Resectional surgery for gallbladder cancer.
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Cholecystectomy↗
Biomedical subjects
I S Benjamin
Publications and source records attributed to I S Benjamin.
The relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver.
BACKGROUND: Portal hypertension is associated with gross haemodynamic disturbances characterised by high cardiac output, low peripheral vascular resistance, increased splanchnic blood flow, and portal systemic shunting. AIMS: To study the relationship between intrahepatic portal systemic shunts and microsphere induced portal hypertension in the rat liver. METHODS: Different sized microspheres were sequentially injected into the portal vein of male Wistar rats. RESULTS: Steady state portal venous pressure was increased by 102.2 (35.6)% (14.9 (3.6) mm Hg) and 272.3 (78.0)% (24.0 (2.2) mm Hg) above the basal pressure following sequential injections of 15 and 80 microns diameter microspheres, respectively. Sequential injection of 15, 40, and 80 microns diameter microspheres in either ascending or descending order of size did not generate further increases in portal venous pressure. A single injection of 1.8 x 10(5) 80 microns microspheres consistently produced a steady state portal venous pressure of 19.0 (1.3) mm Hg but did not approach the much higher value of 36.6 (43.2) mm Hg measured during clamping of the portal vein. These data indicate that the opening of patent intrahepatic shunts was responsible for the reduced pressures observed during microsphere injections and further evidence for this was provided by the location of microspheres in the pulmonary vascular bed. The elevation in portal venous pressure achieved by microsphere injections was not significantly different to that produced in rats subjected to partial portal vein ligation (20.7 (0.5) mm Hg, p > 0.05). Wedged hepatic venous pressure decreased from 6.7 (0.7) to 3.0 (0.6) mm Hg following injection of 80 microns microspheres, suggesting a decrease in total hepatic blood flow. Conversely, injection of 15 microns microspheres induced an increase in wedged hepatic venous pressure from 7.0 (1.0) mm Hg to 12.4 (1.8) mm Hg, indicating a localised redistribution of blood flow at the presinusoidal level of the portal venous vascular network and increased intrahepatic shunt flow. CONCLUSION: It is suggested that there may be a protective pathophysiological role for these shunts when the liver is subjected to changes which induce acute portal hypertension.
Acute Disease↗
The action of ATP on the hepatic arterial and portal venous vascular networks of the rabbit liver: the role of adenosine.
ATP is released from blood vessels during periods of hypoxia and may be responsible for hepatic arterial vasodilatation during instances of reduced hepatic portal venous flow. The role of adenosine in ATP-induced vasodilator and vasoconstrictor responses of the hepatic arterial and portal venous vascular networks respectively was studied in the isolated dual-perfused rabbit liver in vitro to ascertain whether ATP could be catabolised to adenosine during transit through the hepatic parenchyma. Intra-arterial and intra-portal injections of ATP (-10 to -4 log mol/100 g liver) resulted in dose-dependent vasodilatation in the hepatic artery and vasoconstriction in the portal vein. Addition of 8-phenyltheophylline (10 microM), a non-selective P1-purinoceptor antagonist, to the hepatic arterial and portal venous perfusate significantly inhibited the hepatic arterial ED50 for responses to intra-arterial injected ATP from -8.70 +/- 0.22 to -7.63 +/- 0.28 log mol/100 g liver (P < 0.001); it also inhibited hepatic arterial responses to, mid-range, portal venous injections of ATP. The data suggest that the hepatic arterial vasodliatation to ATP is partly mediated via catabolism to adenosine and may be an important mechanism during periods of relative hepatic hypoxia associated with portal flow reduction.
Adenosine↗
Pharmacokinetics of valsartan in patients with liver disease.
OBJECTIVES: Valsartan (CGP 48933), an orally active angiotensin II antagonist, is eliminated mainly by hepatic clearance. To characterize the compound(s) excreted in the bile, biliary excretion of valsartan was investigated by collection of bile after an intravenous dose of valsartan. In addition, to determine the exposure to valsartan when liver function is impaired, a pharmacokinetic study (open, single dose) was performed in patients with mild and moderate impairment of liver function. PATIENTS: Biliary excretion of valsartan (after intravenous administration of 20 mg valsartan) was assessed in a patient who underwent a hepaticojejunostomy with subsequent bile drainage. Exposure to valsartan in patients with mild (n = 6) or moderate (n = 6) impaired liver function (Child's-Pugh classification) and matching (sex, age, and weight) healthy volunteers (n = 12) was studied after oral administration of a single dose of 160 mg valsartan. RESULTS: After intravenous administration, valsartan was eliminated mainly as unchanged drug in the bile. Mean exposure (measured as area under the plasma valsartan concentration-time curve) to valsartan was increased about twofold in both the mild and the moderate groups compared with matched (age, sex, and weight) healthy volunteers. CONCLUSION: These data are consistent with the pharmacokinetics of valsartan in that biliary excretion is the main route of elimination.
