Nitric oxide and portal hypertension.
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Animals↗
Biomedical subjects
J V Sitzmann
Publications and source records attributed to J V Sitzmann.
Intrahepatic cholangiocarcinoma: findings on spiral CT during arterial portography.
To attempt to determine the characteristic imaging features of intrahepatic cholangiocarcinoma on spiral CT during arterial portography (CTAP), spiral CTAP examinations of 17 patients with pathologically confirmed intrahepatic cholangiocarcinoma were reviewed in consensus by three radiologists. The diameter of the tumors ranged from 1 to 12 cm (mean diameter, 6.6 cm). All tumors (100%) were hypoattenuating masses on spiral CTAP. In 11 cases, the tumor was homogeneous in attenuation (65%). Tumor margins were smooth and regular in 11 cases (65%). Vascular invasion was found in 14 cases (82%). Intrahepatic bile duct dilatation was present in seven cases (41%). This review shows that intrahepatic cholangiocarcinoma is associated with a constellation of findings on spiral CTAP. The presence of a low attenuation homogeneous intrahepatic mass with vascular invasion and intrahepatic bile duct dilatation on spiral CTAP images should raise the possibility of intrahepatic cholangiocarcinoma. However, these findings can be associated with other types of primary and secondary malignant hepatic tumors.
Adult↗
Perioperative predictors of morbidity following hepatic resection for neoplasm. A multivariate analysis of a single surgeon experience with 105 patients.
OBJECTIVE: Factors that predict mortality or morbidity risk in consecutive hepatic resections for neoplasm were examined, with controlled variables of surgical technique and experience. SUMMARY BACKGROUND DATA: Hepatic resection has become the therapy of choice for the management of metastatic or primary neoplasms of the liver. Although mortality for this procedure has steadily decreased, associated morbidity remains high. METHODS: One hundred five patients undergoing hepatic resection for malignancy over a 4-year period by a single surgeon to identify preoperative, intraoperative, or postoperative predictors of morbid outcomes were studied. Variables were analyzed using multiple regression in a stepwise, logistic model. RESULTS: Sixty-day hospital mortality was 2.8%, with morbidity occurring in 33%. A significant preoperative predictor of morbidity was serum bilirubin (p > 0.005). Notably, preoperative renal function, or medical illness, did not increase morbid risk. Operative variables increasing risk included extent of resection, blood loss, and operative time (p > 0.005). CONCLUSIONS: Complex hepatic resection can be performed with low mortality, and serum bilirubin is the single most powerful predictor of postoperative complication.
Bilirubin↗
Altered angiotensin-II receptors in human hepatocellular and hepatic metastatic colon cancers.
OBJECTIVE: To characterize angiotensin-II receptor density and affinity in normal and cirrhotic livers and in hepatocellular and metastatic colorectal cancer. SUMMARY BACKGROUND DATA: Several studies have indicated a possible beneficial effect of angiotensin-II as a biologic response modifier in the treatment of hepatic or metastatic colon cancer. This is based on evidence that angiotensin-II will cause a selective increase in arterial vasoconstriction in normal liver compared with tumor. METHODS: Human hepatoma (5), metastatic colon (10), or cirrhotic (3) liver was obtained. Non-tumor-bearing regions served as normal liver. Angiotensin-II receptor binding was determined on membranes with 125I-angiotensin-II and in situ studies were performed using the biotin-avidin detection system. RESULTS: Angiotensin-II receptor density was markedly down-regulated in tumor compared with normal or cirrhotic liver. CONCLUSIONS: A loss of angiotensin-II receptors occurs on the neovasculature of hepatic tumors.
Adult↗
Spiral computed tomography arterial portography with three-dimensional volumetric rendering for oncologic surgery planning. A retrospective analysis.
RATIONALE AND OBJECTIVES: Surgical resection of metastatic neoplasms of the liver can prolong survival of patients. The decision to resect a tumor depends to a great extent on the location of lesions relative to hepatic vasculature. Spiral computed tomography arterial portography (SCTAP) is an excellent technique for preoperative localization of tumors. The addition of three-dimensional rendering of image data sets should enhance the efficiency and accuracy of the interpretation of these data by the surgeon. METHODS: Fourteen patients with surgically and pathologically proven solitary and multiple metastatic hepatic neoplasms underwent SCTAP: Volume data sets thus derived were used to produce life-like three-dimensional animated images through a process known as volumetric rendering. These images were presented to the surgeon, who evaluated them based on several criteria. RESULTS: Accurate and clinically useful images were produced routinely in 13 of 14 patients. CONCLUSIONS: Clinical utility of three-dimensional rendering of SCTAP data sets for preoperative localization of hepatic lesions has been shown retrospectively. A larger, prospective study is suggested to demonstrate the accuracy and efficacy of the technique.
