Evangelos P. Misiakos

Liver transplantation with cavoportal hemitransposition in the presence of diffuse portal, vein thrombosis

BACKGROUND Orthotopic liver transplantation is possible even in the presence of recipient portal vein thrombosis, provided that hepatopetal portal flow to the graft can be restored. On rare occasions this is not possible due to diffuse thrombosis of the portal venous system. In these cases, successful liver transplantation has been considered impossible. Portocaval transposition was introduced in the pretransplantation era to study the effect of systemic venous flow on the liver and has been used in three patients for the treatment of glycogen storage disease. We used portocaval hemitransposition (portal perfusion with inflow from the inferior vena cava) in liver transplantation when portal inflow to the graft was not feasible. We are reporting the collective experience of nine patients from four liver transplant centers. METHODS Cavoportal hemitransposition was used in nine patients. In seven of these cases, the technique was used during the original transplant (primary group). In two cases, it was used after the portal inflow to the first transplant had clotted (secondary group). RESULTS Five of seven patients in the primary group are alive after intervals of 6-11 months. The two patients in the rescue group died. In the successful cases, liver function and histology were indistinguishable from those of conventional liver transplantation. Ascites disappeared within 3-4 months and the patients were able to return to their normal activities. Postoperative variceal bleeding necessitated splenectomy and gastric devascularization in one case and splenic artery embolization in another case. Bleeding was controlled in both these cases. Splenectomy and gastric devascularization were performed prophylactically in one patient with a history of variceal bleeding in order to prevent this complication after transplantation. CONCLUSION Portocaval hemitransposition maybe useful in liver transplantation when hepatopetal flow to the liver graft cannot be established by other techniques. Rescue after failure of conventional technique was not possible in two patients.

Short bowel syndrome: current medical and surgical trends.

Short bowel syndrome is a chronic malabsorptive state usually resulting from extensive small bowel resections. A combination of diarrhea, nutrient malabsorption, dysmotility, and bowel dilatation may constitute the clinical symptomatology of this syndrome. The remaining bowel undergoes a process called adaptation, which may replace lost intestinal function. Chronic complications include nutrient, electrolyte, and vitamin deficiencies. Therapy depends largely on the administration of various factors stimulating intestinal adaptation of the remaining bowel. If the patient despite medical therapy fails to return to oral diet alone, then long-term parenteral nutrition is required. However, long-term parenteral nutrition may gradually induce cholestatic liver disease. Surgical methods may be required for treatment including intestinal transplantation, as a last resort for the treatment of end-stage intestinal failure. The goal of this review is to analyze the clinical spectrum and pathophysiologic aspects of the syndrome, the process of intestinal adaptation, and to outline the medical and surgical methods currently used to treat this complicated group of patients.

Heterotopic sternum transplant in rats: A new model of a vascularized bone marrow transplantation.

We introduced the heterotopic vascularized sternum transplant as a more simple and pure alternative to allogeneic hind limb transplantation for the study of bone marrow transplantation. We report the clinical and histopathological manifestations after transplantation of syngeneic and allogeneic sternal grafts with and without immunossupression with FK‐506. Syngeneic grafts maintained normal histology, whereas allografts showed rejection, which was prevented by FK‐506. FK‐506‐treated allografts developed chimerism that was present throughout the observation period. Transplantation of the sternum may be a valuable model to study vascularized bone marrow transplantation and its effects on repopulation of bone marrow of the host, chimerism, and tolerance.

Inclusion of entire pancreas in the composite liver and intestinal graft in pediatric intestinal transplantation

Abstract: An entire pancreatico–duodenal complex was included in the liver and intestinal graft in eight children who received small‐size grafts. This method showed several advantages compared to the traditional approach. They included reducing time for graft preparation by eliminating donor pancreas resection, no necessity of biliary reconstruction and leaving natural tissue support for blood vessels. The method was not associated with an increased risk of complications such as pancreatitis or rejection. It should be considered in pediatric liver and intestinal transplant recipients who require small‐size grafts.

Current Trends in Laparoscopic Ventral Hernia Repair

Background and Objectives: The purpose of this study was to analyze the surgical technique, postoperative complications, and possible recurrence after laparoscopic ventral hernia repair (LVHR) in comparison with open ventral hernia repair (OVHR), based on the international literature. Database: A Medline search of the current English literature was performed using the terms laparoscopic ventral hernia repair and incisional hernia repair. Conclusions: LVHR is a safe alternative to the open method, with the main advantages being minimal postoperative pain, shorter recovery, and decreased wound and mesh infections. Incidental enterotomy can be avoided by using a meticulous technique and sharp dissection to avoid thermal injury.

