Abstract Background The phosphoinositide 3 kinase (PI3K) pathway is important in the oncogenic function of HER2. Aberrent activation of PI3K is implicated in resistance to trastuzumab and other HER2-targeted therapies and is frequent, with up to 22% of HER2 positive breast cancer having a PIK3CA mutation. Copanlisib is a pan-class 1 PI3K inhibitor that shows particular activity against PI3Kα, the isoform encoded by the PIK3CA gene. Copanlisib has been shown to re-sensitise trastuzumab resistant cell lines to trastuzumab with synergism seen in some cell lines between copanlisib and HER2 targeted therapy. Trial design The study is a phase Ib/II open label, single arm adaptive, multi-centre trial of copanlisib in combination with trastuzumab. Eligible patients are treated with a dose escalation schedule of copanlisib IV on Days 1, 8 and 15 of a 28 day cycle with trastuzumab 2 mg/kg weekly (loading dose of 4 mg/kg in cycle 1). The phase II dose will be based on the maximum tolerated dose (MTD) established in Phase Ib. Patients are treated until radiologic or symptomatic progression, unacceptable toxicity, consent withdrawal or physician's decision. Eligibility criteria Eligible patients must have recurrent incurable or metastatic HER2-positive breast cancer that has progressed on at least one prior line of trastuzumab or T-DM1-based treatment regimen in this setting. Patients with treated and controlled brain metastases are eligible. Participants must have adequate organ function and ECOG PS ≤ 2. Patients recruited for the Phase II part of the study must have a PIK3CA mutation. Patients with uncontrolled arterial hypertension, uncontrolled diabetes or recent clinically serious infections are excluded. Specific aims The primary end point for the phase Ib part of this study is to determine the MTD for the combination. For the phase II study is anti-tumour efficacy, measured by Clinical Benefit Rate (CBR). Secondary end points are evaluation of safety and tolerability, progression-free survival, time to treatment failure, duration of response and overall survival. Incorporated translational endpoints include examination of molecular tumor adaptation in tissue and blood. Given the role of PI3K in cellular glucose metabolism, an additional exploratory objective is to determine if quantitive reduction in metabolic signal on Positron Emission Tomography-Computed Tomography (PET-CT) is predictive of benefit from therapy. Statistical methods To establish the MTD, we use a modified 3+3 design where 3 additional patients will be accrued even if the first 3 patients accrued experience no dose limiting toxicities (DLT) in sequential cohorts for a planned 12 patients. To determine the CBR, a one sample exact binomial test with a one sided significance level of 5%, 19 evaluable patients will provide >80% power to detect a difference between the null hypothesis proportion of 30% for CBR versus the alternative hypothesis proportion of 65%. Present accrual and target accrual There are 9 patients recruited so far to the phase Ib part of this study. Target accrual is 12 and for phase II is 19 patients. Contact information for people with a specific interest in the trial Prof Bryan Hennessy, Beaumont Hospital, Dublin Ireland Funded by Bayer Citation Format: Keegan NM, Walshe J, Gullo G, Kennedy J, Bulger K, Kelly CM, Crown J, Toomey S, Egan K, Kerr J, Given M, Hernando A, Teiserskiene A, Grogan L, Breathnach O, Morris PG, Keane M, Hennessy BT. A phase Ib/II trial of coPANlisib in combination with tratuzumab in pretreated recurrent or metastatic HER2-positive breast cancer “PantHER” [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-06-05.

AIM: To review percutaneous biliary drainage (PBD) procedures performed in Beaumont Hospital, Dublin, Ireland, over a 6-year period, to determine the 30-day morbidity and mortality.MATERIALS AND METHODS: A total of 119 patients undergoing 193 PBD procedures were identified over a 6 year period. Of the patients, 6.7% (eight patients) had stone disease, 63% (75 patients) had a malignancy, and the remainder were diagnosed with other conditions. Standard techniques of PBD and biliary stent insertion were applied, with 73 patients (61%) having same-day procedures and all undergoing gelfoam embolisation of percutaneous tracts. All patients received intravenous prophylactic antibiotics and intravenous hydration prior to PBD.RESULTS: The technical success rate was 97%, with a mean drop of 105 mmol/l between pre-and post-procedure bilirubin. Thirty-day mortality was 10.9% (13 deaths), with major and minor morbidities of 5% (six patients) and 7.6% (nine patients), respectively. Major complications included sepsis in two patients, major haemorrhage in two patients, and renal failure in two patients. Minor complications included infection in seven patients, bile leak causing self-limiting pain in one patient, and minor haemorrhage in one patient.CONCLUSION: The study confirms that PBD and stent insertion is a safe and effective technique in Beaumont Hospital, associated with an overall acceptable morbidity and mortality comparable with other studies. (C) 2016 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

