Cal Matsumoto

One Hundred Nine Living Donor Liver Transplants in Adults and Children: A Single-Center Experience

ObjectiveTo summarize the evolution of a living donor liver transplant program and the authors’ experience with 109 cases. Summary Background DataThe authors’ institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. MethodsDonors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. ResultsAfter ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. ConclusionLiving donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.

Inclusion of the colon in intestinal transplantation.

Purpose of reviewInclusion of the colon as a component of an intestinal graft has evolved over the past two decades. Initially thought to be hazardous and abandoned by many centers, colon inclusion has now proven to be an integral component of the intestinal transplant graft.The purpose of this review is to summarize the history of colon inclusion, the physiology of the colon, surgical techniques of colon inclusion, and outcome data. Recent findingsRecent studies at centers of excellence report the efficacy and safety of colon inclusion in intestinal transplantation. Quality-of-life indicators, stool patterns, fecal continence, and parenteral nutrition weaning were noted to be improved in recipients of colonic inclusion. Complex intestinal transplant case series were reported with no adverse effects of colon inclusion. SummaryColon inclusion provides a necessary function in intestinal transplantation by taking advantages of its physiologic functions of water absorption, residue breakdown, and storage. Current clinical evidence supports the efficacy of selective and cautious use of the colon in intestinal transplantation.

Gastrointestinal infections in solid organ transplant recipients

Purpose of reviewThe population of immunosupressed individuals in the world is increasing every year. Solid organ transplant recipients continue to increase at a steady rate, and with each year, new information on unusual clinical presentations of bacterial, viral, and fungal pathogens emerge. The significant morbidity and mortality from undiagnosed gastrointestinal infections in the solid organ transplant recipient makes it important to diagnose early and understand that many of these pathogens require special methods for detection and isolation. Recent findingsThis review examines the published reports of gastrointestinal infections in solid organ transplant recipients in the past year. Cytomegalovirus infection continues to be an important gastrointestinal pathogen. Gastrointestinal CMV disease has been associated with biliary complications, ischemic colitis, and colocutaneous fistulae after solid organ transplantation. Detection on CMV utilizing qualitative polymerase chain reaction of upper gastrointestinal tract biopsy material has shown to be an accurate method for the detection of CMV. Adenovirus and calicivirus are significant intestinal pathogens after intestinal transplantation and necessitates early diagnosis and treatment. Bacterial pathogens such as Clostridium difficile, Listeria monocytogenes, and Vibrio parahaemolyticus, as well as the fungal pathogen Cryptococcus neoformans, can all present with unusual gastrointestinal symptoms. SummaryAs the number and type of solid organ transplant recipients continues to increase every year, newer pathogens will continue to emerge, as well as more unusual clinical presentations of more established pathogens. Appropriate and timely diagnosis of gastrointestinal tract infection in solid organ transplant recipients is particularly challenging as many symptoms mimic less morbid conditions, infected tissue is not readily accessible for analysis, and many of these pathogens require special processing for diagnosis.

Voriconazole-associated Myositis

Voriconazole is a new triazole antifungal agent that is now the treatment of choice for invasive aspergillosis. Drug-induced myopathy has never previously been reported with voriconazole, although it is recognized with other triazole agents. We present a 34-year-old female African American renal transplant recipient, with a prior history of probable statin-induced myopathy, who developed severe generalized weakness with marked elevation of muscle enzymes and inflammatory changes on T2-weighted fat-suppressed STIR sequence magnetic resonance imaging (MRI) after commencing voriconazole for treatment of invasive aspergillosis. Her symptoms resolved and creatine kinase normalized upon stopping the drug.Given the increased use of triazoles in immunosuppressed and transplant recipients, it is important for rheumatology consultants to include this entity in their differential diagnosis of weakness in such patients.

Chronic mucosal inflammation/inflammatory bowel disease-like inflammation after intestinal transplantation: where are we now?

Purpose of reviewThe purpose of this review is to highlight the similarities between inflammatory bowel disease and the state of the intestine allograft after transplantation. Recent findingsThe mutant nucleotide-binding oligomerization protein 2 (NOD2) gene, which encodes for an intracellular protein that serves as an innate immune system microbial sensor in macrophages, dendritic cells, and certain intestinal epithelial cells, has been recognized as a risk factor in Crohns disease. Similarly, recent studies have also highlighted the contribution the NOD2 mutation may have on intestinal failure itself. More specifically, in intestinal transplant recipients with the NOD2 mutation, the discovery of the reduced ability to prevent bacterial clearance, increased enterocyte stress response, and failure of key downstream expression of important cytokines and growth factors have been implicated as major factors in intestinal transplant outcomes, namely graft loss and septic death. Treatment strategies with anti tumor necrosis factor (TNF) &agr;, similar to inflammatory bowel disease, have been employed in intestinal transplantation with promising results. SummaryIn intestinal transplantation, there is evidence that the classical alloimmunity pathways that lead toward graft dysfunction and eventual graft loss may, in fact, be working in concert with a disordered innate immune system to produce a state of chronic inflammation not unlike that seen in inflammatory bowel disease.

The microbiome and its implications in intestinal transplantation.