Gastroesophageal Reflux Disease: Medical or Surgical Treatment?

Background. Gastroesophageal reflux disease is a common condition with increasing prevalence worldwide. The disease encompasses a broad spectrum of clinical symptoms and disorders from simple heartburn without esophagitis to erosive esophagitis with severe complications, such as esophageal strictures and intestinal metaplasia. Diagnosis is based mainly on ambulatory esophageal pH testing and endoscopy. There has been a long-standing debate about the best treatment approach for this troublesome disease. Methods and Results. Medical treatment with PPIs has an excellent efficacy in reversing the symptoms of GERD, but they should be taken for life, and long-term side effects do exist. However, patients who desire a permanent cure and have severe complications or cannot tolerate long-term treatment with PPIs are candidates for surgical treatment. Laparoscopic antireflux surgery achieves a significant symptom control, increased patient satisfaction, and complete withdrawal of antireflux medications, in the majority of patients. Conclusion. Surgical treatment should be reserved mainly for young patients seeking permanent results. However, the choice of the treatment schedule should be individualized for every patient. It is up to the patient, the physician and the surgeon to decide the best treatment option for individual cases.

Recurrence of desmoid tumor in a multivisceral transplant patient with Gardner's syndrome.

BACKGROUND Desmoid tumors are locally invasive fibromatous tumors, which, in patients with Gardners syndrome, usually occur in the abdominal wall or intra-abdominally. After excision, they tend to recur, often leading to multiple bowel resections. METHODS This is a report of the clinical course of a patient with Gardners syndrome and desmoid tumor who had multiple enterectomies and gradually developed short-gut syndrome. He required prolonged parenteral nutrition, which damaged the liver. The patient underwent a multivisceral transplantation as a life-saving procedure. RESULTS After the transplant, the desmoid tumor recurred in the thoracic wall twice and was successfully resected. It also recurred in the abdominal cavity, compressing the intestinal loops; the tumor was excised uneventfully, leaving the graft intact. The recurrent tumors were all of recipient origin. CONCLUSIONS Intestinal and multivisceral transplantation could be considered in patients with short-gut syndrome caused by recurrent desmoid tumor. In the case of posttransplant tumor recurrence, resection is the only option recommended.

Donor and recipient pretransplant conditioning with nonlethal radiation and antilymphocyte serum improves the graft survival in a rat small bowel transplant model.

Background. Lymphoid tissue within the intestinal graft require immunomodulatory strategies to prevent graft versus host disease (GVHD) after transplant. Herein, we evaluate the potential advantage of donor-specific bone marrow infusions in donor and or recipient preconditioned with total body irradiation and or antilymphocyte serum (ALS) on the incidence of GVHD and rejection after small bowel transplantation. Methods. Heterotopic SBTx was performed from DA to Lewis rats and distributed in nine groups: control group G0 (n=4) and G1 (n=6) without irradiation; recipients in G2 (n=4) were given 400 rd although in groups 3 (n=5), G4 (n=6), G6 (n=5), G7 (n=5), and G8 (n=6) with 250 rd. Donors in G5 (n=4) and G6 were given 250 rd of total body irradiation 2 hours before intestinal retrieval. Donors and recipients in G7 and donors in G8 additionally received ALS (day −5). G1, 2, 3, 5, 6, 7, and 8 were infused with UDBM and G4 with the same amount of TCDBM. Animals received tacrolimus for 15 days and accessed for rejection, GVHD and for chimerism analysis. Results. High mortality due to GVHD was observed in G2, 3, and 4, and correlated with high levels of donor T cells in recipients blood. G0 and G1 showed early acute rejection with progression toward chronic rejection, in contrast to the preconditioned groups. High and low doses of total body irradiation resulted in allogeneic and in a mixed chimerism, respectively. Decrease in donor chimeric cells after 11 weeks in preconditioned groups was correlated with severe allograft rejection. Conclusion. Donor preconditioning with 250 rd and or ALS combined with recipient preconditioning and donor-specific bone marrow infusions prevented GVHD and resulted in a transient mixed chimerism with inhibition of allograft rejection after small bowel transplantation.

