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Welcome to the Why Urology podcast with Dr. Todd Brandt.

This podcast is my personal attempt to teach you about your genito-urinary tract, what can go wrong, and how your urologist may just become your superhero.

The name of the podcast comes from my ongoing need to answer the question that I get so often from patients, friends, and family, “Why Urology? Why did you choose to become a urologist?”

Dec 16, 2017

Today I want to turn our discussion to Kidney Cancer. According to the National Cancer Institute there are three main types of kidney cancer. Renal cell cancer is the most common type in adults and Wilm’s tumors are the most common in children. These types form in the tissues of the kidney. Transitional cell cancer, the same type of cancer that can form in the bladder, forms in the renal pelvis and ureter, the funnel shaped drainage system from the kidney. According to the American Cancer Society, in the United States in 2017, about 64,000 new cases of kidney cancer and renal pelvis cancer are expected and will lead to more than 14,000 deaths. Statistically, about 1 out of every 63 people will get a kidney cancer within his or her lifetime For today’s discussion, I want to focus specifically on Renal Cell Carcinoma, the most common type of kidney cancer in adults. Renal Cell Carcinoma is responsible for over 90% of all cases of kidney cancer. Renal Cell Carcinoma accounts for about 4% of all the adult malignancies and is in the top ten malignancies for both men and women. A man is 1.5 times more likely to get kidney cancer than is a woman. Risk factors for Renal Cell Carcinoma include the following: smoking, obesity and high blood pressure.  Extensive use of NSAIDS has also been implicated. It goes without saying, of course, but I am going to say it anyway. Stop smoking, watch your weight, and control your blood pressure. A family history of renal cell cancer also predisposes you to a risk of kidney cancer. Genetic variants have been identified as the cause of inherited cancer risk in some Renal Cell Carcinoma–prone families; these pathogenic variants are estimated to account for about 5% of Renal Cell Carcinoma cases. Furthermore, having certain conditions or syndromes can also lead to Renal Cell Carcinoma such as von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, hereditary leiomyomatosis, and tuberous sclerosis. Patients with kidney cancer may present with the so-called “classic triad” of symptoms: blood in the urine, pain in the flank or abdomen, and a palpable mass. But this presentation is only common when the tumor is very large. Renal Cell Carcinoma has also received the moniker, “the internist’s tumor” because an interesting facet of kidney cancer is that it may manifest first in something called a “paraneoplastic syndrome” that seems unrelated to the kidney:  hypercalcemia (pseudohyperparathyroidism), erythrocytosis, hypertension, and gynecomastia are all related to hormone like substances made some renal cell carcinomas. More commonly in the day of advanced imaging such as CT or MRI kidney tumors are discovered incidentally (i.e. an incidentaloma) when a person has the imaging done for other reasons and a small, asymptomatic tumor is seen in the kidney. Tumors found incidentally may be very small, even as small as 1 cm, the size of a pea. A CT scan also called computerized axial tomography or CAT scan is an x-ray that makes a series of detailed pictures of areas inside the body by computing x-ray pictures taken from many different angles. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. An MRI or magnetic resonance imaging   is a procedure that uses a magnet and a computer to make a series of detailed pictures. Both the CT and the MRI create a very detailed image of the kidneys and can determine if a tumor is cystic (typically benign) or solid (can be benign or cancerous). A CT scan or MRI cannot tell you if a tumor is cancerous; a cancer can only be diagnosed by biopsy of the tumor or after the tumor is removed. A Renal Cell Carcinoma (RCC) originates from the lining of the proximal convoluted tubule, a part of a series of small tubes in the kidney that filter the blood and then concentrate and transport urine to the renal pelvis and ureter. But doctors didn’t always know that this tumor found in the kidney actually started in the kidney.  In fact, the origin of kidney cancer, where it came from in the body, was not known for many years, and was one of the longest controversies in surgical pathology. The debate started with Dr. Paul Grawitz, a German pathologist, when in 1883, he published his observations on small, yellow renal tumors that had previously been described as lipomas or fatty tumors. Dr. Grawitz compared these small tumors to the normal adrenal gland and hyperplasia of the adrenal gland, and concluded that they represented small ectopic adrenal rests (struma suprarenalis aberrata).  Dr. Grawitz consolidated his theory with further illustrations of intrarenal ectopic adrenal tissue. Dr.  