Luciano Vargas

Calprotectin - A novel noninvasive marker for intestinal allograft monitoring

Objective:To identify a noninvasive screening test for intestinal allograft monitoring. Summary Background Data:Intestinal allograft rejection is difficult to distinguish from other causes of diarrhea and can rapidly lead to severe exfoliation or death. Protocol biopsies are standard for allograft monitoring but may cause serious complications. No noninvasive test has shown clinical utility for monitoring of the intestinal allograft. Methods:Calprotectin levels (n = 68) were measured in this pilot study from ileostomy effluent in patients with histologic evidence of acute rejection (n = 12), viral enteritis (n = 5), and nonspecific inflammation (n = 16) and compared with those with normal allograft histology (n = 35). Results:Median stool calprotectin levels from patients with rejection were significantly higher than those from patients with viral enteritis or normal biopsies [198 mg/kg compared with 7 and 19 mg/kg, respectively (P = 0.0002)]. Receiver operator characteristics suggest the optimal cut-off level to distinguish rejection from other diagnoses is 92 mg/kg with specificity of 77% and sensitivity of 83%. Although false-positive results occurred in 26% of patients with normal biopsies and 30% with nonspecific changes, no treated episode of acute rejection was below the cutoff. In addition, in 2 patients with serial levels, elevations in the calprotectin levels preceded histologic changes by 6 to 18 days. Conclusions:Low stool calprotectin levels correlate well with a low risk for intestinal allograft rejection. If confirmed, biopsies may be reserved in the future for confirmation of rejection, eliminating protocol biopsies, and immunosuppressive changes could potentially be made before allograft injury.

Adenovirus: Current Epidemiology and Emerging Approaches to Prevention and Treatment

Infections caused by adenoviruses are associated with significant morbidity and mortality in both hematopoietic stem cell and solid organ transplant recipients. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung and small-bowel transplant recipients. Management of these infections may be difficult and includes reduction of immunosuppression whenever possible combined sometimes with antiviral therapy (mainly cidofovir). The currently available antiviral therapy is limited by the need for intravenous administration, potentially significant renal and hematologic toxicities. New emerging therapies such as brincidofovir and transfusion of adenovirus-specific T-lymphocytes may increase the available armamentarium for these potentially life-threatening infections.

Is Bacteremic Sepsis Associated With Higher Mortality in Transplant Recipients Than in Nontransplant Patients? A Matched Case-Control Propensity-Adjusted Study

BACKGROUND Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking. METHODS This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis. RESULTS Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture-proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48-45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07-1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71-135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006-.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89-.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09-.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20-.89], P = .025). CONCLUSIONS The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response.

Serial Transverse Enteroplasty Allows Children with Short Bowel to Wean from Parenteral Nutrition

OBJECTIVE To analyze the effects of serial transverse enteroplasty (STEP) on parenteral and enteral calories in children with short bowel syndrome, and examine short- and long-term complications. STUDY DESIGN A retrospective analysis of prospectively-collected data from a large single center cohort of patients undergoing STEP procedure was analyzed. Baseline demographic and clinical information, operative data, and short- and long-term complications were recorded. Detailed growth and nutritional data were obtained for 6 months prior and 12 months following STEP procedure. RESULTS Sixty-eight procedures were performed in 51 patients over a 68-month period. Median bowel length at first STEP was 51 cm with a median length gain of 54%. Repeat STEP patients had longer initial length (77 cm) and reduced length gain (20%). Operative times and blood loss were low, with few complications. Parenteral calorie requirement was stable or rising for 6 months prior to STEP, but decreased to median <20 kCal/kg/d at 1 year postop. Longer length gains were associated with higher risk of stricture formation. Seven children were transplanted, and 60% of nontransplanted children were enterally independent, with the remainder making ongoing progress; 48/51 children are alive at a median of 39 months follow-up. CONCLUSIONS STEP is shown to be safe, well tolerated, and to have definitive benefit in reducing parenteral calorie requirements over the first year following the procedure. It has an important role in achieving enteral independence in children with short bowel syndrome.

Stool Calprotectin Monitoring After Small Intestine Transplantation

Background. Small intestine transplantation is the only life-saving therapy available for patients with intestinal failure and life-threatening complications of parenteral nutrition, but it is still plagued by high levels of early acute rejection. The ability to diagnose rejection noninvasively, ideally before pathologic manifestations, would be a major advance in the care of intestinal transplant patients. Methods. We measured calprotectin levels in 732 stool samples collected, analyzed over from 72 patients having undergone 74 total transplants, and correlated them with clinical indications, ostomy output, and pathologic findings. Results. We found that overall patients with rejection have higher mean levels of stool calprotectin than those without, but because of significant interpatient variability, defining an effective general “cutoff” for the test is difficult. Each patient, in effect, has to act as their own control. Patients experiencing rejection episodes have greater fluctuations in calprotectin levels than those without, suggesting increased “reactivity” within the graft. Our most frequent clinical indicator for biopsy, an increase in ostomy output, had no real relationship to the discovery of rejection. Conclusion. Although more frequent prospective sampling could perhaps demonstrate an advantage in early indication of rejection, based on these data, routine stool calprotectin monitoring is not strongly supported.

