AXIN2 germline testing in a French cohort validates pathogenic variants as a rare cause of predisposition to colorectal polyposis and cancer.

Only a few patients with germline AXIN2 variants and colorectal adenomatous polyposis or cancer have been described, raising questions about the actual contribution of this gene to colorectal cancer (CRC) susceptibility. To assess the clinical relevance for AXIN2 testing in patients suspected of genetic predisposition to CRC, we collected clinical and molecular data from the French Oncogenetics laboratories analyzing AXIN2 in this context. Between 2004 and June 2020, 10 different pathogenic/likely pathogenic AXIN2 variants were identified in 11 unrelated individuals. Eight variants were from a consecutive series of 3322 patients, which represents a frequency of 0.24%. However, loss-of-function AXIN2 variants were strongly associated with genetic predisposition to CRC as compared with controls (odds ratio: 11.89, 95% confidence interval: 5.103-28.93). Most of the variants were predicted to produce an AXIN2 protein devoid of the SMAD3-binding and DIX domains, but preserving the ß-catenin-binding domain. Ninety-one percent of the AXIN2 variant carriers who underwent colonoscopy had adenomatous polyposis. Forty percent of the variant carriers developed colorectal or/and other digestive cancer. Multiple tooth agenesis was present in at least 60% of them. Our report provides further evidence for a role of AXIN2 in CRC susceptibility, arguing for AXIN2 testing in patients with colorectal adenomatous polyposis or cancer.

Preoperative Embolization of Metastatic Spinal Cord Compression with n-Butyl Cyanoacrylate: Safety and Effectiveness in Limiting Blood Loss.

PURPOSE: To evaluate the safety and effectiveness of preoperative embolization with n-butyl cyanoacrylate (nBCA) performed for metastatic spinal cord compression (MSCC) in limiting blood loss (BL). MATERIALS AND METHODS: In this institutional review board-approved retrospective study, clinical records from 2017 to 2022 were reviewed. Twenty consecutive patients (11 men and 9 women; mean age, 65.8 years ± 10.0; range, 45-82 years) underwent 21 preoperative spine tumor embolizations with nBCA. Angiograms were used to calculate the percentage reduction in tumor vascularity, and relevant clinical data (levels studied and embolized, fluoroscopy time [FT], reference dose [RD], and Kerma area product [KAP]) and operative data (BL and operative time [OT]) were analyzed. Adverse events and outcomes were recorded. RESULTS: A median of 2 levels were embolized per procedure (range, 1-5) but 4.9 were studied (range, 1-10). After embolization, tumor blush was reduced by a median of 87.3% (range, 50%-90%). The mean FT was 41 minutes ± 15.4 (range, 16-67 minutes), the mean RD was 1,977.1 mGy ± 1,794.3 (range, 450.2-6,319 mGy), and the mean KAP was 180.5 Gy·cm2 ± 166.2 (range, 30.4-504 Gy·cm2). The adverse event rate was 1 (4.7%) of the 21 embolizations because a weakness of lower extremities related to swelling was observed. Surgery was performed at a mean of 1.4 days ± 1 (range, 1-5 days) after embolization. The mean surgical estimated BL was 432.5 mL ± 328.5 (range, 25-1,100 mL), and the mean OT was 210.1 minutes ± 97.4 (range, 57-489 minutes). CONCLUSIONS: Preoperative embolization of tumors resected for MSCC with nBCA is a safe procedure allowing for performance of surgery with acceptable BL.

Expandable Intravertebral Implant in Cancer-Related Vertebral Compression Fractures: A Retrospective Review of 36 Implantations.

The purpose of this retrospective review was to evaluate SpineJack implantation in cancer-related vertebral compression fractures in 13 consecutive patients (mean age, 62.8 years ± 18.8). A total of 36 devices were inserted at 20 levels (13 [65%] lumbar and 7 [35%] thoracic vertebrae), with a mean Spinal Instability Neoplastic Score of 9.1 ± 2.1. Vertebral height restoration was observed in 10 levels (50%), with a mean height restoration of 5.6 mm ± 2.2 (interquartile range [IQR], 4-7.5). A total of 6 cement leakages were observed in 3 (23%) patients without clinical consequences. No severe adverse events were observed. One adjacent fracture occurred. Average pain scores on the visual analog scale significantly improved from 5.5 ± 1.8 (IQR, 4-7) preoperatively to 1.5 ± 2.2 (IQR, 0-3.3) at 1 month (P < .01) and to 1.5 ± 1.3 (IQR, 0.3-2.8) at 6 months (P < .01). In this small cohort, SpineJack offered pain relief in cancer-related fractures without an observed increase in adverse events.

