An early regional experience with expansion of Milan Criteria for liver transplant recipients.

The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ≤3 lesions, none >5 cm and total diameter <9 cm-[R4 T3]) to receive the same exception points as MC lesions. Kaplan-Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann-Whitney U tests were used to compare patient data. A p-value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging.

Steroid elimination 24 hours after liver transplantation using daclizumab, tacrolimus, and mycophenolate mofetil.

BACKGROUND: Corticosteroids have long been a cornerstone of orthotopic liver transplant (OLTx) immunosuppression. Newer, more potent, agents have successfully allowed for more rapid tapering and discontinuation of corticosteroids in OLTx recipients. We hypothesize that corticosteroids can be safely avoided after the first postoperative day (POD) using these newer agents. METHODS: Thirty adult OLTx recipients were prospectively enrolled in a randomized open-label, institutional review board-approved protocol. Fifteen patients (group A) received our standard regimen of tacrolimus, mycophenolate mofetil, and corticosteroids, and 15 patients (group B) received daclizumab, 2 mg/kg on POD 0 and 14, with tacrolimus, mycophenolate mofetil, and corticosteroids on POD 0 and 1 and then discontinuation. In both groups, mycophenolate mofetil was tapered off between 3 and 4 months after OLTx. Bone mineral densitometry was performed at 1, 3, and 6 months after OLTx. Quantitative hepatitis C virus (HCV) polymerase chain reaction was obtained at days 0, 7, 14, 21, and 28. Retransplant recipients, patients with autoimmune hepatitis, or status 1 or 2A patients were excluded. RESULTS: Patient and graft survival rates were 93% (group A) and 100% (group B) with mean follow-up of 18 months. Patients in group B had more rejection diagnosed (25%) compared with group A (6.7%). Yet, the incidence of biopsy-proven acute rejection requiring steroid therapy was 6.7% in both groups. Hispanic race was common in groups A and B (87% and 74%). A total of six biopsies were performed in group B, with three patients having mild rejection responding to an increase in tacrolimus without the need for corticosteroids. One patient in group B was switched to cyclosporine for severe neurotoxicity and remains on monotherapy with normal graft function. No patient in either group developed a requirement for additional antihypertensive medication. Likewise, there were no patients with new-onset diabetes. The bone mineral densitometry was higher in group B at every time point but did not reach statistical significance. Serum cholesterol level was significantly (P=0.03) lower in group B at 6 months after OLTx. Serum triglycerides were also lower, but the difference was not significant. Quantitative polymerase chain reaction for HCV-positive patients (group A, n=7; group B, n=8) frequently increased after OLTx. There was no correlative decrease associated with daclizumab. At present, two patients in group A have documented HCV recurrence. CONCLUSION: Corticosteroids can be safely avoided after POD 1 with the current regimen. With early follow-up, there is no difference in hypertension or diabetes or bone density. Lipid panels tended to be lower in patients who were not on corticosteroids. Longer term follow-up will be needed to demonstrate the potential advantage of corticosteroid avoidance in regard to hypertension, diabetes, and possibly HCV recurrence.

A new salvage procedure for peritoneal dialysis catheters with exit site infections.

The management of catheter-related infections has become a major challenge in continuous ambulatory peritoneal dialysis treatment. We identified five patients on continuous ambulatory peritoneal dialysis who failed conservative medical management for exit site infections. Each patient underwent incision and debridement along the subcutaneous course of the catheter, exteriorization of the superficial cuff, and establishment of a new exit site at the medial aspect of the wound. This novel technique of incision and debridement along the subcutaneous tunnel and relocation of the exit site has not been described in the literature. In four of five patients, this technique controlled the exit site infection and arrested the progression of the infection to peritonitis, preventing the need for catheter removal.

Anesthetic considerations in patients undergoing percutaneous radiofrequency interstitial tissue ablation.

