When the UNIM lab opened at the Skolkovo Technopark at the beginning of this year, it offered cancer patients around the country the chance to get expert opinions on their tumours by digitalizing slides and sending them to the world’s top specialists. Six months on, Sk.ru visited the lab to find out what exactly goes on in the lab, how business is going and whether a second opinion can really save lives.

The digital slides enable pathomorphologists to zoom in on specific areas and examine the cells in detail, as well as to send them to specialists around the world for second and third opinions. Photo: Sk.ru. 

UNIM’s mission is to improve the accuracy of cancer diagnosis, and accordingly, its treatment. Currently, it is estimated that between 50 and 80 percent of patients are given inaccurate diagnoses, resulting in people undergoing unnecessary operations and chemotherapy, being given the wrong kind of treatment for the cancer they have, or being incorrectly told that they do not have cancer. UNIM, a resident of Skolkovo’s biomed cluster, is trying to change these frightening statistics by ensuring that as many specialists as needed (and at least two) see a patient’s slides and that diagnosis is given based on a collegiate decision.

“Generally, diagnosis is basically devoid of any information technology: the doctor looks at the histological glass slides through the microscope, and that’s it,” says Olga Karpova, head of communications at UNIM.

“We have made this area as digital as possible. We have two software programmes: one that curates the processes inside the lab, and the second is our Digital Pathology, which connects pathomorphologists in a unified worldwide network that allows them to make a collegiate diagnosis.”

The beginning of the process at the UNIM lab - sample preparation - is not so different to that in any other lab specialising in the analysis of biomaterials. Biomaterials are delivered to the lab, where they are photographed in their original state before the doctor examines them, for the record (the initial appearance can be important in determining the diagnosis). The sample is put in a container and labelled with a unique number to ensure that it is both anonymously labelled, but cannot be confused with another patient’s material. 

Olga Karpova, lab manager at UNIM. Photo: Sk.ru.

Next, a mixture of spirit, formalin and paraffin is added to the biological sample to prevent it from decomposing, and a very thin layer (one micron, or one millionth of a metre) is removed from it and put onto a glass slide. Then the sample is put into a machine that colours the cells in vivid pink and purple colours: this helps the doctor to see the individual cells more clearly.

Machine magic

At this point, in the words of Karpova, “the new technology magic begins.” The slide is put into an immunohistochemistry machine that performs selective imaging of the antigens (proteins) in the cells by recording their reaction to various antibodies. This enables the doctors who analyse the slide and other clinical information such as CT and MRI scans to say with great accuracy what kind of cancer it is, and how aggressive it is, says Karpova.

“If we know it’s breast cancer – one of the most common cancers in the world right now – then we test the cells’ reaction to certain antibodies such as progesterone,” says Karpova.

“We look at how the cells react and how many of them do so, and determine what stage the cancer is at and how aggressive it is. Then the doctor writes the diagnosis and prescribes the treatment.”

Because immunohistochemistry machines and testing are very expensive, regular state clinics in Russia do not often have such equipment and cannot run those tests, Karpova said. But what the UNIM lab does next is rarer still: it is done in just two other labs in the world, in the U.S. and the Netherlands, she said.

“Usually at this stage, the doctor looks at the slide through the microscope, and that’s it. We scan everything to create a digital slide, which is sent to the cloud,” explains Karpova. This digital slide can then be sent to the leading experts in that kind of cancer, wherever in the world they happen to be.

The digital scan acts like a microscope, enabling doctors to enlarge areas of interest. In one part of the UNIM lab, doctors pore over scans of histological slides on their computer screens as they write their conclusions.

“We use our Digital Pathology system, which enables a large number of doctors to examine the slide in a short period of time,” says Karpova.

“In many local clinics, doctors might not have seen a particular kind of melanoma before, or rare children’s diseases. We can turn to specialists in this field all over the world.”

For this purpose, UNIM has amassed a database of about 1,500 pathologists. It currently works actively with about 50 specialists, mostly located in Russia and some European countries, which has been sufficient so far, according to Karpova.

“We give people in the regions the chance to have a consultation with the best specialists across the country, and to get a diagnosis within 72 hours. Occasionally there are very difficult cases and we warn patients it will take a little longer, but it’s better to have an accurate diagnosis in the end,” she said.

