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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. mFor 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.

Background: Although tacrolimus-based immunosuppression has made intestinal transplantation feasible, the risk of the requisite chronic high-dose treatment has inhibited the widespread use of these procedures. We have examined our 1990–1997 experience to determine whether immunomodulatory strategies to improve outlook could be added to drug treatment. Study Design: Ninety-eight consecutive patients (59 children, 39 adults) with a panoply of indications received 104 allografts under tacrolimus-based immunosuppression: intestine only (n = 37); liver and intestine (n = 50); or multivisceral (n = 17). Of the last 42 patients, 20 received unmodified adjunct donor bone marrow cells; the other 22 were contemporaneous control patients. Results: With a mean followup of 32 ± 26 months (range, 1–86 months), 12 recipients (3 intestine only, 9 composite grafts) are alive with good nutrition beyond the 5-year milestone. Forty-seven (48%) of the total group survive bearing grafts that provide full (91%) or partial (9%) nutrition. Actuarial patient survival at 1 and 5 years (72% and 48%, respectively) was similar with isolated intestinal and composite graft recipients, but the loss rate of grafts from rejection was highest with intestine alone. The best results were in patients between 2 and 18 years of age (68% at 5 years). Adjunct bone marrow did not significantly affect the incidence of graft rejection, B-cell lymphoma, or the rate or severity of graft-versus-host disease. Conclusions: These results demonstrate that longterm rehabilitation similar to that with the other kinds of organ allografts is achievable with all three kinds of intestinal transplant procedures, that the morbidity and mortality is still too high for their widespread application, and that the liver is significantly but marginally protective of concomitantly engrafted intestine. Although none of the endpoints were markedly altered by donor leukocyte augmentation (and chimerism) with bone marrow, establishment of the safety of this adjunct procedure opens the way to further immune modulation strategies that can be added to the augmentation protocol.

Background: The suppressed production of nitric oxide (NO), associated with endothelial dysfunction, is thought to be a cause of ischemia and reperfusion injury of the liver. But findings of the salutary effects of NO enhancement on such injury have been conflicting. In this study, we tested our hypothesis that NO enhancement would attenuate ischemic liver injury. For this purpose, an NO precursor, L-arginine, and a novel NO donor, FK409, were applied to a 2-hour total hepatic vascular exclusion model in dogs. Study Design: L-arginine was administered IV at a dose of 100 mg/kg twice (n = 5), while 300 mg/kg twice of FK409 was infused continuously into the portal vein (n = 5). The drugs were given to the animals for 30 and 60 minutes before and after ischemia, respectively. Nontreated animals were used as the control (n = 10). Two-week survival, systemic and hepatic hemodynamics indices, liver function tests, energy metabolism, and histopathology were analyzed. Results: Both treatments comparably augmented hepatic tissue blood flow, decreased liver enzyme release, and increased high-energy phosphate restoration during the reperfusion period, all of which contributed to rescuing all of the treated animals from the 2-hour total hepatic ischemia. In contrast, ischemia caused 70% mortality in the control group. Histologically, structural abnormality and neutrophil infiltration were markedly attenuated by the treatments. Systemic hypotension was observed in the animals treated with FK409, however. Conclusions: Our data demonstrate that NO enhancement alleviates the liver injury caused by ischemia and reperfusion. The supplementation of L-arginine, rather than FK409, is considered more applicable to clinical use because of the absence of systemic adverse effects.

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.