Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Opioid-free anesthesia for open radical cystectomy in morbid obesity.

Opioid-free anaesthesia shows evidence about its efectivity and security, even though its risks and benefits are not well defined. Neither are the patient profile or sort of surgery where it could be superior to the conventional opioid-based anaesthetic technique. Aggressive and/or long-lasting surgeries set out several queries on this technique regarding sudden hemodynamic changes, as it does not produce sympatholysis through µ receptor and there is modest experience in this technique. A morbidly obese patient received open radical cystectomy with Bricker-type urinary diversion using infraumbilical incision under OFA protocol, maintaining an adequate hemodynamic stability and excellent analgesia in postoperatory care without using any intraoperative opioids. Opioid-free anaesthesia technique is developing its evidence. However, it is necessary to keep on researching its clinical applications, different drug combinations and solutions to its expected complications.

Patient-centered Outcomes in Breast Cancer: Description of EQ-5D-5L and EORTC-QLQ-BR23 Measurements in Real-world Data and Their Association With Survival.

AIMS: In recent years, major improvements in breast cancer treatments have led to a significant increase in survival. Despite that, this population's quality of life (QoL) information is lacking, especially real-world data. MATERIALS AND METHODS: This was a prospective, multicentre, observational study of female breast cancer patients, without prior systemic treatment, treated between 2012 and 2019 in private health care in Brazil. QoL was assessed by two questionnaires, the EQ-5D-5L and the EORTC-QLQ-BR23. Additional data were retrospectively collected. RESULTS: The study comprised 1372 patients, most with early-stage disease (80.2% stages 0-II). At a median follow-up of 25.6 months, the estimated 3-year overall survival was 93.6%. Patients with locally advanced and metastatic breast cancer had the lowest visual analogue scale scores and the highest symptom burden in all dimensions of EQ-5D-5L, but with the most significant improvement after treatment. With the EORTC-QLQ-BR23 questionnaire, patients undergoing lumpectomy had a better perception of body image. Axillary dissection led to greater arm symptoms after 12 months, radiotherapy enhanced breast symptoms and patients treated with chemotherapy had significant worsening in the effects of systemic therapy compared with endocrine or HER2 therapy. Staging and immunohistochemical subtype correlated with survival and with several QoL parameters, but overall survival was not independently affected by patient-reported outcomes in this cohort. CONCLUSION: Our results show that early diagnosis and access to treatments with fewer side-effects, such as endocrine or targeted therapy, and less aggressive surgeries are the best strategies to achieve a better QoL for breast cancer patients.

Opioid-free anesthesia for open radical cystectomy in morbid obesity. / Anestesia libre de opioides para cistectomía radical laparotómica en obesidad mórbida.

Opioid-free anaesthesia shows evidence about its efectivity and security, even though its risks and benefits are not well defined. Neither are the patient profile or sort of surgery where it could be superior to the conventional opioid-based anaesthetic technique. Aggressive and/or long-lasting surgeries set out several queries on this technique regarding sudden hemodynamic changes, as it does not produce sympatholysis through µ receptor and there is modest experience in this technique. A morbidly obese patient received open radical cystectomy with Bricker-type urinary diversion using infraumbilical incision under OFA protocol, maintaining an adequate hemodynamic stability and excellent analgesia in postoperatory care without using any intraoperative opioids. Opioid-free anaesthesia technique is developing its evidence. However, it is necessary to keep on researching its clinical applications, different drug combinations and solutions to its expected complications.

Rationale, design and methodology of TESEO study: a registry of thrombosis and neoplasia of SEOM (Spanish Society of Medical Oncology).

