The Miami experience with almost 100 multivisceral transplants.

We report our experience with 98 patients who received primary multivisceral transplantations. Three eras can be distinguished based on the evolution of technique, immunosuppression, and monitoring: August 1994 to December 1997 (first era); January 1998 to December 2000 (second era); and January 2001 to present (third era). Sixteen patients were transplanted during the first era, 18 during the second era, and 64 during the third era. Fifty-three patients are alive with a median follow-up of 37.5 months (range: 1 to 116 months). The leading cause of mortality was infection (n = 17), followed by rejection (n = 6). Seven patients required retransplantation and five of them subsequently died. The estimated 3-year survival was 25% +/- 11% for era 1; 44% +/- 12% for era 2; and 58% +/- 7% for era 3. Additionally, 45.3% (29/64) of patients in the third era never developed rejection versus 23.5% (8/34) of patients in the first two eras combined. The percentage of patients who developed a moderate or severe rejection was significantly less in the third era compared with the first two eras combined, 31.6% (20/64) versus 67.6% (23/34). A comparison of the hazard rate of developing severe rejection showed a protective effect of the multivisceral graft (P = .0001). In conclusion, multivisceral transplantation is indicated for patients with short bowel syndrome and extended abdominal catastrophies. Evolution in surgical techniques, immunosuppression, and monitoring have improved patient survival, which is now similar to that of other complex solid organ transplants.

Mucosal fibrosis in intestinal transplant biopsies correlates positively with the development of chronic rejection.

Endoscopic biopsies of intestinal allografts are limited to the superficial layers of the bowel. We investigated whether the presence of mucosal fibrosis in graft biopsies was indicative of chronic allograft rejection. We examined graft biopsies of 182 intestinal transplant recipients for the presence of mucosal fibrosis. Kaplan-Meier analysis showed that within 5 years posttransplantation 33% of intestinal transplant patients had graft biopsies positive for mucosal fibrosis. Although the presence of mucosal fibrosis did not affect patient or graft survival, patients with this lesion were at higher risk of developing chronic allograft enteropathy.

An association of lower serum citrulline levels within 30 days of acute rejection in patients following small intestine transplantation.

INTRODUCTION: In a prospective protocol we studied whether serum citrulline level within 30 days of an acute rejection was predictive of the episode. METHODS: An acute rejection episode was defined as the date of occurrence of any biopsy-proven rejection in which treatment was initiated until two successive biopsies showed no further rejection. We compared the mean citrulline level based on values determined within 30 days of the start of an acute rejection episode with the mean citrulline level measured on the same patient during a rejection-free period. Serum citrulline measurements were available immediately prior to the occurrence of rejection for 22 patients who experienced 37 episodes. RESULTS: For the 12 episodes of mild rejection, the mean serum citrulline level +/- SE (standard error) was 15.0 + 2.3 micromol/L prior to rejection and 18.8 +/- 2.4 micromol/L during the rejection-free periods. A paired t test of the mean differences was not significant (P = 17). For the 25 episodes of moderate or severe rejection, the mean serum citrulline level was 12.4 +/- 1.1 micromol/L before rejection and 18.8 +/- 2.0 micromol/L during the rejection-free periods. A paired t test of the mean difference was statistically significant (P = .002). CONCLUSIONS: Although further study of citrulline as a marker for the early detection of acute rejection episodes is needed, our hope is that its use will help to prevent some of these early episodes from evolving into full-blown moderate or severe grades of rejection.

Intestinal transplantation with alemtuzumab (Campath-1H) induction for adult patients.

