Heung Bae Kim

Serial transverse enteroplasty for short bowel syndrome: a case report.

The patient is a 2-year-old boy born with gastroschisis and midgut volvulus that left him dependent on total parenteral nutrition (TPN). At 11 months of age, a Bianchi procedure was performed increasing the total length of bowel from 72 cm to 130 cm. Although he appeared to have sufficient bowel length, he continued to have malabsorption and could only tolerate 10% of his caloric requirement enterally. A barium study found significant dilatation of the lengthened small bowel. At 23 months, we performed a novel bowel lengthening procedure that we have reported previously in an animal model. The serial transverse enteroplasty (STEP) operation increased the 83 cm of dilated and previously lengthened bowel to 147 cm, making the total small bowel length 200 cm. The patient tolerated the procedure well and began to have semisolid bowel movements. Small intestinal absorptive capacity measured by D-xylose absorption showed a substantial increase from 5 to 12 mg/dL (normal range, >20), implying improved but not completely normal small bowel function. This case shows that the STEP procedure increases intestinal length, can be used after a prior Bianchi, and may result in improved intestinal absorptive capacity. The STEP procedure should be considered a surgical option for children with short bowel syndrome.

Serial Transverse Enteroplasty Enhances Intestinal Function in a Model of Short Bowel Syndrome

Objective/Summary Background Data:Serial transverse enteroplasty (STEP) is a new intestinal lengthening procedure that has been shown to clinically increase bowel length. This study examined the impact of the STEP procedure upon intestinal function in a model of short bowel syndrome. Methods:Young pigs (n = 10) had a reversed segment of bowel interposed to induce bowel dilatation. Five pigs underwent a 90% bowel resection with a STEP procedure on the remaining dilated bowel while 5 served as controls and had a 90% bowel resection without a STEP procedure. Determinations of nutritional status, absorptive capacity, and bacterial overgrowth were conducted 6 weeks after resection. Statistical comparisons were made by 2-sample t test (significance at P < 0.05). Results:The STEP procedure lengthened the bowel from 105.2 ± 7.7 cm to 152.2 ± 8.3 cm (P < 0.01). The STEP animals showed improved weight retention compared with controls (mean, −0.5% ± 1.8% body weight versus −17.6% ± 1.5%, P < 0.001). Intestinal carbohydrate absorption, as measured by d-Xylose absorption and fat absorptive capacity as measured by serum vitamin D and triglyceride levels, were increased in the STEP group versus controls. Serum citrulline, a marker of intestinal mucosal mass, was significantly elevated in the STEP pigs compared with controls. None of the STEP animals but 4 of 5 control animals were noted to have gram-negative bacterial overgrowth in the proximal bowel. Conclusions:STEP improves weight retention, nutritional status, intestinal absorptive capacity, and serum citrulline levels in a porcine short bowel model. A salutary effect upon bacterial overgrowth was also noted. These data support the use of this operation in short bowel syndrome.

In utero bone marrow transplantation induces donor-specific tolerance by a combination of clonal deletion and clonal anergy

BACKGROUND/PURPOSE In utero bone marrow transplantation can induce donor-specific tolerance to postnatal solid organ transplantation, although the mechanisms remain poorly defined. In this study, we investigated the role of clonal deletion and clonal anergy in the maintenance of tolerance in a murine model of in utero bone marrow transplantation. METHODS DBA/2 mice (MIs(a+)) were used as donors of adult bone marrow, and 14-day-gestation fetal Balb/c mice (MIs(a-)) were used as recipients. Tolerance was defined by donor-specific skin graft survival for more than 8 weeks. Clonal deletion was assessed by flow cytometry for Vbeta6 T cell receptor usage. A tolerant animal demonstrating partial deletion of CD4+/Vbeta6+ T cells and a nontolerant animal were selected for analysis of clonal anergy by a proliferation assay using plate-bound anti-Vbeta6 antibody for stimulation with or without exogenous interleukin-2 (IL2). RESULTS Vbeta6+ splenocytes constituted 6.32% of CD4+ T cells in the tolerant animal compared with 9.19% in the nontolerant animal, demonstrating incomplete clonal deletion in the tolerant animal. Stimulation with plate-bound anti-Vbeta6 induced a good proliferative response in the nontolerant animal but a significantly attenuated response in the tolerant animal (P< .001), which was abrogated by the addition of IL2. CONCLUSIONS In this murine model of in utero bone marrow transplantation, the tolerant state is characterized by partial clonal deletion of donor reactive T cells and clonal anergy of nondeleted donor reactive T cells. The anergic state can be abrogated by exogenous IL2, suggesting that the mechanism of anergy is a deficiency of IL2 production.