BACKGROUND AND RATIONALE: Thromboembolic complications are a serious, preventable and common event in cancer patients that contributes to increasing morbidity and mortality. Despite increasing knowledge on cancer-associated thrombosis (CAT), there are still several aspects of diagnosis, clinical management, treatment and prognosis with uncertainties that are under-represented in randomized clinical trials. For this reason, the Spanish Society of Medical Oncology (SEOM) launched in June 2018 a registry of CAT. METHODS/DESIGN: TESEO is an ongoing prospective, non-interventional, multicentric study in consecutive cancer patients with newly diagnosed of thromboembolic event (TEE). Eligibility criteria include being > 18 years with a histologically confirmed diagnosis of cancer and a symptomatic or incidental TEE confirmed with an imaging technique in the previous month or any time after the cancer diagnosis and signing of informed consent. The study consists of two types of integrated but independent prospective registries. Regular CAT sub-registry includes information on patient's cancer´s characteristics, anticoagulant treatment provided and outcome data. Special CAT sub-registry includes variables related to special situations of CAT that comprise patients with severe kidney failure, thrombocytopenia, high risk of bleeding related to the cancer or with coexistence of bleeding and patients who receive new treatments such a targeted therapy, antiangiogenics agents and immunotherapy. The registry considers the status of the cancer and the time to assess how the prognosis is changed based on when the thrombus occurs. Some outcomes such as rethrombosis, major bleeding, tumor progression and survival will be valued in various time intervals including 1, 3, 6 and 12 months after the even in the first year; and then every 6 months until the patient's death. RESULTS: After 18 months and with 35 centers and researchers, the registry has 1128 patients. CONCLUSION: TESEO registry will provide clinical real-world evidence for prevention, treatment and complications of CAT in different scenarios that are under-represented in randomized clinical trials.

Predicted concentrations of anticancer drugs in the aquatic environment: What should we monitor and where should we treat?

Anticancer drugs have been detected in the aquatic environment, they have a potent mechanism of action and their consumption is expected to drastically increase in the future. Consequently, it is crucial to routinely monitor the occurrence of anticancer drugs and to develop effective treatment options to avoid their release into the environment. Prior to implementing a monitoring program, it is important to define which anticancer drugs are more prone to be found in the surface waters. In this study the consumption of anticancer drugs in the Lisbon region (Portugal), Belgium and Haryana state (India) were used to estimate the concentrations that can be expected in surface waters. Moreover, one important aspect is to define the major entry route of anticancer drugs in the aquatic environment: is it hospital or household effluents? The results disclosed in this study showed that in Belgium and Lisbon, 94 % of the total amount of anticancer drugs were delivered to outpatients, indicating that household effluents are the primary input source of these drugs and thus, upgrading the treatment in the domestic wastewater facilities should be the focus.

[Impact of opioid free anaesthesia in bariatric surgery]. / Impacto de la anestesia libre de opioides en cirugía bariátrica.

BACKGROUND: Patients subjected to bariatric surgery present a greater risk of complications due to the use of opioids. The goal is to evaluate the security and suitability of the Opioid Free Anaesthesia (OFA) protocol implemented in the Hospital Universitario Virgen de la Victoria in 2018. METHOD: Prospective study carried out on 38 patients subjected to laparoscopic bariatric surgery under the OFA protocol in the year 2018 at the H.U. Virgen de la Victoria (Málaga, Spain). Variables were gathered to establish haemodynamic control and perioperative pain, which were analysed using Stata v.16. RESULTS: The average age was 43 years, the average body mass index was 48.14 and the average stay in the operating theatre was 178 minutes. Control of hypertensive response following laryngoscopy occurred in 88.1% of the cases. On entering the Post Anaesthesia Care Unit (PACU), SpO2 without a supplementary contribution in the transfer showed a median of 97% with p75 = 95%, while the p75 of pain evaluation by means of Visual Analogue Scale (VAS) was 3, with 68% of patients without pain. On discharge from the PACU, all presented VAS below 4 and it was only necessary to administer a low dose of Pethidine in seven patients. CONCLUSION: The OFA has proved to be secure and achieves optimum pain control. In the reconverted cases, good control of the parameters opens up the possibility of its use in more painful surgeries.

