Closing the knowledge gap on the composition of the asbestos bodies.

Asbestos bodies (AB) form in the lungs as a result of a biomineralization process initiated by the alveolar macrophages in the attempt to remove asbestos. During this process, organic and inorganic material deposit on the foreign fibers forming a Fe-rich coating. The AB start to form in months, thus quickly becoming the actual interface between asbestos and the lung tissue. Therefore, revealing their composition, and, in particular, the chemical form of Fe, which is the major component of the AB, is essential to assess their possible role in the pathogenesis of asbestos-related diseases. In this work we report the result of the first x-ray diffraction measurements performed on single AB embedded in the lung tissue samples of former asbestos plant workers. The combination with x-ray absorption spectroscopy data allowed to unambiguously reveal that Fe is present in the AB in the form of two Fe-oxy(hydroxides): ferrihydrite and goethite. The presence of goethite, which can be explained in terms of the transformation of ferrihydrite (a metastable phase) due to the acidic conditions induced by the alveolar macrophages in their attempt to phagocytose the fibers, has toxicological implications that are discussed in the paper.

How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Impact of a Multidisciplinary Team on Alcohol Recidivism and Survival After Liver Transplant for Alcoholic Disease.

BACKGROUND: Alcohol use disorders have a prevalence of 10% among the population of the United States and Europe and are one of the most frequent causes of liver cirrhosis in the Western world. Currently, alcohol-related liver cirrhosis represents one of the most frequent indications to liver transplant (LT), both as independent cause or associated with hepatitis C virus or hepatitis B virus infections. Starting from 2014, a multidisciplinary team involving surgeons, gastroenterologists, clinical toxicologists, psychiatrists, and psychologists was developed within the Modena Liver Transplant Center. METHODS: We retrospectively reviewed our prospectively maintained institutional database of liver transplants in order to identify cirrhotic patients eligible for LT with a diagnosis of alcohol use disorder. RESULTS: A total of 756 liver transplants were performed at Policlinico University Hospital, University of Modena, and Reggio Emilia, MO, Italy, between November 2000 and November 2017; 102 patients who underwent LT were considered eligible for inclusion in the study. CONCLUSIONS: The multidisciplinary approach, together with blood, urinary, and hair tests, allows identification of early recurrences and improves survival. Further studies are necessary to understand how multidisciplinary teams can change the 6-month rule in patient selection.

Gastric Mucormycosis in a Liver and Kidney Transplant Recipient: Case Report and Concise Review of Literature.

Mucormycosis is an uncommonly encountered fungal infection in solid organ transplantation. The infection is severe and often results in a fatal outcome. The most common presentations are rhino-sino-orbital and pulmonary disease. We describe a rare case of gastric mucormycosis in a patient with a combined liver-kidney transplant affected by glycogen storage disease type Ia. A 42-year-old female patient presented with gastric pain and melena 26 days after transplantation. Evaluation with upper endoscopy showed two bleeding gastric ulcers. Histological examination of gastric specimens revealed fungal hyphae with evidence of Mucormycetes at subsequent molecular analysis. Immunosuppressive therapy was reduced and antifungal therapy consisting of liposomal amphotericin B and posaconazole was promptly introduced. Gastrointestinal side effects of posaconazole and acute T-cell rejection of renal graft complicated management of the case. A prolonged course of daily injections of amphotericin B together with a slight increase of immunosuppression favored successful treatment of mucormycosis as well as of graft rejection. At 2-year follow-up, the woman was found to have maintained normal renal and liver function. We conclude that judicious personalization of antimicrobial and antirejection therapy should be considered to resolve every life-threatening case of mucormycosis in solid organ transplantation.

Multimodal oncological approach in patients affected by recurrent hepatocellular carcinoma after liver transplantation.