Grawitz’s theory stimulated considerable interest and was widely, but not universally, accepted. Other doctors supported the adrenal rest theory by coining the term hypernephroid tumor, which was later amended to “hypernephroma”, to describe these tumors. Vigorous criticism of Grawitz was provided by Oskar Stoerk in 1908, who considered the adrenal origin of renal tumors to be unproved. He compared the relative frequency of renal tumors with the scarcity of malignant epithelial tumors of the adrenal gland and commented on the lack of histological similarity between a hypernephroma and adrenal gland cancer. It wasn’t until 1959 that convincing evidence to settle the debate was offered in the Journal Nature(1960, 186: 402-403)  by Dr. Oberling C who studied the ultrastructure of clear cells from eight renal carcinomas and found that the tumor cell cytoplasm contained numerous mitochondria and deposits of glycogen and fat, with occasional cells containing microvilli along free borders and concluded that these features were more consistent with the epithelial cells of the renal convoluted tubule. Although renal cell carcinoma is now recognized as starting in the kidney, renal cell carcinoma is still sometimes referred to incorrectly as a hypernephroma or a Grawitz tumor. Doctors continue to learn more and more about different types of kidney cancer.  In The 2004 World Health Organization (WHO) classification of genitourinary tumors recognized over 40 subtypes of renal neoplasms, and several more have been added since that time. Let’s transition to how we treat Kidney Cancer. I want to begin by quoting another author. “The treatment for Renal Cell Carcinoma, both, primary and secondary growths, continues to be surgical…a review of the literature indicates that the hope of cure in this tumor lies in the hand of the surgeon.“  Thus begins an article in the Journal of Urology when, in 1964, Dr Charles Robson reviewed 88 cases of kidney cancer that he treated surgically during a 15 year span between 1949 and 1964. Robson’s article is published, along with other groundbreaking articles in Urology, in an anniversary edition of the Journal of Urology, this year celebrating its centennial. You can find the article at www.JU100.org. What was true in 1964 is still true today.  The best hope of cure of Renal Cell Carcinoma is to catch it early and remove it, almost regardless of subtype or predisposing condition. The recommended treatment for renal cell cancer is surgical removal of all or part of the kidney. Different procedures, radical nephrectomy vs. partial nephrectomy, open vs. laparoscopic or robotic, removal of adrenal glands and lymph nodes, may all be appropriate depending on circumstances, tumor size, location and a patient’s other medical problems. A "radical" nephrectomy  removes the entire affected kidney including Gerota's fascia (the fat around the kidney), and may also include the adrenal gland which is on the same side as the affected kidney, and the regional retroperitoneal lymph nodes. This technique is most often used when there is a large tumor present in only one kidney. It is important to note that the other kidney must be fully functional and the patient must be healthy enough to undergo a major surgery and associated risks and complications both during and after the surgery. Smaller renal tumors (usually < 4 cm) are treated by “partial” nephrectomy when possible. The partial nephrectomy involves the removal of the affected tissue only, sparing the rest of the kidney, Gerota's fascia and the regional lymph nodes. This allows for more renal preservation as compared to the radical nephrectomy, and this can have positive long-term health benefits. Nephron-sparing partial nephrectomy is especially important when the patient has other medical concerns such as diabetes or hypertension. Larger and more complex tumors can also be treated with partial nephrectomy by experienced surgeons. Cryotherapy or other ablative techniques can also be done on smaller lesions with good long-term success if chosen for the right patient. Surgery is increasingly being performed via laparoscopic and robotic techniques. Laparoscopic or robotic surgery does not have the large incisions seen in a classically performed radical or partial nephrectomy, but still successfully removes either all or part of the kidney. Visualization and dissection is performed using small incisions (one of my partners calls them “poke holes”) through which we pass high definition cameras and dissecting instruments. Robotic surgery has an advantage over laparoscopic surgery because of the increased dexterity afforded by the robotic instruments. I discussed robotic surgery with one of my partners in episode   of this podcast. Laparoscopic and robotic surgery is associated with shorter stays in the hospital and quicker recovery time. Most cases that I perform are done robotically, with a preference for a partial nephrectomy if possible. Last week I was involved with 5 different operations for renal masses. One of the operations was a radical nephrectomy, 4 others were done as robotic partial