Long lasting response to second-line everolimus in kidney cancer

In the case presented here, everolimus was administered after first line therapy with sunitinib in a patient with metastatic renal cell carcinoma. The safety profile was excellent. The prolonged progression-free survival(PFS) obtained with everolimus in this case is of peculiar interest, as it is a multiple of the median PFS obtained in with everolimus in the regulatory trial. Such finding suggests that a subset of patients with renal cell carcinma may particularly benefit from everolimus.

Benefit of everolimus as a monotherapy for a refractory breast cancer patient bearing multiple genetic mutations in the PI3K/AKT/mTOR signaling pathway

A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.

Hepatitis B reactivation related to everolimus

Reactivation of hepatitis B virus (HBV) during chemotherapy is a well known complication in patients with chronic hepatitis B and cancer.The clinical manifestations range from subclinical elevation of liver enzymes to severe,potentially fatal fulminant hepatitis.Reactivation can occur in a patient with previous inactive HBV infection;either an inactive carrier or a patient with resolved hepatitis.Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved in renal cell carcinoma,neuroendocrine tumours and breast cancer.mTOR inhibitors are a new generation of drugs for targeted treatment;therefore,little about their side effects is known.Here,we report a patient with renal cell carcinoma who experienced a flare of hepatitis B infection during treatment with everolimus.Clinicians should be aware of HBV reactivation in patients who are undergoing treatment with everolimus,and screening for hepatitis B infection and prophylactic antiviral treatment should be considered.

Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor(PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

Benefit of everolimus in treatment of an intrahepatic cholangiocarcinoma patient with a PIK3CA mutation

Intrahepatic cholangiocarcinoma(ICC) is a relatively rare form of liver cancer with a poor prognosis. The therapeutic options for patients with advanced ICC are limited and usually ineffective. There is currently no approved targeted therapy for ICC, although accumulating evidence supports inhibition of the PI3K/Akt/m TOR signaling pathway as a promising therapeutic strategy in the treatment of ICC. Here, we report a patient with stage IV ICC harboring a PIK3 CA mutation who responded well to the m TOR inhibitor everolimus. Computed tomography and magnetic resonance imaging demonstrated shrinkage of the tumor and maintenance of a partial response for 6.5 mo after everolimus treatment as the best response. To the best of our knowledge, this is the first clinical case report in the literature of clinical benefit from everolimus treatment in an ICC patient with PIK3 CA mutation.

Combining cytochrome P-450 3A4 modulators and cyclosporine or everolimus in transplantation is successful

AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the investigators.RESULTS: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved 80% of cyclosporine and 56% of everolimus doses. CONCLUSION: Combining CYP3A4 modulators with CNI or mammalian target of rapamycin inhibitor, in low immunological risk kidney transplant recipients is feasible, effective, safe and affordable even in the long term.

Growth hormone abolishes the negative effects of everolimus on intestinal wound healing

AIM: To investigate whether the simultaneous treatment with human growth hormone (hGH) abolishes the negative effects of everolimus on anastomotic healing.METHODS: Forty-eight male Sprague-Dawley-rats were randomized to three groups of 16 animals each (I: vehicle; II: everolimus 3 mg/kg po; III: everolimus 3 mg/kg po + hGH 2.5 mg/kg sc). Animals were pre-treated with hGH and/or everolimus daily for seven days. Then a standard anastomosis was created in the descending colon and treatment was continued for another seven days. The anastomosis was resected in toto and the bursting pressure was assessed as a mechanical parameter of intestinal healing. Moreover, biochemical (Hydroxyproline, PCNA, MPO, MMP-2 and MMP-9) and histological (cell density, angiogenesis, amount of granulation tissue) parameters of intestinal healing were assessed.RESULTS: Anastomotic bursting pressure was significantly reduced by everolimus and a simultaneous treatment with hGH resulted in considerably higher values (I: 134 ± 19 mmHg, II: 85 ± 25 mmHg, III: 114 ± 25 mmHg; P < 0.05, I vs II; P = 0.09, I vs III and II vs III) Hydroxyproline concentration was significantly increased by hGH compared to everolimus alone (I: 14.9 ± 2.5 μg/mg, II: 8.9 ± 3.6 μg/mg, III: 11.9 ± 2.8 μg/mg; P < 0.05, I vs II/III and II vs III). The number of MPO-positive cells was reduced significantly by hGH compared to everolimus alone (I: 10 ± 1 n/mm², II: 15 ± 3 n/mm², III: 9 ± 2 n/mm²; P < 0.05, I vs II and II vs III), while the number of PCNA-positive cells were increased by hGH (I: 28 ± 3 /mm², II: 12 ± 3 /mm², III: 26 ± 12 /mm²; P < 0.05, I vs II and II vs III). Corresponding to these biochemical findings, HE-histology revealed significantly increased amount of granulation tissue in hGH-treated animals.CONCLUSION: Inhibition of intestinal wound healing by everolimus is partially neutralized by simultaeous treatment with hGH. Both inflammation as well as collagen deposition is influenced by hGH.

