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Objective: To report 2 cases of central pontine myelinolysis (CPM) post liver transplantation in which treatment with plasmapheresis and intravenous immune globulin improved expected neurologic outcome., Case Summary: Two patients who underwent orthotopic liver transplant developed CPM early in their postoperative course. Magnetic resonance imaging of the brain demonstrated severe demyelination of either the pons or the midbrain, respectively. Both patients developed significant neurologic abnormalities, including acute mental status changes, severe muscle weakness, spasticity, and/or prolonged paralysis. Pretransplant laboratory results indicated serum sodium levels fluctuating between 115 mEq/L and 152 mEq/L. Both patients received 6 days of plasmapheresis (PP) followed by 5 consecutive days of intravenous immune globulin (IVIG). Significant neurologic improvement was experienced at 2 and 4 weeks, respectively, after therapy was initiated. Complete resolution of neurologic symptoms was evident at 1 year follow-up., Discussion: Currently, specific guidelines or recommendations for the treatment of CPM are practically nonexistent. CPM remains a neurologic complication that is difficult to treat and may result in permanent significant neurologic sequelae. The etiology and pathogenesis of this disease are unclear, although aggressive osmolar correction, particularly in the setting of hyponatremia, is the main risk factor. While patients may eventually show some improvement with supportive care, progress is often protracted, and complete resolution of symptoms is exceedingly rare. The severity of the midbrain lesions juxtaposed against the rapidity of symptom resolution in these 2 patients alludes to a potential therapeutic benefit after initiation of therapy with PP and IVIG., Conclusions: These cases suggest that prompt recognition of CPM and initiation of PP and IVIG may help modulate its progress and improve long-term neurologic outcome., (© 2011 SAGE Publications.)

Liver transplantation for cholangiocarcinoma (CCA) remains a controversial subject. More than 15 years after, a novel protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation was first used in patients with unresectable hilar CCAs, these methods have yet to reach broad application. Results have confirmed that this approach leads to significantly lower recurrence rates and higher long-term survival rates than other existing treatment modalities. Despite this, protocols to treat patients with CCA are not widespread, and are available at only a handful of transplant programs. At these centers, treatment success may ultimately hinge on regional model for end-stage liver disease scores and waiting time for transplant. While acknowledging these factors as well as a severe organ shortage, it is important that the transplant community not overlook a potentially effective form of therapy for a previously untreatable disease.

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.

This study identifies the major risk factors associated with outcome after liver transplantation, showing that candidates for this surgery can be stratified into differential risk categories at the time of the actual surgery. All the livers used were flushed with University of Wisconsin solution. The study is a retrospective multivariate analysis of 2376 consecutive transplantations performed on 2019 recipients between November 1, 1987, and December 31, 1993. Donor variables studied were age, sex, blood type, cause of death, intensive care unit length of stay, body mass index, use of pressors (dopamine infusion > 10 micrograms/kg/min or continuous infusion of epinephrine or norepinephrine), use of pitressin, cardiopulmonary resuscitation, terminal transaminase levels, serum sodium level at procurement, and total ischemia time. Recipient variables studied were age; sex; blood type; indication for liver transplantation; history of liver transplantation or upper abdominal surgery; United Network for Organ Sharing urgency status; need for mechanical ventilation; primary immunosuppression; and preoperative bilirubin level, prothrombin time, and creatinine level. The variables independently associated with outcome were donor age, female donor sex, ischemia time, recipient age, prior liver transplant, preoperative mechanical ventilation, preoperative bilirubin level, preoperative creatine level, indication for transplantation and primary immunosuppression used. The results of this study not only give us insight into the probable outcomes of individual patients, but also show that this stratification can be useful when comparing results across different groups or in helping to choose the best donor-recipient combination based on the calculated probability of a favorable outcome.

Dysoxia can be defined as ATP flux decreasing in proportion to O2 availability with preserved ATP demand. Hepatic venous beta-hydroxybutyrate-to-acetoacetate ratio (beta-OHB/AcAc) estimates liver mitochondrial NADH/NAD and may detect the onset of dysoxia. During partial dysoxia (as opposed to anoxia), however, flow may be adequate in some liver regions, diluting effluent from dysoxic regions, thereby rendering venous beta-OHB/AcAc unreliable. To address this concern, we estimated tissue ATP while gradually reducing liver blood flow of swine to zero in a nuclear magnetic resonance spectrometer. ATP flux decreasing with O2 availability was taken as O2 uptake (VO2) decreasing in proportion to O2 delivery (QO2); and preserved ATP demand was taken as increasing Pi/ATP. VO2, tissue Pi/ATP, and venous beta-OHB/AcAc were plotted against QO2 to identify critical inflection points. Tissue dysoxia required mean QO2 for the group to be critical for both VO2 and for Pi/ATP. Critical QO2 values for VO2 and Pi/ATP of 4.07 +/- 1.07 and 2.39 +/- 1.18 (SE) ml . 100 g-1 . min-1, respectively, were not statistically significantly different but not clearly the same, suggesting the possibility that dysoxia might have commenced after VO2 began decreasing, i.e., that there could have been "O2 conformity." Critical QO2 for venous beta-OHB/AcAc was 2.44 +/- 0.46 ml . 100 g-1 . min-1 (P = NS), nearly the same as that for Pi/ATP, supporting venous beta-OHB/AcAc as a detector of dysoxia. All issues considered, tissue mitochondrial redox state seems to be an appropriate detector of dysoxia in liver.