Adult↗
Biliary malignancies.
Biliary malignancies, including cancers of the intrahepatic and extrahepatic bile ducts, gallbladder and ampulla, should be considered in the differential diagnosis of patients with obstructive jaundice. Cancers of the intrahepatic bile ducts and ampulla are managed as liver and peri-ampullary tumours respectively. Extrahepatic bile duct cancers are diagnosed by cholangiography and evaluated for resectability by imaging and angiography. Vascular infiltration is the main contra-indication for resection, which may also involve the liver. Every attempt must be made to achieve curative resection, but local resection may be justified even if non-curative. Gallbladder cancers are usually advanced at the time of diagnosis and are unresectable--surgical palliation improves the quality of life by relieving biliary and gastric outlet obstruction. Long-term survival is possible after curative resection in early lesions that are usually diagnosed as an incidental finding after cholecystectomy for presumed gallstone disease. The role of adjuvant therapy in biliary malignancies needs further evaluation.
Bile Duct Neoplasms↗
Cold-storage of rabbit thoracic aorta in University of Wisconsin solution reduces endothelium-independent vasodilation.
Optimum preservation conditions for storage of donor livers and blood vessels are essential for successful transplantation. The blood vessels are used as vascular conduits to facilitate anastomosis of the liver to the recipient's systemic vasculature. Failure of some transplants has been ascribed to thrombosis of these vascular conduits possibly because of alterations in vascular reactivity owing to inadequate storage techniques. To restrict data variability previously associated with studies using a heterogeneous sample of vessels from man, this study investigated changes in vascular reactivity in segments of rabbit thoracic aorta from male, age-matched, New Zealand White rabbits stored at 4 degrees C in either University of Wisconsin solution (UW; Du Pont Pharmaceuticals, UK) or Krebs-Bülbring buffer (KB). Percent vasodilation to acetylcholine remained significantly greater in UW than in KB at -log (M) concentrations of 7.0 (UW = 47.05 +/- 4.26 compared with KB = 13.20 +/- 7.20%; P < 0.001), 6.5 (UW = 66.82 +/- 4.83 compared with KB = 26.60 +/- 9.48%; P < 0.01), and 6.0 (UW = 83.68 +/- 5.26 compared with KB = 31.20 +/- 9.83%; P < 0.001). This was not significantly different to relaxation in unstored arteries and suggested improved endothelial function and structure, confirmed by electron microscopy. Percent vasodilation to sodium nitroprusside was significantly lower in UW than in unstored (D0) arteries at -log (M) concentrations of 7.5 (D0 = 28.27 +/- 4.02 compared with UW = 15.21 +/- 1.82%; P < 0.01), 7.3 (D0 = 52.58 +/- 5.05 compared with UW = 29.23 +/- 1.94%; P < 0.01), 7.0 (D0 = 69.70 +/- 4.85 compared with UW = 49.72 +/- 2.49%; P < 0.05), and 6.4 (D0 = 93.16 +/- 2.93 compared with UW = 71.29 +/- 5.20%; P < 0.05). Percent vasodilation was also lower in UW- compared with KB-stored arteries at -log (M) sodium nitroprusside concentrations of 7.0 (UW = 49.72 +/- 2.49 compared with KB = 64.11 +/- 5.03%; P < 0.05) and 6.4 (UW = 71.29 +/- 5.20 compared with KB = 96.91 +/- 5.96; P < 0.05). Electron microscopy confirmed that this was not a result of degradation of smooth muscle structure. The nitric oxide synthase inhibitor L-NG-nitro-L-arginine methyl ester (100 microM) did not significantly modulate sodium nitroprusside-induced vasodilation in unstored arteries, when endothelial function was maximum, or in UW-stored arteries, suggesting that the reduced responses in UW-stored arteries were not because of increased synthesis of nitric oxide. This reduced relaxation to sodium nitroprusside was therefore nitric oxide-independent and not a result of competition between sodium nitroprusside and endothelial 'nitric oxide donation' for cGMP. In summary, cold-storage preservation with UW reduced endothelium-independent vascular relaxation by mechanisms other than competition with NO; this requires further evaluation.
Acetylcholine↗
External beam and intraluminal radiotherapy for locally advanced bile duct cancer: role and tolerability.
