Effectiveness of Intraoperative Cell Salvage Combined with a Modified Leucocyte Depletion Filter in Metastatic Spine Tumour Surgery

Background To compare the effectiveness of intraoperative cell salvage (IOCS) combined with a modified leucocyte depletion filter (MLDF) with IOCS combined with a regular leucocyte depletion filter (RLDF) in eliminating tumour cells from blood salvage during metastatic spine tumour surgery (MSTS). Methods Patients with a known primary epithelial tumour who underwent MSTS were recruited for this study. Blood samples were collected in 5 stages: from the patients’ vein before anaesthesia induction (S1), from the operative field during tumour manipulation (S2), and from the operative blood after IOCS processing (S3) and after IOCS+RLDF (S4) and IOCS+MLDF (S5) processing. The polyploids of tumour cells in the blood samples were collected and counted with immunomagnetic separation enrichment and fluorescence in situ hybridization. Results We recruited 20 patients. Tumour cells were detected in 14 patients (70%) in S1, 16 patients (80%) in S2, 13 patients (65%) in S3, and 12 patients (60%) in S4. MLDF was added in 8 patients. Tumour cells were detected in only 1 of 8 patients in S5 (12.5%). There were significantly fewer tumour cells in the samples collected after MLDF processing (S5) than in the samples collected after RLDF (S4) and around the tumour (S2) (P = 0.016 and P = 0.039, respectively). Although no significant difference was observed between S4 and S1, a downward trend was observed after IOCS+RLDF processing. Conclusions Tumour cells could be removed by IOCS combined with RLDF from blood salvaged during MSTS, but residual tumour cells remained. The findings support the notion that MLDF eliminates tumour cells more effectively than RLDF. Hence, this technique can be applied to MSTS. Trial Registration ChiCTR1800016162 Chinese Clinical Trial Registry http://www.chictr.org.cn/showproj.aspx?proj=27263

Temozolomide non-responsiveness in aggressive prolactinomas and carcinomas: management and outcomes

Purpose Temozolomide is endorsed as the treatment of choice in aggressive or malignant pituitary adenomas. Herein we describe a case of an aggressive prolactinoma which was resistant to temozolomide and performed a literature review of similar non-responsive aggressive prolactinomas. Methods A 40-year-old female presented with a giant prolactinoma which required cabergoline, transsphenoidal surgery and radiotherapy to achieve near-normal prolactin and apparently no residual tumour. A year later, she presented with multiple cranial nerve involvement due to recurrent tumour extending to the infratemporal fossa. She underwent transfrontal surgery, second radiotherapy and was started on temozolomide. Despite 8 cycles of temozolomide (200mg/m 2, 5/28 day cycle), she had progressive disease and ultimately succumbed to the disease. Pubmed/MEDLINE, Google scholar and prior review articles were searched for manuscripts with aggressive prolactinomas who had been treated with temozolomide. Data on demography, duration of therapy and management outcomes were analysed in those with progressive disease. Literature review We identified 94 cases of aggressive/malignant prolactinomas in the literature who had received temozolomide. Progressive disease despite temozolomide was present in 36 cases (38%). There was a male preponderance (65%) and 40% had aggressive prolactinomas while the rest had carcinomas. Patients received a median of 8 cycles (IQR 3.5-11.5) of temozolomide. MGMT immunostaining was negative in 35%. Overall mortality at the time of publication was 40%, at a duration varying from 2 to 20 years from diagnosis. Conclusion Temozolomide resistance in aggressive/malignant prolactinomas is challenging. Progressive disease on optimal temozolomide treatment entails the use of newer agents.

Successful treatment of pituitary gigantism

Pituitary gigantism is extremely rare, resulting from excessive secretion of growth hormone (GH) before fusion of epiphysial growth plates. We report a case of a 13-year-old boy, who presented with increased statural growth and headaches since the age of 10 years. On physical examination, his height was 180.7 cm (+3.3 SD) and Tanner stage V. Investigation revealed increased levels of serum age-adjusted and sex-adjusted insulin-like growth factor 1 (IGF-1) and failure of GH suppression during an oral glucose tolerance test (OGTT). MRI of the sellar region revealed a pituitary macroadenoma. He underwent transsphenoidal surgery and histopathological evaluation revealed mammosomatotropic adenoma. Three months after surgery, IGF-1 normalised, nadir GH during OGTT was less than 1 ng/mL and no residual tumour was found on the MRI. Genetic testing identified a mutation in the AIP gene. This case emphasises the importance of early diagnosis of gigantism, as treatment delay increases long-term morbidity.

