Metronomic gemcitabine suppresses tumour growth, improves perfusion, and reduces hypoxia in human pancreatic ductal adenocarcinoma.

BACKGROUND: The current standard of care for pancreatic cancer is weekly gemcitabine administered for 3 of 4 weeks with a 1-week break between treatment cycles. Maximum tolerated dose (MTD)-driven regimens as such are often associated with toxicities. Recent studies demonstrated that frequent dosing of chemotherapeutic drugs at relatively lower doses in metronomic regimens also confers anti-tumour activity but with fewer side effects. METHODS: Herein, we evaluated the anti-tumour efficacy of metronomic vs MTD gemcitabine, and investigated their effects on the tumour microenvironment in two human pancreatic cancer xenografts established from two different patients. RESULTS: Metronomic and MTD gemcitabine significantly reduced tumour volume in both xenografts. However, K(trans) values were higher in metronomic gemcitabine-treated tumours than in their MTD-treated counterparts, suggesting better tissue perfusion in the former. These data were further supported by tumour-mapping studies showing prominent decreases in hypoxia after metronomic gemcitabine treatment. Metronomic gemcitabine also significantly increased apoptosis in cancer-associated fibroblasts and induced greater reductions in the tumour levels of multiple pro-angiogenic factors, including EGF, IL-1alpha, IL-8, ICAM-1, and VCAM-1. CONCLUSION: Metronomic dosing of gemcitabine is active in pancreatic cancer and is accompanied by pronounced changes in the tumour microenvironment.

Open abdomen in liver transplantation.

INTRODUCTION: Damage control laparotomy with vacuum assisted closure (VAC) is used for selective cases in trauma. In liver transplantation, VAC has also been applied for management of intra-operative hemorrhage. The primary objective was to evaluate peri-operative blood loss and blood product utilization in VAC compared to primary abdominal closure (PAC) at the index transplant operation. METHODS: Retrospective review of all adults undergoing deceased donor liver transplantation (2007-2011) at a single center tertiary care institution. RESULTS: 201 deceased donor liver transplantations were performed, with 167 PAC and 34 VAC cases. Intra-operative blood loss (4.4L vs 10.7L), cell saver return (1399 ml vs 3998 ml), FFP (7.6U vs 15.9U) and PLT requirements (8.5U vs 18.3U), were all significantly elevated in VAC compared to PAC. VAC patients had significantly increased RBC, FFP, PLT, and total volume requirements during initial ICU admission. 30 PAC cases required on demand laparotomy and most commonly for post-operative bleeding. CONCLUSION: In liver transplantation, application of VAC secondary to massive intra-operative exsanguination was safely utilized. Further evaluation is required to identify long-term morbidity and mortality.

Pathophysiology of apolipoprotein E deficiency in mice: relevance to apo E-related disorders in humans.

Apolipoprotein E (apo E) deficiency (or its abnormalities in humans) is associated with a series of pathological conditions including dyslipidemia, atherosclerosis, Alzheimer's disease, and shorter life span. The purpose of this study was to characterize these conditions in apo E-deficient C57BL/6J mice and relate them to human disorders. Deletion of apo E gene in mice is associated with changes in lipoprotein metabolism [plasma total cholesterol (TC) (>+400%), HDL cholesterol (-80%), HDL/TC, and HDL/LDL ratios (-93% and -96%, respectively), esterification rate in apo B-depleted plasma (+100%), plasma triglyceride (+200%), hepatic HMG-CoA reductase activity (-50%), hepatic cholesterol content (+30%)], decreased plasma homocyst(e)ine and glucose levels, and severe atherosclerosis and cutaneous xanthomatosis. Hepatic and lipoprotein lipase activities, hepatic LDL receptor function, and organ antioxidant capacity remain unchanged. Several histological/immunohistological stainings failed to detect potential markers for neurodegenerative disease in the brain of 37-wk-old male apo E-KO mice. Apo E-KO mice may have normal growth and development, but advanced atherosclerosis and xanthomatosis may indirectly reduce their life span. Apo E plays a crucial role in regulation of lipid metabolism and atherogenesis without affecting lipase activities, endogenous antioxidant capacity, or appearance of neurodegenerative markers in 37-wk-old male mice.

Hepatic hemangioblastoma. An unusual presentation in a patient with von Hippel-Lindau disease.

