Not cancer but a new challenge for me

[Gerri]

After dealing with increasing knee pain for several months I went to my rheumatologist to see if my osteo arthritis was getting worse. After getting xrays taken I got a call from my doctor telling me that I needed to find an orthopedic surgeon because my right knee was 'bone on bone' and my left knee was almost as bad and I would probably need total knee replacement surgery.

I met with the orthopedic surgeon yesterday and was told that while most of the time this is an elective surgery, in my case my 'deformity' (love that!) was such that if I waited too long more damage could occur and surgery would be even more complicated. So, on April 11 I will be undergoing bilateral knee replacement surgery. I am really looking forward to walking pain free but know that the recovery for this procedure (especially bilateral) is quite challenging. I have done plenty of research and have a good idea of what I am up against. I guess I am looking (hoping) for some encouraging words from people who have 'been there and done that' and are happy with the results.

Looking forward to getting some positive feedback.

[AlaskaAngel]

Hi Gerri,

My SO has one knee that is bone-on-bone (we saw the x-rays.... really awful...) He will be having one done this spring once the weather is good enough that he won't have to deal with the weather and ice up here. The factors seem to be 1) how good is the surgeon, 2) whether one's anatomy is favorable, 3) how problematic are other health issues one might have, and 4) getting past the period of discomfort. From what I've seen, most do very well. I'm still going to be holding my breath all the way -- this is personal. So... will keep you posted....

Wishing you the best,

A.A.

[Lani]

I almost NEVER make any recommendations on this site, but I would seriously recommend you reconsider your decision to do both knees at the same sitting.

Just one of many articles on the subject (google entrez pubmed, enter complications bilateral versus unilateral total knee replacement to see more):

article is free so you can view it in its entirety


Clin Orthop Relat Res. 2008 Nov;466(11):2617-27. Epub 2008 Aug 14.
In-hospital complications and mortality of unilateral, bilateral, and revision TKA: based on an estimate of 4,159,661 discharges.
Memtsoudis SG, González Della Valle A, Besculides MC, Gaber L, Sculco TP.

Department of Anesthesiology, Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021, USA.
Abstract
Patients undergoing bilateral total knee arthroplasty (BTKA) may have higher complication rates and mortality than those undergoing a unilateral procedure (UTKA). To evaluate this hypothesis, we analyzed nationally representative data collected for the National Hospital Discharge Survey on discharges after BTKA, UTKA, and revision TKA (RTKA) between 1990 and 2004. The demographics, comorbidities, in-hospital stay, complications, and mortality of each procedure were compared. An estimate of 4,159,661 discharges (153,259 BTKAs; 3,672,247 UTKAs; 334,155 RTKAs) were included. Patients undergoing BTKA were younger (1.5 years) and had a lower prevalence of comorbidities for hypertension (versus UTKA), diabetes, pulmonary disease, and coronary artery disease (versus UTKA and RTKA). The length of hospitalization was 5.8 days for BTKA, 5.3 for UTKA, and 5.4 for RTKA. Despite similar length of hospitalization, the prevalence of procedure-related complications was higher for BTKA (12.2%) compared with UTKA (8.2%) and RTKA (8.7%). In-hospital mortality was highest for patients undergoing BTKA (BTKA, 0.5%; UTKA, 0.3%; RTKA, 0.3%). Patients undergoing BTKA had a 1.6 times higher rate of procedure-related complications and mortality compared with those undergoing UTKA. Outcomes for patients undergoing RTKA for most variables were similar to those for UTKA. BTKA, advanced age, and male gender were independent risk factors for complications and mortality after TKA. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

PMID: 18704616 [PubMed - indexed for MEDLINE]PMCID: PMC2565056Free PMC Article

[Chelee]

Hi Gerri,
So sorry to hear about your upcoming knee surgery. However I do know a couple ppl that have had knee replacements...but not both at the same time. Since you have done much research on this I'm sure you have read all the pro's and con's on it. The first thing that came to my mine when you said bilat knee replacements...was Hugh Downs. He shared his story with his bilat knee replacement on his 20/20 show. It was very interesting. My MIL wanted both her knees fixed at the same time and her ortho would not do it...but I think most of that was due to her age. She was in her 70's by then.


