighty-one 18FDG-PET scans were obtained in 70 patients undergoing evaluation for suspected primary or recurrent pancreatic adenocarcinoma. Of this group, 65 underwent evaluation for suspected primary pancreatic cancer. Nine patients underwent 18FDG-PET imaging before and after neoadjuvant chemoradiation, and in eight patients 18FDG-PET scans were performed for possible recurrent adenocarcinoma after resection. The 18FDG-PET images were analyzed visually and semiquantitatively using the standard uptake ratio (SUR). The sensitivity and specificity of 18FDG-PET and CT were determined for evaluation of the preoperative diagnosis of primary pancreatic carcinoma, and the impact of 18FDG-PET on patient management was retrospectively assessed. RESULTS: Among the 65 patients evaluated for primary tumor, 52 had proven pancreatic adenocarcinoma and 13 had benign lesions. 18FDG-PET had a higher sensitivity and specificity than CT in correctly diagnosing pancreatic carcinoma (92% and 85% vs. 65% and 62%). Eighteen patients (28%) had indeterminate or unrecognized pancreatic masses on CT clarified with 18FDG-PET. Seven patients (11%) had indeterminate or unrecognized metastatic disease clarified with 18FDG-PET. Overall, 18FDG-PET suggested potential alterations in clinical management in 28/65 patients (43%) with suspected primary pancreatic adenocarcinoma. Of the nine patients undergoing 18FDG-PET imaging before and after neoadjuvant chemoradiation, four had evidence of tumor regression by PET, three showed stable disease, and two showed tumor progression. CT was unable to detect any response to neoadjuvant therapy in this group. Eight patients had 18FDG-PET scans to evaluate suspected recurrent disease after resection. Four were noted to have new regions of 18FDG-uptake in the resection bed; four had evidence of new hepatic metastases. All proved to have metastatic pancreatic adenocarcinoma. CONCLUSIONS: These data confirm that 18FDG-PET is useful in the evaluation of patients with suspected primary or recurrent pancreatic carcinoma. 18FDG-PET is more sensitive and specific than CT in the detection of small primary tumors and in the clarification of hepatic and distant metastases. 18FDG-PET was also of benefit in assessing response to neoadjuvant chemoradiation. Although 18FDG-PET cannot replace CT in defining local tumor resectability, the application of 18FDG-PET in addition to CT may alter clinical management in a significant fraction of patients with suspected pancreatic cancer.

Adenocarcinoma↗

PubMed1999

Comparison of arcuate-legged clipped versus sutured hepatic artery, portal vein, and bile duct anastomoses.

Attempts at improving anastomoses have included the development of stapling techniques. Our purpose was to evaluate arcuate-legged clipped versus standard sutured anastomoses of the hepatic artery (HA), portal vein (PV), and bile duct in a porcine liver transplantation model. Two groups of pigs were studied intraoperatively and 1 day after liver transplantation. A control group underwent sutured anastomosis of PV and HA with polypropylene and of bile duct with polydioxanone (n = 8). An experimental group underwent anastomoses with arcuate-legged clips (n = 8). We analyzed the time to perform anastomosis and flows before and at various time points after anastomosis. In addition, patency and histology of the anastomoses were evaluated 1 day after operation, including a fibrin-thrombosis score, medial injury, and inflammation score. Times to complete HA and PV anastomoses were not different between clipped and sutured groups. However, the time was shorter to complete bile duct anastomosis with clips than with sutures (6.3 +/- 1.1 minutes and 13.3 +/- 2.0 minutes, respectively). Flows through HA anastomoses were not different between groups, but flow through the PV was higher in clipped compared with sutured anastomosis (P = 0.06). Patency was 100 per cent with no leaks for all three anastomoses in both groups. Histologic data were similar between vascular anastomotic groups. Sutured bile duct anastomoses revealed mild smooth muscle injury in 75 per cent whereas clipped bile duct anastomoses displayed no smooth muscle injury. We conclude that arcuate-legged clipped anastomosis represents a viable option to sutured anastomoses of the PV, HA, and bile duct anastomoses. Bile duct anastomoses were completed in less than half the time and with less tissue damage documented histologically.

Anastomosis, Surgical↗

PubMed1999

Surgical experience with hepatic colorectal metastasis.

