Participate in the Cycle of Life

Posted on 19/09/2011 by Chris Barry

The following is a speech I gave at the Greentopia Festival, Rochester, New York’s first green festival. But first, see this video testimonial from a woman volunteered to tell the story of her sister who received a liver transplant. She celebrates the challenges and wonders of life and stresses the importance of becoming an organ donor.

My name is Chris Barry and I am a transplant surgeon at the University of Rochester Medical Center. Many of you are probably wondering: what in the world is a transplant surgeon doing here at Greentopia? Well, first and foremost, we have an important message that we want to share with you regarding organ donation. Second, everyone here at Greentopia is passionate about making the world a better place to live, and you are all interested in seeing things from a different perspective, so you guys are a great audience to hear me out.

 

I want to talk with you about an uncomfortable subject. No one really likes to sit around thinking about death, illness, and giving your vital organs to a complete stranger, or even a loved one for that matter. But with a simple, subtle shift in perspective, the subject does not have to be so uncomfortable or creepy. In fact, organ donation and transplantation is an absolutely incredible endeavor that highlights and honors the cycle of life.

The problem with transplantation is that it is so successful.People who would otherwise die from a failing heart or liver, or be burdened with constant dialysis treatments in the case of kidney failure can undergo a life saving and life transforming transplant with remarkably good success rates. The vast majority of organ transplant recipients (over 80%) enjoy long term survival and are able to return to their completely normal lives. This is because our antirejection medicines, our antiinfection medicines, and our surgical techniques have improved to the point where organ rejection is not nearly as common as before and even the sickest of patients can make it through the most complicated of surgeries. This miraculous success has caused transplantation’s number one problem: the donor organ shortage. There are far more people waiting on the list to receive organs than there are suitable organs available and many people die each day waiting on the list.

 

One human being can donate up to eight life saving solid organs: one heart, one liver, two lungs, two kidneys, a pancreas, and intestines. Through donation of tissues such as corneas, bones, and tendons, up to 50 people’s lives can be dramatically improved from just one donor. Heart transplants and liver transplants are sometimes referred to as life saving operations, because without organ replacement the patient will die. But even in the cases where other options are available such as dialysis for patients with kidney failure, transplant not only improves the quality of life for the recipient, but actually results in a longer life span. Our main goal as transplant surgeons and physicians is to give people the chance to live a long and healthy life.

 

There are several unfortunate misperceptions about the process of organ donation. Perhaps the most common one is that if you indicate your willingness to become an organ donor, then health care professionals may not try so hard to save your life if you suffer a serious injury. Nothing could be further from the truth. Everyone involved in the care of a critically ill patient, from the paramedics, to the nurses, to the emergency room and intensive care doctors is dedicated to delivering state of the art and compassionate care to anyone who comes through their doors. By compassionate care, I mean the understanding and respecting of a patient’s previously stated wishes regarding critical illness or end of life care. There are times when heroic measures are necessary and appropriate, and there are times when gentle and dignified comfort care are appropriate. Deciding what type of care is best in any given situation requires close communication between the care givers and the patient, or more often, the patient’s family or loved ones. This is why it is so critical that we all sit down to have serious conversations with those closest to us in our lives to talk about the difficult subjects of living wills, powers of attorney, and organ donation. Without these conversations, misinformed and sometimes tragic decisions might be made even when everyone is trying to do the right thing. In cases where there’s a critical accident or health emergency such as a stroke and the decision is made to do anything and everything possible to save the patient’s life, this is what is done. Only when it is absolutely clear that the miracles of modern medicine would be futile in trying to turn a tragic situation around do we consider backing off on any further heroic measures. Up until this point, no one involved in the organ donation process has been notified.

The team of health care professionals responsible for talking to the family about organ donation is completely separate the team delivering patient care. The doctors taking care of the patient notify the organ recovery network team and they come in to assess the situation and talk to the family about the possibility of organ donation. When consent is obtained, the recovery network team assumes care of the patient and organizes allocation of the organs. The transplant surgeons and physicians up until this point are completely uninvolved in the process. Only when a suitable donor and recipient have been identified do the transplant surgeons come in to perform the surgery to remove the organs and bring them back to their respective centers for transplant. Great care is taken throughout this entire process to deliver unbiased care, to inform the family of all of the possibilities and processes, and to treat the patient with the utmost respect and dignity.
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Another common misunderstanding about transplantation is that the donor and the recipient need to be a perfect match for the transplant to be successful. These days, because our antirejection medicines are so effective in preventing and treating rejection, all that is necessary for a donor and recipient match is a compatible blood type and demonstration that the recipient does not have antibodies (or immune cell proteins) against the donor. This means that completely unrelated people can donate to each other, both for living donor transplant and deceased donor transplant. It’s not uncommon for a husband to donate one of his kidneys to his wife, or vice versa, or for a dear family friend or distant relative to donate to a recipient. It’s actually very unusual for a transplant recipient to lose an organ due to rejection in the first several years after a transplant as long as they’re taking their medicines and checking in with their doctors frequently. Even if rejection does occur, we’re very successful in making it go away with stronger antirejection medicines. We do carefully consider issues such as the medical and social history of the donor and the sizes of the donor and recipient, but genetic relation–other than the special case of identical twins–is not as important as it used to be.

A final misperception about organ donation is that the process is unfair. There is a certain amount of truth to this in that currently there are significant regional disparities among wait lists. Here in New York and in other large population centers such as California, people have to wait longer on the list compared to other places. So if someone has the means to be listed at multiple centers across the country, then their chances of getting a transplant sooner are better. There are efforts afoot to solve these regional disparities and make organ donation more equitable, but wait times still vary from one place to the next. But there are two things that are absolutely illegal in this country. First, you can not sell your organs and, second, important people like politicians and celebrities can not receive preferential treatment. If a transplant center disrupts the waitlist by transplanting someone lower on the list for anything other than medical necessity, then they are shut down by the government. This has actually happened a few times in the past. So, every effort is made to keep the organ allocation system as fair and equitable as possible.

So what if you’re thinking about becoming an organ donor but you’re not quite sure? I submit to you that we don’t just die; we live on in our actions and deeds. We can be remembered by what we did in our lives and the gifts we left after our passing. You have the opportunity to share your life when you pass by being an organ donor. Leaving such a legacy not only directly touches the recipients of your organs and tissues, but all of the family members and loved ones surrounding the recipients of your gifts. You have the power to participate in the cycle of life.

