Regarding non-muscle-invasive bladder cancer and adjuvant chemo/immunotherapy, which of the following statement is FALSE?
Answer C
The effect of early instillation can be explained by the destruction of circulating tumour cells free within the bladder immediately after TUR, or as an ablative effect (chemoresection) of the residual tumour cells at the resection site. In all single instillation studies, the instillation was administered within 24 hours. In absolute values, the reduction was 11.7% (from 48.4% to 36.7%), which implies a 24.2% decrease in the corresponding relative risk. The majority (80%) of patients in this EORTC meta-analysis showing the benefit of single, immediate instillation of intravesical chemotherapy after TURBT had a single tumour.
No prospective data are available showing that the single instillation significantly reduces recurrence rates in patients with recurrent tumours. Nevertheless, there is significant evidence from one subgroup analysis that an immediate instillation might have an impact on the repeat instillation regimen for treatment of patients who are at intermediate- and high-risk of recurrence.
Immediate instillation of chemotherapy has no reported influence on the progression rate or overall survival of patients with NMIBC. Mitomycin C, epirubicin and doxorubicin have all shown a beneficial effect, and none is superior.
Further Reading:
Intravesical immunotherapy results in a massive local immune response characterised by induced expression of cytokines in the urine and bladder wall and by an influx of granulocytes, mononuclear and dendritic cells. Which of the following statements regarding intravesical BCG immunotherapy is FALSE?
BCG is an attenuated mycobacterium developed as a vaccine for tuberculosis that has demonstrated antitumour activity in several different cancers including urothelial cancers. BCG is stored in refrigeration and reconstituted from a lyophilised powder. Connaught, Tice, Armand Frappier, Pasteur, Tokyo and RIVM strains all arise from a common original strain developed at the Pasteur Institute. Treatments are generally begun a minimum of two weeks after tumour resection, allowing time for re-epithelialization, which minimises the potential for intravasation of live bacteria. For the same reason, a urinalysis is usually performed immediately before instillation to further ensure a diminished probability of systemic uptake of BCG. In the event of a traumatic catheterisation, the treatment should be delayed for several days to one week, depending on the extent of injury. After instillation, the patient should try and retain the solution for at least two hours however this is not always possible due to urgency and pain. Fluid, diuretic and caffeine restriction before instillation is essential to limit dilution of the agent with urine and to facilitate retention of the agent for two hours. Patients are instructed to clean their toilet with bleach after voiding and flushing. The original regimen described by Morales included a percutaneous dose, which was discontinued after success using a similar intravesical regimen.
The limits of dissection of a standard pelvic lymphadenectomy in cases of radical cystectomy include the following, EXCEPT:
Answer A
Apart from the B–D above, the limits of dissection of the standard pelvic lymphadenectomy includes the genitofemoral nerve laterally, not the obturator nerve. Many researchers now recommend an extended lymphadenectomy with the cephalad limits of dissection extending up to the aortic bifurcation and including caudally the presacral nodes. Not only does an extended lymph node dissection provide additional data for tumour staging, but survival might also be improved by this technique. Removal of more than 15 lymph nodes has been postulated to be both sufficient for the evaluation of the lymph node status as well as beneficial for overall survival in retrospective studies.
A 69-year-old woman has been diagnosed with muscle-invasive bladder cancer and is considering undergoing radical cystectomy with formation of an orthotopic neobladder. Her GFR is 52 mL/min and she has marked right-sided hydronephrosis. Which of the following statements is TRUE?
Answer D
Patients with significantly decreased renal function are at increased risk of developing chronic acidosis and metabolic abnormalities with a continent diversion. This is due to the reabsorption of electrolytes by the bowel mucosa. There is no exact renal function cut-off below which continent urinary reconstruction should not be performed, but as a general guide, one should generally avoid it if the GFR is <50 mL/min. Abnormal GFR, hydronephrosis, previous bowel surgery with or without adjuvant chemotherapy and/or external beam radiation to the pelvis are not absolute but relative contra-indications for a neobladder. Involvement of the bladder neck is considered an absolute contraindication in both sexes. Quality of life surveys have not shown one type of urinary diversion to be superior over another. Most patients are reasonably well adapted socially, physically and psychologically to their diversion. The key to this adaptation is appropriate and realistic preoperative education. Quality of life surveys have often been underpowered or affected by selection bias. Most such studies in patients with continent urinary diversion suffer from major methodological problems. Unfortunately, there is not a single RCT within the field of urinary diversion. Almost all studies are of Level 3 evidence good-quality retrospective studies, or case series, or Level 4 evidence including expert opinion.
Which of the following statements regarding the use of bowel for urinary diversion is TRUE?
Answer B
Metabolic consequences of the use of bowel for urinary diversion are mainly related to bowel type and length. Considering complications of urinary contact with bowel, the length of time urine is retained, concentration of urinary solutes, urinary pH and osmolality are also important. In an ileal conduit, hydrogen is normally secreted into the lumen in exchange for sodium, whereas bicarbonate is secreted into the lumen in exchange for chloride. In the presence of diluted or hypo-osmolar urine, often seen in the early postoperative period due to low salt intake, one may see a hypovolemic salt-losing state with subsequent acidosis, hyperchloremia and hypokalaemia. Mild metabolic acidosis may be expected in up to 15% of patients after ileal conduit diversion. Due to increased urine contact time and surface the incidence of metabolic acidosis in orthotopic diversions is greater by up to 50%. The principal mechanism leading to the production of acidosis is thought to be ammonium reabsorption in hyperosmolar urine. Chloride and sodium are absorbed, pH in reservoir increases and volume decreases. Absorption of ammonium chloride leads to a hyperchloremic acidosis. Over time, chronic acidosis can lead to bone demineralisation because excess protons in the serum would be buffered against bone minerals. Acidosis may also cause osteoclast activation and potential impairment of vitamin D synthesis. It is important to recognise the clinical signs of metabolic acidosis, such as nausea, lack of appetite, fatigue, weakness and ultimately vomiting. Patients with impaired hepatic and renal function, large bowel surface and long urine-bowel contact are at increased risk of developing this disorder. One should have a high index of suspicion if patients with urinary diversions have non-specific illnesses. Acidosis and electrolyte disturbance should be excluded early. Normal serum pH and bicarbonate do not exclude a severely compensated metabolic acidosis, and blood gas analysis and body weight measurements are required. But many metabolic effects may be subtle and only recognised with continued follow-up (particularly of patients at risk). Metabolic acidosis can be best detected by regular blood gas analysis. The terminal ileum is the sole site of vitamin B12 and of bile acid absorption. If more than 100 cm of distant ileum is resected, lipid malabsorption and therefore also fat-soluble vitamins (A, D, E and K) malabsorption will occur. All patients should be monitored regularly for B12 deficiency following the use of terminal ileum for urinary diversion. If deficiency is confirmed, lifelong supplementation with monthly intramuscular injection is required. The morbidity of radical cystectomy and urinary diversion is up to 75% diversion related.
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