Too bad you can't find some ppl that have been through this to get first hand experience. I rememeber my MIL said she was glad her Ortho talked her out of doing both at the same time once she was home. So I would give what Lani said some serious thought. However I totally understand why you would want them both done at the same time and behind you. That would be a very difficult decision to make for me. Wish you the very best on your upcoming surgery. Keep us posted. Hopefully someone else here that's had it done will chime in.

Chelee

[tricia keegan]

Sorry to hear you're dealing with this Gerri and just wanted to wish you well for the surgery!

[Gerri]

Thanks ladies for your support. AA I will definitely give feedback on what I experience since I will be ahead of your SO.

Lani I really appreciate your input/advice. I have been a member of this board for many years and truly respect your opinion. Quite honestly, you have given me a lot to think about. I will do much more research on this before I make my final decision. Fortunately (in an odd way) I am seeing another ortho in this group (they specialize) for a possible torn rotator cuff - apparently I am falling apart . He also does knees, but related to sports injuries. I will talk to him about the pros and cons of bilateral surgery and may go outside the group for another opinion. The knee guy does mostly minimally invasive surgery so I am hoping that is a plus. I do have more questions now and will definitely try to get some answers.

Please continue to chime in. I would love to hear from others.

[Pam P]

Gerri - I have know experience with the knee replacement surgery but want to add my best wishes for success and pain free knees. Pam

[krisvell]

Gerri;
Good luck with making the right decision for you. I hope all goes well for you. I know this sucks to deal with another challenge and it's not easy, but it's not cancer. That's really good.
Sending Hugs and prayers your way,

Kris...

[Trish]

No advice just good wishes.
Trish

[KirisMum]

Gerri, my Dad had both knees replaced (sequentially, not together) in his early seventies. His comment was that he wished he had done it a lot earlier. :-) I also have several riding friends who have had knee replacements, and I can't think of one who wasn't thrilled to be pain free and walking (and riding!) again. Make sure you do your PT afterwards. Like Lani, I would be wary of having both done at the same time, but maybe your orthopedist has a good reason. Best of luck and keep us posted.

[Lani]

Dr. Max Wicha, of breast cancer stem cell fame, has most discussed at the AACR meeting and others his lab's most recent work which relates IL-6 to the awakening/ activation of breast cancer stem cells in the bone marrow, causing/allowing them to spread to distal organs.

If I would not have answered your inquiry, I would have missed this very important article(note it is the IL6 level in the blood vs the IL5 level in the drainage which is the factor governing what those dormant stem cells "see")

In addition the amount of "angiogenic factors" which can help recruit a blood to supply to any of those newly migratory metastatic cells to help them grow may be related to the amount of surgical stress as reflected below:


J Orthop Sci. 2009 Jul;14(4):437-42. Epub 2009 Aug 7.
Serum concentrations of interleukin-6 in patients following unilateral versus bilateral total knee arthroplasty.
Kugisaki H, Sonohata M, Komine M, Tsunoda K, Someya S, Honke H, Mawatari M, Hotokebuchi T.

Department of Orthopedic Surgery, Faculty of Medicine, Saga University, 5-1-1 Nabeshima, Saga, Japan.
Abstract
BACKGROUND: Surgical stress is known to affect body temperature, white blood cell (WBC) count, C-reactive protein (CRP), and interleukin-6 (IL-6). The aim of the present study was to investigate which parameter is most suitable for quantitative analysis of surgical stress.

METHODS: Unilateral total knee arthroplasty (U-TKA) and bilateral TKA (B-TKA) were selected for the subjects of this study because the B-TKA creates approximately double the surgical stress of the U-TKA. The temperature, WBC count, CRP, and IL-6 in the blood were measured pre- and postoperatively in both groups. The IL-6 in the drainage fluid was also measured after the operation.

