• Peripheral neuropathy is a very common side-effect of chemotherapy and may eventually lead to early discontinuation of treatment.
• Collaboration between research and industry led to the identification and successful testing of a new molecule capable of preventing this neurological complication.
• This molecule could potentially become the first existing treatment to prevent this frequent adverse effect and improve the quality of life of cancer patients.

IDIBELL Researchers of the Neuro-Oncology Unit of Bellvitge University Hospital – Catalan Institute of Oncology, led by Dr. Jordi Bruna, have successfully tested a new molecule capable of preventing the development of peripheral neuropathy induced by chemotherapy in cancer patients, especially in colon cancer cases, the third most common neoplasm in the world. The molecule, which has a completely novel mechanism of action, would be the first treatment against this neurological complication, for which no effective treatment has yet been approved.
One of the main adverse effects of certain chemotherapeutics used in the treatment of cancers is peripheral neuropathy, which can cause tingling, numbness, pain or alterations in the functionality of patients, among others. This complication, so far, has been regarded as a “price to pay” despite having a demonstrated negative impact on the quality of life of the patient, increasing their care expenses and often preventing the complete and effective administration of  the cytostatic treatment, with the potential decrease of survival chances that entails.
Researchers at the HUB-ICO-IDIBELL Unit identified a new molecule – developed by the Catalan laboratory Esteve – as a candidate to prevent the onset of this adverse effect. "Through a public-private partnership, we have been able to design a Phase 2b clinical trial (randomized with placebo), which has allowed us to get a great deal of scientific information – effect on pain, pathophysiology – and draw conclusions as to the potential of the drug in the prevention of neuropathies during cytostatic treatment”, explains Dr. Bruna, who led the trial.
The results of the study prove a decrease in the appearance of disorders associated with nerve dysfunction in those cancer patients who took the new drug. "When the trial was designed, safety data from the previous trials limited the duration of treatment with the new molecule and this meant that we had to work at low doses in relation to the duration of the chemotherapy treatment, but we have nevertheless obtained positive results and now we have enough information to be able to extend the duration of the treatment. Therefore, we hope to obtain even more satisfactory results" the IDIBELL researcher comments.
"Given the usual pace of clinical trials and drug agencies following fast-track approval processes in severe or orphan pathologies, this new drug could potentially reach the market soon, since it would be the first available treatment to avoid this type of neuropathy. In addition, it has other medical uses as a non-opioid analgesic”, adds Bruna. In any case, improving pain control and reducing the occurrence of severe neuropathy is undoubtedly the most prominent benefit of the development of this novel drug..
IDIBELL
www.idibell.cat/modul/news/en/1024/researchers-prove-the-effectiveness-of-a-new-drug-to-prevent-the-onset-and-the-pain-of-chemotherapy-induced-neuropathy