 

For those of you who are more present minded, and I suspect that many people here at Greentopia appreciate the notion of living in the here and now, there’s so much you can do right here, right now. You can talk to your family and loved ones about organ donation and express your wishes so that there is absolutely no doubt how you feel–one way or the other. It’s perfectly fine if you don’t want to be an organ donor, but it’s important that everyone knows this. It’s equally important that if you do want to become an organ donor, that everyone knows. Another thing you can do right now is to register to become an organ donor. Write it down. Make it official. In fact, consider incorporating organ donation decisions into your estate planning. When preparing your living will and power of attorney documents, why not include organ donation documents? Finally, another thing you can consider is whether you would want to be a living organ donor. What if your mother or your child needed a kidney transplant or a liver transplant? Would you be willing to donate one of your kidneys or a part of your liver? This is a difficult question to consider and takes courage to address. The answer may be no, but taking the time and energy to seriously consider such a question is in itself an act of compassion and maturity.

I can’t stress enough the importance of talking about organ donation with your family and loved ones. Unfortunately, it’s not enough to register your intentions. Whenever possible, the family is approached regarding consent for organ donation and if an explicit conversation never took place, consent could be denied by the family even if the individual wanted to be a donor. This issue is particularly pertinent in the 40-55 year old age group. People in this age group are the most likely to be suitable organ donors. Stroke, not motor vehicle accidents or other trauma, is the most common cause of death in organ donors in this country. Unfortunately, people in this age group, the 40 to 55 year olds, are the least likely to be consented for donation because the adult children of these patients feel so uncomfortable about making such an important decision about their parents. We need to talk about these decisions before they need to be made. More and more people these days realize the importance of making living wills and designating powers of attorney early on in life. Why not incorporate organ donation decisions into this process as well? Even if you are adamantly opposed to the idea of organ donation, it’s important that your loved ones know this. It’s never too soon to get one’s house in order.

 

It always amazes me when people come forward to become organ donors. Living donors who give one of their kidneys or a part of their liver to another human being who is suffering are true modern day heroes. And they should always be recognized as such. When a family suddenly loses a child, sibling, or parent to a trauma or medical catastrophe, it seems almost unthinkable that they would consider organ donation at such a tragic time. I can tell you from experience that those families who do consent their loved one for organ donation can and usually do experience a remarkable sense of closure from the act of donation. Parents of a departed child do not want another family to experience the same tragic loss, so to see the life force of their child be perpetuated in another child can often give great comfort. This sharing of life doesn’t make the pain of loss go away, but it offers meaning and purpose on a much greater, spiritual scale.

So I humbly and sincerely ask you to consider participating in the cycle of life. What is the most important thing you can do when you leave this earth? You can save someone else’s life. Or you can save eight people’s lives. You can BE LIFE, you can BE THE MIRACLE OF ORGAN DONATION. Talk to your family and loved ones. Register to become an organ donor. Leave a legacy. THANK YOU.

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bLifeNY: The Challenges of Raising Organ Donation Awareness

Posted on 05/08/2011 by Chris Barry

The field of organ transplantation has become a victim of its own success. With vastly improved antirejection medications, surgical techniques, and medicines to prevent transplant related infections, the chances of long term success for all solid organ transplants are uniformly excellent. The biggest problem in transplant today is that there are far more people waiting for organs than there are suitable donor organs available. In 2006, more than 90,000 individuals were on the wait list for transplant, but only just over 23,000 organs were transplanted from about 14,000 donors. About half of these were from living individuals donating one of their kidneys for transplant. (A much smaller number of living donor liver transplants were also performed.) The other half were from deceased individuals who donated anywhere between one and eight (liver, heart, 2 lungs, 2 kidneys, intestines, and pancreas) organs.

For deceased donation, the vast majority of donors die from cessation of neurologic function (commonly referred to as “brain death”). In this case, heart and lung function can be maintained by mechanical means until the time of surgical organ recovery. Less commonly, death occurring from circulatory collapse (the heart stops beating) can result in successful recovery of organs for donation. In either case, consent for organ donation is obtained by a third party organization that is not affiliated  with the hospital or its caregivers (our local Organ Procurement Organization is Finger Lakes Donor Recovery Network) and is guided by previous documentation of the patient’s wishes regarding donation and/or discussion with family members.

So in this country, organ donation is an opt-in, altruistic system. Individuals express their desire to become donors beforehand with the intent of helping others upon their own passing. When this desire is not explicitly stated, family members are approached for consent. If for whatever reason consent is not obtained, the donation process does not proceed.

Many myths surround organ donation. The three most prevalent are: (1) that by identifying oneself as an organ donor, healthcare providers may cut short lifesaving efforts, (2) donors and recipients need to be a “perfect match”, and (3) the donor organ allocation process is unfair. First, it is absolutely not true that physicians or anyone else on the entire healthcare team is influenced by the red heart “organ donor” designation on a patient’s driver’s license. Only when the miracles of modern medicine appear futile in the face of a devastating injury is the organ donor network team notified. These highly trained professionals approach the family to explain the organ donation process and request consent. Transplant surgeons and other transplant professionals are completely uninvolved in this process. Second, all that is required for a successful transplant is a compatible blood type and absence of antibodies (immune cell proteins) toward the donor in the recipient. This is largely a result of the highly effective antirejection drugs currently used and so people unrelated to the recipient can donate. Third, although there are regional disparities in donor organ availability (Steve Jobs knew this, but did nothing illegal by flying out of his home state to receive a new liver in a timelier fashion), the overall process is as equitable as possible. It is illegal to use money or political influence to get higher up on or bypass the waiting list, and several important efforts are underway to address the regional disparity problem.

Living donors most often come forward out of the goodness of their own heart to give one of their kidneys or a portion of their liver to a family member or otherwise emotionally related recipient. Along with the occasional truly altruistic donor who does not know his or her recipient, these people are modern day heroes who subject themselves to a surgical risk, albeit minimal, for the betterment of another individual. Concerns regarding long term health consequences (none are detectable in large scale statistical analyses between living donors and the general population),

perceived selfish motivations, and undesirable recipient outcomes (the transplant could fail) need to be taken seriously and addressed compassionately.

