[Show abstract][Hide abstract] ABSTRACT: A 57-year-old male with a history of hypercholesterolemia and anxiety but otherwise in good health volunteered to donate the right lobe of his liver to his brother. The operation was performed uneventfully, without transfusion. Postoperatively he did well, until he developed tachycardia, profound hypotension, and coffee ground emesis on postoperative day 3. Despite resuscitative measures, he arrested and expired. Autopsy demonstrated gas gangrene of the stomach as the underlying cause of the hemorrhage and numerous colonies of Gram-positive bacilli were identified. Subsequent polymerase chain reaction (PCR) analysis identified these bacteria to be Clostridium perfringens (C. perfringens) type D. This patient's death was devastating, both to his family and his medical team. The impact of his death has transcended that of an individual occurrence. In conclusion, herein we present the facts and discuss this extraordinary example of florid clostridial infection and toxin-mediated shock. It was completely unexpected and probably unpreventable, and its cause was almost inconceivable.
[Show abstract][Hide abstract] ABSTRACT: Biliary reconstruction represents one of the most challenging parts of right lobe (RL) living donor liver transplantations (LDLTs). Different causes, surgical techniques, and treatments have been suggested but are incompletely defined.
Between June 1999 and January 2002, 96 RL LDLTs were performed in our center. We reviewed the incidence of biliary complications in all the recipients.
Roux-en-Y reconstruction was performed in 53 cases (55.2%) and duct-to-duct was performed in 39 cases (40.6%). Both procedures were performed in 4 cases (4.2%). Multiple ducts (> or =2) were found in 58 grafts (60.4%). Thirty-nine recipients (40.6%) had 43 biliary complications: 21 had bile leaks, 22 had biliary strictures, and 4 had both complications. Patients with multiple ducts had a higher incidence of bile leaks than those patients with a single duct (P=0.049). No significant differences in complications were found between Roux-en-Y or duct-to-duct reconstructions. Freedom from biliary complications was 59% at 1 year and 55% at 2 years. The overall 1-year and 2-year survival rates for patients were 86% and 81%, respectively. The overall 1-year and 2-year survival rates for grafts were 80% and 77%, respectively. Occurrence of bile leaks affected patient and graft survival (76% and 65% 2-year patient and graft survival, respectively, vs. 89% and 85% for those without biliary leaks, P=0.07).
Despite technical modifications and application of various surgical techniques, biliary complications remain frequent after RL LDLT. Patients with multiple biliary reconstructions had a higher incidence of bile leaks. Patients who developed leaks had lower patient and graft survival rates.
[Show abstract][Hide abstract] ABSTRACT: Acute cellular rejection (ACR) after liver transplantation occurs in as much as 70% of patients within the first year. There is very little known about ACR that occurs more than 1 yr after transplant, and it is generally believed that late occurring ACR may be more resistant to medical treatment and is associated with a higher rate of chronic ductopenic rejection and graft loss. A total of 532 recipients with more than 1000 d follow-up and who did not have hepatitis C were identified. Forty-three (8.1%) had biopsy proven late ACR at a mean of 1545 +/- 441 d post-transplant. Additionally, 38 of the 43 (88.4%) patients with late ACR had earlier episodes of ACR before 1000 d post-transplant vs. only 295 of the 488 patients (60.5%) that did not have late ACR (p < 0.01). The incidence of primary sclerosing cholangitis (PSC) was 32.6% among patients with late ACR and 11.1% among patients without late ACR (p < 0.01). The overall patient survival for patients who had late ACR (n = 43) is 81.4% while for patients without late ACR (n = 488) it is 82.0% (p = ns). Patients remain at risk for ACR even after 1000 d post-transplant, particularly those with PSC.
