Portosystemic shunt without surgery.
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Catheterization↗
Biomedical subjects
F E Eckhauser
Publications and source records attributed to F E Eckhauser.
Inhibition of DNA synthesis by somatostatin in rat hepatocytes stimulated by hepatocyte growth factor or epidermal growth factor.
The antiproliferative effects of somatostatin on hepatocytes stimulated by hepatocyte growth factor (HGF) or epidermal growth factor (EGF) were investigated using primary cultures of adult rat hepatocytes. Somatostatin inhibits HGF-induced (at a dose of 10 ng/mL) or EGF-induced (at a dose of 100 ng/mL) 3H-thymidine incorporation into hepatocytes in a dose-dependent manner (10(-10) to 10(-8) M). This inhibition was confirmed by autoradiography. The effect of somatostatin was nontoxic as judged by preserved albumin synthesis, a marker for differentiated hepatocyte function. In the presence or absence of somatostatin, neither HGF nor EGF significantly altered intracellular cyclic adenosine monophosphate (cAMP). We conclude that somatostatin is a potent inhibitor of HGF- or EGF-induced deoxyribonucleic acid synthesis in adult rat hepatocytes. The mechanism of this inhibition appears to be independent of cAMP. The significance of somatostatin in liver regeneration has yet to be assessed.
Animals↗
Transforming growth factor-alpha (TGF-alpha) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats.
Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-alpha (TGF-alpha), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/micrograms DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/micrograms DNA, P less than 0.05). Exogenous TGF-alpha (30 nmol/kg, sc every 12 hr) significantly improved [3H]thymidine incorporation (35.6 +/- 8.2 cpm/micrograms DNA, P less than 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-alpha had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/micrograms DNA, NS). Although the significance of TGF-alpha-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.
Animals↗
Extracorporeal lithotripsy. An important adjunct in the nonoperative management of retained or recurrent bile duct stones.
Retained or recurrent bile duct stones can be successfully removed in up to 80% to 85% of patients with the use of percutaneous or endoscopic techniques. However, problems related to difficult biliary access, large stones, and biliary strictures may decrease the success rate of this approach. We evaluated the safety and efficacy of extracorporeal shock-wave lithotripsy (ESWL) in 16 patients with complicated biliary stones treated prospectively over a 24-month period. Successful stone fragmentation was achieved in 15 patients (94%) using a Dornier HM3 lithotripter (average of 2290 shocks at 22 kV). Three patients (19%) required a second ESWL treatment. Biliary clearance of stone fragments was spontaneous in seven (43%) of the patients and required additional treatment in eight (57%) of the patients. Complications from ESWL were minor and included transient hematuria and ecchymoses at the skin entry site. Extracorporeal shock-wave lithotripsy failed in one patient (6%) with a biliary stricture and surgery was required. At hospital discharge, all patients were asymptomatic and stone free. Treatment with ESWL appears to be a safe and effective adjunct for selected patients with complex biliary stone disease.
Adult↗
Current concepts in the pathophysiology and treatment of portal hypertension and variceal hemorrhage.
Recent studies have demonstrated that increased resistance to portal inflow is not solely responsible for the development of portal hypertension. Increased splanchnic flow has been attributed to a combination of factors, including elevated circulating levels of vasodilators and diminished sensitivity of the splanchnic vasculature to endogenous vasoconstrictors. In selected animal models of portal hypertension, increased splanchnic flow accounts for approximately 40% of the observed elevations in total portal venous pressure. Improved understanding of the pathophysiologic factors responsible for the development of portal hypertension has led to pharmacologic efforts to decrease portal pressure. Current limitations include lack of drug selectivity and specificity and inability to predict and monitor patient responses. Primary treatment options include selective portosystemic shunts, endoscopic sclerotherapy (ES), and orthotopic liver transplantation. ES is more effective in preventing recurrent variceal hemorrhage than medical treatment but is less effective than shunt surgery. In selected studies, ES better maintains hepatic function and may prolong survival compared to primary shunt surgery. ES failures occur in nearly 33% of patients, but "salvage shunts" in these patients appear to be reasonably safe and quite effective in preventing recurrent hemorrhage. Selective shunts are favored because they appear to confer a better quality of life (but not improved longevity) than conventional shunts. Liver transplantation is preferred for patients with end-stage liver disease in whom the predicted mortality of conventional surgery outweighs the survival benefit.