Everolimus vs.Rapamycin for Treating Diabetic Nephropathy in Diabetic Mouse Model

In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic（db/db） mice received everolimus（2 mg/kg every day） or rapamycin（2 mg/kg every day） for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1（TGF-β1）and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal tissue as well as in mesengial cell culture samples.Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy,and in decreasing accumulation and expansion of the extracellular matrix.However,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorption rate.

Use of everolimus in liver transplantation

In recent years, the use of mammalian target of rapamycin inhibitors has gained traction in their use as alternative or adjunct immunosuppressants in the post-liver transplantation(LT) setting. The efficacy of everolimus(EVR) in de novo LT is established and a reasonable time to initiate EVR is 30d from LT surgery. Initiating EVR early post-LT allows for calcineurin inhibitor(CNI) reduction, thus reducing nephrotoxicity in LT recipients. However, data is inadequate on the appropriate timing for conversion from CNI to EVR maintenance in order to achieve optimal renoprotective effect without compromising drug efficacy. Adverse effects of proteinuria, hypercholesterolemia and hyperlipidemia are significantly higher as compared to standard CNI and long-term implications on graft and patient survival in LT is still unclear. Future research to explore strategies to minimise EVR adverse effects will be crucial for the success of EVR as an important alternative or adjunct immunosuppressive therapy in LT.

Everolimus plus long-acting somatostatin analogs in thymic epithelial malignancies

Although thymic epithelial tumors(TETs) are rare in the general population, they represent the most frequently diagnosed primary malignant tumor of the anterior mediastinum. Unlike localized disease, metastatic disease is invariably fatal. While several chemotherapy agents have proven to be effective in TETs, somatostatin analogs are the only targeted agents with an established role in this disease. Everolimus is an m TOR inhibitor with multiple application in oncology. In this report, we show for the first time that everolimus was effective in two heavily pretreated patients with advanced TETs, with a progression-free survival longer than 1 year and minimal toxicity.

Everolimus in de novo liver transplant recipients: a systematic review

BACKGROUND： Everolimus has no nephrotoxicity and is used to treat patients with post-liver transplant chronic renal insufficiency. The present systematic review was to evaluate the efficacy and safety of everolimus in de novo liver transplant patients.DATA SOURCES： Randomized controlled trials comparing everolimus for de novo liver transplant in Pub Med, the Cochrane Library, and Science Direct published up to March 31, 2014 were searched by two independent reviewers. Mean differences and 95% confidence interval（95% CI） for renal function, relative risk（RR） and 95% CI for treated biopsy-proven acute rejection（t BPAR）, graft loss, death, neoplasms/tumor recurrence, and adverse events were collected. Meta-analyses were performed with Rev Man version 5.10.RESULTS： A total of four randomized controlled trials covering 1119 cases were included. The meta-analyses revealed that compared with standard exposure of calcineurin inhibitors（CNIs）, everolimus combined with reduced CNIs improved creatinine clearance（calculated with the Cockcroft-Gault formula） by 5.13 m L/min at one year（95% CI： 0.42-9.84; P=0.03）, and decreased t BPAR（RR： 0.56; 95% CI： 0.35-0.90; P=0.02）. Everolimus initiation with CNIs elimination improved glomerular filtration rate（GFR, measured with the modification of diet in renal disease formula） of 10.42 m L/min/1.73 m2（95% CI： 3.44-17.41; P〈0.01） one year after treatment, but in-creased t BPAR（RR： 1.71; 95% CI： 1.15-2.53; P〈0.01）. Everolimus decreased the risk of neoplasms/tumor recurrence after liver transplant（RR： 0.60; 95% CI： 0.34-1.03; P=0.06）, but was associated with greater risk of adverse events which resulted in drug discontinuation（RR： 1.98; 95% CI： 1.49-2.64; P〈0.01）. CONCLUSIONS： Early introduction of everolimus combined with low-dose or no CNI in de novo liver transplant significantly improves renal function one year post treatment. Everolimus combined with low-dose CNI decreases the risk of t BPAR one year after liver transplant, but everolimus administered without CNIs increases t BPAR.

