Impact of Time to Surgery and Surgical Delay on Oncologic Outcomes for Renal Cell Carcinoma.

PURPOSE: The time between radiographic identification of a renal tumor and surgery can be concerning for patients and clinicians due to fears of tumor progression while awaiting treatment. This study aimed to evaluate the association between surgical wait time and oncologic outcomes for patients with renal cell carcinoma. MATERIALS AND METHODS: The Canadian Kidney Cancer Information System is a multi-institutional prospective cohort initiated in January 2011. Patients with clinical stage T1b or greater renal cell carcinoma diagnosed between January 2011 and December 2019 were included in this analysis. Outcomes of interest were pathological up staging, cancer recurrence, cancer specific survival and overall survival. Time to recurrence and death were estimated using Kaplan-Meier estimates and associations were determined using Cox proportional hazards models. RESULTS: A total of 1,769 patients satisfied the study criteria. Median wait times were 54 days (IQR 29-86) for the overall cohort and 81 days (IQR 49-127) for cT1b tumors (1,166 patients), 45 days (IQR 27-71) for cT2 tumors (672 cases) and 35 days (IQR 18-61) for cT3/4 tumors (563). Adjusting for comorbidity, tumor size, grade, histological subtype, margin status and pathological stage, there was no association between prolonged wait time and cancer recurrence or death. CONCLUSIONS: In the context of current surgeon triaging practices surgical wait times up to 24 weeks were not associated with adverse oncologic outcomes after 2 years of followup.

Quality indicators in the management of bladder cancer: A modified Delphi study.

BACKGROUND: Survival in patients with bladder cancer has only moderately improved over the past 2 decades. A potential reason for this is nonadherence to clinical guidelines and best practice, leading to wide variations in care. Common quality indicators (QIs) are needed to quantify adherence to best practice and provide data for benchmarking and quality improvement. OBJECTIVE: To produce an evidence- and consensus-based list of QIs for the management of bladder cancer. METHODS: A modified Delphi method was used to develop the indicator list. Candidate indicators were extracted from the literature and rated by a 27-member Canadian expert panel in several rounds until consensus was reached on the final list of indicators. In rounds with numeric ratings, a frequency analysis was performed. RESULTS: A total of 86 indicators were rated, 52 extracted from the literature and 34 suggested by the panel. After iterative rounds of ratings and discussion, a final list of 60 QIs spanning several disciplines and phases of the cancer care continuum was developed. CONCLUSIONS: This is the first study to comprehensively produce common QIs representing structure, process, and outcome measures in bladder cancer management. Though developed in Canada, these indicators can be used in other countries with slight modifications to track performance and improve care.

Pathological Upstaging of Clinical T1 to Pathological T3a Renal Cell Carcinoma: A Multi-institutional Analysis of Short-term Outcomes.

OBJECTIVE: To determine the oncological impact of pathological upstaging among patients with clinical T1 (cT1) disease treated by partial nephrectomy or radical nephrectomy. METHODS: The Canadian Kidney Cancer Information System comprises a prospectively maintained multi-institutional database for patients with renal cell carcinoma. Nonmetastatic, cT1 renal cell carcinoma cases were evaluated. Upstaging was defined as pathological T3a disease. Multivariate Cox regression analysis identified predictors for recurrence (local recurrence and/or metastatic disease) whereas logistic regression identified predictors of pathological upstaging. Kaplan-Meier methods estimated survival. RESULTS: Of 1448 eligible cT1 patients, upstaging was observed in 134 (9%). One thousand fifty-eight (73%) were treated by partial nephrectomy. After a median follow-up of 23 months, the 3-year recurrence-free survival was 76% in upstaged patients compared with 93% in those not upstaged (P < .001). Controlling for age, gender, year of surgery, histology, tumor size, surgical approach, and margin status, pathological upstaging was independently associated with disease recurrence (hazard ratio 2.03, 95% confidence interval [CI] 1.12-3.68). Increasing age (odds ratio [OR] 1.02, 95% CI 1.00-1.05), Fuhrman grade (OR 2.47, 95% CI 1.47-4.14), and tumor size (OR 1.16, 95% CI 1.00-1.36) were independently associated with a risk of pathological upstaging. CONCLUSION: Pathological upstaging confers a negative prognosis and highlights the importance of accurate clinical staging. A number of factors have been identified, including some attainable by renal biopsy, which may predict upstaging and provide valuable adjunct information to inform risk stratification and management decisions among patients with cT1 renal masses.

