Acquired cow's milk sensitization after liver transplant in an adult: "clinical implications" and future strategies.

BACKGROUND: Identifying the mechanisms responsible for the development of food allergy in liver transplant recipients is more complex as there are several different clinical scenarios related to the immunological function of the liver. CASE PRESENTATION: We describe the first case of Transplant Acquired Food Allergy (TAFA) to cow milk in an adult following LT from a donor dead because of anaphylactic shock. A 67-year-old woman with primary biliary cirrhosis was referred to the Transplant Center of our hospital because of an acute-on-chronic liver failure. The donor was a 15-year-old girl deceased for anoxic encephalopathy due to food induced anaphylaxis after eating a biscuit. In the donor's history food allergies to cow milk and eggs were present. CONCLUSION: This case emphasizes the need for a standardized assessment of both solid-organ donors and recipients including donor allergy history in order to detect recipients at risk for anaphylaxis due to passive IgE transfer. Despite several reports of TAFA after solid organ, especially liver, an appropriate protocol to avoid risk for the recipient doesn't exist at the moment. The SPT (skin prick test) or specific IgE level are not enough to ensure a correct management in these cases and a correct education of the patients and the medical staff involved is absolutely necessary. It is the first case of milk allergy sensitization after solid organ transplant by passive transfer of IgE.

The FXR agonist obeticholic acid inhibits the cancerogenic potential of human cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive cancer with high resistance to chemotherapeutics. CCA is enriched in cancer stem cells, which correlate with aggressiveness and prognosis. FXR, a member of the metabolic nuclear receptor family, is markedly down-regulated in human CCA. Our aim was to evaluate, in primary cultures of human intrahepatic CCA (iCCA), the effects of the FXR agonist obeticholic acid (OCA), a semisynthetic bile acid derivative, on their cancerogenic potential. Primary human iCCA cell cultures were prepared from surgical specimens of mucinous or mixed iCCA subtypes. Increasing concentrations (0-2.5 µM) of OCA were added to culture media and, after 3-10 days, effects on proliferation (MTS assay, cell population doubling time), apoptosis (annexin V-FITC/propidium iodide), cell migration and invasion (wound healing response and Matrigel invasion assay), and cancerogenic potential (spheroid formation, clonogenic assay, colony formation capacity) were evaluated. Results: FXR gene expression was downregulated (RT-qPCR) in iCCA cells vs normal human biliary tree stem cells (p < 0.05) and in mucinous iCCA vs mixed iCCA cells (p < 0.05) but was upregulated by addition of OCA. OCA significantly (p < 0.05) inhibited proliferation of both mucinous and mixed iCCA cells, starting at a concentration as low as 0.05 µM. Also, CDCA (but not UDCA) inhibited cell proliferation, although to a much lower extent than OCA, consistent with its different affinity for FXR. OCA significantly induced apoptosis of both iCCA subtypes and decreased their in vitro cancerogenic potential, as evaluated by impairment of colony and spheroid formation capacity and delayed wound healing and Matrigel invasion. In general, these effects were more evident in mixed than mucinous iCCA cells. When tested together with Gemcitabine and Cisplatin, OCA potentiated the anti-proliferative and pro-apoptotic effects of these chemotherapeutics, but mainly in mixed iCCA cells. OCA abolished the capacity of both mucinous and mixed iCCA cells to form colonies when administered together with Gemcitabine and Cisplatin. In subcutaneous xenografts of mixed iCCA cells, OCA alone or combined with Gemcitabine or Cisplatin markedly reduced the tumor size after 5 weeks of treatment by inducing necrosis of tumor mass and inhibiting cell proliferation. In conclusion, FXR is down-regulated in iCCA cells, and its activation by OCA results in anti-cancerogenic effects against mucinous and mixed iCCA cells, both in vitro and in vivo. The effects of OCA predominated in mixed iCCA cells, consistent with the lower aggressiveness and the higher FXR expression in this CCA subtype. These results, showing the FXR-mediated capacity of OCA to inhibit cholangiocarcinogenesis, represent the basis for testing OCA in clinical trials of CCA patients.

Surgical Technique Notes of Arterial Vascular Reconstruction During Kidney Transplantation: Personal Experience and Literature Review.