Adult↗
Systemic and portal prostacyclin and thromboxane response to hemorrhage in portal hypertension.
Prostacyclin (PGI2) and thromboxane (Tx-A2) levels increase in hemorrhagic shock. Prostanoids have been implicated as mediators of the systemic and splanchnic hyperemia characteristic of portal hypertension (PHT). We hypothesized that prostanoid pharmacokinetics could be altered during shock in PHT and mediate the poor tolerance of PHT animals to hemorrhage. Hemodynamics and PGI2 and Tx-A2 levels were determined in portal, systemic venous, and arterial vascular beds at baseline and following hemorrhage and resuscitation. Portal and systemic PGI2 levels were elevated at baseline in PHT animals, with no change in resting Tx-A2. Following hemorrhage, PGI2 and Tx-A2 levels increased in normal animals, but were unchanged in PHT. Portal hypertension PGI2 production was elevated at rest, while Tx-A2 levels were diminished. There is a diminished prostanoid response to hemorrhage in PHT animals compared to normal. This abnormality in prostanoid pharmacokinetics may contribute to the abnormal response to hemorrhage in PHT.
Animals↗
Primary malignant neoplasms of the liver: detection with helical CT during arterial portography.
PURPOSE: To assess the sensitivity of helical computed tomography during arterial portography (CTAP) in the detection of primary malignant neoplasms of the liver. MATERIALS AND METHODS: Preoperative helical CTAP examinations of 19 patients (13 men, six women, aged 33-78 years) with primary malignant neoplasms of the liver (hepatoma, n = 12; cholangiocarcinoma, n = 4; angiosarcoma, n = 1; biliary cystadenoma, n = 1; hepatoblastoma, n = 1) were retrospectively reviewed by three radiologists. Imaging findings were correlated with intraoperative and pathologic findings. RESULTS: A total of 29 separate malignant neoplastic nodules (mean diameter, 6.6 cm) were identified in the resected specimens (16 patients) or intraoperatively in three patients. The overall sensitivity of helical CTAP was 72%; for neoplasms with a diameter less than 1.0 cm, 25%; for neoplasms 1.1-2.0 cm and 2.1-4.0 cm, 25% and 67%, respectively; and for neoplasms over 4.0 cm, 100%. CONCLUSION: The overall sensitivity of helical CTAP in the preoperative detection of primary malignant hepatic neoplasms is low.
Adult↗
Hepatic metastases from colorectal cancer: detection and false-positive findings with helical CT during arterial portography.
PURPOSE: To determine the sensitivity and false-positive rate of helical computed tomography during arterial portography (CTAP) in the detection of hepatic metastases from colorectal cancer. MATERIALS AND METHODS: Preoperative helical CTAP was performed to examine 23 patients (10 men and 13 women, aged 43-77 years [mean, 63 years]) who later underwent surgical tumor resection. Imaging findings were retrospectively reviewed by two radiologists and were correlated with intraoperative and histologic findings. RESULTS: Helical CTAP demonstrated 33 of 35 metastases, with diameters of 4-95 mm, that were identified in resected specimens (sensitivity, 94%). The two metastases not demonstrated were 4 and 5 mm in diameter. Five false-positive lesions were found in four patients, yielding a false-positive rate of 17% by patient analysis and 13% by lesion analysis. CONCLUSION: The sensitivity of helical CTAP in the preoperative detection of hepatic metastases is high, and its false-positive rate compares favorably with that of conventional CTAP, but future comparative studies are needed to determine which is the better modality.
Colorectal Neoplasms↗
Altered adenylyl cyclase activities and G-protein abnormalities in portal hypertensive rabbits.
Portal hypertension (PHT) is characterized by splanchnic hyperemia due to a reduction in mesenteric vascular resistance. We hypothesized that alterations in the activity of a guanine-nucleotide regulatory protein (G-protein) might be partially responsible for the marked circulatory disturbances observed in PHT. We, therefore, determined alterations in adenylyl cyclase/cAMP system in prehepatic portal hypertensive rabbits and correlated these changes to the activity of a G-protein. Basal and G-protein-stimulated adenylyl cyclase activities were lower in the PHT superior mesenteric artery (22-26%) and thoracic aorta (31-46%) membranes, but higher (178-321%) in portal vein. The functional activity of Gi alpha proteins (pertussis toxin-catalyzed ADP-dependent ribosylation) increased in the PHT superior mesenteric artery and thoracic aorta, but decreased in portal vein. Immunodetection revealed an increase in the Gi alpha protein subunits (Gi alpha 1/Gi alpha 2 and Gi alpha 3/Go alpha) in PHT thoracic aorta, without any change in Gs alpha proteins; and a decrease in the amount of Gi alpha proteins in PHT portal vein. There was no change in the amount of Gs alpha/Gi alpha in the PHT superior mesenteric artery. We conclude the hemodynamic alterations of PHT are associated with intrinsic alterations in G-protein-enzyme effector systems. These alterations are vessels specific and suggest a possible unique global derangement underlying the vasculopathy of PHT.
