Endobronchial indocyanine green instillation to identify the intersegmental plane for successful segmentectomy.

The traditional indications for lobectomy for resectable Non-small Cell Lung Cancer (NSCLC) may be set to change. Recently, anatomical segmentectomy (AS) versus lobectomy as an approach for early-stage NSCLC has been described in phase 3 randomised controlled trials. The demand for methods to facilitate AS may increase as a consequence. We describe three cases of AS using the combination of endobronchial infiltration of indocyanine green (ICG) to identify the intersegmental plane (critical for the performance of AS), and Computed Tomography (CT) guided methylene blue injection for lesion localisation. The operations were completed successfully demonstrating satisfactory post-operative outcomes including lesion resection with clear surgical margins and acceptable length of stay. We believe that endobronchial instillation of ICG and CT-guided methylene blue injection for lesion localisation show promise as a technique to complement parenchymal sparing thoracic oncological surgery.

Reversal of collateral ventilation using endoscopic polymer foam in COPD patients undergoing endoscopic lung volume reduction with endobronchial valves: A controlled parallel group trial.

BACKGROUND AND OBJECTIVE: We have previously described reversal of collateral ventilation (CV) in a severe chronic obstructive pulmonary disease (COPD) patient with endoscopic polymer foam (EPF), prior to endoscopic lung volume reduction (ELVR) with valves. The aim of this study was to investigate the efficacy of this in a larger cohort and compare outcomes with a similar cohort with no CV. METHODS: Patients with severe COPD, with the left upper lobe (LUL) targeted for ELVR, were assessed for CV with high resolution computed tomography (HRCT). If fissure completeness was >95% they were enrolled as controls for valves alone (endobronchial valve control group [EBV-CTRL]). If fissure completeness was 80%-95%, defects were mapped to the corresponding segment, where EPF was instilled following confirmation of CV with CHARTIS. EBVs were inserted 1 month afterwards. RESULTS: Fourteen patients were enrolled into both arms. After 6 months, there were significant improvements in both groups in forced expiratory volume in 1 s (FEV1; +19.7% EPF vs. +27.7% EBV-CTRL, p < 0.05); residual volume (RV; -16.2% EPF vs. -20.1% EBV-CTRL, p = NS); SGRQ (-15.1 EPF vs. -16.6 EBV-CTRL p = NS) and 6 min walk (+25.8% EPF [77.2 m] vs. +28.4% [82.3 m] EBV-CTRL p = NS). Patients with fissural defects mapped to the lingula had better outcomes than those mapped to other segments (FEV1 +22.9% vs. +16.3% p < 0.05). There were no serious adverse reactions to EPF. CONCLUSION: EPF successfully reverses CV in severe COPD patients with a left oblique fissure that is 80%-95% complete. Following EBV, outcomes are similar to patients with complete fissures undergoing ELVR with EBV alone. EPF therapy to reverse CV potentially increases the number of COPD patients suitable for ELVR with minimal adverse reactions.

Preoperative Progressive Pneumoperitoneum Revisited.

Incisional hernia represents a common and potentially serious complication of open abdominal surgery, with up to 20% of all patients undergoing laparotomy subsequently developing an incisional hernia. This incidence increases to as much as 35% for laparotomies performed in high-risk patients and emergency procedures. A rarely used technique for enabling closure of large ventral hernias with loss of domain is preoperative progressive pneumoperitoneum (PPP), which uses intermittent insufflation to gradually stretch the contracted abdominal wall muscles, increasing the capacity of the abdominal cavity and allowing viscera to re-establish right of domain. This assists in tension-free closure of giant hernias which may otherwise be considered inoperable. This technique may be used on its own, or in conjunction with preoperative Botulinum Toxin A to confer paralysis to the lateral oblique muscles. These two complementary techniques, are changing the way complex hernias are managed.

Safety and tolerability of Miltuximab® - a first in human study in patients with advanced solid cancers.