BACKGROUND: Arterial vascular anomalies in patients undergoing kidney transplantation (KT) are correlated with a higher incidence of early surgical complications, potentially causing graft loss. Arterial reconstruction allows patients to overcome these surgical challenges, thus minimizing the risk of poor outcomes. The aim of the present study is to retrospectively investigate the safety and effectiveness of the multiple arterial reconstruction technique with a Teflon patch in case of an unavailable aortic patch: to do so, surgical complications, graft function, and patient survival were evaluated. METHODS: During the period January 2009 to August 2016, 202 adult deceased-donor KTs were performed at our center. Group A (n = 27; reconstruction of multiple arteries) and Group B (n = 175; control group) were compared. RESULTS: No differences were observed between the 2 groups in terms of early postoperative course, with no vascular complication observed in Group A. No vascular patch infections were reported, nor longer cold ischemia time rates. Similarly, long-term survival rates were similar between the 2 groups. CONCLUSIONS: The Teflon-patch arterial reconstruction technique appears to be safe and effective, with an acceptable balance of benefits and potential risks of using a prosthetic material. Studies based on larger series are needed to further validate this approach.

Pre-Emptive Therapy for the Treatment of Cytomegalovirus After Kidney Transplantation.

BACKGROUND: Cytomegalovirus (CMV) represents the leading cause of viral infection in kidney transplantation patients. The aim of the present study was to evaluate the efficacy and safety of pre-emptive anti-CMV therapy. MATERIALS AND METHODS: We performed a retrospective analysis based on data from 227 consecutive patients transplanted from 2010 to 2015, of whom 38 (16.6%) were from a living donor, considering: incidence of rejection, CMV organ localization, and graft and patient survival. All patients underwent induction immunosuppressive therapy followed by maintenance therapy consisting of corticosteroids, antimetabolites, and tacrolimus (median basal dose = 5.3 ng/mL). The timing for the detection of plasma CMV-DNA in the post-transplantation period was: weekly (first month), quarterly (second through twelfth month), and then half-yearly. RESULTS: CMV viremia was positive in 98 of 227 (43.1%) patients, with an average of 248,482 copies/mL (range: 250 copies/mL to 9,745,000 copies/mL) and the first positivity after a median period of 2.5 months from kidney transplantation (range: 0.2 months to 43 months). A total of 49 of 227 (21.5%) patients were treated with antivirals: 27 of 49 (55.1%) because of CMV organ localization (gastrointestinal = 20, lungs = 3, kidney = 2, liver = 2). Fourteen of 227 (6.1%) patients had a rejection episode, 7 (3.1%) of which were CMV-related. Fifteen of 227 (6.6%) patients died (noninfectious CMV-related complications = 8, cardiovascular causes = 6, bleeding complications = 1). CONCLUSION: Our experience confirms the validity of the pre-emptive anti-CMV therapy in renal transplantation patients.

Delayed Introduction of Everolimus in De Novo Renal Transplanted Patients: A Single-Center Experience.

INTRODUCTION: Immunosuppressive protocols containing everolimus (EVR) preserve good renal function in kidney transplantation (KT), although they are often complicated by several adverse events. We have evaluated the efficacy and safety of a protocol with late (1 month after KT) EVR introduction. MATERIAL AND METHODS: This study randomized 49 de novo patients undergoing KT between September 2012 and June 2014 into 2 groups: group A (n = 24) with late EVR introduction and tacrolimus reduction, and group B (control group; n = 25) with a standard immunosuppressive regimen. Primary aims were 1-year patient and graft survivals and acute rejection rates. Secondary aims were related to wound, metabolic, and hematologic complications. RESULTS: Patient and graft survivals were similar in both groups. One year after KT, median serum creatinine was inferior in group A (1.4 vs 1.8 mg/dL; P = .004). Late acute rejection (8.3 vs 12.0%; P = 1.0) and wound complication (4.2 vs 4.0%; P = 1.0) rates were similar. Higher cholesterol and triglycerides and lower platelets and hemoglobin levels were observed in group A. CONCLUSIONS: In our experience, delayed introduction of EVR shows similar results with respect to its early introduction, contemporaneously presenting fewer wound complications and lymphoceles. A higher rate of metabolic and hematologic complications are, however, observed in patients under EVR therapy. Further multicenter studies should be performed to confirm these preliminary results.

Multiple Organ Failure Associated With Coxsackie Virus in a Kidney Transplant Patient: Case Report.