OBJECTIVE: Hepatocellular Carcinoma (HCC) represents the fifth most common malignancy and the third cancer-related cause of death worldwide. Liver transplantation (LT) is an excellent treatment for patients with small HCC associated with cirrhosis. The purpose of this review is to investigate the possible strategies for the treatment of HCC recurrence after LT based on current clinical evidence. MATERIALS AND METHODS: A systematic literature search was performed independently by two of the authors using PubMed, EMBASE, Scopus and the Cochrane Library Central. The search was limited to studies in humans and to those reported in the English language. RESULTS: Thanks to the introduction of strict selection criteria, LT for HCC has achieved a survival rate of 85% at five years. However, the recurrence of HCC after transplantation remains a serious problem that affects about 20% of post-transplant cases. While most recurrences occur within the first 2 years, late recurrences have been described. The prognosis of recurrence is poor despite numerous proposals of the therapeutic option. Lower levels of immunosuppressive therapy and use of mammalian targets of rapamycin (mTORs) is a potential preventive strategy to reduce HCC recurrence post-Lt. Surgical resection and locoregional therapies (mainly TACE and RFA) play a very important role and are associated with improved survival. Conversely, multikinase inhibitors such as Sorafenib and their association with mTOR inhibitors play a role in cases of advanced HCC recurrence not suitable for the surgical or ablative approach. CONCLUSIONS: Treating HCC recurrence is a multidisciplinary workup involving hepatologists, surgeons, oncologists and radiologists in order to offer a patient-tailored therapy.

Multimodal approach of advanced gastric cancer: based therapeutic algorithm.

Gastric cancer (GC) is the third leading cause of cancer death in both sexes worldwide, with the highest estimated mortality rates in Eastern Asia and the lowest in Northern America. However, the availability of modern treatment has improved the survival and the prognosis is often poor due to biological characteristics of the disease. In oncology, we are living in the "Era" of target treatment and, to know biological aspects, prognostic factors and predictive response informations to therapy in GC is mandatory to apply the best strategy of treatment.The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC. The purpose of this review, according to the recently published English literature, is to summarize existing data on prognostic aspects and predictive factors to response to therapy in GC and to analyze also others therapeutic approaches (surgery and radiotherapy) in locally, locally advanced and advanced GC. Moreover, the multidisciplinary approach (chemotherapy, surgery and radiotherapy) can improve the prognosis of GC.

Kidney Transplantation in HIV-Infected Recipients: Therapeutic Strategy and Outcomes in Monocentric Experience.

BACKGROUND: In Human immunodeficiency virus (HIV)-positive patients undergoing kidney transplantation, outcomes and immunosuppression (IS) protocol are not yet established due to infectious and neoplastic risks as well as to pharmacokinetic interactions with antiretroviral therapy (TARV). METHODS: We report a retrospective, 1-center study on 18 HIV+ patients undergoing, between October 2007 and September 2015, kidney transplantation (13 cases) or combined kidney-liver transplant (5 cases). Inclusion criteria for transplant were based on the Italian National Transplant Center protocol. IS regimen was based on quick tapering of steroids and the use of mTOR inhibitors (mTORi) with low dose of calcineurin inhibitors (CNI). In the early post-transplant period, TARV was based on enfuvirtide, raltegravir, plus 1 or more nucleoside analogues. RESULTS: In a mean follow-up of 3.1 years, patient survival rate at 1 and 3 years was, respectively, 86.6% and 84.6%, whereas graft survival was 81.2% and 78.6%. Cumulative rejection rate was 20.0% and 26.6% (1- and 3-year results). Median eGFR (MDRD) was 58.8 mL/min and 51.9 mL/min at 1 and 3 years. We had 9 cases of clinically relevant infections (2 Pneumocystis jirovecii pneumonia, 1 pulmonary aspergillosis, 2 severe sepsis, and 4 HCV reactivation) as well as 1 case (5.5%) of HIV reactivation. CONCLUSIONS: IS therapy based on mTORi and low CNI dose ensures good graft survival, low rate of acute rejection, limited drug toxicity, and control of HIV disease. TARV has no significant interaction with IS therapy.

Vacuum-Assisted Closure Therapy in Patients Undergoing Liver Transplantation With Necessity to Maintain Open Abdomen.

BACKGROUND: Negative-pressure wound therapy (NPWT) has been recognized as a valid method of temporary abdominal closure. The role of open abdomen (OA) in the management of abdominal sepsis has been a controversial issue. Recent experimental and clinical studies have indicated that vacuum-assisted closure (VAC) is associated with superior outcomes in the treatment of OA conditions, but sufficient proof of efficacy and effectiveness is lacking. METHODS: We enrolled in this observational study all patients who had undergone liver transplantation (LT) for all causes between 2007 and 2014 in whom we needed to use VAC therapy, describing the pathology that led to the complication, length of hospitalization, graft survival, microbial identifications, and causes of death. RESULTS: We enrolled 11 patients-6 men (55%) and 5 women (45%), from 41.92 to 64.96 years old (mean, 57.62 ± 6.56 years) -who went to LT for different pathologies. The mean hospital stay was 56.72 ± 36.40 days (range, 8-133 days). Graft survival was 35.65 ± 31.61 months (range, 1.51-89.19 months). Six of 11 patients died (55%) of different causes; in particular, 4 patients died 1 to 3 months after the procedures that led to the condition of OA for septic shock and subsequent multi-organ failure. CONCLUSIONS: Complications related to the use of NPWT, such as painful management and bleeding, are rare and mild when the device is used properly. Although studies are needed to verify the real cost/benefit ratio in this application of VAC therapy, we consider it a useful means to treat the OA condition.