574 Giant left atrial myxoma in ischaemic stroke

Aims Primary cardiac tumours are rare; most are benign, and of these, around half are myxomas, often located in the left atrium. Clinical presentation is variable. Ischaemic stroke is a rare, although real and potentially fatal, complications of cardiac myxomas. Methods and results We present a case of a 51-year-old man, ex- smoker, obese, with a history of hypertension and COPD, presented to our emergency department with right-sided hemiplegia and aphasia caused by ischaemic stroke. Brain computed tomography revealed cerebral perfusion deficit. The patient was underwent intravenous thrombolytic strategy and intubated transferred in Reanimation. TTE showed a large left atrial mass attached to the interatrial septum, with a friable appearance, suggestive of myxoma. The 2D and 3D TEE detected a giant space-occupying mass (60 × 20 mm diameter) in the left atrium, coral-like, and with a friable appearance, the most apical portion prolapsed into the left ventricle during diastole, causing fixed obstruction to flow in the left ventricular inflow tract. Computed tomography angiography (CTA) confirmed the giant mass in the left atrium. In view of the risk of imminent embolization, the emergent surgical excision of the tumour was performed. The tumour and its neck, including part of the atrial septum, were fully resected and the atrial septum was directly closed. Subsequent histopathological findings confirmed the diagnosis of atrial myxoma. Post-operative echocardiography showed no residual tumour. Symptomatic cardiac myxoma may present with one of the three classic clinical presentations of the Goodwin’s triad, which include intracardiac obstruction, constitutional symptoms, and embolism. The obstructive pattern mimics mitral or tricuspid valve disease and results from atrioventricular valve obstruction. Constitutional or systemic manifestations include fatigue, fever, weight loss, arthralgia, myalgia, erythematous rash, and laboratory findings such as anaemia and elevated ESR, CRP, and globulins. Systemic embolization from myxoma occurs in around a third of cases. Of these, the most serious is cerebrovascular embolism, which may result in cerebral stroke. In addition, embolization of coronary arteries, kidneys, intestines, and extremities can also occur. The tumour size, location, and macroscopic appearance, along with mean platelet volume and platelet count, are closely associated with embolic events. Echocardiography remains the method of choice for diagnosis and morphological characterization of myxoma. Two patterns have been established by echocardiography: round, with a solid appearance and a firm surface, and polypoid, with an irregular outline and a friable surface. The incidence of systemic embolization is higher in those with an irregular and friable surface, as well as in polypoid tumours and those that prolapse into the ventricle. Once a diagnosis of myxoma is established, surgical resection is the only effective treatment and should be performed immediately, in view of the risk of embolic complications. Conclusions With this case report, we stress the fundamental importance of echocardiography in new onset of neurological deficit to prevent potentially fatal outcomes.

O-P03 A composite polymeric nanoparticle as a sensitiser for sonodynamic therapy (SDT)-based treatment of pancreatic cancer

Background Pancreatic cancer remains one of the most recalcitrant forms of cancer with poor prognosis and limited treatment options. SDT is a novel, targeted approach to the treatment of solid tumours. Based on the generation of cytotoxic reactive oxygen species (ROS) following the exposure of a sonosensitiser to ultrasound, the approach is designed to extracorporeally target less accessible lesions. Here we describe the production of a poly(lactic-co-glycolic acid) (PLGA), polyethyleneimine (PEI), Rose Bengal (RB) and indocyanine green (ICG) containing composite nanoparticles and describe their use in SDT-mediated treatment of pancreatic cancer using both in vitro and in vivo target models. Methods Nanoparticles were prepared using an oil in water emulsion and solvent diffusion-based approach. These were designated RB-ICGNP. In vitro SDT treatment consisted of exposing BxPC3 (human PDAC cells), T110029 (murine PDAC cells) or hPSC (immortalised human pancreatic stellate cells) to RB-ICGNP and subsequently treating with ultrasound for 30 s at a frequency of 1 MHz, a power density of 3.0 W/cm2 (SATP) using a duty cycle of 50% at a pulse repetition frequency of 100 Hz. For in vivo studies, BxPC3 (xenograft) and T110029 (syngeneic) tumours were treated with a power density of 3.5 W/cm2 ultrasound for 3.5 min. Results Conclusions Using in vitro and in vivo (human xenograft and murine syngeneic) models of pancreatic cancer, RB-ICGNP composite nanoparticles may be employed as a sensitiser for SDT-based treatment of pancreatic cancer. Since pancreatic stellate cells were more sensitive to SDT, the latter may have an impact on tumour stroma. Staining of residual tumour tissues from SDT-treated animals for connective tissue (stroma) confirmed the latter. Since tumour stroma presents a significant challenge to treatment of pancreatic cancer and represents a negative prognostic marker, the impact delivered by SDT may be exploited to potentiate alternative therapeutic approaches.

