Fatigue after liver transplantation: effects of a rehabilitation program including exercise training and physical activity counseling.

BACKGROUND: It is hypothesized that increasing physical fitness and daily physical activity can lead to a reduction in fatigue. However, standard medical care following liver transplantation seldom includes rehabilitation that focuses on physical fitness and physical activity. OBJECTIVE: The aim of this study was to explore whether a rehabilitation program can reduce fatigue in recipients of liver transplants. Furthermore, effects on physical fitness, physical activity, and cardiovascular risk were studied, and adherence, satisfaction, and adverse events were assessed. DESIGN: This was an uncontrolled intervention study. SETTING: The study took place in an outpatient rehabilitation clinic. PATIENTS: Eighteen recipients of a liver transplant who were fatigued participated in a 12-week rehabilitation program including physical exercise training and counseling on physical activity. The primary outcome measure was fatigue. Other outcome measures were: aerobic capacity, muscle strength, body fat, daily physical activity, lipid profile, and glycemic control. All measurements were performed before and after the rehabilitation program. Adherence, satisfaction, and adverse events were registered. RESULTS: After the program, participants were significantly less fatigued, and the percentage of individuals with severe fatigue was 22% to 53% lower than before the program. In addition, aerobic capacity and knee flexion strength were significantly higher, and body fat was significantly lower after the program. Participants were able to perform physical exercise at the target training intensity, no adverse events were registered, and attendance (93%) and mean patient satisfaction (8.5 out of 10, range=7-10) were high. LIMITATIONS: No control group was used in the study. CONCLUSIONS: A rehabilitation program consisting of exercise training and physical activity counseling is well tolerated and seems promising in reducing fatigue and improving fitness among recipients of liver transplants.

Location of lymph node involvement in patients with esophageal adenocarcinoma predicts survival.

BACKGROUND: The location of positive lymph nodes has been abandoned in the seventh classification of the TNM staging system for esophageal adenocarcinoma. The present study evaluates whether distribution of involved nodes relative to the diaphragm in addition to TNM 7 further refines prediction. METHODS: Pathology reports of patients who underwent esophagectomy between 2000 and 2008 for adenocarcinoma of the esophagus were reviewed and staging was performed according to the seventh UICC-AJCC staging system. In addition, lymph node involvement of nodal stations above and below the diaphragm was investigated by endoscopic ultrasonography (EUS) in a separate cohort of patients who were scheduled for esophagectomy between 2008 and 2009 at two institutions. Survival was calculated by the Kaplan-Meier method, and multivariate analysis was performed with a Cox regression model. RESULTS: Some 327 patients who had undergone esophagectomy for cancer were included. Multivariate analysis revealed that patients with from three to six involved lymph nodes in the resection specimen on both sides of the diaphragm had a twofold higher chance of dying compared to patients with the same number of involved lymph nodes on one side of the diaphragm. EUS assessment of lymph node metastases relative to the diaphragm in 102 patients showed that nodal involvement on both sides of the diaphragm was associated with worse survival than when nodes on one side or no nodes are involved [HR (95 % CI) 2.38 (1.15-4.90)]. CONCLUSIONS: A combined staging system that incorporates distribution of lymph nodes relative to the diaphragm refines prognostication after esophagectomy as assessed in the resected specimen and pretreatment as assessed by EUS. This improved staging has the potential to have a great impact on clinical decision making as to whether to embark upon potentially curative or palliative treatments.

Persistent fatigue in liver transplant recipients: a two-year follow-up study.

BACKGROUND: Fatigue after liver transplantation (LTx) is a major problem that is associated with lower daily functioning and health-related quality of life (HRQoL). This study aimed to assess changes over time in fatigue following LTx. We also examined daily functioning and HRQoL changes over time and assessed the influence of fatigue and changes in fatigue on daily functioning and HRQoL. We determined whether sleep quality, anxiety, and depression were associated with fatigue. METHODS: We identified 70 LTx recipients who had previously participated in a cross-sectional study and reassessed them after two yr to determine changes in level of fatigue, daily functioning, and HRQoL. We also assessed sleep quality, anxiety, and depression after two yr. RESULTS: Level of fatigue and level of daily functioning were unchanged at follow-up. HRQoL domains remained stable or worsened. Fatigue was a significant predictor of daily functioning and all HRQoL domains (p < 0.01). Change in fatigue was a significant predictor of daily functioning and the HRQoL domains of "physical functioning,""vitality," and "pain" (p < 0.05). Sleep quality, anxiety, and depression were associated with fatigue severity (r = 0.35 to r = 0.60, p < 0.05). CONCLUSION: This longitudinal study shows that fatigue is a chronic problem after LTx and that daily functioning and HRQoL do not improve over time. This study supports the need for intervention programs to address fatigue after LTx.

Noninvasive functional liver blood flow measurement: comparison between bolus dose and steady-state clearance of sorbitol in a small-rodent model.