•Endovascular techniques can be used to treat Angio-Seal vascular closure device related stenotic, occlusive and embolic complications.•A range of techniques can be employed including thrombolysis, angioplasty and stent placement.•This can avoid surgery, particularly in medically unfit patients.

Internal iliac artery (IIA) embolisation is commonly performed prior to endovascular aneurysm repair (EVAR) of aortoiliac aneurysms to prevent type 2 endoleaks via the internal iliac arteries. The safety of this procedure is controversial due to the high incidence of pelvic ischaemic complications.

PURPOSE:This prospective pilot study was undertaken to evaluate the feasibility and effectiveness of using a radiation absorbing shield to reduce operator dose from scatter during lower limb endovascular procedures.MATERIALS AND METHODS:A commercially available bismuth shield system (RADPAD) was used. Sixty consecutive patients undergoing lower limb angioplasty were included. Thirty procedures were performed without the RADPAD (control group) and thirty with the RADPAD (study group). Two separate methods were used to measure dose to a single operator. Thermoluminescent dosimeter (TLD) badges were used to measure hand, eye, and unshielded body dose. A direct dosimeter with digital readout was also used to measure eye and unshielded body dose. To allow for variation between control and study groups, dose per unit time was calculated.RESULTS:TLD results demonstrated a significant reduction in median body dose per unit time for the study group compared with controls (p = 0.001), corresponding to a mean dose reduction rate of 65 %. Median eye and hand dose per unit time were also reduced in the study group compared with control group, however, this was not statistically significant (p = 0.081 for eye, p = 0.628 for hand). Direct dosimeter readings also showed statistically significant reduction in median unshielded body dose rate for the study group compared with controls (p = 0.037). Eye dose rate was reduced for the study group but this was not statistically significant (p = 0.142).CONCLUSION:Initial results are encouraging. Use of the shield resulted in a statistically significant reduction in unshielded dose to the operator's body. Measured dose to the eye and hand of operator were also reduced but did not reach statistical significance in this pilot study.

BACKGROUND:Chronic mesenteric angina is a rare condition with high morbidity and mortality, which occurs due to stenosis or occlusion in the mesenteric vessels commonly due to atherosclerosis. Typically, patients present with worsening postprandial abdominal pain, chronic weight loss and fear of food. The condition can be treated by surgical bypass, but also by percutaneous transluminal angioplasty and stenting of the affected mesenteric arteries.AIM:To assess the mid-term outcomes in patients treated by endovascular stenting for chronic mesenteric ischaemia (CMI).METHODS:Six patients were treated for symptomatic CMI. In total, six severely stenosed vessels were stented including the superior mesenteric artery (n = 5) and coeliac artery (n = 1). A retrospective review of these patients was performed with end points including symptom recurrence, major morbidity and mortality. The mean follow-up was 16.5 months (range 5-28 months).RESULTS:Initial clinical success was observed in all six patients. Four patients were clinically asymptomatic, but died within 18 months after the procedure from other conditions. One patient suffered from recurrence of symptoms. Only one patient died as a consequence of mesenteric artery re-stenosis.CONCLUSION:Stenting of mesenteric vessels has shown excellent early and mid-term clinical success in selected patients. Though no direct comparison with open revascularization surgery was performed in this case series, technical and mid-term clinical success is promising.

