G. Gondolesi

Desarrollo de un modelo experimental de ligadura portal asociada a transección parenquimatosa (ALPPS) en ratas

BACKGROUND Liver failure might be a cause of death after major hepatectomies. The ALPPS technique appears to be a promising strategy to avoid it, however no experimental studies supporting this procedure have been previously described. The aim was to develop an experimental model of ALPPS in rats. METHOD Experimental. A total of 30 Sprague Dawley rats were used. To develop the ALPPS procedure, ligation of the left portal branch of the middle lobe (LM) was performed. This demarcates the left side (SILM) from the right side (SDLM); parenchyma transection was performed following the demarcated line. The animals weight, volume and weight of both LM were analyzed. Sacrifice at 3, 7 and 14 days after the procedure (10 per group) was performed. RESULTS No bleeding or ascites were observed during the postoperative period. The LM increased by 24.1, 86.9 and 120.4% at 3, 7 and 14 days. The SDLM increased by 34.4, 78.8 and 102.0% at 3, 7 and 14 days. The SILM decreased 42.6, 64.8, and 79.3% at day 3, 7 and 14 days respectively. CONCLUSION The ALPPS procedure can be performed in rats, achieving the expected results. Comparison studies to 2 staged hepatectomy will be necessary.

What Is the Normal Small Bowel Length in Humans? First Donor-Based Cohort Analysis

Normal small bowel length (SBL) has been reported within a wide range, but never studied in a cohort of either pediatric or adult deceased donors. Between 5/2006 and 2/2011, SBL was measured in all grafts procured for intestinal transplantation at a single center and used for either isolated intestinal transplant (15) or multiorgan transplants (5) employing a standardized method. SBL was the only not significantly different variable among pediatric and adult donors divided by age 16. Furthermore, donors were classified in 3 groups: group 1: Height < 70 cm, group 2: 71–150 cm and group 3: ≥ 151 cm. Mean age was: 0.58, 5.6, 22.01 years, respectively. Mean height and weight were 65.8, 123.2, 166.1 cm (p = 0.001) and 6.9, 23.8, 65.2 kg (p = 0.001), for each group. The SBL by group was: 283.0, 324.7, 356.0 cm, remaining as the only nonsignificant variable (p = 0.06), in contrast to BMI, BSA (p = 0.001). The SBL/height ratio: 4.24, 2.7, 2.12 (p = 0.001; rho: –0.623) or SBL/BSA ratio was 8.36, 3.7, and 2.03, respectively (p : 0.0001; rho: –0.9). SBL does not increase with growth like other anthropometric variables. The SBL/height ratio significantly decreases with growth; however, bowel diameter increases, which needs further evaluation.

Defining the Nonreturn Time for Intestinal Ischemia Reperfusion Injury in Mice

Among the abdominal organs, the intestine is probably the most sensitive to ischemia reperfusion injury (IRI), a phenomenon that occurs in many intestinal disorders. Few studies have reported in detail the impact of intestinal ischemia time in mice. We evaluated the effect of various warm intestinal ischemia times in an intestinal IRI model in mice. Adult male Balb/c mice were divided into 4 groups that differed in intestinal ischemia time: G1, 30; minutes; G2, 35 minutes; G3, 40 minutes; and G4, 45 minutes. Histological evaluation showed average Park scores as follows: G1 0.6 ± 0.55; G2 1.8 ± 0.45; G3 4.8 ± 2.25; and G4 5 ± 1.79. All animals from G1 survived 30 hours. G2 animals showed intermediate behavior with all succumbing between 18 and 30 hours postprocedure. G3 and G4 displayed similar survival results with animals succumbing before 6 hours after intestinal reperfusion. These data showed that Park index scores of 3 or higher were related to early death. We concluded that the 5 minutes between 35 and 40 minutes is the critical limit, after which all mice die after reperfusion. This result may represent a valuable tool for future research in mice.

Current Status of Allograft Tolerance in Intestinal Transplantation

Solid organ transplantation has become a clinical practice after the development of different immunosuppressive drugs that allowed controlling rejection. The price to be paid for that is the permanent risk of infections and malignancies and a significant drug-associated toxicity. The establishment of transplant tolerance has been the “holy grail” for transplantation medicine since its beginnings. Different experimental approaches and clinical trials resulted in the accumulation of knowledge on mechanisms and strategies that favor the establishment of tolerance without achieving the objective of autonomous allograft tolerance in the clinical field. Development of tolerance in intestinal transplantation constitutes a challenging situation due to several particular features that contribute to the generation of a strong allogeneic response. In the present review, we summarize the different immune mechanisms that may contribute to allograft tolerance. The different barriers that should be bypassed in intestinal transplantation to tolerate the graft are discussed. Finally, we revise the strategies that were applied with different degrees of success in the clinical field including the most promising recent approaches and the forthcoming candidates in the field that might be translated into clinical trials in the near future.