Radiofrequency (RF) interstitial tissue ablation is a new, minimally invasive procedure for patients with liver cancer who are not candidates for conventional therapy. The percutaneous RF ablation therapy involves placing a needle electrode under ultrasound guidance into a selected portion of the tumor and heating the tissue between 90 degrees C and 100 degrees C. The ablation procedure can be done under monitored anesthesia care on an outpatient basis. The patient's ability to cooperate with regard to breathing is critical for accurate needle placement. Intravenous sedation must be meticulously titrated to maintain a delicate balance of patient cooperation and optimal comfort.

Impact of recipient MELD score on resource utilization.

The model for end stage liver disease (MELD) system prioritizes deceased donor organs to the sickest patients who historically require higher healthcare expenditures. Limited information exists regarding the association of recipient MELD score with resource use. Adult recipients of a primary liver allograft (n = 222) performed at a single center in the first 27 months of the MELD system were analyzed. Costs were obtained for each recipient for the 12 defined categories of resource utilization from the time of transplant until discharge. True (calculated) MELD scores were used. Inpatient transplant costs were significantly associated with recipient MELD score (r = 0.20; p = 0.002). Overall 1-year patient survival was 85.0% and was not associated with MELD score (p = 0.57, log rank test). Recipient MELD score was significantly associated with costs for pharmacy, laboratories, radiology, dialysis and physical therapy. Multivariate linear regression revealed that MELD score was most strongly associated with cost compared to other demographic and clinical factors. Recipient MELD score is correlated with transplant costs without significantly impacting survival.

Renal allograft torsion associated with prune-belly syndrome.

We report a 26-month-old child diagnosed with prune-belly syndrome and end-stage renal disease who received intraperitoneal implantation of an adult cadaveric renal graft which functioned very well for approximately 6 weeks. The patient then presented with acute renal failure which was proved to be secondary to torsion of the graft, twisting the artery and vein. The ureter was wrapped 360 degrees around the graft. These conditions resulted in loss of the graft and nephrectomy. Ours is the second report of such an occurrence; the first was from a living-related kidney donor. We believe the lack of abdominal wall tone contributes to graft mobility and risk of torsion of the kidney. We recommend that nephropexy be considered in these patients. In addition, the risk of torsion must be at the forefront of the differential diagnosis in a prune-belly renal transplant patient with acute onset of oliguria. Renal sonography with Doppler should be employed as soon as possible so that the graft can be saved.

Exposure to Mycobacterium tuberculosis (MTB) in a renal transplant candidate: what further preoperative screening tests are available?

Despite negative preoperative screening for MTB, a renal candidate demonstrated active tuberculous lymphadenitis (TL) in a deep iliac node intraoperatively during living related renal transplantation. With intraoperative discovery of TL, both donor nephrectomy and renal transplant were aborted. The authors present this case of TL to discuss whether additional preoperative screening tests are available to document previous exposure to MTB in a renal transplant candidate. The diagnosis and treatment of MTB in patients on routine hemodialysis are reviewed. The authors review the operative case to emphasize that critical intraoperative measures must be taken to minimize operative and postoperative morbidity in the donor and recipient. Finally, the literature for current antibiotic regimens in the treatment of TL is reviewed.

Gallbladder carcinoma producing alpha-fetoprotein.

Alpha-feto protein (AFP) is a clinically useful marker for hepatocellular carcinoma, hepatoblastoma, and nonseminomatous testicular tumors. Elevated serum AFP can also occur with tumors of the gastrointestinal tract, pancreas, lung, kidney, and urachus. Serum AFP can also be minimally elevated in nonmalignant conditions including acute and chronic hepatitis, cirrhosis, and pregnancy. Reports of gallbladder carcinoma that elaborate AFP are extremely rare, and almost all represent papillary carcinomas. Until now, there have been only two reports in the world literature that describe undifferentiated gallbladder carcinoma with elevated serum AFP. The authors present one case of undifferentiated gallbladder carcinoma and another case of poorly differentiated gallbladder carcinoma with increased serum AFP. In both cases, serum AFP was particularly useful in documenting metastatic recurrence of gallbladder carcinoma.