BACKGROUND: Alemtuzumab (Campath-1H [C1H]) is a humanized monoclonal antibody directed against the CD 52 antigen that is present on the surface of T cells, B cells, natural killer cells and monocytes. We studied its application in intestinal transplantation. METHODS: This is a retrospective review of adult patients who underwent intestinal transplantation between December 1994 and May 2005. Group 1: non-C1H group (n = 39); group 2: C1H group (n = 37). C1H was administered as an induction immunosuppression in four doses (0.3 mg/kg), or in two doses (30 mg/kg). Tacrolimus levels were maintained at low level (5-10 ng/dL). No maintenance steroids were given. RESULTS: One-year survival of group 1 and group 2 patients were 57% and 70%, respectively. This difference is not statistically significant. Of 37 patients in group 2, 21 are alive. The incidence of rejection was lower in group 2 (P < .005). Average current tacrolimus level is 6.97 +/- 3.98 ng/dL. Seventeen patients (81%) are steroid free, and 15 (71%) are maintained solely on tacrolimus. There was no graft versus host disease in group 2. CONCLUSIONS: Our preliminary data suggest that C1H can provide effective immunosuppression for intestinal transplantation. Incidence of rejection was less with this regimen using low maintenance tacrolimus and minimal steroids.

Refractory ascites after liver transplantation: an analysis of 1058 liver transplant patients at a single center.

A retrospective study of 1058 liver transplant recipients was performed to determine: (i) the incidence, etiology, timing, clinical features and treatment of refractory ascites (RA), (ii) risk factors for RA development, (iii) predictors of RA disappearance, (iv) predictors of survival following RA and (v) the impact of RA on patient survival. Sixty-two patients (5.9%) developed RA and its disappearance occurred in 27/62 cases. Patients having hepatitis C virus (HCV) had a significantly higher hazard rate of developing RA (p < 0.00001). No other baseline characteristic was associated with RA. Cox stepwise regression analysis of the hazard rate of RA disappearance found two significant factors: HCV recurrence as the reason for developing RA implied a poorer outcome (p = 0.006), whereas an unknown reason implied a favorable outcome (p = 0.02). In addition, survival following RA was significantly poorer among patients having bacterial peritonitis or HCV recurrence. Finally, the mortality rate was significantly (nearly 8.6 times) higher in patients following RA development while it was ongoing (p < 0.00001); however, if the RA disappeared, then the additional risk of death also disappeared. This study illustrates the importance of developing an optimal treatment strategy to (i) effectively treat RA if it develops and (ii) prevent hepatitis C recurrence.

The impact of Campath 1H induction in adult liver allotransplantation.

BACKGROUND: We report our experience with Campath 1H in adult liver allotransplantation. METHODS: Between December 2001 and February 2004, 77 patients underwent liver transplantation using Campath 1H induction and low-dose maintenance tacrolimus immunosuppression. The control group consisted of 50 patients with similar baseline characteristics and the same eligibility criteria, transplanted under our standard Tacrolimus/steroids regimen. Hepatitis C patients were excluded from the study. RESULTS: Patient and graft survival were similar for both groups. The incidence of rejection was significantly lower in the Campath vs the control group (51% vs 65% at 12 months, P = .009). Tacrolimus trough levels and conversion from Tacrolimus or the addition of other immunosuppressive drugs due to nephrotoxicity were also significantly lower in the Campath 1H group. CONCLUSION: Campath 1H induction with low-dose Tacrolimus maintenance immunosuppression is an effective regimen in reducing acute rejection in adult liver transplantation, while maintaining lower tacrolimus levels and less nephrotoxicity than our conventional immunosuppressive regimen.

Transplantation for the treatment of intra-abdominal fibromatosis.