Many efforts exist to increase organ donation, but to date have been insufficient. Public education campaigns and efforts to increase the pool of available organs such as encouraging living donation, splitting livers in order to perform two transplants from one donor, and increased use of donors after circulatory determination of death (formerly referred to as “non heart beating donors”) are all actively in place. Even consideration of incentives to donate such as tax breaks or payment of funeral expenses are being considered, but this is controversial. Unfortunately, the growth of people on the waiting list continues to outpace the pool of available donors.
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We feel that the primary impediment to organ donation is inadequate education. People don’t like to think about or talk about dying or giving away their vital organs to a stranger or even loved one. A shift in perspective is absolutely necessary, both on an individual level and on a cultural level. To this end, the University of Rochester Division of Solid Organ Transplant has initiated a grassroots effort:bLifeNY.org. We are enlisting the help and enthusiasm of socially conscious college and high school students, other academic centers such as the Rochester Institute of Technology New Media program, cutting edge professional media services such as the Philipson Group, and anyone else who wants to help to develop social media portals, video testimonials and blogs, and other creative approaches to bring about this desperately needed perspective shift regarding organ donation.

There are different audiences to reach and therefore different approaches will be necessary. Young people might be more responsive to participating in the real social network, blogging and tweeting about their thoughts and ideas on donation. Minority communities should hear the message from their own trusted leaders in culturally appropriates contexts. Different spiritual traditions deserve the utmost respect and understanding and religious leaders could ideally focus on the notion that donation pays homage to the cycle of life and respects the preciousness of human life.

The 40-60 year old demographic in this country is particularly interesting. This group represents the largest source of donor organs (stroke, not trauma, is the most common cause of organ donor death), but they are the least likely to consent to donation. This is probably because no family conversations on donation ever occurred and when it comes time for the family members to give consent, adult children feel uncomfortable making this important decision. Perhaps incorporating donation decisions with other end of life plans such as living wills and powers of attorney is a worthwhile educational strategy for the 40-60s.

Awareness requires enabling a shift in perspective to occur. We endeavor to create a societal shift. Individual shifts are highly personal and can take time, so it’s all about compassionate education and sending out appropriate messages to different groups of people.

So what can you do? First, ask yourself: what’s the most important thing you can do when you die? You can save someone else’s life. Or eight people’s lives. Talk to your family and loved ones. Let your wishes be known. Register to become an organ donor. Leave a legacy.

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The Challenge of Alcoholism in Liver Transplantation

Posted on 01/06/2011 by Chris Barry

As a transplant surgeon, I actually do more for the care of my patients than just operate. Below is an excerpt from one of my notes describing a woman who unfortunately relapsed into alcoholism after her liver transplant.

“Dear Doctors: Mrs. A (not her real initial; her “A” stands for alcoholic) was admitted to our service last night to evaluate her cough and ascites. As you know, she is a woman with alcoholic cirrhosis status post liver transplant several years ago that was complicated by recurrent alcoholism causing cirrhosis of her liver allograft. She began drinking one year after her transplant and went on to develop end stage liver disease with portal hypertension requiring a TIPS (transjugular intrahepatic portosystemic shunt). Over the past several months she has been readmitted to the hospital with pneumonias and complications related to her liver disease. She continued to drink alcohol despite our admonishments and efforts to get her into alcohol dependency treatment programs. During her last admission for treatment for pneumonia, she did not drink during her one month stay in the hospital and she has remained abstinent since discharge. She has not been to rehab and she does not participate in a recovery program such as Alcoholics Anonymous. Given her most unfortunately recalcitrant case of alcoholism, she is not a candidate for retransplant.”

(I then describe her physical exam, laboratory findings, imaging studies, my assessment of her current medical state, and my plan for her medical management, the extensive details of which I will spare you.)

I go on to say:

“In terms of her alcoholism, I am continuing her thiamine, folate, and multivitamins, but I do not believe she needs benzodiazepines for DT (delirium tremens) prophylaxis given that she has been abstinent for over one month. I had a frank discussion with her telling her that she will die if she continues to drink and that her untreated alcoholism precludes her candidacy for retransplantation. Given her MELD score of 20, she has a 25% risk of mortality in 90 days. Either development of an infection or complications from TIPS revision can result in hepatic decompensation which may be unsalvageable by transplant even if she were a candidate. I will have our Transplant Social Worker and Transplant Psychiatrist see her (again), but alcoholism is an insidiously tricky disease in that any real change has to come from the affected individual and this is excruciatingly difficult when alcohol seems the only viable source of comfort in that person’s mind. I do not judge Mrs. A’s behavior as a moral weakness, rather, I understand that she suffers from a devastating, life threatening disease in which she is the only one who can help herself recover. Given that she may continue to engage in passive suicide despite her telling us that she wants to become sober, I am consulting the Palliative Care Service. Our entire team has been chosen to care for Mrs. A and, as such, we will endeavor to support her fully according to her stated wishes.

I will continue to keep you informed as to Mrs. A’s course, as I know you are sincerely invested in the well being of your patients.

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The vast majority of patients receiving liver transplants for alcoholic cirrhosis do not lose their new livers because of recurrent alcohol use. In fact, alcoholic cirrhotics as a group enjoy outstanding long term outcomes after successful liver transplant. Although transplant programs go to great lengths to evaluate a transplant candidate’s commitment to sobriety (and thereby “estimate” an individual’s risk for relapse after transplant), this can be extremely challenging given the wildly unpredictable behaviors induced by the disease of alcoholism.

We review the patient’s drinking history and its consequences in their lives, have the patient meet with our Transplant Social Worker and Psychiatrist, discuss the patient in a multidisciplinary selection conference with all team members present (surgeons, hepatologists, psychiatrists, social workers, ethicists, nurses, pharmacists, financial planners, and nutritionists), and require a 6 month period of documented abstinence from alcohol and other drugs.

Sometimes we say no to listing a candidate for transplant. This means they will die of their liver failure instead of having the chance to live a longer and much healthier life with a new liver. Sounds rather “Roman coliseum”, but transplant donor organs are precious resources. Too many people die just waiting for appropriate donors to offer their gifts. If it is clear that a candidate is not interested moving forward in life and staying healthy by any means necessary, then we are morally obligated not to transplant them. Those in the throes of alcoholism can engage in unthinkable behaviors as a result of the intense physical dependency induced by the substance: disinterest in self care and living, dishonesty to one’s self and everyone else, extreme narcissism and delusion…the list goes on. So we look for indicators like family and social support and, most importantly, the patient’s own actions toward accepting a sober lifestyle. These are imperfect and emotionally charged metrics, but we do the best we can in dealing with this still poorly understood disease.