The UNIM lab is home to powerful equipment that is rare in Russian hospitals. Photo: Sk.ru.

Second opinion

Patients who ask for a second opinion from UNIM rarely do so in vain.

“Very often we change the diagnosis, from the stage the cancer is at to the diagnosis itself. Often this is because there was no immunohistochemistry machine where they were given the diagnosis,” says Karpova.

Recently, the lab took on a case from Kazakhstan: a 14-year-old boy who had been diagnosed with a testicular tumour, and undergone four sessions of chemotherapy and an operation to remove one of his testicles and the surrounding lymph nodes, said Karpova, noting that chemotherapy is toxic to the human body.

“His mother wasn’t convinced by what they were doing and sent us his slides. It was very difficult to diagnose, we tested about 20 antibodies on it, but in the end it turned out that the tumour was benign, so he shouldn’t have had anything else cut out of him, nor should he have had chemotherapy,” she recounted.

Another case involved a 33-year-old woman who had been diagnosed with lung cancer and was due to begin chemotherapy. The UNIM lab determined that her tumour was in fact also benign, meaning chemotherapy would only have damaged her lungs.

Alexei Remez, director general of UNIM. Photo: Sk.ru.

The UNIM lab receives about 200 samples of biomaterials a week, from all over Russia as well as neighbouring countries including Kazakhstan, Uzbekistan, Ukraine and Belarus, said Karpova.

Some patients find out about the lab themselves and send their slides to UNIM for a second opinion. Others are patients at private cancer clinics with which UNIM has agreements and whose doctors contact the lab in order to give the most accurate diagnosis possible, she said.

“We also have several agreements with state clinics, mainly in remote regions such as Tyumen, Arkhangelsk and the Jewish Autonomous Region,” said Karpova, noting that some regions have just one specialist who cannot manage the workload on their own.

“They prepare the cells themselves and send us scans, and our doctors diagnose the cases. It’s an example of telemedicine in action, and enables patients to get help from leading Russian specialists,” she said.

UNIM is also working on the use of artificial intelligence to improve diagnosis, developing neural networks that would help pathologists in their work. A system has already been developed to determine the aggressiveness of the cancer.

“Usually pathologists count for themselves the number of bad cells (stained a darker red brown) among the good ones, shown in purple and pink,” explains Karpova, gesturing to the screen of one of the doctors examining a scan. “Here, in just two seconds, the system counts them for us.”

Skolkovo brand

UNIM was founded in 2013, and became a resident company of the Skolkovo Foundation back in 2015 after winning the diagnosis systems category of the OncoBioMed competition jointly organised by the foundation and the Federal Agency of Scientific Organisations. The company previously worked from other labs, but soon realised they needed their own dedicated space.

“Our aim was to show how a digital lab could work and to develop this field, and we built our own lab using investment,” says Karpova.

Initial reservations ahead of the move about the location of the Skolkovo Technopark on the outskirts of Moscow vanished swiftly, and “we are extremely happy with Skolkovo,” she said.

“The atmosphere, ecosystem and environment created by Skolkovo are just what we need. If we worked from a hospital, it would be completely different,” she said, adding that the Skolkovo brand had been a big help in promoting UNIM’s development in Russia’s regions.

Photo: Sk.ru.

The lab employs about a dozen people, and is fully immersed in the Skolkovo ecosystem: it has the status of a shared resource centre, meaning it can perform paid services for other Skolkovo startups that need to use its equipment, and works closely with the Sk BioLab, a shared lab for biomed startups at the Technopark.

UNIM is looking ahead to the opening of the Moscow International Medical Cluster later this year, and hopes to cooperate with the centre, particularly if the cluster does not have its own pathomorphology lab.

Skolkovo also provided consulting support via its investment service last year when UNIM raised an undisclosed sum of investment from Medme, a strategic investor on the digital medicine market.

“We believe the field of remote interpretation and diagnosis is a highly promising one,” Ilya Slutsky, a managing partner at Medme, said at the time.

“Today, histological and immunohistochemical research is the only definitive diagnosis method in the world. At the same time, in many areas, and not only in Russia, there is a huge deficit of pathologists and specialists. UNIM’s service helps to solve this problem.”