Hyperinsulinemic hypoglycemia in adolescents: case report and systematic review.

BACKGROUND: Hyperinsulinemic hypoglycemia is the most common cause of severe and persistent hypoglycemia in neonates and children. It is a heterogeneous condition with dysregulated insulin secretion, which persists in the presence of low blood glucose levels. CASE PRESENTATION: We report a case of a 15 year-old male with hyperinsulinemic hypoglycemia, who underwent a subtotal pancreatectomy after inadequate response to medical therapy. Pathological examination was positive for nesidioblastosis (diffuse ß-cell hyperplasia by H-E and immunohistochemical techniques). The patient's blood glucose levels normalized after surgery and he remains asymptomatic after 1 year of follow-up. The systematic review allowed us to identify 41 adolescents from a total of 205 cases reported in 22 manuscripts, from a total of 454 found in the original search done in PubMed and Lilacs. CONCLUSIONS: Although very well reported in children, hyperinsulinemic hypoglycemia can occur in adolescents or young adults, as it happens in our reported case. These patients can be seen, treated and reported by pediatricians or adult teams either way due to the wide age range used to define adolescence. Most of them do not respond to medical treatment, and subtotal distal pancreatectomy has become the elected procedure with excellent long-term response in the vast majority.

Pancreas Transplantation at a Single Latin-American Center; Overall Results with Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Simultaneous pancreas-kidney transplantation (SPK) has become the treatment of choice for type 1 diabetes mellitus (T1DM) patients with chronic renal failure. Type 2 diabetes mellitus (T2DM), was once considered to be a contraindication for pancreas transplantation; however, it has been accepted as a new indication, under strict criteria. Although favorable results have increase the indication for T2DM in developed countries, there have been no reports of long-term results for this indication from Latin American centers. METHODS: From April 2008 to March 2016, patients receiving SPK or pancreas transplant alone (PTA) for T2DM were included and compared with T1DM recipients. Variables were compared between groups with the use of χ2 and t tests; Kaplan-Meier with log rank was used for patient and graft survivals; P < .05 was considered to be significant. RESULTS: A total of 45 SPK and 1 PTA were performed, 35 (76.1%) for T1DM and 11 (24.5%) for T2DM. Mean pre-transplantation C-peptide was significantly higher in the T2DM group (P = .01); HbA1c was higher in the T1DM group (P = .03). No differences were found in weight, body mass index, and pre-transplantation glycemia. Patient survivals for T1DM recipients were 88.2% and 84.8% at 1 and 5 years, respetively, versus 100% and 74.1% for T2DM recipients (P = .87). CONCLUSIONS: Our initial prospective experience in a single Latin American center showed that medium- and long-term outcomes for T1DM and T2DM individuals receiving pancreas transplants are similar, under strict selection criteria.

Paneth and intestinal stem cells preserve their functional integrity during worsening of acute cellular rejection in small bowel transplantation.

Graft survival after small bowel transplantation remains impaired due to acute cellular rejection (ACR), the leading cause of graft loss. Although it was shown that the number of enteroendocrine progenitor cells in intestinal crypts was reduced during mild ACR, no results of Paneth and intestinal stem cells localized at the crypt bottom have been shown so far. Therefore, we wanted to elucidate integrity and functionality of the Paneth and stem cells during different degrees of ACR, and to assess whether these cells are the primary targets of the rejection process. We compared biopsies from ITx patients with no, mild, or moderate ACR by immunohistochemistry and quantitative PCR. Our results show that numbers of Paneth and stem cells remain constant in all study groups, whereas the transit-amplifying zone is the most impaired zone during ACR. We detected an unchanged level of antimicrobial peptides in Paneth cells and similar numbers of Ki-67+ IL-22R+ stem cells revealing cell functionality in moderate ACR samples. We conclude that Paneth and stem cells are not primary target cells during ACR. IL-22R+ Ki-67+ stem cells might be an interesting target cell population for protection and regeneration of the epithelial monolayer during/after a severe ACR in ITx patients.

Right Extended Split Liver Transplantation Compared With Whole Liver Transplantation: Lessons Learned at a Single Center in Latin America-Results From a Match Case-Control Study.