We report a case of multiple capillary hemangioblastomas of the liver occurring in a patient with von Hippel-Lindau disease and a history of previous cerebellar and spinal hemangioblastomas. Although rare examples of this tumor have previously been recorded in the pancreas, kidney, and urinary bladder, this appears to be the first recorded case with hepatic involvement. The histology and immunohistochemical appearance of this neoplasm are identical with those of the cerebellar tumor. We believe it represents a separate primary neoplasm rather than metastatic disease.

The quality of initial function following renal transplantation determined by creatinine elimination kinetics. Comparison of Minnesota antilymphocyte globulin and cyclosporine induction immunosuppression.

To compare the effect of type of induction immunosuppression on the quality of initial renal allograft function, we identified 35 cadaver donor kidney pairs in which one recipient of a kidney from a given pair received induction immunosuppression with Minnesota antilymphocyte globulin (MALG group) while the recipient of the contra-lateral kidney received cyclosporine from day zero (CsA group). In the absence of an existing quantitative measure to assess and compare the status of those grafts that function primarily, we defined the half-life of creatinine elimination (t1/2SCr) as such an outcome measure based on a review of creatinine elimination kinetics. All organs were procured with in-situ perfusion and en-bloc removal. Total cold storage times, rewarm times, and perioperative management were comparable for the two groups. In the MALG group, the mean t1/2SCr) was not different from that in the CsA group (1.38 +/- 0.96 days vs 1.35 +/- 1.2 days P = NS). Multiple regression analysis performed on the differences in recipient age, number of DR-B locus matches, total cold ischemia time, rewarm time, and central venous pressure at reperfusion of a given donor pair demonstrated no significant impact of any of these differences on the difference in t1/2SCr for the same pair set in this sample. The nadir of serum creatinine achieved in the first five days posttransplant was somewhat higher in the CsA group (234 +/- 131 mumol/L) as compared with the MALG group (200 +/- 132 mumol/L) but the difference was not significant. A similar nonsignificant trend was observed in the comparison of mean serum creatinine values at 30 days posttransplant (MALG group: 158 +/- 62 mumol/L vs. CsA group: 200 +/- 141 mumol/L). Only one of seventy recipients (CsA group) was dialyzed within the first 5 days posttransplant for an overall incidence of ATN of less than 2%. Fourteen of 35 (40%) recipients in both groups received treatment for acute rejection. The mean time to first treatment for acute rejection episode was shorter in the CsA group than the MALG group (10 +/- 8 days vs 23 +/- 24 days, P = 0.055). Graft survival at one year was not different for the two groups (92% vs. 87% for the MALG and CsA groups respectively, P = NS).(ABSTRACT TRUNCATED AT 400 WORDS)

Specificity of the commonly used enzymatic assay for plasma cholesterol determination.

AIM: To assess the specificity and sensitivity of the commonly used enzymatic colorimetric test for plasma cholesterol determination. METHODS: Interference with an enzymatic method for cholesterol measurement by several non-cholesterol sterols (beta sitosterol, campesterol, stigmasterol, stigmastanol, desmosterol, and lathosterol) was assessed. Some of these compounds are present in plasma at higher than normal concentrations either in rare genetic disorders, such as phytosterolaemia, or after the consumption of phytosterol enriched foods. RESULTS: The non-cholesterol sterols were detected by the assay in a linear manner. There was no competitive interference in the presence of cholesterol. CONCLUSIONS: This crossreactivity may affect the diagnosis and treatment of non-cholesterol dyslipidaemias, including phytosterolaemia and cerebrotendinous xanthomatosis. Similarly, changes in plasma lipid compositions after the consumption of phytosterol enriched foods cannot be specifically determined by this enzymatic assay. Until a more specific enzymatic assay is developed, alternative methods such as gas chromatography should be used to differentiate between cholesterol and non-cholesterol sterols.

Emergency management of choledochal cysts in adult patients.