Relapse can happen, just like any other disease, but it is not universal nor is it necessarily fatal if the affected one gets help immediately. We have to be present for those who suffer. Sometimes we can help, other times all we can do is be there. And in that case, that’s more than enough.

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Protein Okay for Cirrhotics

Posted on 18/04/2011 by Chris Barry

I was just seeing a patient in liver transplant clinic today with end stage liver disease secondary to fatty liver disease leading to Non Alcoholic Steatohepatitis (NASH) and cirrhosis. She was miffed with her primary care physician because he had told her to limit her dietary protein intake because of her cirrhosis and our Transplant Nutritionist just finished telling her that dietary protein is okay. All those missed opportunities for hamburgers and steak! I am sympathetic to both this patient and her physician.

Most medical students since the 1940s have been taught that hepatic encephalopathy (a state ranging from confusion to full on coma) can be exacerbated by eating protein rich foods. The theory is that the amino acids in protein contain nitrogenous compounds that can be converted into ammonia, which goes to the brain and causes encephalopathy. Normally, ammonia and other neurotoxins are filtered out by the liver. But when the liver is scarred down (cirrhotic) and otherwise not functioning well, the toxin containing blood from the intestines bypasses the liver via collateral circulation and directly enters the systemic vascular system. The brain does not like ammonia and other junk from the intestinal circulation and encephalopathy ensues. So no meat for the cirrhotic patient the dogma goes.

A study published by Cordoba, et al., in the July 2004 issue of Journal of Hepatology randomized 30 cirrhotics hospitalized because of encephalopathy and fed half of them a low protein diet and the other half a normal protein diet. Both groups had similar outcomes despite the different diets. Although both groups were found to have the same rate of protein synthesis in their bodies, those fed the low protein diet had a higher rate of protein breakdown. The implication being that low protein diets make the already malnourished states of the cirrhotic patients worse.
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What made this paradigm shift possible is that these days we are very good at managing hepatic encephalopathy with two medicines: lactulose and rifaxamin. Lactulose is a liquid that causes one to have frequent bowel movements and thereby decreases that amount of bacteria in the colon that convert protein (or other nitrogen containing foods) to ammonia and other toxins. It also changes the pH in the intestines so that toxin formation is less efficient. There are probably other mechanisms afoot, but this is what we teach our medical students today. Rifaxamin is an oral antibiotic that is not absorbed into the circulation, so it stays in the intestines and kills toxin producing bacteria. Both medicines are reasonably well tolerated (well, lactulose makes you poop a lot, so too much can make you dehydrated, and rifaxamin is expensive) and they are very good at controlling encephalopathy.

So the current clinical thinking is to have cirrhotics eat well (including normal protein intake) to combat the muscle wasting and generalized malnutrition associated with end stage liver disease and manage the encephalopathy with effective medications. Tell your doctor, but be gentle: we know what we are taught and knowledge is always changing all around us!

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Fatty Liver Disease

Posted on 11/04/2011 by Chris Barry

The “Metabolic Syndrome”, defined by the International Diabetes Federation as the presence of central obesity (or increased waist circumference) plus any two of the four following conditions: insulin resistance, high blood levels of triglycerides (fat), low levels of HDL (High Density Lipoprotein, or the “good” cholesterol), or high blood pressure, is a true disease epidemic in Western countries.

The Metabolic Syndrome is caused by overeating foods high in fat and sugar and inadequate physical activity, which lead to obesity, Type II diabetes, hyperlipidemia, and hypertension. There is probably a genetic component involved as well, but anyone who is obese is at high risk. If unchecked, heart disease, fatty liver disease, and all of the complications associated with diabetes inevitably progress to threaten the lives of all those with this syndrome.

Non Alcoholic Fatty Liver Disease (NAFLD) is the hepatic (liver cell) manifestation of the Metabolic Syndrome and is the most common cause of chronic liver injury in the Western world. NAFLD can progress to Non Alcoholic Steato-Hepatitis (NASH), which is a chronic inflammation of the liver leading to cell death, fibrosis, and cirrhosis. NASH is becoming the most common cause of end stage liver disease requiring liver transplantation.

                                                                               Prevalence of

                                                              NAFLD        and        NASH

 General Population:                             20-30%                       2-3%

 Morbidly Obese:                                    90%                             37%

 General Pediatric:                                  3%

Obese Pediatric:                                     53%
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Type II Diabetics:                                  70%

As you can see from this table, up to 30% of the general population (in Western countries) has fatty liver disease, or accumulation of fat droplets within the cells of the liver). A smaller, but not insignificant, portion of the general population has NASH. In morbidly obese people (defined as a Body Mass Index of 35 kg/m2 or greater), NAFLD and NASH are far more prevalent (90% and 37%, respectively). Quite concerning is the childhood obesity problem, with 3% of all children and 53% of obese children having fatty livers. 70% of those with Type II Diabetes (by far the most common type) have NAFLD. Although these data are from Western countries, the problem is global. The World Health Organization estimates that over one billion people are overweight (BMI>25), of whom 300 million are obese (BMI>30).

People with NAFLD or NASH have an increased risk of developing liver cancer (Hepatocellular Carcinoma or “HCC”). Independent associations of liver cancer and diabetes or heart disease that have been reported in the scientific literature can be explained by the fact that most with the Metabolic Syndrome also have fatty liver disease.

Currently, the management of fatty liver disease involves dietary restriction and modification of the types of food eaten as well as increased exercise. For the Metaboloc Syndrome, medicines exist to treat cholesterol and lipid levels, high blood pressure, and diabetes. But for NAFLD, no highly effective medical treatment exists yet. Investigational drugs (that are nowhere near being ready for general use in humans) include the antioxidants silymarin and nitro-aspirin.

Interfering with the endocannabinoid system (yes, the molecules naturally produced in our bodies that interact with marijuana) by receptor blockade (CB-1&2) may help NAFLD.

But for advanced disease when behavioral modifications are not effective, bariatric surgery is the accepted treatment in appropriate candidates.

