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50 Cards in this Set
- Front
- Back
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Urothelial cancers of the upper urinary tract are more common in men than in women. Is this trend also true for bladder cancer?
What about racial biases for bladder cancer? |
Yes, it is about three times more common in men than in women.
More common among whites, about twice, than African Americans and Hispanic Americans |
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The incidence of bladder cancer has increased significantly over the past 2‐3 decades. With the incidence among men increasing even faster than that of women. Why is this trend confusing?
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The incidence of bladder cancer increases with age and women live on average about 5 years longer than men. As the population ages you would think that this would cause the incidence to increase in women more than in men.
Women are now engaged in roles that that weren’t necessarily exposed to 20‐30 years ago, such as environmental agents that are known to cause bladder cancer, chemicals, tobacco, etc. |
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How does the incidence data differ from mortality data for bladder cancer in regards to ethnicity and gender?
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Even though whitey males get it more commonly than all others, the mortality from the disease is much higher in Caucasian women, and even higher still in African American women. Women have a higher than 30% increased risk of dying from bladder cancer than men do.
The prognosis for bladder cancer in Hispanics is better than Caucasians. |
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What are risk factors for bladder cancer?
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*Age, as well as Caucasian race and male gender
*Occupations with increased risk – barbers, beauticians, physicians, drill press operators, autoworker, painter, truck driver, leather worker, metal worker, machiner, dry cleaner, etc. *Cigarette smoking & exposure – fourfold higher incidence *Infections & long term irritation such as chronic foley catheterization or bladder calculi *Analgesic abuse, particularly with phenacetin *Schistosoma cystitis *Pelvic irradiation – twofold to fourfold increased risk *Cyclophosphamide treatment – up to 9x increased risk *Misc stuff such as Blackfoot disease, being a renal transplant patient, some chinese herb *Interestingly, genetics do not appear to be a risk factor |
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Explain the differences between von brunn’s nests, cystitis cystica, and cystitis glandularis.
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Von brunn’s nests are benign islands of urothelium situated in the lamina propria. Cystitis cystica occurs when the urothelium of von brunn’s nests undergo eosinophilic liquefaction in the center of the islands and appear cystic. Cystitis glandularis occurs when the islands have undergone glandular metaplasia, and this is believed to be a precursor to adenocarcinoma.
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What is an inverted papilloma and what conditions is it associated with?
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This is a benign lesion that is the same as a papilloma however instead of growing into the lumen it is inverted into the stroma of the bladder. It is associated with conditions such as chronic inflammation or obstruction, as such it may be covered with squamous metaplasia or cystitis cystica as well as normal urothelium.
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What is vesical leukoplakia that can be seen on cystoscopy?
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It is squamous metaplasia with marked keratinization. It is believed to be a response to a noxious stimulus in the bladder and is believed to be a pre‐malignant lesion with transformation to SCC in 20% of cases.
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What cytogenetic associations do CIS and muscle-invasive bladder cancers have in common that supports their direct relationship?
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Loss of chromosome 17p, deletions and/or mutations of the TP53 gene and its products
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What is the difference between the following lesions histologically?
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Papilloma – rare, but if it truly is a benign papilloma it is usually found by itself. It has a fibrovascular stalk with no histological abnormalities and no more than 7 cell layers. Benign, almost never recurs.
Well differentiated tumors (papillary urothelial neoplasm of low malignant potential, or PUNLMP) – contains more than 7 cell layers, mild anaplasia, rare mitotic figures, base to surface maturation, slightly irregular; often recur. Moderately differentiated tumors (Low grade urothelial carcinomas) – greater disturbance of base to surface cellular maturation, loss of cellular polarity, nuclear to cytoplasm ratio is greater, prominent nucleoli Poorly differentiated tumors (High grade urothelial carcinomas) – no differentiation from base to surface layer of cells, frequent mitotic figures, high nuclear to cytoplasm ratio |
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What are risk factors for nonbilharzial SCC of the bladder?
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Chronic infections, bladder stones, chronic indwelling catheters, bladder diverticulae, cigarette smoking
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You are seeing a patient in Dr. Sutherland’s clinic with bladder cancer who was born with exstrophy. What type of cancer are they most likely to have? In patients with adenocarcinoma of the bladder that are not primary what are potential origins?
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Adenocarcinoma.
Adenocarcinoma found in the bladder is either primarily vesical, which is rare, from the urachus, or is a metastatic lesion. Potential origins include the rectum, prostate, stomach, ovary, endometrium, and breast. |
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A patient with urachal carcinoma s/p excision has what stage by definition?