Introduction of everolimus in kidney transplant recipients at a late posttransplant stage

This minireview focuses on the current knowledge about the introduction of everolimus(EVL),a mammalian target of rapamycin inhibitor,with calcineurin inhibitor(CNI)elimination or minimization in kidney transplant recipients at a late posttransplant stage.Within,we have summarized two major clinical trials,ASCERTAIN and APOLLO,and seven other retrospective or nonrandomized studies.In the open-label multicenter ASCERTAIN study,the estimated glomerular filtration rate(eGFR)at 24 mo after conversion was not significantly different between three groups-EVL with CNI elimination,CNI minimization and continued CNI unchanged-at a mean of 5.4 years after transplantation.However,recipients with baseline creatinine clearance higher than 50 mL/min had a greater increase in measured GFR after CNI elimination.In the open-label multicenter APOLLO study,adjusted e GFR within the on-treatment population was significantly higher in the EVL continuation group than in the CNI continuation group at 12 mo after conversion at a mean of 7 years posttransplantation.Other studies on recipients without adverse events and already having satisfactory renal function showed favorable graft function by EVL late-induction with CNI elimination or reduction.These studies showed that chronic allograft nephropathy,CNI nephrotoxicity,CNI arteriolopathy,cancer and viral infection(especially cytomegalovirus infection)may be good indications for late conversion to EVL.

Multiple indications for everolimus after liver transplantation in current clinical practice

AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical practice.METHODS: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients(7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation andpost-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo(range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo(range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of patients.CONCLUSION: Everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation.

The Role of Everolimus in the Treatment of Breast Cancer

The development of resistance to chemotherapy, endocrine therapy and anti HER2 agents in breast cancer is an important and common problem that impacts in the management of patients, particularly in the metastatic setting. This resistance has been explained in part by the activation of signal transduction pathways, including the PI3K/AKT/mTOR. The blockade with mTOR inhibitors such as everolimus is a new target agent for therapy that attempts to enhance treatment efficacy and restore tumor sensitivity. In this review article, we present the data about the use of everolimus for the treatment of breast cancer in all tumor phenotypes. Future studies that evaluate biomarkers for treatment response are needed to identify the specific populations that have the highest benefit of this new targeted therapy.

Everolimus immunosuppression reduces the serum expression of fibrosis markers in liver transplant recipients