The good news is that fatty livers can become normal again when appropriate measures are taken. If NAFLD progresses to NASH, however, the process is unlikely to reverse with our current therapies, even surgery. Although the best way to definitively diagnose NAFLD and NASH is to perform a liver biopsy, we and others are actively investigating noninvasive means of assessing fatty liver disease in order to decrease the frequency of biopsies and to gauge response to therapeutic interventions.

The best medicine is preventive medicine. So watch what you eat, how much you eat, and get some exercise (even a gentle stroll can significantly help and water aerobics are great for those with physical limitations). Easier said than done, but it is certainly possible. As much as I enjoy operating, I would prefer that you take care of yourself as best you can so that I won’t have to perform a liver transplant or liver cancer resection on you!

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A Conversation About Kidney Transplantation

Posted on 31/03/2011 by Chris Barry

Here is a typical conversation that I have with a potential kidney transplant recipient.

Dr. Barry: Good morning. Your Nephrologist has referred you to our center for evaluation of your kidney transplant surgical candidacy. I understand that the cause of your end stage renal disease is Diabetes Mellitus Type II and that you are not yet on dialysis.

Pt: yes, that’s correct.

Dr. Barry: Do you have any friends or family members that are interested in donating a kidney to you?

Pt: I’m not sure. How does one become a donor?

Dr. Barry: Living donor kidney donation involves identifying a family member or an emotionally related donor (e.g., spouse or good friend) who has a compatible blood type with the recipient, is in good health and has no risk of kidney problems in the future such as diabetes or high blood pressure. If a donor is identified who meets these initial criteria, he or she will then undergo an extensive psychosocial evaluation, physical exam, laboratory tests including more detailed screens for immunologic compatibility and imaging tests (X rays and MRI scan) to assure normal anatomy and absence of intrinsic kidney disease.

Pt: What is the risk to the donor?

Dr. Barry: If the donor passes our rigorous screening procedures, then we will arrange for a simultaneous surgical procedure in which the donor’s kidney is removed and immediately transplanted into the recipient. We almost always perform the donor surgery laparoscopically (see video of left kidney removal or right kidney removal), using small incisions, and the patient stays in the hospital for two to three days. The risks include adverse reactions to general anesthesia, bleeding, infection and possible conversion from a laparoscopic to open procedure. These risks are minimal and the chances of having to perform an open procedure are less than 1%.

Pt: What are the advantages of living donor kidney transplant?

Dr. Barry: The main benefit is that we can perform the transplant within months of identifying a suitable donor. The waiting time for a deceased donor transplant (formerly called cadaveric transplant) is 4 to 5 years here in our region. Also, living donor kidneys are more likely to function immediately, lessening the likelihood of the recipient needing temporary dialysis after the transplant. Finally, living donor kidney transplant recipients enjoy better long term graft survival.

Pt: Can I have a transplant before going on dialysis?

Dr. Barry: Yes, but if your kidney function is not too bad, we need to wait until you are closer to needing dialysis. If we perform a transplant too soon, the benefits of receiving a new kidney are cancelled out. We measure your creatinine and creatinine clearance to help us decide the optimal timing of your transplant before going on dialysis.

Pt: Will you remove my own kidneys during the transplant?

Dr. Barry: Usually we don’t have to do this. However, if you have a kidney disease that causes ongoing problems, for example, multiple blood transfusions, persistent kidney infections or intestinal blockage, then we would consider removing your own kidneys. The two most common medical conditions requiring “native nephrectomy” (removal of your own kidneys) are Congenital Reflux Disease and Polycystic Kidney Disease. If you have these diseases, we would decide based on your symptoms or complications whether you would need to have your kidneys removed.

Pt: If I needed to have my own kidneys removed, when would you do this?

Dr. Barry: My practice is to remove the native kidneys at the time of transplantation. This requires a slightly longer stay in the hospital because the surgical incision (cut) is bigger, but the benefit is that the patient only has to undergo one surgical procedure and one general anesthetic. Occasionally, we will perform the removal of your own kidneys prior to the transplant in a separate procedure.

Pt: Getting back to living donor kidney transplantation, what if I have no friends or family members who can donate, or what if I am uncomfortable about asking anyone to do this?

Dr. Barry: That’s perfectly fine. It’s especially important to realize that if you are uncomfortable about asking anyone to donate, then you shouldn’t do so. Organ donation is a gift and it should come from the heart, not by emotional coercion. Financial coercion for organ donation is illegal in the United States.

If you are on the deceased donor kidney transplant list, the waiting time can be up to 3-4 years. We do have a voluntary program, the “Extended Criteria Donor (ECD) Program”, that allows people on the list to wait for less time (2-3 years) if they are willing to accept kidneys that are slightly outside our normal criteria for acceptance.

Pt: What exactly do you mean by this?

Dr. Barry: Normally, when a donor becomes available, the surgeon is called to accept the organ. If the patient is older, has had diabetes or high blood pressure or has had a stroke, then the surgeon may not think that this is the best organ. But, if the donor is not too old and has not had diabetes or hypertension for a long time, we will perform additional tests on the kidney, including a biopsy, to determine if the kidney will work. We then offer this organ to our recipient patients participating in the ECD program. It is completely voluntary and if the patient does not want to accept the ECD organ, he or she will not be penalized in terms of their listing status. Patients participating in the ECD program are also on the “regular” list and they always have the option to choose between either types of organ.

Pt: What is the surgery like?

Dr. Barry: The kidney transplant operation is a straightforward procedure. The surgery takes about two hours and starts with an incision (usually about 6 to 8 inches) from your pubic bone up to your hip bone. We place the new kidney in your pelvis and connect it to the blood vessels in your groin as well as connecting the kidney to your bladder.

Pt: How long do I stay in the hospital?
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Dr. Barry: Most people stay five days.

Pt: What are the potential complications?

Dr. Barry: Complications for this surgery are rare, but include adverse reactions to the general anesthetic medicines, bleeding, infection, blood clots in the artery or vein going to the kidney, twisting or “kinking” of these blood vessels, a leak of urine where we connect the kidney to the bladder, a narrowing of the connection to the bladder, or a fluid collection around the kidney after the surgery, usually either blood or lymphatic fluid.

Pt: What happens if I get one of these complications?

