Use of tissue plasminogen activator in liver transplantation from donation after cardiac death donors.

Ischemic-type biliary stricture (ITBS) occurs in up to 50% after liver transplantation (LT) from donation after cardiac death (DCD) donors. Thrombus formation in the peribiliary microcirculation is a postulated mechanism. The aim was to describe our experience of tissue plasminogen activator (TPA) administration in DCD-LT. TPA was injected into the donor hepatic artery on the backtable (n = 22). Two recipients developed ITBS including one graft failure. Although excessive postreperfusion bleeding was seen in 14 recipients, the amount of TPA was comparable between those with and without excessive bleeding (6.4 ± 2.8 vs. 6.6 ± 2.8 mg, p = 0.78). However, donor age (41 ± 12 vs. 29 ± 9 years, p = 0.02), donor BMI (26.3 ± 5.5 vs. 21.7 ± 3.6 kg/m(2) , p = 0.03), previous laparotomy (50% vs. 0%, p = 0.02) and lactate after portal reperfusion (6.3 ± 4.6 vs. 2.8 ± 0.9 mmol/L, p = 0.005) were significantly greater in recipients with excessive bleeding. In conclusion, the use of TPA may lower the risk of ITBS-related graft failure in DCD-LT. Excessive bleeding may be related to poor graft quality and previous laparotomy rather than the amount of TPA. Further studies are needed in larger population.

The "white clot syndrome" in hepatic transplantation.

Heparin-associated thrombocytopenia and thrombosis (Type II HAT), the "white clot syndrome," has not been previously reported as a cause for fulminant hepatic failure after liver transplantation. Thrombocytopenia and the use of heparin are common events in the newly transplanted patient. A man who was transplanted for sclerosing cholangitis, and re-exposed to heparin, is described with thrombocytopenia, thrombosis of all hepatic vessels, and heparin antibodies. Type II HAT is an immune phenomenon that can apparently occur despite T-cell-directed immunosuppression. Suspicion is a key element in establishing diagnosis. We no longer use heparin routinely in liver transplant cases.

Neurologic complications of liver transplantation.

Nineteen adult patients underwent 21 orthotopic liver transplants at the Cleveland Clinic between November 1984, and August 1986. Eight of 19 (42%) patients developed seizures. One patient suffered a single seizure, and seven patients had multiple, generalized seizures. Two of these seven patients became comatose after several days of seizure activity. Over several weeks, both of these patients regained consciousness--however, they exhibited a cerebellar-type syndrome, manifested as severe ataxia, weakness, and dysarthria. Both patients have improved, but remain neurologically impaired. Laboratory evaluation included serum electrolytes, magnesium, osmolality, and cyclosporine levels. Neurologic testing consisted of cerebrospinal fluid (CSF) analysis, computed tomographic (CT) scanning, and electroencephalography (EEG). Although the CSF protein was mildly elevated in two patients, all cultures remained sterile. None of the CT scans demonstrated any abnormalities. In five patients, the EEG showed generalized slowing consistent with diffuse encephalopathy. Other factors associated with seizures in transplant patients were analyzed, including fluid retention, hypertension, high-dose steroids, hypomagnesemia, graft dysfunction, and demyelinization. Many of our patients had the first three of these factors, since all but one developed their seizures within the first ten postoperative days. Only one patient had mild hypomagnesemia. Trough cyclosporine levels (whole blood, HPLC) were not in the toxic range (greater than 500 ng/mL). The serum osmolality was elevated in all four patients in whom it was measured, ranging from 309 to 341 mOsm/kg. Only three patients exhibited graft dysfunction--two moderate and one severe. The cause of neurologic toxicity following transplantation is unclear. Although many factors have been implicated, no common denominator has emerged. Several reports have linked cyclosporine with seizures and other neurologic problems, such as the cerebellar-type syndrome exhibited in two of our patients. Future studies should include magnetic resonance (MR) imaging of the head and measuring osmolality and cyclosporine levels in the blood and CSF.

The prevalence of coronary artery disease in liver transplant candidates over age 50.

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

Hepatic resection in 128 patients: a 24-year experience.

