Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer.

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.

Early Aspirin Nonresponders Identification by Routine Use of Aggregometry Test in Patients With Left Ventricle Assist Devices Reduces the Risk of Pump Thrombosis.

Left ventricular assist device (LVAD) management is very challenging since many adverse events can occur in ongoing patients. Inadequate anticoagulation treatment can lead to life-threatening situations like ischemic stroke or pump thrombosis. The main intention of our study was to investigate if early identification of aspirin nonresponders by using aggregometry can improve anticoagulation management, reducing the risk of pump thrombosis. METHODS: From December 2010 to May 2018, 24 patients were implanted with a HeartMate II (HMII), 6 received a HeartWare HVAD system--full support VAD (HVAD), and 22 received a HeartMate III (HMIII). All patients were maintained with a target INR of 2.0 to 3.0. When the aggregometry test revealed a normal platelet function, 100 mg of aspirin were initiated. Only aspirin nonresponders were early identified by repeating the aggregometry after 7 days of aspirin administration. In acetylsalicylic acid nonresponder patients, 75 mg of clopidogrel was used, and the patients were tested again. Ticlopidine (250 mg) was used when clopidogrel was unsuccessful. RESULTS: Four patients required modification in antiplatelet therapy. Three patients (5%), 2 HVAD and 1 HMII, suffered from pump thrombosis. One patient died as a consequence of a large intracranial hemorrhagic event following thrombolytic treatment. One patient required a pump exchange; in 1 patient, thrombolytic infusion was conducted successfully. CONCLUSION: Reported rates of pump thrombosis at 12 months for patients implanted with commonly used LVADs were 6% to 12% for axial-flow pumps and 8% with centrifugal-flow devices. In our series, the reported 5% overall incidence of pump thrombosis encourages the routine use of an aggregometry test for early identification of aspirin nonresponders.

Pump Speed Optimization in Patients Implanted With the HeartMate 3 Device.

BACKGROUND: Pump speed optimization in patients implanted with a ventricular assist device represents a major challenge during the follow-up period. We present our findings on whether combined invasive hemodynamic ramp tests and cardiopulmonary exercise testing (CPX) can help optimize patient management. METHODS: Eighteen patients implanted with a HeartMate 3 (HM3) device underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 4 speed settings. Speed changes were in steps of 200 revolutions/min (rpm). Evaluation of functional capacity by CPX was conducted according to the modified Bruce protocol. RESULTS: Only 30% of patients had normal PCWPs at their original rpm settings. In going from lowest to highest speeds, cardiac output improved by 0.25 ± 0.35 L/min/step (total change, 1.28 ± 0.3 L/min), and PCWP decreased by 1.9 ± 0.73 mm Hg/step (total change, 6 ± 1.6 mm Hg). CVP and systolic blood pressure did not change significantly with rpm. The rpm assessment was adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in all patients. On CPX, all patients demonstrated good performance (peak VO2, 16.8 ± 3.5 mL/kg/min). CONCLUSION: Hemodynamic ramp testing provides an objective means of optimizing rpm, and has the potential to provide good exercise tolerance.

Pulse Oximeter Usefulness for Blood Pressure Monitoring in Patients Implanted With Latest-Generation Continuous-Flow Device HeartMate 3.

INTRODUCTION: The measurement of blood pressure (BP) and the management of hypertension in patients with continuous-flow ventricular assist devices (CF-VADs) can present unique challenges. Patients with CF-VADs often do not have a palpable pulse, and therefore traditional blood pressure measurement by auscultation or automated cuff is less reliable. We tested the efficacy of blood pressure estimation using sphygmomanometry combined with finger pulse oximetry only after a hemodynamic optimization was effected to make the values estimated approximately similar to mean arterial pressure. METHODS: Fifteen consecutive patients with a mean age of 57.8 ± 11.2 years were implanted with HeartMate 3 between November 2015 and March 2017. All patients underwent pump speed optimization by conducting a ramp test during right heart catheterization. The patients were prospectively studied during the follow-up period and mean arterial pressure was estimated using 3 different methodologies: Doppler ultrasound, pulse oximeter, and automated blood pressure cuff. For each method 3 consecutive evaluations were conducted during 3 follow-up visits. RESULTS: For each patient, 9 different evaluations were obtained (3 for each method). The overall success rate was 100% for blood pressure assessment conducted with Doppler ultrasound and pulse oximeter and 80%-87% for automated monitor evaluations. The first 2 methodologies were 100% successful, while the third was 60% successful. Pearson's correlation analyses for the Doppler ultrasound and pulse oximeter measurements showed a good correlation when evaluations conducted with the same method were compared. A high variability emerged between estimations obtained by using an automated monitor and a poor correlation was found when this method was compared to the Doppler ultrasound and pulse oximeter measurements. CONCLUSION: According to our results, the pulse oximeter method showed a high success rate and a good correlation level with the standard procedure. Our data encourage the use of oximeters for domiciliary blood pressure assessment in patients implanted with a continuous flow device.

