A Modified Single Mercedes Incision Surgical Technique for Simultaneous Liver Kidney Transplant: A Case Series Report.

BACKGROUND: The traditional approach in simultaneous liver-kidney transplantation (SLKT) involves two separate and sequential incisions. We describe modification of the classic Mercedes incision which limits the operation to a single incision yet provides and maintains adequate exposure enabling safe dual-allograft transplantation. METHODS: Modification of the standard Mercedes incision includes bilateral, subcostal, muscle splitting incision 4-finger-breadths below the rib-edge with a midline, cephalad incision, and inferior±medial, ipsilateral extension on the side of intended iliac fossa laterality for renovascular and ureteroneocystostomy anastomosis. RESULTS: Five consecutive patients (3 women/2 men; mean age, 49 years; median BMI, 29.8 kg/m2) underwent SLKT for end-stage liver disease and progressive hepatorenal syndrome via modified Mercedes incision approach (at a median MELD of 37) without an additional kidney transplant incision, extraperitoneal exposure, or addition of wound retractors. Two out of the five patients experienced post-op wound complications, including one with delayed wound healing and superficial dehiscence in a diabetic patient. All patients have normal dual-allograft function with four out of five beyond six months and one at two months post-transplantation. CONCLUSION: Modified Mercedes incision technique is safe and feasible. Lowering the subcostal incisions with unilateral, inferomedial extension allows adequate visualization of the lower abdominopelvic area without compromising exposure of the upper abdomen for both renal and liver allograft implantation, respectively. Further studies are needed to prove the theoretical benefits of this technique.

Kidney Transplantation in United States Native Americans: Breaking Barriers.

Advances in the field of solid-organ transplantation (SOT), namely evolution of surgical techniques, developments in immunosuppressive therapies and efforts to maximize utilization of donor allografts (deceased and living), have resulted in growing numbers of SOT performed annually in the United States (U.S.) (36,529 total organs and 21,167 kidneys transplanted in 2018). However, the Native American/American Indian (NA/AI) people of the U.S. experience enormous socioeconomic barriers such as poverty, lack of adequate healthcare, poor health literacy and geographic isolation which limit access to SOT resulting in low rates of organ donation and transplantation, poor quality of life and shorter life expectancy. The NA/AI population is at increased risk for end-stage renal disease secondary to the high prevalence of diabetes mellitus. We review existing challenges to kidney transplantation in NA/AI patients and discuss potential solutions which could improve equitable delivery of specialized healthcare to this underprivileged population.

High-dose hydroxocobalamin in end-stage liver disease and liver transplantation.

Distributive shock is a serious complication in patients with chronic or end-stage liver disease, and can be exacerbated by vasoplegia in this patient population. Vasoplegic syndrome (VS) is a state of shock refractory to catecholamines and vasopressin that is often multifactorial in liver failure patients, and can occur in any phase of liver transplantation (LT) [i.e., pre-transplantation, intraoperative, and post-transplantation]. Methylene blue (MB) has been a well-established pharmacologic therapy for VS. However, it has been known to cause dose-related toxicity. Hydroxocobalamin (HXC) is not currently FDA approved for the management of VS, but studies have demonstrated its ability to cause an increase in systolic blood pressure by hypothesized mechanisms with only minimal side effects. To date, only three other reports have demonstrated the use of HXC in LT patients, which highlighted its use both intraoperatively and post-transplantation. Our report illustrates the utility of HXC in four LT patients with VS. Two of these cases illustrate the usefulness of HXC in the pre-transplantation period, which has never been previously reported. HXC is a useful pharmaceutical agent in the management of VS, especially if contraindications to MB exist or in cases of MB-resistant vasoplegia. Further studies with large sample sizes are necessary to ascertain the optimal dosage of HXC in LT patients.

Modified Mercedes Single Incision for Combined Liver Kidney Transplant: A Case Series Report.