The records of 128 patients who underwent hepatic resection at the Cleveland Clinic Foundation between 1960 and 1984 were reviewed. Sixty patients (47%) had major resections and 68 patients (53%) had wedge or segmental resections. One hundred five patients had malignant tumors; 29 were primary liver tumors and 78 were metastatic (61 from a colorectal primary). Twenty-three patients had benign hepatic tumors. The overall operative mortality rate was 7% (7.6% for malignant tumors and 4.3% for benign lesions). Survival rate after resection of a hepatocellular carcinoma (22 patients) at 3, 5, and 10 years was 50%, 33%, and 12%. Survival rate after resection of colorectal metastases at 3, 5, and 10 years was 44%, 28%, and 21%. Overall survival was better for patients who were less than 56 years of age (p = 0.003) and for patients with no tumor at the line of resection (p less than 0.001). In patients with colorectal metastases, survival after wedge or segmental resection was better than after a major anatomic resection (p = 0.004). In these patients, the number or size of the metastases, the time interval between resection of the primary tumor and of the hepatic metastases, and/or the presence of mesenteric lymph node metastases were not significant. Most patients with primary malignant tumors require major hepatic resection. Patients with benign tumors and metastatic colorectal carcinomas require resection only to the extent that the tumor is sufficiently encompassed.

Liver resection using total vascular exclusion.

BACKGROUND: Total vascular exclusion (TVE) is a technique of liver resection that includes controlling both the suprahepatic and infrahepatic vena cava in addition to portal inflow at the time of parenchymal transection. We report a series of 61 liver resections in 60 patients using this technique. METHODS: A retrospective review of 61 procedures in 60 patients using TVE between 1990 and 1997 was carried out. No patient had cirrhosis. Parameters analyzed included age, gender, diagnosis, procedure, operative time, clamp time, intraoperative transfusion requirements, postoperative laboratory studies, length of stay (intensive care unit, ward), mortality, and morbidity. RESULTS: TVE was sustained hemodynamically in all patients. The mean age of the 34 men and 27 women was 56 years (+/- 15 years); 21% were older than 70 years. Eleven percent of the patients had benign lesions; 70% of the malignant tumors were metastatic. Seventy-five percent of the procedures were major or extended lobectomies. The mean operative and clamp times were 330 +/- 83 and 39 +/- 13.2 minutes, respectively; 68% had clamp times of < 45 minutes. The mean intraoperative red blood cell units was 1.45 +/- 1.93, with a range of 0 to 8 units; 48% required no transfusion and 80% received 2 units or less. There was 1 perioperative death for a mortality rate of 1.6%. The morbidity rate was 36%, which included 4 patients with postoperative liver dysfunction. Complications were not associated with transfusion but with clamp times exceeding 45 minutes. Liver dysfunction occurred with clamp times more than 60 minutes, particularly if the remaining liver parenchyma was histologically abnormal or the remnant was small. CONCLUSIONS: TVE is hemodynamically safe, even in patients older than 70 years. Blood loss during parenchymal transection is minimal; mortality and morbidity are low. The optimal clamp time is less than 45 minutes. Liver dysfunction is associated with clamp times exceeding 1 hour, particularly if the remaining parenchyma is abnormal or small.

Results of surgical treatment of periampullary tumors: a thirty-five-year experience.

Data on 126 consecutive patients with periampullary tumors resected at the Cleveland Clinic between January 1950 and December 1984 were reviewed. One hundred five patients underwent pancreatoduodenal resection, 10 patients total pancreatectomy, and 11 patients local resection of the tumor. The site of tumor was ampulla of Vater (59), head of the pancreas (30), duodenum (20), and distal common bile duct (11). Six patients had benign disease. The operative mortality rate for radical resection for the entire period was 7.8%; it has declined to 5.4% since 1974. The operative mortality rate for local resection was 9.1% (one patient). The overall 5-year survival rate for all malignant tumors of the periampullary area was 28% and 25.5% for invasive adenocarcinoma. Survival was affected primarily by location and histologic findings. The 5-year survival rate for adenocarcinoma of the ampulla of Vater was 37.2%, 27.5% for the duodenum, 16.7% for the distal common bile, and 4.3% for the pancreas (p = 0.0001). Papillary adenocarcinoma had a 5-year survival rate of 49.2% in contrast to 18.4% for nonpapillary ductal adenocarcinoma (p = 0.002). Patients with ampullary adenocarcinoma treated by local resection had a 5-year survival rate of 40.9%. These data justify continued use of a selective radical approach in the resection of most periampullary tumors with local resection for small tumors in high-risk patients.

Liver transplantation in Ohio.