[Show abstract][Hide abstract] ABSTRACT: Posttransplantation allograft malignancy of donor origin is a rare complication after liver transplantation. In the case described, subjective fevers and nonspecific abdominal complaints nearly 6 months following cadaveric liver transplantation in a young woman prompted an evaluation which was remarkable for a large central liver mass. A poorly differentiated squamous cell carcinoma was diagnosed, but was unresectable at exploration. The tumor was confined to the liver. Histocompatibility testing using polymerase chain reaction (PCR) amplification techniques identified both donor and recipient HLA alleles. The patient was treated with chemoembolization, systemic chemotherapy and cessation of immunosuppression. Repeat biopsy 2 months later showed the tumor to be completely necrotic. With decompensated liver disease, she was relisted and retransplanted. More than 2 years later she remains disease-free with complete pathological remission. This is the only reported case of squamous cell carcinoma of donor origin arising in a transplanted liver.
American Journal of Transplantation 03/2004; 4(2):278-82. · 6.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2+/-6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34+/-40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option.
Journal of Gastrointestinal Surgery 03/2004; 8(2):208-12. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Liver transplantation is the best therapeutic option for patients with end-stage liver disease from primary sclerosing cholangitis. Primary sclerosing cholangitis is associated with a markedly increased risk of cholangiocarcinoma, which adversely affects survival. Approximately 20% to 30% of cholangiocarcinomas are localized in the distal bile duct. Pancreatoduodenectomy is the curative therapy for cholangiocarcinomas in this location.
We reviewed our data on a patient with primary sclerosing cholangitis-related end-stage liver disease and a simultaneous distal bile duct tumor, which was treated with a combined right-lobe, living-donor liver transplantation and pancreatoduodenectomy.
The patient was discharged 32 days post-transplantation. He is currently alive 1 year after the procedure with no evidence of recurrent cancer.
Combined living-donor liver transplantation and pancreatoduodenectomy is feasible and allows timely and elective surgical control of carefully selected distal bile duct tumors in the setting of end-stage liver disease.
Journal of the American College of Surgeons 12/2003; 197(5):765-9. · 4.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Resection offers the only potential cure of hilar cholangiocarcinoma. Portal bifurcation involvement is often thought to contraindicate resection. We reviewed our experience with aggressive surgical management in 28 patients with hilar cholangiocarcinoma.
All patients underwent hepatectomy and bile duct resection with hepaticojejunostomy. In 10 cases (group 1) the portal bifurcation was involved, necessitating portal resection and reconstruction; 18 (group 2) had no portal involvement. Frozen section of duct margins was routine. Survival was estimated using the Kaplan-Meier method and compared with the log-rank test.
Portal reconstruction in group 1 was by graft interposition (1), venoplasty using the posterior wall of the right portal vein (2), or end-end anastomosis (7). Hepatectomies included right trisegmentectomy (8), right lobectomy (4), and left lobectomy (16); 20 (71%) had concomitant caudate resection. Median survival was 18 months in group 1 and 32 months in group 2 ( P, not significant [NS]). One-, 3-, and 5-year survivals were 60%, 22%, and 22%, respectively, in group 1 and 70%, 47%, and 38%, respectively, in group 2 ( P= 0.319).
Portal involvement by hilar cholangiocarcinoma does not contraindicate resection.
Journal of Hepato-Biliary-Pancreatic Surgery 02/2002; 9(2):237-41. · 1.60 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cadaveric liver transplantation for hepatocellular carcinoma (HCC) is limited by donor organ availability. This report reviews our initial experience with living donor liver transplantation (LDLT) for HCC. Since August 1998, a total of 71 adults have undergone LDLT; 27 (38%) for HCC. Underlying diagnoses included hepatitis C in 17, hepatitis B in eight, cryptogenic cirrhosis in one, and primary biliary cirrhosis in one. Four patients had recurrent HCC after resection. Patients with tumors measuring 5 cm or larger received a single dose of intravenous doxorubicin intraoperatively and six cycles of doxorubicin at 3-week intervals beginning 6 weeks postoperatively. All HCC patients are followed with CT scans and alpha-fetoprotein measurements every 3 months during the first 2 years after transplant. Mean waiting time to transplant for patients with HCC was 83 days, compared to 414 (P = 0.001) days for 50 patients with HCC who were transplanted with cadaveric organs during this period. At median follow-up of 236 days, there have been four deaths due to non-tumor-related causes and one death from recurrence; recurrence has been observed in one other patient. LDLT permits expeditious transplantation in patients with early HCC, and provides access to transplantation for patients with HCC exceeding the United Network of Organ Sharing criteria for prioritization who are, in effect, barred from receiving cadaveric organs.