Percutaneous low-pressure bone stenting to control cement deposition in extensive lytic lesions.

OBJECTIVE: To evaluate low-pressure bone stenting combined with cementoplasty in extensive lytic lesions. METHODS: A single-centre study involving four consecutive patients (four women) with extensive lytic tumours was performed. The average age was 65 years. Surgical treatment was not indicated or not wished for by the patients. Institutional review board approval and informed consent were obtained. Percutaneous consolidation was performed by an interventional radiologist under fluoroscopy guidance. Follow-up was assessed using the visual analogue scale (VAS). RESULTS: Under general (n = 2) or local (n = 2) anaesthesia, five 11-gauge bone biopsy needles were advanced in four lesions. Five auto-expandable uncovered stents (10-14 mm diameter and 40-60 mm long) were inserted. In all cases, bone cement was successfully placed into the tumours. The volume of cement that was injected through the cannulas into the stents was 5-10 mL. Using VAS, pain decreased from more than 9/10 preoperatively to less than 2/10 after the procedure for all patients (p < 0.05). No complications occurred during the follow-up (8-19 months). CONCLUSION: This study suggests that cementoplasty combined with low-pressure bone stenting could allow effective bone stabilization resulting in pain relief. KEY POINTS: • Low-pressure bone stenting is possible. • This technique improves cement injection control. • The procedure allows effective bone stabilization resulting in pain relief.

Percutaneous consolidation of loosened spine arthrodesis under CT and fluoroscopy guidance by radiologists: a new useful technique.

OBJECTIVE: The objective was to evaluate percutaneous computed tomography (CT) and fluoroscopy-guided injection of bone cement for consolidation of loosened posterior arthrodesis performed by radiologists. METHODS: A single-centre prospective study involving four consecutive patients (three women, one man) suffering from screw loosening (three at the vertebral level, one at the iliac wing level) after Posterior Lumbar Interbody Fusion (PLIF) treatment was done. The average age was 80 years. Surgical treatment was not indicated or not wished for by the patients. Institutional review board approval and informed consent were obtained. Percutaneous consolidation was performed by an interventional radiologist under CT and fluoroscopy guidance. The path of the trocars was made outside loosened screws bilaterally. Follow-up was assessed using the Visual Analog Scale (VAS). RESULTS: In all cases, bone cement was successfully placed around the loosened screw. The mean volume of cement that was injected was 3 ml. No cement leakage was observed. No neurological complication occurred. Using VAS, pain decreased from more than 9/10 preoperatively to less than 2/10 the day after the procedure for all patients (p < 0.05). CONCLUSION: This study suggests that loosening of spine arthrodesis could be successfully treated by percutaneous injection of bone cement under CT and fluoroscopy guidance. KEY POINTS: • PLIF is one of the surgical techniques for spinal arthrodesis. • Treatment indications are degenerative disease or instability following trauma, tumour, or infection. • Screw loosening is a frequent complication that can occur after surgery. • Percutaneous facet consolidation under dual guidance seems to be a feasible technique. • The procedure is performed under local anaesthesia using a minimally invasive approach.

Prostatic Artery Embolization for Benign Prostatic Obstruction: Single-Centre Retrospective Study Comparing Microspheres Versus n-Butyl Cyanoacrylate.

PURPOSE: To compare the safety and efficacy of n-butyl cyanoacrylate glue (NBCA) versus microspheres for prostatic artery embolization (PAE) in patients with benign prostatic obstruction (BPO). MATERIALS AND METHODS: This institutional review board-approved, single-centre, retrospective study included consecutive patients undergoing PAE from September 2017 to July 2020. Age, medical history, previous treatment, pre- and post-PAE prostatic volumes and International Prostate Symptom Scores (IPSSs) were systematically analysed. Procedural duration, dosimetry, immediate and delayed complications were recorded. Patients at the beginning of the study were treated with microspheres and patients at the end of the study with NBCA. The main outcome measures were the absolute and relative changes in IPSS at 3 months. Statistical analyses comprised unpaired t-tests, Wilcoxon tests, Chi-2 tests, uni- and multivariate linear regressions. RESULTS: Sixty-two patients were included (median age: 65.9 years). Thirty-two patients were treated with microspheres and 30 with NBCA. There were no significant baseline differences between the two groups except for the baseline PSA (P = 0.0251). Average procedural and fluoroscopy times, and radiation exposure were significantly lower in the NBCA group versus the microspheres group (80.7 ± 22.5 versus 112 ± 42.1 min [P = 0.0011], 24.2 ± 9.6 min versus 42.1 ± 20.2 min [P = 0.0001], 12,004.6 ± 6702 uGy.m2 versus 25,614.9 ± 15,749.2 uGy.m2 [P = 0.0001], respectively). Immediate complications were all minor, and there were no significant differences between the two groups (4/32 [12.5%] with microspheres versus 7/30 [23.3%] with NBCA, P = 0.4335), nor for delayed complications (P = 1). No association was found between the PAE techniques and the absolute change in IPSS at 3 months (-10.2 ± 7.9 with microspheres versus -9.5 ± 7.6 with NBCA, P = 0.7157). CONCLUSION: PAE using NBCA was safe and effective for symptomatic BPO, with faster procedures, lower radiation exposure and similar safety and efficacy compared to microspheres. Operator learning curve could have biased the procedural times and radiation exposure between groups favouring NBCA.