RESULTS: The temperature, WBC count, CRP, and IL-6 in the blood significantly increased on the first day after the operation in both groups. There were significant differences between the two groups in the WBC count (P < 0.05) and the IL-6 level in the blood (P < 0.05) on the first day after the surgery. There were no significant differences between the two groups for the CRP and IL-6 levels in the drainage fluid. The relative proportions--(B-TKA/U-TKA) x 100 (%)--were 170.4% for the operating time, 219.4 % for total blood loss, 200.0% for blood transfusion, 100.3% for temperature, 128.9% for WBC count, 127.4% for CRP, and 246.5% for the IL-6 level in the blood.

CONCLUSIONS: The serum IL-6 level may best reflect surgical stress and could therefore be a quantitative marker of surgical stress.

PMID: 19662479

[Barbara H.]

My mother-in-law had both knees replaced, but not at the same time. The first time she went to rehab and hated it. She felt fine, but they would not allow her to leave until her coumadin level was at the correct level. After the second surgery she decided to come directly home from the hospital. She walked into the house, up the stairs and started setting the table for my daughters birthday. The visiting nurse the next day said that that she had never seen anything like it. My mother-in-law is 86 and that was only a few years ago. I live in the Boston area and would highly recommend her surgeon.
Good luck, Gerri.
Barbara H.

[Lani]

more on IL6:

Princeton scientists discover mechanism involved in breast cancer's spread to bone





IMAGE: Associate Professor of Molecular Biology Yibin Kang (right) with research collaborator Nilay Sethi, a dual degree student who recently finished his Ph.D. in molecular biology at Princeton and is now...
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In a discovery that may lead to a new treatment for breast cancer that has spread to the bone, a Princeton University research team has unraveled a mystery about how these tumors take root.

Cancer cells often travel throughout the body and cause new tumors in individuals with advanced breast cancer -- a process called metastasis -- commonly resulting in malignant bone tumors. What the Princeton research has uncovered is the exact mechanism that lets the traveling tumor cells disrupt normal bone growth. By zeroing in on the molecules involved, and particularly a protein called "Jagged1" that sends destructive signals to cells, the research team has opened the door to drug therapies that could block this disruptive process. Doctors at other medical centers who have reviewed the research have found it promising.

"Right now we don't have many treatments to offer these patients," said Yibin Kang, an associate professor of molecular biology at Princeton who led the research team. "Doctors can manage the symptoms of this bone cancer, but they can't do much more. Our findings suggest there could be a new way of treatment," one that could slow or halt these bone tumors.

Breast cancer spreads to the bone in 70 to 80 percent of patients with advanced breast cancer, and it can also spread to the brain, lung and liver. Metastatic bone cancer is also a frequent occurrence among patients with advanced prostate, lung and skin cancers. In findings that will be published online in the journal Cancer Cell on Feb. 3, the team's research shows that breast tumor cells are able to give bone cells the wrong instructions through a process known as cell signaling -- with disastrous effects for the patient.

The billions of cells in a living human body must communicate to develop, repair tissue, and effectively maintain normal physiological functions. Cell signaling is part of a complex system that enables them to do that but, in patients with cancer, the relationship between signaling molecules and the molecules that communicate with them has gone awry.

Signaling molecules are those that can be received and read by a cell through a receptor molecule on its surface. Once the signaling molecules connect with a receptor, their union sets off a process that leads to the receiving cell changing its behavior. The sequence of events that follows involves a signaling pathway, which is a group of molecules that work together, one molecule activating the next until a specific function is carried out, such as renewing an organ's cells. There are many such signaling pathways.





IMAGE: Research by Yibin Kang (right), an associate professor of molecular biology at Princeton, has uncovered the exact mechanism in individuals with advanced breast cancer that lets traveling tumor cells disrupt...
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But in the case of metastatic breast cancer, a disruptive pathway is formed. The signaling molecule, also known as a ligand, connects with a receptor molecule on certain bone cells and activates a cellular pathway that ultimately disrupts healthy bone renewal. Kang's team identified the signaling molecule as Jagged1, and the receptor molecule as one that activates a cellular pathway known as the "Notch pathway."

This finding gives cancer researchers a specific target, Kang said -- that of developing ways "to neutralize Jagged1's destructive power" and keeping it from interfering with normal bone growth.