Adenosine Diphosphate Ribose↗
Prostacyclin production in acute, chronic, and long-term experimental portal hypertension.
BACKGROUND: Chronic portal hypertension (PHT) is characterized by a high portosystemic shunt (PSS) and increased splanchnic blood flow. It has been suggested that the splanchnic vasodilator, prostacyclin (PGI2), mediates this increased flow. We studied splanchnic PGI2 production both in normal rabbits and in three groups of rabbits after partial portal vein ligation (PVL-PHT): acute (within 30 minutes of ligation), chronic (3 weeks after ligation), and long-term (3 months after ligation) to determine whether increased splanchnic production is a mechanism for the elevated PGI2 in PHT. METHODS: Levels of 6-keto prostaglandin F1 alpha were determined by radioimmunoassay, and splanchnic hemodynamics were measured with Doppler flowmetry in four groups of rabbits: portal normotensive rabbits, and PVL-PHT rabbits 30 minutes, 3 weeks, or 3 months after partial PVL. Splanchnic PGI2 production (PGI2 PROD) was then calculated. RESULTS: Portal pressure and PSS in chronic and long-term groups were significantly elevated in all groups compared with normals (p < 0.001). Splanchnic blood flow initially fell from 84 +/- 4.8 to 37.4 +/- 7 ml/min/100 gm immediately and then rose to 144.7 +/- 9.6 ml/min/100 gm and 137 +/- 15 ml/min/100 gm at 3 weeks and 3 months after ligation, respectively. PGI2 production rose immediately after partial portal ligation from 62 +/- 10 to 164 +/- 4.1 ng/min/100 gm and remained elevated thereafter. CONCLUSIONS: The mechanism for elevated PGI2 in acute PHT is unclear, but in chronic and long-term PHT, it is probably due in part to increased splanchnic PGI2 production.
Acute Disease↗
Hormonal and splanchnic hemodynamic alterations following hepatic resection.
Reported hemodynamic changes after partial hepatectomy (PH) include elevations in portal blood flow and pressure (Ppv). The etiology of these changes is unknown. We studied degree of portosystemic shunt (PSS), splanchnic artery blood flow and resistance (Qspl, Rspl) as well as prostacyclin (PGI2), glucagon, and insulin response in rats undergoing 75% hepatectomy. The results showed that following an immediate threefold rise in portal PGI2, a hemodynamically significant PSS developed at 48 hr. The PGI2 changes paralleled the increase in portal flow (Qpv), pressure (Ppv), PSS and the decrease in Rspl. Glucagon levels also rose immediately postresection, but fell to normal prior to resolution of both PSS and hyperemia. There was no significant change in insulin or glucose levels after resection. This implies a relationship between PSS and the release of a prostanoid effecting Qpv, Qspl, and Rspl, which relates to, and possibly mediates, the hemodynamic changes following liver resection. We conclude that PH is a model of acute PHT, and that the altered splanchnic hemodynamic could relate to hepatic regeneration.
Animals↗
Improved survival for hepatocellular cancer with combination surgery and multimodality treatment.
Forty-one hepatic resections for malignant hepatomas were done in 35 consecutive patients from August 1985 to 1990. Twenty-one patients presented initially with resectable lesions and underwent resection for curative intent. Fourteen patients initially presented with unresectable intrahepatic disease. These patients underwent combined radiation and chemotherapy. Radiation consisted of external beam in all patients and 131I-antiferritin in 10 patients. Greater than 50% tumor reduction was noted in all patients, and resection then was performed. Six patients recurred and were re-resected. Complications occurred in 15 patients (36%), with no difference between groups. There were no perioperative deaths. Five-year actuarial survival was 45% and 48% for resection and multimodality. The authors conclude that some patients with unresectable intrahepatic hepatoma may successfully be converted to resectable by multimodality radiation/chemotherapy. The survival of these patients is similar to that of primary resected patients. Further, multiple, sequential resections appear to significantly prolong survival and can be performed with an acceptable morbidity and mortality rates.