O-P04 Sonodynamic Therapy Complements PD-L1 Immune Checkpoint Inhibition in a Murine Model of Pancreatic Cancer

Background The emergence of immune checkpoint inhibitors (ICI’s) in the past decade has proven transformative in the area of immuno-oncology. The PD-1 / PD-L1 axis has been particularly well studied and monoclonal antibodies developed to block either the receptor (anti PD-1) or its associated ligand (anti PD-L1) can generate potent anti-tumour immunity in certain tumour models. However, many “immune cold” tumours remain unresponsive to ICI’s. Sonodynamic therapy (SDT) is a targeted anti-cancer treatment that uses ultrasound to activate a sensitiser with the resulting generation of reactive oxygen species (ROS) causing direct cell death. SDT has also been shown to stimulate the adaptive immune system in a pre-clinical cancer model. We investigate the ability of combining ICI and microbubble mediated SDT at controlling tumour growth in a bilateral pancreatic cancer model. Methods Preparation of O2MB-RB are shown below (scheme 1). Cytotoxicity of SDT and immunotherapy in-vivo are illustrated below (Figure 1). Figure 1 highlights that T110299 cells were subcutaneously implanted in the right and left dorsum of C57 mice. Group 1 received an IP injection of anti-mouse PD-L1 antibody (10mg/kg). After 2 hours, mice in this group received an IV injection of O2MB-RB suspension while receiving ultrasound applied to the right-hand-side (target) tumour. Group 2 received the same as Group 1 but no anti PD-L1 antibody; Group 3 received anti-PD-L1 antibody alone and Group 4 remained untreated. Flow cytometry analysis were carried out to investigate tumour infiltrating CD4+ and CD8+ T-lymphocytes. Results The results demonstrated a significant 287% decrease in tumour volume when compared to untreated animals 11 days following the initial treatment with SDT, which reduced further to 369% when SDT was combined with anti-PD-L1 ICI treatment. Analysis of residual tumour tissues remaining after treatment revealed increased levels of infiltrating CD4+ and CD8+ T-lymphocytes (respectively 4.65 and 3.16-fold more) in the off-target tumours of animals where the target tumour was treated with SDT and anti-PD-L1, when compared to untreated tumours. These results suggest that SDT treatment elicits an adaptive immune response that is potentiated by the anti-PD-L1 ICI in this particular model of pancreatic cancer. Conclusions In conclusion, microbubble mediated SDT treatment of a target tumour in a bilateral tumour model of pancreatic cancer, enables growth control at both the target and off-target tumours which is further enhanced when combined with anti-PD-L1 ICI treatment. Combining SDT with anti-PD-L1 ICI treatment, which is also well tolerated, could provide an attractive treatment option for pancreatic cancer, particularly for patients with advanced disease who may not be physically capable of undertaking a toxic chemotherapy regimen.

P-OGC94 Outcomes of oesophagectomy post endoscopic mucosal resection

Background Within developed nations, oesophageal adenocarcinoma has the greatest incidence of any solid organ tumour with number escalating on a yearly basis. A recent expert review by the AGA suggests that high grade Barrett’s dysplasia and intramucosal adenocarcinoma are better treated endoscopically rather than oesophagectomy and that endoscopic management is a reasonable alternative to oesophagectomy for selected patients with low risk pT1b tumours.. Risk factors for nodal involvement and recurrence have been suggested by Lee et al (1). This study aims to review the pathological and clinical outcomes following oesophagectomy post EMR. Methods Results Conclusions Whilst some low risk patients had residual tumour at oesophagectomy, these findings were similar to Nelson et al 3; recurrent/recurrent local tumour could be potentially managed by repeat EMR. The absence of nodal metastasis in this small series is consistent with the AGA recommendation of EMR as a reasonable alternative to oesophagectomy for patients with selected low risk pT1b tumors.