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Dr. Pruthi states that by definition these patients are T3 disease at least.
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The next patient in Dr. Sutherland’s clinic is a small boy that was referred to you because he had a bloody mucoid discharge from his umbilicus as well as some mucous looking stuff in his urine. What is his probable diagnosis? What might you see on a plain film of his pelvis?
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This patient most likely has urachal carcinoma based on the presentation. A plain film might show some calcifications at the area of the dome of the bladder or level of the urachus.
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What are the most common sites of mets in bladder cancer? What are the common sites of distant vascular spread for bladder cancer?
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Pelvic lymph nodes. Specifically, paravesical nodes in 16%, obturator nodes in 74%, external iliac nodes in 65%, and presacral nodes in 25%
Liver, lung, bone, adrenals, intestines |
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True or False. Most bladder cancers are superficial papillary TCCs upon initial diagnosis.
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True. 55-60% are superficial papillary TCCs initially (keep in mind Chapter 76 says 70%), although the majority will recur, and 10-20% will develop invasive or metastatic disease. 40‐45% of bladder cancers are high grade, more than half of which are muscle invasive or worse at diagnosis.
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What blood group is associated with bladder cancer?
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Lewis blood group
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What are some chromosomal abnormalities that are associated with bladder cancer?
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*Deletion of chromosome 9 – This is more commonly associated with superficial bladder cancers.
*Deletion of chromosome 17p – This is more commonly associated with invasive bladder cancers, this is the location of the TP53 tumor suppressor gene. *Deletion or mutation of chromosome 13q – RB gene is located here, this is also associated with aggressive cancer. |
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We know that cytopathology isn’t 100% sensitive for bladder cancer and that there are about 10‐20% false negative results. What about specificity, are there false positive results?
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False positives occur in 1-12%, secondary to cellular atypia, inflammation, or changes associated with radiation or chemo
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A patient is referred with a CT urogram finding a filling defect in the bladder consistent with a malignancy, and he initially presented with gross hematuria. What is the next step?
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You should set the patient up for cystoscopy under anesthesia with biopsy, flexible cysto is a waste of resources in this case.
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You do a flexible cystoscopy on a patient with microscopic hematuria and their bladder appears to be normal. You do bladder washing at the time of cystoscopy. When you follow these washings up you determine that there is the indication of high grade lesions. You schedule the patient for cystoscopy under general anesthesia. Once you enter the bladder with the rigid cystoscope you look around to find a normal appearing bladder, what should you do?
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Random sample biopsies. It is likely that the patient has CIS that is not visible under regular white light cystoscopy.
There isn’t a standard, but you can take a biopsy of each lateral wall, the anterior dome, the posterior wall, the trigone, and the prostatic urethra. Most people omit the prostatic urethra. |
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From what are small cell carcinomas of the bladder derived, and what is the typical prognosis?
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Neuroendocrine stem cells or dendritic cells, but they may be mixed with elements of TCCs
They are aggressive, and usually respond to, but are not often cured by, cisplatin-based chemo |
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What is sarcoma botryoides?
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This is rhabdomyoscarcoma of the bladder in young children at the base of the bladder with a characteristic polypoid shape.
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What percent of bladder tumors are non-muscle invasive (Ta, T1, and CIS) at presentation?
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70%. (Of these, Ta = 70%, T1 = 20%, CIS = 10%)
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Is there a difference in the risk that a patient has for bladder cancer with gross hematuria versus microscopic hematuria? What percentage of these patients will have bladder cancer for each group?
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The patient with gross hematuria has a significantly higher risk of bladder cancer than a patient with microscopic hematuria. Microscopic hematuria is around 0.5-10.5% and gross hematuria is 13-34.5%.
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Other than hematuria, what other symptom is an indication for upper tract imaging and cystoscopy to rule out urothelial carcinoma?
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Unexplained irritative voiding symptoms
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What is the treatment modality of choice for visible, non-muscle invasive bladder tumors?
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TURBT
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You have a patient in your clinic that is a 70 year old man with smoking history, that was referred from an outside PCP with microscopic hematuria. The patient states that he was having no symptoms at the time, has no history of stone disease, and did not have a catheter at the time. While in the clinic you run a urinalysis on the patient that is negative for hematuria. Does this patient warrant a cystoscopy?
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According to the text if the patient is in the age range for bladder cancer and have one episode of hematuria then they probably warrant a cystoscopy, because the hematuria is intermittent not constant. There is some disagreement about this but it seems that at least several urinalysis must be negative before foregoing a cystoscopy. This patient is in the right age range and has risk factors for bladder cancer, just doing the cysto on this patient might be the right answer.