MATERIALS AND METHODS: During the last 9 years we treated 14 patients with a diagnosis of intra-abdominal fibromatosis. The 11 patients who received an intestinal allograft included isolated intestine (n = 6), liver-intestine (n = 1), intestine-kidney (n = 1), multivisceral (n = 1), multivisceral-kidney (n = 1), multivisceral-no liver (n = 1). Three patients received an intestinal autograft after partial abdominal evisceration and ex vivo tumor resection. Three patients additionally underwent an abdominal wall allograft. RESULTS: At follow-up until August 2004, all autotransplant patients are alive. Four intestinal transplant patients died within the first postoperative month. There were three graft losses. A patient who lost his graft early postoperatively was retransplanted but died of sepsis shortly there after. Two more patients lost their graft due to severe rejection and were retransplanted successfully. Two patients developed desmoid tumor recurrence in their abdominal or thoracic wall. Ten patients are alive 1 to 9 years posttransplantation. Nine have fully functioning grafts and one patient requires TPN supplementation at night due to dysmotility of her autograft. CONCLUSION: Intestinal allo-, or autotransplantation combined with transplantation of the abdominal wall can be lifesaving for patients suffering from extensive intra-abdominal fibromatosis.

Logistics and technique for procurement of intestinal, pancreatic, and hepatic grafts from the same donor.

OBJECTIVE: To assess a technique for simultaneous recovery of the intestine, pancreas, and liver from the same donor. SUMMARY BACKGROUND DATA: With the more frequent use of pancreatic and intestinal transplantation, a procurement procedure is needed that permits retrieval of both organs as well as the liver from the same cadaveric donor for transplantation to different recipients. It is believed by many procurement officers and surgeons, however, that this objective is not technically feasible. METHODS: A technique for simultaneous recovery of the intestine, pancreas, and liver was used in 13 multiorgan cadaver donors during a 26-month period, with transplantation of the organs to 33 recipients. The intestine was removed from 11 donors separately and in continuity with the pancreas in the other 2. Six additional pancreases were excised and transplanted separately. Thirteen livers were retrieved, one of which was discarded because of steatorrhea. Ten of the remaining 12 livers were transplanted intact; the other 2 were split in situ and used as reduced-size hepatic allografts in four recipients. RESULTS: None of the 11 intestinal, 6 pancreatic, 2 intestinal-pancreatic, or 14 whole or partial liver allografts sustained serious ischemic injury or were lost as a result of technical complications. One liver recipient died 25 months after surgery of recurrent C virus hepatitis. The other 32 recipients had adequate allograft function with a mean follow-up of 8 months. CONCLUSION: It was possible using the described technique to retrieve intestine, pancreas, and liver allografts safely from the same donor and to transplant these organs to different recipients.

Liver transplantation for hepatocellular carcinoma: a proposal of a prognostic scoring system.

BACKGROUND: The current staging system of hepatocellular carcinoma established by the International Union Against Cancer and the American Joint Committee on Cancer does not necessarily predict the outcomes after hepatic resection or transplantation. STUDY DESIGN: Various clinical and pathologic risk factors for tumor recurrence were examined on 344 consecutive patients who received hepatic transplantation in the presence of nonfibrolamellar hepatocellular carcinoma to establish a reliable risk scoring system. RESULTS: Multivariate analysis identified three factors as independently significant poor prognosticators: 1) bilobarly distributed tumors, 2) size of the greatest tumor (2 to 5 cm and > 5 cm), and 3) vascular invasion (microscopic and macroscopic). Prognostic risk score (PRS) of each patient was calculated from the relative risks of multivariate analysis. The patients were grouped into five grades of tumor recurrence risk: grade 1: PRS = 0 to < 7.5; grade 2: PRS = 7.5 to < or = 11.0; grade 3: PRS > 11.0 to 15.0; grade 4: PRS > or = 15.0; and grade 5: positive node, metastasis, or margin. The proposed PRS system correlated extremely well with tumor-free survival after liver transplantation (100%, 61%, 40%, 5%, and 0%, from grades 1 to 5, respectively, at 5 years), but current pTNM staging did not. CONCLUSIONS: 1) Patients with grades 1 and 2 are effectively treated with liver transplantation, 2) patients with grades 4 and 5 are poor candidates for liver transplantation, and 3) patients with grade 1 do not benefit from adjuvant chemotherapy.

Liver resection combined with excision of vena cava.

