Two cases of Norwalk virus enteritis following small bowel transplantation treated with oral human serum immunoglobulin

Abstract:  Protracted diarrhea is a challenging problem after small bowel transplantation. We report two patients who developed Norwalk virus enteritis after small bowel transplantation. Both received oral HSIG with resolution of diarrhea within 48 h.     

Modified temporary end-to-side portocaval shunt in liver and small bowel transplantation

Piggyback orthotopic liver transplantation (LTx) has permitted the elimination of extra-corporeal venovenous bypass. In some instances, an internal temporary portocaval shunt has to be constructed in order to prevent hemodynamic instability. We describe a technique in which a donor iliac vein graft is used to bridge the distance between the portal vein and vena cava in cases where a direct shunt cannot be constructed. This technique can be applied to liver Tx as well as to liver and small bowel Tx.     

Current status of small bowel transplantation in children

Small bowel transplantation is gradually changing from an experimental procedure to a very desirable and viable treatment option in children with irreversible intestinal failure due to either short bowel syndrome or functional impairment. Long term total parenteral nutrition and home parenteral nutrition would be necessary to manage these children in the absence of a small bowel transplant programme. Parenteral nutrition is also associated with complications which can result in chronic liver disease. In India, there is no infrastructure for this treatment option and even if it was there the cost of this method of treatment is likely to be more than the cost of post-operative immunosuppression. Small bowel can be transplanted as an isolated graft, in combination with the liver or as part of a multiviscera! transplant. The operative techniques have been standardised. Major post-operative complications result from sepsis and lymphoproliferative diseases. The best results have been obtained with a combined liver and small bowel transplant.     

Herpes simplex colitis in a child with combined liver and small bowel transplant

Herpes simplex virus (HSV) has been a rare cause of gastrointestinal (GI) infection, especially in immunocompromised patients. A variety of GI sites may be involved; however, only three reported cases of HSV colitis have been documented in the literature. To our knowledge, this is the first report of HSV colitis in a small bowel transplant recipient.     

Pattern of growth after pediatric living-donor small bowel transplantation

The aim of our study was to analyze growth in children who underwent LDSB. The question was whether these children obtain linear growth and improvement of the Z-score for height and weight after the transplant. Three children with a mean age of 24 months underwent living-donor intestinal transplantation with 150 cm of terminal ileum. At a mean follow-up of 27 months height increased from 82.5 to 97.5 cm although Z-score for height did not improve, -2.679 to -2.675. Mean weight increased from 11.4 to 14.2 kg while Z-score for weight went from -1.916 to -2.409. Although these data are pertinent to only three children and the follow-up is slightly longer than two yr, it appears that while long-term survival and independency from TPN is achieved, only linear growth might be expected and catch-up growth does not occur.     

Renal function and histology in children after small bowel transplantation

Boyer O, Noto C, Patey‐Mariaud De Serre N, Gubler M‐C, Dechaux M, Goulet O, Niaudet P, Lacaille F. Renal function and histology in children after small bowel transplantation. Abstract: CKD is a frequent long‐term complication after SBTx. CNIs are a well‐known factor, but probably not the only cause. We assessed the incidence, risk factors, and severity of CKD in 27 children with SBTx (15 combined liver/SBTx) and prednisone/TAC‐based maintenance immunosuppression. Median follow‐up was seven yr (3–21). A renal biopsy was performed in 14 patients, 1–18 yr post‐SBTx. A reduced GFR was observed in 17 children (63%) during the follow‐up with none requiring dialysis. CNI toxicity was observed in 11/14 biopsies, as early as two yr post‐transplant, and could occur with a normal mGFR. The dose of TAC was reduced by 50% in 13 patients with CKD and/or significant kidney histological lesions, and six were also given MMF. This led to a significant improvement in renal function: mGFR normalized in eight patients and improved or stabilized in five. No rejection occurred. At last follow‐up, 37% had CKD stage 2 and 15% had CKD stage 3. In conclusion, CKD is frequent in children after SBTx and probably multifactorial. Less nephrotoxic immunosuppressive protocols may improve mGFR and should be further considered. The kidney histology helps in designing personalized immunosuppression strategies for patients.     