During operations, it can be difficult for surgeons to avoid severing crucial nerves because they look so much like other tissue. A new non-invasive approach that uses polarized light to make nerves stand out from other tissue could help surgeons avoid accidentally injuring nerves or assist them in identifying nerves in need of repair.
Although nerve injuries are a known complication for many types of surgery, surgeries involving the hand and wrist come with a higher risk because of the dense networks of nerves in this area. There are a few techniques available to help doctors identify nerves, but they have various limitations such as not providing real-time information, requiring physical contact with the nerve or requiring the addition of a fluorescent dye. 
Cousins, Kenneth and Patrick Chin, developed the idea independently from any institute to use an optical technique known as collimated polarized light imaging (CPLi) to identify nerves during surgery. Kenneth later joined a research group led by Thomas van Gulik, a surgeon at the Academic Medical Center, and brought along a working prototype which has been further developed into a practical system that can be deployed in the operating room.
In The Optical Society (OSA) journal Biomedical Optics Express, the researchers report that a surgeon using CPLi technology was able to correctly identify nerves in a human hand 100 percent of the time, compared to an accuracy rate of 77 percent for the surgeon who identified nerves using only a visual inspection.
CPLi uses a polarized beam of light to illuminate the tissue. When this light passes through a nerve, the tissue’s unique internal structure reflects the light in a way that is dependent on how the nerve fibre is oriented compared to the orientation of the polarization of the light. By rotating the light’s polarization, the reflection appears to switch on and off, making the nerve tissue stand out from other tissue. For this application, it was important to use light that was collimated, meaning all the light waves were parallel to each other, to maximize the amount of light reflected by the tissue.
“We adapted the optics used for CPLi so that they could be incorporated in a surgical microscope, which can be placed above the surgical area,” said Kenneth Chin. “The resulting system can be used in a wide range of surgical fields where superficial nerves need to be identified.”
After testing their technique on animal tissue, the researchers used it to examine 13 tissue sites from the hand of a human cadaver. A surgeon looked for nerve tissue at these sites by eye under typical surgical illumination while a different surgeon used CPLi for an independent assessment. Histological evaluation was then used to verify the presence of nerve tissue at each site. The surgeon using visual inspection correctly identified nerve tissue in 10 of the 13 cases while the surgeon using CPLi correctly identified nerve tissue in all cases.
With patient consent, the researchers also used CPLi to successfully identify nerve tissue during a procedure to relieve pain in the wrist. They plan to do additional tests of the technique during live surgery to better understand how the optical reflection of nerves might vary among patients and under various surgical conditions. 

The Optical Society
www.osa.org/en-us/about_osa/newsroom/news_releases/2017/new_tool_aims_to_make_surgery_safer_by_helping_doc/

Researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) have developed a proof-of-concept nanosystem that dramatically improves the visualization of tumours. The platform achieves a five-fold increase over existing tumour-specific optical imaging methods. The novel approach generates bright tumour signals by delivering “quantum dots” to cancer cells without any toxic effects.
Xiangyou Liu, Ph.D., and Gary Braun, Ph.D., developed the method in the laboratories of Kazuki Sugahara, M.D., Ph.D., adjunct assistant professor at SBP and adjunct associate research scientist at Columbia University, and Erkki Ruoslahti, M.D., Ph.D., distinguished professor at SBP.
“Tumour imaging is an integral part of cancer detection, treatment and tracking the progress of patients after treatment,” says Sugahara. “Although significant progress has been made in the last two decades, better and more sensitive detection, such as the method we are developing, will contribute to more personalized and potentially more effective interventions to improve the clinical outcomes of cancer patients.”
The new method utilizes quantum dots, QDs—tiny particles that emit intense fluorescent signals when exposed to light—and an “etchant” that eliminates background signals. The QDs are delivered intravenously, and some of them leave the bloodstream and cross membranes, entering cancer cells. Fluorescent signals emitted from excess QDs that remain in the bloodstream are then made invisible by injecting the etchant.
“The novelty of our nanosystem is how the etchant works,” explains Braun. The etchant and the QDs undergo a “cation exchange” that occurs when zinc in the QDs is swapped for silver in the etchant. Silver-containing QDs lose their fluorescent capabilities, and because the etchant can’t cross membranes to reach tumour cells, the QDs that have reached the tumour remain fluorescent. Thus, the entire process eliminates background fluorescence while preserving tumour-specific signals.
The method was developed using mice harbouring human breast, prostate and gastric tumours. QDs were actively delivered to tumours using iRGD, a tumour penetrating peptide that activates a transport pathway that drives the peptide along with bystander molecules—in this case fluorescent QDs—into cancer cells. iRGD methodology was originally developed in Ruoslahti’s lab.
To our knowledge, this is the first in vivo example of a background-destroying etchant being used to enhance the specificity of imaging,” says Sugahara. “We are encouraged that we were able to achieve a tumour-specific contrast index (CI) between five- and ten-fold greater than the general cut-off for optical imaging, which is 2.5.”
“Moving forward we will focus on developing our novel nanosystem to work with routine imaging tests like PET scans and MRIs. In our studies with mice, we use optical imaging, which isn’t always practical for humans,” Sugahara explains.

