Identification of DNA Repair-related Genes as Biomarkers Reflecting MSI, TMB, and TIL in Colorectal Cancer.

BACKGROUND/AIM: There are no established biomarkers for immune checkpoint inhibitors (ICI) in colorectal cancer (CRC) with microsatellite stability (MSS) or proficient mismatch repair (pMMR). Therefore, this study aimed to identify biomarkers for ICI benefit in patients with pMMR by analyzing the down-regulated DNA repair-related genes involved in highly immunogenic and immune responses, and comparing their expression levels and clinical features. MATERIALS AND METHODS: Mismatch repair (MMR), tumor-infiltrating lymphocytes (TIL), and tumor mutation burden (TMB) were evaluated in 13 CRC cases and mRNA expression levels of 95 DNA repair-related genes were measured. DNA repair-related genes with reduced mRNA expression in the high immunogenicity and high immune response groups were identified. Then, the mRNA expression levels of the identified DNA repair-related genes were measured in 135 patients with CRC. Hierarchical cluster analysis was performed using the mRNA expression levels to compare the clinicopathological characteristics of each cluster. RESULTS: ATR, LIG4, and RAD52 mRNA levels were significantly down-regulated in the high immunogenicity group. GADD45B, SMUG1, and XRCC6 mRNA levels were significantly down-regulated in the high immune response group. Cases in the cluster with reduced mRNA expression of the six genes were pMMR cases. CD8 mRNA expression level was higher in this cluster than in the other clusters. CONCLUSION: Decreased mRNA expression levels of ATR, LIG4, RAD52, GADD45B, SMUG1, and XRCC6 genes were associated with high cytotoxic T cell and TMB levels, suggesting that these genes could serve as biomarkers for ICI efficacy in pMMR cases.

Safety of Early Bevacizumab Administration after Central Venous Port Placement for Patients with Colorectal Cancer.

Bevacizumab (BEV) requires an adequate withdrawal period to avoid BEV-related complications during major surgery. However, the safety of BEV administration immediately after surgical placement of the central venous (CV) port, a minor surgery, is still unclear. This study aimed to investigate whether BEV is safe when administered early after CV port placement. We retrospectively evaluated 184 patients with advanced colorectal cancer (CRC) treated with a BEV-containing regimen and divided them into two groups according to the interval between CV port implantation and chemotherapy initiation, with the early administration group being ≤7 days and late administration group being >7 days. Complications were then compared between the two groups. The early-administration group was significantly older and had a higher rate of colon cancer than the late-administration group. Overall, 24 (13%) patients developed CV port-related complications. Male sex was a risk factor for complications (odds ratio [OR], 3.154; 95% CI, 1.19-8.36). The two groups showed no significant difference in the frequency of complications (p = 0.84) or patient characteristics (after the inverse probability of treatment weighting, p = 0.537). In conclusion, the frequency of complications is not affected by the timing of BEV initiation after CV port implantation. Thus, early BEV administration after CV port placement is safe.

Nontraumatic perforation of the small intestine caused by true primary enteroliths associated with radiation enteritis: a case report.

BACKGROUND: True primary enterolithiasis is an uncommon condition, and nontraumatic perforation of the small intestine (NTPSI) is also an unusual entity. Therefore, NTPSI due to true primary enteroliths is an exceptionally rare complication. Moreover, enterolithiasis and radiation enteritis are also unique combinations. Herein, we present an exceedingly rare case of NTPSI induced by multiple true primary enteroliths associated with radiation enteritis. CASE PRESENTATION: A 92-year-old woman with acute abdominal pain was transferred to our hospital because a computed tomography (CT) scan performed by her family doctor revealed free air and fluid collection within her abdomen. Our initial diagnosis was upper gastrointestinal perforation, and we selected nonoperative management (NOM) with adnominal drainage. Although her general condition was stable, jejunal juice was drained continuously. Given that the CT performed 10 days after onset demonstrated perforation of the small intestine and adjacent concretion, we performed an emergency partial resection of the small intestine and jejunostomy. The resected bowel was 1 m in length and had many strictures that contained multiple enteroliths in their proximal lumens. The patient's postoperative course was uneventful. The enteroliths were composed of deoxycholic acid (DCA). She was diagnosed with peritonitis due to NTPSI derived from multiple true primary enteroliths associated with radiation enteritis, as she had previously undergone hysterectomy and subsequent internal radiation therapy. CONCLUSIONS: Clinicians should consider the rare entity of true primary enteroliths associated with radiation enteritis in NTPSI cases with unknown etiologies.