The outcome of 134 patients undergoing hepatic resection for colorectal metastasis was studied. Current follow-up was available in 98 per cent of patients, for more than 5 years in 58 patients, and totaling 360 patient-years. Patients (52% male) had an average age of 62 +/- 1 years (standard error of the mean). Time lapse between the primary colon surgery and hepatic resection was a median of 16 months and a mean of 19 +/- 1 months. Thirty-two (24%) were operated on within 6 months for both their primary tumor and hepatic metastasis. Intensive care unit and total hospital length of stay were a median of 1 and 7 days, respectively. Pathology reports demonstrated that on average there were 2.0 +/- 0.1 lesions, with the largest lesion measuring 4.4 +/- 0.2 cm. In 72 per cent of patients, the lesions were found in one lobe only. CEA was elevated in 83 per cent of patients preoperatively and was 60 +/- 11 ng/mL before and 4.0 +/- 0.5 ng/mL after hepatic resection. Patient survival was 81 per cent at 1 year, 50 per cent at 3 years, 36 per cent at 5 years, and 23 per cent at 10 years. Actual 5- and 10-year survival was 22 of 58 (38%) patients and 4 of 21 (19%) patients respectively. Disease-free survival was 58 per cent at 1 year, 27 per cent at 3 years, 16 per cent at 5 years, and 12 per cent at 7 years. Survival was much better for one to four lesions than for five or more lesions (P < 0.01). Several other potential risk factors did not affect survival, including whether the patient received chemotherapy after hepatic resection. There were 36 (43%) patients who recurred with hepatic involvement only, 27 (32%) including hepatic involvement and 21 (25%) with nonhepatic involvement only. There were 15 patients who went on to receive repeat hepatic resections, with a 5-year survival of 74 per cent and disease-free survival of 58 per cent. Hepatic resection provides the best outcome of any form of therapy for selected patients with isolated hepatic metastasis.

Colectomy↗

PubMed1999

Antiperistaltic Roux-en-Y biliary-enteric bypass after bile duct injury: a technical error in reconstruction.

Bilioenteric reconstruction using a Roux limb of jejunum is a well-established surgical option for the reconstruction of the proximal bile duct. Previous studies discussing short- and long-term complications of biliary-enteric anastomosis have focused on technical aspects, such as the use of anastomotic stenting or the level of the biliary tree used. We report two cases of previously unreported complications after hepaticojejunostomy that resulted from a technical error in constructing the Roux limb. Within a 3-month period, two patients were referred to our institution with recurrent cholangitis after biliary reconstruction for injuries sustained during laparoscopic cholecystectomy. Reexploration disclosed major technical flaws in the construction of the Roux limb used for biliary drainage. Antiperistaltic limbs had been constructed in both patients: one from the distal ileum and one from the conventional location in the jejunum. In both cases, isoperistaltic reconstruction of the Roux limbs resolved the recurrent cholangitis. Cholangitis after biliary-enteric bypass can arise from a variety of etiologies and lead to anastomotic narrowing or ineffective drainage of the biliary tree. Review of the literature failed to disclose reports of technically flawed Roux limb construction as a cause of cholangitis. We present these cases to highlight the devastating consequences of antiperistaltic construction of the Roux limb. We hope that by publishing the role of this avoidable error in recurrent cholangitis after biliary-enteric bypass we may help prevent its future occurrence.

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↗

PubMed1998

Evaluation of benign vs malignant hepatic lesions with positron emission tomography.