BACKGROUND: Since its inception in 1984, the Ohio Solid Organ Transplantation Consortium has tracked liver transplantation outcomes for its five member institutions. Presented herein is a 12-year summary of this data analyzed to determine whether, with increasing experience, outcomes have improved in a cost-effective manner. METHODS: Between July 1984 and June 1996, 1,063 liver transplants were performed in Ohio in 943 patients (772 adults and 171 children), of which 943 were primary and 120 were retransplants (13%). Outcome comparisons were made for three eras: 1984-1988, 1988-1992, and 1992-1996. RESULTS: The percentage of urgent (United Network for Organ Sharing status 1 and 2) transplants has decreased (62% to 41%), whereas that of homebound patients has increased (38% to 59%). Average time on the waiting list has increased from 39 to 165 days, and the average length of stay has decreased from 44 to 27 days. Patient survival at 1-year increased in each era (64%, 80%, and 82%, respectively). Although actual hospital charges have remained relatively constant, they have decreased substantially when compared in 1985 dollars as corrected for inflation. CONCLUSIONS: Patients undergoing liver transplantation in Ohio are now listed earlier in the course of their disease and wait longer for their transplant, but enjoy a better chance of survival, have a shorter hospital stay, and a relatively less expensive operation. These data indicate that with increased experience, the Ohio Solid Organ Transplantation Consortium liver transplantation teams perform liver transplantation in a more cost-effective manner.

Early patency of the carotid artery after endarterectomy: digital subtraction angiography after two hundred sixty-two operations.

During a 12-month period of study, 265 patients (mean age 65 years) underwent a total of 314 carotid endarterectomies for the management of previous transient cerebral ischemia (39%), prior stroke (10%), or severe asymptomatic carotid stenosis (51%). Five patients (1.6%) died within 30 days of operation, but only three deaths (1%) were related to carotid reconstruction. Six patients (1.9%) experienced postoperative strokes, including 1.6% of those with previous transient ischemia, 9.7% of those with prior strokes (P less than 0.02), and 0.6% of those with asymptomatic carotid stenosis before operation. Digital subtraction angiography (DSA) was performed during the same hospital admission following 262 procedures in a group of 214 patients, including all patients who had postoperative neurologic complications. Seven of these operations were limited to external carotid endarterectomy. The internal carotid artery was entirely normal in 239 (94%) of the remaining 255 DSA studies. The external carotid artery was normal on 238 (93%) of 255 DSA examinations, but was occluded on 12 (4.7%). A focal intimal defect corresponding to the apical arteriotomy suture was found in nine internal carotid arteries (3.6%), but these lesions did not appear to be hemodynamically significant. The internal carotid artery contained over 30% stenosis in two patients (0.8%) and was occluded in five (1.9%). Two of these five patients had neurologic complications, but four others with operative strokes had normal angiograms. Asymptomatic postoperative thrombosis of the internal carotid artery was documented in only three patients (1.2%).

Trends in bile duct injuries from laparoscopic cholecystectomy.

Bile duct injuries are a serious complication of cholecystectomy. Laparoscopic cholecystectomies (LC) were originally associated with an increased incidence of injuries. Patients referred to a tertiary center were reviewed to assess the trends in the number, presentation, and management. Seventy-three patients were referred over a 6-year period with a maximum of 17 patients referred in 1992, but the number has not declined substantially over time. The persistent number of referrals is a consequence of ongoing injuries. One third of injuries were diagnosed at LC, and the use of cholangiography has not increased. The number of cystic duct leaks has not decreased and they represent 25% of all cases. The level of injury has remained unchanged with Bismuth types I and II in 37% and types III and IV in 38%. Excluding patients with cystic duct leaks, 58% were referred after a failed ductal repair. Definitive treatment with biliary stenting was successful in 37%, and 34 patients (47%) required a biliary-enteric anastomosis. Complications occurred in 18 patients (25%) including seven with postoperative stricture or cholangitis. No biliary reoperations have been performed at a mean follow-up of 36 months.

Surgical management of portal hypertension and esophageal varices. 10 year experience.

The results of 157 operations performed for portal hypertension and esophageal varices on 148 patients at the Cleveland Clinic in the 10 year period between 1970 and 1980 are reported. One hundred four shunt procedures and 53 ligation procedures were performed. The overall operative mortality rate of 13 percent did not differ significantly from the 11 percent rate reported from this institution in 1971. A comparatively higher rate of recurrent variceal hemorrhage and a lower rate of encephalopathy reflected our increased use of selective shunts and ligation procedures. There was no improvement in overall long-term survival, which was approximately 50 percent. The two most important factors in predicting the results of all operations for esophageal varices continue to be assessment of preoperative liver function and the timing of the operation. The best results were obtained in patients with good liver function who had an elective operation. Our data suggest that the portacaval shunt is associated with a higher incidence of late mortality, largely as a result of liver failure; therefore, our preference now is to perform a distal selective splenorenal shunt procedure whenever possible. If a selective shunt procedure cannot be performed, we advocate either a mesocaval shunt or a ligation procedure, depending on patient risk and the suitability of veins for a shunt procedure.