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You are doing a cystoscopy under general anesthesia on a patient with a lesion in a bladder diverticulum that was diagnosed on office cysto previously. Should you attempt to resect the lesion?
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It should be sampled rather than resected based on the risk of perforation with attempt at endoscopic treatment. This patient should have either a partial cystectomy or total cystectomy.
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What are other factors in a patient besides grade and stage that might make them a higher risk patient in regards to the bladder cancer itself? In other words what other things might you want to know about a patient with high grade T1 disease that might make them high risk in regards specifically to their bladder cancer?
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Size of the lesion
Multiplicity of lesions Status of the rest of the urothelium, in other words was CIS seen as well Presence or absence of lymphovascular invasion on pathology specimen |
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What cytokines are preferentially upregulated in the immune response stimulated in the bladder after BCG therapy? Is the cell mediated response primarily Th1 or Th2?
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nterferon-γ and IL-2
Primarily Th1 response is induced that ultimately leads to cell-mediated cytotoxic mechanisms |
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What is the most frequent chromosomal alteration with bladder cancer?
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*Loss of heterozygosity at chromosome 9 is the most common chromsomal alteration of bladder cancer across all stages and grades.
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So what gene is located at the major site of chromsomal alteration in all bladder cancers?
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*The spot or locus is 9p21. A spot on the short arm of chromsome 9. This is the site of the CDKN2A gene which encodes p16, which is an inhibitor of CDK, or cyclin dependent kinase. So it being lost will lose one of the stops for cell cyle progression.
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What is the importance of DNA methylation?
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DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring (cytosine and adenine are two of the four bases of DNA). This modification can be inherited through cell division.
DNA methylation is a crucial part of normal organismal development and cellular differentiation in higher organisms. DNA methylation stably alters the gene expression pattern in cells such that cells can "remember where they have been" or decrease gene expression; for example, cells programmed to be pancreatic islets during embryonic development remain pancreatic islets throughout the life of the organism without continuing signals telling them that they need to remain islets. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. However, the latest research shows that hydroxylation of methyl group occurs rather than complete removal of methyl groups in zygote.[1] In addition, DNA methylation suppresses the expression of viral genes and other deleterious elements that have been incorporated into the genome of the host over time. DNA methylation also forms the basis of chromatin structure, which enables cells to form the myriad characteristics necessary for multicellular life from a single immutable sequence of DNA. DNA methylation also plays a crucial role in the development of nearly all types of cancer |
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What gene LOH is preferentially found in advanced cases of bladder cancer?
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*This would be LOH at 17p which is the location of TP53.
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Among bladder cancer patients how common is small cell cancer of the bladder?
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Frequency of 0.7% in bladder cancer patients...very rare disease.
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What is the proposed pathophysiology of small cell cancer of the bladder?
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Pathogenesis of SCCB is not well defined. However, several hypotheses were proposed to
explain the origin of SCC in the bladder. The most important hypotheses were: 1. malignant transformation of bladder neuroendocrine cells gives rise to bladder SCC. This hypothesis was supported by the fact that neuroendocrine cells were found previously in the urinary bladder [16]; 2. SCCB arises from urothelial metaplastic changes [1,17]; and a third and more powerful theory suggests that the origin of SCCB may be a multipotential common stem cell that has the ability to differentiate into various cell types depending on the influence of specific transformation or progression-related gene. This may explain the coexistence of SCCB with TCC, and the heterogeneity of the immunohistochemical staining (cytokeratin and endocrine markers) [18-20]. |
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What genetic changes have been seen in Small cell carcinoma of the bladder?
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A Comparative genomic hybridization (CGH) study has demonstrated chromosomal
deletions at 10q, 4q, 5q and 13q [18,29]. These regions are frequently deleted in human tumours and known to carry some tumour suppressor genes: PTEN located at 10q23 and the retinoblastoma gene located at 13q14 [30]. Additions of DNA sequences have been reported at 5p, 6p, 8q and 20q [18,29]. However, no clear single genetic lesion has been characterized. Other studies are necessary to define the role of molecular genetics in the diagnosis of SCCB |
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What is the common stage presentation for small cell carcinoma of the bladder?
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In most cases, the diagnosis is made at advanced stages (T3-T4/N+/M+) (figure 2A) [31].