BACKGROUND: Despite the progressively increasing gap between patients waiting for liver transplant under the Model for End-stage Liver Disease MELD system and the availability of deceased donor organs, the use of right extended split liver grafts (RESLG) has not been accepted by all centers. In this study, we compared the results obtained using RESLG vs a group of matched whole liver graft (WLG) recipients at a single center in Latin America. METHODS: A single-center retrospective review performed between August 2009 and December 2015. RESULTS: Fifteen RESLGs were implanted to recipients between 13 and 70 years of age; 80% were performed ex situ. The "biological MELD" score for the RESLG group was 17.5 ± 5.6, and it was 12.8 ± 4.5 for the WLG group (P = .01). Cold ischemia times were significantly longer in RESLG recipients compared with WLG recipients (528 minutes vs 420 minutes; P < .01). No significant differences were found in biliary (leak or strictures P = .40) and arterial complications (hepatic artery thrombosis, P = .06). RESLG patients benefited from a considerable reduction on their waiting time in list. The 1-, 3-, and 5-year patient survival rates were 93%, 93%, and 93% respectively, for RESLG recipients vs 100%, 95.7%, and 86.1%, respectively, for WLG recipients. The 1-, 3-, and 5-year graft survival rates were 79.4%, 79.4%, and 79.4% for RESLG recipients and 89.7%, 89.7%, and 89.7% for WLG recipients, respectively. No statistical differences were observed. CONCLUSION: RESLG allows expeditious transplantation for low MELD recipients. Its use should be expanded in Latin America and worldwide as a valid alternative to increase the donor pool as it has been used in other regions.

Use of Nonvascularized Abdominal Rectus Fascia After Liver, Small Bowel, and Multiorgan Transplantation: Long-Term Follow-up of a Single-Center Series.

BACKGROUND: The abdominal wall may be severely compromised in the vast majority of intestinal and multiorgan transplant candidates, and sometimes as a consequence of complex liver transplantation. Multiple options have been described to overcome this problem, varying from component separation to the extreme need of performing an abdominal wall transplantation. The aim of the present paper is to report the largest and longest-term results of patients that received an abdominal rectus fascia (ARF) after liver, intestinal, or multiorgan transplantation at a single transplant center. METHODS: This is a retrospective report of a prospectively collected dataset of all the patients that received ARF during liver, isolated intestine, combined, or multiorgan transplantation at Fundación Favaloro from May 2006 to June 2016. RESULTS: A total of 19 out of 528 patients (3.5%) that underwent abdominal organ transplant received an ARF graft: 17 patients after receiving an intestine-containing graft, and 2 after liver retransplantations. Three patients required changing the ARF, 2 with a synthetic mesh and 1 with another ARF. Five patients required late reoperations: A relaparotomy was performed by transecting the ARF without encountering adhesions on the inner ARF surface. None of the 2 patients who received liver retransplantations and ARF developed acute or chronic ventral defects. CONCLUSIONS: The use of ARF is a simple and reliable surgical option to close abdominal wall defects during transplantation, the fascia adequately incorporates to the abdominal wall, allowing it to be transected and resutured in the long term and preserving the integrity of the peritoneal layer.

Thomas Starzl, Video Interview for His Living Legend Award at the ISBTS 2015.

At the 14th International Small Bowel Transplant Symposium, (ISBTS2015) held in Buenos Aires, a session to recognize the pioneers that have dedicated their lives to make our current field possible was organized. Dr Thomas Starzl received the first Living Legend Award. A video interview was obtained at his office, edited, and later presented during the scientific meeting. More than 600 people saw Dr Starzl's interview, which captivated the audience for 40 minutes, before smiles, tears and the final applause erupted at the conclusion. We would like to share this video with all of you to inspire the current generations and the generations to come. The manuscript has the main parts of the interview, which can also be accessed at http://isbts2015.tts.org/starzl.mp4.

Long-Term Outcomes of Intestinal and Multivisceral Transplantation at a Single Center in Argentina.

