Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study

Abstract

Background Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033.

Impact of Dietary Patterns on H. pylori Infection and the Modulation of Microbiota to Counteract Its Effect. A Narrative Review

“…Helicobacter pylori , considered the main bacterium responsible for gastric disease and long-term complications [ 1 ], is a Gram-negative bacterium that colonizes the stomach [ 2 ]. Infection with H. pylori is very prevalent around the world.…”

“…It is estimated that 48.6% of the global adult population is affected [ 3 ]. All patients infected with H. pylori suffer from inflammation of the gastric mucosa (chronic gastritis), while, in some cases, the disease becomes more developed (e.g., peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma) [ 2 , 4 ]. In fact, H. pylori is responsible for 90–95% of duodenal ulcers and 70–85% of gastric ulcers [ 5 ].…”

“…Infection during early childhood is associated with an augmented risk of coeliac disease [ 14 ]. Findings from epidemiologic studies point to H. pylori as an initiator of gastric cancer [ 2 , 15 ]. Moreover, this bacterium has been included as a class I carcinogen of gastric cancer development in the World Health Organization’s International Agency for Research on Cancer since 1994 [ 16 ].…”

Cisplatin for cancer therapy and overcoming chemoresistance

“…The long-life expectancy achieved by cisplatin-based treatment in TC survivors can be compromised by long-term adverse effects of platinum compound therapy that persists in blood plasma and urine which could give rise to second cancers [ 114 ]. TC survivors are thus at high risk of developing gastrointestinal (GI) cancers, and specifically colorectal carcinoma as a secondary complication of cisplatin treatment, although the originating mechanisms are not understood [ 114 ]. A dose-response relationship in cisplatin therapy and the emergence of second GI tract malignancies have been reported extending up to 35 years after recovery from TC [ 114 ].…”

“…TC survivors are thus at high risk of developing gastrointestinal (GI) cancers, and specifically colorectal carcinoma as a secondary complication of cisplatin treatment, although the originating mechanisms are not understood [ 114 ]. A dose-response relationship in cisplatin therapy and the emergence of second GI tract malignancies have been reported extending up to 35 years after recovery from TC [ 114 ]. A multicentre study of TC survivors treated with cisplatin-based regimens proposed that colorectal cancer surveillance with faecal immunochemical testing after 8 years from recovery would safeguard against the development of GI tract-malignancies in TC patients that are in remission [ 114 ].…”