Report of 111 Consecutive Patients Enrolled in the International Serial Transverse Enteroplasty (STEP) Data Registry: A Retrospective Observational Study

BACKGROUND The International Serial Transverse Enteroplasty (STEP) Data Registry is a voluntary online database created in 2004 to collect information on patients undergoing the STEP procedure. The aim of this study was to identify preoperative factors that are significantly associated with transplantation or death or attainment of enteral autonomy after STEP. STUDY DESIGN Data were collected from September 2004 to January 2010. Univariate and multivariate logistic regression analyses were applied to determine the predictors of transplantation or death or enteral autonomy post-STEP. Time to reach full enteral nutrition was estimated using a Kaplan-Meier curve. RESULTS Fourteen of the 111 patients in the Registry were excluded due to inadequate follow-up. Of the remaining 97 patients, 11 patients died and 5 progressed to intestinal transplantation. On multivariate analysis, higher direct bilirubin and shorter pre-STEP bowel length were independently predictive of progression to transplantation or death (p = 0.05 and p < 0.001, respectively). Of the 78 patients who were 7 days of age or older and required parenteral nutrition at the time of STEP, 37 (47%) achieved enteral autonomy after the first STEP. Longer pre-STEP bowel length was also independently associated with enteral autonomy (p = 0.002). Median time to reach enteral autonomy based on Kaplan-Meier analysis was 21 months (95% CI, 12-30). CONCLUSIONS Overall mortality post-STEP was 11%. Pre-STEP risk factors for progressing to transplantation or death were higher direct bilirubin and shorter bowel length. Among patients who underwent STEP for short bowel syndrome, 47% attained full enteral nutrition post-STEP. Patients with longer pre-STEP bowel length were significantly more likely to achieve enteral autonomy.

Long-term nutritional and clinical outcomes after serial transverse enteroplasty at a single institution

PURPOSE Serial transverse enteroplasty (STEP) is a novel technique to lengthen and taper bowel in patients with intestinal failure. First described in 2003, initial data and reports have demonstrated favorable short-term outcomes, but there is limited published data on long-term outcomes of the procedure. Our aim was to assess clinical and nutritional outcomes after the STEP procedure. METHODS After obtaining institutional review board approval, we reviewed all records of patients (n = 16) who underwent the STEP procedure at our institution from February 2002 to February 2008. Patients were observed for a median time of 23 months (range, 1-71) postoperatively. Analyses of z scores for weight, height, and weight-for-height, and progression of enteral calories were performed using longitudinal linear models with random effects. RESULTS Of the 16 patients (10 male), the median age at time of surgery was 12 months (interquartile range, 1.5-65.0). The mean increase in bowel length was 91% +/- 38%. After the STEP procedure, patients had increased weight-for-age z scores of 0.03 units per month (P = .0001), height for age z scores of 0.02 units per month (P = .004), and weight-for-height z scores of 0.04 units per month (P = .02). Patients had improved enteral tolerance of 1.4% per month (P < .0001). Six patients (38%) transitioned off parenteral nutrition (median, 248 days). Long-term complications included catheter-related bacteremia (n = 5), gastrointestinal bleeding (n = 3), and small bowel obstruction (n = 1). Two patients ultimately underwent transplantation. There were no deaths. CONCLUSIONS In pediatric patients with intestinal failure, the STEP procedure improves enteral tolerance, results in significant catch-up growth, and is not associated with increased mortality.

Rapid recurrence of nonalcoholic fatty liver disease after transplantation in a child with hypopituitarism and hepatopulmonary syndrome

Nonalcoholic fatty liver disease (NAFLD) has been reported in adults with hypothalamic or pituitary dysfunction, and some have progressed to end stage liver disease requiring transplantation. We report a teenager who intially presented with hypoxia due to intrapulmonary shunting, found to have NAFLD and cirrhosis associated with a hypothalamic tumor and panhypopituitarism. The NAFLD recurred very quickly after a successful liver transplant. Hepatopulmonary syndrome may be more common in cirrhosis associated with pituitary dysfunction than in other types of cirrhosis. (Liver Transpl 2005;11:108–110.)

In utero bone marrow transplantation induces kidney allograft tolerance across a full major histocompatibility complex barrier in Swine.

Background. In utero hematopoietic stem-cell transplantation has been shown to induce donor-specific tolerance in small-animal models. However, tolerance has been difficult to achieve in large-animal studies. Methods. Outbred swine underwent in utero transplantation of fully major histocompatibility complex (MHC)-mismatched CD3-depleted bone marrow mixed with fresh bone marrow to achieve a final CD3 content of 1.5%. Transplantation was performed at 50 to 55 days’ gestation and two animals survived long term and demonstrated multilineage peripheral blood hematopoietic chimerism. These two long-term survivors were analyzed for in vitro evidence of donor-specific tolerance by mixed leukocyte reaction (MLR), cell-mediated lysis (CML), and antibody testing and in vivo by kidney transplantation. Results. Both animals demonstrated in vitro donor-specific unresponsiveness by MLR and CML and did not demonstrate anti-donor antibody production. Donor matched kidney transplants were performed without immunosuppression and functioned for more than 100 days, with no evidence for rejection. Conclusions. The authors demonstrate conclusively that in utero transplantation of fully MHC-mismatched bone marrow in swine can lead to engraftment and stable multilineage hematopoietic chimerism and tolerance to postnatal donor MHC-matched kidney transplantation without the need for immunosuppression.