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

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 evaluate 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 x 10(6) cells), groups 5 and 6 received two infusions at days 0 and 4 (75 x 10(6) cells each), groups 7 and 8 received two infusions at days 4 and 10 (75 x 10(6) cells each), and groups 9 and 10 received five infusions at days 4, 10, 15, 20 and 25 (30 x 10(6) 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.     

EBV-negative lymphoproliferative disease with hyper-IgA, in a child with combined liver and small bowel transplantation

A 4-year-old boy presented 14 months after liver and small bowel transplantation with fever, diarrhea, elevated liver enzymes, thrombocytopenia and autoantibodies. Total gammaglobulins level was normal but the level of plasma IgA1 was very high. The blood PCR for Epstein-Barr virus (EBV) was negative. The ileal biopsy disclosed a lymphoplasmacytic infiltration. The EBER probe was negative on the small bowel biopsies. The child was considered as suffering from a non-EBV-induced posttransplant lymphoproliferative disorder (PTLD). The high IgA level was presumed to be secreted by proliferating plasma cells in the transplanted bowel. Immunosuppression was reduced; but the efficacy was incomplete and an anti-CD20 antibody was added. There was complete resolution of symptoms and normalization of the IgA level. As IgA1 is mostly of intestinal origin, this unusual presentation of PTLD should lead to a high suspicion of a small bowel proliferating process.     

Autologous-allotopic ileum mucosa transplantation for small bowel elongation. A morphological study

Introduction Since a standard therapy for short bowel syndrome does not yet exist, every search for new surgical methods would be worthwhile. In previous studies we could show that autologous-allotopic ileum mucosa transplantation is feasible. After a modification of our technique a vascularized colon muscle coat lined completely with transplanted ileum mucosa could be engendered.Method In 12 young beagles autologous ileum mucosa was transplanted in a demucosed vascularized transverse colon segment. The colon coat-ileum mucosa complex was anastomosed with the small bowel immediately after transplantation, 4 weeks later the animals were sacrificed and histology specimens were harvested from the colon coat-ileum mucosa complex, normal ileum and normal colon. After fixation in 2.5% glutaraldehyde the samples were frozen (–40°C) and 14 µm sections were stained with hemalaun and eosin. The lumen diameter, the mucosa, submucosa and colon muscle coat thickness, as well as the mucosal crypt depth were evaluated.Results The diameter of the colon coat-ileum mucosa-complex was smaller than the diameter of normal ileum and colon with no significant stenosis. There were no marked differences in thickness of mucosa and depth of the mucosal crypts compared to the controls, but the transplanted mucosa showed a slightly higher rate of shortened villi. The submucosal layer was thicker following transplantation and showed good neovascularization. The circular muscle layer of the transplanted colon coat was up to 178% thicker and the thickness of the transplanted longitudinal muscle layer differed between 58% and 143% in comparison to normal colon.Conclusions Only a few histologic differences between transplanted and normal ileum mucosa could be observed after autologous-allotopic ileum mucosa transplantation. Therefore a nearly normal function of the colon coat-ileum mucosa complex has to be expected. Long term experiments of the histologic changes as well as further functional studies are on-going in order to finally apply autologous-allotopic ileum mucosa transplantation clinically.     

Successful long‐term outcome after combined hematopoietic stem cell transplantation and small bowel transplantation: A case report and review of the literature

Combining HSCT with SOT is an unusual and challenging undertaking given the complexities of immune modulation, the need to balance comorbidities, and the cumulative potential for complications. Early life‐threatening complications include infections and related effects, graft rejection, and GVHD can be expected to be increased especially if the HSCT is indicated for high‐risk cases such as individuals with severe combined immune deficiency and SOT that includes an intestine graft. Herein, we report such a case. Our patient is unique as a long‐term survivor. We review the literature and the features of our case, especially the timing of transplants and human leukocyte antigen matching for HSCT that resulted in a successful outcome and discuss how this may be applied to others in the future.     