Incidental Intra-Hepatic Cholangiocarcinoma and Hepatocholangiocarcinoma in Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cholangiocarcinoma (CCA) is an aggressive malignancy of the biliary tract that is a challenging issue for the medical community, with increasing incidence. Risk factors for CCA are similar to those known for hepatocellular carcinoma (HCC), such as cirrhosis, chronic hepatitis B and C, obesity, diabetes, and alcohol. We describe the outcome and the management of patients who underwent liver transplantation (LT) with an incidental diagnosis of intrahepatic (iCCA) or hepatocholangiocarcinoma (CHC). METHODS: From 2000 to May 2015, 655 LT were performed LT at the Liver Transplant Center in Modena, Italy. We retrospectively reviewed the pathological data of the explanted livers, finding 5 cases of iCCA or CHC. The pathological examination of the explanted livers showed 1 case of iCCA; 1 case of multifocal HCC associated with a nodule of iCCA; 2 cases of CHC associated with nodules of HCC; and 1 case of CHC associated with iCCA. Mean disease-free survival (DFS) was 15.49 months (1.55-42.04) and mean overall survival (OS) was 24.76 months (3.91-75.49). All patients died of recurrent tumor progression. RESULTS: iCCA incidental finding after LT affects patient outcomes, massively causing OS and DFS reduction. We stress the necessity of a more accurate selection of the candidates whenever an augmented risk of iCCA or CHC is present. CONCLUSIONS: Further investigations are required to better understand the role of LT in these patients and to define the best management for them once they have been transplanted and the histological examination reveals the presence of iCCA or CHC.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Intrahepatic blood flow redistribution after temporary occlusion of the middle hepatic vein during right lobe liver donation: report of a case.

INTRODUCTION: One of the critical factors that influence graft function after live donor liver transplantation is the presence or absence of global or sectorial liver congestion. Many authors advocate for routine middle hepatic vein (MHV) reconstruction because it is often difficult to determine when the MHV or one of its major branches have functional significance. Predictive tests to assess hemodynamic and functional significance of the MHV and its tributaries are still under study. CASE REPORT: We have described a novel intraoperative manipulation and Doppler ultrasonographic evaluation that led to the decision to include the MHV with the right lobe graft.

Long-term maintenance of sustained virological response in liver transplant recipients treated for recurrent hepatitis C.

BACKGROUND: The recurrence of hepatitis C viral infection is common after liver transplant, and achieving a sustained virological response to antiviral treatment is desirable for reducing the risk of graft loss and improving patients' survival. AIM: To investigate the long-term maintenance of sustained virological response in liver transplant recipients with hepatitis C recurrence. METHODS: 436 Liver transplant recipients (74.1% genotype 1) who underwent combined antiviral therapy for hepatitis C recurrence were retrospectively evaluated. RESULTS: The overall sustained virological response rate was 40% (173/436 patients), and the mean follow-up after liver transplantation was 11±3.5 years (range, 5-24). Patients with a sustained virological response demonstrated a 5-year survival rate of 97% and a 10-year survival rate of 93%; all but 6 (3%) patients remained hepatitis C virus RNA-negative during follow-up. Genotype non-1 (p=0.007), treatment duration >80% of the scheduled period (p=0.027), and early virological response (p=0.002), were associated with the maintenance of sustained virological response as indicated by univariate analysis. Early virological response was the only independent predictor of sustained virological response maintenance (p=0.008). CONCLUSIONS: Sustained virological response achieved after combined antiviral treatment is maintained in liver transplant patients with recurrent hepatitis C and is associated with an excellent 5-year survival.

Multiple ways to manage portal thrombosis during liver transplantation: surgical techniques and outcomes.