Esophageal and Gastric Varices↗
The liver plays an important role in the regulation of somatostatin-14 in the rat.
Since little is known about the in vivo disposition of circulating somatostatin-14 (SRIF-14), we examined hepatic processing of SRIF-14 in the rat. Three minutes after the intraportal injection of iodine 125 (125I)-labeled SRIF-14, 16.0 +/- 2.0% of the injected dose is localized to the liver. In the presence of unlabeled SRIF-14, hepatic uptake can be decreased by 68%. Five minutes after the intraportal injection of 125I-SRIF-14, 9.5 +/- 1.4% of the tracer is localized to the liver, more than any other organ tested. Serial collections of bile reveal peak radioactivity at between 10 and 20 minutes. Simultaneous administration of unlabeled SRIF-14 decreases biliary radioactivity by 40%. HPLC analysis of radioactive bile reveals a chromatographic profile similar to that of intact SRIF and is 73% immunoprecipitable by an anti-SRIF antibody. Pretreatment with chloroquine, a lysosomal enzyme inhibitor, does not significantly decrease biliary radioactivity. We conclude that the data are consistent with saturable hepatic uptake and predominantly nonlysosomal transcellular transport.
Animals↗
Inhibitory effects of somatostatin on rat hepatocyte proliferation are mediated by cyclic AMP.
Somatostatin (SS-14) is known as an antigrowth factor for a variety of cell types, including gastrointestinal mucosa, exocrine pancreas, lymphocytes, and some tumors. We have recently identified and biochemically characterized SS-14-binding protein on rat liver plasma membranes (S. E. Raper, P. C. Kothary, and J. DelValle, Gastroenterology 96: A408, 1989; P. C. Kothary et al., Digestion 46 (Suppl 1): 58, 1990). We hypothesized that SS-14 may affect liver growth as well and investigated cellular mechanisms of this phenomenon focusing on the second messenger cAMP. Freshly isolated rat hepatocytes were plated on tissue culture dishes coated with Matrigel (laminin, heparan sulfate, and type IV collagen). The medium was not supplemented with serum or hormones. Either dibutyryl-cAMP (1 mM) or isobutylmethylxanthine (IBMX, 0.1 mM) was added in the presence or absence of SS-14 (10 nM). DNA synthesis was estimated by the rate of [3H]thymidine incorporation into DNA and by the labeling index (an autoradiographic measurement of the number of labeled nuclei). SS-14 significantly inhibited both [3H]thymidine incorporation and labeling index of rat hepatocytes stimulated by dibutyryl-cAMP or IBMX. SS-14 also inhibited intracellular cAMP accumulation stimulated by IBMX. We conclude that SS-14 exerts at least part of its antiproliferative effects via the adenylate cyclase system. Further study using other signal transduction systems may yield more information about mechanisms of hepatocyte growth.
1-Methyl-3-isobutylxanthine↗
Reconstruction of the abdominal wall by placement and early excision of prosthetic mesh.
A technique is described by which large abdominal wounds may be managed. This technique combines the use of prosthetic mesh to minimize undue tension with early excision as a means of avoiding late wound complications.
Abdominal Muscles↗
Injection sclerotherapy-induced esophageal strictures. Risk factors and prognosis.
