We investigated the relationship between preoperative comorbidity and postoperative survival after intestinal transplantation. Each patient received a score for preoperative comorbidity. Each comorbidity was given a score based on the degree it impaired function (score range 0–3). A total score was derived from the summation of individual comorbidity scores. Patients (72 adults (M : F, 33 : 39)) received an isolated intestinal graft (27) or a cluster graft (45). Mean (standard deviation) survival was 1501 (1444) days. The Kaplan-Meier analysis revealed a significant inverse association between survival and comorbidity score (logrank test for trend,
Over the last decade, intestinal transplantation has become an established treatment modality in the management of intestinal failure. The preoperative status of patients has been found to influence the outcome of surgery [
Preoperative comorbidity was transformed into a numerical score to allow service analysis to take place. This work was conducted according to the requirements of the institution. The score was compared to subsequent survival. Comorbidity factors included were loss of venous access and impairment of organs or systems not corrected by transplantation. Each factor was scored 0–3. A score of 3 indicated a functional abnormality not fully corrected by treatment of a severity approaching a contraindication for transplantation. A score of 1 describes a characteristic which does not present an immediate risk but which may develop into a risk factor in the future. A score of 2 indicates an abnormality of function which is corrected by ongoing treatment and conveys moderate risk (Table
Pretransplant risk assessment score for intestinal and multivisceral transplantation in adults. The score was assigned to the severity of each comorbidity resulting in a cumulative comorbidity score.
Score | Degree of comorbidity |
---|---|
0 | Normal |
| |
1 | Comorbidity with no significant functional impairment requiring treatment: (mild hypertension, slight glucose intolerance—diet controlled, mild exercise-induced asthma, renal impairment—slightly impaired GFR reduced by 10% only, smoker without respiratory dysfunction, and past history of depressive illness) |
| |
2 | Comorbidity requiring treatment to prevent functional impairment—deemed to present a slightly increased surgical risk: (treated hypertension, mild coronary artery disease without symptoms, DM-oral hypoglycemics, mild asthma—stable on intermittent therapy, renal impairment—moderately reduced GFR 10–25%, smoker with mild respiratory dysfunction but no symptomatic limitation, treated and resolved depression). |
| |
3 | Comorbidity that despite treatment causes functional impairment and presents a moderate risk to surgery: (poorly controlled hypertension, angina controlled by Tx—minor vessel disease, DM—insulin dependent, renal impairment—moderately reduced GFR 25–50%, treated but unresolved depression, COPD with mild symptoms requiring occasional treatment during exacerbations) |
Venous access: after loss of two major venous access points each additional loss scores one point.
Following the loss of 2 large venous access sites suitable for parenteral nutrition and high flow infusions (i.e., internal jugular, subclavian, and femoral vein), each subsequent loss was given a score of 1.
Patients were selected for transplantation according to the conventional indications as previously published [
The data were collected prospectively during routine preoperative evaluation at the transplant centres at the University of Cambridge, United Kingdom, and University of Miami, United States of America, from 1997 to 2003. The analysis was undertaken retrospectively. Patient data were consecutively entered into a database as a routine at each institution from which data were acquired for the analysis. Where comorbidity data were incomplete, patients were excluded from the analysis; this was undertaken without knowledge of their subsequent survival.
The primary outcome measured was median recipient survival with 95% confidence interval (CI) and was calculated by Kaplan-Meier (KM) approach with comparison using logrank test. The accuracy of the comorbidity score to predict postoperative survival was tested by using Harrell’s C statistic which estimates the proportion of accurate predictions. A Harrell’s C index varies from 0.5 to 1 reflecting no discrimination to perfect discrimination, respectively.
Student’s
The donor and patient demographics are detailed in (Tables
Donor demographics.
Variables | Results |
---|---|
Mean age (yrs ± SD) | 21.18 ± 11.27 |
Mean weight (kgs ± SD) | 57.37 ± 18.61 |
CMV mismatch (%) | 21.16% |
Cold ischemic time (min) | 434 ± 117.1 |
Recipient demographics.
Variables | Results |
---|---|
Mean age (yrs ± SD) | 35.76 ± 10.63 |
Sex (M : F) | 1 : 1.49 |
Race (%) | |
Caucasian | 75.06% |
Afro-Caribbean | 14.42% |
Hispanic | 10.52% |
Mean weight (kgs ± SD) | 51.95 ± 13.92 |
Mean time on the waiting list (days ± SD) | 68.95 ± 18.47 |
Pre-op place (hospital : home) | 1 : 1.35 |
Pre-Tx albumin (g/dL ± SD) | 3.268 ± 0.688 |
Thrombosed veins (mean ± SD) | 1.495 ± 1.291 |
HLA mismatch (mean ± SD) | 1.035 ± 1.076 |
Indication for transplant (%) | |
Short gut | 33.33% |
Motility disorders | 16.67% |
Neoplasms | 18.05% |
Mucosal defects | 13.51% |
Others | 18.33% |
Types of transplant (%) | |
Multivisceral (MVT) | 38.37% |
Modified MVT | 24.65% |
Intestine alone | 36.98% |
Warm ischemic time (minutes ± SD) | 39.35 ± 12.07 |
Patients received either an isolated intestinal graft (
The cause of intestinal failure in recipients was most commonly short gut syndrome (33%), and the most frequent procedure in this cohort was multivisceral transplantation (intestine, liver, and additional organs) in 38%, followed by isolated intestine (37%), and modified multivisceral (intestine and other organs excluding liver) 25% (Table
Most patients received Alemtuzumab (Campath 1H) induction immunosuppression, and the mean (SD) number of rejection episodes per patient was
Peri- and postoperative data.
