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Biomedical subjects

M E Clouse

Publications and source records attributed to M E Clouse.

At least 19 recordsLinked to original sources

Multimodality treatment of hepatocellular carcinoma in a hepatobiliary specialty center.

OBJECTIVES: To review the experience of the treatment of hepatocellular carcinoma by a single multimodality team during a 6-year period, including all patients who were referred for possible surgical intervention, to evaluate prognostic factors at presentation, and to determine the results of the different modalities of treatment that were used. DESIGN: Retrospective study of 154 patients who were referred to our Hepatobiliary Surgical Unit with the diagnosis of hepatocellular carcinoma from January 1988 through August 1995. SETTING: Tertiary care center. RESULTS: Methods of treatment included surgical resection (n=49), transplantation (n=22), hepatic artery chemoembolization (n=30), systemic chemotherapy (n=25), and no treatment (n=22). Predictive prognostic factors included coexisting cirrhosis, symptoms at presentation, and abnormal liver function test results. Unfavorable tumor characteristics were size (diameter, >5 cm) and multicentricity. For patients who underwent surgical exploration, advanced staging according to the manual of the American Joint Committee on Cancer, vascular invasion, and a margin of less than 1 cm in the group for patients who underwent resection impacted negatively on the prognosis. The median survival (42.4 months) for the group of patients who underwent resection was significantly higher than that for the groups of patients who did not undergo resection. Chemoembolization was associated with significantly better survival results than was systemic chemotherapy. CONCLUSIONS: Hepatic resection offers the best chance at cure for patients with hepatocellular carcinoma. The high association between hepatocellular carcinoma and cirrhotic liver disease makes surgical resection, even in favorable tumor types, a difficult task based on low hepatic reserve whose tumors are considered unresectable can be considered for chemoembolization. Liver transplantation should be reserved for selected patients with cirrhotic liver disease who have tumors (diameter, <5 cm) in the contest of neoadjuvant protocols.

Adolescent

Severe ascites: efficacy of the transjugular intrahepatic portosystemic shunt in treatment.

PURPOSE: To evaluate the transjugular intrahepatic portosystemic shunt (TIPS) as primary treatment in patients with cirrhosis and severe ascites. MATERIALS AND METHODS: A TIPS placement was attempted in 54 consecutive patients with intractable ascites. Clinical assessment findings, shunt patency, complications, and survival were analyzed. RESULTS: A TIPS was successfully placed in 50 patients (93%). Follow-up for clinical effectiveness in 51 patients was a mean of 285 days (range, 1-981 days). Forty patients (78%) gained clinical benefit from the shunt. Of these, 29 (57%) had a complete response (required no further paracentesis) and 11 patients (22%) had a partial response (required less frequent but additional paracentesis for control of ascites). The absence of preprocedure renal insufficiency (creatinine < 1.5 mg/dL [< 130 mumol/L]) was the only characteristic identified as an indicator of clinical success (P < .05). Eleven patients (22%) required shunt revision during follow-up to gain or prolong control of symptoms. Cumulative survival in the population evaluated for clinical efficacy was 53% at 6 months and 48% at 1 year. A complete response was the only variable that indicated increased survival (P < .05; R2 = 12%) with a 6-month survival rate of 76% and a 1-year rate of 71%. CONCLUSION: TIPS placement appears to be effective as a primary treatment of patients with cirrhosis and severe ascites.

Adult

Time-of-flight MR angiography of the portal venous system: value compared with other imaging procedures.

OBJECTIVE: The purpose of this study was to retrospectively compare two-dimensional time-of-flight MR angiography with other imaging procedures in the evaluation of the portal venous system in 152 consecutive patients. MATERIALS AND METHODS: The findings on MR angiography performed on 152 patients to depict breath-hold, two-dimensional time of flight MR angiography. Selective arterial presaturation, bolus tracking, and three-dimensional reconstruction were used routinely. Findings were correlated with findings on sonography (104 patients), CT (8 patients), and conventional digital subtraction angiography (19 patients) as well as surgery (23 patients). RESULTS: Agreement between results of MR angiography and alternative types of imaging was excellent (99%). Agreement with sonography (100 of 104), CT (8 of 8), conventional angiography (18 of 19), and surgery (23 of 23) was good. Visualization of varices and spontaneous shunts by MR angiography was superior to that by other imaging techniques. CONCLUSION: Our experience shows that time-of-flight MR angiography is reliable and accurate for depicting portal venous anatomy. MR angiography shows vessels that are not visible with sonography. Complicated pathology is clearly visualized in a way that is not possible with other techniques.

Angiography, Digital Subtraction

In vivo microscopic assessment of hepatic microcirculation during liver allograft rejection in the rat.