OBJECTIVES: Miltuximab® is a chimeric antibody targeting Glypican-1 (GPC-1), a cell surface antigen which is overexpressed in solid cancers. Miltuximab® has shown promising safety and efficacy in radioimmunotherapy models of prostate cancer. This first in human study used Miltuximab® radiolabelled with Gallium-67 ([67Ga]Ga-DOTA-Miltuximab®). The primary study endpoint was to establish safety and tolerability of Miltuximab®. Secondary endpoints were biodistribution, tumour targeting and pharmacokinetic analysis. METHODS: Four cohorts of three patients (9 with advanced prostate cancer, 2 with pancreatic and 1 with bladder cancer) were dosed with 1 mg, ~250 MBq of [67Ga]Ga-DOTA-Miltuximab®. Cohort 1 received [67Ga]Ga-DOTA-Miltuximab® alone, while cohorts 2-4 were pre-infused with increasing doses (3.5, 11.5 and 24 mg, respectively) of unlabelled Miltuximab®-DOTA 1 hour prior to [67Ga]Ga-DOTA-Miltuximab®. Safety and tolerability were assessed by clinical and standard laboratory assessments. Patients underwent whole body gamma-camera scans and SPECT/CT scans up to 144 h post-infusion. Total organ radiation exposure was determined by dosimetry of whole-body gamma scans. RESULTS: The dosing regimen was well tolerated, with no drug-related adverse events observed. Liver and spleen uptake of [67Ga]Ga-DOTA-Miltuximab® was observed. Liver uptake was reduced by pre-infusion of unlabelled Miltuximab®-DOTA. Dosimetry analysis showed a favorable exposure profile. [67Ga]Ga-DOTA-Miltuximab® targeting to tumour sites was observed in two prostate cancer patients who had failed enzalutamide treatment. Higher doses of unlabelled antibody achieved lower liver uptake and increased antibody serum half life. CONCLUSIONS: This study is the first in human for Miltuximab® a first in class antibody targeting GPC-1. The trial met its primary endpoint of safety, demonstrating its potential as a safe and tolerable monoclonal antibody. This safety data, together with targeting to tumour lesions and biodistribution information supports the further clinical development of Miltuximab® as a theranostic agent in a planned Phase I human trial.

When the Conventional Treatment Fails: A Rare Approach to Superior Mesenteric Arterial Embolization.

Retroperitoneal haemorrhage is a rare but potentially life-threatening event. It may occur either spontaneously or secondary to percutaneous vascular access procedures, trauma, or ruptured aortic, iliac, or mesenteric aneurysms. As a result, the clinical presentation is variable. Computed tomography and/or angiography are vital for diagnosis. Management may range from conservative treatment for stable patients to emergency laparotomy or embolization for catastrophic haemorrhage. Direct percutaneous puncture of a deep intra-abdominal pseudoaneurysm is an accepted but infrequently performed technique due to a number of diagnostic and technical challenges. We describe the successful percutaneous transabdominal angioembolization of a superior mesenteric artery rupture in a 77-year-old woman with a large retroperitoneal haematoma. This was performed after a conventional femoral transarterial approach was unsuccessful.

Changes in ventilation and perfusion following lower lobe endoscopic lung volume reduction (ELVR) with endobronchial valves in severe COPD.

BACKGROUND: We have previously reported significant improvements in ventilation and perfusion (VQ) and V/Q matching in the contralateral lung, especially the non-targeted lower zone in patients with severe COPD following upper lobe ELVR with endobronchial valves. However, V/Q changes after lower lobe ELVR have not been described. METHODS: Seven patients with lower lobe heterogeneous emphysema underwent unilateral lower lobe ELVR at Macquarie University Hospital. Lung function tests, 6-minute walk tests (6MWT), St George's Respiratory Questionnaire (SGRQ) and planar differential VQ scans were performed at baseline and at 1, 3 and 12 months post-ELVR. RESULTS: Compared to baseline, patients showed significant improvements in FEV1 (0.83 ± 0.09L-0.97 ± 0.12L, p < 0.05), 6MWD (200.33 ± 56.54 m-274.24 ± 48.03 m, p < 0.05) and SGRQ (61.13 ± 5.33-42.86 ± 6.99, p < 0.05) at 3 months after ELVR. This improvement was maintained at 12 months. There was a corresponding significant improvement in the differential ventilation (30.21 ± 3.04%-37.82 ± 3.76%, p < 0.05) and perfusion (31.77 ± 2.53%-35.60 ± 2.58%, p < 0.05) of the contralateral non-targeted upper zone. CONCLUSIONS: Within the limitations of a small sample size, we have found that in heterogeneous severe COPD patients undergoing ELVR targeting the lower lobes, there are clinical and PFT improvements similar to that reported in ELVR targeting upper lobes. Contralateral improvement in V/Q matching also occurs following lower lobe ELVR with the greatest improvement in the contralateral upper zone, suggesting the contralateral upper lobe should be the least affected lobe if the lower lobe is targeted in ELVR. These findings need to be confirmed in a study with a larger number of patients.