Role of radiation after operative palliation in cancer of the proximal bile ducts.

Cancer of the proximal bile ducts continues to pose a formidable problem to even the most experienced biliary surgeon. From 1977 through 1985, 51 patients with histologically confirmed proximal bile duct cancers underwent surgical treatment. The lesion was confined to the hilar region in 30 patients; there was extensive hepatic infiltration or distant metastatic disease in 21 patients. One patient underwent resection. Biopsy only was performed in six patients. In the remaining 44 patients, transtumoral dilation and intubation were performed. These 44 patients were further analyzed with regard to how survival was affected by the presence of metastatic disease and by the adjunctive use of radiation therapy. Mean survival in those patients with metastatic disease (n = 16) was 6.1 months, and survival was not improved by the use of postoperative radiation. In the absence of metastatic or advanced local disease, however, the addition of external beam radiation did significantly extend the mean survival from 4.5 to 12.2 months and the median survival from 2.2 to 12.2 months. The operative mortality for the series was 14% and postoperative complications occurred in 18 patients. These findings suggest that the addition of external beam radiation improves survival in patients undergoing palliative treatment of hilar tumors. Further confirmation of the value of radiation awaits prospective investigation.

Current management of cholangiocarcinoma.

Most bile duct cancers are multicentric, slow-growing, and only locally invasive adenocarcinomas. Approximately half involve the hepatic bifurcation. Percutaneous cholangiography is successful in over 90% of patients and is virtually diagnostic for proximal tumors. Therapeutic options include percutaneous intubation, surgery, radiation, and chemotherapy, though responses to the latter have been minimal. Percutaneous or endoscopic intubation as definitive therapy is generally reserved for elderly patients or those with advanced disease. Surgical procedures include resection, bypass, dilatation and stenting, and biopsy alone. Fewer than half of all upper bile duct cancers are resectable, so most patients have palliative procedures. Although several studies suggest a survival advantage with the addition of radiotherapy, no confirmatory data is available. The prognosis for cholangiocarcinoma remains dismal.

Indications for gastric bypass in palliative operations for pancreatic carcinoma.

This review was undertaken to determine whether there are specific factors which predict the development of gastric outlet obstruction (GOO) in patients with pancreatic carcinoma. One hundred forty-two patients with biopsy proven pancreatic carcinoma had palliative operations of whom 74 had gastric bypass (GB). Of the 68 who did not, four died after biliary bypass. The 64 patients who remained at risk for GOO are the subject of this report. Seven of those patients developed GOO in the postoperative period and were compared with the 57 who did not. No significant difference was found between the two groups when they were compared on the basis of 20 historic, laboratory, and operative finding criteria. These data indicate that accurate prediction of subsequent GOO is not possible based on available objective data. Because GB creation does not increase operative blood loss, operative time, postoperative stay, or postoperative morbidity, and because prediction of need is difficult, prophylactic GB should be applied very liberally.

Long-term results of the surgical management of chronic pancreatitis.

To investigate the long-term results of surgical management of chronic pancreatitis, we reviewed the hospital records of 50 consecutive patients who underwent surgery for chronic pancreatitis between 1975 and 1985. The principal indications for surgery were abdominal pain (100%), pseudocyst (24%), and biliary obstruction (42%). Surgeries included pancreatic duct drainage (56%), distal pancreatic resection (20%), and drainage of a pancreatic pseudocyst (24%). Follow-up averaged 5.2 years (range 5 to 11 years). Reoperation was required in 31 patients during the extended follow-up period. Principal indications for reoperation were abdominal pain (93%), recurrent pancreatic pseudocyst (32%), and uncertainty of the diagnosis of chronic pancreatitis (26%). Subsequent operations included cholecystectomy (35%), pseudocyst drainage (32%), splanchnicectomy (16%), and pancreatic biopsy (16%); and eliminated abdominal pain in 24 patients (83%). The diagnosis of chronic pancreatitis was not revised in any case. At most recent follow-up, 30 patients (60%) were well and without abdominal pain, 12 (24%) experienced intermittent abdominal pain, and one (2%) had continued abdominal pain that required narcotics. Five patients (10%) died of other causes, and two (4%) were lost to follow-up. We conclude that pain, the principal symptom of chronic pancreatitis, can be eliminated or reduced in the majority of patients by appropriate surgical therapy.