Journal of Gastrointestinal Surgery 01/2002; 6(1):102-7. · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macroregenerative nodules (MRNs), probably representing a pathway for human hepatocarcinogenesis, are generally classified into type I MRNs (or ordinary adenomatous hyperplasia) and type II MRNs (or atypical adenomatous hyperplasia), on the basis of imprecise definitions of cytological and architectural atypia. It is currently believed that type II MRNs are probably true precursors of hepatocellular carcinoma (HCC), whereas type I lesions may simply represent large regenerative nodules. A series of 155 consecutive adult cirrhotic liver explants were examined for evidence of MRNs, HCC, and liver cell dysplasia (LCD) of large and small cell types, and their appearance, in terms of proposed classification schemes, was reviewed. There was evidence indicating that the presence of either type of MRN was associated with an increased incidence of HCC (all MRNs, P < .00019; type I MRNs, P < .067; type II MRNs, P < .012) compared with cirrhotic livers without MRNs. A subset of younger patients with a large (uncountable) number of MRNs in their livers, who did not show any increased incidence of carcinoma, was identified. Excluding these cases from statistical analysis, all associations were strengthened, implying either that malignant progression had not had time to occur in this younger population or that these nodules were simply large regenerative nodules without malignant potential. MRNs from these livers were histologically indistinguishable from MRNs occurring in more limited numbers, although atypical changes other than large cell type LCD were less frequent. No independent association between LCD of large cell type and HCC was found in the entire series. Deleting this feature from the criteria for cytological atypia resulted in a stronger association of both types of MRNs with HCC (redefined type II MRNs/HCC, P < .0001; redefined type I MRNs/HCC, P < .0306). Some of the type II MRNs remaining after exclusion of large cell type LCD showed “borderline” changes insufficient for a diagnosis of HCC, but most type II MRNs (82%) contained expansile “nodule-in-nodule” growth patterns. The conclusions of this report are that (1) histological examination of type I MRNs is insufficient in many cases to distinguish large regenerative nodules from neoplastic ones; (2) LCD of large cell type should not be used as a criterion for terming an MRN atypical; and (3) expansile “nodule-in-nodule” formation in MRNs should be considered to represent evidence of architectural atypia.
[Show abstract][Hide abstract] ABSTRACT: Alteration of speech is a rare but distressing complication of orthotopic liver transplantation (OLT). We describe a characteristic speech disorder identified in a large series of consecutive patients undergoing OLT. Between 1988 and 1993, 525 adults underwent OLT. For all recipients with neurologic complications, we reviewed clinical findings, imaging and electrophysiologic test results, and perioperative laboratory data. Five patients (ages 23-52; UNOS status 3-4) exhibited a characteristic pattern of stuttering dysarthria, leading to complete loss of speech production, occasionally with elements of aphasia. In four of the five patients, right-sided focal seizures were subsequently noted. All cases presented within the first 10 postoperative days and improved with 1 month of cessation of cyclosporin (CyA), although halting, monotonous speech was evident to some degree in all five for up to 1 year. There was no correlation between onset of symptoms and CyA levels. None of the patients has clinical or radiologic findings suggestive of central pontine myelinolysis or akinetic mutism. EEGs and Spect scan results were consistent with dysfunction in the left frontotemporoparietal regions of the brain. A characteristic speech disorder, which may be described as cortical dysarthria or speech apraxia, occurs in approximately 1% of adults undergoing OLT. Prompt recognition of this syndrome and temporary cessation of CyA therapy may favorable affect the course.