The hemodynamic alterations in hepatic microvasculature during acute rejection of rat liver allografts was studied using in vivo fluorescence microscopy. ACI rat livers were transplanted into Lewis (allograft) or ACI (isograft) recipients. Microscopy was performed on days 3 (n = 7) and 6 (n = 7) in allografts, and on day 6 (n = 7) in isografts. Naive ACI livers (n = 7) served as nontransplant controls. Changes in sinusoidal blood perfusion, microvascular structure, and leukocyte-endothelial interactions were observed and quantitated. Six days after transplantation, acinar perfusion was markedly impaired in allografts and was accompanied by a lower percentage of perfused sinusoids (59 +/- 8%, mean +/- SEM, P < 0.01) relative to isografts (89 +/- 3%) and nontransplant controls (100 +/- 0%). The hepatic cord width in allografts was significantly greater than in isografts or in nontransplant controls, indicating swelling of parenchymal and sinusoidal lining cells. Furthermore, the number of leukocytes adhering to the sinusoidal endothelium significantly increased in allografts. Adherence to postsinusoidal venules was more prominent in allograft livers (4025 +/- 1400/mm2 of vascular endothelial surface) compared with that in isografts (574 +/- 77/mm2) and nontransplant controls (185 +/- 28/mm2). These microcirculatory alterations in allografts were significant even on day 3. The results show extensive abnormalities of the microcirculatory hemodynamics in rejecting liver allografts which were associated with increased leukocyte adherence to microvascular endothelium. Our findings may provide strategic information for the prevention and treatment of allograft rejection.

Animals

Biliary intervention by means of percutaneous puncture of the antecolic jejunal loop.

PURPOSE: To evaluate the safety and efficacy of biliary intervention performed by means of percutaneous transjejunal access. MATERIALS AND METHODS: In 28 patients with conventional antecolic Roux-en-Y choledochojejunostomy or hepaticojejunostomy loops, 41 attempts were made at direct percutaneous entry into the jejunal loop. Indications for previous surgery included sclerosing cholangitis, orthotopic liver transplantation, cholangiocarcinoma, bypass of benign iatrogenic strictures, and bypass of choledochal cyst. Roux-en-Y loops were directly accessed with single-wall, 19-gauge needles after localization by review of previous cholangiograms or computed tomographic (CT) scans and localization of surgical clips with fluoroscopy. RESULTS: The transjejunal approach was successful in 36 of 41 attempts. In 30 cases, transhepatic puncture was entirely avoided. There were four minor complications and one major complication of biliary sepsis. No procedure-related deaths occurred. CONCLUSION: This transjejunal approach is an effective and safe route for a variety of percutaneous biliary procedures in patients with biliary-enteric anastomoses.

Anastomosis, Roux-en-Y

Portal vein: US-guided localization prior to transjugular intrahepatic portosystemic shunt placement.

To mark the portal vein prior to transjugular intrahepatic portosystemic shunt (TIPS) placement, metallic coils adjacent to (n = 18) and a wire within (n = 18) the portal vein were placed with ultrasonographic (US) guidance. The mean number of punctures for successful portal vein entry was 3.0 with coils and 2.9 with a wire, and the mean total procedure time was 127.5 and 110.0 minutes, respectively (differences, not significant), and mean time at US was 20 and 10 minutes, respectively.

Adult

31P nuclear magnetic resonance spectroscopic evaluation of liver preservation solutions.

The individual effects of verapamil and 2 antioxidants on perfused rat liver nucleoside triphosphate (NTP) recovery following cold storage in University of Wisconsin (UW) solution was assessed using 31P nuclear magnetic resonance spectroscopy. The pharmacological agents were added to UW solution and were present only during organ storage. NTP recovery was significantly higher for the 24-hr UW + 40 microM verapamil group as compared with the 24-hr UW group. None of the other pharmacological agents caused a significant increase in NTP recovery. These findings suggest that addition of verapamil to UW organ preservation solution may result in better poststorage liver function.

Acetylcysteine

31P NMR assessment of orthotopic liver rejection in a rat model.

31P NMR spectroscopy was used serially to study rejecting (ACl-->LEW) and nonrejecting (ACl-->ACl) orthotopic liver transplants in rats. Recipients were evaluated on post-transplant days 1, 3, 5, 7, 9, and 11. The relative changes in phosphomonoester (PME), inorganic phosphate (Pi), high-energy phosphates and pH were studied. The earliest significant difference between the rejecting and nonrejecting groups was a decrease in the alpha-NTP peak area on Day 5. This was followed by significant decreases in beta-NTP and pH, and increases in PME and Pi on Day 7. High-resolution 31P NMR spectra of perchloric acid extracts demonstrated the PME increase to be due mainly to elevated phosphoethanolamine. Using the parameter (Pi + PME)/(alpha + beta + gamma-NTP), rejecting livers were distinguished from nonrejecting livers at a moderate stage of rejection.