Pretransplant chemotherapy in pediatric hepatocellular carcinoma.

The prognosis for pediatric patients with hepatocellular carcinoma is poor, except for fewer than half the patients, who can be rendered disease-free with conventional liver resection. Multicentric, bilobar liver cancer remains unresectable, even after radiation and chemotherapy. Liver transplantation alone for primary hepatic cancer has had limited success. Chemotherapy has been reserved for use after transplantation, with little demonstrable benefit. A pilot program of pretransplant chemotherapy was undertaken. Four adolescent patients with unresectable, multicentric, bilobar hepatocellular carcinoma were staged noninvasively, underwent chemotherapy followed by a final staging laparotomy, and then had liver transplantation. Three of the four patients survived and have no evidence of recurrence 84, 67, and 47 months after diagnosis and 76, 65, and 44 months after transplantation. Pretransplant chemotherapy has four potential advantages: (1) minimized risk of posttransplant opportunistic infections, (2) less tumor bulk at the time of transplantation, (3) fewer local recurrences, and (4) a lower rate of metastasis.

The acute abdomen in the geriatric patient.

Evaluating an elderly patient with an acute abdomen is a challenging clinical problem. THe diagnosis is more difficult to secure in this age group, because it is difficult to obtain an accurate history, and physical findings are more subtle. The major factors that increase mortality include associated medical diseases, emergent operations, and delay in recognition and treatment of the problem. Patients with widespread malignancy and generalized peritonitis fare poorly, but operative mortality in the geriatric group has improved significantly because of more prompt diagnosis, aggressive resuscitation, precise monitoring, and expedient but definitive procedures. As the proportion of elderly patients in the population continues to rise, it becomes increasingly important to evaluate and manage this problem expediently.

Hepatic artery infusion chemotherapy for colorectal liver metastases.

Twenty-two patients with hepatic colorectal metastases had Infusaid pumps implanted for hepatic artery infusion chemotherapy, or HAIC. Prior to pump placement, 19 of the 22 patients received percutaneous HAIC with 5-fluorouracil and citrovorum factor. Floxuridine, 0.2 mg/kg/d, was administered via the Infusaid pump and was alternated with saline solution every 2 weeks. HAIC responsiveness was defined as a 50% or greater reduction in the sum of all diameters of measured lesions on computerized tomography scans and no evidence of extra-hepatic tumor. Nine patients (41%) had a favorable response to HAIC; four (18%) had a partial response to percutaneous HAIC and five (23%) were considered pump responders. All responders had pretreatment liver replacement of less than 50%. The mean survival after pump placement was 13.6 months for responders and 11.1 months for non-responders. Although there were no operative deaths, the morbidity rate was 36%, and 31% of patients manifested significant chemotherapy toxicity. While toxicity is not insignificant and there is no survival benefit, the Infusaid pump is a reliable drug delivery system for HAIC, and may result in regression of colorectal liver metastases in patients with less than 50% hepatic replacement.

Selective bowel decontamination with quinolones and nystatin reduces gram-negative and fungal infections in orthotopic liver transplant recipients.

Gram-negative and fungal infections are the most important cause of morbidity and mortality after liver transplantation, especially in the first postoperative month. From February 1989 to February 1990, all liver transplant recipients at The Cleveland Clinic Foundation, Cleveland, Ohio, were placed on a selective bowel decontamination regimen employing oral quinolones and nystatin beginning at the time they were put on the active waiting list for transplantation and continuing until the fourth postoperative week. The incidence of gram-negative and fungal infections for these patients was compared against a historical control group. Selective bowel decontamination was well tolerated and highly effective in reducing early serious gram-negative and fungal infections. This regimen may also reduce mortality.

Management of variceal bleeding in the 1990s.

BACKGROUND: Variceal bleeding is a common and serious problem. OBJECTIVE: To review the current management of patients with variceal bleeding. SUMMARY: Therapeutic options now include pharmacologic reduction of portal hypertension, endoscopic obliteration of varices, placement of decompressive shunts (both surgical and percutaneous), and liver transplantation. Each of these options may be required in different settings. A nonselective beta blocker can prophylactically reduce the risk of an initial bleed. Acute variceal bleeding is best managed by endoscopic sclerosis. Selection of therapy to prevent recurrent bleeding should be based on a full evaluation of the risk of bleeding and of liver failure. CONCLUSIONS: Successful management requires a multidisciplinary team, full patient evaluation, and selection of appropriate therapy.