Oncological safety of hysteroscopy in endometrial cancer.

OBJECTIVE: It has been suggested that the manipulation of neoplastic tissue during hysteroscopy may lead to dissemination of tumor cells into the peritoneal cavity and worsen prognosis and overall survival. The goal of this study was to assess the oncological safety comparing hysteroscopy to Pipelle blind biopsy in the presurgical diagnosis of patients with endometrial cancer. METHODS: We performed a retrospective multicentric study among patients who had received primary surgical treatment for endometrial cancer. A multivariate statistical analysis model was used to compare relapse and survival rates in patients who had been evaluated preoperatively either by hysteroscopy or Pipelle biopsy. The relapse rate, disease-free survival, and overall survival were assessed as the main outcomes. The histological type, tumor size, myometrial invasion, International Federation of Gynecology and Obstetrics (FIGO) stage, surgical approach, use of a uterine manipulator, and adjuvant treatment were also included in the analysis. RESULTS: A total of 1731 women from 15 centers were included: 1044 in the hysteroscopy group and 687 in the Pipelle sampling group. 225 patients relapsed during the 10 year follow-up period: 139 (13.3%) in the hysteroscopy group and 86 (12.4%) in the Pipelle sampling group. There is no evidence of an association between the use of hysteroscopy as a diagnostic method and relapse rate (HR 1.24, 95% CI 0.92 to 1.66; p=0.16), lower disease-free survival (HR 1.23, 95% CI 0.92 to 1.66; p=0.15), or overall survival (HR 0.95, 95% CI 0.70 to 1.29; p=0.76). CONCLUSION: Hysteroscopy is a safe diagnostic method for patients with endometrial cancer with no impact on oncological outcomes when compared with sampling by Pipelle.

Metabolic syndrome before liver transplantation: does it have an impact on post liver transplantation outcome?

INTRODUCTION: Metabolic syndrome (MS) and cardiovascular risk factors are common in liver transplant (LT) candidates and recipients. Cardiovascular events and de novo tumors are increasingly common causes of mortality in liver transplant recipients. The aim of this study were (i) assess the prevalence of MS in LT recipients and its growth over the years and (ii) determine if the presence of MS pre-LT is associated with a higher risk of post-LT cardiovascular events (CVE), de novo tumors or early and late survival. PATIENTS AND METHODS: A retrospective study was performed that included LT recipients from January 2012 to December 2017. Baseline features (MS before LT and at 1year post-LT) and outcomes (CVE, de novo tumors and survival) were recorded. RESULTS: 483 recipients were included, MS was present in 20% of pre-LT with an increasing prevalence over time, from 16% in 2012 to 34% in 2017 (p=0.025). One-year post-LT, an additional 12% had developed de novo MS. At a median of 56-months follow-up, 13% developed a CVE and 9% a de novo tumor. One and 5-yr survival rates were 91% and 83% in those with pre-LT MS and 93% and 85% in those without (p=0.94).The presence of MS before LT was independently associated with a higher risk of post-LT CVE (HR: 2.66 IC (95%): 1.6-4.4 p< 0.001), but not with de novo tumors (p=0.94) nor early and late survival (p=0.58 and p=0.87). CONCLUSION: Pre-LT MS is increasing among LT candidates and is associated with a higher risk of post-LT morbidity CVE yet without affecting mortality. .

Endometrial cancer: predictors and oncological safety of tumor tissue manipulation.

PURPOSE: The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results. METHODS: We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen. RESULTS: A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479). CONCLUSION: Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.

Preoperative sampling in endometrial cancer: evaluation of the histopathological agreement with definitive surgical specimen.