BACKGROUND: The traditional approach in combined liver-kidney transplantation involves 2 separate and sequential incisions. We describe a modification of the standard Mercedes incision that allows a single-incision operation while providing and maintaining adequate exposure to enable safe dual-allograft transplantation. METHODS: Modification of the standard Mercedes incision includes bilateral, subcostal, muscle splitting incision 4 fingerbreadths below the rib edge with a midline, cephalad incision and inferior ± medial ipsilateral extension on the side of intended iliac fossa laterality for renovascular and ureteroneocystostomy anastomosis. RESULTS: Five consecutive patients (3 women/2 men; mean age, 49 years; median body mass index, 29.8 kg/m2) underwent combined liver-kidney transplantation for end-stage liver disease and progressive hepatorenal syndrome via a modified Mercedes single-incision approach (at a median Model for End-stage Liver Disease of 37) without an additional kidney transplant incision, extraperitoneal exposure, or addition of wound retractors. Two out of the 5 patients experienced postoperative wound complications, including 1 with delayed wound healing and 1 with superficial dehiscence. All patients have normal dual-allograft function at or beyond 6 months posttransplantation. CONCLUSIONS: The modified Mercedes single-incision technique is safe and feasible. Lowering the subcostal incisions with unilateral, inferomedial extension allows adequate visualization of the lower abdominopelvic area without compromising exposure of the upper abdomen for both renal and liver allograft implantation. Further studies are needed to prove the theoretical benefits of this technique.

Kidney Transplant Outcomes in Indigenous People of the Northern Great Plains of the United States.

BACKGROUND: Indigenous people experience higher rates of end-stage renal disease as well as negative predictive factors that undermine kidney transplantation (KT) success. Despite these inequalities, data suggest that short-term outcomes are comparable to those of other groups, but few studies have examined this effect in the Northern Great Plains (NGP) region. METHODS: We performed a retrospective database review to determine outcomes of KT in Indigenous people of the NGP. White and Indigenous people receiving a KT between 2000 and 2018 at a single center were examined. RESULTS: A total of 622 KT recipients were included (117 Indigenous and 505 White). Indigenous patients were more likely to smoke, have diabetes, have higher immunologic risk, receive fewer living donor kidneys, and have longer waitlist times. In the 5 years after KT there were no significant differences in renal function, rejection events, cancer, graft failure, or patient survival. At 10 years posttransplant, Indigenous patients had twice the all-cause graft failure (odds ratio = 2.06; 95% confidence interval, 1.25-3.39) and half the survival rate (odds ratio = 0.47; 95% confidence interval, 0.29-0.76); however, this effect was not maintained once the effects of race, sex, smoking status, diabetes, preemptive transplant, high panel reactive antibody status, and transplant type were adjusted for. CONCLUSIONS: KT outcomes in Indigenous patients in the NGP region are similar to those of White patients 5 years posttransplant, with differences emerging at 10 years that could be diminished with greater emphasis on correcting modifiable risk factors.

Spontaneous Chylous Ascites After Liver Transplantation Secondary to Everolimus: A Case Report.

Chylous ascites (CA) is an uncommon entity with several etiologies. Only a few cases of CA have been reported as a complication after liver transplantation (LT). Most of these cases occurred within 1 month after surgery and typically resulted from traumatic intraoperative injury leading to disruption of lymphatics. Although peripheral lymphedema has been frequently correlated with use of calcineurin inhibitors, associated spontaneous CA has only been reported in a few cases after renal transplantation. We report a case of delayed spontaneous CA after LT caused by the use of the mammalian target of rapamycin (mTOR) inhibitor everolimus. Everolimus was introduced in our patient early after transplantation because of tacrolimus-induced microangiopathy, and years later the patient presented with spontaneous CA. After excluding other causes of CA, everolimus was discontinued, and immunosuppression was maintained by increasing prednisone and continuing mycophenolate mofetil. Additionally, the patient was treated with percutaneous drain placement and began a low-fat, high-protein diet. One month later the patient had complete resolution of symptoms with no recurrence of ascites. To our knowledge, this is the first case of delayed-onset CA caused by everolimus after LT.

Early Cardiopulmonary Cryptococcus neoformans Infection After Liver Transplant: A Case Report.