Actuarial Analysis↗
Effect of portosystemic shunting on PGI2 and glucagon levels in humans.
OBJECTIVE: This study determined if the proposed mediators of splanchnic blood flow, prostacyclin and glucagon, were elevated in patients with portal hypertension undergoing portal systemic shunts. SUMMARY BACKGROUND DATA: Chronic portal hypertension results in increased portal venous pressure and increased splanchnic blood flow. Animal studies have suggested prostacyclin or glucagon, potent vasodilators, as potential mediators of this increased flow. Correlative clinical studies have been difficult to perform due to the wide variation in degree of portal-systemic shunting and the frequent association of parenchymal liver disease in patients with cirrhosis. METHODS: The authors measured portal and systemic hemodynamics in PGI2 and glucagon levels in patients with portal hypertension due to cirrhosis (partial portal systemic shunt) and Budd-Chiari syndrome (complete portal systemic shunt) undergoing portal systemic shunts and in porto normotensive patients undergoing exploratory laparotomies. RESULTS: PGI2 levels in portal hypertension were significantly increased over normal, and prostacyclin in Budd-Chiari patients were increased significantly over patients with cirrhosis. Both PGI2 and portal venous pressure decreased significantly after portal systemic shunting, and prostacyclin levels correlated directly with portal venous pressure (R = 0.37, p < 0.05). CONCLUSIONS: This is the first evidence in humans supporting the hypothesis that PGI2 is elevated in portal hypertension and is related to both the degree of portal venous obstruction and portal pressure. PGI2 probably has a role in the abnormal splanchnic hemodynamics of human portal hypertension.
Adult↗
Regional chemotherapy devices: effect of experience and anatomy on complications.
PURPOSE: Regional hepatic arterial infusion (HAI) devices have been used for 17 years, but reports of unacceptably high complication rates have led to controversy about their use. Inadequate or misdirected infusion has been reported to occur in up to 45% of patients. We evaluated whether surgeon experience or presence of variant arterial anatomy related to risk of coagulation. MATERIALS AND METHODS: We reviewed 70 patients undergoing placement of HAI catheters. Surgeons were classed as experienced after 10 procedures and arterial anatomy was evaluated angiographically with confirmation at operation. Complications were categorized as technical (17%) or chemotherapy-related (16%). RESULTS: Inexperienced surgeons had a technical complication rate of 37% (80% of the patients involved had standard anatomy), while experienced surgeons had a technical complication rate of 7% (P < .01). Experienced surgeons had no complications in patients with standard anatomy, while inexperienced surgeons had a 42% (eight of 19) complication rate in similar patients (P < .01). CONCLUSION: We conclude that technical complications are closely associated with surgeon experience and arterial anatomy.
Adult↗
Misperfusion of the liver during hepatic artery infusion chemotherapy: value of preoperative angiography and postoperative pump scintigraphy.
OBJECTIVE: One purpose of this study was to determine if patients who have anatomic variations in their hepatic arteries are at increased risk for complications associated with the use of intrahepatic arterial infusion pumps. We also tried to determine the value of perfusion studies obtained with 99mTc-microspheres or 99mTc-macroaggregated albumin in detecting postoperative hepatic or visceral misperfusion and in predicting complications in patients with anatomic variants despite pre- or intraoperative attempts to correct the arterial abnormality. SUBJECTS AND METHODS: We prospectively compared findings on scintigrams obtained after delivering the radionuclide through intrahepatic arterial infusion pumps with anatomic variations in hepatic arteries seen on celiac and superior mesenteric hepatic arteriograms obtained before placement of the pump in 49 consecutive patients with colon carcinoma metastatic to the liver. RESULTS: Despite pre- or intraoperative attempts to correct arterial abnormalities to ensure optimal perfusion of the liver in 24 patients with hepatic arterial anomalies seen on preoperative arteriograms, only two patients had normal findings on postoperative perfusion studies performed with 99mTc-microspheres and/or 99mTc-macroaggregated albumin. Abnormalities included perfusion of extrahepatic organs, including the spleen in 12 patients, stomach in seven, bowel in four, and pancreas in three. Eight patients had no perfusion of the left lobe of the liver, and three had no perfusion of the right lobe. Two patients had minimal or no perfusion of both lobes. In 23 of 25 patients with no demonstrable variations in vascular anatomy on preoperative celiac and superior mesenteric arteriograms, findings on hepatic pump scintigrams were normal. Of the 24 patients with abnormal scintigraphic findings, 20 had subsequent clinical complications. However, only two of the 25 patients with normal scintigraphic findings had clinical complications. CONCLUSION: Our results indicate that patients with anatomic variations in the hepatic arterial system are at high risk for misperfusion during chemotherapy despite pre- or intraoperative efforts to alter the perfusion for chemotherapeutic agents delivered by intrahepatic arterial infusion pumps. Misperfusion can be detected by using pump scintigraphy, and therefore patients should be closely monitored with 99mTc-macroaggregated albumin perfusion studies to ensure successful delivery of the chemotherapeutic agents and to avoid serious clinical complications caused by inadvertent perfusion of other organs.