BACKGROUND: Portal vein thrombosis (PVT) is a well-recognized complication of chronic liver disease with a prevalence ranging from 1% to 16%. MATERIALS AND METHODS: We performed a retrospective review of 447 consecutive patients who underwent liver transplantation (OLT) between October 2000 and December 2011 comparing 51 recipients with PVT (study group) with 399 without PVT (control group). The aim of this study was to determine the impact of pre-existent PVT on the surgical procedure, to identify specific preventable perioperative complications, and based on our studies and other works, to determine whether this group of patients are acceptable candidates for OLT. RESULTS: Among the 51 patients with PVT, 44 showed partial and 7 complete thrombosis. In 47 cases, we performed a thromboendovenectomy. There were six anastomoses at the confluence of the superior mesenteric vein (SMV) and one, with a venous graft interposition. In four complete thrombosis recipients we performed an extra-anatomic by pass between the main trunk of the SMV and the donor portal vein. Compared with the control group, regarding preoperative characteristics, PVT patients were older at the time of transplantation (P = .001) and had a higher use of TIPS (P = .02). The operative characteristics showed a longer warm ischemia time in the PVT group (46.9 ± 22.5 vs 39.3 ± 15 min; P = .004). There were significant differences in postoperative evaluations, nor in the complication rates. Overall survivals at 10 years were similar: 61.7% versus 65.3%; (P = .9). CONCLUSION: Although PVT was associated with greater operative complexity, it had no influence on postoperative complications or overall survival.

Endovenous 808-nm diode laser occlusion of perforating veins and varicose collaterals: a prospective study of 482 limbs.

BACKGROUND: Endovenous laser ablation (EVLA) was performed in the treatment of great and small saphenous veins (GSVs, SSVs), perforating veins (PVs), and varicose collaterals (VCs). OBJECTIVE To verify the outcome in PVs and VCs. MATERIALS AND METHODS: Four hundred eighty-two limbs of 306 patients were studied. EVLA was performed on 167 GSVs, 52 SSVs, and 534 PVs of 303 limbs and on VCs of 467 limbs; 133 GSVs were stripped, 300 of saphenofemoral junctions (SFJs) and 45 saphenopopliteal junctions (SPJs) were interrupted. Limbs were selected using duplex ultrasound examination and photographs; PVs-VCs diameter (<4 mm) and VC length were measured. EVLA was performed using a 808-nm diode laser, 0.6-mm fibers, continuous emission, 4 to 10 W, and 10 to 20 J/cm. Follow-up on 467 limbs occurred over a mean 27.5 months (range 3 months to 6 years); 98 limbs were followed up for longer than 4 years. RESULTS: Operating time range from 10 to 30 minutes per limb. Blood vaporization, thrombosis, fibrosis, and atrophy prevailed in PVs and in the large VCs (>4 mm) and massive coagulation in the smaller (<4 mm). High rate of occlusion was seen, with different rates of patent PV-VC mainly in diameter >6 mm. Thirty-nine out of 511 patent PVs (7.6%) and 96 out of 778 VCs (12-13%) were re-treated using EVLA or foam sclerotherapy. Minor complications occurred in 88 of the 778 (11%). CONCLUSIONS: EVLA of PVs and VCs is effective and faster than surgery in 2- to 6-mm PVs and VCs using an 808-nm diode laser.

University of Modena experience in HIV-positive patients undergoing liver transplantation.

INTRODUCTION: Highly effective antiretroviral therapy in the last decade has increased the survival rates of HIV-positive patients, yielding a greater number of HIV patients suffering from liver-related disease. Liver transplantation (LT) is the only curative treatment for end-stage liver disease (ESLD) associated or not with hepatocellular carcinoma (HCC). PATIENTS AND METHODS: From June 2003 to September 2010, 23 patients underwent cadaveric donor LT for ESLD at our institution. Inclusion criteria followed the Italian Protocol for LT in HIV-positive patients. Immunosuppressive regimens were based on cyclosporine or tacrolimus, eventually switched to Rapamycin. RESULTS: The median CD4 T-cell count was 275/mmc (range=119-924). All patients were affected by ESLD, which was associated with HCC in 14 cases. Ten patients were within the Milan criteria and four patients exceeded them but were within the San Francisco criteria. Conversion from calcineurin inhibitors (CNI) to rapamycin occurred in ten cases. Hepatitis C virus (HCV) recurrence occurred in 13/21 HCV-positive patients. Acute cellular rejection occurred in eight patients with one developing chronic cellular rejection. Overall patient and graft survivals at 80 months were 50% and 45% respectively. DISCUSSION: LT in HIV-positive patients is a feasible procedure, even if in our experience was burdened by a greater incidence of complications including HCV recurrence and infection compared with HIV-negative patients.