A Novel Implant for the Prophylactic Treatment of Impending Pathological Fractures of the Proximal Femur: Results from a Prospective, First-in-Man Study.

OBJECTIVES: To prospectively evaluate a novel implant, Y-STRUT® (Hyprevention, Pessac, France), designed to provide prophylactic reinforcement of the proximal femur in metastatic patients. METHODS: Ten patients presenting lytic lesions of the proximal femur were to be treated. The device consisted of two components implanted in the proximal femur, combined with bone cement. Patients were followed at 2, 6 and 12 months to record technical feasibility, safety and efficacy parameters of the procedure. RESULTS: All patients (62 years, 67% male) presented a pertrochanteric lesion shown on imaging with an average Mirels' score of 9.42 (range 8-11). Procedures were performed by interventional radiologists, under general anesthesia in 97 ± 28 min, with 9.2 ± 3.1 ml of cement injected. Hospitalization duration was 2.3 ± 1.4 days. A median follow-up of 237 days (range 24-411) was reported. Wound healing was achieved in all patients, with no case of wound infection, bleeding, leakage or inflammation. Among the patients evaluated, 86% could resume walking at hospital discharge. Visual Analogue Scale decreased from 3.6 ± 2.9 before treatment to 1.3 ± 0.8 at 1 year. OHS-12 score increased from 30 ± 10 at baseline to 37 ± 6 at 1 year. CONCLUSIONS: Results from this first-in-man study conducted in patients with metastatic bone disease show the feasibility and the safety of the intervention, with a short hospitalization, when performed following the operating instructions. Initial data showing pain-level diminution and increase in OHS-12 score indicate that both symptomatic and functional conditions of the patients were improved 1 year after the implantation of this novel implant. LEVEL OF EVIDENCE: Level 4, Case Series.

Phase I study of axitinib and everolimus in metastatic solid tumours and extension to metastatic renal cell carcinoma: Results of EVAX study.

PURPOSE: Anti-angiogenic and mammalian target of rapamycin inhibitors have shown efficacy in solid tumours. Reported combination of both drugs was deemed to be too toxic. Due to a potential favourable safety profile of axitinib (AX), a phase I study combining everolimus (EV) and AX for solid tumours was explored. EXPERIMENTAL DESIGN: Patients (pts) with advanced cancers were enrolled in an escalation phase I study to investigate the safety of the combination. Pharmacokinetic profile and functional vascular imaging were performed. An extension to pts with naive metastatic renal cell carcinoma (MRCC) was explored. RESULTS: 15 pts were included over three different dose levels (DLs); DL 0: AX 3 mg BID (twice daily)/EV 5 mg OD (once daily); DL 1: AX 5 mg BID/EV 5 mg OD and DL 2: AX 5 mg BID/EV 10 mg OD for 28 d. One dose-limiting toxicity (DLT) was reported at DL 0: grade (Gr) III diarrhoea and one DLT at DL 2: Gr III asthenia. Three severe adverse events (AEs) in two pts were unexpected: jaw osteonecrosis, recurrent renal failure and cardiomyopathy. Maximum tolerated dose (MTD) was level 2. After 1st cycle, Gr III or Gr II AEs of interest were mainly asthenia, diarrhoea and anorexia. All pts but one showed tumour shrinkage. Partial responses (PRs) were seen in one pt with bladder carcinoma and in one pt in 1st line MRCC in the escalating phase. In the extension phase in naive MRCC treated at MTD, five pts had a PR and one pt had a prolonged stable disease. CONCLUSION: The recommended dose for phase II is AX 5 mg BID/EV 10 mg OD.