BACKGROUND: This study was designed to review our experience with combined partial hepatectomy and vena caval replacement for primary and metastatic liver tumors. STUDY DESIGN: The medical records of all the patients who underwent liver resection and excision of the vena cava over a period of 13 years and 4 months at a single institution were analyzed. The types of tumors fell into four categories: 1) metastatic, 2) primary leiomyosarcoma of the inferior vena cava, 3) tumors with direct extension to the liver, and 4) cholangiocarcinoma. RESULTS: The perioperative mortality was 11% related to technical complications and hepatic insufficiency. Other important complications included biliary fistula and liver abscess; patients recovered from these complications without sequelae. Six of nine patients are alive with a followup from 6 months to 156 months (median 66.5 months), and three of them are free of disease. The most common sites of recurrence were lung, liver, and brain. The patients with leiomyosarcoma of the cava and pheochromocytoma who underwent these combined procedures had the longest survival. CONCLUSIONS: This small series confirms the feasibility of obtaining longterm survival after excision of tumors that have involved portions of the liver and the vena cava. Innovative variations on the method of vena caval replacement and increased awareness of these complex surgical techniques will expand the indications of hepatic resection.

Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system.

BACKGROUND: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. STUDY DESIGN: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S(t) = [So(t)]exp(R-Ro), where So(t) is the survival rate of patients with none of the identified risk factors and Ro = 0. RESULTS: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R= 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). CONCLUSIONS: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies.

Treatment of hilar cholangiocarcinoma (Klatskin tumors) with hepatic resection or transplantation.

BACKGROUND: Because of the rarity of hilar cholangiocarcinoma, its prognostic risk factors have not been sufficiently analyzed. This retrospective study was undertaken to evaluate various pathologic risk factors which influenced survival after curative hepatic resection or transplantation. METHODS: Between 1981 and 1996, 72 patients (43 males and 29 females) with hilar cholangiocarcinoma underwent hepatic resection (34 patients) or transplantation (38 patients) with curative intent. Medical records and pathologic specimens were reviewed to examine the various prognostic risk factors. Survival was calculated by the method of Kaplan-Meier using the log rank test with adjustment for the type of operation. Survival statistics were calculated first for each kind of treatment separately, and then combined for the calculation of the final significance value. RESULTS: Survival rates for 1, 3, and 5 years after hepatic resection were 74%, 34%, and 9%, respectively, and those after transplantation were 60%, 32%, and 25%, respectively. Univariate analysis revealed that T-3, positive lymph nodes, positive surgical margins, and pTNM stage III and IV were statistically significant poor prognostic factors. Multivariate analysis revealed that pTNM stage 0, I, and II, negative lymph node, and negative surgical margins were statistically significant good prognostic factors. For the patients in pTNM stage 0-II with negative surgical margins, 1-, 3-, and 5-year survivals were 80%, 73%, and 73%, respectively. For patients in pTNM stage IV-A with negative lymph nodes and surgical margins, 1-, 3-, and 5-year survivals were 66%, 37%, and 37%, respectively. CONCLUSIONS: Satisfactory longterm survivals can be obtained by curative surgery for hilar cholangiocarcinoma either with hepatic resection or liver transplantation. Redefining pTNM stage III and IV-A is proposed to better define prognosis.

[Hilar and peripheral cholangiocarcinomas]. / Colangiocarcinomas hiliares y periféricos.

Cholangiocarcinoma is the most frequent malignant neoplasm of the bile ducts. It continues to be a diagnostic and therapeutic challenge because of its form of growth and intimate relation with hepatic hilus structures. While cholangiocarcinomas situated distal to the biliary confluence have well-defined characteristics and treatment, cholangiocarcinomas situated in or proximal to the biliary confluence are problematic. A study was made of the so-called intrahepatic cholangiocarcinomas by establishing two types, peripheral and hilar. Their features and therapeutic options are analyzed and published results are reviewed.