INTRODUCTION: Viral myocarditis can emerge with various symptoms, including fatal arrhythmia and cardiogenic shock, potentially evolving in chronic myocarditis or dilatative cardiomyopathy. We report a case of a kidney transplant patient affected by coxsackie viral myocarditis. METHODS: A 49-year-old man was admitted to our hospital with dyspnea and fever in August 2014. He underwent living donor kidney transplantation in 1986 and polar graft resection for papillary carcinoma in 2012. RESULTS: The initial investigation showed pulmonary congestion, pancreatitis, increased serum troponin I, and increased liver enzyme levels. Echocardiogram revealed an ejection fraction (EF) of 20% and PAPS 45 mm Hg. He underwent coronary stent implantation, started hemodialysis, and continued on low-dose steroid immunosuppressive therapy. The clinical course improved rapidly, but endomyocardial biopsy showed acute myocarditis. Further investigation revealed a high antibody titer against coxsackievirus B4 and B5. Pancreatic enzyme levels normalized 2 months after patient admission; his cardiac condition improved after 6 months. The patient has been followed for 1 year, and his left ventricular EF is stable (45%). CONCLUSIONS: Viral myocarditis represents a serious clinical condition requiring a fast therapeutic intervention. This patient's clinical course suggests that changes in his immunosuppressive therapy were associated with progressive amelioration of his viral myocarditis.

Diaphragmatic hernia as a spontaneous sequela of a surgically-treated left infiltrating renal tumor: a case report.

A diaphragmatic hernia is a protrusion of abdominal structures within the thoracic cavity through a defect in the diaphragm, which can be either congenital or acquired. Diaphragmatic rupture, as a sequela following abdominal surgery, is rarely documented. Approximately 80% of the reported cases, the injury occurred on the left side. We discuss a case of a 37 year-old male who underwent a left nephrectomy with ipsilateral adrenalectomy and diaphragmatic resection, by direct reconstruction that developed the sequela of a diaphragmatic hernia. We chose a surgical transthoracic approach for herniation repair.

Early right hepatectomy for severe liver trauma: a case report.

Liver is frequently involved and injured in blunt abdominal trauma. Although over the last three decades the management of blunt hepatic trauma has gradually shifted toward nonoperative approach whit a significant reduction in overall mortality, surgery remains the main option for hemodinamically unstable patients whit severe liver injuries. A 16-yr-old male in good health suffered a blunt abdominal trauma from a sport accident falling while playing football resulting in a grade V liver injury according to the American Association for the Surgery of Trauma Organ Injury Score. He underwent first to liver packing and next to an early right hepatectomy to arrest the clinical condition impairment In high grade liver injuries, liver resection makes possible to effectively control bleeding, remove necrotic tissue and prevent complications as bile leak. Nevertheless when patient's clinical condition continue to deteriorate despite optimal management a quickly and experienced hands performed hepatectomy may solve the situation.

Spontaneous Bilateral Adrenal Haemorrhage after Duodenopancreatectomy: a case report.

it is difficult to diagnose because of its nonspecific presentation. This condition frequently occurs in association with an extreme physical stress and may lead to acute adrenal insufficiency or death if not promptly and properly treated. We report a rare case of acute bilateral adrenal hemorrhage with adrenal insufficiency following duodenopancreatectomy for ampulloma in absence of surgical complications. Early diagnosis and corticosteroid replacement with aggressive management of the precipitating pathology are essential to enable a successful outcome.

Adult Wilms tumor: Case report.

Wilms tumor (WT) occurs infrequently in adults. Even rarer is adult WT with extension by direct intravascular spread into the right side of the heart. The present report describes a WT with intracaval and intracardiac extension in a 38-year-young man. In addition, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable hemorrhages and tumor fragmentation. We report the results of a surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. The morphologic and immune-histochemical findings confirmed the diagnosis.

Conversion from twice-daily to once-daily Tacrolimus administration in liver transplant patient: results of long term follow-up.

OBJECTIVES: The aim of this study was to assess the long term effects of once-daily tacrolimus (OD-TAC) in a cohort of stable liver recipients converted from the twice daily tacrolimus (TD TAC), with a particular attention on the possible effects on renal function. PATIENTS AND METHODS: Between September 2008 and September 2010 conversion from TD-TAC to OD-TAC was proposed in adult stable liver transplant recipients who were followed as outpatients in our Transplant centre. Conversion from TC-TAC to OD-TAC was based on a 1 mg: 1 mg proportion. Tacrolimus through levels, laboratory parameters, metabolic disorders and any adverse events were evaluated at 1, 3, 6, 12 and 24 months after conversion. Renal function was evaluated using creatinine plasma levels and estimated glomerular filtration rate (GFR) derived from the Modification of Diet in Renal Disease (MDRD). Analysis of variance and t test for paired data were utilised for the comparison of the results obtained at the scheduled controls. RESULTS: Sixty-five patients were enrolled in the study (50 males, 15 females, mean age 59±8 years). Median time since liver transplant (LT) was 39 months (range: 6 to 83 months). All patients were followed for a minimum of 12 months. Ninety per cent of patients stabilized their blood levels within 45 days. Liver function, glucose and plasma lipids concentration and arterial blood pressure remained stable during the study. Renal function improved during the 24 months of follow-up. No adverse events or acute rejection episodes were recorded during the study. CONCLUSIONS: Considering the advantage on patient compliance, the equivalent efficacy and the adequate safety of OD-TAC formulation may represent a useful option in liver transplant patients, with a possible advantage on renal function.