Congenital cystic dilation of the biliary tree is rarely considered as cause of cholangitis in the adult patient. Emergency operation in seven adults with unsuspected choledochal cysts resulted in reoperation in all seven. Each patient presented with right upper quadrant pain, a mass, and cholangitis or jaundice. Abdominal ultrasonography incorrectly identified the cyst as a dilated gallbladder in three of the patients. All initial emergency drainage procedures required subsequent modification to cyst excision and Roux-Y reconstruction. From review of the experience presented and the literature to date, we recommend that otherwise stable patients be managed nonsurgically and undergo endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography to plan primary single-stage excisional operation. Patients requiring emergency decompression should have cholecystostomy or choledochostomy for good control without compromising subsequent operation. At the time of excision, a technical consideration not previously reported is the presence of small daughter cysts in Calot's triangle which must be distinguished from the hepatic bile ducts. The surgical literature has frequently addressed the problems of elective surgery for choledochal cysts; however, emergency complications requiring urgent operative intervention are seldom addressed. We believe emergency intervention should correct the urgent complication without compromising the definitive surgical treatment.

Evaluation of 50 consecutive segmental hepatic resections.

The development of increasingly sensitive imaging techniques along with improved follow-up and screening of high-risk patients has led to hepatic tumors, both primary and secondary, being detected while still at an early stage. Improved understanding of hepatic anatomy along with advances in surgical technique has led to the ability to undertake hepatic resections based on the segmental hepatic anatomy as described by Couinaud. The purpose of this paper is to assess the safety, technique, and oncologic efficacy of segmental hepatic resection. Fifty consecutive patients undergoing segmental hepatic resection during a 3-year time period ending in January 1992 were reviewed. Parametric statistical analysis was undertaken using Student's t-tests. Overall mortality was 2% with a morbidity rate of 8%. Transfusion requirements were 1 +/- 1.5 U; however, cirrhotic patients showed a significantly increased transfusion requirement of 2.0 +/- 1.3 U versus 0.7 +/- 1.3 U (p = 0.03). Sixty percent of patients required no transfusion at all. The mean duration of inflow occlusion was 42 +/- 17 minutes. Resection margins were clear of tumor by greater than 1 cm in 48 of 50 patients. Segmental hepatic resection is a safe and effective technique that occasionally may offer advantages over formal resection. Some aspects of the technique are reviewed.

Hepatocellular carcinoma. A comparison of Oriental and Caucasian patients.

Hepatocellular carcinoma is a very malignant tumor that affects both Caucasian and Oriental populations. In the Caucasian patient, it frequently arises in a background of cirrhosis, most commonly the alcoholic type. In the present study, the alpha-feto-protein level was increased in less than half of the Caucasian patients. In comparison, hepatocellular carcinoma in Oriental patients most often occurs in livers with postinfectious cirrhosis. In the present study, both hepatitis B surface antigen and an increased alpha-fetoprotein level were present in three of four patients. If the tumor is present, however, it appears to behave similarly in both ethnic groups. Without resection, the prognosis is poor, regardless of the presence or absence of underlying cirrhosis or hepatitis B surface antigen status. A tissue diagnosis of hepatocellular carcinoma is most readily made by ultrasonographically guided fine-needle aspiration, which has an 81 percent sensitivity. The most important factor affecting survival is surgical resection. Clearly, the stage at diagnosis is also crucial, but even in more advanced disease, operation can improve survival. It also appears that an increased carcinoembryonic antigen level above normal or a markedly increased alpha-fetoprotein level or both are associated with poor survival. However, whether this is a reflection of tumor size alone, or in fact represents a more aggressive tumor is uncertain and will require further study.

Typhlitis: selective surgical management.

Typhlitis is a neutropenic enterocolitis of varying severity. Its incidence is increasing, particularly in patients with acute myelogenous leukemia undergoing high dose cytosine arabinoside chemotherapy. The onset is heralded by prodromal fever, watery or bloody diarrhea, abdominal distension, and nausea during the phase of severe neutropenia. The symptoms may then localize to the right lower quadrant with an associated increase in systemic toxicity. The diagnosis can be confirmed in these and other less specific cases by serial reexamination and abdominal radiographs, ultrasonography, computerized tomograms, or radionucleotide scans. The mainstay of management is complete bowel rest with nasogastric suction and total parenteral nutrition. Broad-spectrum combination antibiotics are essential, as is the avoidance of laxatives or antidiarrheal agents. Granulocyte support may be helpful. Patients with a history of nonspecific gastrointestinal complaints or of true typhlitis, successfully managed nonoperatively, should have prophylactic bowel rest and total parenteral nutrition instituted at the beginning of further chemotherapy. Patients with ongoing severe systemic sepsis who do not respond to chemotherapy and those with overt perforation, obstruction, massive hemorrhage, or abscess formation require surgical intervention. All necrotic material must be resected, usually by a right hemicolectomy, ileostomy, and mucous fistula. Divided ileostomy for less severe cases may be useful. Failure to remove the necrotic focus in these severely immunocompromised patients is fatal. With adequate recognition of typhlitis and its precipitating factors, the incidence of complications can be reduced through prevention and timely surgical intervention. Although typhlitis developed in a quarter of our acute myeloblastic leukemia patients, use of this combined approach was successful in all cases.

