Introduction

The role of capsule endoscopy (CE) for the surveillance of small-bowel (SB) cancer in asymptomatic Lynch syndrome (LS) patients has been questioned in recent years, with contradicting results. The overall lifetime risk of SB cancer in this population is around 4-5%, with an age-dependent pattern [1]. Besides, recent data highlight that, depending on the affected path_MMR gene, the frequencies of tumors other than colorectal cancer vary and that affected patients develop subsequent cancers later in life. The aim of this meta-analysis is to evaluate the diagnostic yield (DY) of CE as a screening tool in asymptomatic LS patients.

Aims & Methods

A systematic literature search was conducted in Pubmed, Embase and Web of Science to identify all studies evaluating SB cancer surveillance with CE in asymptomatic LS patients. The primary outcome was the evaluation of the DY of CE in consecutive screening rounds, for both CE-identified pathology and histologically-confirmed pathology (i.e., adenoma or adenocarcinoma). Pooled estimates of DY were calculated from random effects models.

Results

Five studies including 583 patients were identified for data extraction and statistical analysis [2-6] [Table]. The estimated pooled DY for CE-identified pathology was 8% in the first screening round (95% confidence interval [CI] 4-12%) and 6% in the second (95% CI 2-10%). Limiting the analysis to histologically-confirmed pathology, the pooled DY of the second-round screening dropped to 0% (95% CI 0-6%). The time interval between screening rounds was approximately 2 years.
Adenomas were detected in 8 patients (4 males) with a median age of 47.5 years (interquartile range [IQR] 19), while adenocarcinomas were diagnosed in 8 patients (5 males) with a median age of 62.5 years (IQR 17.25). MLH1 was the most involved path_MMR pathogenic variant (9 out of 16 patients), followed by MSH2 and MSH6 (5 and 2 patients, respectively). No adenocarcinomas were detected in MSH6 carriers, as only adenomas were found in 2 patients, with a considerably higher median age than MSH2 and MLH1 adenoma carriers (70.5 years versus 43.5 and 45). No predominance was observed according to the anatomical location (duodenum, n=6; jejunum, n=6; ileum, n=4).

Conclusion

The detection of adenocarcinoma appeared to have a 15-year delay compared to adenomas, supporting a rather slow adenoma to carcinoma transition.
A surveillance strategy starting from the age of 50, with a time interval between procedures lengthened to at least 5 years (instead of 2) could likely be more effective in reducing the burden of advanced disease, both in terms of cost-effectiveness and efficacy. Prospective data may reveal whether a potential SB surveillance might benefit from gene-associated differences in cancer risk, similar to the recent de-escalation of CRC screening recommendations in MSH6 and PMS2 carriers [7].
In conclusion, although the DY of CE is high in detecting SB lesions in LS, the low number of positive examinations eventually resulted in an even lower number of true-positive patients, with a pooled yield proximate to 0%.
The results of this study confirm that SB cancer surveillance with CE with a 2-year interval in asymptomatic LS individuals is not an effective screening strategy.

References

[1] Dominguez-Valentin M, Sampson JR, Seppälä TT, et al. Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database. Genet Med 2020;22:15–25.
[2] Saurin J-C, Pilleul F, Soussan EB, et al. Small-bowel capsule endoscopy diagnoses early and advanced neoplasms in asymptomatic patients with Lynch syndrome. Endoscopy 2010;42:1057–62.
[3] Haanstra JF, Al-Toma A, Dekker E, et al. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy. Gut 2015;64:1578–83.
[4] Haanstra JF, Al-Toma A, Dekker E, et al. Incidence of small bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy. Endosc Int Open 2017;5:E622–E626.
[5] Perrod G, Samaha E, Perez-Cuadrado-Robles E, et al. Effectiveness of a dedicated small bowel neoplasia screening program by capsule endoscopy in Lynch syndrome: 5 years results from a tertiary care center. Ther Adv Gastroenterol 2020;13:1756284820934314.
[6] DeJesse J, Vajravelu RK, Dudzik C, et al. Uptake and outcomes of small intestinal and urinary tract cancer surveillance in Lynch syndrome. World J Clin Oncol 2021;12:1023–36.
[7] Peltomäki P, Nyström M, Mecklin J-P, et al. Lynch syndrome genetics and clinical implications. Gastroenterology 2023 Jan 24;S0016-5085(23)00050-1. doi:10.1053/j.gastro.2022.08.058 [Online ahead of print]

Introduction

Hepatocellular carcinoma (HCC) is the leading cause of death in patients with cirrhosis. Indeed, several risk stratification scores have been developed to anticipate early detection in order to better codify their management, including the Toronto Hepatocellular Carcinoma Risk Index (THRI). It is a simple and validated tool that has been developed to predict the risk of HCC in patients with cirrhosis and is mainly based on the following parameters: etiology, age, sex and platelet count.
The objective of this study was to evaluate the reliability of the THRI score in predicting the occurrence of hepatocellular carcinoma.

Aims & Methods

We conducted a monocentric retrospective study collecting all cirrhotic patients over an 8-year period [2008-2015]. Clinico-biological data, disease severity, and long-term outcomes were collected.
THRI was calculated for all patients, and were classified according to HCC risk into three levels : low HCC risk (<120), intermediate HCC risk (between 120 and 240), and those with high HCC risk (>240).
A statistical study using the SPSS tool was carried out. The performance of this score was evaluated with the area under the receiver operating characteristics curve (AUROC).

Results

We included 120 cirrhotic patients with an M/F sex ratio equal to 0.5. The mean age was 57 years [14-85]. The most frequent aetiology of cirrhosis were viral C (49%) and viral B (31%). The mean overall survival was approximately 6 years after diagnosis.
Twenty-five patients developed HCC during follow-up (20.8%). Patients who developed HCC had a higher THRI score than those who did not develop HCC : 264.8 ± 48.6 versus 232.3 ± 64.8, respectively with p-value = 0.008
Patients with a low risk of HCC were 5 (4.2%), none of whom had developed HCC. Fifty-eight patients (48.3%) were at intermediate risk, 12% of them (N=7) had developed HCC. The remaining 57 patients (47.5%) were at a high risk and 31.6% of them (N=18) developed HCC during their follow-up.
The AUROC for the THRI to predict HCC was 0.649 ([95% CI 0.533–0.765]. The cutoff THRI value in predicting the occurrence of HCC was 235.5 with a sensitivity of 72% and a specificity of 50%.

Conclusion

According to our study, the THRI score appears to be an effective tool for predicting the occurrence of HCC in cirrhotic patients. Its good sensitivity allows to identify the high-risk HCC population for early screening.