nephrectomy. The nephrectomy done last week was for a very large renal mass and required an incision, the first incision I have made for my practice in several months. In 1964 Dr. Robson used the thoraco-abdominal or trans-peritoneal abdominal approach to remove a kidney, and his name became almost synonymous with a thoraco-abdominal incision, an incision that opens the chest cavity as well as the abdominal cavity. Urologists rarely use the thoraco-abdominal approach today, but use an abdominal incision only when a large incision is needed. He described the operation succinctly but effectively and I will read from his article. “After reflection of the colic flexure, dissection should begin on the medial border of the tumor. The renal vein is identified and the renal artery is dissected free from its posterior aspect. The artery should be ligated before the vein wherever this is possible, thus disturbing the hemodynamics as little as possible. The value of a preoperative aortogram, besides its diagnostic features, might be emphasized here, because it will definitely identify the position of the renal artery and, also, if there is an accessory artery present or if there is an abnormal division of the renal artery, the surgeon is forewarned. The perinephric fat and overlying peritoneum are removed with the primary growth and, where possible, the para-aortic and para-caval lymph nodes from the bifurcation of the aorta to the crus of the diaphragm. If the tumor is very large, it may be necessary to remove it before the gland dissection is carried out.” The principles that Robson defines in his brief description of the operation, specifically understanding the vascular anatomy prior to the operation and early identification and ligation of the renal artery still hold today, and are the foundation for today’s careful anatomical dissection and improved outcomes, regardless of whether the procedure is done robotically or with a large incision. As I read through his description I realized that with the exception of the extended lymph node dissection, last week I used a trans-peritoneal subcostal incision and performed the surgery just as he described. Dr. Robson argued in his article that the prognosis for renal cell carcinoma is dependent upon 5 factors and/or a combination of these: 1) involvement of adjacent structures by direct extension, 2) presence or absence of distant metastases, 3) involvement of the regional lymph nodes, 4) gross invasion of the renal vein or its main tributaries and 5) histological grade of the tumor. Robson created a staging system with 4 different stages based on whether the tumor was in the kidney or invaded the perirenal fat, had lymphatic or vascular involvement, or had metastasized. We now use a more detailed TNM Staging System, but there are still 4 stages of cancer. A tumor confined to the kidney and less than 7 cm across is Stage 1, if it is greater than 7 cm it is stage 2. Stage 3 is a tumor of any size that is invading the fat around the kidney or resides in a nearby lymph node. Stage 4 is any invasion into the adrenal gland, distant lymph nodes or other metastasized to other organs. Taken as a whole, if cancer is only in the kidneys, it can be cured roughly 80-90% of the time with surgery. More specific subsets show a five-year survival rate of around 90–95% for tumors less than 4 cm. For larger tumors confined to the kidney without venous invasion, survival is still relatively good at 80–85%. For tumors that extend through the renal capsule and out of the local fascial investments, the survivability reduces to near 60%. Survivability decreases significantly in cases where the cancer is stage 4 or metastasized. But even in cases of metastatic disease, long term prognosis continues to improve with changing chemotherapy regimens. Factors such as general health and fitness or the severity of their symptoms at presentation impact the survival rates. The earliest reference suggestive of tumor arising in the kidney was made by Daniel Sennert in his text Practicae Medicinae, first published in 1613. Sennert wrote, “Moreover the hard swelling of bad kidneys which has the capacity to throw a person into cachexia and dropsy, is for the greater part incurable”.  That is not true today.  Today with advanced techniques and diagnostic tools we are able to find kidney cancers early and remove them or control them effectively if they have spread. And, as I said, we are still learning.  Dr. Robson’s article in 1964 advanced our knowledge and surgical expectations for patients with kidney cancer. Laparoscopy, robotic surgery, advanced CT, MRI and Ultrasound imaging have also moved us forward. Newer chemotherapy and immunotherapy regimens will continue to improve the survivability of the disease but, for now, I will leave you quoting Dr. Robson again, “…the hope of cure in this tumor lies in the hands of the surgeon.”   https://en.wikipedia.org/wiki/Paul_Grawitz http://uscapknowledgehub.org/site~/98th/pdf/companion09h02.pdf https://www.cancer.gov https://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb7/BB7.pdf