Expanded criteria for hepatocellular carcinoma after liver transplantation: a 20-year evolution.

BACKGROUND/AIM: Milan Criteria (MC) consent excellent survivals for hepatocellular carcinoma (HCC) after liver transplantation (LT). However, several new expanded criteria were proposed, with the intent to increase the HCC patients eligible for LT, maintaining acceptable recurrence rates. The aim of the present study was to analyze a cohort of HCC patients, evaluating the evolutions in its management during the last 20 years and comparing the disease-free survivals among three different periods. METHODOLOGY: HCC patients (n = 122) were transplanted and stratified in three periods: 1st (1988-1998, liberal selection), 2nd (1999-2003, use of MC) and 3rd (2004-2008, use of UCSF criteria). The three periods were analyzed and their survivals were compared. RESULTS: Statistical differences were reported at univariate analysis regarding to both dimensional (total tumor diameter) and biological (alpha feto-protein, microvascular invasion) HCC features. Comparing the 5-year survival rates, a progressive increase was observed in the three periods (62.6%, 87.9% and 88.4%, respectively), with a significant difference between 1st and the second periods (p = 0.008). CONCLUSIONS: In our experience, use of UCSF criteria is safe, with a contemporaneous increased number of transplants and better survivals. Introduction of new selection criteria, also based on biological features, is on the way.

Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease.

Hepatic resection for giant haemangioma in a patient with a contemporaneous adult polycystic liver disease. According to Gigot classification, and to the characteristics of haemangioma surgery in these patients can be considered safe. We report the case of a 55 year-old man affected by an adult polycystic liver disease (PCLD) and a contemporaneous symptomatic haemangioma of the III segment. At the preoperative imaging scans, APCLD was classified in a type II grading according to Gigot classification. The patient underwent surgery: a wedge resection of the III segment with the exportation of the haemangioma and a fenestration of a large cyst placed in the VIII segment were performed. Post-operative course was regular and the patient was discharged uneventfully in post-operative 9th day, with a total regress of the initial symptoms. APCLD and haemangioma are two benign conditions that do not require surgery except if they cause important symptoms, such as pain. The good clinical conditions of the patient, the moderate gravity of the APCLD and the particular exofitic localisation of the cavernous haemangioma gave us the possibility to make a safe surgery for the patient. To the best of our knowledge, this is the first case reported in literature in which a liver resection for haemangioma in patient with APCLD was performed. In conclusion, liver resection for haemangioma is not contraindicated, mainly if it is symptomatic, even in the contemporaneous presence of an APCLD.

Later diagnosed with a neuroendocrine tumor, case report of a 60-year-old.

Neuroendocrine tumours of the colon and rectum are infrequent. Clinical manifestations are not different from standard adenocarcinoma. Symptoms are non specific; the most common are abdominal pain, nausea and vomiting, weight loss and gastrointestinal blood loss. We report an advanced case of transverse colon neuroendocrine carcinoma with multiple metastasis. When these tumours are diagnosed, they have distance disease related to a poor prognosis for the patient. Surgery is the treatment that can offer a greater chance of survival to these patients.

Glasgow coma score and tumor necrosis factor α as predictive criteria for initial poor graft function.

Initial poor graft function (IPGF) is a major factor influencing the clinical outcome after liver transplantation (LT), but there is no reliable method to assess and predict graft dysfunction. To help clinicians determine prognosis in the early postoperative period, individual parameters and complex scoring systems have been suggested, but most of them are inaccurate because of the multifactorial nature of transplantation courses. Therefore, the aim of our study was to retrospectively evaluate predictive criteria for retransplantation. Forty-two patients were enrolled in this study: 18 who experienced primary non-function (PNF) and 24 with delayed graft function (DGF). All of the patients were treated with the Molecular Adsorbent Recirculating System (MARS). They were into 3 subgroups: patients who survived without LT (n = 20; 47.7%); patients who underwent LT (n = 16; 37%), and patients who died before transplantation (n = 6; 14%). Stepwise multivariable logistic regression analysis was performed with the intent to find the risk factors for LT or death after MARS treatment (second analysis). Receiver operating characteristic (ROC) curves were performed on significant variables in the logistic regression model with the intent to individually predict variables for LT or death. After a stepwise multivariable logistic regression analysis enrolling all of the previously reported features only 2 variables, tumor necrosis factor (TFN)-α and Glasgow coma score (GCS) score, were statistically significant. TNF-α was an unique independent risk factor for retransplantation or death after MARS treatment (odds ratio [OR] 1.235; P = .013). Conversely, GCS score was protective against retransplantation or death (OR 0.150; P = .003). Starting from these assumptions, a predictive model was created using these 2 variables. On ROC analysis, the combined score showed an area under the curve greater than that of the 2 variables considered separately. Validating these results with a larger number of patients, we considered these 2 factors as subjective parameters to determine outcomes and the difference between PNF and DGF.