Dr. Barry: Often, they can be treated without surgery, but sometimes another surgery is required. For example, problems with the blood vessels, leaking of urine or a collection of lymphatic fluid all may need an additional surgery to fix definitively. We rarely have to perform a second surgery, but they are usually minor procedures and most always result in a complete resolution of the problem.

Pt: Does the new kidney start working right away?

Dr. Barry: Usually it does, but sometimes the new kidney is “stunned” or “sleepy” and it doesn’t start working immediately. This is more common with deceased donor kidney transplants but can, very rarely, happen even with living donor kidney transplants.

Pt: What happens if my new kidney is “sleepy”?

Dr. Barry: Sometimes patients will require dialysis after their transplant operation until the kidney starts working. If it is a simple matter of delayed kidney function (that is, if there are no technical or surgical complications and there is no rejection), then kidney will most always “wake up”. In these cases, the need for dialysis can last anywhere from a few days to a few weeks.

Pt: What about rejection?

Dr. Barry: You will have to take anti-rejection medicines every day after you receive your kidney transplant. These days, our medicines are so effective in preventing and treating rejection that it’s extremely unusual for someone to lose their kidney because of rejection in the first several years after transplant. Nonetheless, about 20% of all kidney transplant recipients experience an episode of rejection in the first few years.

Pt: How can I tell if I am experiencing rejection?

Dr. Barry: Usually, there are no symptoms, but occasionally patients have tenderness over their new kidney, fevers or decreased urine output. More commonly, you will be feeling fine and we detect an abnormally elevated creatinine level on your routine blood tests. First we will make sure that your anti-rejection drug levels are not too high, that you do not have a urinary tract infection and that you have been keeping yourself well hydrated: all of these things can cause the creatinine to be elevated. Then, we will perform an ultrasound of your new kidney to make sure that there are no technical problems such as blood clots in the kidney, problems with the connection to the bladder, or fluid collections around the kidney. If the ultrasound is normal, then we will perform a biopsy of your kidney.

Pt: Is that another operation?

Dr. Barry: No. A biopsy is performed by placing a small needle through the skin after numbing the skin with local anesthesia. It can be performed as an outpatient procedure.

Pt: What if the biopsy shows rejection?

Dr. Barry: Depending on the type of rejection and the degree of rejection, we will treat you with the appropriate anti-rejection medicine. If the rejection is mild, we will give you intravenous steroids for two or three days. If it is more severe, then we will use more powerful antibody medicines for up to five days. These treatments almost always completely reverse the rejection. So, as long as we catch the rejection in a timely fashion, losing the new kidney would be a very rare occurrence.

Pt: What are the risks of taking anti-rejection medicines?

Dr. Barry: In general, there are risks of certain types of infection and certain types of cancer. In the first three months, your risk for infections is highest, so we give you medicines to prevent certain types of bacterial, viral and fungal infections. After three months, we stop these prophylactic medicines and keep your anti-rejection medicines going at reduced doses. The risks for cancer, particularly skin cancer and lymph node cancer, is slightly higher than the general population. We recommend that you avoid prolonged sun exposure and that you always use appropriate protection from the sun. Regular routine physical exams and blood tests are important for early detection of cancer.

Pt: Do the anti-rejection medicines have any other side effects?

Dr. Barry: Ironically, one of the major side effects of Cyclosporine and tacrolimus is kidney toxicity. We are able to avoid this by regularly checking the levels of these drugs in your blood and adjusting your doses appropriately. Cellcept, another anti-rejection medicine, can cause stomach upset, abdominal pain, or diarrhea. Sometimes we have to lower the dose of this medicine or substitute another very similar drug that is less likely to have these side effects. Finally, steroids can have many die effects such as diabetes, growth delay in children, osteoporosis, facial and skin changes, or neurologic problems such as difficulty sleeping or euphoria. However, we are very aggressive about rapidly decreasing your steroid dose over a period of several weeks after your transplant, so that many of these potential problems are avoided. Many patients have to take insulin shots after their transplant, but often the need for insulin shots eventually goes away as the steroid dose is lowered.

That essentially covers all that you need to know about your kidney transplant operation. Do you have any other questions?

Pt: Not at the moment, but I’ll contact you if I do. Thank you very much for your time.

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Surgery in the Cirrhotic Patient

Posted on 20/03/2011 by Chris Barry

For this particular article, I am focusing on general surgical procedures such as hernia repair, gall bladder removal, and liver cancer resection in patients with cirrhosis. This information is applicable to other types of surgery, such as cardiac, colon, breast, and orthopedic procedures. I’ll talk about liver transplantation in a future post.

Cirrhosis, or terminal scarring of the liver, has a multitude of causes, not just excessive alcohol intake or infection with viruses such as Hepatitis B or C. There are inborn metabolic defects, autoimmune processes, toxic ingestions (sometimes of prescribed medications), a predisposition to accumulate fat in the liver, and other genetic predispositions that can all result in cirrhosis. When cirrhosis sets in, many people ultimately progress to end stage liver disease with “portal hypertension”. The portal venous system drains all of the blood from our intestines and directs it to the liver, where toxins are cleared and nutrients are processed. When the liver is terminally scarred, this portal venous flow backs up and forms connections with other veins, thereby bypassing the liver.

This is not good.

Several potentially dangerous consequences occur. The spleen enlarges (“splenomegaly”) and traps platelets (the blood cells that are essential for forming clots). Large and fragile varicose veins begin to form in the esophagus and other places. Fluid builds up in the abdominal cavity (“ascites”) and legs (“edema”). The intestinal toxins normally neutralized by the liver (such as ammonia and others) go to the brain and cause confusion or even coma (“encephalopathy”).

And there’s more bad stuff that can happen that I don’t have time to go into.

How bad a patient’s liver disease is can be reasonably estimated by various scoring systems that are based on laboratory values and findings on physical exam. The two most useful are the Child-Turcotte-Pugh scale and the MELD score.Chil_Turcotte-Pugh ScaleThe former (often referred to simply as the Child’s scale) takes into account the degree of encephalopathy and ascites, as well as blood test results to gauge how well the liver is functioning (bilirubin excretion, albumin synthesis, and blood clotting factor production) to form three classes: Child’s A, B, and C. Child’s A cirrhotics have well compensated liver disease and don’t have significant problems with confusion, spontaneous bleeding, or abdominal fluid accumulation. Child’s C cirrhotics, on the other hand, are quite symptomatic, sick, and tenuous.