Cryptococcal infection (CI) is an uncommon fungal disease that poses a particular fatal risk to liver transplant (LT) recipients because of the potential rapid development and dissemination of the disease. Depending on the pathophysiology, CI may manifest with a wide range of clinical presentations that may delay early diagnosis and timely treatment. Additionally, most anticryptococcal therapies may threaten LT recipients owing to the associated hepatotoxicity of these medications. We report a case of a 25-year-old woman who received an LT for cryptogenic cirrhosis and developed rapidly progressive CI with pulmonary, myocardial, and cerebral involvement within a month of transplantation. She presented with severe pulmonary hypertension refractory to medical management and subsequently died despite our efforts. Herein, we review the etiology of cryptococcosis, the natural history of cryptococcal disease, and standard treatments for CI, and we highlight peculiarities of Cryptococcus neoformans infection in solid organ transplant recipients.

Liver transplantation and pancreatic resection: a single-center experience and a review of the literature.

Liver transplantation may occasionally be indicated in patients with unique clinical scenarios. Little is known regarding the outcomes of patients who have had a pancreatic resection prior to, in combination with, or after liver transplantation. A retrospective review of all patients undergoing liver transplantation from March 1998 to March 2008 identified 17 patients who also underwent pancreatic resection. An additional literature review was performed. Five underwent pancreatic resection prior to liver transplantation (1.7, 3.6, 3.8, 6.8, and 8.1 years), another 9 underwent pancreatic resection together with liver transplantation, and 3 underwent pancreatic resection after liver transplantation (2.2, 2.6, and 3.8 years). Indications for pancreatic resection included cholangiocarcinoma (n = 6), neuroendocrine tumor (n = 5), pancreatic cancer (n = 2), gastrointestinal stromal tumor (n = 1), periampullary adenocarcinoma (n = 1), duodenal adenomas (n = 1), and benign pancreatic mass (n = 1). Indications for liver transplantation were metastatic neuroendocrine tumor disease (n = 5), primary sclerosing cholangitis (n = 5), hepatitis C virus (n = 2), metastatic gastrointestinal stromal tumor (n = 1), Klatskin tumor (n = 1), alcohol cirrhosis (n = 1), alpha-1 antitrypsin deficiency (n = 1), and chemotherapy-induced cirrhosis (n = 1). One patient died intraoperatively, 7 patients died of tumor recurrence, 2 patients died from transplant complications, and 7 patients are still alive. Pancreatic resection-related complications included 4 pancreatic fistulas. A literature review confirmed liver transplantation/pancreatic resection-related complications. In conclusion, liver transplantation and pancreatic resection remain uncommon, and a good outcome can be achieved. Recurrence of malignant disease is the main factor limiting survival, and specific morbidity may be related to pancreatic resection and liver transplantation.

Long-term outcomes of donation after cardiac death liver allografts from a single center.

Organ shortage continues to be a major challenge in transplantation. Recent experience with controlled non-heart-beating or donation after cardiac death (DCD) are encouraging. However, long-term outcomes of DCD liver allografts are limited. In this study, we present outcomes of 19 DCD liver allografts with follow-up >4.5 years. During 1998-2001, 19 (4.1%) liver transplants (LT) with DCD allografts were performed at our center. Conventional heart-beating donors included 234 standard criteria donors (SCD) and 214 extended criteria donors (ECD). We found that DCD allografts had equivalent rates of primary non-function and biliary complications as compared with SCD and ECD. The overall one-, two-, and five-yr DCD graft and patient survival was 73.7%, 68.4%, and 63.2%, and 89.5%, 89.5%, and 89.5%, respectively. DCD graft survival was similar to graft survival of SCD and ECD in non hepatitis C virus (HCV) recipients (p > 0.370). In contrast, DCD graft survival was significantly reduced in HCV recipients (p = 0.007). In conclusion, DCD liver allografts are durable and have acceptable long-term outcomes. Further research is required to assess the impact of HCV on DCD allograft survival.

Utility of fiber-optic bronchoscopy in pulmonary infections among abdominal solid-organ transplant patients: A comprehensive review.