BACKGROUND: In most malignant cells, the relatively low level of glucose-6-phosphatase leads to accumulation and trapping of [18F]fluorodeoxyglucose (FDG) intracellularly, allowing the visualization of increased uptake compared with normal cells. OBJECTIVES: To assess the value of FDG positron emission tomography (PET) to differentiate benign from malignant hepatic lesions and to determine in which types of hepatic tumors PET can help evaluate stage, monitor response to therapy, and detect recurrence. DESIGN: Prospective blinded-comparison clinical cohort study. SETTING: Tertiary care university hospital and clinic. PATIENTS: One hundred ten consecutive referred patients with hepatic lesions 1 cm or larger on screening computed tomographic (CT) images who were seen for evaluation and potential resection underwent PET imaging. There were 60 men and 50 women with a mean (+/-SD) age of 59 +/- 14 years. Follow-up was 100%. INTERVENTIONS: A PET scan using static imaging was performed on all patients. The PET scan imaging and biopsy, surgery, or both were performed, providing pathological samples within 2 months of PET imaging. All PET images were correlated with CT scan to localize the lesion. However, PET investigators were unaware of any previous interpretation of the CT scan. MAIN OUTCOME MEASURES: Visual interpretation, lesion-to-normal liver background (L/B) ratio of radioactivity, and standard uptake value (SUV) were correlated with pathological diagnosis. RESULTS: All (100%) liver metastases from adenocarcinoma and sarcoma primaries in 66 patients and all cholangiocarcinomas in 8 patients had increased uptake values, L/B ratios greater than 2, and an SUV greater than 3.5. Hepatocellular carcinoma had increased FDG uptake in 16 of 23 patients and poor uptake in 7 patients. All benign hepatic lesions (n = 23), including adenoma and fibronodular hyperplasia, had poor uptake, an L/B ratio of less than 2, and an SUV less than 3.5, except for 1 of 3 abscesses that had definite uptake. CONCLUSIONS: The PET technique using FDG static imaging was useful to differentiate malignant from benign lesions in the liver. Limitations include false-positive results in a minority of abscesses and false-negative results in a minority of hepatocellular carcinoma. The PET technique was useful in tumor staging and detection of recurrence, as well as monitoring response to therapy for all adenocarcinomas and sarcomas and most hepatocellular carcinomas. Therefore, pretherapy PET imaging is recommended to help assess new hepatic lesions.

Adolescent↗

PubMed1998

Hepatic uptake of amino acids immediately after liver transplantation is well preserved despite altered plasma profiles.

BACKGROUND: The liver is one of the principal organs responsible for the uptake and release of amino acids in the body. The ability of the transplanted liver to clear plasma amino acids is associated with a functioning allograft. However, clinical assessment is limited by the inability to access the portal vein postoperatively. Therefore, using a porcine liver transplant model, we examined (1) the plasma levels of amino acids presented to the new hepatic allograft and (2) the capacity of the new allograft to clear these amino acids from the circulation. MATERIALS AND METHODS: Two groups of commercially bred pigs were studied: a control group (n = 8) underwent laparotomy and a transplanted group (n = 6) underwent orthotopic liver transplantation (LT) using veno-venous bypass. All pigs had catheters placed in the carotid artery and portal and hepatic veins and ultrasonic transit time flow probes placed around the hepatic artery and portal vein. Plasma profiles of 23 amino acids were analyzed by high-pressure liquid chromatography. Hepatic balances of amino acids, using arteriovenous difference techniques coupled with hepatic blood flows, were also analyzed on postoperative day 1. RESULTS: Neither portal vein blood flow (703 +/- 74 ml/min vs 666 +/- 82 ml/min) nor hepatic artery blood flow (322 +/- 43 ml/min vs 209 +/- 59 ml/min) was significantly different between the control and the transplanted groups, respectively. The transplanted group had significantly increased plasma levels of alanine (135 +/- 13 mumol/l vs 382 +/- 72 mumol/l), hydroxyproline (30 +/- 5 mumol/l vs 60 +/- 9 mumol/l), methionine (25 +/- 2 mumol/l vs 55 +/- 10 mumol/l), ornithine (36 +/- 5 mumol/l vs 141 +/- 33 mumol/l), phenylalanine (84 +/- 5 mumol/l vs 120 +/- 12 mumol/l), threonine (75 +/- 9 mumol/l vs 159 +/- 27 mumol/l), and tryptophan (17 +/- 2 mumol/l vs 31 +/- 4 mumol/l). The transplanted group also had significantly decreased plasma levels of isoleucine (122 +/- 12 mumol/l vs 85 +/- 8 mumol/l) and taurine (71 +/- 7 mumol/l vs 35 +/- 7 mumol/l). These individual amino acid changes were not accompanied by impairment in the net hepatic amino acid balance or the hepatic fractional extraction of amino acids between the two groups. CONCLUSION: These results suggest that the circumstances associated with liver transplantation alter the fasting amino acid profile immediately postoperatively. However, liver transplantation does not impair the normal hepatic allograft uptake of most plasma amino acids. Thus, the changes observed in the circulating levels of amino acids may represent alterations in nonhepatic production and/or utilization. Furthermore, altered plasma amino acid profiles following liver transplantation are not necessarily indicative of impaired hepatic allograft amino acid metabolism.

Amino Acids↗

PubMed1998

Clinical experience with cryosurgery for advanced hepatobiliary tumors.