Sanford Burnham Prebys Medical Discovery Institute (SBP) http://tinyurl.com/yczo8jyt

Rising rates of opioid prescriptions have been linked to the opioid epidemic, and a significant number of opioid deaths have been linked to prescriptions written by surgeons.  However, new study results suggest that a more vigilant prescribing guideline for surgeons could reduce by as much as 40 percent the number of opioid pills prescribed after operations, and still meet patients’ pain management needs.
Lead study author Richard J. Barth Jr., MD, and colleagues at Dartmouth Hitchcock Medical Center in Lebanon, NH, have suggested the guideline. “We specifically looked at the number of opioid pills that surgical inpatients took the day before discharge from the hospital, and we found that this number was the strongest predictor of how many opioid pills the patients would use after discharge,” Dr. Barth said.
The recommendation does not mean patients won’t get enough pills to manage their pain after they leave the hospital. “The guideline was based on satisfying at least 85 percent of patients’ home opioid requirement,” Dr. Barth said.
The study included 333 hospital inpatients discharged to home after six different types of general surgery operations: bariatric procedures; operations on the stomach, liver, and pancreas; ventral hernia repair; and colon operations. The researchers followed up with the patients after discharge by using questionnaires and phone surveys; 90 percent of the discharged patients completed the follow-up process. The study group did not include any chronic opioid users.
This study represents the first time that specific guidelines have been proposed for prescribing opioids upon discharge after general surgery operations that require inpatient admission. Although some states have adopted laws to curb opioid prescriptions, they are ambiguous. Dr. Barth noted that several New England states limit doctors to prescribing a seven-day supply of opioids, but they include no limits on dosing. “So a seven-day supply could be 84 pills or 21 pills,” he said.
The researchers found that patients typically took only a fraction of the opioids prescribed at discharge once they went home. While 85 percent of patients were prescribed an opioid after they went home, only 38 percent of prescribed opioid pills were taken. The study also looked at why a small fraction of patients took more opioids than the new guidelines called for. “Over half of them were taking opioids for non-pain-related reasons, such as to sleep better, or because they felt they should take all the pills the physician prescribed and other various and sundry reasons,” Dr. Barth said.
Patients who undergo operations have a higher risk of becoming chronic opioid users than non-surgical patients do, according to previously published research Dr. Barth and his colleagues cited.1–4 Also, unused opioid pills laying around the home contribute to chronic opioid use; 71 percent of chronic opioid users receive their pills through diversionary methods like a relative’s unused prescription.4,5
The guideline Dr. Barth and colleagues developed recommends the following schedule for post-discharge prescription based on the number of opioid pills taken the day before discharge: no pills for patients who took no opioids the day before they left the hospital; 15 pills for those who took one to three pills the day before; and 30 pills for those who took four or more pills on their last day in the hospital.
“This guideline was true for multiple different operations,” Dr. Barth said. “It didn’t matter whether someone had a colon operation, liver procedure or hernia repair; no matter what type of general surgery operation they had, this association held throughout all procedures studied. So the beauty of this finding is that one guideline would apply for multiple different surgical procedures.”
A second factor that influenced patient opioid use after surgery was age. “Patients who were older ended up taking fewer opioids than younger patients,” he said. Patients younger than age 60 averaged about 13 pills after discharge while those 60 and older averaged four pills.
The increased use of e-prescribing—in which a physician can send an electronic prescription directly to a pharmacy—is another factor that should encourage physicians to write prescriptions for fewer pills after surgery. “With e-prescribing, patients don’t have to come back to the clinic if they need more pills,” Dr. Barth said.
The guideline has already been adopted at Dr. Barth’s institution and can easily be applied at other centers, he said.
American College of Surgeons
www.facs.org/media/press-releases/2017/opioids113017