BACKGROUND: Intestinal failure (IF) patients received parenteral nutrition (PN) as the only available therapy until intestinal transplantation (ITx) evolved as an accepted treatment. The aim of this article is to report the long-term outcomes of a series of ITx performed in pediatric and adult patients at a single center 9 years after its creation. PATIENTS AND METHODS: This is a retrospective analysis of the ITx performed between May 2006 and January 2015. Diagnoses, pre-ITx mean time on PN, indications for ITx, time on the waiting list for types of ITx, mean total ischemia time, and warm ischemia time, time until PN discontinuation, incidence of acute and chronic rejection, and 5-year actuarial patient survival are reported. RESULTS: A total of 42 patients received ITx; 80% had short gut syndrome (SG); the mean time on PN was 1620 days. The main indication for ITx was lack of central venous access followed by intestinal failure-associated liver disease (IFALD) and catheter-related infectious complications. The mean time on the waiting list was 188 days (standard deviation, ±183 days). ITx were performed in 26 children and 14 adults. In all, 32 procedures were isolated ITx (IITX); 10 were multiorgan Tx (MOT; 3 combined, 7 multivisceral Tx (MVTx), 1 modified MVTx and 2 with kidney); 2 (4.7 %) were retransplantations: 1 IITx, 1 MVTx, and 5 including the right colon. Thirteen patients (31%) received abdominal rectus fascia. All procedures were performed by the same surgical team. Total ischemia time was 7:53 ± 2:04 hours, and warm ischemia time was 40.2 ± 10.5 minutes. The mean length of implanted intestine was 325 ± 63 cm. Bishop-Koop ileostomy was performed in 67% of cases. In all, 16 of 42 Tx required early reoperations. The overall mean follow-up time was 41 ± 35.6 months. The mean time to PN discontinuation after Tx was 68 days (P = .001). The total number of acute cellular rejection (ACR) episodes until the last follow-up was 83; the total number of grafts lost due to ACR was 4; and the total graft lost due to chronic rejection was 3. At the time of writing, the overall 5-year patient survival is 55% (65% for IITx vs 22% for MOT; P = .0001); 60% for pediatric recipients vs 47% for adults (P = NS); 64% when the indication for ITx was SG vs 25% for non-SG (P = .002). CONCLUSIONS: At this center, candidates with SG, in the absence of IFALD requiring IITx, showed the best long-term outcomes, independent of recipient age. A multidisciplinary approach is mandatory for the care of intestinal failure patients, to sustain a rehabilitation and transplantation program over time.

Modified liver-free multivisceral transplantation for a metastatic small bowel neuroendocrine tumor: a case report.

Neuroendocrine tumors originating from the small bowel frequently metastasize to the lymph nodes and/or liver. Although surgical extirpation of the primary tumor and locoregional metastases epitomizes the management of patients with such tumors, this is not always possible with conventional surgical techniques. Nonresectable, slow-growing tumors involving the mesenteric root represent a generally accepted indication for deceased donor intestinal and multivisceral transplantation. Furthermore, vascularized sentinel forearm flaps offer opportunities for monitoring graft rejection and tailoring immunosuppression regimens. Here, we report the first documented case of modified liver-free multivisceral transplantation preceded by neoadjuvant 177-lutetium peptide receptor radionuclide therapy in a patient with a small bowel neuroendocrine tumor and extensive lymph node metastases in the mesenterium. At a follow-up of 21 months the patient is biochemically and radiologically disease-free.

Immunological status of isolated lymphoid follicles after intestinal transplantation.

Intestinal transplantation (ITx) faces the challenge of grafting a high immunogenic organ, which is certainly one of the major obstacles for intestinal allograft acceptance. The allograft has to guarantee the proper functioning of the mucosal immune machinery under immunosuppressive conditions. Recently, it has been elucidated that isolated lymphoid follicles (ILFs) are an indispensable part of mucosal immunity to maintain IgA synthesis and consequently to control commensal microflora. No data about these follicular structures in the setting of ITx are available so far. Therefore, we addressed the question whether constitution, integrity and function of allograft ILFs are disturbed by immunosuppressive regimen. We compared allograft ILFs from terminal ileum of transplant patients with ILFs from nontransplant patients via flow cytometry, quantitative real-time polymerase chain reaction and immunohistochemistry. We found that host leukocytes rapidly repopulate allograft ILFs and that maintenance immunosuppressive regimen, tacrolimus and corticosteroids, does not affect their cellular integrity and function. However, allograft ILFs revealed a higher maturation state than control samples and IgA positive plasma cells were increased in number in allograft mucosa. Our results open the path for a better understanding of allograft mucosal immunity.

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.

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.

Effect of ischemia-reperfusion on the incidence of acute cellular rejection and timing of histologic hepatitis C virus recurrence after liver transplantation.