At the Memorial Sloan-Kettering Cancer Center in New York City, Jacqueline Bromberg, a physician who also studies breast cancer, said the findings of Kang's team are promising.

"The bone is the most common site for metastasis in patients with breast cancer," said Bromberg, who met Kang several years ago while he was a postdoctoral fellow at Sloan Kettering. She noted that although there are treatments that can slow these tumors, such as estrogen-blockers, radiation and chemotherapy, "we have few therapies which effectively eradicate bone metastasis."

At the University of Indiana School of Medicine in Indianapolis, oncology professor Theresa Guise said the Princeton discoveries "show critical interactions between the tumor cells and bone cells." She added that the team has made a valuable contribution to research in that it "has dissected the contribution of the tumor and the micro-environment in this process."

FINDING HAS LINK TO EARLIER BREAST CANCER WORK

The research builds on earlier work begun six years ago by Kang's laboratory that looked at how several different signaling pathways promote the spread of cancer to the bone. In a study published in the journal Nature Medicine in 2009, Kang showed that a pathway known as TGF beta plays a role in the growth of bone tumors. But until the recent study, it was not clear that Jagged1 plays a crucial role in that process. Before the current work focused on identifying the series of interconnected events that create the network of destructive pathways, Kang and Nilay Sethi, a dual degree student who recently finished his Ph.D. in molecular biology at Princeton, worked to find first which of the signaling molecules were at work in patients with breast cancer that had metastasized to the bone.

"It turned out that tumor samples from patients with breast cancer that had spread to the bone had higher levels of Jagged1," said Sethi, who is now completing his medical degree at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School.

The current research shows that, when the Jagged1 signaling molecule binds to its receptor molecule on the bone-producing cells, the interaction turns on the signaling pathway called Notch, and that leads to dramatic changes in bone growth. "It's like a key finding its matching lock, and opens a floodgate of information," Kang said. "Unfortunately, in this case, the Jagged1-Notch signaling is misused by cancer cells to serve a destructive purpose."

In healthy bone, specialized bone cells called osteoclasts scour the bone surface and use a combination of enzymes and acids to break down the old bone. Then another group of bone cells called osteoblasts deposit a new layer of bone matrix to rebuild the bone tissue. Working just like cellular excavators and paving machines, the bone-scrubbing osteoclasts and bone-building osteoblasts work in sync every day to renew the bone and maintain its strength. When these cells' activity gets out of balance, bone diseases can result.

While tumor cells lack the specialized tools that osteoclasts have to break down the bone, they are able to use the destructive Jagged1 molecule to disrupt the balanced activity of bone renewal, forcing the osteoclasts and osteoblasts to behave in a way that allows the tumor cells to invade the bone, Kang explained.

For example, by activating Notch signaling in osteoclasts, Jagged1 makes osteoclasts mature more quickly from their precursor cells, known as monocytes. A massive accumulation of these bone-scouring osteoclasts becomes the front line of the invasive force of tumor cells. That speeds up the breakdown of bone tissue and clears the way for tumor cells to expand into a malignant mass in the bone.

"Meanwhile, Jagged1 instructs the osteoblasts to secrete elevated levels of Interleukin-6, a tumor growth factor, so the cancer grows even faster," Kang said. "It's a one-two punch."

Creating further damage, the breakdown of the bone matrix releases a large quantity of another protein called TGF-beta, another signaling molecule that is embedded in the bone matrix during the bone-building process. In their earlier work published in 2009, Kang and colleagues showed that the TGF-beta protein derived from bones fuels the malignant growth of bone metastasis.

In the current study, some experiments conducted by Sethi established a surprising new link between TGF-beta and the Jagged1 molecule in bone metastasis.

"When tumor cells use the hijacked osteoclasts to break down the bone and release TGF-beta, it signals back to tumor cells to further stimulate the expression in Jagged1 in tumor cells," Sethi said. "The link between the Jagged1/Notch and TGF-beta pathways establishes a vicious cycle, essentially driving the unstoppable expansion of tumor and the destruction of skeletal tissues."

