Prevalence of emotional distress in newly diagnosed lung cancer patients.

GOALS OF WORK: Distress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients. PATIENTS AND METHODS: Between November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools. MAIN RESULTS: Fifty (51%) patients reported clinically significant distress (>or=4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation = 0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p < 0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R(2) = 0.12. CONCLUSIONS: The prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.

Liver transplantation for autoimmune hepatitis and the success of aggressive corticosteroid withdrawal.

Our center has attempted to minimize corticosteroid (CS) use in all of our orthotopic liver transplantation (OLT) recipients. Because patients with autoimmune hepatitis (AIH) typically require CSs after transplantation, we reviewed our experience in this cohort of patients to determine (1) patient outcomes including recurrent disease and (2) long-term requirements for CS use in AIH patients. From 1988 to 2006, 1102 OLTs were performed in 1032 adult patients at the University of Colorado, of whom 66 (6%) with AIH received 68 allografts. Recurrence was defined by a clinically worsening examination and histological evidence from biopsy. Bivariate and multivariate analyses were used to evaluate predictors of CS withdrawal. Twelve potential predictors of CS discontinuation were considered: age, gender, presence of inflammatory bowel disease (IBD), type of graft (cadaver or living donor), recurrence of AIH, warm ischemia time, follow-up time (time since transplant), and immunosuppressants (cyclosporine, tacrolimus, sirolimus, azathioprine, and mycophenolate mofetil). Overall survival at 5 years was 91%. The 1- and 5-year recurrence-free survival was 88% and 59%, respectively. Risk (incidence) of recurrent AIH at 1, 3, and 5 years was 12%, 26%, and 36%, respectively. Disease recurred in 23 of 66 patients or 34.8%. Of the 23 patients who developed recurrent disease, none received a second transplant because of recurrent disease. CSs were withdrawn in 50% of patients at the time of review. Only 2 factors on multivariate analysis were strongly associated negatively with CS withdrawal: (1) an increasing dose of the immunosuppressant and (2) the presence of IBD. Controlling for these other factors, we found that recurrent disease did not strongly influence CS withdrawal. In conclusion, outcomes in AIH patients were quite favorable, and none of the patients required retransplantation for recurrent AIH. With a CS minimization approach, one-half of the patients were able to remain CS-free.

Comprehensive cost comparison of adult-adult right hepatic lobe living-donor liver transplantation with cadaveric transplantation.

BACKGROUND: An important long-term consideration for living-donor liver transplantation (LDLT) is the expense compared with cadaveric-liver transplantation. LDLT is a more complex procedure than cadaveric transplantation and the cost of donor evaluation, donor surgery, and postoperative donor care must be included in a cost analysis for LDLT. In this study, we compare the comprehensive cost of LDLT with that of cadaveric-liver transplantation. METHODS: All costs for medical services provided at our institution were recorded for 24 LDLT and 43 cadaveric recipients with greater than 1 year follow-up transplanted between August 1997 and April 2000. The donor costs include donors evaluated and rejected, donors evaluated and accepted, donor right hepatectomy costs, and donor follow-up costs (365 days postdonation). LDLT and cadaveric recipient costs include medical care 90 days pre-LDLT, recipient transplant costs, and recipient follow-up costs (365 days posttransplant) including retransplantation. Cost is expressed as an arbitrary cost unit (CU) that is a value between $500 to $1,500. RESULTS: Total LDLT costs (evaluations of rejected donors+evaluations of accepted donors+donor hepatectomy+donor follow-up care for 1 year+pretransplant recipient care [90 days pretransplant]+recipient transplantation+recipient 1-year posttransplant care)= 162.7 CU. Total mean cadaveric transplant costs (pretransplant recipient care [90 days pretransplant]+recipient transplantation [including organ acquisition cost]+recipient 1-year posttransplant care)= 134.5 CU, (P =ns). CONCLUSIONS: The total comprehensive cost of LDLT is 21% higher than cadaveric transplantation, although this difference is not significant.

