Contemporaneous Portal-Arterial Reperfusion during Liver Transplantation: Preliminary Results

We prospectively compared sequential portal-arterial revascularization (SPAr, group 1 no. 19) versus contemporaneous portal-hepatic artery revascularization (CPAr, group 2 no. 21) in 40 consecutive liver transplantation (LT). There were no differences in the demographics characteristics, MELD score, indication to LT, and donor's parameters between the two groups. CPAr had longer warm ischemia 66 ± 8 versus 37 ± 7 min (P < .001), while SPAr had longer arterial ischemia 103 ± 42 min (P = .0004). One-year patient's and graft survival were, respectively, 89% and 95% versus 94% and 100% (P = .29). At median followup of 13 ± 6 versus 14 ± 7 months biliary complications were anastomotic stenosis in 15% versus 19% (P = .78), and intrahepatic nonanastomotic biliary strictures in 26% versus none (P = .01), respectively, in SPAr and CPAr. CPAr reduces the incidence of intrahepatic biliary strictures by decreasing the duration of arterial ischemia

The Effect of Endurance Training on Pulmonary V˙O2 Kinetics in Solid Organs Transplanted Recipients

BACKGROUND: We investigated the effects of single (SL-ET) and double leg (DL-ET) high-intensity interval training on O2 deficit (O2Def) and mean response time (MRT) during square-wave moderate-intensity exercise (DL-MOD), and on the amplitude of V˙O2p slow component (SCamp), during heavy intensity exercise (DL-HVY), on 33 patients (heart transplant = 13, kidney transplanted = 11 and liver transplanted = 9). METHODS: Patients performed DL incremental step exercise to exhaustion, two DL-MOD tests, and a DL-HVY trial before and after 24 sessions of SL-ET (n = 17) or DL-ET (n = 16). RESULTS: After SL-ET, O2Def, MRT and SCamp decreased by 16.4% ± 13.7 (p = 0.008), by 15.6% ± 13.7 (p = 0.004) and by 35% ± 31 (p = 0.002), respectively. After DL-ET, they dropped by 24.9% ± 16.2 (p &lt; 0.0001), by 25.9% ± 13.6 (p &lt; 0.0001) and by 38% ± 52 (p = 0.0003), respectively. The magnitude of improvement of O2Def, MRT, and SCamp was not significantly different between SL-ET and DL-ET after training. CONCLUSIONS: We conclude that SL-ET is as effective as DL-ET if we aim to improve V˙O2p kinetics in transplanted patients and suggest that the slower, V˙O2p kinetics is mainly caused by the impairment of peripherals exchanges likely due to the immunosuppressive medications and disuse

Mitochondrial apurinic/apyrimidinic endonuclease 1 enhances mtDNA repair contributing to cell proliferation and mitochondrial integrity in early stages of hepatocellular carcinoma

Background: Hepatocellular carcinoma (HCC) is the leading cause of primary liver cancers. Surveillance of individuals at specific risk of developing HCC, early diagnostic markers, and new therapeutic approaches are essential to obtain a reduction in disease-related mortality. Apurinic/apyrimidinic endonuclease 1 (APE1) expression levels and its cytoplasmic localization have been reported to correlate with a lower degree of differentiation and shorter survival rate. The aim of this study is to fully investigate, for the first time, the role of the mitochondrial form of APE1 in HCC. Methods: As a study model, we analyzed samples from a cohort of patients diagnosed with HCC who underwent surgical resection. Mitochondrial APE1 content, expression levels of the mitochondrial import protein Mia40, and mtDNA damage of tumor tissue and distal non-tumor liver of each patient were analyzed. In parallel, we generated a stable HeLa clone for inducible silencing of endogenous APE1 and re-expression of the recombinant shRNA resistant mitochondrially targeted APE1 form (MTS-APE1). We evaluated mtDNA damage, cell growth, and mitochondrial respiration. Results: APE1's cytoplasmic positivity in Grades 1 and 2 HCC patients showed a significantly higher expression of mitochondrial APE1, which accounted for lower levels of mtDNA damage observed in the tumor tissue with respect to the distal area. In the contrast, the cytoplasmic positivity in Grade 3 was not associated with APE1's mitochondrial accumulation even when accounting for the higher number of mtDNA lesions measured. Loss of APE1 expression negatively affected mitochondrial respiration, cell viability, and proliferation as well as levels of mtDNA damage. Remarkably, the phenotype was efficiently rescued in MTS-APE1 clone, where APE1 is present only within the mitochondrial matrix. Conclusions: Our study confirms the prominent role of the mitochondrial form of APE1 in the early stages of HCC development and the relevance of the non-nuclear fraction of APE1 in the disease progression. We have also confirmed overexpression of Mia40 and the role of the MIA pathway in the APE1 import process. Based on our data, inhibition of the APE1 transport by blocking the MIA pathway could represent a new therapeutic approach for reducing mitochondrial metabolism by preventing the efficient repair of mtDNA