As a medical student, Sethi said he is acutely aware of the consequence of bone metastasis. "These patients suffer a lot. They have fractures, severe bone pain and debilitating nerve compression," he said. In addition, as the bone breaks down, calcium builds up in the blood, causing other life-threatening complications.

BLOCKING DESTRUCTIVE PATHWAY A POTENTIAL TREATMENT PATH

The key to stopping the process appears to be finding a way to neutralize the Jagged1 signaling molecule or its receptor Notch.

Kang has several ideas on how scientists may learn how to do just that. One way to interrupt the destructive process is to put a roadblock in the Notch pathway. There is a way to do that by halting the activity of gamma secretase -- an enzyme that plays a key role when the Notch pathway is activated --because without it the delivery of instructions to bone cells cannot be completed. The pharmaceutical firm Merck & Co. has developed one such experimental drug that stops gamma secretase, known as a gamma secretase inhibitor or GSI, and the company has provided it to Kang's lab to support his team's work.

The drug has already shown promise treating metastatic bone cancer, Kang said. In animal experiments, the inhibitors have been proven to block the disease-causing signaling between tumor cells and bone cells, communication mediated by Jagged1 and Notch. Kang said GSI can reduce bone metastasis significantly, along with a dramatic reduction of bone destruction.

He hopes his team's new data showing that GSIs appear to work to halt the spread of cancer to the bone will result in clinicians starting a clinical trial of GSI to fight breast cancer metastases in the near future.

According to Kang, there are few drugs currently available to relieve symptoms associated with bone metastases, and none is able to completely stop the cancer. If Kang's findings lead to a drug that can halt or slow this process, it could affect the 200,000 patients that the NCI estimates are diagnosed every year with breast cancer. It might work for some other cancer patients as well, Kang said.

Sloan-Kettering's Bromberg said Kang's recent discovery "underlies the importance of targeting the environmental milieu" in which disease develops, in this case the activity of the Notch signaling pathway and specific interactions between cancer cells and the specialized cells that break down and rebuild bone.

###
Kang's work was funded by the New Jersey Commission on Cancer Research, the San-Francisco-based Brewster Foundation founded by 1969 Princeton alumnus Leonard Schaeffer, U.S. Department of Defense, American Cancer Society, Merck & Co., the National Institutes of Health and the Champalimaud Foundation in Lisbon, Portugal.

[ammebarb]

Hi Gerri. I'm sorry you are having to do the knee surgeries, but very glad that this is a problem for which there is a fix! My husband had both of his done (sequentially), and my brother in law had his done at the same time. Both had good recoveries and excellent results. My brother in law went to a rehab facility for a few days following his surgery. My hubby came home, but traveled to religiously do his rehabilitation. Both say that they are glad they had the surgeries done. My husband had lived with knee pain and a cumbersome brace for about seven years before his was accomplished. He said that his pain immediately following the surgery wasn't worse than the pain he had endured for such a long time. I hope you make the decision that is right for you and that you have the same great results my "guys" have had.

Barb A.

[Gerri]

Thanks so much for all your good wishes. I really appreciate your thoughtfulness. And yes, thank goodness this is fixable.

Barb: I am so happy to hear that surgery worked out so well for both your 'guys'. It really helps to hear of that surgery was successful with both options.

I saw the 'shoulder guy' today and got the results of my MRI. I do have some tearing, not of the rotator cuff, but of the muscles surrounding it. Not sure exactly what that means but it doesn't mean surgery for now. I will be starting physical therapy next week and hope that helps with my pain.

I talked to the PA of the 'knee guy' about having single vs bilateral surgery done. If I have one done at a time, I am concerned about causing more damage to the other leg as I heal. She said I would probably be okay, but it is possible to cause more damage if I wait too long to get the second one done. She also told me that my deformity (I am extremely knock kneed now) is so severe that if I have only one leg done it will be noticably longer than the other leg and this could make it hard to walk on that leg while the other one heals. (I have actually lost almost two inches in height the last few years and will get some of that back when my knees are fixed.) By having both legs done, I am worried about being able to support my weight with my upper body because of my shoulder pain. Looks like either way I am faced with potential problems. The PA recommended that I wait until I have had physical therapy to see if my upper body strength improves and make my decision in a month. I am okay with that and have my first appointment on Monday. It looks like I have a little time to make my decision.