Magnetic attraction leading to a small bowel obstruction in a child

Foreign body ingestion in small children is common yet only 1% of cases require operative management of associated complications (Arana et al. in Eur J Pediatr 160:468-472, 2001). A 6-year-old boy was referred to our institution with a 12 h history of abdominal pain. This pain was diffuse and crampy in nature and associated with multiple episodes of non-bilious, non-bloody emesis. On evaluation he was stable and his abdomen demonstrated slight distention and tenderness without peritoneal signs. Plain abdominal radiographs demonstrated some distended loops of small bowel and a radio-opaque foreign object within the mid-abdomen. A small bowel obstruction secondary to foreign body ingestion was diagnosed and an emergent laparotomy performed. Upon exploration, a transition zone was noted near the ileocecal valve. Further exploration revealed the obstruction to be caused secondary to the apposition of two small (8 mm) magnets, one in the proximal ileum and the other near the ileocecal valve, resulting in an internal hernia. The magnets were easily separated relieving the obstruction and both were removed via two small bowel enterotomies. After being presented with the magnets, his parents suspected that they came from the clothes of a Polly Pocket (Mattel, Inc., El Segundo, CA) doll. The patient had an uneventful post-operative course and was discharged to home on the second post-operative day. This case demonstrates the complications that may occur with multiple magnet ingestion. It highlights the need for close observation and early surgical intervention in children with a suspected history of foreign body ingestion, a clinical picture of gastrointestinal distress, and radiographic evidence of a radio-opaque foreign object.     

Necrotizing fasciitis following liver and small intestine transplantation

Necrotizing fasciitis is a rare, subcutaneous infection. It can occur in patients after solid-organ transplantation. We herein report two patients who developed necrotizing fasciitis following combined liver and small intestine transplantation. The first patient experienced this infection 4 yr after transplantation and 1 yr after the closure of the ileostomy. The second patient suffered from necrotizing fasciitis 2 days after the transplant. Both cases were diagnosed on the physical findings, culture of subcutaneous lavage, and the computed tomography findings. The site of entrance of the organism was not clear in either case. Both patients had a fulminant course and died within 1 week from the onset, despite aggressive surgical intervention. Therefore, necrotizing fasciitis has to be recognized as a potential complication of intestinal transplantation.     

Repeated fecal microbiota transplantation in a child with ulcerative colitis

We report the case of an 11‐year‐old girl with ulcerative colitis refractory to conventional therapy, who was subsequently treated successfully with repeated fecal microbiota transplantation (FMT). The patient was steroid dependent despite several infliximab treatments, and colectomy was proposed to improve quality of life. After repeated FMT, she was able to maintain remission with on minimal dose of steroid. Although her fecal microbiota was dysbiotic before FMT, it was restored to a similar pattern as the donor after repeated FMT.     

Effects of isolated small bowel transplantation on liver dysfunction caused by intestinal failure and long-term total parenteral nutrition

It has not been fully determined whether isolated small bowel transplantation (ISBTx) can reverse liver dysfunction caused by intestinal failure requiring long-term total parenteral nutrition (TPN). A boy with congenital microvillus inclusion disease presented with vomiting and severe diarrhea since the first day of life and had been managed by TPN since then. He suffered from catheter-related sepsis several times. At 14 yr of age he developed progressive hepatosplenomegaly with thrombocytopenia and coagulopathy. He underwent ISBTx with an ileal graft from his blood-identical grandmother at the age of 16 yr. Oral feeding was started on the 14th day after ISBTx and gradually increased. TPN was completely withdrawn after 5 months. Liver was palpated 5 cm below the costal margin before ISBTx, while it became non-palpable 5 months after ISBTx. Serum liver enzyme levels and prothrombin time normalized in the 5 months following ISBTx. Liver biopsy showed marked steatosis, slight cholestasis, and mild bridging fibrosis before ISBTx. Although histological examination of liver biopsy revealed complete disappearance of steatosis 7 and 11 months after ISBTx, liver fibrosis remained unchanged. This clinical experience has shown that although steatosis and cholestasis are reversible after successful ISBTx and withdrawal of TPN, liver fibrosis may remain unchanged.     