Plasma clearance of D-sorbitol, a nontoxic polyol, occurs predominantly in the liver and has been used to measure functional liver blood flow after bolus and steady- state intravenous administration. However, it is not known which of these two administration methods is superior. Therefore, plasma D-sorbitol clearance was studied in an animal model both after a bolus dose and under steady-state (SS) conditions and compared directly with liver blood flow, under normal conditions, and after the induction of endotoxin (LPS) sepsis. Adult male Wistar rats (526 +/- 38 g body wt; n = 27) were anesthetized and mechanically ventilated. Hemodynamics, hepatic arterial flow, and portal venous flow were measured. Two groups were studied, namely healthy animals that served as controls and a sepsis group that received 5 mg/kg LPS intravenously (Escherichia coli O127:B8). Each animal received either a SS infusion (0.1 mg/100 g body wt per min) or a bolus (3 mg/100 g body wt) of a 5% D-sorbitol solution intravenously in a randomized order. After the initial measurements and a 60-min pause time in between (T(1/2,sorbitol) = 9 min), a crossover was done. The hepatic clearance of D-sorbitol in the control group showed a good correlation between bolus and SS (Spearman's r = 0.7681, P = 0.0004), and both techniques correlated well with total liver blood flow (TLBF) (r = 0.7239, P = 0.0023 and r = 0.7226, P = 0.0023, respectively). Also in the sepsis group there was a good correlation between bolus and SS sorbitol clearance (r = 0.6655, P = 0.0182). In the sepsis group, only the SS clearance correlated with TLBF (r = 0.6434, P = 0.024). In conclusion, in normal and under septic conditions, hepatic clearance of D-sorbitol either by bolus or a SS infusion is comparable. In healthy animals, this also correlated well with TLBF but not in septic conditions. However, this is expected because of the changes in the liver microcirculation, shunting, and decreased hepatocyte function in sepsis.

Functional analysis of CD4+ CD25bright T cells in kidney transplant patients: improving suppression of donor-directed responses after transplantation.

BACKGROUND: The role of CD4(+) CD25(bright) regulatory T cells (Treg) in controlling alloreactivity is established, but little is known whether antigen-specific Treg are induced in fully immunosuppressed kidney transplant patients. METHODS: The frequency and function of CD25(bright) T cells of nine stable kidney transplant patients before and 0.5-2 yr after transplantation were measured. Patients received triple therapy consisting of cyclosporine, mycophenolate mofetil and prednisone. To investigate the influence of transplantation and immunosuppression on Treg function, we compared their suppressive capacities pre- and post-transplantation using mixed lymphocyte reactions and kept the CD25(-/dim) effector T-cell (Teff) population constant. RESULTS: After transplantation, the percentage of CD4(+) CD25(bright) T cells significantly decreased from 8.5% pre-transplant to 6.9% post-transplant (median, p = 0.05). However, the lower percentage of post-transplant CD4(+) CD25(bright) T cells was not associated with reduced, but rather improved suppressor function of these cells. The proliferative response of pre-transplant Teff to donor-antigens was more profoundly suppressed by post-transplant Treg than by pre-transplant Treg (pre-transplant 18% vs. post-transplant 55% median, p = 0.03) and was comparable against third party antigens at a CD25(bright):CD25(-/dim) ratio of 1:20. CONCLUSIONS: In immunosuppressed kidney transplant patients, the donor-directed suppressive capacity of CD4(+) CD25(bright) regulatory T cells improved, which may contribute to the development of donor-specific hyporesponsiveness against the graft.

High-volume versus low-volume for esophageal resections for cancer: the essential role of case-mix adjustments based on clinical data.

BACKGROUND: Most studies addressing the volume-outcome relationship in complex surgical procedures use hospital mortality as the sole outcome measure and are rarely based on detailed clinical data. The lack of reliable information about comorbidities and tumor stages makes the conclusions of these studies debatable. The purpose of this study was to compare outcomes for esophageal resections for cancer in low- versus high-volume hospitals, using an extensive set of variables concerning case-mix and outcome measures, including long-term survival. METHODS: Clinical data, from 903 esophageal resections performed between January 1990 and December 1999, were retrieved from the original patients' files. Three hundred and forty-two patients were operated on in 11 low-volume hospitals (<7 resections/year) and 561 in a single high-volume center. RESULTS: Mortality and morbidity rates were significantly lower in the high-volume center, which had an in-hospital mortality of 5 vs 13% (P < .001). On multivariate analysis, hospital volume, but also the presence of comorbidity proved to be strong prognostic factors predicting in-hospital mortality (ORs 3.05 and 2.34). For stage I and II disease, there was a significantly better 5-year survival in the high-volume center. (P = .04). CONCLUSIONS: Hospital volume and comorbidity patterns are important determinants of outcome in esophageal cancer surgery. Strong clinical endpoints such as in-hospital mortality and survival can be used as performance indicators, only if they are joined by reliable case-mix information.

Use of large-diameter metallic stents to seal traumatic nonmalignant perforations of the esophagus.

BACKGROUND: Surgery for traumatic, non-malignant perforation of the esophagus in patients presenting more than 24 hours after its occurrence carries a high morbidity and mortality. Covered metallic stents have been used to effectively seal perforations in individual patients with Boerhaave's syndrome. METHODS: Eleven consecutive patients presented with esophageal perforation that was caused by Boerhaave's syndrome (n = 5), resection of an epiphrenic diverticulum (n = 2), rigid esophagoscopy (n = 2), extended gastric resection (n = 1), or pneumatic dilation for achalasia (n = 1). A large diameter Flamingo Wallstent (proximal/distal diameters, 30/20 mm) (7 patients) or a large diameter Ultraflex stent (proximal/distal diameters, 28/23 mm) (4 patients) was placed. Pleural cavities were drained with thoracostomy drains, and antibiotics were administered. RESULTS: The median time from perforation to stent insertion was 60 hours (range, 24 hours to 28 days). The perforation was totally sealed in 10 of 11 patients. Two patients underwent esophageal resection because of incomplete sealing of the perforation or incomplete drainage of the pleural cavity and mediastinum. The other 9 patients recovered uneventfully and resumed a normal diet within 7 to 18 days. In 7 patients, the stents were retrieved endoscopically after a median of 7 weeks (range, 6 to 14 weeks), whereas two patients refused to have the stent retrieved (in one, the stent migrated into the stomach; the other patient died 6 months after stent placement from an unrelated cause). CONCLUSIONS: Traumatic perforation of the esophagus can be treated successfully with large diameter metallic stents, together with adequate drainage of the thoracic cavity.