[Laparotomy in a patient under opioid free anesthesia]. / Laparotomía en un paciente bajo anestesia libre de opiáceos.

Obese patients subjected to bariatric surgery have a high probability of presenting complications that worsen with the use of opioids and can be reduced thanks to anaesthetic techniques like opioid-free anaesthetics (OFA). The risk of having to convert the laparoscopic surgical technique into open surgery is one of the criticisms aimed at this anaesthetic modality, facing the possibility of there not being a correct sympathetic or nociceptive control. We present the case of a patient scheduled for laparoscopic bariatric surgery who, while maintaining OFA, was converted to open surgery (exploratory laparoscopy), with correct control achieved of both haemodynamics and perioperative pain.

Characterization of metals in PM1 and PM10 and health risk evaluation at an urban site in the western Mediterranean.

PM1 and PM10 samples collected in the urban center of Elche during two years were analyzed by Energy Dispersive X-Ray Fluorescence in order to determine the concentrations of the following metals: K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Sr and Ba. The influence of traffic and Saharan dust intrusions on PM levels and metal content was studied in this work. The results indicate that the coarse fraction was affected more by variations in traffic intensity than the submicron fraction. The concentrations of Ca, commonly used as a tracer of road dust, showed the highest decreases during the weekends due to the reduction in traffic-induced resuspension. In contrast, Saharan events had a greater impact on the levels of other metals such as Ti and Fe, significantly affecting their seasonal variability. High concentrations of V and Ni compared with the values found at larger urban areas were observed. This could be attributed to a significant contribution from soils, Saharan dust and even ship emissions. Enrichment factors calculated using Ti as a reference element indicate that Zn and Cu are predominantly emitted by anthropogenic activities. In fact, Saharan dust intrusions had a minor influence on the average concentrations of these metals. Non-carcinogenic health hazards associated with exposure to airborne metals were lower than the safety threshold (hazard quotient < 1). Carcinogenic risks for Cr (VI) and Ni were between 10-6 and 10-4 and, therefore, within the range considered acceptable by the US EPA.

Tissue factor variants induce monocyte transformation and transdifferentiation into endothelial cell-like cells.

Essentials Monocytes (Mo) transdifferentiate into endothelial cell-like (ECL) cells. Mo induce tissue factor (TF) expression and secretion in microvascular endothelial cells (mECs). TF interacts with Mo in a paracrine fashion, inducing their transdifferentiation into ECL cells. TF generates a positive feedback crosstalk between Mo and mECs that promotes angiogenesis. SUMMARY: Background Monocytes (Mo) increase neovascularization by releasing proangiogenic mediators and/or transdifferentiating into endothelial cell-like (ECL) cells. Recently, we have reported that Mo-microvascular endothelial cells (mECs) crosstalk induces mEC-tissue factor (TF) expression and promotes angiogenesis. However, the effect of TF on Mo remains unknown. Objective Here, we analyzed whether TF might exert angiogenic effects by inducing transdifferentiation of Mo. Methods Full-length TF (flTF) and alternatively spliced TF (asTF) were overexpressed in mECs, and their supernatants were added to Mo cultures. CD16 positivity and expression of vascular endothelial cell (VEC) markers in Mo were analyzed by fluorescence activated cell sorting. The capacity to form tube-like structures were visualized in three-dimensional cultures. Results In mECs flTF and asTF expression and release were increased in cultures with Mo-conditioned media. TF variants induced expansion of a CD16+ Mo subset and Mo transdifferentiation into ECL-cells expressing VEC markers that can form new microvessels. CD16+ Mo exposed to TF showed an increased expression of VE-cadherin, von Willebrand factor (VWF) and eNOS. Mo cultured with supernatants obtained from TF-silenced mECs did not transdifferentiate to ECL-cells or expressed VEC markers. Blocking ß1-integrin in Mo significantly blocked the effects of the TF variants. Conclusions Mo induce mECs to express and release TF, which drives CD16- Mo to transform into CD16+ Mo and to transdifferentiate into ECL-cells that can form new microvessels. Our results reveal a TF-mediated positive feedback between mECs and Mo that stimulates Mo differentiation and induces angiogenesis.

