A team led by researchers from the Stanford University School of Medicine has demonstrated a way to diagnose cancer without resorting to surgery, raising the possibility of far fewer biopsies.

For this first-in-humans clinical trial, women with either breast or ovarian tumours were injected intravenously with microbubbles capable of binding to and identifying cancer.

Jurgen Willmann, MD, a professor of radiology at Stanford, is lead author, and Sanjiv ‘Sam’ Gambhir, MD, PhD, professor and chair of radiology, is the senior author of the study.

For the study, 24 women with ovarian tumours and 21 women with breast tumours were intravenously injected with the microbubbles. Clinicians used ordinary ultrasound to image the tumours for about a half-hour after injection. The high-tech bubbles clustered in the blood vessels of tumours that were malignant, but not in those that were benign.

The ultrasound imaging of patients’ bubble-labelled tumours was followed up with biopsies and pathology studies that confirmed the accuracy of the diagnostic microbubbles.

Medical microbubbles are spheres of phospholipids, the same material that makes up the membranes of living cells. The bubbles are 1 to 4 microns in diameter, a little smaller than a red blood cell, and filled with a harmless mixture of perfluorobutane and nitrogen gas.

Ordinary microbubbles have been approved by the Food and Drug Administration and in clinical use for several years now. But such microbubbles, a kind of ultrasound ‘contrast agent,’ have only been used to image organs like the liver by displaying the bubbles as they pass through blood vessels. Up to now, the bubbles couldn’t latch onto blood vessels of cancer in patients.

The microbubbles used in this study were designed to bind to a receptor called KDR found on the tumour blood vessels of cancer but not in healthy tissue. Noncancerous cells don’t have such a receptor. Under ultrasound imaging, the labelled microbubbles, called MBKDR, show up clearly when they cluster in a tumour. And since benign breast and ovarian tumours usually lack KDR, the labelled microbubbles mostly passed them by.

In this small, preliminary safety trial, the technique appeared to be both safe and very sensitive, said Willmann, who is chief of the Division of Body Imaging at Stanford. And it also works with ordinary ultrasound equipment. ‘So, there’s no new ultrasound equipment that needs to be built for that,’ he said. ‘You can just use your regular ultrasound and turn on the contrast mode – which all modern ultrasound equipment has.’

Stanford Medicinemed.stanford.edu/news/all-news/2017/04/ultrasound-and-microbubbles-flag-malignant-cancer-in-humans.html

For patients with colorectal cancer that has metastasised to the liver, having a primary tumour on the left side, as opposed to the right side of the colon, is known to be a significant advantage in terms of treatment response.
But now a new study, presented here at the ESMO 19th World Congress on Gastrointestinal Cancer, suggests this imbalance may be at least partially redressed.
Reversing the usual pattern, patients whose liver metastases had spread from right-sided primary tumours (RSP) had a 36% better survival rate after treatment with a combination of first-line chemotherapy and selective internal radiation therapy (SIRT) using Y-90 resin microspheres, compared to chemotherapy alone, according to the study.
This same treatment combination was no better than chemotherapy only in patients with left-sided primary tumours (LSP).
“These findings are good news for patients with right-sided primary tumours, who have a much worse prognosis and fewer treatment options than patients with left-sided tumours,” said study investigator Guy van Hazel, MD, from the University of Western Australia in Perth, Australia.
“We are excited because hitherto no treatment apart from the addition of bevacizumab to chemotherapy has improved the dismal outcome of liver metastases coming from right-sided primary tumours.”
The analysis included 739 patients from two completed studies called SIRFLOX (SF) and FOXFIRE-Global (FFG).
All patients had liver-only or liver-dominant metastatic colorectal cancer (mCRC), and had been randomised to receive either standard chemotherapy alone, or combined with SIRT. The chemotherapy regimen was mFOLFOX6, and most patients received bevacizumab as well.
Information on the patients’ primary tumour location was recorded at the start, with 24% having right-sided and 73% left-sided disease (the remaining 3% had primary tumours on both sides of the colon, or the primary tumour site was unknown).
Overall, outcomes were not different between the chemotherapy alone and chemotherapy plus SIRT groups, with median overall survival (OS) and progression-free survival (PFS) around 24 months and 11 months, respectively.
However, when the investigators examined patients with RSP and LSP separately they saw a clear difference.
Patients with liver metastases from RSP had significantly better OS when SIRT was added to their chemotherapy compared to those who had chemotherapy alone (22.0 vs. 17.1 months, respectively; p=0.007; Hazard Ratio [HR]: 0.64 [95% CI: 0.46-0.89]), but this was not the case for patients with LSP (24.6 vs. 25.6 months; p=0.279; HR: 1.12 [0.92-1.36]).
“That means that RSP patients treated with chemotherapy plus SIRT have a 36% reduced risk of dying at any time point,” said van Hazel.
There was also a 27% improvement in PFS, although this was not statistically significant.
“This is the first time that location of primary tumour has been linked to radiation therapy,” said van Hazel, and although it’s possible that it may only apply to patients receiving first-line therapy, he said it opens a new treatment option for these patients.

ESMO
www.esmo.org/Press-Office/Press-Releases/Right-sided-Colorectal-Tumours-An-Internal-Radiation-Advantage?hit=ehp

A new technique developed by researchers at Lawrence Livermore National Lab promises to improve accuracy and lower costs of real-time assessment of kidney function, reports an article published this week by SPIE, the international society for optics and photonics.

The paper explores the use of multimodal autofluorescence and light scattering to evaluate functional changes in the kidneys after ischemic injury. Conditions including accumulated arterial plaque or blood clots restrict the flow of oxygen and glucose to organs, and prolonged periods of such ischemia can compromise function.