More than 95% of SCCB cases are diagnosed at muscle invasive stage T2 or more [5- 8,9,11,12]. As an example, in a large MD Anderson series of 88 cases, only 4.5% (4 patients) were diagnosed at superficial stage of the disease (Ta/T1), while 40.1% (n=36) were diagnosed at stage T2, 28.3% (n=25) were diagnosed at stage T3 -T4a (stage III) and 26.1% (n=23) were diagnosed at stage T4b-M+ (stage IV) |
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What should staging for small cell carcinoma of the bladder include as far as imaging and why?
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Based on two large studies, the most frequent sites of metastasis were pelvic and
retroperitoneal lymph nodes (28.6% - 53%), liver (23.8% - 47%) (Figure 2B), bone (23.8 - 33%), brain (7.9% - 16%) and lung (9.5% - 13%) [5,12]. Consequently, the staging of SCCB should include computed tomography scan of the pelvis, abdomen chest, brain, and bone scan. |
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You are evaluating a patient that has biopsy proven T2 high grade bladder cancer. As part of their evaluation in referral to your multidisciplinary clinic the patient gets a CT scan of the abdomen and pelvis to evaluate for metastatic disease. How accurate is this imaging modality in predicting node positive disease at the time of cystectomy?
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The range given for sensitivity for nodes is 50-85%. There are obviously a significant number of false negatives.
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You are doing the pre-op on a male patient in Dr. Wallen clinic for radical cystoprostatectomy. This is a younger patient and he strongly desires to undergo an orthotopic ileal neobladder as opposed to a urinary conduit. How can you determine if this patient is a candidate for this type of diversion? Does this patient need to be marked by the ostomy nurses anyway?
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The patient that is willing to undergo an orthotopic continent diversion such as an ileal neobladder needs to be a younger, healthier more motivated patient. These patients have to understand the risks associated with this type of diversion such as leaking, especially at night, and retention requiring the need to be able to self-cath, especially women as their rate of urinary retention is higher than those in male patients. Risks that have been associated with urethral involvement include prostatic urethral involvement, prostatic stromal involvement, and CIS. For women risks would include CIS, bladder cancer location at the trigone or bladder neck, or a positive margin at surgery.
Yes. Both male and female patients that are requesting an orthotopic continent diversion such as an ileal neobladder after radical cystectomy must understand that if the frozen margins of the posterior urethra are positive intra-operatively then they will not be candidates for this type of urinary diversion and must undergo a conduit. |
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You see a patient in Dr. Pruthi’s Tuesday clinic that is s/p radical cystoprostatectomy with ileal conduit about 5 years out from his surgery. He has been having over the past several months bloody discharge from his penis. What should you do?
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You set him up for cysto and biopsy and find that the patient has high grade invasive urothelial cancer at the urethral stump. You then set him up for urethrectomy.
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What is the number that we often use for cure rate after radical cystectomy for clinically locally confined disease?
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~ 50%
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How is prognosis related to both number of nodes removed at lymphadenectomy and number of positive nodes? What is lymph node density and how does it relate to prognosis?
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Prognosis improves with the number of nodes removed at pelvic lymphadenectomy
Prognosis worsens with the number of positive nodes found at the time of surgery Lymph node density is simply the ratio of positive nodes to the total number of nodes removed at surgery; prognosis worsens as lymph node density rises. |
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What is the mortality rate for radical cystectomy? What is the overall complication rate?
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Mortality = 1-2%
Complication rate = 25% |
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How common is a uretero-enteric stricture encountered after an ileal conduit?
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Strictures in a refluxing anastomosis is very uncommon, about 3%.
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How common is a bowel obstruction seen after radical cystectomy?
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This is also relatively rare at about 4-10% of patients, but less than 10% will require surgery to correct the problem.
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What do the authors conclude about the efficacy of neoadjuvant radiation and neoadjuvant chemotherapy prior to cystectomy in patients with locally advanced disease?
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Preop radiation: does not significantly improve disease specific survival
Neoadjuvant Chemo: May increase survival in these patients by 5-6% |
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What do the authors say about adjuvant chemotherapy following cystectomy?
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No usefulness in organ-confined cancer T1-T2
May provide some survival advantage to patients with locoregional disease and pelvic lymph node involvement. However, this has been difficult to prove due to difficulty accruing sufficient numbers of patients to demonstrate small survival advantages |
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Systemic chemo is routinely used to treat patients with metastatic disease. What combinations are typically used? How frequently do they produce a complete response?
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Methotrexate, vinblastine, doxorubicin, and cisplatin = MVAC; 20% complete response (old standard of care)
Gemcitabine, cisplatin = GC; 40% complete response rate (new standard of care) Taxol or Taxotere (taxoids) with cisplatin; 25 – 83% |