A comparison of 4D flow MRI-derived wall shear stress with computational fluid dynamics methods for intracranial aneurysms and carotid bifurcations - A review.

BACKGROUND: 4D flow MRI is a relatively quick method for obtaining wall shear stress (WSS) in vivo, a hemodynamic parameter which has shown promise in risk stratification for rupture of cerebrovascular diseases such as intracranial aneurysms and atherosclerotic plaques. The accuracy of such measurements is still largely unknown. OBJECTIVE: To quantify the accuracy of 4D flow MRI-derived wall shear stress values for intracranial aneurysms and carotid bifurcations. METHOD: We performed a review of all original research articles which compared the magnitudes of WSS derived from 4D flow MRI with corresponding values derived from computational fluid dynamics (CFD) within both intracranial aneurysms and carotid bifurcations. RESULT: For intracranial aneurysms and carotid bifurcations, 4D flow MRI-derived WSS estimations are generally lower in magnitude compared to WSS derived by CFD methods. These differences are more pronounced in regions of higher WSS. However, the relative distributions of WSS derived from both methods are reasonably similar. CONCLUSION: Pooled analysis suggests that WSS magnitudes obtained by 4D flow MRI are underestimated, while the relative distribution is reasonably accurate, the latter being an important factor for determining the natural history of intracranial aneurysms and other cerebrovascular diseases. 4D flow MRI shows enormous potential in providing new risk stratification parameters which could have significant impact on individualized treatment decisions and improved patient outcomes.

Preoperative progressive pneumoperitoneum complementing chemical component relaxation in complex ventral hernia repair.

BACKGROUND: A rarely used technique for enabling closure of large ventral hernias with loss of domain is preoperative progressive pneumoperitoneum (PPP), which uses intermittent insufflation to gradually stretch the contracted abdominal wall muscles, increasing the capacity of the abdominal cavity. This allows the re-introduction of herniated viscera into the abdominal cavity and assists in closure of giant hernias which may otherwise be considered inoperable. METHODS: This was a prospective study assessing 16 patients between 2013 and 2015 with multi-recurrent ventral hernia. All patients were treated preoperatively with both Botulinum Toxin A (BTA) injections to the lateral abdominal wall muscles to confer flaccid paralysis, and short-term PPP to passively expand the abdominal cavity. All patients underwent serial abdominal CT imaging, with pre- and post-treatment circumference measurements of the peritoneal cavity and hernia sac, prior to undergoing operative mesh repair of their hernia. RESULTS: The mean hernia defect size was 236 cm2, with mean 28 % loss of domain. The mean overall duration of PPP was 6.2 days. The mean gain in abdominal circumference was 4.9 cm (5.6 %) (p 0.002) after BTA and PPP. Fascial closure and mesh hernia repair were performed in all 16 patients, with no patients suffering from postoperative abdominal hypertension, ventilatory impairment, or wound dehiscence. There are no hernia recurrences to date. Eight patients (50 %) experienced PPP-related complications, consisting of subcutaneous emphysema, pneumothorax, pneumomediastinum, pneumocardium, and metabolic acidosis. No complication required intervention. CONCLUSIONS: PPP is a useful adjunct in the repair of complex ventral hernia. It passively expands the abdominal cavity, allowing viscera to re-establish right of domain. At the same time, it helps to minimize the risks of postoperative abdominal compartment syndrome and the sequelae of fascial closure under tension. However, its benefits must be carefully weighed with the risk of serious complications, such as infection, perforation, pneumothorax, and pneumomediastinum.