Arterioportal fistulae following segmental liver transplantation in a child

We report a case of arterio-portal fistulae in a 12-month-old-child following a segmental liver transplantation. The fistula, probably the result of mass ligature of a vascular pedicle during back table allograft reduction, is to our knowledge the first such case reported. Diagnosed on the third post-operative day, the fistula was successfully managed with transcatheter coil embolization. The child is well and asymptomatic, 33 months after transplantation. In addition to those seen in whole organ transplantation, there are a few complications specifically related to segmental transplantation. These complications, although infrequent, are a direct consequence of the back table liver partition, as in the case herein reported.     

Management of end-stage central venous access in children referred for possible small bowel transplantation

The 3-year survival after small bowel transplantation (SBTx) has improved to between 73% and 88%. Impaired venous access for parenteral nutrition can be an indication for SBTx in children with chronic intestinal failure. AIM: To report our experience in management of children with extreme end-stage venous access. SUBJECTS: The study consisted of 6 children (all boys), median age of assessment 27 months (range, 13-52 months), diagnosed with total intestinal aganglionosis (1), protracted diarrhea (1), and short bowel syndrome (4), of which gastroschisis (2) and malrotation with midgut volvulus (2) were the causes. All had a documented history of more than 10 central venous catheter insertions previously. All had venograms, and 1 child additionally had a magnetic resonance angiogram to evaluate venous access. Five of 6 presented with thrombosis of the superior vena cava (SVC) and/or inferior vena cava. METHODS: Venous access was reestablished as follows: transhepatic venous catheters (5), direct intra-atrial catheter via midline sternotomy (4), azygous venous catheters (2), dilatation of left subclavian vein after passage of a guide wire and then placing a catheter to reach the right atrium (1), radiological recanalization of the SVC and placement of a central venous catheter in situ (1), and direct puncture of SVC stump(1). Complications included serous pleural effusion after direct intra-atrial line insertion, which resolved after chest drain insertion (1), displacement of transhepatic catheter needing repositioning (2), and SVC stent narrowing requiring repeated balloon dilatation. OUTCOME: Four children with permanent intestinal failure on assessment were offered SBTx, 3 of which were transplanted and were established on full enteral nutrition; the family of 1 child declined the procedure. In the remaining 2 children in whom bowel adaptation was still a possibility, attempts were made to provide adequate central venous access as feeds and drug manipulations were undertaken. One of them received liver and SBTx nearly 3 years after presenting with end-stage central venous access, because attempts to achieve independence from parenteral nutrition had failed. The other child died immediately after a transhepatic venous catheter placement, possibly from a nutritional depletion syndrome as no physical cause of death was found. Direct intra-atrial catheters in transplanted children proved to be adequate for the management of uncomplicated transplantation, although the usual infusion protocol had to be modified considerably, and the lack of access would have been critical if massive blood transfusion had been required during the transplant procedure. CONCLUSION: It was possible to reestablish central venous access in all cases. However, this was time consuming and difficult to assemble a skilled team consisting of one of more: surgeon, cardiologist, interventional radiologist, and transplant anesthetist. Small bowel transplantation is easier and safer with adequate central venous access, and we advocate liaison with an SBTx center at an early stage.     