AIM: To evaluate the expression of serum fibrosis markers in liver transplantation(LT) recipients on everolimus monotherapy compared to patients on an anti-calcineurin regimen.METHODS: This cross-sectional case-control study included LT patients on everolimus monotherapy(cases)(E)(n = 30) and matched controls on an anticalcineurin regimen(calcineurin inhibitors, CNI), paired by etiology of liver disease and time since LT(n = 30). Clinical characteristics, blood tests and elastography were collected. Serum levels of transforming growth factor-β(TGF-β), angiopoietin-1, tumor necrosis factor(TNF), platelet derived growth factor, amino-terminal propeptide of type Ⅲ procollagen(PⅢNP), hyaluronicacid(HA), VCM-1(ng/m L), interleukin(IL)-10, interferoninducible protein 10(IP-10), vascular endothelial growth factor and hepatocyte growth factor(HGF)(pg/m L) were determined by enzyme-linked immunosorbent assay. Expression of these markers between E and CNI was compared. Stratified analysis was done according to factors that may influence liver fibrosis. Variables are described with medians(interquartillic range) or percentages.RESULTS: A total of 60 patients [age: 59(49-64), hepatitis C virus(HCV): n = 21(35%), time from LT: 73 mo(16-105)] were included. Patients had been on everolimus for a median of 15 mo. No differences in inflammatory activity, APRI test or liver elastography were found between the groups. No significant differences were observed between the groups in serum levels of PⅢ NP, metalloproteinase type = 1, angiopoietin, HGF, IP-10, TNF-α, IL-10 and vascular cell adhesion molecule. Patients on E had a lower expression of TGF-β [E: 12.7(3.7-133.6), CNI: 152.5(14.4-333.2), P = 0.009] and HA [E: 702.89(329.4-838.2), CNI: 1513.6(691.9-1951.4), P = 0.001] than those on CNI. This difference was maintained in the stratified analysis when recipient age is more than 50 years(TFG-β1: P = 0.06; HA: P = 0.005), in patients without active neoplasia(TFG-β1, P = 0.009; HA: P = 0.01), according to time since LT(> than 5 years, TFG-β1: P = 0.001; HA: P = 0.002), related to previous history of biliary complications(HA: P = 0.01) and HCV recurrence(HA: P = 0.004). Liver transplant recipients with everolimus monotherapy had less serum expression of TGF-β y HA than matched patients with anti-calcineurins. This difference remains when classifying patients according to donor age and time since LT. Due to the small sample size, when examining patients with a prior history of biliary complications or recurrent HCV, the difference was nonsignificant but trends towards the lower expression of TFG-β1 in the everolimus group. Mammalian target of rapamycin(m TOR) plays a role in the transformation of quiescent hepatocellular stellate cell to their activeprofibrotic state, and experimental models have demonstrated the potential activity of m TOR inhibition in attenuating fibrogenesis.CONCLUSION: This study supports a possible role of everolimus in liver fibrosis modulation after LT in a clinical setting and suggests that tailoring immunosuppression could avoid fibrosis progression in the allograft.

Safety and performance of the EverProTM everolimus-eluting coronary stent system with biodegradable polymer in a real-world scenario

BACKGROUND The EverProTM(Sahajanand Laser Technology Ltd.,India)everolimus-eluting coronary stent system(EES)is a second-generation drug-eluting stent with a biodegradable polymer.AIM To determine the safety and performance of the EverProTM EES in patients with coronary artery disease(CAD)during a 1-year clinical follow-up.METHODS This observational,retrospective,single-center study enrolled patients who had been implanted with the EverProTM stent between June 1,2018 and January 31,2019,and had completed a 1-year follow-up period after the index procedure.The primary clinical endpoint was major adverse cardiac events(MACE)at 6 mo defined as the composite of cardiac death,myocardial infarction(MI),and target lesion revascularization(TLR).Secondary endpoints were the incidence of TLR at 1,6 and 12 mo follow-up,MACE at 1 and 12 mo follow-up,and stent thrombosis up to 1 year after the index procedure.RESULTS The study population comprised 77 patients(98 lesions).A total of 37(48.1%)patients had comorbid hypertension.In total,26(33.8%)patients presented with ST segment elevation MI and 10.4%patients with non-ST segment elevation MI.Treated lesions were located mainly in the left anterior descending artery(49%)followed by the right coronary artery(29.6%),left circumflex(12.2%)and obtuse marginal(9.2%)arteries.The majority of patients were with single-vessel disease(79%),22.2%of lesions had a mild to severe thrombus load,and 94.9%were American College of Cardiology/American Heart Association type B or C.De novo stenting was performed in 96.9%of patients and 3%were treated for in-stent restenosis.Procedural success was attained in all patients.In-hospital or followup MACE and stent thrombosis were not reported during the 1-year follow-up period.CONCLUSION These findings suggest that the EverProTM EES is a safe and effective treatment option with no MACE or stent thrombosis reported during the 1-year study period in patients with CAD.

Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients

AIM: To determine the clinical reasons for conversion to everolimus(EVL) and long-term outcomes in heart transplant(HT) recipients.METHODS: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT recipients.RESULTS: Two hundred and twenty-two patients were included(mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity(30%), chronic allograft vasculopathy(20%) and neoplasms(17%). The doses and mean levels of EVL at baseline(conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors(CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d(P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL(P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL(P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min(P < 0.001). There were 37 episodes of acute rejection in 24 patients(11%). The most frequent adverse events were oedemas(12%), infections(9%) and gastrointestinal problems(6%). EVL was suspended in 44 patients(20%). Since the database was closed at the end of the study, no further followup data is available.CONCLUSION: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

Everolimus Associated with Activated Vitamin D for Post-Transplant Increase Epstein-Barr-Virus Load Treatment. Two Case Reports

Post-transplant lymphoproliferative disease (PTLD) is an uncommon but life-threatening complication of solid-organ and blood stem-cell transplants. It is caused by an uncontrolled expansion of B lymphocytes infected with Epstein-Barr virus (EBV). It responds poorly to therapy, including reduction of immunosuppression, interferon, antivirals or chemotherapy. Therefore the optimal strategy for management is currently focused on prevention. Some centers have already introduced chemoprophylaxis and/or preemptive strategies using EBV viral load as a surveillance. Some experimental studies suggest that mTOR inhibitors inhibits growth of human EBV-transformed B lymphocytes and vitamin D had an immune response to EBV. We report two cases of an increased of blood BKV viral load after renal transplantation that were successfully treated with everolimus in association with calcitriol. This report suggests that everolimus associated with calcitriol could be an effective and safe treatment for the prevention of PTLD in transplant recipients.

Radical Operation and Everolimus Therapy for Rectal Neuroendocrine Tumor with Liver Metastases: A Case Report with Review of the Literature

Neuroendocrine tumors (NETs) are often misdiagnosed because they can involve any part of the body and have non-specific symptoms. Here, we report a case of a 39-year-old man with rectal neuroendocrine tumor (RNET) and hepatic metastases treated with a combination of radical surgery and Everolimus therapy. The patient complained of abdominal distension, pain, and constipation of one month duration. Enhanced CT scan of the abdomen, colonoscopy and Biopsy findings confirmed the diagnosis of rectal neuroendocrine tumor. As the anatomical structures were clear and the masses seemed to be resectable, we decided to initiate treatment with radical operation and Everolimus therapy. The patient has responded well to the treatment with no evidence of recurrence after 4 years of follow-up. This case is interesting because of the rarity of this neoplasm and its initial misdiagnosis as a giant hepatic carcinoma (hepatoma). It also demonstrates that a combination of curative surgical resection and Everolimus is a good option in a patient with large colorectal neuroendocrine tumors and massive hepatic metastases.

Preliminary Clinical Outcomes after Implantation of Newer-Generation Biodegradable Polymer-Coated Everolimus-Eluting Stent in “Real-World” Patients with Coronary Artery Disease

Background and Objective: In the contemporary practice, the use of drug-eluting stents is still associated with low mortality benefits, restenosis and stent thrombosis. To address these issues, newer generation, thin-strut, biodegradable polymer coated stents has been designed. Thus, the aim of the study is to assess the safety and clinical performance of the Everoflex (Sahajanand Medical Technologies Pvt. Ltd., Surat, India), a newer generation biodegradable polymer coated everolimus-eluting stent, in unselected “real-world” patients with coronary artery disease. Methods: It is a multicentre, retrospective, non-randomized, single-arm study enrolling all the consecutive patients who underwent implantation with the Everoflex for coronary artery disease from April 2014 to March 2016. The primary end-point of the study is 30-day major adverse cardiovascular events (MACE) rate, which consists of cardiac death, myocardial infarction, target lesion revascularization and target vessel revascularization. Stent thrombosis was also analyzed and reported. Results: A total of 340 patients were intervened successfully with 395 everolimus eluting stents (1.3 ± 0.6 stents per patient). Out of total patients (58.7 ± 10.5 years), 77.9% were male and comorbidities like diabetes and hypertension were observed in 31.2% and 35.3% patients, respectively. According to ACC/AHA classification, there were 34.4% type B lesions and 53.2% type C lesions, indicating a higher proportion of complexity involved. Moreover, 57.9% patients had multivessel disease and there were 15.4% total occlusions. At 30 days, follow-up was completed in 100% patients. The MACE was found to be 1.5%, which is a composite of 1.2% cardiac death and 0.3% target lesion revascularization. Stent thrombosis at 30 days was found to be 0.3%. Conclusion: The low incidence of MACE and stent thrombosis clearly depicts excellent safety and clinical performance of the Everoflex in unselected real world patients with coronary artery disease.