INTRODUCTION: There have been reports that suggest cryosurgical techniques may be a useful adjunct to surgical resection or even a viable alternative treatment for hepatobiliary malignancies. Our objective was to evaluate the clinical results following cryoablation in conjunction with surgical resection for advanced hepatic tumors. MATERIALS AND METHODS: Thirty-two consecutive procedures in 31 patients with advanced liver tumors treated with cryosurgical ablation were evaluated. Cryosurgery was applied: (1) to achieve a > 1-cm tumor-free margin when standard surgical margins were close (2) with or without standard surgical resection to manage multiple tumors (3) with hepatic arterial portocath placement to increase tumor response. Cryoablation was applied to 47 of 105 lesions--independently in 4 patients and in combination with hepatic resection in 28 procedures. RESULTS: Cryoablation was used in 11 procedures because of close surgical margins. In 21 operations cryosurgery was used for primary ablation. In 17 of these 21 patients both cryosurgery and resection were used for different lesions; in 4 cryosurgery alone was used. Transient changes in hepatic enzymes, PT, PTT, and platelets were at maximum on Postoperative Days 1-3. Surgical mortality and morbidity rates were 6 and 60%, respectively. Coagulation abnormalities were common: at least 30% reduction in platelets occurred in all patients and greater than a 50% reduction occurred in 19 of 32 (59%). Twenty patients had a PT > 15 s and 6 of these 20 also had a platelet count < 50,000. Associated complications included one wound hematoma, two GI hemorrhages, one intracranial hemorrhage, and one hepatic hemorrhage from the cryosurgical site. The actuarial patient survivals were 90, 59, 33, and 22% at 6, 12, 24, and 36 months, respectively. CONCLUSIONS: This report helps define the risks and results of cryosurgical ablation as a complement to surgical resection for advanced hepatobiliary tumors. Management of lesions contiguous to major blood vessels may include either the Pringle maneuver or total vascular isolation. Since these procedures can have significant morbidity, we urge cautious application of cryosurgery for advanced hepatobiliary tumors in selected otherwise unresectable patients.

Adult↗

PubMed1998

Experience with neoral versus sandimmune in primary liver transplant recipients.

We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 +/- 1.9 days in the Neoral group vs 7.8 +/- 4.9 days in the Sandimmune group. (P < 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P < 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P < 0.05). Two patients (13%) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60%) with 12 episodes of rejection in the Sandimmune group (P < 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early post-transplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year post-transplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24% in these 59 patients compared to our historical experience of 70% using Sandimmune.

Adult↗

PubMed1998

Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors.

BACKGROUND: Patients with advanced metastatic carcinoid tumors who have disease progression despite conventional therapy are left with few therapeutic options. Hepatic artery chemoembolization (HACE) may play a role in palliating these patients' symptoms. METHODS: Fifteen patients with biopsy-proven advanced bilobar hepatic carcinoid metastases who demonstrated progression of symptoms and/or tumor size despite treatment with somatostatin analogues were treated with intra-arterial chemotherapy and HACE to determine efficacy and safety. Five days of intra-arterial 5-fluorouracil (1 g/m2) were followed by HACE with adriamycin (60 mg), cisplatin (100 mg), mitomycin C (30 mg), and polyvinyl alcohol (Ivalon); 200 micron to 710 micron). Patients were continued on octreotide at the same dose (150 to 2000 microg subcutaneous q 8 hours) before, during, and after the procedure. RESULTS: Efficacy of treatment was assessed by comparing pretreatment and 3-month clinical, laboratory, radiographic, and quality of life parameters. Symptoms were improved in 8 of 12 patients who had diarrhea, 7 of 12 who had flushing, 9 of 12 who had abdominal pain, and in 4 of 7 who had malaise. Elevated tumor markers decreased in all patients. Biochemical markers (mean +/- SE) at 3 months decreased by 60% +/- 6% for 5-HIAA, 75% +/- 10% for chromogranin A and 50% +/- 7% for neuron-specific enolase. Tomographic assessment revealed tumor liquefaction in 10 of 13 patients. The Karnofsky performance status improved from a mean of 66 +/- 2 to 84 +/- 2 (P <0.001). Median follow-up was 16 months, with 13 deaths occurring from 1 week to 71 months after treatment. CONCLUSIONS: Hepatic artery chemoembolization improves symptoms of carcinoid syndrome, has a high tumor response rate, and improves short-term quality of life in this group of patients with advanced hepatic carcinoid disease.

Adult↗