Autoantibodies to red blood cell antigens occur frequently with hemolysis among pediatric small bowel transplant recipients: Clinical implications and management

Reports have linked pediatric solid organ transplant recipients with the development of hemolytic autoimmune antibodies, especially in the setting of the immunosuppressant tacrolimus. This study aims to identify whether these observations also occurred at an institution that frequently performs pediatric multivisceral transplants and to characterize the treatment and outcome. Chart review was performed on all patients with RBC autoantibodies. Laboratory and clinical data were used to identify hemolysis. For transplant recipients with RBC autoantibodies, the type of transplant and outcome of the AIHA were profiled. One hundred twenty‐eight patients were identified with RBC autoantibodies, of which 22 patients were solid organ transplant recipients, including 18 SB graft recipients. Sixteen of the 18 had evidence of hemolysis. The incidence rate of AIHA in this population is estimated to be 10%, resulting in significant cost. Treatment included immunosuppressant modulation, steroids, IVIG, and plasma exchange, with 12 of the 16 patients responding. RBC autoantibodies occur in up to 10% in pediatric SB transplant recipients, with high cost of obtaining compatible blood. Neither tacrolimus nor receipts of a donor spleen were associated with the development of AIHA. Treatment using steroids and IVIG appears to be effective.     

Living related small bowel transplantation in children: 3-dimensional computed tomography donor evaluation

The evaluation of the small bowel vascular anatomy of living small bowel donors (LSBD) is usually performed with conventional angiography (CA). Recently, angio computed tomography (CT) has become a valid study of the vascular anatomy for kidney and liver living donors. We studied the applicability of angio CT with 3-D reconstruction (3-D-ACT) in the evaluation of LSBD. Potential LSBDs for pediatric transplant underwent both CA and 3-D-ACT to evaluate the anatomy of the distal branches of the superior mesenteric artery and vein. Angio-CT was performed with General Electric Lightspeed Scanner. The 3-D reconstruction was performed on the TeraRecon workstation. Adverse reactions, contrast dosage, test duration, invasiveness, hospital-stay, patient discomforts and accuracy were evaluated. Four potential donors (four female; mean age: 30.5 yr; mean BMI: 28.4) underwent both tests. Adverse reactions correlated to contrast agent used (90 mL CA, 150 mL 3-D-ACT) were not reported. CA required a hospitalization of 6 h as opposed to immediate discharge after the 3-D-ACT. The CA required the placement of transfemoral catheter and therefore greater patient discomfort than with 3-D-ACT. The 3-D-ACT arterial images were rated as equivalent to CA, however, 3-D-ACT venous images were rated better than the CA in all cases. CT-angiography with 3-D reconstruction is an acceptable method for vascular evaluation. When compared with routine angiography, it is less invasive, better tolerated and faster, but does require a significantly greater volume of venous contrast. 3-D-ACT also offers a better evaluation of the venous phase, and thus may become the test of choice to evaluate the vascular anatomies of LSBD candidates.     

Hematopoietic stem cell transplantation in a CD3 gamma-deficient infant with inflammatory bowel disease

Partial or total CD3 chain expression defects including CD3 gamma, epsilon, delta, and zeta chain are among the autosomally inherited SCID presenting with T-B+NK+ phenotype with lymphopenia. The clinical findings are generally severe in all except for CD3 gamma deficiency. Here we present a 10-month-old CD3 gamma deficient boy with IBD. The patient had suffered from intractable diarrhea, recurrent pulmonary infections and oral moniliasis since two months of age. Following the first allogeneic HSCT from his HLA-identical (6/6) sister after a reduced intensity regimen, a second transplantation was performed five months later. On day +19 after second transplantation, the CD3 TCR alpha/beta chain expression increased to 66% with development of full donor chimerism (98.6%). A significant improvement in diarrhea, perianal lesions, and rectal fistula was observed suggesting an improvement in inflammatory bowel disease. The patient died at home on day +50 with a sudden respiratory failure secondary to an undetermined infection. The case was interesting being the first reported case with SCID and inflammatory bowel disease who responded very well to HSCT by full recovery of intractable diarrhea, failure to thrive, laboratory findings, and improvement of fistula formation.