Neo-Suprahepatic Cava: A Case Report of a Modified Technique for Domino Liver Transplantation

Domino liver transplantation, introduced in 1997, originally consisted of a graft from a patient with familial amyloidotic polyneuropathy used as a donor for a compatible recipient, thus increasing the pool of hepatic grafts for liver transplantation. The aim of this report was to present a modification on the technique for outflow reconstruction in domino liver transplantation first proposed by Liu et al and Cescon et al. In this description we proposed a new technique that differs from the one mentioned above by performing a neo-suprahepatic cava, constructed using only an iliac vein graft, facilitating the anastomosis as if it was a regular cadaveric liver transplant.

Analysis of immune cells draining from the abdominal cavity as a novel tool to study intestinal transplant immunobiology

During intestinal transplant (ITx) operation, intestinal lymphatics are not reconstituted. Consequently, trafficking immune cells drain freely into the abdominal cavity. Our aim was to evaluate whether leucocytes migrating from a transplanted intestine could be recovered from the abdominal draining fluid collected by a peritoneal drainage system in the early post‐ITx period, and to determine potential applications of the assessment of draining cellular populations. The cell composition of the abdominal draining fluid was analysed during the first 11 post‐ITx days. Using flow cytometry, immune cells from blood and draining fluid samples obtained the same day showed an almost complete lymphopenia in peripheral blood, whereas CD3+CD4+CD8‐, CD3+CD4‐CD8+ and human leucocyte antigen D‐related (HLA‐DR)+CD19+ lymphocytes were the main populations in the draining fluid. Non‐complicated recipients evolved from a mixed leucocyte pattern including granulocytes, monocytes and lymphocytes to an exclusively lymphocytic pattern along the first post‐ITx week. At days 1–2 post‐Itx, analysis by short tandem repeats fingerprinting of CD3+CD8+ sorted T cells from draining fluid indicated that 50% of cells were from graft origin, whereas by day 11 post‐ITx this proportion decreased to fewer than 1%. Our results show for the first time that the abdominal drainage fluid contains mainly immune cells trafficking from the implanted intestine, providing the opportunity to sample lymphocytes draining from the grafted organ along the post‐ITx period. Therefore, this analysis may provide information useful for understanding ITx immunobiology and eventually could also be of interest for clinical management.

Immunosuppressive therapies after intestinal transplant modulate the expression of Th1 signature genes during acute cellular rejection. Implications in the search for rejection biomarkers.

Acute cellular rejection (ACR) and infections are leading causes of graft loss and death in intestinal transplant patients. Our aim was to evaluate the impact of maintenance immunosuppressive therapies on the expression of pro‐inflammatory mediators in small bowel at ACR diagnosis.

Intrapancreatic Common Hepatic Artery Arising From the Superior Mesenteric Artery, a Challenging Anatomic Variation in a Multiorgan Harvesting

INTRODUCTION Understanding abdominal vascular anatomy is crucial for multiorgan recovery. In this case report, we have described a common hepatic artery that arises from the superior mesenteric artery but follows an intrapancreatic course. METHODS The donor was ideal for multiorgan recovery and the recipient was a 29-year-old woman awaiting a second transplant owing to primary nonfunction of her first engrafted organ. The indication for transplantation was secondary biliary cirrhosis. A type I diabetic recipient on dialysis therapy was awaiting the kidney and pancreas. RESULTS The urgent condition of our liver recipient combined with the anatomical finding prioritized liver procurement, therefore the pancreas was discarded. CONCLUSIONS The recognition of all anatomic variations will allow us to improve the use of the scarce resource of deceased donor organs.

Serum albumin level during intestinal exfoliative rejection: a potential predictor of graft recovery and patient outcome

Exfoliative rejection is a severe complication after intestinal transplant. The assessment of mucosa histology is restricted to the area reached by endoscopy. We aim to evaluate the serum albumin (SA) value as a parameter of graft damage and clinical prognosis in intestinal exfoliative rejection (ExR). The present study is a retrospective analysis of 11 episodes of ExR occurred in a cohort of 26 patients. SA levels were measured 24 h after diagnosis and twice a week thereafter and then correlated with parameters of clinical and graft histological recovery (HR). During ExR, all patients had very low SA levels, reaching a minimum average of 1.9 ± 0.3 g/dL. According to the value of albumin levels at ExR diagnosis, the patients were grouped finding a correlation with their clinical evolution. Six ExR episodes presented with severe hipoalbuminemia (<2.2 g/dL; p < 0.05) that correlated with worse patient and graft outcome, ranging from graft loss and need for re‐transplantation to delayed clinical and HR. SA at ExR diagnosis may be an indicator of the severity of the ExR process, and it could also be used as an early predictor of patient and graft outcome.

Trasplante intestinal en pediatría: análisis de la primera serie de receptores en la Argentina

The present is a retrospective analysis of all pediatric patients that underwent intestinal transplant from March 2006 to March 2010, describing demographics, indications, contraindications, clinical follow up and survival in a single center in Argentina. Based on the results shown one can conclude that intestinal transplant should be considered as a valid treatment for patients with intestinal insufficiency and complications related to parenteral nutrition. The results of our program are similar to those reported in the international Intestinal Transplant Registry. This opens a new perspective to a special population that otherwise would not have any other therapeutic option.