Everolimus Reduces Cancer Incidence and Improves Patient and Graft Survival Rates after Kidney Transplantation: A Multi-Center Study

Kidney transplantation can prevent renal failure and associated complications in patients with end-stage renal disease. Despite the good quality of life, de novo cancers after kidney transplantation are a major complication impacting survival and there is an urgent need to establish immunosuppressive protocols to prevent de novo cancers. We conducted a multi-center retrospective study of 2002 patients who underwent kidney transplantation between 1965 and 2020 to examine patient and graft survival rates and cumulative cancer incidence in the following groups categorized based on specific induction immunosuppressive therapies: group 1, antiproliferative agents and steroids; group 2, calcineurin inhibitors (CNIs), antiproliferative agents and steroids; group 3, CNIs, mycophenolate mofetil, and steroids; and group 4, mammalian target of rapamycin inhibitors including everolimus, CNIs, mycophenolate mofetil, and steroids. The patient and graft survival rates were significantly higher in groups 3 and 4. The cumulative cancer incidence rate significantly increased with the use of more potent immunosuppressants, and the time to develop cancer was shorter. Only one patient in group 4 developed de novo cancer. Potent immunosuppressants might improve graft survival rate while inducing de novo cancer after kidney transplantation. Our data also suggest that everolimus might suppress cancer development after kidney transplantation.

Early colorectal cancer from “de novo” carcinogenesis with submucosal invasion: a case report and review of the literature

Background: Colorectal cancer (CRC) mostly develops through the traditional “adenoma-carcinoma sequence”, however there is a rare “de novo” carcinogenic pathway in which cancer originates from normal mucosa. Here, we report a case of early CRC caused by “de novo” carcinogenesis with submucosal invasion and conduct a literature review of this special type of CRC.Case presentation: A 66-year-old man underwent a screening colonoscopy that revealed a polyp-like lesion (type 0-IIa+IIc in the Paris classification) approximately 0.5 cm in diameter in the descending colon. The patient underwent endoscopic submucosal dissection (ESD); postoperatively, he was pathologically diagnosed with moderately differentiated adenocarcinoma without an adenomatous component from the “de novo” carcinogenic pathway, accompanied by submucosal invasion to a depth of 600 μm. There was no venous or lymphatic permeation, and the margins were negative. A year later, follow-up examinations did not reveal tumour recurrence.Conclusions: Early “de novo” cancer has a low incidence and a low discovery rate through endoscopy. In this case report, we provide informative details about the presentation of such cancers under endoscopy and further support for the aggressive malignant potential of early “de novo” cancer. The development of advanced CRC can be effectively prevented, and the prognosis of these patients can be improved with active early treatment.

De Novo Cancer Incidence after Cholecystectomy in Korean Population

Cancer development after cholecystectomy remains debatable. We estimated the major cancer incidence rates after cholecystectomy stratified by age and sex. Methods: The records of 408,769 subjects aged >20 years were extracted from the National Health Insurance database from 2008 to 2016. The risks of major cancers were compared between the cholecystectomy and general populations using standardised incidence ratios (SIR). Results: The overall cancer incidence was comparable between cholecystectomy patients and the general population. However, patients aged <65 years who underwent cholecystectomy had a higher cancer risk than those aged ≥65 years and the general population (SIR 2.62; 95% confidence interval [CI] 2.15–3.08; SIR 1.36, 95% CI 1.32–1.40; and SIR 0.90, 95% CI 0.87–0.92 in men and SIR 1.91; 95% CI 1.71–2.10; SIR 1.07; 95% CI 1.03–1.10; and SIR 0.90; 95% CI 0.87–0.94 in women aged 20–34, 35–64, and ≥65 years at cholecystectomy). Colorectal and liver cancer incidences after cholecystectomy were higher than those in the general population regardless of age group and sex (SIR, 1.55 for colorectal cancer in men and women; SIR, 1.25 and 1.51 for liver cancer in men and women, respectively). However, for other major cancers, the risk was higher in patients who underwent cholecystectomy at a younger age than in those who underwent cholecystectomy at an age ≥65 years. Conclusion: Patients with cholecystectomy, especially those undergoing cholecystectomy at a younger age, need preventive strategies based on the cancer type.

Cancer Development and Mortality Differences in Patients with Glomerulonephritis after Renal Biopsy: A Single Center Retrospective Cohort Study

Background: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. Methods: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 671 patients who are inappropriate for the analysis, 929 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents used during follow-up were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. Results: During a mean follow-up period of 52.4 (range: 1.0–166.7) months, 49 subjects (5.3%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.17 (95% confidence interval (CI): 5.3–9.51) relative to the general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model adjusted for confounding variables revealed that patients with a pathologic diagnosis of MN had an increased risk of cancer development, with a hazard ratio of 2.6 [95% CI: 1.32–5.30]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 5.95; 95% CI: 1.36–26.09, P=0.018) than those without cancer, but there was a non-significant difference in ESRD development. Conclusions: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

Spending for Advanced Cancer Diagnoses: Comparing Recurrent Versus De Novo Stage IV Disease

PURPOSE: Spending for patients with advanced cancer is substantial. Past efforts to characterize this spending usually have not included patients with recurrence (who may differ from those with de novo stage IV disease) or described which services drive spending. METHODS: Using SEER-Medicare data from 2008 to 2013, we identified patients with breast, colorectal, and lung cancer with either de novo stage IV or recurrent advanced cancer. Mean spending/patient/month (2012 US dollars) was estimated from 12 months before to 11 months after diagnosis for all services and by the type of service. We describe the absolute difference in mean monthly spending for de novo versus recurrent patients, and we estimate differences after controlling for type of advanced cancer, year of diagnosis, age, sex, comorbidity, and other factors. RESULTS: We identified 54,982 patients with advanced cancer. Before diagnosis, mean monthly spending was higher for recurrent patients (absolute difference: breast, $1,412; colorectal, $3,002; lung, $2,805; all P < .001), whereas after the diagnosis, it was higher for de novo patients (absolute difference: breast, $2,443; colorectal, $4,844; lung, $2,356; all P < .001). Spending differences were driven by inpatient, physician, and hospice services. Across the 2-year period around the advanced cancer diagnosis, adjusted mean monthly spending was higher for de novo versus recurrent patients (spending ratio: breast, 2.39 [95% CI, 2.05 to 2.77]; colorectal, 2.64 [95% CI, 2.31 to 3.01]; lung, 1.46 [95% CI, 1.30 to 1.65]). CONCLUSION: Spending for de novo cancer was greater than spending for recurrent advanced cancer. Understanding the patterns and drivers of spending is necessary to design alternative payment models and to improve value.

Cancer and mTOR inhibitors in kidney transplantation recipients

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.