Introduction The purpose of this study was to explore whether basic endovascular skills acquired using proficiency-based simulation training in superficial femoral artery (SFA) angioplasty translate to real-world performance. Methods Five international experts were invited to evaluate a preliminary 28-item rating scale for SFA angioplasty using a modified Delphi study. To test the procedural scale, 4 experts and 11 final-year medical students then performed 2 SFA angioplasties each on the vascular intervention simulation trainer simulator. Thereafter, 10 general surgical residents (novices) received didactic training in SFA angioplasty. Trainees were then randomized with 5 trainees receiving further training on the vascular intervention simulation trainer simulator up to proficiency level. All 10 trainees then performed 1 SFA angioplasty on a patient within 5 days of training. The trainees’ performance was assessed by 1 attending consultant blinded to the trainees’ training status, using the developed procedural scale and a global rating scale. Results Four items were eliminated from the procedural scale after the Delphi study. There were significant differences in the procedural scale scores between the experts and the students in the first trial [mean (SD), 94.25 (2.22) vs. 74.90 (8.79), P = 0.001] and the second trial [95.25 (0.50) vs. 76.82 (9.44), P < 0.001]. Simulation-trained trainees scored higher than the controls on the procedural scale [86.8 (5.4) vs. 67.6 (6), P = 0.001] and the global rating scale [37.2 (4.1) vs. 24.4 (5.3), P = 0.003]. Conclusions Basic endovascular skills acquired using proficiency-based simulation training in SFA angioplasty do translate to real-world performance.

T-fastener gastropexy is widely performed as part of gastrostomy insertion. The current literature recommends removal of T-fasteners at 2 weeks. We present a series of patients in whom T-fasteners were removed at 2 days with no major complications. We removed T-fasteners in 109 patients (male-to-female ratio 59:50, age range 18 to 88 years, mean age 62 years) at 2 days after gastrostomy insertion. Indications for gastrostomy included amytrophic lateral sclerosis, cerebrovascular accidents, head and neck carcinoma, multiple sclerosis, and others, including brain tumours and chronic inflammatory demyelinating polyneuropathy. No peritubal leaks or other major complications were seen in the study population. In the study group, 15 minor complications were recorded (14%), including localised infection and pain, both of which resolved on removal of T-fasteners. We conclude that it is feasible and safe to remove T-fasteners at 2 days.

The aim of this study was to evaluate our experience with the retrievable Cook Celect inferior vena cava (IVC) filter (William Cook, Europe) with regard to insertion, efficiency, ease of retrieval, and any associated complications. A retrospective review was performed of 115 patients (41 female, 74 male, mean age 47.97 years) who underwent Cook Celect IVC filter insertion between December 2005 and October 2007. Filter insertion was successful in all patients. Of the 115 filters inserted, 57 have been successfully retrieved (49.6%) to date. The successful retrieval rate from attempted retrieval was 93.4%. The mean dwell time of successfully retrieved filters was 114.9 days (range 14-267 days). Failed retrievals were due to a thrombosed vena cava (n = 1) and endothelialisation of the filter (n = 3). In the failed retrieval group the mean implantation time was 142 days (range 78-211 days). While this is the first retrospective clinical study on the Cook Celect filter, results to date are promising. We demonstrated an efficacious filter with a high successful retrieval rate of 93.4% and a low complication rate. The filter was assessed with extended dwell times (range 14-267 days). Failed retrieval secondary to hook endothelialisation continues to be an issue with this filter. We recognize that a limitation of our study was the lack of systematic follow-up for clinically silent complications. Further studies to evaluate longer term outcomes and effectiveness of this filter are warranted.

This study aimed to assess the role of percutaneous vertebroplasty (VP) in the management of acute traumatic burst fractures. We describe three cases where percutaneous VP was carried out for traumatic non-osteoporotic burst vertebral fractures. For clinical symptoms and the effect of the VP procedure to be assessed, all patients completed a visual analogue scale and a mobility score before the procedure and at day 1 and 3 months post procedure. Improvements in both pain and mobility scores immediately post procedure were seen in all patients, and these results persisted at 3-month follow up. Percutaneous VP provided a successful, minimally invasive treatment of these patients' traumatic fractures while avoiding major surgical procedures and associated surgical morbidity and complications.