Correlation between physiological assessment and outcome after liver transplantation.

BACKGROUND: Critical shortages of organ donors for transplantation require appropriate utilization of this scarce resource. The purpose of this study was to assess whether use of physiological parameters of preliver transplant recipients is helpful in determining eventual outcome. METHODS: Between October 1989 and June 1999, 215 liver transplants were performed on 199 patients at the Vancouver Hospital nad Health Sciences Centre. Thirty-one patients undergoing transplantation between May 1993 and June 1994 were retrospectively evaluated to obtain a minimum 5-year follow-up. Variables examined included pretransplant activation status (status 1, at home; status 2, hospitalized; status 3, admitted to intensive care; status 4, mechanical ventilation), simplified acute physiological score (SAPS), Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II, and APACHE III scores at the time of transplantation. The scores were correlated to posttransplant mortality and functional outcome. RESULTS: The 5-year mortality for status 1 patients was 14.3% versus 30% for patients listed as status 2 or greater (P = not significant). There were no significant differences in any of the physiological scoring assessments with regard to posttransplant mortality or functional assessment. Of the surviving patients, 18 of 22 who were employed, in school, or active at home pretransplant returned to their pretransplant activity. CONCLUSIONS: Detailed physiological scoring systems are no more accurate in predicting outcome after liver transplant than current listing status parameters.

Indocyanine green clearance as a predictor of successful hepatic resection in cirrhotic patients.

Twenty-two cirrhotic patients who underwent hepatic resection from July 1989 to March 1991 at Vancouver General Hospital were analyzed prospectively in order to determine whether there was any preoperative evaluation of liver function that would help identify those patients who would not survive hepatic resection. Patients were analyzed on the basis of age, type of resection, and a variety of so-called standard liver function tests. In addition, all patients were evaluated preoperatively with an indocyanine green (ICG) clearance test, a relatively new test that we attempted to evaluate in terms of its role in hepatic resection in cirrhotic patients. Parametric statistical evaluation used included Student's t-test and multivariate regression, as well as discriminate analysis. The nonparametric evaluation used was the Wilcoxon rank sum test. Overall, the 30-day mortality rate was 18%, with those patients who did not survive resection having a significantly lower ICG clearance than those who underwent successful resection (p less than 0.0001). No other liver function test was useful in determining the outcome of resection. Similarly, neither age nor type of resection appeared to influence outcome. Use of discriminate analysis (p = 0.0029) allowed the identification of a cutoff point for ICG clearance below which hepatic resection should not be attempted.

Mesohepatectomy.

BACKGROUND: Formal anatomic (lobar) or extended hepatectomies are recommended for liver malignancies located centrally within the liver (Couinaud's segments IVA, IVB, V, and VIII). Mesohepatectomy, resection of central hepatic segments and leaving the right and left segments in situ, removes large central tumors preserving more functioning liver tissue than either extended left or right hepatectomy. Mesohepatectomy is a seldom used, technically demanding procedure, and its application is yet to be defined. METHODS: Medical charts of 244 consecutive liver resection patients were reviewed retrospectively. Eighteen patients were treated with mesohepatectomy. Six patients had metastatic liver tumor (MLT), 11 had hepatocellular carcinoma (HCC), and 1 had gallbladder adenocarcinoma. The operative results were compared with groups of patients treated by lobar hepatectomy (n = 71) and extended left or right hepatectomy (n = 43). RESULTS: The mean mesohepatectomy operative time was 238 versus 304 minutes in the extended group. Inflow occlusion mean time was longer in the mesohepatectomy group than in extended procedures, 45 versus 39 minutes (P = not significant). Comparing the extended hepatectomy group, the mesohepatectomy group had a mean operative estimated blood loss 914 cc versus 1628 cc (P <0.01), postoperative hospital stay 9 versus 16 days (P = 0.054) and volume of resected liver 560cc versus 1500cc (P <0.01) respectively. The late complication rate was lower in the mesohepatectomy group than in the extended group and was comparable to the lobar hepatectomy group (P = 0.05). CONCLUSIONS: Despite its technical demands, mesohepatectomy should be considered as an alternative to extended hepatectomy for selected patients with primary and secondary hepatic tumors localized in middle liver segments, as its complication rate, postoperative recovery, and preserved liver tissue compare favorably with extended hepatic resection.