The MELD score (Model for End Stage Liver Disease) uses a complex linear regression formula to transform a patient’s bilirubin (a measure of how well the liver is excreting bile), creatinine (a measure of kidney function), and INR (a measure of how thin the blood is) test values into a number between 6 (“normal”) and 40 (“you need a liver transplant”).? This score accurately predicts a patient’s chance of dying over time if no medical or surgical interventions are performed. This scoring system is used to determine where liver transplant candidates are on the waiting list: the sicker your liver, the higher your MELD score, and the higher you are on the list.

Dose in the range of 600 cheapest cialis to 1000 mg 3 daily. It lessens indications of Raynaud’s phenomenon which is a top pharmaceutical industry in supplying quality trademark pills. levitra cialis viagra Carnitine and Acety l-Carnitine- help to bring viagra generico uk https://pdxcommercial.com/property/1541-sw-market-street-portland-oregon-97201/ excess fats into the energy producing parts of your cells (mitochondria) so that these fats can be used as energy rather than building up and causing damage. However in reality this pill works buy levitra line to increase the blood circulation to the male genitals and thereby boosts the male libido. Both Child’s and MELD are important in gauging risk for cirrhotic patients who need surgery. (In general Child’s A is equivalent to a MELD of <10, Child’s B is MELD 10-15, and Child’s C is MELD >15). Potential complications in operating on a cirrhotic patient, whether it’s a simple hernia repair or big liver resection for cancer (see video here), include bleeding, kidney injury or failure, onset or worsening of ascites, infection, poor wound healing, failure to thrive after the operation, or outright liver decompensation. The worse the liver disease is to begin with, the higher the risks of complications or even death.

The actual risk of a cirrhotic going into liver failure after surgery is not well defined, but we can infer general percentages from other well measured data. For example, 50% of all postoperative deaths in cirrhotic patients are caused by liver failure. The risk of dying from a liver cancer resection in a Child’s A cirrhotic is between 4.5-8%. Therefore, the risk of a Child’s A cirrhotic going into liver failure after a liver resection is between 2-4%.

Certainly, the degree of liver disease and the complexity of the operation are important factors. For surgery not involving the liver, there is a >40% mortality risk in a Child’s C cirrhotic. For liver resection, the mortality risk is so high in Child’s C patients that the surgery should not be performed. (In fact, the only operation a Child’s C cirrhotic should receive is a liver transplant!).

The current medical consensus is that Child’s A patients are relatively safe to operate on, but surgery should be performed in the context of expert medical care and by surgeons who are experienced in operating on cirrhotics (i.e., go to a liver transplant center for optimal results). The one caveat to Child’s A being okay for surgery is that if the patient has portal hypertension, it’s best to avoid surgery if at all possible. If necessary, the portal hypertension can be relieved with TIPS (“Transjugular Intrahepatic Portosystemic Shunt”) prior to surgery.

Same with Child’s B: portal hypertension is usually a deal breaker. If a Child’s B patient does not have portal hypertension, then surgey can be relatively safe as long as all attempts are made preoperatively to maximize liver function, control symptoms, and protect other organ systems. If a toxin is present (such as alcohol) or the liver is otherwise transiently inflamed, then time must be taken for things to settle down before going to surgery. If the patient has ascites, then measures must be taken to control it prior to surgery (i.e., diuretic medicines or TIPS). If the kidney function is borderline, then protective medicines and hydration are needed to prevent kidney failure postoperatively.

Ideally, the care of a cirrhotic patient needing general surgery needs to be multidisciplinary from a thoughtful, experienced, and tightly interactive team involving surgeons, anesthesiologists, hepatologists, critical care experts, nephrologists, and infectious disease experts. With careful preoperative, interoperative, and postoperative attention to detail, skill, and knowledge, patients with well compensated or moderately compensated cirrhosis can safely undergo just about any surgical procedure.

 

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Liver and Kidney Transplantation in People with HIV

Posted on 13/03/2011 by Chris Barry

Transplanting people with HIV infection for end stage organ disease was, not too long ago, considered inappropriate because of the unknown long term outcomes and the fear that administering antirejection drugs to patients with a preexisting immunosuppressive viral infection would lead to unacceptable complications and deaths. Recent experience, however, has surprisingly shown that people with well controlled HIV infection can be successfully transplanted with excellent outcomes comparable to the general population.

The reasons for this success are threefold. First, combinations of medicines to manage HIV infection, termed HAART (Highly Active Anti Retroviral Therapy), are so effective that most people with HIV can live relatively normal lives with undetectable viral replication in their blood, robust immune systems (as measured by normal CD4 T cell counts), and freedom from progression to AIDS. As a result, people with HIV are living long lives and the incidence of chronic diseases, such as end stage renal and liver disease is increasing in this population.

Second, current immunosuppressive therapy for transplant recipients is extremely effective in preventing loss of the transplanted organ (or “graft”) due to rejection. Rejection episodes still do occur, but their frequency and severity is significantly reduced with current therapy. In addition, if rejection does occur, we have at our disposal many more powerful immunosuppressive medicines to completely reverse the process. So it is actually quite rare in this day and age for someone to lose their graft due to rejection in the first several years after transplant as long as they are taking their medicines and checking in with their doctors regularly.

Third, our medicines to prevent and treat opportunistic infections in immunosuppressed patients have come a long way. For example, in the past an invasive cytomegalovirus infection in an immunosuppressed patient was life threatening, requiring intravenous therapy and associated with a high mortality rate. Nowadays, this type of infection can often be managed as an outpatient with oral medications. This vast improvement in opportunistic infection prevention and treatment has greatly benefitted both the transplant and HIV populations.

End stage organ failure, including liver disease and kidney disease, is increasing in incidence in people with HIV. Chronic liver disease as a result of coinfection with Hepatitis B and C viruses is particularly prevalent in the HIV infected population. Common causes of end stage renal disease, such as diabetes and hypertension, affect those with HIV. In addition, HIV itself can lead to kidney failure (an entity termed “HIV Associated Nephropathy” or HIVAN). HIVAN is the most common cause of renal failure among people with HIV as well as the third most common cause of end stage renal disease in African Americans between the ages of 20-60 years.