Liver transplantation for the Budd-Chiari syndrome.

A retrospective study was performed that analyzed 23 patients who had an orthotopic liver transplantation for the Budd-Chiari syndrome with end-stage liver disease. Patient follow-up was as long as 14 years. The technical considerations relevant to the Budd-Chiari syndrome were discussed. There have been no serious complications of postoperative anticoagulation. Three patients, all of whom died, had recurrence of the Budd-Chiari syndrome. No other patient has had evidence of recurrent Budd-Chiari syndrome on postoperative liver biopsies. One-, 3-, and 5-year actuarial survival was 68.8%, 44.7%, and 44.7%, respectively. It was concluded that orthotopic liver transplantation is the most effective treatment for patients with the Budd-Chiari syndrome and end-stage liver disease.

Endothelin-stimulated nitric oxide production in the isolated Kupffer cell.

Endothelin (ET) is a potent peptide mediator exhibiting a wide variety of effects in both the parenchymal and nonparenchymal hepatic cells. In the Kupffer cell, ET activates several transmembrane signaling pathways to generate numerous second messengers including the phospholipase C-generated products inositol-1,4,5-trisphosphate and diacylglycerol and the cyclooxygenase product prostaglandin E2 via specific ETB-type receptors. In addition to these findings, we have now demonstrated that endothelin stimulates the production of nitric oxide (NO) in the Kupffer cell in a time- and concentration-dependent manner. Western blot analysis indicates that ET-stimulated NO production occurs though activation of the inducible form of the nitric oxide synthase enzyme. These findings have important implications as the stimulation of NO production by ET may be part of the physiological response to inflammation or infection. Elevated levels of ET and NO have been found to be associated with numerous hepatic pathophysiological conditions that may contribute to derangements in the vascular system seen in these conditions.

Endoscopic biliary stent migration with small bowel perforation in a liver transplant recipient.

Intestinal perforation from a migrated biliary stent is a rare complication after endoscopic stent placement for benign biliary stricture. We provide the first description of stent migration and distal small-bowel perforation after stent placement for biliary anastomotic stricture in a liver transplant recipient. We review the current literature on the diagnosis and management of stent migration and intestinal perforation after endoscopic or percutaneous stent placement for benign and malignant biliary strictures. Early diagnosis and treatment of biliary stent migration and subsequent intestinal perforation are essential in transplant patients, in whom immunosuppression sometimes blunts signs and symptoms of intestinal perforation.

Investigation and control of aspergillosis and other filamentous fungal infections in solid organ transplant recipients.

Filamentous fungal infections are associated with high morbidity and mortality in solid organ transplant patients, and prevention is warranted whenever possible. An increase in invasive aspergillosis was detected among solid organ transplant recipients in our institution during 1991-92. Rates of Aspergillus infection (18.2%) and infection or colonization (42%) were particularly high among lung transplant recipients. Epidemiologic investigation revealed cases to be both nosocomial and community-acquired, and preventative efforts were directed at both sources. Environmental controls were implemented in the hospital, and itraconazole prophylaxis was given in the early period after lung transplantation. The rate of Aspergillus infection in solid organ transplant recipients decreased from 9.4% to 1.5%, and mortality associated with this disease decreased from 8.2% to 1.8%. The rate of Aspergillus infection or colonization among lung transplant recipients decreased from 42% to 22.5%; nosocomial Aspergillus infection decreased from 9% to 3.2%. Cases of aspergillosis in lung transplant recipients were more likely to be early infections in the pre-intervention period. Early mortality in lung transplant recipients decreased from 15% to 3.2%. Two cases of dematiaceous fungal infection were detected, and no further cases occurred after environmental controls. The use of environmental measures that resulted in a decrease in airborne fungal spores, as well as antifungal prophylaxis, was associated with a decrease in aspergillosis and associated mortality in these patients. Ongoing surveillance and continuing intervention is needed for prevention of infection in high-risk solid organ transplant patients.