Dr. Vladimir Iakovlev, Pathologist

Mesh Medical Device News Desk, December 7, 2017 ~ Dr Vladimir Iakovlev is an Associate Professor of Laboratory Medicine and Pathobiology, University of Toronto; Director of Cytopathology, St. Michael’s Hospital, Toronto, Canada.

He has examined over 50o specimens of mesh explants, taken from patients experiencing complications associated with both hernia and pelvic mesh.

Pathologists examine the tissue around the device and play the role of detective to determine a cause of death. He is being called into advise the coroner in the recent death of a 42-year-old Windsor, Ontario woman, who suffered complications from a TVT Exact mesh implant. Dr. Iakovlev will advise which tissues will need to be sampled.

At this time, there is no official cause of death specifically related to mesh infections.  Often sepsis is listed as a cause of death, or an uncontrollable blood bacterial infection, but the cause of sepsis is not identified.

Mesh News Desk interviewed Dr. Iakovlev about the steps he takes in his detective work.

Laparoscopic photos B. Rosenberg Prolene hernia system eroded

Q: What do you find in the body near a mesh implant?

A: “There is a degree of complexity. Based on the pathologists’ knowledge we’ve accumulated over 200 years about changes involving any foreign body.  There is an inflammatory reaction as the body recognizes the foreign body is harmful. It wants to get rid of it, digest or expel it. The first reaction is an inflammatory reaction.

“Since any surgery makes a surgical pocket, the space is filled with fluid. The same thing happens around implants. This clotted fluid forms the mold for future tissue to form granulation tissue, which matures to scar tissue.  If a foreign body cannot be destroyed, the body tries to isolate it. It makes a fibrous capsule which is the same as scarring.

“Mesh is porous and scar forms inside and outside the mesh.

“We need to remember that our soft tissues heal by laying scar tissue. Mesh cannot be integrated by normal tissue in humans. There is also foreign body inflammation which damages tissue and is a stimulus for further fibrosis or scarring.

“The problem with meshes is that the porous ones have scar tissue inside the pores. As granulation tissue matures into scar it can pull the mesh fibers together and the entire mesh shrinks.  The main problem with scarring and inflammation is mesh shrinkage.

Mesh explant, St. Michael’s Hospital, CTV Mesh Misery

“Nerves can grow into and around the mesh. This tells us that the tissue can sense what is going on. As any innervated tissue it can feel pain too. Also, those nerves that grow into the mesh can get trapped and deformed there. Nerves can be effected by migration as well when the mesh moves.

“We know mesh doesn’t stay stationary, it can migrate, fold or bunch up. The tissues around mesh are not strong enough to hold it. In some people it is just millimeters, in some centimeters. We know that even implants and nails in the bones can still slowly migrate.

“Some mesh migrates through the spermatic cord inside the groin. In the pelvis, meshes can migrate or erode internally into the bladder or rectal wall.

“It can deform, fold and bunch up. It can happen during, right after, or many months and years after surgery. Tissues in the vaginal wall have elastic and muscle fibers so they can contract and expand. In mesh, once it’s folded it’s folded and stays folded. There is no mechanism to stretch it back.”

Biofilm

Q: What about the role of biofilms in harboring infection?

A: “Biofilm is a loose term. People can mean different things using it. They may mean coat of bacteria or proteins. Generally, we don’t have to reinvent the bicycle. Foreign bodies have been known forever as a potential source or reservoir for infection. The surface and some small spaces in the implants can harbor bacteria. That is why we try to remove all bullets, splinters and dead tissues.

“As I mentioned foreign body type inflammation and other standard pathological processes related to foreign bodies have been known for a long time, some over 100 years. For example, foreign body reaction studies are from the late 1800s. Look at Russian scientist Eli Metchnikoff in Paris, who gave the first description of these immune responses.

“Any foreign object can provide shelter for bacteria. For bacteria, it’s difficult to survive on native tissues because they are protected by the immune system.  But a foreign object provides shelter for bacteria. That’s been known for a long, long time.