PURPOSE: The main goal of this study is to assess the diagnostic agreement between preoperative biopsy and definitive histology of the surgical specimen to determine which sampling method is most suitable for diagnosis of early-stage endometrial cancer. METHODS: We performed a retrospective multicentric study to assess the correlation between three endometrial sampling methods (hysteroscopy, pipelle and D&C) in patients who had undergone preoperative endometrial biopsy and received primary surgical treatment for endometrial cancer. The primary objective was the agreement rate between hysteroscopy (HSC), endometrial biopsy (pipelle) and dilatation and curettage (D&C). RESULTS: A total of 1833 women who underwent preoperative sampling at 15 centers were included: 1042 biopsies were performed by HSC, 703 by pipelle and 88 by D&C. All three methods presented a moderate diagnostic concordance (κ = 0.40-0.61) with the definitive specimen's histology: HSC (κ = 0.47), pipelle sampling (κ = 0.48) and D&C (κ = 0.48). Likewise, a subgroup analysis was performed by histological subtype comparing HSC and endometrial biopsy, showing that neither is superior as a diagnostic method. CONCLUSIONS: According to this study, the use of pipelle sampling could become an adequate diagnostic method in endometrial cancer due to its similar agreement to HSC, ease of use and affordability.

MicroRNA-4732-3p Is Dysregulated in Breast Cancer Patients with Cardiotoxicity, and Its Therapeutic Delivery Protects the Heart from Doxorubicin-Induced Oxidative Stress in Rats.

Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFß and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.

Real-life experience with 4 years of golimumab persistence in ulcerative colitis patients.

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 ± 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 ± 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p = 0.037 and p = 0.008, respectively). During a follow-up of 17.25 ± 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

Leiomyosarcoma of the inferior vena cava--a very rare case report.

The authors present a case report of a patient with abdominal pain that began 6 months before hospital admission. Ambulatory abdominal echography and computed tomography (CT) revealed partial thrombosis of the inferior vena cava (IVC) with right atrial extension. During hospitalization, magnetic resonance imaging (MRI) revealed aspects suggesting a tumoral lesion of the right atrium, rather than a thrombus, with tumoral extension to the IVC. The echocardiogram showed images suggesting a right atrial tumor. Transesophageal echocardiography confirmed the diagnosis. During surgery, an IVC tumor was found invading the right atrium, which histopathology confirmed as a leiomyosarcoma. The authors present this case because this type of tumor is rare (21 cases worldwide at this anatomic site), it is difficult to diagnose, and its management has not been adequately described. The authors review the literature relevant to this case.

Renal cortical necrosis secondary to thrombotic microangiopathy in the context of acute promyelocytic leukaemia blast crisis.

A 37-year-old patient was transferred to Haematology from the ENT Emergency Department where he had been admitted due to tonsillitis. He displayed anaemia and leukopenia and had agranulocytosis in the study. A day later the patient had blast crisis, and was diagnosed with myeloid acute leukaemia. Due to blast crisis the patient experienced sudden back pain, with oliguria and renal function deterioration followed by anaemia, in the context of haemolysis consistent with thrombotic microangiopathy, and as such, we were consulted. We began treatment with plasmapheresis and on the following day we performed haemodialysis (we carried out a total of 12 sessions of plasmapheresis until haemolysis disappeared). Five days later there was respiratory failure, and the patient was consequently transferred to the Intensive Care Unit, where he continued treatment with plasmapheresis and haemodialysis. The patient remained anuric thereafter, requiring haemodialysis, with no sign of renal recovery. Once platelet levels normalised with haematology chemotherapy, a percutaneous renal biopsy was performed, which confirmed the diagnosis of cortical necrosis. Finally, the patient underwent renal replacement therapy by regular haemodialysis.

Treatment by long haemodialysis sessions with high cut-off filters in myeloma cast nephropathy: our experience.