Ileocecal Fistula Caused by Multiple Foreign Magnetic Bodies Ingestion

The incidence of accidental foreign body (FBs) ingestion is 100,000 cases/year in the US, with over than 80% of cases occurring in children below 5 years of age. Although a single FB may pass spontaneously and uneventfully through the digestive tract, the ingestion of multiple magnetics can cause serious morbidity due to proximate attraction through the intestinal wall. Morbidity and mortality depend on a prompt and correct diagnosis which is often difficult and delayed due to the patient's age and because the accidental ingestion may go unnoticed. We report our experience in the treatment of an 11-year-old child who presented to the emergency department with increasing abdominal pain, vomiting, diarrhea, and fever. Surgery evidenced an ileocecal fistula secondary to multiple magnetic FB ingestion with attraction by both sides of the intestinal wall. A 5-centimeter ileal resection was performed, and the cecal fistula was closed with a longitudinal manual suture. The child was discharged at postoperative day 8. After one year, the patient's clinical condition was good

Impact of Power Outages on Developing Countries: Evidence from Rural Households in Niger Delta, Nigeria

Nigeria is suffering from the worst energy crisis in its history, resulting in its rural communities being subjected to massive power outages, daily. Energy promotes economic well-being and makes social life worthwhile such that youths are less disposed to violent crimes. This study investigated the consequences of power outages on the social-economic life of rural households in the Niger Delta region of Nigeria. Primary data were collected through a semi-structured questionnaire circulated among unemployed youth, students, housewives, businessmen and professionals in the area. The study focused on the relationship between power outage and its impact on the everyday life of the people. This study adopted a descriptive research design using 1000 randomly selected members of 44 rural households in the areas mostly affected by incessant power outages. It was found that stunted economic growth, reduced leisure time as well as heightened criminality and insecurity are some of the major results of rampant power outages among rural households in the Niger Delta. It is concluded that power outages have severe negative impact on the social and economic lives of the people. The findings from this research would help improve the outlook of rural communities in Nigeria and other developing countries. Keywords: Nigeria, Power outage, Energy, Electricity, Rural households

Postoperative trends and prognostic values of inflammatory and nutritional biomarkers after liver transplantation for hepatocellular carcinoma

11noPreoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival &gt;1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.openopenopenPravisani R.; Mocchegiani F.; Isola M.; Lorenzin D.; Adani G.L.; Cherchi V.; De Martino M.; Risaliti A.; Lai Q.; Vivarelli M.; Baccarani U.Pravisani, R.; Mocchegiani, F.; Isola, M.; Lorenzin, D.; Adani, G. L.; Cherchi, V.; De Martino, M.; Risaliti, A.; Lai, Q.; Vivarelli, M.; Baccarani, U

Liver transplantation as last-resort treatment for patients with bile duct injuries following cholecystectomy: A multicenter analysis