BACKGROUND AND PURPOSE: Cholangiocarcinoma is rare but carries a poor prognosis. Radiotherapy has been used either as an adjuvant treatment following surgical resection of tumour or for palliation. The purpose of this study was to assess the feasibility and morbidity of accelerated external beam radiotherapy with or without intraluminal radiotherapy in the treatment of locally advanced bile duct cancer. MATERIALS AND METHODS: Thirty eight patients were treated. Surgical procedures performed prior to radiotherapy were extended hepatectomy (3), hepaticojejunostomy with tumour resection (6), palliative biliary-enteric bypass (6), biopsy (4), Whipple's procedure (1), gastrojejunostomy (1) and cholecystectomy (1). Twenty patients received external beam radiotherapy (ERT). Six patients received one Phase of ERT and 12 received two Phases, separated by a 2-week gap. Dose per Phase was 22.5 Gy in 10 twice daily fractions. After 1989, dose per Phase was increased to 27.5 Gy. One patient received Phase I ERT (30.0 Gy) using conventional fractionation and one patient received an uninterrupted, conventionally fractionate course of treatment (50.0 Gy). Fourteen patients received both ERT and intraluminal radiotherapy (IRT) using iridium-192 (192Ir) wire passed through a percutaneous, transhepatic catheter (median dose, ERT 23.8 Gy + IRT 40.0 Gy). In addition, four patients received IRT alone (median dose 45.0 Gy at 1 cm radius). Patients were followed for at least 42 months. RESULTS: Median overall survival was 15 months. Overall survival for the whole group at 1,2 and 3 years was 59.6%, 32.5% and 16.2%. Thirty four patients died of disease. Radiotherapy caused acute toxicity in seven patients. According to RTOG/EORTC criteria toxicity was Grade 1 in four cases, Grade 2 in two cases and Grade 3 in one case. Two patients developed gastrointestinal bleeding as a late complication of radiotherapy. CONCLUSIONS: Accelerated external beam radiotherapy with or without intraluminal radiotherapy is feasible and associated with acceptable toxicity when used in the management of advance cholangiocarcinoma.
Bile Duct Neoplasms↗
Postcholecystectomy bile duct strictures. Management and outcome in 130 patients.
OBJECTIVE: To evaluate management strategies for the treatment of patients with postcholecystectomy bile duct strictures. DESIGN: Retrospective study. SETTING: The Hepatobiliary Unit of Hammersmith Hospital, London, England. PATIENTS: One hundred thirty consecutive patients referred for treatment of postcholecystectomy bile duct strictures. The majority (80 patients [61.5%]) had undergone multiple operative procedures before referral, and 81 (62.3%) had undergone at least one previous stricture repair. At referral, more than half of the patients had a stricture involving the confluence of the bile ducts (n = 78 [60%]), and 23 (17.7%) had evidence of portal hypertension. MAIN OUTCOME MEASURES: Perioperative mortality, stricture recurrence, and long-term outcome. RESULTS: One hundred twenty-two patients (94%) underwent operative treatment: 110, stricture repair alone; four, portosystemic shunt and stricture repair; and eight, miscellaneous operative procedures. Among the 110 patients treated by stricture repair alone, there was an operative mortality rate of 1.8% (n = 2), and 79 patients (76%) had a good result, with no biliary symptoms and no need for intervention during mean follow-up of 7.2 years (range, 1 to 13 years). Twenty-two patients (21%) required either radiological intervention or operative revision of the biliary-enteric anastomosis, but 11 (50%) of these patients subsequently did well and had no biliary symptoms. Thus, 90 patients (87%) had a good or excellent long-term result after initial or follow-up treatment. There were no deaths among the 108 patients who underwent stricture repair alone by direct suture techniques. Factors influencing mortality included hypoalbuminemia, an elevated serum bilirubin level, and the presence of liver disease and portal hypertension. Preoperative factors influencing failure of the stricture repair in long-term follow-up included discontinuity of the right and left ducts at the time of stricture repair (Bismuth grade 4) and three or more previous attempts at operative repair before referral to our center. CONCLUSIONS: Operative repair of bile duct strictures using direct sutured techniques remains the procedure with which alternative methods will need to be compared, with close attention to long-term outcome.
Adult↗
Changes in E-cadherin immunoreactivity in the adenoma-carcinoma sequence of the large bowel.
