Cost-effectiveness of intestinal transplantation for adult patients with intestinal failure: a simulation study.

BACKGROUND: Home parenteral nutrition (HPN) and intestinal transplantation (ITx) are the 2 treatment options for irreversible intestinal failure (IF). OBJECTIVE: This study simulated the disease course of irreversible IF and both of these treatments--HPN and ITx--to estimate the cost-effectiveness of ITx. DESIGN: We simulated IF treatment in adults as a discrete event model with variables derived from the Dutch Registry of Intestinal Failure and Intestinal Transplantation, the Intestinal Transplant Registry, hospital records, the literature, and expert opinions. Simulated patients were enrolled at a rate of 40/mo for 10 y. The maximum follow-up was 40 y. Survival was simulated as a probabilistic function. ITx was offered to 10% of patients with <12 mo of remaining life expectancy with HPN if they did not undergo ITx. Costs were calculated according to Dutch guidelines, with discounting. We evaluated the cost-effectiveness of ITx by comparing models conducted with and without ITx and by calculating the cost difference per life-year gained [incremental cost-effectiveness ratio (ICER)]. RESULTS: The average survival was 14.6 y without ITx and 14.9 y with ITx. HPN costs were €13,276 for treatment introduction, followed by €77,652 annually. The costs of ITx were ∼€73,000 during the first year and then €13,000 annually. The ICER was €19,529 per life-year gained. CONCLUSION: Our simulations show that ITx slightly improves survival of patients with IF in comparison with HPN at an additional cost of €19,529 per life-year gained.

Histopathologic and molecular evaluation of the Organ Procurement and Transplantation Network selection criteria for intestinal graft donation.

BACKGROUND: The Organ Procurement and Transplantation Network (OPTN) has formulated criteria for the selection of donors for intestinal transplantation. To date, however, no study has correlated histologic findings of intestinal injury with the OPTN criteria. We aimed to describe histopathologic and molecular features of allograft injury in relation to donor conditions defined by the OPTN criteria. MATERIALS AND METHODS: Graft histology (Park Score), Claudin-3 staining, systemic inflammatory markers (C-reactive protein/lipopolysaccharide-binding protein) and expression of heat shock protein 70, heme oxygenase 1, and interleukin 6 were evaluated in multiorgan deceased donors (donation after brain death [DBD] and donation after cardiac death [DCD]). RESULTS: Ninety-seven samples (52 jejunum/45 ileum) were recovered from 59 donors (46 DBD/13 DCD). The OPTN criterion cold ischemia time correlated with histologic injury (Park score) to which the jejunum appeared more susceptible than the ileum. Claudin-3 staining was higher, and heat shock protein 70 expression lower in donors meeting the OPTN criteria compared with donors not meeting the criteria and in DBD versus DCD. In DBD donors, interleukin 6 expression was higher compared with DCD donors and inversely related to C-reactive protein. CONCLUSIONS: Our multiparameter analysis suggests that the OPTN criteria can be discriminative concerning intestinal graft quality. Our data suggest that DCD intestinal allografts are qualitatively inferior and that the jejunum is more sensitive to ischemia than the ileum.

Small bowel preservation for intestinal transplantation: a review.

Intestinal transplantation has become the therapy of choice for patients with intestinal failure and life-threatening complications from total parenteral nutrition. Results, however, remain inferior as compared with other transplant types with the quality of the organ graft as the most important factor of outcome after transplantation. The intestine is extremely sensitive to ischemia. Unfortunately, a relatively long ischemic preservation period is inevitable. The current standard in organ preservation [cold storage (CS) with University of Wisconsin solution] was developed for kidney/liver preservation and is suboptimal for the intestinal graft despite good results for other organs. This review aimed at appraising the results from the use of previously applied and recently developed preservation solutions and techniques to identify key areas for improvement. As the studies available do not reveal the most effective method for intestinal preservation, an optimal strategy will result from a synergistic effect of different vital elements identified from a review of published material from the literature. A key factor is the composition of the solution using a low-viscosity solution to facilitate washout of blood, including amino acids to improve viability, impermeants and colloids to prevent edema, and buffer for pH-homeostasis. Optimizing conditions include a vascular flush before CS and luminal preservation. The most effective composition of the luminal solution and a practical, clinically applicable optimal technique are yet to reach finality. Short-duration oxygenated arterial and/or luminal perfusion have to be considered. Thus, a tailor-made approach to luminal preservation solution and technique need further investigation in transplant models and the human setting to develop the ultimate technique meeting the physiologic demands of the intestinal graft during preservation.