Background Liver transplantation (LT) has been used as a last resort in patients with end-stage liver disease due to bile duct injuries (BDI) following cholecystectomy. Our study aimed to identify and evaluate factors that cause or contribute to an extended liver disease that requires LT as ultimate solution, after BDI during cholecystectomy. Methods Data from 8 high-volume LT centers relating to patients who underwent LT after suffering BDI during cholecystectomy were prospectively collected and retrospectively analyzed. Results Thirty-four patients (16 men, 18 women) with a median age of 45 (range 22-69) years were included in this study. Thirty of them (88.2%) underwent LT because of liver failure, most commonly as a result of secondary biliary cirrhosis. The median time interval between BDI and LT was 63 (range 0-336) months. There were 23 cases (67.6%) of postoperative morbidity, 6 cases (17.6%) of post-transplant 30-day mortality, and 10 deaths (29.4%) in total after LT. There was a higher probability that patients with concomitant vascular injury (hazard ratio 10.69, P=0.039) would be referred sooner for LT. Overall survival following LT at 1, 3, 5 and 10 years was 82.4%, 76.5%, 73.5% and 70.6%, respectively. Conclusion LT for selected patients with otherwise unmanageable BDI following cholecystectomy yields acceptable long-term outcomes

Association between the donor to recipient ICG-PDR variation rate and the functional recovery of the graft after orthotopic liver transplantation: A case series

Background: Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated. Materials and methods: Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction. Objective: To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score. Results: 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver's ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson's test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012). Conclusion: The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values

Regeneration of Graft Livers and Limited Contribution of Extrahepatic Cells After Partial Liver Transplantation in Humans

Background Liver regeneration is still not fully understood. Partial liver transplantation (LT) can provide the opportunity to investigate the mechanisms of liver regeneration, including the contribution of extrahepatic cells to liver regeneration. Methods Of 61 patients transplanted with partial liver graft between August 1997 and October 2006, 56 patients were studied, including 49 adults and 7 children. Sequential computed tomography volumetric analysis was performed for volume measurement, while proliferating cell nuclear antigen (PCNA) labeling index was investigated for liver cell proliferation in nonprotocol liver biopsy specimens. In addition, 15 male recipients who had female liver grafts were investigated in order to detect Y chromosomes as extrahepatic cells in nonprotocol liver biopsy specimens. Results Graft volume per standard liver volume was markedly increased after adult-to-adult living-donor (LD) LT. In pediatric transplants, there was no volume increase over time. PCNA labeling index was vigorous in adult-to-adult LDLT in the early period after LDLT. No Y chromosome was evident in hepatocytes from female-donor male-recipient grafts during or after liver regeneration. However, in the cases of failing grafts of this type, many Y-chromosome-positive cells were observed in the graft liver. The character of those cells was CD34(−), CK9(−), hepatocyte-specific antigen(−), and CD68(+/−). Conclusion In adult-to-adult LDLT, vigorous liver regeneration occurs in the graft liver, demonstrated by not only volumetric but cell kinetic analysis. Involvement of extrahepatic cells in normal liver regeneration seems limited

A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients

<p>Abstract</p> <p>Background</p> <p><it>BCR-ABL </it>kinase domain (KD) mutation is the major mechanism contributing to suboptimal response to tyrosine kinase inhibitors (TKI) in <it>BCR-ABL</it>-positive chronic myeloid leukemia (CML) patients. T315I mutation, as one of the most frequent KD mutations, has been shown to be strongly associated with TKI resistance and subsequent therapeutic failure. A simple and sensitive method is thus required to detect T315I mutation at the earliest stage.</p> <p>Methods</p> <p>A single-tube allele specific-polymerase chain reaction (AS-PCR) method was developed to detect T315I mutation in a mixture of normal and mutant alleles of varying dilutions. Denaturing high performance liquid chromatography (DHPLC) and direct sequencing were performed as a comparison to AS-PCR.</p> <p>Results</p> <p>T315I mutant bands were observed in the mixtures containing as low as 0.5-1% of mutant alleles by AS-PCR. The detection sensitivity of DHPLC was around 1.5-3% dilution whereas sequencing analysis was unable to detect below 6.25% dilution.</p> <p>Conclusion</p> <p>A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method.</p