We have used an avidin-biotin immunoperoxidase technique to localise epithelial cadherin (E-cadherin), a calcium-dependent cell-cell adhesion molecule, in 107 paraffin-embedded sections from 93 patients consisting of 24 with colorectal adenoma, 55 with rectal carcinoma and 14 with liver metastases. The corresponding primary colorectal tumours were also studied in these cases. E-cadherin was expressed by normal colorectal epithelial cells with typical membranous staining at the intercellular junctions. Loss of normal membranous E-cadherin expression and presence of cytoplasmic staining were found frequently in adenomas larger than 1 cm (P < 0.01), with high grade dysplasia and villous histology (P < 0.01). In primary rectal cancers, loss of membranous expression correlated with high tumour grade. No correlation was seen with Dukes and Jass stage, local extramural spread and 5-year recurrence rate. Complete loss of membranous E-cadherin immunoreactivity was seen in 7/14 (50%) liver metastases in which 6/7 (86%) showed intense membranous E-cadherin immunoreactivity in the corresponding primary tumour. Our data indicate that changes in E-cadherin immunoreactivity and cellular localisation correlate with size, severe dysplasia in adenomas and tumour grade in carcinomas. However, there seems to be no correlation between loss of membranous E-cadherin immunoreactivity and the invasive and metastatic potential of the carcinomas.
Adenoma↗
Hepatic function during prolonged isolated rat liver perfusion using a new miniaturized perfusion circuit.
Previous designs of isolated rat liver perfusion circuits used for toxicological investigations are often expensive, cumbersome, or traumatic in relation to hepatic biocompatibility following extended perfusion times. A new, miniaturized circuit that incorporates a novel design of organ bath, to maintain a buoyant preparation, and a high-efficiency miniaturized membrane tubing oxygenator is described. Livers from male Sprague-Dawley rats were perfused continuously for 6 hr in vitro using rat blood diluted to a perfusate hematocrit of 9.75 +/- 0.35% with Krebs-Henseleit buffer (KHB). Hepatic function was evaluated by measurement of perfusion pressure, flow rate, bile volume production, bile bilirubin content, hepatic oxygen uptake (HOU), bromosulphthalein (BSP) removal, hepatic enzyme activities, and electrolyte concentrations, and finally by histological examination. Perfusion pressure and flow rate remained stable at 8.7 +/- 1.7 mmHg and 1.92 +/- 0.06 mL min-1 g-1 liver, respectively. Bile volume production and HOU were maximal at 784 +/- 84 microL h-1 and 0.99 micromol/L min-1 g-1 respectively. Erythrocyte damage in the perfusate was evaluated by measurement of reduction in perfusate hematocrit from 9.75 +/- 0.35% to 9.27 +/- 0.24%, and increases in plasma free hemoglobin, which rose from 85.8 +/- 12.3 mg% to 650.1 +/- 53.3 mg% over the 6-hr perfusion period studied. Using bile volume production, hepatic oxygen uptake, and the liberation of plasma free hemoglobin as the most sensitive indices of adverse conditions, the new circuit was capable of supporting an isolated perfused rat liver for periods of up to 6 hr under close-to-physiological conditions.
Animals↗
Pancreatic carcinoma.
The management of patients with pancreatic carcinoma poses many problems. The diagnosis is usually made late, generally because the patients present late, but it is not unusual to find patients who have had many negative investigations for vague upper abdominal symptoms only to be diagnosed as having pancreatic carcinoma many months later. Staging the disease is equally difficult and often inaccurate. The results of treatment are to date discouraging even in those patients diagnosed early. But the outlook is not totally dismal; in recent years the results for surgical resection of pancreatic lesions have improved; adjuvant treatment may finally be having an effect, although small, on this relentless disease. The most notable inroad made in the management of pancreatic cancer in the last 10 years is the improvement in palliation due to the use of the endoprosthesis. In spite of the poor results we must continue to search actively for more accurate methods of diagnosis and better methods of treatment.
Antigens, Neoplasm↗
The transhepatic response to noradrenaline in the rabbit liver: the influence of arterioportal pressure gradient.
The dose-related responses of the hepatic arterial and portal venous vascular beds to bolus administration of noradrenaline (10(-10)-10(-4) mol), injected into the hepatic artery and portal vein, were studied in the isolated dual-perfused rabbit liver at both basal and raised tone. The transhepatic ratio, defined as the ratio between the intra-arterial molar ED50 dose and the intraportal dose required to give the same arterial response, was calculated for arterial and venous responses to noradrenaline. At basal tone, the transhepatic ratio for hepatic arterial vasoconstrictive responses was 500. Portal venous vasoconstrictive responses were similar in potency independent of injection site but differed significantly in analysis of dose-response slope and maximal response. At raised tone, the arterio-portal pressure gradient increased by 68.5 mmHg and there was a 10-fold increase in the transhepatic ratio for hepatic arterial responses, while the portal venous responses remained unchanged. These results demonstrate that arterio-portal pressure gradient has a powerful effect on transhepatic action of noradrenaline, and suggest a pre-sinusoidal site for the generation of both hepatic arterial and portal venous vascular resistance.