Simeprevir in combination with sofosbuvir in treatment-naïve and -experienced patients with hepatitis C virus genotype 4 infection: a Phase III, open-label, single-arm study (PLUTO).

BACKGROUND: Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and subsequent hepatocellular carcinoma. HCV genotype 4 is found widely in the Middle East, Egypt and Africa, and has also spread into Europe. There are limited data available regarding the use of direct-acting antiviral agents in HCV genotype 4-infected patients with cirrhosis. AIM: To evaluate in the phase III, open-label, single-arm PLUTO study the efficacy and safety of 12 weeks of simeprevir (HCV NS3/4A protease inhibitor) plus sofosbuvir (HCV nucleotide-analogue NS5B polymerase inhibitor) in treatment-naïve and (peg)interferon ± ribavirin-experienced HCV genotype 4-infected patients, with or without compensated cirrhosis. METHODS: Adult patients with chronic HCV genotype 4 infection received simeprevir 150 mg once-daily and sofosbuvir 400 mg once-daily for 12 weeks. The primary efficacy endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). Safety was also assessed. RESULTS: Forty patients received treatment; the majority were male (73%) and treatment-experienced (68%). Overall, 7/40 (18%) patients had compensated cirrhosis. All patients achieved SVR12 [100% (Clopper-Pearson 95% confidence interval: 91-100%)]. Adverse events, all Grade 1 or 2, were reported in 20/40 (50%) patients. No serious adverse events were reported and no patients discontinued study treatment. Grade 3 treatment-emergent laboratory abnormalities were noted in 2/40 (5%) patients. CONCLUSIONS: Treatment with simeprevir plus sofosbuvir for 12 weeks resulted in SVR12 rates of 100% in treatment-naïve and -experienced patients with HCV genotype 4 infection with or without compensated cirrhosis, and was well tolerated. [NCT02250807].

General anesthesia in patients with syndrome of Poland. / Anestesia general en paciente con síndrome de Poland.

The increased use of surgery as a treatment or as an alternative for improvement means that we have a larger number of patients in the operating theatre, including those who suffer from rare diseases. Poland Syndrome is a rare congenital disease associated with muscle development. These patients may have a broad spectrum of abnormalities, which include thoracic anomalies, which can alter the ventilatory management at the level of the airway; the possible onset of malignant hyperthermia. This leads the anaesthetist to take certain preventive measures. We report the case of a patient with Poland syndrome operated for the placement of a breast prosthesis. We avoid halogenated agents, and use a Total Intravenous Anaesthesia with propofol. The appearance of muscle spasms as a result of the use of propofol, forced us into a second anaesthesia to perform total intravenous anaesthesia with Midazolam.

Effectiveness and safety of continuous ultrasound-guided femoral nerve block versus epidural analgesia after total knee arthroplasty. / Eficacia y seguridad del bloqueo femoral continuo guiado con ecografía frente a la analgesia epidural en el postoperatorio de artroplastia total de rodilla.

OBJECTIVES: Total knee arthroplasty is associated with severe postoperative pain. The aim of this study was to compare continuous ultrasound-guided femoral nerve block with continuous epidural analgesia, both with low concentrations of local anaesthetic after total knee arthroplasty. MATERIAL AND METHODS: A prospective, randomised, unblinded study of 60 patients undergoing total knee replacement, randomised into two groups. A total of 30 patients received continuous epidural block, while the other 30 received continuous ultrasound-guided femoral nerve block, as well as using 0.125% levobupivacaine infusion in both groups. Differences in pain control, undesirable effects, and complications between the two techniques were assessed, as well as the need for opioid rescue and the level of satisfaction with the treatment received during the first 48hours after surgery. RESULTS: No differences were found in demographic and surgical variables. The quality of analgesia was similar in both groups, although in the first six hours after surgery, patients in the epidural group had less pain both at rest and with movement (P=.007 and P=.011). This difference was not observed at 24hours (P=.084 and P=.942). Pain control at rest in the femoral block group was better at 48hours after surgery than in the epidural group (P=.009). The mean consumption of morphine and level of satisfaction were similar. Epidural analgesia showed the highest rate of side effects (P=.003). CONCLUSIONS: Continuous ultrasound-guided femoral nerve block provides analgesia and morphine consumption similar to epidural analgesia, with the same level of satisfaction, but with a lower rate of side effects after total knee arthroplasty.