Posterior wall as atypical localization of left atrial myxoma : Diagnosis and management.

Atrial myxomas are the most common benign cardiac neoplasms. Although the majority occur in the left atrium (LA) and are attached to the interatrial septum (75-80 % of cases), they can arise from any part of the LA and the cardiac chambers. We report the case of a 65-year-old woman who presented with features of worsening dyspnea and persistent headache. During transthoracic echocardiography, a suspected cardiac myxoma was found arising from the posterior wall of the LA.

CO(2) pneumoperitoneum induces in vitro hypoxic response culminating in apoptosis of human neuroblastoma cells.

The ablative role of minimally invasive surgery (MIS) in neuroblastoma (NB) is still controversial due to the possible CO2 pneumoperitoneum side-effects on tumor aggressiveness. It is known that CO2 produces hypoxic condition with changes in tumor microenvironment influencing cell functions. Here we investigated whether CO2 exposure affects the transcription factor HIF-1α and the apoptotic signalling pathway in SH-SY5Y NB cells. SH-SY5Y cells were exposed to a pressure of 15 mmHg CO2 (100%) for 4 h (T0) and then moved to normal condition for 24 h (T24). In control and CO2 -exposed cells, we analyzed the mRNA levels and DNA binding activity of HIF-1α. We also evaluated the proliferative activity and cell viability as well as caspase-9/3 cleavage and nuclear fragmentation. A significant increase in HIF- 1α activation was observed in SH-SY5Y cells exposed to CO2 compared to control cells. CO2 treatment also decreased the proliferation rate and the percentage of viable cells. In addition, the expression and cleavage of caspase-9 and -3 were significantly increased in NB cells exposed to CO2. These data correlated with apoptotic feature observed in CO2 -treated NB cells. Our findings show that CO2 -induced hypoxic condition exerts cytotoxic effects on NB cells by eliciting mitochondrial apoptotic pathway and thereby improving the understanding of the possible clinical impact of CO2 pneumoperitoneum on NB behaviour.

Mechanical circulatory support in advanced heart failure: single-center experience.

BACKGROUND: Currently, ventricular assist device (VAD) or total artificial heart (TAH) mechanical support provides an effective treatment of unstable patients with advanced heart failure. We report our single-center experience with mechanical circulatory support therapy. METHODS: From March 2002 to December 2012, 107 adult patients (mean age, 56.8 ± 9.9 y; range, 31-76 y) were primarly supported on temporary or long-term VAD or TAH support as treatment for refractory heart failure at our institution. Temporary extracorporeal radial VAD support (group A) was established in 49 patients (45.7%), and long-term paracorporeal and intracorporeal VAD or TAH (group B) in 58 patients (54.2%). Left ventricular (LVAD) support was established in 55 patients (51.4%; n = 33, Heartmate II; n = 6, Heartmate I XVE; n = 4, Heartware HVAD; and n = 12, Centrimag) and biventricular (BVAD/TAH) support (group B) in 28 patients (26.1%; n = 10, Thoratec paracorporeal; n = 2, Heartware HVAD, n = 1, Thoratec implantable; n = 1, Syncardia TAH; and n = 14, Centrimag). The temporary Centrimag was the only device adopted as isolated right ventricular (RVAD) support, and it was inserted in 24 patients (22.4%). RESULTS: In group A, overall mean support time was 10.2 ± 6.6 days (range, 3-43 d). In group B, LVAD mean support time was 357 ± 352.3 days (range, 1-902 d) and BVAD/TAH support time was 98 ± 82.6 days (range, 8-832 d). In group A, the overall success rate was 55.1% (27 patients). In group B, LVAD overall success rate was 74.4% (32 patients) and BVAD/TAH success rate was 50% (7 patients). Overall heart transplantation rate for both groups was 27.1% (n = 2, group A; n = 27, group B). Overall 1-year and 5-year survivals after heart transplantation were 72.4% (n = 21) and 58.6% (n = 17), respectively. CONCLUSIONS: Mechanical circulatory support is an effective strategy even in cases of end-stage heart failure according to our experience. Further improvement of VAD and TAH technologies may support their adoption as an encouraging alternative to heart transplantation in the near future.

Natural history of non-operative treatment for renal injuries in children.