Gastric intramucosal pH (pHi) is often calculated by the Henderson-Hasselbalch equation, using arterial plasma [HCO3-]ap and PCO2 measured in saline obtained from a silastic balloon tonometer after equilibration in the lumen of the stomach. A pHi value less than approximately 7.3 pH units is often taken as evidence of intestinal ischemia. An alternative measure is tissue PCO2 (PtCO2)-PaCO2 difference [P(t-a)CO2]. The idea is that PtCO2 will increase slightly relative to PaCO2 as O2 supply decreases, and then increase strikingly when flow decreases to a critical value, because of liberation of CO2 from tissue Hco3- by anaerobically generated strong acid. A third method is arterial plasma pH (pHap)-pHi difference [pH(ap-i)]. We used mathematical simulations to test the hypotheses that calculated pHi is independent of arterial acid-base status; and pH(ap-i) provides the same information as does P(t-a) CO2. Using the Van Slyke version of the arterial whole blood [standard base excess] ([SBE]aWB) equation, it was found that a change in [SBE]aWB at constant PaCO2 and constant PtCO2 produces a change in calculated pHi (P = 0), such that the relation between changing [SBE]aWB and changing pHi is predictable by a single polyomial equation (R2 = .999). pH(ap-i) avoids this confounding influence of [SBE]aWB. However, it was further shown that pH(ap-i) can be associated with a wide range of P(t-a)CO2, depending on the magnitude of pH(ap-i), and on the PaCO2 at which P(t-a)CO2 is measured. We conclude that P(t-a)CO2 is a more reliable index of gastric oxygenation than is pHi alone or pH(ap-i).

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.

The incidence of native portal vein thrombosis (PVT) in liver transplant recipients has been reported to range from 2.1 to 13.8%. We have identified an inordinately high incidence of PVT in a consecutive series of U.S. veterans receiving liver transplants. Between October 1989 and February 1994, 88 consecutive U.S. veterans received 99 orthotopic liver transplants under primary Tacrolimus (Prograf, formerly FK506) based immunosuppression. A number of clinical features were examined in an effort to identify risk factors for PVT and outcome was compared to patients without PVT. Native PVT was present in 23/88 (26%) patients. All of these patients were male U.S. veterans with a mean age of 47 years. When compared to the 65 patients without PVT, we found no significant difference with respect to underlying liver disease, age, Childs-Pugh score (mean = 12), UNOS status as defined prior to April 1995 (95% UNOS 3 or 4), previous abdominal surgery, or liver volume. Median blood loss for patients with PVT (21 units of packed red blood cells) was greater than for those without PVT (14 units, P = 0.04). Portal thrombectomy was performed in 11 patients, 11 patients required mesoportal jump grafts, and 1 patient had an interposition graft. Standard veno-venous bypass was used in 10 patients with single bypass utilized for the remainder. Actuarial patient survival for all patients at 1, 2, and 4 years was 88, 85, and 79%, respectively. There was no significant difference in patients with or without PVT. Patients with PVT had poorer graft survival than patients without PVT (86% vs 65%, 1 year; 81% vs 65%, 2 years; 81% vs 61%, 4 years; P = 0.03); however, this was not related to technical problems with the portal venous inflow. PVT occurred in 26% of U.S. veterans undergoing liver transplantation. These patients had significantly higher operative blood loss and poorer graft survival. The high incidence of postnecrotic cirrhosis in a predominantly male group of patients with advanced disease, as is evident by the high mean Childs-Pugh score and UNOS status, perhaps accounts for our observations.

Background: The selection of patients for resective therapy of hepatic colorectal metastases remains controversial. A number of clinical and pathologic prognostic risk factors have been variably reported to influence survival., Methods: Between January 1981 and December 1991, 204 patients underwent curative hepatic resection for metastatic colorectal cancer. Fourteen clinical and pathologic determinants previously reported to influence outcome were examined retrospectively. This led to a proposed TNM staging system for metastatic colorectal cancer (mTNM)., Results: No operative deaths occurred (death within 1 month). Overall 1-, 3-, and 5-year survivals were 91%, 43%, and 32%, respectively. Gender, Dukes' classification, site of primary colorectal cancer, histologic differentiation, size of metastatic tumor, and intraoperative blood transfusion requirement were not statistically significant prognostic factors (p > 0.05). Age of 60 years or more, interval of 24 months or less between colorectal and hepatic resection, four or more gross tumors, bilobar involvement, positive resection margin, lymph node involvement, and direct invasion to adjacent organs were significant poor prognostic factors (p < 0.05). In the absence of nodal disease or direct invasion, patients with unilobar solitary tumor of any size, or unilobar multiple tumors of 2 cm or smaller (stages I and II) had the highest survival rates of 93% at 1 year, 68% at 3 years, and 61% at 5 years. Unilobar disease with multiple lesions greater than 2 cm (stage III) resulted in 1-, 3-, and 5-year survivals of 98%, 45%, and 28%, respectively. Patients with bilobar involvement (multiple tumors, any size, or a single large metastasis) (stage IVA) had survival rates of 88% at 1 year, 28% at 3 years, and 20% at 5 years (p < 0.00001). Patients with nodal involvement or extrahepatic disease (stage IVB) experienced the poorest outcome with 1-, 3-, and 5-year survivals of 80%, 12%, and 0%, respectively (p < 0.00001)., Conclusions: The proposed mTNM staging system appears to be useful in predicting the outcomes after hepatic resection of metastatic colorectal tumors.