“We get the bullet out because it may get infected. We get rid of all dead tissue and the foreign object to clear up an infection.

“Even if bone fragments go necrotic, due to insufficient blood supply, it can become infected.”

 

Prolene mesh

Q: Does it depend on the mesh?

A: “Yes. Some mesh types can harbor more infections and limit ability of immune system to kill the bacteria. The microporous meshes have small pores where the bacteria can get stuck.

“Neutrophils, a type of immune cell, cannot move well and kill bacteria. Multifilament or braided meshes are in that category. However, generally all meshes can contain infection, it is just some have higher risk and some lower.”

 

Dr. Vladimir Iakovlev showoing mesh eroding through the bladder, CTV Mesh Misery

Q: What do tissues tell you about mesh-related cause of death?

A: “When doing an autopsy, and I’ve done a number of them, we can answer several questions. One is immediate cause of death. Also we can collect information which can be used to answer other questions.

“Doing an autopsy one needs to be thorough and approach with open mind.  Examine entire body and all organs, heart, brain, lungs, kidneys. Collect all information and tissue samples for later microscopy. Look for changes and sample more tissue in areas that are affected by a disease, previous surgery etc. Then all information comes together from history, gross findings, microscopy and toxicology.

“One would need to look at the chart information, check previous blood tests. Autopsy may or may not show answers for all questions. Generally, if we focus on chronic infection, whether it is related or not to the immediate cause of death, it can be of different sources including urosepsis. A cause of it can be recurrent UTI spikes, or something in the kidney, bladder or elsewhere in the genitourinary system that leads to recurrent infection.

“In any death there is the immediate cause of death then there are the background conditions. Sometimes it is more complicated than seems.

“For example, if during an argument a person punched in face and falls from stairs, sustains trauma but also is found to have a heart disease at autopsy. The injury itself was substantial but not likely not lethal on its own. Also without the incident he likely would not have a heart attack at the time. So, did he die from the punch and fall or natural causes such as a heart condition? It’s not black and white sometimes.

“I know little more about meshes, where they are placed and changes that can be there. In this case I’m not the official person doing the autopsy, I was only asked to share my knowledge in this specific field, what tissue can be preserved.  Autopsy is done by the coroner’s office and they will do their assessment.”

 

Macrophages at work, Stonybrook Medicine

Q: In your experience what have you seen at mesh sites?

A: “Pathology has drifted from autopsies to now surgical specimens. Every lump is being biopsied. Biopsies and excisions are overwhelmingly higher in volume than autopsies. Regular pathologists mainly look at biopsies and excised tissues.

“Similarly, all removed implants come to pathologists. Then it depends on a pathologists’ knowledge and experience how much they can describe. We see scarring or fibrosis, we see foreign body type inflammation, we see nerves and sometimes small parts of other organs. If mesh is infected we see neutrophils. It is hard to see bacteria if they are in small numbers, but neutrophils that come to kill the bacteria are easier to see.

(More on neutrophils here, which help fight infection by ingesting microorganisms.  Microphage/ Macrophage – present in the blood that migrates to tissue in the inflammatory immune response. See the human immune system here. )

“All of these changes are well known.  There are only few issues that need to be studied. For example, leachables from plastics can have some effect. That has to be studies. As far as I know we do not know exactly what can leach from plastics and what are the effects of these substances on our tissues.

“I read articles that some plasticizers and other chemicals leaching from the labware can have effect on cell cultures in laboratory experiments. See more here and here.

“The substances also appear to leach from plastic syringes into the fluid that contain, if they are stored for a long time.  Some patients feel a stale, metallic or plastic taste in the mouth after injections, when compared to a freshly filled syringe.”

LEARN MORE:

 MND, What’s Added to Plastic Mesh, March 7, 2017
https://www.meshmedicaldevicenewsdesk.com/whats-added-plastic-mesh/

CTV, Mesh Misery
https://www.youtube.com/watch?v=rCFu5NIo0bI