Reduced ischemia-reoxygenation injury in rat intestine after luminal preservation with a tailored solution.

BACKGROUND: The intestine is extremely sensitive to ischemic preservation and reoxygenation injury. Current vascular perfusion and cold storage with University of Wisconsin (UW) solution neglect the intestinal lumen and the ongoing mucosal metabolism during hypothermia. This study was designed to test the effects of luminal preservation with an alternative preservation solution in addition to the common vascular flush with UW solution on graft viability after preservation and ex vivo reoxygenation. METHODS: Rat intestine was preserved on ice for 6 hr in UW solution or Williams Medium E with additional buffering, impermeants, and a colloid (WMEplus) after being stapled or after flushing and filling the lumen with the respective preservation solution. Tissue slices were prepared from fresh and preserved intestines and were incubated with oxygen for 6 hr at 37°C to assess the viability after reoxygenation. RESULTS: Directly after preservation, histologic damage was mild and unaffected by preservation strategy. Contrary to luminal preservation, closed preservation resulted in significantly decreased ATP levels compared with control. Reoxygenation aggravated damage and revealed differences between the strategies. Luminal preservation better maintained the ATP levels and histologic integrity (vs. closed preservation) for both solutions. Histomorphologic integrity was superior after preservation with WMEplus (vs. UW solution). Expression of stress responsive genes was least up-regulated in the slices from tissue preserved luminally with WMEplus. CONCLUSIONS: In conclusion, preservation and reoxygenation injury can be attenuated by luminal preservation with WMEplus.

Intestinal transplantation (ITx): "who, when and how?" a general overview

O transplante de órgãos se tornou parte importante da medicina moderna. O transplante de intestino (ITx) foi introduzido no final da década de 1960 como um procedimento heróico para tratar falência do intestino. O Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foi um dos pioneiros mundiais neste procedimento. Com a evolução biotecnológica na medicina, o transplante de intestino emergiu na década de 1990 como a única e permanente opção terapêutica para pacientes com falência intestinal irreversível. Àquele tempo, os resultados clínicos eram, ainda, desapontadores, principalmente devido às altas taxas de infecção pós-operatória e rejeição do enxerto. Entretanto, houve um grande desenvolvimento do transplante intestinal e multivisceral graças à melhoria da terapia imunossupressora, ao refinamento das técnicas cirúrgicas e dos cuidados pós-transplantes. O objetivo deste estudo é oferecer um panorama sobre quando o ITx deve ser indicado e sobre como o procedimento deve ser realizado...

Organ transplantation has become a substantial part of modern medicine. Intestinal transplantation (ITx) was introduced in the late sixties as a heroic procedure to treat intestinal failure. The Clinic Hospital of University of São Paulo Medical School is one of the world’s pioneer in this procedure. With the biotechnological evolution in medicine, intestinal transplantation emerged in the 1990s as the only curative, permanent therapeutic option for patients with irreversible intestinal failure. At that time, the clinical results were also disappointing mainly due to the high rates of post-operative infectious complications and graft rejection. However, the development of intestinal and multivisceral transplantation has been profound owing to the progress in immunosuppressive therapy, refinement of surgical techniques and post-transplant care. This study aims to give a general overview about when the ITx must be considered an option of treatment and how it must be done...

Esophageal atresia without distal tracheoesophageal fistula: high incidence of proximal fistula.

BACKGROUND: This retrospective study was performed to test our suspicion that the incidence of esophageal atresia with proximal fistula in our institution is much higher than is generally reported. METHODS: The charts of all patients with esophageal atresia and/or tracheoesophageal fistula admitted in the period 1982 to 2000 were analyzed. The type of atresia and/or tracheoesophageal fistula was noted, and the relative incidence was calculated and compared with the relative incidence in a cumulative series of 3492 patients taken from 9 published studies. RESULTS: In the period under study, 123 patients with esophageal atresia and/or tracheoesophageal fistula were identified. The relative incidence of esophageal atresia without distal fistula was statistically not different (10.6% in the present series against 8.49% in the reference group). A statistically significant difference in the relative incidence of esophageal atresia with proximal fistula, however, was found: 5.69% in the present series against 1.05% in the reference group (P < .0001). Looking at the subgroup of patients without a distal fistula, more than half of the patients did have a proximal fistula. CONCLUSIONS: The relative incidence of esophageal atresia with proximal fistula in this series of children with esophageal atresia and/or tracheoesophageal fistula is significantly higher than reported in the literature. This is on the account of the subgroup of patients without a distal fistula in which the incidence of a proximal fistula is more than 50%. Especially in this subgroup, the existence of a proximal fistula should be ruled out preoperatively.