Injection sclerotherapy (IS) has become an effective modality for the treatment of bleeding esophageal varices. Despite improvements in equipment, sclerosant solutions and operator technique, injection sclerotherapy-induced esophageal strictures (ISES) remain a significant cause of patient morbidity. To analyze the risk factors and prognosis of ISES, the records of 117 patients who underwent IS over a 6-year period at a single teaching institute were reviewed. The predictive value of multiple risk factors including the patient's age, Child's risk classification, previous bleeding episodes, etiology of varices, cumulative amount of sclerosant used, and the number of IS treatments were determined using ANOVA. A P value of less than 0.05 was considered significant. In all cases, a free-hand injection technique, flexible endoscopes and sodium morrhuate were used. During a mean follow-up period of 228 days (1-1,469 days), 41 patients (35%) died and 24 patients (20.5%) developed symptomatic strictures. The cumulative amount of sclerosant used (81.4 +/- 9.5 ml) and the number of IS treatments (6.5 +/- 0.7) required in the stricture group was significantly greater than in the nonstricture group (49.1 +/- 2.7 and 4.0 +/- 0.3, respectively). The risk of stricture formation did not correlate with the volume of sclerosant injected per treatment, cause of varices, number of previous bleeds, or Child's hepatic risk class. A mean of 3.6 +/- 4.5 dilations was required for treatment of established strictures and 18 patients (75%) required r 4 dilations. One esophageal perforation occurred following dilation. Mortality correlated with hepatic risk class as 30/41 (73%) of deaths occurred in Child's C patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Esophageal Stenosis↗
Portal venous barium intravasation complicating barium enema examination.
Venous intravasation of contrast is a potentially life-threatening complication of the barium enema examination. A patient in whom portal venous contrast intravasation was nearly fatal is presented, and the significant morbidity and mortality from this unusual event is reviewed. Since barium infiltration into the venous system almost always occurs in the setting of altered mucosal integrity, this examination should be used cautiously in patients with inflammatory bowel disease or diverticulitis. Prompt recognition and rapid resuscitation are critical to the survival of patients with contrast intravasation.
Adult↗
Combination chemo-radiation therapy for jaundice due to focal malignant obstruction of the major bile ducts.
Twenty patients with focal malignant obstruction of the major bile ducts (6 cholangiocarcinoma, 8 colorectal, 3 hepatoma, 2 unknown primary, and 1 gastric cancer) were treated on a protocol examining the toxicity and efficacy in relieving jaundice of external beam radiation therapy (4500 cGy in 300 cGy fractions) combined with continuous hepatic arterial (15 patients) or peripheral venous (5 patients) fluorouracil infusion. Toxicity of this regimen consisted of anorexia with mild nausea and vomiting in 55% of patients and gastric ulceration (responsive to medical management) in 15% of patients. One patient exhibited transient grade 2 hepatic toxicity and one had asymptomatic grade 4 leukopenia. Of 14 patients treated without prior biliary drainage, 8 exhibited a decrease in bilirubin levels from a mean of 14.5 mg/dl to 1.5 mg/dl. Four of six patients with biliary drainage catheters at the start of treatment were able to have them removed without reobstruction. For the 8 responding patients among those who did not have cholangiocarcinomas, the median response duration was 5 months with a median survival from treatment of 6.5 months. For the 4 responding patients with cholangiocarcinoma, the median response duration was 16 months with a median survival from treatment of 20 months. All responders did not have a return of jaundice due to reobstruction of the major ducts (until death or to the present). All responders who have died did so due to tumor progression outside of the treated field except for one who died of unrelated causes. The mean number of proven or presumed episodes of cholangitis per patient was virtually identical in those without (1.8) and those with stents/tubes (1.4, p = 0.561). This regionally focused combined modality cytotoxic therapy was able to relieve obstruction in the majority of patients without excess morbidity (including a lack of any detectable increase in sepsis). Thus, it appears feasible to consider randomized studies of this cytotoxic approach versus standard mechanical drainage procedures to define the relative risks and benefits of each.
Adult↗
Microgastrinomas of the duodenum. A cause of failed operations for the Zollinger-Ellison syndrome.
Gastrinomas are now being detected at an earlier stage than was formerly the case. Furthermore, with the ability to control acid secretion, emphasis has been placed on identifying gastrinoma patients who are potentially curable by tumor resection rather than by palliative gastrectomy. Despites estimates suggesting that 20-40% of sporadic gastrinoma patients can be successfully resected for cure, as many as 40% of such patients have occult tumors that elude detection. In an effort to better localize gastrinomas, we have used percutaneous transhepatic venous (THVS) gastrin sampling over the past 10 years. From 1978 to 1988, THVS was used in 46 patients in whom there was no other evidence of metastatic gastrinoma by conventional studies. Gastrinomas were found at operation in all but one patient. The purpose of this report is to emphasize that occult tumors are most often found in the duodenal wall, and frequently they may be no greater than 2 mm in diameter. Five recent cases illustrate that these small tumors or microgastrinomas may be the sole source of hypergastrinemia and can be cured by local excision. These recent cases emphasize that microgastrinomas are not usually palpable through the duodenal wall. They may be detected only after duodenotomy and meticulous evaluation of the mucosa by eversion and direct palpation. Duodenotomy and intraluminal exploration should be considered an essential component of the operation for patients with extrapancreatic gastrinomas.