Animals↗
Penman Lecture. From Langenbuch to laparoscopes--the growth of a specialty.
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Biliary Tract Surgical Procedures↗
Second opinions in laparoscopic cholecystectomy.
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Cholangiopancreatography, Endoscopic Retrograde↗
Hepatic resection with a long sheathed needle: a simple technique.
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Hemostasis, Surgical↗
An evaluation of whether duration of perfusion alters vascular responses in the isolated dual-perfused rabbit liver.
The isolated dual-perfused rabbit liver has been used to characterize hepatic arterial vascular receptors. These hepatic arterial responses are reproducible for 2.5 hr. Further studies in relation to the assessment of portal venous responses using this model require longer periods of perfusion. This study was designed to determine if this model is suitable for the assessment of hepatic arterial and portal venous vascular responses over a 5-hr perfusion period. Hepatic arterial responses were consistent to all agents during 5 hr of perfusion. Portal venous responses to the direct smooth muscle acting agents, sodium nitroprusside and adenosine, were constant, but the vasoconstrictor responses to acetylcholine and adenosine 5'-triphosphate (agents that cause an endothelium-independent vasoconstriction and an endothelium-dependent vasodilatation) were potentiated. Coarse measurements of liver function were also performed and suggested that the liver remained viable for the 5 hr of perfusion. These results suggest a decrease in the ability of the endothelium of the portal venous vasculature to respond to vasoactive substances as duration of perfusion increases. The possible reasons for this are discussed.
Acetylcholine↗
Aspiration cytodiagnosis of pancreatic endocrine tumours.
We have reviewed fine needle aspirates from 11 patients with pancreatic endocrine tumours and evaluated the diagnostic criteria as well as those proposed in the literature in an attempt to formulate reliable criteria for the cytological diagnosis of these tumours. As expected, no single criterion was reliable for diagnosis: however, cells with rounded or polygonal rather than a columnar shape, cytoplasmic granularity, and eccentricity of round or oval nuclei with a finely stippled, evenly distributed chromatin pattern were features which, taken together, usually enabled one to make a reliable diagnosis. A striking feature of the smears was the cellular monotony and absence of pleomorphism of the tumour cells. Immunocytochemistry and electron microscopy identified tumour products and confirmed the diagnosis.
Adenoma, Islet Cell↗
The transhepatic action of ATP on the hepatic arterial and portal venous vascular beds of the rabbit: the role of nitric oxide.
1. The effect of bolus administration of adenosine 5'-triphosphate (ATP) into the portal vein on hepatic arterial pressure (the transhepatic action of ATP) and portal venous pressure, and the contribution of nitric oxide towards these responses, was studied in the in vitro dual-perfused rabbit liver. 2. At basal tone, hepatic arterial and portal venous vasoconstriction followed ATP injection, while at a tone raised with methoxamine (10(-6)-10(-5) M) ATP caused hepatic arterial vasodilatation, and a phasic vasodilatation followed by vasoconstriction in the portal venous vascular bed. 3. To determine whether the transhepatic arterial dilatation was due to the diffusion of nitric oxide (NO) from the portal venous vasculature, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), an inhibitor of NO synthesis, was infused selectively into the portal vein. L-NAME infusion potentiated portal venous vasoconstriction to ATP (-log M ED50 5.32 +/- 0.31 to 6.51 +/- 0.43, P < 0.05, Student's paired t test) indicating the possible inhibition of a NO-mediated vasodilator component of the portal venous response to ATP. There was, however, no demonstrable difference in the transhepatic arterial vasodilatation induced by ATP during this infusion. 4. Simultaneous perfusion of both the hepatic arterial and portal venous inflows with L-NAME (100 microM) resulted in a significant decrease in the amplitude of hepatic arterial responses to ATP demonstrating that these responses were ultimately mediated by an NO-dependent mechanism. 5. This study has thus demonstrated a vasodilator component of the portal venous response to ATP that is NO-mediated. It also provides evidence that it is not portally-derived NO, but NO released from the hepatic arterial vascular bed, that accounts for the hepatic arterial vasodilatation to intra-portal administration of ATP. This implies that ATP itself, and not a second messenger, diffuses from the portal venous to hepatic arterial vascular bed to elicit the hepatic arterial response.
Adenosine Triphosphate↗