Transplant International 02/1995; 8(3):234-7. · 3.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytologic analysis was performed on 128 bile specimens collected by schedule from 12 liver transplant recipients over a 4-month period. Clinical diagnoses at the time of specimen collection were determined retrospectively, as follows: clinically stable, 75; acute rejection, 15; CMV hepatitis, 1; systemic infection, 8; ischemic injury, 24 (all within the first 4 days postop); nonclassifiable, 5. Bile analysis was done by a blinded investigator. Specimens contained ductal epithelial cells (EC) and inflammatory cells (IC), which were counted using Cytospin slide preparations. Greater than 10 cells/slide were seen in 93.3% of rejections, 91.7% of ischemic injuries, 100% of systemic infections, and 14.6% of stable patients. In samples collected after POD 4, IC were seen in 86.7% of rejections, yielding a specificity of 94.4% (P less than 0.001). If lymphoblastic cells were also seen, the specificity increased to 96.6%. Five specimens were obtained the day before the clinical diagnosis of rejection; all demonstrated IC. Seven specimens were obtained 3 days after beginning therapy for rejection. In 5 the bile contained no IC, and clinical improvement occurred; in the 2 in whom IC were found, further therapy was subsequently required. IC were seen in 5 of 8 specimens taken when systemic infection was present; the clinical setting allowed differentiation from rejection. Only 1 case of CMV hepatitis was included, thus no conclusions can be drawn for this entity. Cytoplasmic vacuolization of EC was observed in 30% of cases, in these, cyclosporine levels were significantly higher (989.9 +/- 356.9 vs. 672.8 +/- 421.2, P = 0.02). In summary, bile cytology analysis aides in the monitoring of the onset and duration of rejection. It may be an indicator of persistent rejection, and it may help prevent overimmunosuppression in those cases with normal cytological findings.
[Show abstract][Hide abstract] ABSTRACT: Macroregenerative nodules, also called nodules of adenomatous hyperplasia, have been well documented in Japan. Extensive studies support the hypothesis that in the Japanese population these lesions represent a possible pathway for hepatocarcinogenesis. However, reporting of these lesions in non-Japanese populations has so far been rare. We examined 44 sequential cirrhotic hepatectomy specimens from adult patients who underwent orthotopic liver transplantation at our institution. All livers were serially sectioned every 0.5 cm. Macroregenerative nodules were defined as regenerative nodules at least 1 cm in diameter. Forty-eight macroregenerative nodules were found in 11 livers (25% of livers). The antecedent diseases in these livers included hepatitis C (3), alcoholism (2), primary biliary cirrhosis (2) (one with iron overload), cryptogenic cirrhosis (2), hepatitis B (1) and α1-antitrypsin deficiency (1). The macroregenerative nodules often differed from the surrounding nodular parenchyma in color, texture or the degree to which they bulged beyond the cut liver surface. Three livers contained grossly apparent hepatocellular carcinomas. Microscopically, macroregenerative nodules could be classified as those with (type 2) and without (type 1) dysplasia. Four livers had type 1 lesions, two had type 2 lesions and five had lesions of both types. We found 36 type 1 lesions in all and 12 type 2 lesions, 3 containing foci of microscopic carcinoma. All hepatocellular carcinomas arose in livers containing macroregenerative nodules (either type). Liver cell dysplasia, large-cell or small-cell, was observed in cirrhotic nodules of 27 livers. Microscopic or macroscopic hepatocellular carcinoma occurred in three livers with large-cell but not small-cell dysplasia and in one liver without dysplasia. We conclude that macroregenerative nodules are common in non-Japanese cirrhotic patients, occur in a wide range of chronic liver diseases and may represent precancerous lesions in this population. (HEPATOLOGY 1993;16:949–955.)