Back before HAART was available, the experience with transplanting people with HIV was dismal. In the post HAART era, however, results have proven to be comparable to transplanting those without HIV. A pilot study performed at the University of California San Francisco beginning in 2002 showed that one year patient and graft survival in liver and kidney transplant recipients with well controlled HIV was not statistically different than results in patients without HIV (see Figure).

people with HIV, HIV transplant, HIV liver transplant, HIV kidney transplant, Dr. Peter Stock, Dr. Chris Barry, bLifeNY, UCSF, URMC

How does an erection occur? It is said that you must avoid excessive use of these order viagra online pills. For IUI to work, your fallopian tubes buy soft cialis must be open and healthy. A stressed out person is likely to experience one or more of the following symptoms: ordering levitra from canada Negative Thoughts: Ideas of hopelessness, helplessness and excessive worry are very common. There seems to be considerable relationship between cheap viagra pills various thyroid conditions and impotence. “Well controlled HIV” specifically means that the virus is not actively replicating, the T cell component of the immune system is intact and robust, and there are no active opportunistic infections while on a stable HAART regimen.

Recently, a multi-institution study on kidney transplant and HIV was published in the New England Journal of Medicine by Dr. Peter Stock and colleagues. The one year patient survival was 94.6% and the kidney graft one year survival was 90.4%. These results are almost as good as the general population.

People with HIV, HIV transplant, kidney transplant, Dr. Peter Stock, Dr. Chris Barry, UCSF, bLifeNY, URMC

Stock, et al., NEJM 2011

There are some challenges with this endeavor, however. First, rejection episodes are higher in kidney transplant recipients with HIV. Rates were reported as high as 40%, compared to expected rates of 15-20% in the general population. Fortunately, these rejection episodes were most often reversible.

A second problem is that of drug-drug interactions between certain antirejection drugs and the “protease inhibitor” HAART drugs such as Kaletra. Fortunately, newer HAART medicines are now available, specifically the “integrase inhibitor” class of drugs, that do not have such profound interactions with the antirejection drugs.

The experience with transplanting patients with HIV has been surprising in many regards. Perhaps most interesting is that giving antirejection drugs does not result in reactivation of HIV. This observation necessitates a shift in how we think about the HIV disease process. That is, HIV infection results in a more complex immunomodulatory process rather than simple T cell immunosuppression. Another surprise is that transplantation in people with well controlled HIV results in similar outcomes as compared to the general population. This, more than anything, is a testament to the incredible advances in treating and managing HIV infection as well as associated opportunistic infections. Finally, that transplant recipients with HIV are even able to mount an immune response to their grafts, let alone significant and robust responses, again shows us how little we actually know about the HIV disease process. This experience is indeed proving to be fascinating to transplant surgeons and physicians, infectious disease experts, and basic science virologists alike.

Future directions for transplantation in people with HIV include increasing our experience with integrase inhibitors to minimize drug-drug interactions, continuing long term follow up of HIV positive transplant recipients, and using the HIV positive transplant experience to increase our knowledge of the basic molecular virology and pathophysiology of HIV infection.  At the University of Rochester Medical Center, we have assembled a team of dedicated doctors to begin offering kidney transplantation to people with HIV and we are already evaluating a number of people for their transplant candidacy.

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Why Biopsy Liver Cancer?

Posted on 07/03/2011 by Chris Barry

Liver cancers, especially when early in their genesis, are usually asymptomatic. Often they are detected when an ultrasound scan, a CT scan or MRI are performed for other reasons, or when a patient has underlying liver disease (cirrhosis of any cause increases one’s risk of developing liver cancer). So when an imaging study reveals a suspicious lesion in the liver and it has certain defining characteristics, the current medical practice is to proceed with treatment without obtaining a biopsy of the tumor unless there is some doubt as to whether it is truly cancerous or not. The main reason for not biopsying is that we do not what to do with the information.

The Pathologist can tell us that the biopsy shows a well differentiated (good) or poorly differentiated (bad) tumor, but this information does not direct our therapeutic approach. Currently, a liver cancer is a liver cancer and they are all treated similarly. Our only metrics of an individual tumor’s biology are how big is it, how many are there, and how fast is it growing. (Spread outside of the liver, or metastatic disease, and tumor invasion into the liver’s blood vessels are also important considerations in directing therapy.)

There is a panoply of treatment options for liver cancer, including surgical resection, arterial injections of chemotherapy (TACE) or radioactive beads (yttrium-90) directly into the tumor, tumor ablations techniques (such as radiofrequency ablation (RFA), irreversible electroporation (IRE), microwave, and cryotherapy), chemotherapy, radiation, and liver transplantation. Which one of these therapies to choose is a great challenge to the physicians caring for a patient with liver cancer and demands a multidisciplinary approach consisting of teams of surgeons, hepatologists, oncologists, interventional radiologists, imaging scientists, and pathologists.

One great hope of medicine today is to move toward “personalized medicine“. That is, the individual patient is treated according to his or her own disease process. For example, liver cancer is a heterogeneous process with some patients’ tumors displaying inherently favorable tumor biology and others with unfavorable (i.e., aggressive) biology. If we could make sense of the tumor’s inherent biology from a biopsy specimen, then we could tailor our treatment to achieve the best possible outcome for the individual patient.
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I believe (as do many others) that we are on the cusp of realizing this goal of personalized medicine in the care for patients with liver cancer. With the advent of the Human Genome Project where we now know almost every gene encoded in the DNA of a human cell, and the subsequent development of extremely powerful genomic analysis techniques that can show which genes are “expressed” (on or off) in a cell, we have in principle all of the tools to begin deciphering a tumor’s biologic behavior and to which treatments it will best respond.

Lee and colleagues published in the journal Hepatology a study that defined two subclasses of liver cancer (“HCC” or hepatocellular carcinoma) based on their global gene expression patterns. One group had a favorable prognosis and the other group had a poor prognosis. Hoshida and colleagues published an article in the New England Journal of Medicine demonstrating that genetic information residing in the liver tissue adjacent to tumors also can help predict a patient’s overall survival. Budhu and colleagues showed recently that micro RNA expression patterns can define liver tumors that have the propensity for metastatic spread. Work in our lab shows that micro RNA patterns can distinguish patients who have had tumor recurrence after liver transplant.

Hopefully, we are rapidly approaching an era where the information from liver tumor biopsies will help direct individual therapies and to permit better distinction of which patients are ideal candidates for liver transplant. The hope is not if we will ultimately achieve these goals, but that we will achieve them soon.

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