Spontaneous nonhemophiliac hemarthrosis is an unusual entity, which has been little described. We present three cases of spontaneous recurrent hemarthrosis post total knee replacement (TKR) and successful management with embolization. Three male patients were referred to our service for angiography and treatment of recurrent hemarthrosis post TKR. In all three patients antegrade ipsilateral common femoral artery punctures and selective angiography of the geniculate branches were performed with a microcatheter. Abnormal vasculature was noted in all cases. Subsequent embolization was performed with Contour (Boston Scientific, Target Vascular, Cork, Ireland) embolization particles (150–250 and 250–355 μm) in two patients and microcoils in the third (TornadoR; Cook Inc., Bloomington, IN, USA). Technical success was 100%. One patient had a recurrence of symptoms requiring a repeat procedure 6 months later. No complications were encountered. Selective angiography and particle embolization is an effective technique for management of this unusual but problematic postoperative sequelae.

Historically, fine-needle aspiration cytology (FNAC) has varying sensitivity, specificity and accuracy in the diagnosis of abdominal lesions with a high insufficient sampling rate. We compared 20-G fine-needle trucut biopsy (FNTB) with FNAC results in the biopsy of solid abdominal tumours. A retrospective review of 171 (128x 20-G FNTB and 43x FNAC) ultrasound-guided biopsies of abdominal tumours on 157 patients (male : female 85:72, mean age 61.25 years) were carried out. One hundred and seventy-one biopsies were carried out: liver 109, pancreas 19, lymph node 10, omentum 5, right iliac fossa mass 6, adrenal 6 and others 16. An average of 2.06 and 1.97 passes (range 1-4) were carried out per FNTB and FNAC, respectively. A definitive diagnosis was made in 122/128 biopsies (95.3%) and 32/43 biopsies (74.4%) for FNTB and FNAC, respectively. Diagnoses consisted of metastatic liver disease (74/171), pancreatic adenocarcinoma (10/171), lymphoma (8/171) and others (33/171) and benign (29/171). No significant complications occurred in either group. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 87, 100, 100, 50, 84.4 and 93.1, 100, 100, 60, 71.4 for FNTB and FNAC, respectively. A greater and more consistent positive diagnosis rate is yielded by 20-G FNTB (95.3%) than FNAC (74.4%). The diagnostic accuracy of FNTB is 84.4% compared with 69.8% for FNAC. A greater insufficient sampling rate occurs with FNAC (25.6%) than with FNTB (4.7%). For abdominal biopsy, 20-G FNTB needles have a much higher yield than FNAC with no increase in complications. FNTB is the preferred choice, particularly where cytological assistance at the time of biopsy is unavailable.

In this study, the efficacy and safety of the Angioseal vascular closure device post antegrade puncture of the common femoral artery (CFA) for lower limb vascular interventional procedures are evaluated. A retrospective analysis of the medical records of 60 consecutive patients who were referred for interventional procedures in the superficial femoral artery (SFA) or popliteal artery (popl. art.) was performed. Antegrade puncture was successfully performed in 58 of 60 patients (96.6%). Indications included right SFA angioplasty (n = 35), left SFA angioplasty (n = 17), right popl. art. angioplasty (n = 5), and left popl. art. angioplasty (n = 1). Hemostasis was achieved by, on an intention-to-treat basis, the Angioseal vascular closure device in 46 patients and manual compression in 12 patients. Manual compression was used instead of Angioseal because of severe calcified arterial wall plaques (n = 7), failed deployment of the Angioseal (n = 4), and left SFA dissection (n = 1). There were no major recorded complications in the Angioseal group despite the use of antiplatelet or anticoagulant medications. Twenty-three (50%) of the patients in the Angioseal group were discharged within 24 h. Thirty-seven of the 46 patients who received an Angioseal device had undergone a previous ipsilateral CFA puncture (time range, 2 days to 56 months; mean, 6.2 months). Nine of these patients had undergone ipsilateral Angioseal deployment in the previous 3 months. We conclude that the Angioseal vascular closure device is a safe and efficient means of achieving hemostasis post antegrade puncture.

We present the study of a 58-year-old man who underwent percutaneous management of a high-output chylothorax following cardiac bypass graft surgery. The patient presented to a peripheral hospital 3 weeks postoperatively following cardiac bypass graft surgery with shortness of breath. A chest radiograph taken on arrival to the emergency department showed a large left-sided pleural effusion. Subsequent intercostal chest tube insertion drained a large amount of chylous fluid. The patient was treated conservatively with no improvement until undergoing a CT-guided needle disruption of lymphatics with good effect. This case is presented to show the minimally invasive treatment methods that are available in the management of high-output chylothorax.