Adult↗
Effects of nitric oxide and cyclooxygenase inhibition on splanchnic hemodynamics in portal hypertension.
Portal hypertension is associated with splanchnic hyperemia and increased plasma levels of prostacyclin. Recently, nitric oxide was proposed as a mediator of this arterial vasodilatation. We hypothesized that portal hypertension alters the relative contribution of prostacyclin and nitric oxide to splanchnic vasomotor control. We studied the relationship of nitric oxide and prostaglandins in normal and portal-hypertensive (3 wk after partial portal vein ligation) male rabbits at baseline and following increasing doses of indomethacin, LG-nitro-L-arginine methylester or both. L-arginine was used as the control. Aortic, central and portal venous pressures were measured directly. Blood flow in the superior mesenteric artery was measured by means of an ultrasonic flow probe, and resistance was calculated. LG-nitro-L-arginine methylester produced vasoconstriction (increased resistance and decreased blood flow in the superior mesenteric artery) in normal and portal-hypertensive rabbits, although in portal hypertensive animals resistance and superior mesenteric artery blood flow remained significantly different than that in normal rabbits because of preexisting hyperemia. L-arginine reversed the effect of LG-nitro-L-arginine methylester. Cyclooxygenase blockade induced dose-dependent vasoconstriction in normal and portal-hypertensive animals. Indomethacin induced further vasoconstriction after LG-nitro-L-arginine methylester and reduced portal venous pressure in portal-hypertensive animals. We conclude that this indicates an amplified role for some prostaglandin, probably prostacyclin, in portal hypertension hemodynamics. It also implies that the two vasodilators act by way of independent mechanisms.
Animals↗
Biliary tract anomalies associated with intestinal malrotation in the adult.
Intestinal malrotation is a rare disorder typically beginning in childhood. In the adult it is an uncommon diagnosis, and it usually begins with bowel obstruction. It is a congenital anomaly only once reported to be associated with other gastrointestinal abnormalities in an adult. We reviewed all patients with intestinal malrotation at the Johns Hopkins Hospital during the past 7 years to determine the incidence of associated biliary tract anomalies. Eight adult patients were found to have complete malrotation of the gut. Four patients (50%) had an associated abnormality of the biliary tree. Two of four patients had a clinical presentation consistent with biliary tract disease rather than intestinal malrotation. Two patients underwent exploration; the gallbladder was found to arise from the left lobe of the liver. Two patients underwent exploration; in these patients the porta hepatic structures were anterior to the duodenum (complete anteroposterior portal hepatic malrotation). None of the biliary abnormalities were suspected before surgery. Malrotation was diagnosed before operation in only two of the eight patients. We conclude that intestinal malrotation is rare in the adult, and it can be associated with biliary tract anomalies or disease. In an adult with suspected intestinal malrotation and biliary tract disease, the surgeon should be aware of possible variable or abnormal extrahepatic choledochal anatomy.
Abnormalities, Multiple↗
Patterns of ileal recurrence in Crohn's disease. A prospective randomized study.
To gain information on the pathogenesis of ileal recurrence, 86 patients with Crohn's disease undergoing their first ileocolic resection were randomized to receive either an end-to-end (n = 47) or side-to-end (n = 39) anastomosis. The demographic and clinical characteristics of both groups were similar. There were no statistically significant differences between the two groups in postoperative complications or in the subsequent development of symptomatic or documented recurrences. Among the 43 patients with follow-up in the end-to-end anastomosis group, there were 10 documented ileal recurrences (23%), and all involved distal ileum in the characteristic preanastomotic location. Among the 35 patients with follow-up in the side-to-end anastomosis group, there were 11 documented recurrences (31%, not significant). The ileal recurrence pattern could be determined accurately in five of these 11 patients and involved the ileum adjacent to the colon, but spared the distal ileum in the blind pouch. This study suggests that the fecal stream and reflux of colonic contents are important factors in determining the pattern of ileal recurrence after ileocolectomy for Crohn's disease.
Adult↗