Aged↗
Albumin utilization in a university hospital.
The inappropriate use of high-priced agents such as human serum albumin significantly contributes to the rising cost of medical care. A utilization review was conducted at the University of Michigan Hospital in order to identify the appropriateness of use of this agent. Criteria were developed and prescribing was retrospectively evaluated for 81 patients. Of the 935 units administered to these patients, 692 (74 percent) were judged to be inappropriate. This inappropriate use accounted for a projected annual expenditure of nearly $281,000. Interventions have previously demonstrated success in improving prescribing.
Drug Utilization↗
Operative timing and patient survival following distal splenorenal shunt.
The importance of "operative timing" in cirrhotic patients with variceal hemorrhage is often underemphasized. To evaluate the effects of immediate versus delayed selective portasystemic decompression on hepatic function, operative mortality, and long-term patient survival, we reviewed the records of 77 patients who underwent distal splenorenal shunts (DSRS) over a 14-year period. A hepatic risk status score was calculated at the time of the index bleed (HRS1) or presentation and again just prior to operation (HRS2). Variables analyzed included age, sex, prior bleeding episodes, time from index bleed to operation, transfusion requirements, and etiology of cirrhosis. Operative mortality rates for immediate versus delayed DSRS were 46.2 per cent and 17 per cent, respectively. HRS improved significantly in elective DSRS patients from 1.46 to 1.30. Predictors of HRS2 included HRS1 and time in days from the index bleed to operation. The most important predictor of early survival for all patients after elective DSRS was the HRS2; however, for patients who underwent elective DSRS and survived, HRS1 was a better predictor of length of survival than HRS2. No other variable analyzed accurately predicted survival. We conclude that HRS can be expected to improve with supportive inhospital therapy; improved HRS at the time of operation is associated with decreased operative mortality; and the extent of liver disease as determined by HRS1 appears to be the chief determinant of long-term patient survival.
Female↗
A prospective study of clinically and endoscopically documented colonic ischemia in 100 patients undergoing aortic reconstructive surgery with aggressive colonic and direct pelvic revascularization, compared with historic controls.
Clinically and endoscopically proved ischemia of the colon complicates elective aortic reconstruction in 1% to 2% and 6% to 7% of cases, respectively. Operative mortality exceeds 60% when transmural infarction occurs. A prospective study of colonic ischemia was undertaken in 100 male patients (mean age, 62.4 +/- 7.9 years) undergoing operation for aortic aneurysms (58) or aortoiliac occlusive disease (42). Conventional aortic surgery was undertaken in 88 patients, and in 12 patients adjunctive procedures to enhance colonic perfusion were performed 14 times, including IMA reimplantation (8), direct bypass to the internal iliac artery (4), and anastomosis of an aortofemoral bypass limb to adjacent common iliac artery (2). Colonoscopy was performed within 24 to 48 hours of aortic reconstruction. Three patients had endoscopic evidence of colonic ischemia. Transmural infarction did not develop in any patient, and bowel resections or diverting colostomies were not necessary. Three patients died, none manifesting colonic ischemia. The 12% utilization of adjunctive procedures to enhance blood flow in the colon was substantially greater than the 4% frequency of an earlier experience from our institution in which nearly half of the 5.7% operative mortality was attributed to colonic infarction. Attention to factors contributing to ischemia of the colon, and more frequent adjunctive revascularization of the colon, may lessen this complication of aortic reconstructive surgery.
Angiography↗
Malignancy and concomitant primary hyperparathyroidism.