I want to thank everyone again for the support and well wishes. It means so much to me.

[Lani]

From Max Wicha's latest article(note the information on IL6):

Many human cancers, including breast cancer, may be driven by a population of cells that display stem cell properties. These properties include self-renewal, which drives tumorigenesis, and differentiation, which contributes to cancer cell heterogeneity. There is increasing evidence that these cancer stem cells (CSC) mediate tumor metastasis and, by virtue of their relative resistance to chemotherapy and radiation therapy, may contribute to treatment resistance and relapse following therapy (1).

Self-renewal and cell fate determination of normal stem cells are regulated by both cell intrinsic and cell extrinsic pathways. The dysregulation of these pathways resulting in stem cell expansion may be a key event initiating carcinogenesis. Developmental pathways such as Notch, Hedgehog, and Wnt play an important role in normal stem cell function and are frequently deranged in cancers (2–5). Extrinsic signals that regulate stem cell behavior originate in the stem cell microenvironment or niche. This niche contains extracellular components as well as multiple cell types.

Although there is little information on the composition and function of CSC niches, it is clear that tumor growth and metastasis is highly dependent on the tumor microenvironment. This microenvironment is composed of tumor-associated fibroblasts, endothelial cells, adipocytes, and immune cells, all of which have been shown to play a role in tumor growth and metastasis (6). Mesenchymal stem cells (MSC), which can be defined as multipotent mesenchymal stromal cells, are a heterogeneous subset of stromal stem cells that can be isolated from many adult tissues; proliferate as adherent cells; have fibroblast-like morphology; form colonies in vitro; and can differentiate into adipocytes, osteocytes, and chondrocytes (7). Recently, through the use of mouse breast cancer models, it has been shown that bone marrow–derived MSCs may be recruited to the sites of developing tumors, thus, influencing their metastatic potential (8). It has been shown that MSCs can produce IL6 (9, 10) and can stimulate tumor growth through the paracrine production of secreted IL6 (11). Both IL6 and IL8 have been implicated in the regulation of CSCs (12, 13).

WHY WOULD YOU WANT TO CHANCE STIMULATING YOUR TUMOR GROWTH or
"awakening and activating your dormant breast cancer stem cells in your bone marrow to cause them to divide, migrate and form macrometastases"
by producing more IL6 (246.5% more IL6 in the blood with bilateral knee replacement than with unilateral knee replacement)

Not trying to scare you, just hoping you will show moderation and do one knee at a time, giving you a leg to stand on as your shoulder won't be too much use holding you up and may not stand up to the strain of bearing all or part of your body weight.

Think before you leap!

[Gerri]

Lani,

I am taking into consideration all of the information you have sent my way. One thing I need to do is speak to the surgeon again. I had four medical appointments that day and did not ask a lot of questions. I didn't even tell him about my shoulder problems because I did not know exactly what was causing my pain. He has left the decision of having one or both knees done up to me. I chose bilateral because I just want it over and done with but I am seriously considering changing it to one at a time.

My surgeon is a hip and knee specialist and came highly recommended. He is Dr. Steve Barnett with the Orthopedic Specialty Institute in Orange County and is a member of the AAHKS. From what I understand he does the majority of knee replacements at St. Joseph's Hospital in Orange. I live in Southern California and can travel to Los Angeles, Orange and San Bernardino County if I choose to seek a second opinion.

Thanks for the info, sobering, but thought provoking to be sure.

[Lani]

results available!

Lani

[Trish]

If bilateral knee arthroplasty causes approx twice the surgical stress and (I presume twice the risk of stirring up tumour growth) wouldn't two unilateral operations do so but in two episodes? I'm not suggesting bilateral would be better but just wanted to clarify.Thanks Lani and all the best for your decision making and surgery Gerri.
Trish

[Lani]

the increase in IL6 was 246.5%--considerably MORE than doubled