Pulmonary infections are frequent complications in abdominal solid-organ transplantation (aSOT) which may threaten patient and allograft survival. Accurate diagnosis and treatment of pulmonary infections in this population can be challenging. Immunosuppressive therapy not only increases the risk of acquiring opportunistic and non-opportunistic infections, but it also impairs the inflammatory responses associated with microbial invasion which in an otherwise normal host produce clinical and radiologic responses that allow for early identification of the offending pathogen. Serologic testing is not a reliable diagnostic modality. Direct microbiological sampling is often necessary to make a definitive diagnosis early in the clinical course to optimize timely, targeted therapy while reducing the risk of developing antimicrobial resistance, and minimize adverse effects of therapy, if any. Fiber-optic bronchoscopy (FOB) with bronchoalveolar lavage (BAL) or transbronchial lung biopsy (TBB) offers such diagnostic advantage and possesses a potential therapeutic value too. This comprehensive review discusses the potential benefits of FOB alongside its risks and complications, indications and contraindications, and techniques. Additionally, the essay highlights FOB's utility and yield specifically with regard to type and timing of infections in aSOT patients.

Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C.

Although recurrent hepatitis C virus (HCV) after liver transplantation (LT) is universal, a minority of patients will develop cirrhosis within 5 years of surgery, which places them at risk for allograft failure. This retrospective study investigated whether 2 serum fibrosis markers, serum hyaluronic acid (HA) and YKL-40, could be used to predict rapid fibrosis progression (RFP) post-LT. These markers were compared with conventional laboratory tests, histological assessment, and hepatic stellate cell activity (HSCA), a key step in fibrogenesis, as assessed by immunohistochemical staining for alpha-smooth muscle actin. Serum and protocol liver biopsy samples were obtained from 46 LT recipients at means of 5 +/- 2 (biopsy 1) and 39 +/- 6 (biopsy 2) months post-LT, respectively. RFP was defined as an increase in the fibrosis score >or= 2 from biopsy 1 to biopsy 2 (a mean interval of 33 +/- 6 months). The ability of parameters at biopsy 1 to predict RFP was compared with the areas under receiver operating characteristic curves (AUROCs). Of the 46 subjects, 15 developed RFP. Serum HA and YKL-40 performed significantly better than conventional parameters and HSCA in predicting RFP post-LT for HCV at biopsy 1, with AUROCs of 0.89 and 0.92, respectively. The accuracy of serum HA >or= 90 microg/L and YKL-40 >or= 200 microg/L in predicting RFP at biopsy 1 was 80% and 96%, respectively. In conclusion, we found that elevated levels of serum HA and YKL-40 within the first 6 months after LT accurately predicted RFP. Larger studies evaluating the role of serum HA and YKL-40 in post-LT management are warranted.

Primary alveolar soft-part sarcoma of the liver: anomalous presentation of a rare disease.

Alveolar soft-part sarcoma is a highly vascular soft-tissue tumor that is uniformly malignant. It comprises less than 1 per cent of all soft-tissue sarcomas. Patients with alveolar soft-part sarcoma most frequently are aged 15 to 35 years, and the soft tissues of the lower extremities typically are affected. In the pediatric population, it most frequently occurs in the head and neck and particularly affects the tongue and orbit. Alveolar soft-part sarcoma has been described as a primary lesion in the trunk, upper extremities, and retroperitoneum; more novel locations include the mediastinum, female genital tract, stomach, bone, and larynx. Numerous case reports describe alveolar soft-part sarcoma in diverse anatomic locations, but this report is, to our knowledge, the first documentation of primary alveolar soft-part sarcoma of the liver. We describe a 47-year-old woman with such a manifestation. Despite surgical resection and numerous chemotherapeutic regimens, this patient had widespread metastasis and died approximately 2 years after the diagnosis was established.

Transplant Critical Care: Is there a Need for Sub-specialized Units? - A Perspective.

The critical care involved in solid-organ transplantation (SOT) is complex. Pre-, intra- and post-transplant care can significantly impact both - patients' ability to undergo SOT and their peri-operative morbidity and mortality. Much of the care necessary for medical optimization of end-stage organ failure (ESOF) patients to qualify and then successfully undergo SOT, and the management of peri-operative and/or long-term complications thereafter occurs in an intensive care unit (ICU) setting. The current literature specific to critical care in abdominal SOT patients was reviewed. This paper provides a contemporary perspective on the potential multifactorial advantages of sub-specialized transplant critical care units in providing efficient, comprehensive, and collaborative multidisciplinary care.