Hepaticoduodenostomy is an alternative to Roux-en-Y hepaticojejunostomy for biliary reconstruction in live donor liver transplantation.

INTRODUCTION: A Roux-en-Y hepaticojejunostomy (HJ) is usually performed during live donor liver transplantation (LDLT) when a duct-to-duct reconstruction is not possible. However, direct anastomosis of the bile duct to the duodenum (hepaticoduodenostomy [HD]) is an alternative technique for biliary repair that has been previously used for conventional biliary surgery and at our center for cadaveric liver transplant. We provide the first evidence that HD is an alternative technique for biliary reconstruction in LDLT. METHODS: We performed a total of 71 LDLT between 2002 and 2008. An end-to-end anastomosis was used in 30 patients. Forty-one patients had a biliary enteric anastomosis in which seven were reconstructed with an HD. Accessory ducts were fashioned into a common duct or implanted into the duodenum separately. RESULTS: There were no patient deaths or retransplants in a follow-up period that ranged from 90 to 771 days after surgery. One patient was diagnosed with cholangitis that responded to intravenous antibiotics and removal of the stent by endoscopy. CONCLUSIONS: This preliminary case series suggests that that HD is a feasible alternative to HJ biliary anastomosis when a duct-to-duct anastomosis cannot be performed. HD offers the possible advantage of simple postoperative access to the biliary system by endoscopy and avoids complications caused by HJ bowel anastomosis.

Clinically recurrent primary sclerosing cholangitis following liver transplantation: a time course.

Orthotopic liver transplantation (OLT) is the treatment of choice for patients with end-stage primary sclerosing cholangitis (PSC). This study sought to chronicle the natural history of PSC recurrence following OLT and identify clinical variables that may contribute to disease reemergence. From 1988 to 2006, 1102 OLTs were performed in 1032 adults at the University of Colorado Health Sciences Center. Of these, 130 patients (12.6%) with PSC received 146 allografts. Recurrence was defined by a clinically worsening examination and radiographic evidence. A total of 9 potential predictors were considered, using both bivariate log rank and multivariate Cox analysis, including: age > 55, gender, surgical technique (piggyback technique), presence of inflammatory bowel disease, intact colon before transplant, or cholangiocarcinoma (CCA), cold ischemia time, sirolimus-based immunosuppression, and graft type. The 1, 5, and 10-year recurrence-free survival was 91%, 76%, and 61%, respectively. The crude incidence of disease recurrence was 22 of 130 patients or 16.9%. Patients' risk of recurrent PSC at 1, 5, and 10 years was 2%, 12%, and 20%, respectively (mortality censored). Of the 22 patients that developed recurrent disease, 7 received a second transplant. Of the 9 factors considered, the presence of CCA prior to OLT is significantly predictive of disease recurrence [risk ratio (RR) = 3.77; P = 0.0038]. Once a patient was diagnosed with recurrent disease, the median survival without receiving a second transplant was 39.1 months (95% confidence interval: 27.6-50.6 months). In conclusion, recurrent PSC following OLT is a formidable but protracted problem following OLT. Patients may require a second transplant following reemergent disease with reasonable survival benefit.

Predictors of long-term outcome following liver transplantation for hepatocellular carcinoma: a single-center experience.