Liver resection for hilar and peripheral cholangiocarcinomas: a study of 62 cases.

OBJECTIVE: To analyze a single center's 14-year experience with 62 consecutive patients with hilar (HCCA) and peripheral (PCCA) cholangiocarcinomas. SUMMARY BACKGROUND DATA: Long-term survival after surgical treatment of HCCA and PCCA has been poor. METHODS: From March 1981 until December 1994, 62 consecutive patients with HCCA (n = 28) and PCCA (n = 34) underwent surgical treatment. The operations were individualized and included local excision of the tumor and suprapancreatic bile duct, lymph node dissection, vascular reconstruction, and subtotal hepatectomy. Clinical and pathologic risk factors were examined for prognostic influence. RESULTS: Patients were followed for a median of 25 months (12-102 months). Postoperative morbidity and mortality (at 30 days) were 32% and 14%, respectively, for HCCA and 24% and 6% for PCCA. The survival rates for HCCA and PCCA were 79% (+/-8%) and 67% (+/-8%) at 1 year; 39% (+/-10%) and 40% (+/-9%) at 3 years; and 8% (+/-7%) and 35% (+/-10%) at 5 years, respectively. The median survival was 24 (+/-4) months for HCCA and 19 (+/-8) months for PCCA. The disease-free survival rates for HCCA and PCCA were 85% (+/-10%) and 77% (+/-9%) at 1 year; 18% (+/-11%) and 41% (+/-12%) at 3 years; and 18% (+/-11%) and 41% (+/-12%) at 5 years, respectively. Nearly 80% of these patients had TNM stage IV tumors. With HCCA, no risk factors were associated with patient survival. For PCCA, multiple tumors (relative risk [RR] = 3.5; 95% confidence interval [CI] = 1.2-10.5) and incomplete resection (RR = 8.3; 95% CI = 2.3-29.6) were independently associated with a worse prognosis. For HCCA, there was a trend for lower disease-free survival in females (p = 0.056; log rank test). For PCCA, tumor size >5 cm was the only factor associated with disease recurrence (p = 0.024; log rank test). CONCLUSIONS: Even though rare, 5-year survival by resection can be achieved in both HCCA and PCCA, but new adjuvant treatments are clearly needed.

Hepatic resection and transplantation for peripheral cholangiocarcinoma.

BACKGROUND: Recent publications have questioned the role of orthotopic liver transplantation (OLT) in treating advanced or unresectable peripheral cholangiocarcinoma (Ch-Ca). STUDY DESIGN: We reviewed our experience with Ch-Ca to determine survival rates, recurrence patterns, and risk factors in 54 patients who underwent either hepatic resection or OLT between 1981 and 1994. Liver transplantation was performed in patients with unresectable tumors (n = 12) and in those with advanced cirrhosis (n = 8). There were 33 women (61%) and 21 men (39%), with a mean age of 54.3 years. The median followup period was 6.8 years. Prognostic risk factors were analyzed by univariate and multivariate analyses. RESULTS: Mortality within 30 days was 7.4%. Overall patient and tumor-free survival rates were 64% and 57% at 1 year, 34% and 34% at 3 years, and 26% and 27% at 5 years after operation. Thirty-two patients (59.3%) experienced tumor recurrence. Univariate analysis revealed that multiple tumors, bilobar tumor distribution, regional lymph node involvement, presence of metastasis, positive surgical margins, and advanced pTNM stages were significant negative predictors of both tumor-free and patient survival. Multivariate analysis revealed that positive margins, multiple tumors, and lymph node involvement were independently associated with poor prognosis. When patients with these three negative predictors were excluded, the patient survivals at 1, 3, and 5 years were 74%, 64%, and 62%, respectively. CONCLUSIONS: Both hepatic resection and OLT are effective therapies for Ch-Ca when the tumor can be removed with adequate margins, the lesion is singular, and lymph nodes are not involved.