Hypercalcemia is associated with a few primary malignant neoplasms and with a variety of tumors that have spread by metastases. Hyperparathyroidism is a diagnosis that is usually not considered in these patients. At our institution, 18 patients with malignant tumors presented over a 6-year period with hypercalcemia caused by hyperparathyroidism. There were five men and 13 women with a mean age of 48 years (range 24-87 years). Primary tumors in these patients included colon carcinoma (four cases), breast carcinoma (four cases), lymphoma (four cases), thyroid carcinoma (four cases), Paget's disease (one case), and lung carcinoma (one case). Metastases of the primary tumor occurred in seven patients, and in 11 patients the tumor was not metastatic or recurrent. Serum levels of calcium, phosphate, and chloride averaged 11.8 mg/dl, and 100 mEq/liter, respectively. C-terminal parathyroid hormone (PTH) levels ranged from 300 to 1,900 pg/ml with an average of 1,150 pg/ml (normal 50-340 pg/ml). At operation, a single parathyroid adenoma was discovered in 15 patients, and four-gland hyperplasia was noted in three patients. In all cases, serum levels of calcium returned to normal after operation. We conclude that patients with malignant tumors and concomitant hypercalcemia should be evaluated for the possibility of hyperparathyroidism. In cases of primary hyperparathyroidism, elevated C-terminal PTH level should be diagnostic. If hyperparathyroidism is determined to be the cause of hypercalcemia, neck exploration and parathyroidectomy are indicated.
Adenocarcinoma↗
Diagnostic dilemmas in patients with cystic neoplasms of the pancreas.
Cystic neoplasms of the pancreas (CNP) are rare lesions that can be difficult to diagnose preoperatively. Twenty patients with cystic neoplasms of the pancreas including five microcystic adenomas, six benign mucinous cystic neoplasms, three malignant mucinous cystic neoplasms, two solid and papillary epithelial neoplasms, and four cystic neuroendocrine tumors were treated at a single institution between 1962 and 1987. The average duration of symptoms prior to diagnosis was 10 months. Five patients were asymptomatic. Forty percent of patients presented with an abdominal mass. Plain abdominal x-rays and UGI barium contrast studies were never diagnostic. Ultrasonography, computerized tomography (CT) and visceral angiography aided in the correct diagnosis in 28%, 36%, and 75% of patients studied, respectively. Overall a correct diagnosis was made preoperatively in only 35% of patients. Twelve of 13 patients were correctly diagnosed at laparotomy with intraoperative biopsy. Without biopsy the mass was misdiagnosed at laparotomy in five of six cases. CNP must be suspected in any patients who present with an upper abdominal mass with or without abdominal pain and no history of pancreatitis. CT may be diagnostic in up to one third of cases and should be obtained routinely to demonstrate the proximity of the lesion to other structures. Visceral angiography should also be obtained prior to operation. A generous incisional biopsy should be obtained of all pancreatic cysts that are not to be resected.
Adult↗
Completion gastrectomy for postsurgical gastroparesis syndrome. Preliminary results with 15 patients.
Postsurgical gastroparesis syndrome (PGS) is a complex disorder characterized by postprandial nausea, vomiting, and gastric atony without evidence of mechanical gastric outlet obstruction. These symptoms can be disabling and are frequently unresponsive to drug therapy. Fifteen patients with documented PGS, including 13 women and two men, were recently treated by completion gastrectomy (CG) over a 5-year period. Gastric emptying study (GES) was markedly prolonged in 12 of the patients studied, and improved partially in only one patient (8%) with the administration of metoclopramide alone or combined with other gastrokinetic drugs. Patients were evaluated both before and after surgery, using a modified Visick rating system and a severity of symptoms (SS) score based on seven gastrointestinal (G.I.) and five systemic variables. All 15 patients underwent CG and reconstruction with a 50 cm Roux-en-Y limb. There were no operative deaths or complications related to the esophagojejunal anastomosis. Mean postoperative follow-up was 13.9 months, with a range of 2-65 months. After CG, the Visick rating and overall SS score improved significantly. The improvement in SS score was primarily due to a significant decrease in G.I. symptoms with little or no change in systemic symptoms. Overall, 86% of patients reported a satisfactory clinical result. CG, while seemingly radical, can be performed with low risk, and for properly selected patients with PGS, may be the treatment of choice.
Adult↗