UNLABELLED: Multiple myeloma (MM) is the uncontrolled proliferation of plasma cells with variable amounts of production of immunoglobulins or their chains. Acute renal failure can be a symptom of MM, and it is sometimes its form of presentation. Circulating free light chains (FLC) could lead to renal failure due to their intratubular precipitation, causing a cast nephropathy. The treatment of myeloma, adequate hydration and the removal of FLC by apheresis techniques are currently the treatments that are accepted for this disease. Several apheresis techniques have been attempted for the removal of FLC, with long haemodialysis sessions with filters for the removal of these light chains (high cut-off filters) being proposed as the most effective treatment for myeloma nephropathy. METHODS: We report 5 cases of myeloma nephropathy: three had cast nephropathy (CN) diagnosed by renal biopsy and the other two had a high probability of CN (FLC levels >500 mg/l). They were treated with long haemodialysis sessions with a high cut-off membrane. All patients had suffered acute renal failure; four required renal replacement therapy and one patient had advanced renal failure. In all patients, FLC levels were very high. They received specific treatment for myeloma in addition to high cut-off haemodialysis until they achieved FLC levels of <500 mg/l. RESULTS: Four of the five patients recovered renal function, and became independent of dialysis. The progression time for myeloma from the time the first symptoms appeared varied (1-6 months). The number of treatment sessions ranged from 8-16. The patient with the longest progression time required more sessions and did not recover renal function. CONCLUSIONS: Long haemodialysis sessions with high cut-off filters in addition to specific myeloma chemotherapy seems to be an effective treatment for acute renal failure due to myeloma nephropathy. The early initiation of treatment could be a determining factor for the response.

Incidence of acute myocardial infarction in the evolution of dialysis patients.

BACKGROUND: Although the estimated frequency of coronary artery disease (CAD) in patients on dialysis is very high, there is considerable variation in the studies published to date regarding the rate of acute myocardial infarction (AMI) in these patients. OBJECTIVE: To establish the incidence of AMI and to analyse the characteristics and consequences of this entity on the clinical progression of incident dialysis patients. METHODS: We recorded AMI in the patients treated in our dialysis unit between 01/01/1999 and 31/12/07. The variables assessed were: prior diagnosis of diabetes, hypertension, CAD (AMI or lesions observed in coronary angiography), ischaemic cerebrovascular accident, advanced peripheral artery disease (PAD), atrial fibrillation and tobacco use. Biochemical analyses included: urea, creatinine, haematocrit, calcium, phosphorous, iPTH, lipids and albumin. Follow-up lasted until transplant, death, loss to follow-up or study end in Dec. 2010. RESULTS: Of the 576 patients recruited (aged 64.6 ± 16 years), 24.7% had diabetes, 82.3% were on haemodialysis (17.7% on peritoneal dialysis), and 34 (5.9%) had a previous diagnosis of CAD. In a follow-up lasting a mean of 40.2 ± 32 months (1931.5 patient-years), 40 patients (6.9%) suffered an AMI. The incidence was 2.13/100 patient-years. The patients without CAD had an incidence of 1.84/100 patient-years and those with a previous diagnosis of CAD had an incidence of 7.53/100 patient-years. In 22.5% of patients, AMI happened in the first 3 months of dialysis, and 37.5% in the 1st year. Of the 40 AMI, 15 were with ST-segment elevation (incidence: 0.79/100 patient-years) and 25 were non ST-segment elevation (incidence: 1.33/100 patient-years). The factors that predicted the occurrence of AMI in dialysis were older age (OR: 1.037; 95% CI: 1.009-1.067; P=.011), previous CAD (OR: 3.35; 95% CI: 1.48-7.16; P=.004), and diabetes as a cause of nephropathy (OR: 2.96; 95% CI: 1.49-5.86; P=.002). In-hospital mortality was 30%, with 72.5% of deaths occurring in the 1st year and 82.5% in the 2nd; 80% of the patients who underwent a coronary angiography had multi-vessel disease. CONCLUSIONS: The incidence of AMI in incident dialysis patients is high. In previous coronary disease patients, the incidence is 3-fold higher. Post-infarction mortality is very high and multi-vessel disease is very frequent.