Animals

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

PURPOSE OF THE STUDY: To evaluate the effectiveness of chemoembolization of the liver with doxorubicin and iopamidol emulsified in ethiodized oil for the treatment of metastatic neuroendocrine tumors. PATIENTS AND METHODS: Twenty patients with hepatic islet cell or carcinoid metastases were treated with selected hepatic arterial embolization consisting of an emulsion of doxorubicin and iopamidol emulsified in ethiodol followed by Gelfoam powder embolization. Fifteen patients had failed intravenous chemotherapy. Two of the patients with carcinoid tumors had three embolizations over 4 and one 6 years earlier with gelatin sponge only. RESULTS: In 14 patients with hormonally active tumors, hormones secretion decreased 90% (range 69-98%) in 10 days with relief of symptoms in all patients. Average tumor size decrease was 84%. Average hospital stay was 8 days. Six patients are alive and asymptomatic at 14-33 months postembolization. Fourteen patients have died 2-16 months postembolization. Ten patients died 2-37 months postembolization from progressive liver disease. One of these patients was 103 months post-Gelfoam embolization and 13 months postchemoembolization. In 8 patients, the pancreas was the primary site: 5 were nonfunctioning islet cell carcinomas, 1 glucagonoma, 1 gastrinoma and 1 carcinoid. The primary site in 1 patient with carcinoid was the bronchus, and the primary site was unknown in 1 patient with gastrinoma. The remaining 4 patients died with liver disease under control from renal failure, peritonitis, carcinoid heart failure and generalized bone metastases. The response rate was 95% with median duration of response 8.5 months. The median survival was 24 months. CONCLUSION: Chemoembolization with doxorubicin and iopamidol emulsified in ethiodized oil is less morbid than embolization with particulate matter alone, is more convenient and less costly, and it is less morbid than the effects of systemic chemotherapy. The median survival, duration and response compare favorably with other reported therapies.

Adenoma, Islet Cell

Hepatic arterial chemoembolization for metastatic neuroendocrine tumors.

BACKGROUND: Patients with neuroendocrine neoplasma, even with metastases to the liver, often have indolent disease and are treated conservatively. However, when debilitating symptoms from hormonal syndromes or mass effect arise, more aggressive treatment may be warranted. METHODS: Thirty-nine chemoembolization procedures were performed in 30 patients with significant symptoms, with carcinoids and islet cell tumors. An emulsification of intraarterial doxorubicin, iodized oil, and water-soluble contrast was followed by embolization with absorbable gelatin powder or pledgets. RESULTS: Twenty-seven patients exhibited subjective improvement in clinical symptoms. Hormonal markers and/or tumor size decreased by at least 50% in 79% of patients. Inclusion of minor responses raises this to 92%. Seven complications were noted, and no procedure-related deaths occurred. Median survival was 24 months after chemoembolization or 53 months after diagnosis. Computed tomographic features of tumor vascularity, distribution of metastatic lesions, and distribution of ethiodized oil were not clearly correlated with outcome. Presence of a nonresected primary tumor had a negative effect on survival. CONCLUSIONS: Compared with previously described treatments for neuroendocrine liver metastases, this technique appears to be more effective and to be associated with less morbidity, and is recommended for patients with significant symptoms who have failed to respond to more conservative therapy and who are not surgical candidates.

Adult

Hepatic utilization of exogenous nucleotide precursors for restoration of ATP after cold ischemia in rats.

The study objective was to assess hepatic utilization of exogenous adenosine or adenine to enhance ATP recovery in rat liver after cold ischemia. ATP was measured noninvasively by 31P nuclear magnetic resonance (NMR) in perfused livers before and after 18 h of cold ischemia. The hepatocellular concentration of ATP during the initial postischemic reperfusion without adenosine or adenine coinfusion was 60% of that in fresh liver. The ATP increased significantly (P < 0.001) to 139% and 82% of baseline in postischemic livers coinfused for 90 min with adenosine or adenine (final concentration, 1 mmol/L), respectively. Less than 0.5% of the excess adenosine was catabolized to uric acid. In conclusion, adenosine and, to a lesser extent, adenine are salvaged by liver after extended cold ischemia to enhance ATP restoration. Provision of these ATP precursors, as components of an enteral formulation may facilitate the repletion of liver ATP and foster early resumption of liver function after an ischemic insult.

Adenine

A rat fatty liver transplant model.

A rat model of fatty liver transplantation has been developed to study primary nonfunction in fatty liver grafts. ACI rats were fed with a diet deficient in choline and methionine for 7, 14, 28, and 42 days. Fat content in the pretransplant livers was examined by gas chromatography and histology. The main constituent of the fatty droplets was determined to be triglyceride. The triglyceride concentration reached a maximum by day 14 and remained constant for an additional 28 days. Histology revealed an absence of necrosis in 14- and 28-day fatty livers but scattered hepatocytic necrosis and inflammation in 42-day fatty livers. After being given cold (UW stored, 4 degrees C) or warm (37 degrees C) ischemia, the fatty liver was orthotopically transplanted into normal ACI rats. The one-week survival of fatty liver grafts after 6, 12, 18, and 24 hr cold preservation was 5/5, 5/6, 3/8, 0/6 for 14-day fatty liver and 5/5, 4/6, 0/8, 0/6 for 42-day fatty livers. The survival of normal liver grafts was 5/5, 6/6, 5/9, 2/8, respectively. Increased survival rate was correlated with the absence of hepatocytic necrosis. The survival after 15 and 30 min warm ischemia prior to transplant was 5/5, 2/6 for normal liver grafts and 4/7, 0/6 for 28-day fatty liver graft, respectively. Fatty livers were less resistant to damage induced by cold or warm ischemia.

Animals