A narrative review of intrahepatic cholangiocarcinoma: a surgical curative option.

BACKGROUND AND OBJECTIVE: Cholangiocarcinoma (CCA) is the second commonest primary liver malignancy. Nowadays, the only available treatment with curative intent of intrahepatic cholangiocarcinoma (iCCA) is surgical resection, with a 5-year overall survival (OS) of 25-40%. However, recurrence rate remains high. In this comprehensive review, we describe the newest surgical strategies for iCCA management, including vascular resection, the role of mini-invasive surgery, liver transplant, strategies for future liver remnant augmentation, and the role of neoadjuvant therapies. METHODS: A review of medical databases (PubMed, Scopus and Cochrane Database) was conducted selecting most relevant articles in English language without a specific timeframe. KEY CONTENT AND FINDINGS: Multifocal presentation, vascular, perineural invasion, and lymph nodes involvement are associated with poor outcome. Prognostic factors are being investigated to improve therapeutic approach and outcomes. The role of lymph nodes dissection remains debated. Harvesting at least 6 lymph nodes is recommended to ensure accurate nodal staging. Liver transplantation (LT) recently represented a treatment option only in patients with unresectable early disease (≤2 cm). CONCLUSIONS: Surgical resection remains the only potentially curative treatment for patients with CCA, but continue understanding in diagnosis, operative technique and chemotherapies are changing the landscape in the prognosis. Multicentric and randomized studies are necessaries in the future research with the intent to personalize the treatments, improve patient selection for the resection and reduce recurrence rate.

Pilot, Open, Randomized, Prospective Trial for Normothermic Machine Perfusion Evaluation in Liver Transplantation From Older Donors.

Ex situ normothermic machine perfusion (NMP) might minimize ischemia/reperfusion injury (IRI) of liver grafts. In this study, 20 primary liver transplantation recipients of older grafts (≥70 years) were randomized 1:1 to NMP or cold storage (CS) groups. The primary study endpoint was to evaluate graft and patient survival at 6 months posttransplantation. The secondary endpoint was to evaluate liver and bile duct biopsies; IRI by means of peak transaminases within 7 days after surgery; and incidence of biliary complications at month 6. Liver and bile duct biopsies were collected at bench surgery, end of ex situ NMP, and end of transplant surgery. Interleukin (IL) 6, IL10, and tumor necrosis factor α (TNF-α) perfusate concentrations were tested during NMP. All grafts were successfully transplanted. Median (interquartile range) posttransplant aspartate aminotransferase peak was 709 (371-1575) IU/L for NMP and 574 (377-1162) IU/L for CS (P = 0.597). There was 1 hepatic artery thrombosis in the NMP group and 1 death in the CS group. In NMP, we observed high TNF-α perfusate levels, and these were inversely correlated with lactate (P < 0.001). Electron microscopy showed decreased mitochondrial volume density and steatosis and an increased volume density of autophagic vacuoles at the end of transplantation in NMP versus CS patients (P < 0.001). Use of NMP with older liver grafts is associated with histological evidence of reduced IRI, although the clinical benefit remains to be demonstrated.

Clinical use of an immune monitoring panel in liver transplant recipients: A prospective, observational study.

Immunosuppressive therapy greatly contributed to making liver transplantation the standard treatment for end-stage liver diseases. However, it remains difficult to predict and measure the efficacy of pharmacological immunosuppression. Therefore, we used a panel of standardized, commonly available, biomarkers with the aim to describe their changes in the first 3 weeks after the transplant procedure and assess if they may help therapeutic drug monitoring in better tailoring the dose of the immunosuppressive drugs. We prospectively studied 72 consecutive patients from the day of liver transplant (post-operative day #0) until the post-operative day #21. Leukocytes, neutrophils, lymphocytes (CD4+, CD8+), natural killer cells, monocytes, immunoglobulins and tacrolimus serum levels were measured on peripheral blood (at day 0, 3, 7, 14, 21 after surgery). Patients who developed infections showed significantly higher CD64+ monocytes on post operative day #7. IgG levels were lower on post operative day #3 among patients who later developed infections. We also found that a sharp decrease in IgA from post operative day #0 to 3 (-226 mg/dL in the ROC curve analysis) strongly correlates with the onset of infections among HCV- patients. No specific markers of rejection emerged from the tested panel of markers. Our results show that some early changes in peripheral blood white cells and immunoglobulins may predict the onset of infections and may be useful in modulating the immunosuppressive therapy. However, a panel of commonly available, standardized biomarkers do not support in improving therapeutic drug monitoring ability to individualize immunosuppressive drugs dosing.

The challenges of diagnosing thrombotic thrombocytopenic purpura in the critically ill. A case report.

Thrombotic thrombocytopenic purpura (TTP) is associated with high mortality rates. TTP may have various and different presentations depending on the organs involved. It is now recognized to be the consequence of reduction of blood levels of the disintegrin and metalloprotease with thrombospondin motifs (ADAMTS)-13. Prompt diagnosis of TTP is paramount, because plasma exchange is the only treatment capable of improving patient's survival with a dual mechanism: removal of anti-ADAMTS-13 auto-antibodies and infusion of the active protease available in the fresh frozen plasma. We report herein on the challenges in diagnosing TTP-like complications of post-surgical facial surgery in a young male patient.

Fever, mental impairment, acute anemia, and renal failure in patient undergoing orthotopic liver transplantation: posttransplantation malaria.

A case of post-transplant malaria is described. The patient presented fever and severe anemia after orthotopic liver transplantation. Diagnosis was made only after the review of donor characteristics. Although a high parasitemia was found at the moment of diagnosis, the treatment with quinine and doxycycline was successful. Donor epidemiology should always be considered for a prompt diagnosis of rare tropical diseases in the graft recipients.

Early morbidity after pancreas transplantation.

This study aims to evaluate and compare the early outcome of both pancreas-alone transplantation (PTA) and simultaneous kidney-pancreas transplantation (SPKT) focusing on the complications affecting the first month after the procedures. The records of all patients who underwent PTA or SPKT were reviewed. We considered the length of ICU stay, the need for postoperative ventilatory support, hemodynamic and metabolic data (arterial pH, serum glucose, need for exogenous insulin), infectious diseases incidence, microbiological colonization rate and any kind of postoperative complication arising during the first month after the transplantation. PTA recipients underwent a quicker surgery (P < 0.01) with shorter ICU stay (P < 0.05) and a lower need for postoperative mechanical ventilation (P < 0.05). They also had a higher hemodynamic stability (P < 0.05) with less cardiological complications (P < 0.05) in the intra- and postoperative phases; bacterial colonisation was also less frequent in PTA recipients (P < 0.05). On the contrary, no significant difference was noted with regard to postoperative nausea/vomiting, sudden myocardial death, ICU re-admissions, graft function, rate of rejection, grafts explantation and re-transplantation. PTA could be considered as preemptive for severe diabetic complications in patients with long-lasting severe type I diabetes. However, establishing the correct timing of PTA is of paramount importance in order not to expose the patients early to risks arising from a major surgery and heavy immunosuppressive treatments.