Orthotopic liver transplantation (OLT) is increasingly being applied for cure in patients with cirrhosis and concomitant hepatocellular carcinoma (HCC). In recipients with limited tumor burden, OLT achieves reasonable long-term outcome. This study sought to identify clinical and pathologic variables predictive of long-term disease-free survival and the presence of vascular invasion. From 1992 to 2006, 130 patients underwent OLT for cirrhosis and HCC. Malignancy was diagnosed in 107 patients prior to OLT and in 23 patients on pathologic examination of the explant. Nine clinical and pathologic variables were considered including: TNM stage, nodularity, vascular invasion, Milan criteria, incidental lesion, differentiation, tumor size, preOLT transarterial chemoembolization (TACE), and administration of sirolimus-based immunosuppression. The overall incidence of HCC recurrence was 17% with the majority (82%) being stage III. Cumulatively, tumor recurrence-free survival (RFS) is 84, 74, and 67% at 1, 3, and 5 years respectively. Independent predictors of RFS included stage III and poorly differentiated lesions (P<0.05). Furthermore, stage III tumors and those >3.5 cm in size were predictive of vascular invasion. Importantly, preOLT, TACE and postOLT sirolimus had no influence on survival. Pathologic variables including tumor stage and grade have a significant impact on outcome. Importantly, it seems that TACE and sirolimus had no beneficial effect.

Impact of pretransplant diagnosis of hepatocellular carcinoma on cadveric liver allocation in the era of MELD.

The allocation system based on the Model for End-stage Liver Disease (MELD) has led to more patients diagnosed with hepatocellular carcinoma (HCC) being transplanted. We hypothesized that more patients misdiagnosed with HCC are also being transplanted, leading to inappropriate organ allocation. Therefore, we retrospectively analyzed all liver transplants at our center from July 14, 2000, to October 22, 2002 (N = 172; 129 pre-MELD, 43 post-MELD), comparing pretransplant HCC diagnosis to explant histology. Thirty patients met the United Network for Organ Sharing (UNOS) diagnostic criteria for pretransplant HCC diagnosis. There were 25 men (median age, 52.5 yr), and 80% had hepatitis C. The proportion of patients transplanted who had an HCC diagnosis increased from 12% (15/129) pre-MELD to 35% (15/43) post-MELD implementation (P < 0.01). Three of 15 (20%) transplanted pre-MELD and 5 of 15 (33%) transplanted post-MELD lacked HCC in the explant (P = 0.10). Of the three false-positives pre-MELD, one was Status 2B already, and two received living-donor livers. Of the 5 false-positives post-MELD, three had score upgrades that led to early transplantation (13 to 29, 20 to 29, and 9 to 24) while two had MELD scores of 35 and 36 already. The percentage of organs that could have gone to patients with more advanced liver disease without HCC increased from 0% (0/129) pre-MELD to 7% (3/43) post-MELD (P < 0.01). Since the implementation of MELD, the proportion of patients transplanted who had an HCC diagnosis nearly tripled, and a small but significant proportion of organs are now going to patients misdiagnosed with HCC. More stringent HCC diagnostic criteria will be required to decrease the effect that misdiagnosis has on organ allocation.

Model for End-Stage Liver Disease score does not predict patient or graft survival in living donor liver transplant recipients.

Although living donor liver transplantation (LDLT) is a successful procedure for most recipients, outcomes in patients who undergo transplantation as United Network for Organ Sharing status 2A are marginal. There are no published data on living donor liver transplant recipient outcomes relative to Model for End-Stage Liver Disease (MELD) scores. Such information could be useful in living donor liver transplant recipient selection. We retrospectively analyzed all non-fulminant hepatic failure, right hepatic lobe, adult-to-adult living donor liver transplant recipients at our center between August 1997 and March 2002. We calculated MELD scores at the time of LDLT and correlated scores with 1-year patient and graft survival and hospital days during the 90-day post-LDLT period. There were 62 recipients with greater than 6 months of follow-up: 38 men, 24 women; mean age, 47.9 years; 42 white, 1 black, 17 Hispanic, and 2 Asian patients. Twenty-nine patients had hepatitis C virus infection; 4 patients, hepatitis C virus infection and alcoholic liver disease; 4 patients, alcoholic liver disease; 4 patients, cryptogenic cirrhosis; 13 patients, primary sclerosing cholangitis; 5 patients, autoimmune hepatitis; and 3 patients, primary biliary cirrhosis. Mean and median MELD scores were 15.2 and 13, respectively (range, 6 to 40). One-year patient and graft survival were 59 of 62 patients (95%) and 52 of 62 patients (84%), respectively. There was no statistically significant difference between median MELD scores of dead versus living patients (15 v 13; P =.15) or patients who underwent retransplantation versus those who did not (16.5 v 13; P =.30). Mean and median hospital days in the 90-day post-LDLT period were 23.7 and 16.0 days, respectively. Living donor liver transplant recipients with a MELD score of 18 or greater had significantly more hospital days compared with recipients with a MELD score less than 18 (35.2 v 19.8 days; P =.01). In conclusion, MELD scores did not predict post-LDLT patient or graft survival at 1 year. However, higher MELD scores (> or =18) were associated with more hospital days during the 3-month post-LDLT period.