Treatment of fibrolamellar hepatoma with subtotal hepatectomy or transplantation.

Fibrolamellar hepatoma (FL-HCC) is an uncommon variant of hepatocellular carcinoma (HCC), distinguished by histopathological features suggesting greater differentiation than conventional HCC. However, the optimal treatment and the prognosis of FL-HCC have been controversial. Follow-up studies are available from 1 year to 27 years, after 41 patients with FL-HCC were treated with partial hepatectomy (PHx) (28 patients) or liver transplantation (13 patients). In this retrospective study, the effect on outcome was determined for the pTNM stage and other prognostic factors routinely recorded at the time of surgery. Cumulative survival at 1, 3, 5, and 10 years was 97.6%, 72.3%, 66.2%, and 47.4%. Tumor-free survival at these times was 80.3%, 49.4%, 33%, and 29.3%. The TNM stage was significantly associated with tumor-free survival. Patients with positive nodes had a shorter tumor-free survival than those with negative nodes (P < .015). Patient survival was most adversely affected by the presence of vascular invasion (P < .05). FL-HCC is an indolently growing tumor of the liver, which usually was diagnosed in our patients at a stage too advanced for effective surgical treatment of most conventional HCC. Nevertheless, long-term survival frequently was achieved with aggressive surgical treatment. When a subtotal hepatectomy could not be performed, total hepatectomy (THx) with liver transplantation was a valuable option.

Risk factors and predictive indexes of early graft failure in liver transplantation.

A retrospective analysis of 462 consecutive liver transplantations has been carried out. These were divided into two groups, according to whether they failed within 90 days (Group I) or survived longer than 90 days (Group II). Twenty-five donor and recipient variables were analyzed. In the univariate analysis, the only donor variable that was significantly different between the two groups was age (45.3 +/- 16.9 years in Group I vs 37.9 +/- 15.4 years in Group II, p < 0.001). There were five recipient variables significantly associated with early graft failure: history of previous liver transplantations (p < 0.0001), United Network for Organ Sharing 4 status (p = 0.003), primary diagnosis (p = 0.001), preoperative serum creatinine (1.97 +/- 1.5 mg/dL in Group I vs 1.46 +/- 1.2 mg/dL in Group II, p = 0.005), and preoperative total serum bilirubin (13.5 +/- 14.4 mg/dL in Group I vs 8.4 +/- 11.4 mg/dL in Group II, p = 0.003). In the multivariate analysis, only three variables were independently associated with outcome: donor age greater than 45 years, abnormal (> 1.5 mg/dL) recipient preoperative creatinine, and a history of previous liver transplantation.

Long-term results after liver transplantation for primary hepatic epithelioid hemangioendothelioma.

BACKGROUND: Hepatic epithelioid hemangioendothelioma (PHEHE) is a multifocal, low-grade malignant neoplasia characterized by its epithelial-like appearance and vascular endothelial histogenesis. The outcome of 16 patients treated with orthotopic liver transplantation (OLT) is the subject of this report. METHODS: A retrospective study of 16 patients with HEHE (7 men, 9 women) with ages ranging from 24 to 58 years (mean 37 +/- 10.6 years). Follow-up intervals ranged from 1 to 15 years (median of 4.5 years). RESULTS: Actual patient survival at 1, 3, and 5 years was 100, 87.5, and 71.3%, respectively. Disease-free survival at 1, 3, and 5 years was 81.3, 68.8, and 60.2%, respectively. The 90-day operative mortality was 0. Involvement of the hilar lymph nodes or vascular invasion did not affect survival. The 5-year survival of HEHE compares favorably with that of hepatocellular carcinoma at the same stage (stage 4A): 71.3 versus 9.8% (p = 0.001) CONCLUSIONS: The long-term survival obtained in this series justifies OLT for these tumors even in the presence of limited extrahepatic disease.