Medium aperture meso-caval shunts reliably prevent recurrent variceal hemorrhages.

BACKGROUND: Objectives of partial medium aperture mesocaval shunts (MCS) include reduction of portal hypertension to prevent recurrent variceal hemorrhage, preservation of portal flow through liver while maintaining an intact porta hepatis to facilitate a future liver transplant (OLTx). PATIENTS AND METHODS: Fifteen patients were retrospectively analyzed to review the indications for the procedure, its short- and long-term complications as well as patency and functional status of the shunt. They were followed for a period of 21 months. RESULTS: The perioperative and long-term mortality rate was 0%. Rebleeding rate perioperatively and in follow-up was 0%. Early shunt nonfunction was 13% and post-shunt encephalopathy (PSE) was 20%. The encephalopathy was grade I to II and controlled medically. Abdominal ultrasound and Doppler confirmed 13 patent shunts (2 patients did not agree to ultrasound) with preserved hepatopetal flow in 10. CONCLUSIONS: Medium aperture MCS utilizing ringed polytetrafluoroethylene (PTFE) grafts safely and reliably prevent recurrent variceal hemorrhage. Encephalopathy is infrequent and mild. This technique preserves the portal venous anatomy making a future OLTx technically easier.

Human amnion as a bioprosthesis for bile duct reconstruction in the pig.

Despite technical advances in management, the complication of late stricture formation and biliary sepsis still occur in bile duct reconstruction. In an attempt to avoid bilioenteric anastomosis, which bypasses the biliary sphincter mechanism, various biologic and artificial materials have been employed clinically and experimentally to replace the damaged bile duct. No satisfactory biliary replacement material has yet been found. In the experimental model of bile duct stricture that has been presented, human amnion bile duct injuries mimicking those seen in clinical practice were repaired using human amnion as a free graft. Noncircumferential duct loss appeared to be satisfactorily repaired using amnion, and the amnion repair was found to be as good as or superior to plastic repair; however, circumferential duct loss was not adequately repaired with the amnion graft.

Surgical management of choledochal cysts.

Choledochal cysts are an unusual cause of biliary obstruction with up to 85% of reported cases being of the type I variety, that is, fusiform dilations of the common bile duct. Recommended management of this type I cyst is complete surgical excision; however, difficulties arise in type IVa cysts when the cystic dilation extends up into the intrahepatic biliary tree. The purpose of this study is to review the management of choledochal cysts with particular reference to the type IVa variety. Statistical analysis of outcome differences was undertaken using Fisher's exact test. A total of 23 consecutive patients with choledochal cysts seen at our institution in a 5-year period were reviewed: 8 patients had type I cysts, 1 patient had a type III cyst, and 14 patients had type IVa cysts. All type I cysts underwent complete cyst excision with hepaticojejunostomy and modified Houston loop formation. Of 14 patients with type IVa cysts, 13 underwent complete excision of the extrahepatic portion of the cyst with hepatico- and cystojejunostomy and modified Hutson loop formation. One patient required hepatic lobectomy. With a mean follow-up of 33 months, 4 patients with type IVa choledochal cyst have had episodes of recurrent cholangitis, with access to the library tree being achieved via the Hutson loop in 3 of the 4 patients. Three of these cases represented anastomotic strictures that were treated nonoperatively. We concluded that recurrent cholangitis and anastomotic stricture after resection of type IVa choledochal cysts is frequent and recommend Hutson loop formation at the time of primary resection.

Aprotinin reduces the need for blood products during liver transplantation.