Purpose of reviewThis article summarizes the complex interplay between the microbiota and host immune responses, and its impact on intestinal transplantation and allograft rejection. Recent findingsRecent findings highlight the importance of Paneth cells as crucial producers of antimicrobial peptides that control the intestinal host-microbial interface as well as the essential role of NOD2 as a master regulator of antimicrobial host defenses. Moreover, complex interactions between innate and adaptive immune responses have been shown to critically shape host antimicrobial Th17 responses, which may be key for the pathogenesis of inflammatory bowel diseases and intestinal allograft rejection. SummaryA growing body of evidence indicates that crosstalk between the microbiome and innate and adaptive host immunity determines alloimmune responses and outcomes in intestinal transplantation. Elaboration of this emerging field might lead to novel mechanistic insight into these complex interactions and allow for new therapeutic approaches.

Advances in allograft monitoring after intestinal transplantation.

Purpose of reviewThe intestinal allograft, with an enormous lymphoid load, is a highly immunogenic organ which elicits a strong alloimmune response. In the early posttransplant period, a robust graft biopsy protocol via a temporary ileostomy is utilized for surveillance to detect rejection. In the later posttransplant period, after enteral continuity is reestablished, graft biopsies via a colonoscopy become more cumbersome. Alternative methods for intestinal allograft monitoring other than graft biopsy are of particular interest. Recent findingsBiomarkers and diagnostic tools, such as granzyme B, perforin, fecal calprotectin, citrulline, donor-specific antibody, and zoom video endoscopy have all been studied for application as reliable methods of performing intestinal allograft surveillance. Each modality has the capability to monitor a separate and unique process in the host-allograft immune response. SummaryThe goal to find a reliable, reproducible, and noninvasive method for intestinal graft monitoring remains an elusive one. Many of the current modalities available only serve to act as complementary tests in conjunction with astute clinical observations. Graft biopsy remains the gold standard for monitoring the intestinal allograft.

Regimens for intestinal transplant immunosuppression

Purpose of reviewDue to recent advances in surgical technique, immunosuppression, and antiviral therapy, intestinal transplant has become a valid treatment for intestinal failure. Successful primary closure of the abdominal wall following transplantation is not always feasible for a variety of reasons. Factors contributing to difficult closure include the history of previous surgery with loss of abdominal laxity and a contracted intra-abdominal compartment often combined with a history of fistulae or ostomies. Primary closure under tension is contraindicated. Further, traditional reconstructive techniques are usually not appropriate in this patient population. Therefore, the development of alternate techniques to achieve abdominal closure is an important aspect in intestinal transplantation. Recent findingsWe will discuss and highlight the various approaches to deal with this problem both before and after transplantation. We will highlight recent approaches proposed in the literature including reduced size grafts, use of a prosthetic patch, and abdominal wall transplantation. SummaryAs the number of intestinal and multivisceral transplants increases nationally and internationally, surgeons will need to be equipped with strategies to navigate the unique challenges that these patients present, especially regarding abdominal wall management.

Lymphatic Leak After Intestinal Transplantation: Aspects of the Donor Technique

The rich component of lymphatics makes the intestine prone to leaks of lymph after transplantation secondary to their transection during procurement. We describe our technique for isolation and ligation of the small lymphatics at the root of the mesentery during the procurement of the small intestine and report our experience with the management of lymphatic leaks posttransplant.

Current Immunosuppression in Abdominal Organ Transplantation

Organ transplantation has saved the lives of thousands of patients beginning from the mid 1950s. At the end of 2007 the Organ Procurement and Transplantation Network (OPTN) database recorded 183,222 people living with a functioning graft in the United States (Wolfe et al., 2010). Over the last two decades survival rates have continued to improve and currently 81-91% of kidney transplant recipients and 74-79% of liver transplant recipients are alive 5 years post-transplant (Wolfe et al., 2010). This success is a dramatic improvement compared to the early era of transplantation and is the result of advances in organ preservation, surgical technique, intensive care and immunosuppression. Particularly, the development of potent immunosuppressive medications has contributed significantly to the success of organ transplantation by reducing the incidence of rejection and graft loss. In recent large studies the incidence of acute rejection is reported as low as 8-15% 1 year after kidney transplant (Ekberg et al., 2009) and graft loss due to acute rejection has now become very uncommon. Clinical immunosuppression after organ transplantation has come a long way over the last fifty years. It started with total body irradiation, steroids and azathioprine (see Starzl, 2000 for a review on the history of immunosuppression). The rationale behind total body irradiation was to control the immune response to the allograft by ablation of the bone marrow, a similar principle applied today with the use of depleting agents (see below). Other early attempts at controlling the bone marrow and obtain lymphocyte depletion included splenectomy, thymectomy and thoracic duct drainage, but these had limited success. Instead, anti-lymphocyte globulin (ALG), prepared from the serum of horses or rabbits inoculated with human lymphocytes, was introduced in 1966 with the aim of mitigating cellular immunity using heterologous antibodies. (Starzl et al., 1967) From the early 1960s to 1980s post-transplant immunosuppression consisted of azathioprine, high dose corticosteroids and antilymphocyte globulin. Cyclosporine was introduced in the early 1980s, followed by monoclonal antibodies, then by tacrolimus in the 1990s and lately by mycophenolic acid and sirolimus (see list below). Immunosuppression regimens have changed since the early era of transplantation as a result of the development of new drugs. Furthermore, the number of available drugs continues to increase. This article will describe the immunosuppressive drugs currently used in clinical transplantation and will focus on recent developments. We will also review current organ-specific IMS protocols