Parvovirus Associated Fulminant Hepatic Failure and Aplastic Anemia Treated Successfully With Liver and Bone Marrow Transplantation. A Report of Two Cases

Aplastic anemia (AA) has been observed in nearly a third of patients undergoing liver transplantation (LT) for non‐A‐E fulminant hepatic failure (FHF). Few of these patients have been successfully managed with sequential LT and bone marrow transplantation (BMT). No causative agent has been identified for the FHF or AA in these reported cases. At our center, two patients, aged 15 years and 7 years, respectively, underwent sequential living‐related LT and living‐unrelated BMT. These patients are 10/9 years and 5/4 years post‐LT/BMT. Human parvovirus B19 (HPV‐B19) was established as the causative agent for FHF in both these patients by polymerase chain reaction. This report presents the first two cases associating HPV‐B19 with FHF and AA who underwent sequential LT and BMT with excellent outcomes.

Left lobe liver transplants.

Despite its vast potential, concerns about donor safety continue to limit the expansion of living-donor liver transplantation (LDLT) in Western countries. In light of the technical refinements, relatively lower risk of complications with left lobe (LL) LDLT with comparable outcomes, and the overriding concern for donor safety, there is renewed interest in using LL allograft as the first choice for LDLT; thereby, fundamentally shifting the risks of LDLT from the donor to the recipient. There is ample evidence that LL LDLT when performed with graft inflow modification where indicated, has long-term outcomes as good as cadaveric LT.

Risk of Intestinal Malignancy in Patients With Short Bowel Syndrome

Background: Postresection intestinal adaptation is an augmented self-renewal process that might increase the risk of malignant transformation in the intestine. Furthermore, patients with short bowel syndrome (SBS) have other characteristics that might increase this risk. Our aim was to determine the incidence of new intestinal malignancy in SBS patients. Methods: We reviewed the records of 500 adult SBS patients identified from 1982–2013. There were 199 men and 301 women ranging in age from 19–91 years. Follow-up from the time of diagnosis of SBS ranged from 12–484 months. A total of 186 (37%) patients were followed >5 years. Results: The cause of SBS was postoperative in 35% of patients, malignancy/radiation in 19%, mesenteric vascular disease in 17%, Crohn’s disease in 16%, and other in 13%. Twenty-eight (6%) patients received growth stimulatory medications. Fifteen percent of patients had a prior total colectomy. Twenty-eight (6%) patients underwent intestinal transplantation, and 115 (23%) patients had a previous abdominal malignancy, including colorectal cancer in 43 patients. Thirty-six (7%) received radiation therapy. Recurrent colon cancer was found in 2 patients, one at a stoma and the other with lung metastases. New colon cancer was found in 1 patient (0.2%), a 62-year-old woman with long-standing Crohn’s disease. Conclusion: The incidence of colon cancer in this heterogenous group of patients with SBS was similar to that of the normal population. This suggests that the risk of developing a new colon cancer in patients with SBS is not increased.

Invasive pneumococcal infections in pediatric liver-small bowel-pancreas transplant recipients

Children undergoing LSBPTx are at increased risk of IPI due to splenectomy. We aimed to describe the clinical features and outcomes of IPI in pediatric LSBPTx recipients. Between 2008 and 2016, 122 LSBPTx children at our center were retrospectively reviewed. Nine patients had 12 episodes of IPI; the median age at first infection was 3.5 years (range: 1.5‐7.1 years). The median time from transplant to first infection was 3 years (range: 0.8‐5.8 years). Clinical presentation included as follows: pneumonia (n = 1), bacteremia/sepsis (n = 7), pneumonia with sepsis (n = 1), meningitis with sepsis (n = 2), pneumonia and meningitis with sepsis (n = 1). The overall risk for IPI was 7.4% or 0.9% per year. The mortality rate was 22%. Seven (78%) children had received at least one dose of PCV13, four (44%) patients had received 23‐valent pneumococcal polysaccharide vaccine prior to IPI. All patients were on oral penicillin prophylaxis. In conclusion, despite partial or complete pneumococcal immunization and reported antimicrobial prophylaxis, IPI in LSBPTx children can have a fatal outcome. Routine monitoring of pneumococcal serotype antibodies to determine the timing for revaccination might be warranted to ensure protective immunity in these transplant recipients.

Laparoscopic endoscopic combined surgery for removal of migrated coil after embolization of ruptured splenic artery aneurysm

Abstract Splenic artery aneurysm is the most common visceral arterial aneurysm. Rupture of aneurysm is a rare event but associated with a high mortality. Endovascular coil embolization of bleeding splenic artery aneurysm has emerged as a promising minimal invasive treatment and considered safer than open surgery in selected patients. Nevertheless, several complications related to coils have been reported, the rarest being coil migration and erosion. We report a case of splenic artery coil migration into the stomach and its successful removal by laparoscopic endoscopy combined surgery.