Serum Levels of Interleukin-34 During Acute Rejection in Liver Transplantation.

INTRODUCTION: Accumulating evidence indicates that interleukin (IL)-34 participates in T-cell homeostasis and tolerance due to the ability of IL-34 to trigger apoptosis of Th1, Th17, and Tc1 cells, but spare Th2 cells and Treg. In addition, IL-34 exerts anti-inflammatory effects by impairing leukocyte adhesion and transendothelial migration, and reducing the secretion of proinflammatory cytokines. The aim of our study was to investigate the time course of serum levels of IL-34 during hepatic allograft rejection. METHODS: Serum levels of IL-34 were determined in 20 healthy subjects and 45 hepatic transplant recipients. These patients were divided into 2 groups: group I was composed of 15 patients with acute rejection, and group II was composed of 30 patients without acute rejection. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy. RESULTS: The concentrations of IL-34 were higher in the rejection group vs nonrejection group during the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-34 serum levels than the controls at all times after liver transplantation. CONCLUSIONS: Our preliminary results could be related to the recent finding that IL-34 may play an immune-suppressive role in liver transplantation. In our case, although we must be cautious with serum data, increased IL-34 would help to control alloresponse during rejection and protect from graft lost.

Intraepithelial lymphocytes subsets in different forms of celiac disease.

AIM: The enumeration of intraepithelial lymphocytes subsets (total, γδ, and CD3(-) IELs) by flow cytometry (FCM), named as IEL lymphogram, constitutes a useful tool for celiac disease (CD) diagnosis. The aim of this study was to quantify IELs by FCM and their diagnostic value to differentiate active, silent and potential CD. METHODS: Prospective study of 60 active and 20 silent CD patients, and 161 controls in which duodenal biopsy and IEL quantification by FCM was performed. RESULTS: Active and silent CD patients had significant higher levels of both total and γδ IELs than absent CD patients (P < 0.0001 and P < 0.0001, P = 0.012 and P < 0.011; respectively). Active and silent CD patients had significant lower levels of CD3(-) IELs than absent CD patients (P < 0.047 and P < 0.009, respectively). Moreover, they were lower in silent than in active CD patients (P = 0.002). Changes of IELs subsets were more marked in children than adults active CD. The optimal IEL lymphogram cut off values for active CD diagnosis were: ≥10, ≥15 and ≤9 %, and with better performance characteristics for silent CD: ≥ 11, ≥10 and ≤5 %. CONCLUSION: The evaluation of IELs subsets by FCM is useful to confirm diagnosis of active and silent CD.

LRP5 associates with specific subsets of macrophages: Molecular and functional effects.