BACKGROUND: Bleeding complications and blood product consumption have been a major concern during liver transplantation. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood-product consumption. PATIENTS AND METHODS: Use of blood-products (packed red cells, frozen plasma, platelets, and cryoprecipitate) was analyzed both during the three stages of orthotopic liver transplantation and during total hospitalization of the 26 patients transplanted without aprotinin and the subsequent 40 patients with aprotinin. A similar analysis was performed for 15 patients immediately before and after the introduction of aprotinin to eliminate the "learning curve" effect for liver transplantation. The effect of epsilon-amino-caproic acid was analyzed as 13 patients received neither epsilon-aminocaproic acid nor aprotinin and 13 patients received epsilon-aminocaproic acid but not aprotinin. RESULTS: There was a significant reduction in total hospital use of cryoprecipitate, frozen plasma, platelets, and red cells in the aprotinin-treated patients. This reduction was seen during the anhepatic and reperfusion stages of liver transplantation. There was no difference in blood product consumption between the groups who were or were not treated with epsilon-aminocaproic acid. CONCLUSION: Aprotinin significantly reduces the need for red cell, frozen plasma, platelet, and cryoprecipitate transfusion use during orthotopic liver transplantation, and appears to be more efficacious than epsilon-aminocaproic acid.

Radiofrequency ablation followed by resection of malignant liver tumors.

BACKGROUND: Radiofrequency ablation (RFA) has recently been used to treat liver tumors, but few clinical reports have described the pathological characteristics of radiofrequency ablation in human specimens. This study delineates the gross pathologic and histochemical changes induced by RFA in benign and malignant human liver tissue and confirms the tumor necrosis described in early clinical reports. METHODS: Ten patients with metastatic tumors of the liver received a single treatment of ultrasound-guided percutaneous RFA to 12 tumors. Hepatic resection was carried out within 6 weeks of RFA. Specimens were stained with standard hematoxylin and eosin stain followed by oxidative stain to determine if there was evidence of viable tumor within the zone of ablation. RESULTS: Nine of the 12 ablations were resected. Microscopic examination within the zone of ablation showed successful ablation in 8 of the 9 resected ablations. CONCLUSIONS: Percutaneous RFA creates well-circumscribed areas of tumor necrosis with apparent cell death using an oxidative stain. Further investigation is encouraged to determine the clinical effectiveness of radiofrequency ablation in the complete destruction of liver tumors for palliative or curative intent.

Post-surgical shunt hepatopulmonary syndrome in a case of non-cirrhotic portal hypertension: lack of efficacy of shunt reversal.

Hepatopulmonary syndrome, a consequence of significant liver disease and portal hypertension, is thought to be secondary to the effects of vasoactive substances, normally inactivated in the liver, on the pulmonary vasculature. We report a patient with preserved hepatic function who underwent a decompressive surgical porto-systemic shunt for non-cirrhotic portal hypertension. This patient developed hepatopulmonary syndrome with dyspnoea and oxygen desaturation 2 years post-surgical shunt. Over the next 7 years, the patient's respiratory function became increasingly impaired although hepatic function remained preserved. Because of the hypothesized role of porto-systemic shunting in the aetiology of this syndrome, the surgical shunt was successfully reversed angiographically. No improvement in dyspnoea or oxygen saturation occurred and liver transplantation was undertaken. Six months post-transplant, the patient has decreased his oxygen requirements and is free of dyspnoea. Our experience supports the causal role of porto-systemic shunting in the pathogenesis of hepatopulmonary syndrome but suggests that merely decreasing the extent of porto-systemic shunting is not beneficial. Liver transplantation remains the only reliable therapeutic modality available to these patients.

Oral cholecystography after liver transplantation in man.

Orthotopic liver transplantation has been performed in Cambridge since 1967. In order to prevent complications resulting from the biliary drainage techniques, the donor gall bladder was interposed between the donor and recipient common bile duct as a vascularised pedical graft. The procedure, first performed in 1976, has been employed where possible ever since. Six patients having had this technique performed, and who remained well six months to six years after liver graft, underwent oral cholecystography. Four patients opacified the interposed gall bladder and the gall bladder contracted in response to cholecystography or a fatty meal. This is the first time oral cholecystography has been used in these patients. The detail is such that it can be used to follow non-jaundiced liver-grafted patients.