Effect of antiviral chemoprophylaxis on adverse clinical outcomes associated with cytomegalovirus after liver transplantation.

OBJECTIVE: To assess t he association be tweencytomegalovirus (CMV) serology of donor and recipient and adverse outcomes afterliver transplantation in the era of effective antiviral chemoprophylaxis. PATIENTS AND METHODS: We performed a retrospective cohort study of 193 consecutive patients undergoing their first liver transplantation between February 1998 and July 2000 with targeted and preemptive ganciclovir chemoprophylaxis. Patients were divided into 4 groups by CMV serology of donor and recipient: donor-/recipient-; donor-/recipient+; donor+/recipient+; and donor+/recipient-. Survival to the end points of retransplantation, death, or survival to 1 year after transplantation (whichever occurred first) was assessed. Rates of bacterial, fungal, and CMV Infection and of CMV disease were recorded and compared. RESULTS: No significant differences were observed in the rates of retransplantation, death, or survival to 1 year among the 4 groups of patients. Despite significantly higher rates of CMV infection in the donor+ groups, there were no differences in the rates of bacterial or fungal Infection or of CMV disease. Rejection occurred least frequently in the donor-/recipient- group. CONCLUSION: The adverse effects of CMV on outcomes after liver transplantation have been diminished in the era of effective antiviral chemoprophylaxis.

Spectrum of pneumonia in the current era of liver transplantation and its effect on survival.

OBJECTIVE: To examine the frequency and microbial pattern of pneumonia and its effect on survival in the current era of orthotopic liver transplantation (OLT). PATIENTS AND METHODS: At the Mayo Clinic in Jacksonville, Fla, the medical records of consecutive patients who underwent their first OLT between February 1998 and January 2001 were retrospectively reviewed through the end of the first year posttransplantation. RESULTS: Of 401 study patients, 20 developed pneumonia; estimates of incidence with corresponding 95% confidence interval (CI) at 1 and 12 months were 3% (1%-5%) and 5% (3%-7%), respectively. Pseudomonas aeruginosa was the predominant microorganism identified (in 8 of 14 patients) during the first month after transplantation. Between the second and sixth months, 2 of the 4 cases of pneumonia were due to fungal infections of Aspergillus fumigatus. Cytomegalovirus was associated with Aspergillus in 1 patient. No other viral or Pneumocystis carnil pneumonia was diagnosed. There were only 2 cases of pneumonia between 7 months and 1 year after transplantation, neither of which was fungal. Approximately 40% (95% CI, 14%-58%) of patients with pneumonia died within 1 month after diagnosis. The relative risk of mortality in the first month after onset of pneumonia was estimated to be 24 (95% CI, 10-54), which is strong evidence of increased risk of mortality with pneumonia (P<0.001). CONCLUSIONS: Pneumonia appears to occur less often after OLT than previously reported but still has a substantial negative effect on survival. In the early period after OLT, P. aeruginosa continues to be the predominant organism causing pneumonia.

Donor age affects fibrosis progression and graft survival after liver transplantation for hepatitis C.

BACKGROUND: The use of liver allografts from an older donor (OD) (age>50 years) is a widespread strategy to manage the disparity between supply and demand of organs for liver transplantation. This study determines the effect of OD allografts on fibrosis progression and graft survival after liver transplantation in patients with and without infection caused by hepatitis C virus (HCV). METHODS: All patients undergoing liver transplantation at our center from March 1998 to December 2001 were analyzed. Protocol liver biopsies were performed at 1, 16, and 52 weeks after transplantation and yearly thereafter. One liver pathologist scored all biopsy specimens for modified hepatic activity index (0-18) and fibrosis (0-6). RESULTS: A total of 402 patients (167 with HCV and 235 without HCV) underwent liver transplantation during the study period. Among patients with HCV, baseline characteristics of OD recipients were similar to younger donor (YD) (age<50 years) recipients. In patients with HCV, graft survival was shorter in OD graft recipients than in YD recipients (P<0.001). In patients without HCV, graft survival was independent of donor age. In patients with HCV, a fibrosis score of 3 or greater was present in 17% of OD recipients at 4 months and in 26% at 12 months after transplantation, compared with 8% of YD recipients at 4 months and 13% at 12 months (P<0.001). CONCLUSIONS: Liver transplantation with OD grafts is associated with rapid progression of fibrosis and decreased graft survival in patients with HCV, but not in patients without HCV. OD grafts should be considered preferentially for patients without HCV.