Innate and acquired immunity is involved in the progression of atherosclerosis. The molecular mechanisms ruling monocyte to macrophage (Mø) differentiation are not yet fully understood. Different subtypes of plaque macrophages that have differentiated from monocytes recruited from circulating blood, have been characterized based on surface epitopes. We have recently shown that LRP5, a member of the LDL receptor superfamily supporting Wnt signalling, has an important role in monocyte to macrophage differentiation. The aim of this study was to investigate whether the CD16- and CD16+ macrophage subsets found in human atherosclerotic plaques have a differential LRP5 expression/function and Wnt signalling potential. We show for the first time that LRP5 expression is significantly higher in human CD16+Mø derived from CD14(+)CD16(+) monocytes than in CD16-Mø macrophages derived from CD14(+)CD16(-) monocytes. LRP5 is not found in human healthy vessel or arterial intimal thickening but is found in advanced human atherosclerotic lesions co-localizing only with the CD16+Mø macrophage subset. LRP5 expressing macrophages infiltrate the deep layers of atherosclerotic plaques towards the intima-media boundaries showing increased migratory activity and higher phagocytic activity. The equivalent for human patrolling CD14(+)CD16(+) monocytes in mice, CD115(+)GR1(low) monocytes, also show an increased expression of LRP5. In summary, classical CD14(+)CD16(-)monocytes that differentiate into CD16-Mø do not express LRP5. Instead, human monocytes expressing LRP5 differentiate into CD16+Mø antiinflammatory macrophages. These antiinflammatory macrophages are found in advanced atherosclerotic human plaques. Thus LRP5 is a signature of the anti-inflammatory defensive phenotype of macrophages.

The role of new immunosuppressive drugs in nonmelanoma skin cancer in renal transplant recipients.

INTRODUCTION: Nonmelanoma skin cancer (NMSC) is the most common malignancy in patients who have received a solid organ transplant. Multiple factors are involved in the onset of posttransplant NMSC. OBJECTIVES: To analyze the relationship between new immunosuppressive drugs and the onset of NMSC in renal transplant recipients. METHOD: This was a combined retrospective and prospective observational study in which we studied 289 patients who received a kidney transplant between January 1996 and December 2010 at Hospital Universitario Doctor Peset in Valencia, Spain. RESULTS: Seventy-three patients (25.2%) developed 162 NMSCs over a median follow-up of 72 months. There were no statistically significant differences in the onset of NMSC on comparing different induction therapy strategies involving monoclonal and polyclonal antibodies. NMSCs occurred less frequently in patients treated with mammalian target of rapamycin (mTOR) inhibitors than in those treated with other immunosuppressive regimens, although the differences were not statistically significant. Three of 5 patients with recurrent NMSC who were switched from calcineurin inhibitors to mTOR inhibitors developed additional NMSCs despite the change. CONCLUSIONS: Induction therapy with monoclonal and polyclonal antibodies in renal transplant recipients is not associated with an increased risk of NMSC. While mTOR inhibitors are associated with a lower risk of posttransplant NMSC, it remains to be determined whether a switch to these drugs is useful in the management of patients who develop multiple NMSCs.

Polycystic liver in the adult (PLA) in Spain: analysis of a structured survey analyzing the experience and attitude of gastroenterologists in Spain.

BACKGROUND: Polycystic liver in the adult (PLA) is a rare disease characterized by chronic liver enlargement. OBJECTIVE: To analyse gastroenterologists´ involvement in, experience with, and attitude toward diagnosing, monitoring, andtreating patients with PLA in Spain. METHODS: Each of seven study coordinators contacted 15 specialists in their geographic area about participating in the study via an online structured survey. RESULTS: Of the 105 clinics contacted, 88 completed the questionnaire, with a mean of 3 patients being followed per practice, although 6 clinics were following more than 20 patients with PLA. Patients were being followed mainly by the Department of Hepatology (81 %) and/or the Department of Gastroenterology (33 %). The majority of patients were diagnosed (98 %) and monitored (97 %) using liver ultrasound. When diagnosed, 76 % of patients were under 50 years of age, females predominating.The primary treatment objective for the patients was symptomatic management. Pharmacotherapy was prescribed by 28 % of physicians: Somatostatin analogues, primarily, followed by mTOR inhibitors. One-third of the clinics indicated that they had patients who had undergone liver transplant and/or surgery. CONCLUSIONS: Ultrasound is the diagnosing and monitoring method of choice. Among the clinics using pharmacotherapy for symptomatic management, somatostatin analogues were the drugs of choice. These clinics´ infrequent use of invasive procedures suggests that they perceive the various invasive techniques as not very effective.