BACKGROUND: Because of a critical shortage of deceased donor (DD) livers, more extended criteria allografts are being utilized; these allografts are at increased risk for ischemia-reperfusion injury (IRI). We assessed whether, in a large cohort of patients transplanted for hepatitis C virus (HCV) either via a DD or live donor (LD), there was a relationship between the degree of IRI and the frequency and timing of acute cellular rejection (ACR) and histologic HCV recurrence. METHODS: During an 8-year study, patients were separated into four groups based on peak alanine aminotransferase (ALT) levels and three groups based on severity of IRI on postreperfusion liver biopsy. RESULTS: The mean follow-up time of 433 DD and 44 LD recipients was 1212 days. We noted a strong correlation in DD between peak ALT and the histologic degree of IRI (P = .01). There was no difference in the incidence or grade of ACR among the four groups. There was no correlation between the severity of IRI and the incidence or time to histologic recurrence of HCV. CONCLUSIONS: The magnitude of peak ALT correlated with the severity of IRI on postreperfusion liver biopsy. Among this large HCV cohort, there was no correlation between the severity of IRI and the incidence or timing of histologic HCV recurrence or incidence of ACR.

Strongyloides hyperinfection syndrome after intestinal transplantation.

Strongyloides stercoralis is a helminth with the ability to autoinfect the human host and persist asymptomatically for several years. Immunosuppression can accelerate autoinfection and result in Strongyloides hyperinfection syndrome (SHS), which is associated with significant morbidity and mortality. Immunosuppressed solid organ transplant recipients, particularly in the setting of rejection, are at increased risk for reactivation of latent infections, such as Strongyloides. We describe a case of SHS in an intestinal transplant recipient; we hypothesize that she acquired the infection from the donor. We also review the current literature and address both prophylaxis and treatment of strongyloidiasis in the solid organ transplant patient.

Accurate method for clinical assessment of right lobe liver weight in adult living-related liver transplant.

INTRODUCTION: Prior to transplantation of segmental liver grafts to adult recipients, it is crucial to confirm that the graft size is safe for the donor, yet adequate for the recipient's metabolic needs. Computed tomography (CT) and magnetic resonance imaging (MRI) are the current best standards. We applied a new formula to estimate right liver lobe weight in living donors and compared our results with CT and MRI. METHODS: Between August 1998 and December 20, 91 adults received right lobes from living donors. Donor liver volumes were assessed by CT or MRI. Actual weights of right lobe grafts were determined after back table flushing. We estimated whole liver weights using the formula: 772 x body surface area (BSA). Right lobe liver weight was calculated as 57% of the estimated whole liver weight (R-57). RESULTS: Mean actual right lobe weight (n = 90) was 855.83 +/- 183.4 g. Estimated right lobe weight was 858.08 +/- 90.80 (R-57, P = NS); 1077.35 +/- 263.07 mL for CT (P = .0001), and 1185.07 +/- 350.10 mL for MRI (P = .0001). Mean graft-recipient weight ratio (GRWR) was 1.23%; there was no significant difference with R-57 GRWR but there was a difference from CT and MRI-GRWR (P = .001). The proportion of cases of estimated right lobe weight and GRWR within 20% of the corresponding actual value were 80% and 90%, respectively, for R-57 versus 36% and 43% for the imaging studies (P = .0001). CONCLUSION: With readily available software to calculate BSA, physicians can predict right lobe weight knowing only the donor's height and weight. CT and MRI will only be necessary for anatomic liver mapping.

A simple new formula to assess liver weight.

INTRODUCTION: In cadaveric or segmental liver transplantation, accurate assessment of graft volume is desirable but not always easy to achieve based on donor morphometric data. We sought to establish a simple, reliable formula for accurate prediction of liver volume. METHODS: Data from 1,413 cadaveric adult and pediatric liver donors were analyzed using simple and multiple regression analysis. Liver weight (LW) was plotted against age, height, body weight (BW), body surface area (BSA) or body mass index (BMI); a formula was developed using simple regression: LW (g) = 772 (g/m(2)) x BSA, r = 0.73, P <.01. For donors with BSA 1.0, there was no significant difference between the actual and the estimated mean LW as calculated by the new formula. For pediatric donors, there was no significant difference between estimated and actual mean liver weight with any formula. When the new formula was applied, the difference between the actual and the estimated liver weight was acceptable (<20%) in 1040 (73.6%) cases. In all races, there was no significant difference between actual and estimated mean liver weight as calculated by this formula. CONCLUSIONS: A simple formula to calculate liver weight in donors with BSA >1.0 is: LW = 772 x BSA, and for donors with BSA

Noninvasive preoperative evaluation of biliary anatomy in right-lobe living donors with mangafodipir trisodium-enhanced MR cholangiography.