Orthotopic liver transplantation for inflammatory myofibroblastic tumor of the liver hilum

Inflammatory myofibroblastic tumor is a rare gastrointestinal neoplasm. The authors report the case of a 5-year-old girl who initially presented with gastric outlet obstruction secondary to an inflammatory myofibroblastic tumor along the lesser gastric curvature. A subtotal gastrectomy and wedge resection of a left hepatic lobe nodule were performed. Obstructive jaundice developed one month postoperatively. Computerized tomography, percutaneous transhepatic cholangiography, and selective celiac and mesenteric arteriography showed a mass that involved the left hepatic lobe, with concomitant high-grade biliary obstruction and portal venous encasement. Percutaneous biliary drainage was performed. During laparotomy, the tumor was found to be unresectable, and the patient was referred to the Liver Transplant Service at The Childrens Hospital of Philadelphia. A total hepatectomy with temporary portocaval shunt was performed, leaving the inferior vena cava in situ. At the back table, an ex vivo left trisegmentectomy was performed, followed by reimplantation of the posterior segment of the right hepatic lobe. The reimplanted liver segment functioned poorly, and completion hepatectomy with portocaval shunt was performed 24 hours postoperatively, because of severe coagulopathy, intraabdominal bleeding, and hemodynamic instability. The patients condition stabilized, and she was listed for urgent liver transplantation. The anhepatic state was managed with intermittent plasmapheresis. She had transplantation 72 hours later, and was discharged from the hospital 3 weeks postoperatively after an uneventful recovery. She remains disease-free and has normal liver function 8 months after transplantation.

Deceased-Donor Split-Liver Transplantation in Adult Recipients: Is the Learning Curve Over?

BACKGROUND Infants have the highest wait-list mortality of all liver transplantation candidates. Deceased-donor split-liver transplantation, a technique that provides both an adult and pediatric graft, might be the best way to decrease this disproportionate mortality. Yet concern for an increased risk to adult split recipients has discouraged its widespread adoption. We aimed to determine the current risk of graft failure in adult recipients after split-liver transplantation. STUDY DESIGN United Network for Organ Sharing data from 62,190 first-time adult recipients of deceased-donor liver transplants (1995-2010) were analyzed (889 split grafts). Bivariate risk factors (p < 0.2) were included in Cox proportional hazards models of the effect of transplant type on graft failure. RESULTS Split-liver recipients had an overall hazard ratio of graft failure of 1.26 (p < 0.001) compared with whole-liver recipients. The split-liver hazard ratio was 1.45 (p < 0.001) in the pre-Model for End-Stage Liver Disease era (1995-2002) and 1.10 (p = 0.28) in the Model for End-Stage Liver Disease era (2002-2010). Interaction analyses suggested an increased risk of split-graft failure in status 1 recipients and those given an exception for hepatocellular carcinoma. Excluding higher-risk recipients, split and whole grafts had similar outcomes (hazard ratio = 0.94; p = 0.59). CONCLUSIONS The risk of graft failure is now similar between split and whole-liver recipients in the vast majority of cases, which demonstrates that the expansion of split-liver allocation might be possible without increasing the overall risk of long-term graft failure in adult recipients. Additional prospective analysis should examine if selection bias might account for the possible increase in risk for recipients with hepatocellular carcinoma or designated status 1.

Preservation of intestinal motility after the serial transverse enteroplasty procedure in a large animal model of short bowel syndrome

INTRODUCTION Serial transverse enteroplasty (STEP) has been shown to improve bowel function in short bowel syndrome. The effect of the STEP procedure on intestinal motility is not known, but some have hypothesized that it could disrupt bowel innervation and thus impair intestinal motility. METHODS Growing Yorkshire pigs (n = 7) underwent 3 operations at 6-week intervals: (1) reversal of 50 cm of jejunum, (2) 90% bowel resection +/- STEP to the proximal dilated bowel (4 STEP, 3 control), and (3) implantation of serosal strain gauges. At each operation, baseline and post-octreotide small intestinal motility was studied with continuously perfused manometry catheters using non-anticholinergic anesthesia. In addition, awake monitoring was performed using strain gauge analysis 1 week after the third operation. Characteristics of phase III of the migrating motor complex (MMC) were compared between and within groups using t test, chi(2), and analysis of variance, with significance set at P < .05. RESULTS Manometry data from the third surgery revealed no differences between groups or compared with baseline within groups for the presence and characteristics of phase III of the MMC. Specifically, the mean amplitude and frequency of phase III after octreotide, and both the mean baseline and mean octreotide-stimulated motility indices were equivalent. The duration of phase III after octreotide stimulation was significantly increased in the STEP animals, suggesting a potential benefit of the STEP procedure. Strain gauge analysis, performed in awake animals, confirmed no differences between the groups for basal and octreotide-stimulated characteristics of phase III of the MMC. CONCLUSIONS These preliminary data suggest that the STEP procedure in a porcine model of short bowel syndrome does not interfere with baseline or hormonally stimulated motility within the small bowel. These findings further support the STEP procedure as a safe option for the surgical management of short bowel syndrome.