Recent advances in liver transplantation.

Advances in liver transplantation continue to evolve but are hampered by continued increasing shortages in donor organs. This has resulted in a high incidence of patients dying while on the United Network for Organ Sharing waiting list. Indeed, we continue to assess ways of expanding the donor pool by using marginal donors, living donor liver transplantation, split liver transplantation, domino transplantation, and hepatic support systems to prolong survival long enough for the patient to undergo liver transplantation. Changes in the liver allocation policy to reduce the number of people dying while waiting for an organ are discussed. Implementation of the model for end-stage liver disease allocation system should help alleviate the problem of increasing deaths of patients while on the waiting list. Recurrent disease, particularly recurrent hepatitis C, continues to be a major problem, and effective therapy is needed to prevent both progression of hepatitis C and recurrence in the graft and avoid retransplantation. The use of pegylated interferon in combination with ribavirin holds promise for improving the success in overcoming recurrent hepatitis C. Finally, advances in immunosuppression have reduced the incidence of acute cellular rejection and chronic rejection. However, these therapies have been fraught with metabolic complications that are now affecting quality of life and long-term survival. Tailoring immunosuppressive regimens to the individual patient is discussed.

Cerebrospinal fluid drainage and cranial decompression prolong survival in rats with fulminant hepatic failure.

Fulminant hepatic failure (FHF) is a devastating disease. Liver transplantation is the definitive treatment. However, a third of these patients die due to brain edema before a donor becomes available. Cerebrospinal fluid (CSF) drainage and decompressive craniectomy have been used to treat brain edema in brain trauma and hemispheric stroke. However, their role in brain edema associated with FHF has not been examined. In this study we evaluated the potential effects of CSF drainage and decompressive craniectomy on survival in FHF using an experimental model in rats. In CSF drainage experiments all animals had ventriculostomy placed. Five days later FHF was induced with d-galactosamine. Those FHF rats that progressed into comatose stages either received CSF aspiration or did not. In separate experiments the study rats had either a decompressive craniectomy or a sham procedure. FHF was induced 5 days later. We found that both CSF drainage and decompressive craniectomy significantly increased survival of FHF rats compared with the controls: 53.2 +/- 1.1 vs. 48.7 +/- 1.5 h (P = 0.031), and 69.4 +/- 3.9 vs. 53.7 +/- 3.2 h (P = 0.009), respectively. In conclusion, these findings suggest that CSF drainage and decompressive craniectomy may increase the window of opportunity for liver transplantation.

Disseminated Bartonella infection following liver transplantation.

Bartonella henselae has not only been identified as the causative agent of cat scratch disease, but it is also associated with other significant infectious syndromes in the immunocompromised population. We describe two cases of B. henselae associated diseases in liver transplant recipients who both had contact with cats. The first recipient developed localized skin manifestation of bacillary angiomatosis in association with granulomatous hepatitis. He tested positive for Immunoglobulin G (IgG) antibodies against B. henselae. The second patient developed axillary lymphadenopathy, with biopsy showing necrotizing granulomatous inflammation and polymerase chain reaction studies were positive for B. henselae DNA. Her serology for bartonellosis showed a fourfold rise in antibody titers during her hospitalization. Both patients responded to treatment with Azithromycin in combination with Doxycycline. These were the only cases within a series of 467 consecutive liver transplants performed in 402 patients performed during a 4-year period. Although bartonellosis is a rare infection in liver transplantation recipients, it should always be included in the differential diagnosis of patients presenting with fever, central nervous system (CNS) symptoms, skin lesions, lymphadenopathy, and hepatitis especially if prior contact with cats is reported.