An unusual case of hepatic carcinosarcoma.

We report a rare case of a hepatic carcinosarcoma with rabdomyosarcomatous differentiation in its sarcomatous component. A 71-year old Caucasian female patient underwent a liver resection for a 4-cm lesion developed on an underlying HCV-related cirrhosis. Post-operative course was uneventful and the patient was discharged 5 days after surgery. At pathology, the tumor presented the features of hepatocellular carcinoma and rhabdomyosarcoma Three months later the patient experienced a liver recurrence, dying 2 months later for systemic disease. The reported case presents several peculiarities, i.e. the female gender, the HCV-related cirrhotic status, and the European origin of the patient. However, the outcome of our case confirms that this neoplasm pursues a highly aggressive course with poor prognosis.

Does caval reconstruction technique affect early graft function after liver transplantation? A preliminary analysis.

BACKGROUND: In the past decades, the inferior vena cava (IVC) reconstruction technique has undergone several evolutions, such as biopump, piggyback technique (PB), and laterolateral approach (LLPB). Several advantages are reported comparing the PB technique to biopump use. However, comparison between PB and LLPB has not been as well investigated. The aim of this study was to compare the results in terms of immediate graft function and intermediate graft survival among 3 subgroups characterized by distinct caval reconstruction techniques. METHODS: We retrospectively analyzed a cohort of 200 consecutive adult patients who underwent liver transplantation from January 2001 to December 2009. The patients were stratified according to 3 caval reconstructive techniques: biopump (n=135), PB (n=32) and LLPB (n=33). RESULTS: The LLPB group showed the shortest cold and warm ischemia times and the best immediate postoperative graft function. Survival analysis revealed LLPB patients to present the best 1-year graft survival rates: namely, 90.9% versus 75.0% and 74.1% among the PB and biopump groups, respectively (log-rank tests: LLPB vs biopump: P=.03; LLPB vs PB: P=.05). In our experience, LLPB showed the best graft survivals with an evident reduction in both cold and warm ischemia times. However, it is hard to obtain an irrefutable conclusion owing to the retrospective nature of this study, the small sample, and the different periods in which the groups were transplanted. CONCLUSIONS: LLPB technique was a safe procedure that minimized the sequelal of ischemia-reperfusion damage. This technique yielded results superior to venovenous bypass. No definitive conclusions can to be obtained in this study comparing classic PB or LLPB.

Survival after kidney transplantation does not differ with 50-59- or over 60-year-old expanded-criteria donors.

BACKGROUND: Use of expanded-criteria donors (ECDs) for kidney transplantation has progressively increased in the past years with the intent to improve the number of available grafts. However, it is still uncertain if ECD kidneys have worse survivals than standard-criteria ones. The aim of this study was to retrospectively analyze a cohort of ECD patients comparing the 2 subgroups of 50-59- and >60-year-old donors in terms of donor, recipient, and transplant features and survival rates. METHODS: Ninety-one cases were analyzed. The cohort was stratified into 2 subgroups according to donor age: group 1, age 50-59 years (n=26); and group 2, age ≥60 years (n=67). RESULTS: Group 2 represented older donors and a higher percentage of donors with a previous history of hypertension. In Group 1, preharvest creatinine values showed higher results. No difference was detected regarding patient and graft survivals, with 5-year survival rates of 92.3% versus 86.7%, and 70.8% versus 69.8%, respectively. The best way to select the donors is still under debate. In our experience, a biopsy-driven selection was performed exclusively for group 2 ECDs. Considering the similar survivals obtained, we speculated that an accurate biopsy-based selection of older grafts allows one to avoid "bad" donors from the allocation system, thereby obtaining improved survival results. CONCLUSIONS: Biopsy-driven pretransplantation selection appears to be the main system to optimize results, to achieve outcomes similar to nonbiopsied younger donors. Routine biopsies also in the younger subgroup of ECD may achieve a further improvement in survival.