Different immunosuppressive regimens and recurrence of primary sclerosing cholangitis after liver transplantation.

Primary sclerosing cholangitis (PSC) is the fourth leading diagnosis in liver transplant recipients in the United States. The disease is known to recur in 15% to 30% of liver transplant recipients. We set out to investigate how different immunosuppression regimens affected natural history of PSC after liver transplantation at our center. We reviewed records of all patients who underwent a liver transplantation at our institution in between 1988 and 2000 and had a diagnosis of PSC at the time of liver transplantation. Primary sclerosing cholangitis recurred in 15 of 71 patients (21.1%) who had complete records and survived more than 30 days after liver transplantation. Although recurrence of primary sclerosing cholangitis was most often seen (but not statistically significantly so) in patients who received maintenance corticosteroids, the time to recurrence was not significantly different between those who were treated with maintenance, those who were not successfully weaned, and those who successfully weaned off corticosteroids within 3 months after liver transplantation. Orthoclone (OKT3) therapy (Ortho-Biotech, Inc., Raritan, NJ) was associated with a higher risk of primary sclerosing cholangitis recurrence (29% versus 10%, P <.05). Recurrence was not influenced by immunosuppression with either cyclosporine or tacrolimus. Coexistent inflammatory bowel disease was a cause of failure to wean off corticosteroids, was associated with a shorter time to recurrence of sclerosing cholangitis, and was responsible for significant comorbidity (colon cancer in 7.3%). Primary sclerosing cholangitis recurrence is commonly seen after liver transplantation. More immunosuppression seems to be detrimental to the outcome of our patients with sclerosing cholangitis: use of OKT3 was associated with a greater incidence of recurrence. Length of corticosteroid use did not affect timing or risk of recurrence, and because it has been proven that early corticosteroid withdrawal after liver transplantation is beneficial, we continue to recommend this practice.

Sirolimus as primary immunosuppression in liver transplantation is not associated with hepatic artery or wound complications.

Sirolimus is a new immunosuppressive agent increasingly being used in liver transplant recipients. There is concern that sirolimus may be associated with wound complications and hepatic artery thrombosis (HAT). We have used sirolimus as primary immunosuppression in 170 liver transplant recipients and therefore reviewed our experience with wound complications and HAT in our cohort of patients. Records of all 170 patients administered sirolimus as primary immunosuppression and 180 historic controls were reviewed. Numbers of wound and hepatic artery complications were recorded, as well as the prevalence of obesity, reoperation, diabetes, and OKT3 use, all of which are risk factors for wound complications. The prevalence of wound complications was 12.4% in sirolimus-treated patients compared with 13.9% in historic controls (P = not significant [NS]). The prevalence of hepatic artery complications was 5.3% in sirolimus-treated patients compared with 8.3% in historic controls (P = NS). The prevalence of obesity and OKT3 administration was significantly lower in sirolimus-treated patients. Multivariate analysis failed to show an association between sirolimus therapy and hepatic artery or wound complications. The prevalence of wound and hepatic artery complications is not different in liver transplant recipients administered sirolimus as part of a primary immunosuppressive regimen compared with historic controls.