Variables | Results |
---|---|
Induction agents (%) | |
Corticosteroids | 13.90% |
Daclizumab (Zenapax) | 16.66% |
Alemtuzumab (Campath) | 69.44% |
Number of rejection episodes (mean ± SD) | 1.22 ± 1.34 |
Severity of rejection episodes per patient |
|
Mild | 1.419 ± 0.662 |
Moderate | 0.391 ± 0.718 |
Severe | 0.318 ± 0.547 |
Rejection-free period (days) (mean ± SD) | 357.63 ± 21.54 |
Posttransplant hospital stay (days) (mean ± SD) | 60.69 ± 45.57 |
Individual patient comorbidity scores and their postoperative survivals were found to correlate inversely (
Km survival curves were plotted for patients grouped according to comorbidity score (dashed line: comorbidity 0 + 1; continuous line: comorbidity 2 + 3; dotted line: comorbidity 4 + 5; and dashed/dotted line: comorbidity >6). Logrank test for trend indicated a significant increase in rate of death with comorbidity score, and compared with comorbidity 0 + 1, the hazard ratios for death were found to increase with comorbidity score, 1.94 (0.76–5.82), 5.07 (3.31–36.17), and 13.77 (46.3–120100), respectively; the difference became significantly greater than group 0 + 1 at group 4 + 5 (
The survival of patients receiving isolated intestinal grafts was compared to those who underwent multivisceral transplantation. Kaplan-Meier analysis revealed no difference in survival between patients receiving isolated and multivisceral transplantation: logrank (Mantel-Cox) test:
The accuracy of the score to predict postoperative survival was evaluated using the receiver-operator characteristic analysis. A receiver-operator curve (ROC curve) was constructed for survival prediction at 1, 3, 5, and 10 years. The Harrell’s C statistic was calculated for each curve and represents the overall accuracy when assessed in terms of specificity and sensitivity at all possible points. The C statistic indicated very good or excellent accuracy of the comorbidity score at all times frames (Figure
Receiver-operator curve (ROC) analysis for predicting death at postoperative time intervals. | ||||||
---|---|---|---|---|---|---|
Time point assessed | Area under ROC curve |
Standard error | 95% confidence interval | Significance |
Number of control subjects | Number of patients |
1 yr | 0.88 | 0.049 | 0.788–0.981 | <0.0001 | 34 | 20 |
3 yrs | 0.85 | 0.054 | 0.742–0.954 | <0.0001 | 28 | 28 |
5 yrs | 0.88 | 0.057 | 0.7761–0.9905 | <0.0001 | 13 | 29 |
10 yrs | 0.92 | 0.040 | 0.8454–1.003 | <0.0001 | 10` | 33 |
Receiver-operator curves were calculated to assess accuracy of survival prediction at 1, 3, 5, and 10 years postoperative (continuous line, dashed line, dashed/dotted line, and dotted line, resp.). The accuracy of the comorbidity score is indicated by the area under the curve (Harrell’s “C” statistic) and was very good or excellent for predictions at each time frame with associated “C” statistics of 0.88, 0.85, 0.88, and 0.92, respectively.
We recognise that the interpretation of these data should be undertaken in the context that there will be differences in the protocols of transplant centres which might have an influence on the relative importance of comorbidity on survival. For instance, the majority of patients in our cohort received Alemtuzumab as induction therapy which may have made the impact of comorbidity more significant. There will also be additional influences on survival, particularly in the long term, that are not included in this analysis. Nevertheless, in this cohort of patients, our results indicate that the degree of preoperative comorbidity appears to predict posttransplant survival following small intestinal and multivisceral transplantation in adults. The predictive value of the comorbidity score might allow better patient selection, focus on pretransplant optimization, and facilitate informed consent for the procedure. Patients who have a low comorbidity score might be considered for earlier transplantation or even preemptive transplantation, where transplantation is offered at the time of developing intestinal failure. This would be particularly appropriate for those with high risk circumstances, where they are likely to have a reduced life expectancy on PN [
As postoperative survival improves poor quality of life, it is likely to become a more frequent indication for transplantation. Under these circumstances, it will be crucial to predict postoperative survival for individual patients to better evaluate the risk/benefit ratio of transplantation and facilitate informed consent, and the comorbidity score might also be of considerable use for this purpose. As the role of other factors, such as the presence of HLA antibodies, becomes clearer, this scoring system may be improved by their inclusion [
In conclusion, the numeric score (comorbidity score) developed to allow us to semiquantify preoperative comorbidity appears to be an accurate and convenient method of assessing risk using preoperative risk factors. A future multicentre international prospective study to evaluate this survival risk factor is important to confirm our initial observation and may lead to a useful clinical tool in the selection and timing of patients for transplantation.
Standard deviation
Confidence interval
Parenteral nutrition
Diabetes mellitus
Chronic obstructive pulmonary disease
Kaplan-Meier
Male
Female
Spearman’s correlation coefficient
Receiver-operator characteristic
Quality of life
Years
Grams
Decilitre
Multivisceral.
The authors of this paper have no conflict of interests.
S. J. Middleton, R. Sivaprakasam, C. Pither, S. M. Gabe, M. Dawwas, N. V. Jamieson, and A. J. Butler took part in the design and analysis of the study and preparation of the paper. A. G. Tzakis, S. J. Middleton, E. R. Island, T. Hidenori, and S. Nishida took part in the methods and data collection.