In ‘Predictive assessment of kidney functional recovery following ischemic injury using optical spectroscopy,’ the authors report on their evaluation of various optical signatures to predict kidney viability and suggest a noncontact approach to provide clinically useful information in real time.

While other current work in this area uses expensive multiphoton and laser-based techniques, the authors reduced expenses by switching to camera-based imaging.

Currently, there is no real-time tool to measure the degree of ischemic injury incurred in tissue or to predict the return of its function. The inability to decisively determine tissue functional status runs two great risks: that dysfunctional tissue may be transplanted, increasing the morbidity and mortality of the patient; and that much-needed functional kidney tissue may be discarded.

In their study, Rajesh Raman of Lawrence Livermore National Lab and co-authors Christopher Pivetti and Christoph Troppmann of the University of California Davis, Rajendra Ramsamooj of California Northstate University, and Stavros Demos of Lawrence Livermore acquired autofluorescence images of kidneys in vivo under 355, 325, and 266 nm illumination. Light-scattering images were collected at the excitation wavelengths while using a relatively narrow band light centred at 500 nm.

The images were simultaneously recorded using a multimodal optical imaging system. The recorded signals were then analysed to obtain time constants, which were correlated to kidney dysfunction as determined by a subsequent survival study and histopathological analysis.

Analysis of the light-scattering and autofluorescence images suggests that variations in tissue microstructure, fluorophore emission, and blood absorption spectral characteristics, combined with vascular response, contribute to the behaviour of the recorded signals. These are used to obtain tissue functional information and enable the ability to predict post-transplant kidney function.

This information can also be applied to the prediction of kidney failure when visual observation cannot, almost immediately following an injury.

Reviewers of the article suggested other promising applications for future development, and envisioned this approach being used as a screening tool for assessing kidney viability prior to transplant. In particular, they said, these cost-effective screening methods could benefit healthcare in developing countries.

SPIE spie.org/about-spie/press-room/press-releases/optical-spectroscopy-improves-predictive-assessment-of-kidney-function-4-may-2017

The biocompatible near-infrared 3D tracking system used to guide the suturing in the first smart tissue autonomous robot (STAR) surgery has the potential to improve manual and robot-assisted surgery and interventions through unobstructed 3D visibility and enhanced accuracy, according to a study. The study successfully demonstrates feasibility in live subjects (in-vivo) and demonstrates 3D tracking of tissue and surgical tools with millimeter accuracy in ex-vivo tests. More accurate and consistent suturing helps reduce leakage, which can improve surgical outcomes.

Authored by the development team from Sheikh Zayed Institute for Pediatric Surgical Innovation at Children’s National Health System and funded by the National Institutes of Health, the study explains the design of the 3D tracking system with near-infrared fluorescent (NIRF) markers and, using robotic experiments, compares its tracking accuracies against standard optical tracking methods. At speeds of 1 mm/second, the team observed tracking accuracies of 1.61 mm that degraded only to 1.71 mm when the markers were covered in blood and tissue.

‘A fundamental challenge in soft-tissue surgery is that target tissue moves and deforms, becomes occluded by blood or other tissue, which makes it difficult to differentiate from surrounding tissue,’ says Axel Krieger, Ph.D., senior author on the study and program lead for Smart Tools at the Sheikh Zayed Institute. ‘By enabling accurate tracking of tools and tissue in the surgical environment, this innovative work has the potential to improve many applications for manual and robot-assisted surgery.’

The system is made up of small biocompatible NIRF markers with a novel fused plenoptic and near-infrared (NIR) camera tracking system, enabling 3D tracking that can overcome blood and tissue occlusion in an uncontrolled, rapidly changing surgical environment. Krieger explains that the NIR imaging has the potential to overcome occlusion problems because NIR light penetrates deeper than visual light.

‘This work describes the ‘super human eyes’ and a bit of ‘intelligence’ of our STAR robotic system, making tasks such as soft tissue surgery on live subjects possible,’ explains Peter C. Kim, M.D., vice president and associate surgeon in chief of the Sheikh Zayed Institute.

EurekAlert www.eurekalert.org/pub_releases/2017-02/cnhs-b3t021717.php

A large nuclear cardiology laboratory has slashed its average radiation dose by 60% in eight years, according to new research presented at ICNC 2017 and published in JACC: Cardiovascular Imaging. The study in over 18,000 patients shows dose reductions were achieved despite a large number of obese patients.
Medical societies advocate getting radiation doses as low as is reasonably achievable. There are ways to do this but surveys show that adoption of new technologies, which cost money, and new testing algorithms, which take more physician time, has been slow.
This study assessed the impact on radiation dose of modifying protocols and introducing new hardware (cameras) and post processing software in a large nuclear cardiology laboratory network in Kansas City.
The study included the 18,162 single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) studies performed at all four of the Saint Luke’s Mid America Heart Institute nuclear cardiology laboratories from 1 January 2009 to 30 September 2016. SPECT MPI shows how well blood flows through the muscle of the heart and is primarily performed to diagnose the cause of chest pain or to help manage patients with known coronary artery disease.
Protocols were modified by performing stress-only tests where possible, which saves the radiotracer dose from the rest scan. Stress and rest scans are still required in some patients since shadowing from body parts can look like a lack of blood flow and two scans can clarify the findings. Technetium tracers are now used instead of thallium 100% of the time at one-third of the radiation dose.
Small field of view cameras which have advanced post processing, and a new generation of camera systems which are more sensitive and need less radiotracer injected into the body, have both been introduced. These camera systems are equipped with advanced processing which enhances the nuclear pictures and need less radiation or shorter image acquisition times.

Mid America Heart Institute, Kansas City, MO, USAhttps://www.escardio.org/The-ESC/Press-Office/Press-releases/large-nuclear-cardiology-laboratory-slashes-radiation-dose-by-60-in-eight-years