Residual renal function after partial or radical nephrectomy for renal cell carcinoma.

Renal cell carcinoma (RCC) is often detected incidentally and early. Currently, open partial nephrectomy and laparoscopic total nephrectomy form competing technologies. The former is invasive, but nephron-sparing; the other is considered less invasive but with more loss of renal mass. Traditionally, emphasis has been placed on oncologic outcomes. However, a patient with an excellent oncologic outcome may suffer from morbidity and mortality related to renal failure. Animal models with hypertension and diabetic renal disease indicate accelerated progression of pre-existing disease after nephrectomy. Patients with RCC are older and they have a high prevalence of diabetes and hypertension. The progression of renal failure may also be accelerated after a nephrectomy. Our analysis of the available literature indicates that renal outcomes in RCC patients after surgery are relatively poorly defined. A strategy to systematically evaluate the renal function of patients with RCC, with joint discussion between the nephrologist and the oncologic team, is strongly advocated.

A near-fatal case of sepsis with an antibiotic-resistant organism complicating a routine transrectal prostate biopsy in a health care worker.

A 58-year-old physician with an elevated prostate specific antigen developed severe septic shock following a repeat transrectal prostate biopsy despite standard preoperative prophylactic protocol. This case highlights the significance of harbouring antibiotic-resistant bacteria and the risk of previous quinolone exposure. We believe this case may herald a rare but potentially serious consequence of increasingly common antibiotic resistance and that high-risk patients should be studied to determine their likelihood of carrying antibiotic-resistant flora in their genitourinary/gastrointestinal tract.

Reovirus salvage of squamous cell cancer-contaminated wounds.

PURPOSE: To assess the susceptibility of human squamous cell carcinoma to reovirus infection in vitro and in vivo using a murine model of cancer-contaminated wounds. METHODS: The University of Michigan squamous carcinoma 22B cell line was cultured and inoculated with reovirus in vitro. The effect of the reovirus was assessed with microscopy and a standard 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay. We used the previously established cancer-contaminated wound SCID mouse model to test saline and reovirus irrigation in vivo. Fifty-five mice were used; 15 were controls, 20 had immediate irrigation, and 20 had delayed irrigation. Surgical sites were assessed for palpable tumour biweekly. RESULTS: The microscopy and MTT assay both showed evidence of reovirus-mediated squamous cancer cell lysis. The control mice grew palpable tumours in 80% of the wounds. Immediate irrigation with saline delayed the onset of palpable tumour and demonstrated a persistent reduction in the rate of development of palpable tumours (p = .004 compared with controls). This effect disappeared when the saline irrigation was delayed, resulting in a tumour development rate that was not significantly different from that of the control. Wounds that were irrigated with reovirus, both immediately and delayed, did not produce palpable tumour (p < .0005 when compared with controls). CONCLUSIONS: (1) The University of Michigan squamous cell carcinoma 22B cell line is susceptible to reovirus in vitro. (2) Immediate irrigation with saline resulted in a significant delay in clinically evident tumour growth and a reduction in the rate of tumour development in the SCID mouse model. (3) The reovirus irrigation resulted in a significant reduction of tumour development in both the immediate and delayed groups in the SCID mouse model. (4) The efficacy of the reovirus irrigation in the delayed group suggests that the major mechanism of action is through a selective and specific targeting of implanted cancer cells.

Telomere shortening in kidneys with age.

The histology and function of the kidney deteriorates with age and age-related diseases, but the mechanisms involved in renal aging are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stresses that increase replication. This study explored the relationship between age and telomere length in surgical samples from 24 human kidneys, which were either histologically normal (17) or displayed histologic abnormalities (7). Telomere loss was assessed by two independent methods: Southern blotting of terminal restriction fragments (TRF) and slot blotting using telomere-specific probes. The results of these methods correlated with each other. The mean TRF length determined by Southern blotting in cortex was about 12 kb pairs (kbp) in infancy and was shorter in older kidneys. The slope of the regression line was about 0.029 kbp (0.24%, P = 0.023) per year. Telomere DNA loss in cortex by the slot blot method was 0.25% per year (P = 0.011). By both methods, the telomere loss in medulla was not significant and was less than in cortex. Comparisons of TRF length from 20 paired samples from cortex and medulla showed that TRF was greater in cortex than medulla, with the differences being greater in young kidneys and lessening with age due to telomere loss in cortex. These findings indicate that telomeres shorten in an age-dependent manner in the kidney, either due to developmental factors or aging, particularly in renal cortex.