AIM: Kidney is one of the solid organs injured in blunt abdominal traumas. Conservative management is well recognized in adults, but is still controversial in children. We performed a retrospective review regarding children with renal injuries observed at our Centre, analyzing the importance of a prompt diagnosis and the role of conservative treatment according to the degree of renal injury and natural history. METHODS: We reviewed 15 cases of blunt abdominal trauma with renal injuries observed during a period of 11 years. The diagnosis was confirmed by abdominal computed tomography (CT) scan and ultrasonography (US). Conservative treatment started monitoring the hemodynamic stability, the hematocrit value, the hemoglobin, the red cell count, the urine analysis. If necessary blood transfusion was performed. A follow-up from 1 month to 2 years monitored the lesions healing. RESULTS: Age of patients varied from 3 to 15 years (mean age = 6.3). Nine were males and six females. Two patients had an associated spleen lesion, thirteen had an isolated renal injury. Injury grades were classified as follows: grade I, 5 cases; grade II, 3 cases; grade III, 5 cases and grade IV, 2 cases. Non operative management was successful in 14 out of 15 cases; 1 patient with grade IV required a partial nephrectomy. At follow-up good healing of the lesions was observed. CONCLUSION: Most of renal injury related to abdominal trauma can be successfully and safely managed conservatively. Hemodynamic stability, a prompt clinical and instrumental diagnosis and grading of lesions by CT are necessary to start an effective non operative treatment.

Long-term mechanical support with the HeartMate II LVAS.

BACKGROUND: The use of left ventricular assist devices (LVAD) is an accepted therapy for patients with refractory heart failure. The HeartMate II is a small (350 g), implantable, axial-flow pump (nonpulsatile flow), which is designed to support the left ventricle for extended periods of time. Here we have reported our initial single-center clinical experience with this device as a bridge to heart transplantation. MATERIALS AND METHODS: Between March 2002 and December 2008, 18 transplantable adult patients were supported on long-term HeartMate II LVAS at our institution. The cohort included 15 men with an overall mean age of 52 +/- 8.4 years (range, 31-64 years). Primary indications for implantation were ischemic cardiomyopathy (CMP; n = 13) and idiopathic CMP (n = 5). All heart failure patients were New York Heart Association (NYHA) functional class IV. None of them had undergone prior open heart surgery. Implantation was performed via cannulation of the left ventricular apex and ascending aorta, and in each case was an elective procedure. RESULTS: Mean support time was 217 +/- 212.3 days (range, 1-665 days). Early (30-day) mortality was 27.7% (n = 5) due to multiple organ failure and sepsis as main causes of death. Bleeding requiring reoperation occurred in 6 cases (33.3%). Cerebral hemorrhage occurred in 1 case. There were 2 driveline infections and no device failure. Twelve subjects (66.6%) were successfully discharged home. Overall, 9 patients (50%) underwent transplantation and 3 are awaiting a suitable organ (2 were discharged home and 1 is in hospital). At latest follow-up, the survival rate after heart transplantation was 66.6% (n = 6). CONCLUSIONS: Long-term HeartMate II LVAS can successfully bridge patients to heart transplantation. Good mid- and long-term results may support the use of this device even for a permanent solution in nontransplantable subjects.

An uncommon case of associate intrinsic and extrinsic stenosis of the duodenum in newborn.

The incidence of congenital combinations of extrinsic and intrinsic compression of duodenum is uncommon. The authors report a rare case of a neonate with a duodenal stenosis due to the contemporary presence of an annular pancreas and wind sock web. The diagnostic strategies and management will be discussed.

Can epsilon-aminocaproic acid balance the off-pump bleeding advantage?

BACKGROUND: Aprotinin improved the control of bleeding in patients undergoing surgery with cardiopulmunary bypass, but its use was halted because of the risk of bovine spongiform encephalopathy. We then started to use epsilon-aminocaproic acid and the results in the control of bleeding were satisfactory. To assess its effectiveness in the control of postoperative bleeding precisely, we compared the results for patients operated on for myocardial revascularization on-pump and treated with epsilon-aminocaproic acid with those for patients who decidedly bleed less: off-pump patients. METHODS: Two groups of patients who had had either on- or off-pump double aortocoronary bypass surgery were retrospectively reviewed for postoperative bleeding. These two almost homogeneous group had two grafts only: left anterior descending and circumflex arteries operated on with cardiopulmonary bypass and treated with the epsilon-aminocaproic acid, and left anterior descending and right coronary arteries operated on off-pump. RESULTS: Postoperative bleeding through chest drainage at 4 h was 265+/-91.7 mL in the off-pump group and 328.4+/-131.4 mL in the on-pump group (p=0.004). But at 24 h it was 671.6+/-311.5 mL in the off-pump group and 827.8+/-514.4 mL in the on-pump group (p=0.07). CONCLUSIONS: epsilon-Aminocaproic acid is effective in controlling postoperative bleeding in patients operated on for myocardial revascularization with the aid of cardiopulmonary bypass.