BACKGROUND: Accurate preoperative radiologic imaging is essential to assess the vascular and biliary anatomy of right-lobe living donors and to ensure their safety. Volumetric magnetic resonance cholangiography (MRCP) using Mangafodipir trisodium (Mn-DPDP) contrast has been recently proposed to evaluate the biliary anatomy of living donor candidates. METHODS: During their preoperative evaluation, 18 right-lobe (RL) living donors underwent 3D Mn-DPDP-enhanced MRCP in addition to the standard thin- and thick-slab MRCP imaging. Immediately prior to hepatectomy all 18 RL donors underwent intraoperative cholangiography (IOC) via the cystic duct. We compared the efficacy of these different radiologic techniques to actual intraoperative IOC findings. RESULTS: Sixty-eight intrahepatic bile ducts were identified on IOC, 67(98.5%) by Mn-DPDP-enhanced 3D MRCP, 41 (60%) by thick-slab SSFSE imaging, and 35 (51%) by thin-slice SSFSE imaging. Mn-DPDP-enhanced 3D MRCP detected 100% (n = 5) of the anomalous origins of the right bile duct, and thick-slab MRCP detected 20% (n = 1) and thin-slab MRCP detected 0%. Anterior and posterior right intrahepatic bile ducts were identified by MnDPDP-enhanced 3D MRCP 100% of the time, by thick-slab SSFSE imaging 35% of the time, and by thin-slice SSFSE imaging only 12% of the time. CONCLUSIONS: Mn-DPDP-enhanced 3D MRCP imaging was highly sensitive and specific in identifying variants of the intrahepatic bile ducts. This technique should be included in the standard protocol of preoperative radiologic evaluation of RL living donor candidates.

Trasplante hepático ortotápico en ratas. Técnica quirúrgica, complicaciones y sus tratamientos / Orthotopic liver transplantation in rats

The orthotopic rat liver transplant model is a widely used technique in transplantation research. It has many advantages over other animal transplant models because of its availability and low cost. However, it must be emphasized that success with the rat model requires thorough training. The aim of this paper is to describe the microsurgical technique involved in 60 rat liver transplants and to discuss the complications and their treatments. Forty-nine liver transplants were performed at the Experimental Laboratory of the University Hospital, Ontario, Canada (ELUH) and 11 were performed at the Laboratorio de Trasplante de Organos de la Facultad de Ciencias Medicas de La Plata, Buenos Aires. Argentina (LTO). Among the transplants performed at the ELUH, the observed complications were haemorrhage (n = 4), pneumothorax (n = 1), anastomotic failure (n = 15), bile leak (n = 3), and bile duct necrosis (n = 9). The remaining 17 rats at the ELUH were healthy at day 7 after surgery. Animal survival immediately postop, at 24 hours postop and at 7 days postop was achieved with the 9th, 20th and 21st transplants respectively. At the LTO, 3 rats died as a result of anaesthetic complications. Seven-day animal survival was achieved with the 11th transplant. We beleive that the description of the orthotopic rat liver transplantation technique, as well as the discussion regarding complications and their management, can be useful for researchers interested in performing liver transplantation in rats

Trasplante hepático ortotápico en ratas. Técnica quirúrgica, complicaciones y sus tratamientos / Orthotopic liver transplantation in rats

The orthotopic rat liver transplant model is a widely used technique in transplantation research. It has many advantages over other animal transplant models because of its availability and low cost. However, it must be emphasized that success with the rat model requires thorough training. The aim of this paper is to describe the microsurgical technique involved in 60 rat liver transplants and to discuss the complications and their treatments. Forty-nine liver transplants were performed at the Experimental Laboratory of the University Hospital, Ontario, Canada (ELUH) and 11 were performed at the Laboratorio de Trasplante de Organos de la Facultad de Ciencias Medicas de La Plata, Buenos Aires. Argentina (LTO). Among the transplants performed at the ELUH, the observed complications were haemorrhage (n = 4), pneumothorax (n = 1), anastomotic failure (n = 15), bile leak (n = 3), and bile duct necrosis (n = 9). The remaining 17 rats at the ELUH were healthy at day 7 after surgery. Animal survival immediately postop, at 24 hours postop and at 7 days postop was achieved with the 9th, 20th and 21st transplants respectively. At the LTO, 3 rats died as a result of anaesthetic complications. Seven-day animal survival was achieved with the 11th transplant. We beleive that the description of the orthotopic rat liver transplantation technique, as well as the discussion regarding complications and their management, can be useful for researchers interested in performing liver transplantation in rats (AU)