[18F]Fluoromethylcholine PET/CT for CNS lymphoma assessment: a new tool

Background Central nervous system (CNS) lymphomas are a rare subset of lymphoma, which are associated with a poor outcome. The gold standard for CNS imaging is with gadolinium-enhanced magnetic resonance imaging (MRI); however, there are a number of limitations, including some patients with small persistent abnormalities from scarring due to focal haemorrhage or from a previous biopsy, which can be difficult to discern from residual tumour. [18F]Fluoromethylcholine positron emission tomography–computed tomography (FCH-PET/CT) uses an analogue of choline, which due to the upregulation of choline kinase in tumour cells, allows increased uptake of FCH. As there is minimal background grey matter uptake of FCH, FCH-PET/CT can be used in CNS imaging and provide a useful tool for response assessment. Methods This is a cohort study, where we identified 40 patients with a diagnosis of primary or secondary CNS lymphoma between 1st November 2011 and 10th October 2019. Results 26 of the 40 patients (65%) had concordant results. Of the discordant results, 11 out of 14 had partial response (PR) on MRI but showed a metabolic complete response (mCR) on FCH-PET. The overall response rates (ORR) were similar between the two modalities (90% for MRI versus 95% with FCT-PET/CT). Conclusion We conclude that FCH-PET/CT is a reasonable alternative mode of imaging to gadolinium-enhanced MRI brain imaging, providing a new tool for assessment of CNS lymphoma.

Malignant peripheral nerve sheath tumour transformation of histological benign vestibular schwannoma after stereotactic radiosurgery in patients without neurofibromatosis

Stereotactic radiosurgery (SRS) poses a minimal but important risk for tumour transformation, typically occurring 8–10 years after the treatment. Malignant peripheral nerve sheath tumour (MPNST) is the most common tumour arising from a vestibular schwannoma treated with SRS, with only 14 cases previously reported. We present the fifteenth case and describe its evolution and clinical course. A 56-year-old man without a history of neurofibromatosis was diagnosed 9 years prior with a vestibular schwannoma. SRS to the residual tumour was given 3 months later. During the current hospitalisation, he was reoperated where histology confirmed a MPNST. All 15 MPNST cases were analysed, showing a 77% female predominance presenting a malignant transformation at a mean age of 51. The diagnosis was made at a mean time of 74 months after SRS. The mean survival time after diagnosis was 16 months. MPNST arising from benign vestibular schwannoma after SRS treatment is an uncommon but devastating complication.

Risk scores to predict mortality 2 and 5 years after surgery for colorectal cancer in elderly patients

Background The aim of this study was to identify predictors of mortality in elderly patients undergoing colorectal cancer surgery and to develop a risk score. Methods This was an observational prospective cohort study. Individuals over 80 years diagnosed with colorectal cancer and treated surgically were recruited in 18 hospitals in the Spanish National Health Service, between June 2010 and December 2012, and were followed up 1, 2, 3, and 5 years after surgery. Sociodemographic and clinical data were collected. The primary outcomes were mortality at 2 and between 2 and 5 years after the index admission. Results The predictors of mortality 2 years after surgery were haemoglobin ≤ 10 g/dl and colon locations (HR 1.02; CI 0.51–2.02), ASA class of IV (HR 3.55; CI 1.91–6.58), residual tumour classification of R2 (HR 7.82; CI 3.11–19.62), TNM stage of III (HR 2.14; CI 1.23–3.72) or IV (HR 3.21; CI 1.47–7), LODDS of more than − 0.53 (HR 3.08; CI 1.62–5.86)) and complications during admission (HR 1.73; CI 1.07–2.80). Between 2 and 5 years of follow-up, the predictors were no tests performed within the first year of follow-up (HR 2.58; CI 1.21–5.46), any complication due to the treatment within the 2 years of follow-up (HR 2.47; CI 1.27–4.81), being between 85 and 89 and not having radiotherapy within the second year of follow-up (HR 1.60; CI 1.01–2.55), no colostomy closure within the 2 years of follow-up (HR 4.93; CI 1.48–16.41), medical complications (HR 1.61; CI 1.06–2.44), tumour recurrence within the 2 years of follow-up period (HR 3.19; CI 1.96–5.18), and readmissions at 1 or 2 years of follow-up after surgery (HR 1.44; CI 0.86–2.41). Conclusion We have identified variables that, in our sample, predict mortality 2 and between 2 and 5 years after surgery for colorectal cancer older patients. We have also created risks scores, which could support the decision-making process. Trial registration ClinicalTrials.gov, NCT02488161.