Apoptosis and rejection in rat intestinal transplantation : Correlation with FK 506 doses and donor specific bone marrow infusions

BACKGROUND Our purpose was to investigate the occurrence and the evolution of apoptosis of enterocytes during acute and chronic rejection in an experimental model of allogeneic heterotopic small bowel transplantation (SBTx). METHODS Forty-five rats were divided in 10 experimental groups according to the dose of FK506 administration and donor bone marrow infusions (DBMI). Groups 1 and 2 did not received BMI. Groups 3 and 4 received 150x106 cells at day 0, groups 5 and 6 received 75x106 cells at days 0-4, groups 7 and 8 received 75x106 cells at days 4 and 10, and groups 9 and 10 received 30x106 cells at days 4, 10, 15, 20, and 25. Animals of groups 1, 3, 5, 7, and 9 were immunosuppressed with 0.5 mg/kg FK 506, although the remaining groups with 1 mg/kg FK 506, from day 0 to 4 after transplant. Fragment end labeling of DNA was used to detect apoptosis. RESULTS The number of apoptotic cells detected was highest at day 15 (184+/-154) and then progressively decreased thereafter (day 30=159+/-197; day 45=80+/-167; day 60=0). The number of apoptotic enterocytes was found increased during mild (151+/-108) and moderate (281+/-161) allograft rejection, although a low apoptotic rate was observed in cases without rejection (59+/-13) and during severe (53+/-131) and chronic rejection (46+/-136). Furthermore the number of labeled cells was found inversely correlated with fibrosis (P<0.0001). There was no correlation between apoptosis and the presence or absence of DBMI; however, at day 15 rats receiving 1 mg/day of FK 506 had a significantly lower number of apoptotic cells detected (127+/-103 vs. 233+/-174; P<0.02). CONCLUSIONS In this study the number of apoptotic cells correlated positively with mild and moderate rejection episodes. In case of severe and chronic rejection a low apoptotic rate was found due probably to extensive necrosis and fibrosis of the mucosa. These data suggest an important role of apoptosis in acute and chronic intestinal rejection in a rat model of intestinal transplantation. Determination of apoptosis in allografts might represent an early sign of small bowel rejection and a useful marker in defining the degree of rejection and its outcome/prognosis.

Correlation between allograft survival and chimeric state after bone marrow infusion in rat small bowel transplantation

Abstract: Methods to enhance natural microchimerism, which occurs after any successful organ transplant, are currently explored using unmodified donor bone marrow both in experimental and in clinical trials. Because of the potential immunomodulatory effects of donor bone marrow cells, we performed this study to evaluated the effect of single and multiple donor‐specific bone marrow infusions (DSBMI) on chimerism and small bowel allograft survival in a fully histoincompatible rat model. Forty‐five male DA rats and 45 female Lewis rats were used as donors and recipients, respectively, for a heterotopic small bowel transplant. Animals were separated into 10 groups according to the number of bone marrow infusions and immunosuppressive protocol used. Control groups (groups 1 and 2) did not receive any bone marrow infusion, groups 3 and 4 received one infusion at day 0 (150 × 106 cells), groups 5 and 6 received two infusions at days 0 and 4 (75 × 106 cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 × 106 cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 × 106 cells each). Animals in groups 1, 3, 5, 7 and 9 were immunosuppressed with 0.5 mg/kg FK506 while the remaining groups were immunosuppressed with 1 mg/kg FK506, from day 0 to 4 after transplant. Every 15 days, the chimeric state was determined by flow cytometry in order to detect cells expressing DA rat class I antigen, and small bowel biopsies were obtained from ileostomies. Animals in all groups showed minimal to moderate acute rejection at day 15 after transplant, however, vascular rejection (vasculitis, arteritis) was observed in only bone marrow groups (100% in 0.5 mg/kg and 42.1% in 1 mg/kg FK506 groups). On day 30, 58.3% of bone‐marrow‐infused animals and 66.6% of controls showed severe acute and early chronic rejection. The chimeric levels varied from 0 to 12% after transplant and were significantly higher in bone‐marrow‐infused groups compared with controls (p < 0.05). We conclude that modulation of immune response with short‐course immunosuppression and a single or multiple DSBMI did not improve allograft or recipient survival. The inability to achieve a stable chimeric state did not allow us to determine the effect of chimerism on graft and recipient survival after small bowel transplantation