To properly pickle a leaky tumor

Give it a shot of alcohol Jello and come back next week. It could be gone, says one study

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P Rajendran

Hamsters

The effect of high-viscosity ethanol was tested in a hamster model. Photo: Pixabay/Creative Commons

While you always can have too much of a good thing, the reverse may be true for alcohol – that is, if you’re only using it to fight tumors.

Alcohol (or, to be more specific, ethanol) has been associated with cancer. But it can also destroy a tumor, as long as it is injected into the offending mass and not allowed to leak out. Of course, keeping ethanol in leaky tissue is not easy. One possible answer: make a nice thick goo of it.

Cancer researchers at Duke University led by Nirmala Ramanujam were especially frustrated because unlike other forms of tumor destruction, alcohol does not need complicated machines, and can be remarkably cheap for cancer treatment (less than $5 per treatment). Now if it only could be kept in place…

This helps people who have cancers in organs that can seal in the injected alcohol – such as in the heart, the pancreas, and the adrenal and parathyroid glands. The researchers needed to know what to do in the case of tumors in other areas – like in their own area of focus, cervical and breast cancers.

Robert Morhard, the first author of the paper on the new gel published in Scientific Reports, told Truly Curious, “Cervical precancerous lesions form on the top of the cervix and can be detected with a device our lab has been developing for a few years now.” The device, the pocket colposcope, costs about $250, is far less expensive than those in standard use, the kind that can look like anything from a TV studio camera to a thinner, taller version of < a href=https://en.wikipedia.org/wiki/WALL-E>Wall-E.

Nirmala Ramanujam, director of the Center for Global Women’s Health Technology at the university, did not think it made sense to provide such screening tech if there was no effective treatment. And so they decided to address treatments, preferably inexpensive ones.

The Global Women's Health Technology Lab at a meeting with potential collaborators

The Global Women’s Health Technology Lab at a meeting with potential collaborators on their pocket colposcope. Also seen are first author Robert Morhard (far left) and lab director Nimmi Ramanujam (fifth from right in the second row).


According to Morhard, “After lots of reading (lots…) we found ethanol ablation, or the direct injection of ethanol into the tumor to destroy the malignant cells. Many extraordinary groups have pioneered this in the past and we completely rely on their hard work and brilliance now.”

First described by the Sugiura and four other researchers from Japan in 1983, the process first involved injecting ethanol into encased liver tumors, which were otherwise very hard to treat. The method has been fine-tuned since but remained effective only when there was no possibility of the ethanol leaking.

“We tried this on tumors we had grown in the hamster cheek pouch and it didn’t work very well,” Morhard said. “Even when injecting high volumes of ethanol, only 4 out of 12 tumors went away. After a lot more reading …we learned about how complex injections really are.”

The team concluded that thickening up the ethanol could possibly make it stay in place long enough to kill the tumor and not just give the patient a tiny high.

“One of our collaborators suggested ethyl cellulose, which increases the viscosity of ethanol-based solutions,” Morhard said.

Cellulose, found in wood, cotton, etc, is a long string of glucose molecules hooked together by oxygen. Ethyl cellulose, a derivative of cellulose, relies on more oxygen bonds to form a net that increases the viscosity of any ethanol mixed in it. Ethyl cellulose is also a food stabilizer and thickener, so has been checked for safety, so the idea of using it to thicken the alcohol sounded good.

Ethyl cellulose

“We tried this and in the process of testing we realized that since ethyl cellulose is not water-soluble it forms a gel when you mix it with water,” Morhard said. “Tumors (and all tissue) are water-based. This means that when you inject ethyl cellulose-ethanol into the tumor a gel forms and retains the ethanol in the tumor. This greatly enhanced efficacy.”

So, in the study, chemically-induced tumors in hamsters’ cheek pouches were given either pure ethanol injections or the ethyl cellulose-ethanol Jello. The pure ethanol group was further divided into two subgroups, one getting injections of pure ethanol that were four times the tumor’s volume, the other got alcohol one-fourth the volume of the offending mass.

The researchers had many other things to try and fail and learn from before they got results.

For example, they tried to ensure a slow rate of injections (0.1 milliliters per hour) to ensure that pressure would not cause the tumors to spring leaks. That was fine for the pure ethanol group, not so much for the ethyl cellulose-ethanol gel. They concluded that while that technique was fine for the free-flowing pure ethanol, the gel needed more pressure to get into the cracks, and that a moderate 10 milliliters per hour worked best. Then they had to ensure they had enough hamsters with tumors at the right size for treatment.

They injected the hamsters, and measured the size of the tumors on the first, second, fourth and seventh day. If a tumor was still growing, they were injected again, being treated as new tumors.

According to the paper, “As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively.” That is, even flooding the mass with four times is volume of ethanol only caused a third of the cells died.

“In contrast,” the paper added, “ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors.”

It added: “Of the 7 tumors injected with 3% ethyl cellulose at 10 mL/hr, 6 out of 7 completely regressed by day 7, and 7 out of 7 completely regressed by day 8. Of the 5 tumors injected with pure ethanol at 10 mL/hr, 0 out of 5 regressed completely.”

Ethanol vs ethyl cellulose-ethanol against tumors

The tumor volume in percentage over time. The graph on the left shows that hamsters who got pure ethanol injections did far worse on average than those that got ethyl cellulose with ethanol injections (right).

The paper admits that only one kind of tumor and tissue were studied, that the sample size was small (eight hamsters), and that the damage to surrounding tissue or the chance of new tumors popping up were not addressed. But this study was a proof-of-concept and has much promise.

As the paper concluded, “Given the general lack of accessibility to surgery or alternative tumor treatments in developing countries and the promising results presented in this study, enhanced ethanol ablation is a promising method to meet the unmet clinical need of rising cancer mortality that challenges healthcare systems in developing countries.”

Details about the team’s work at Center for Global Women’s Health Technologies
Details about the Pocket Colposcope