The influence of neoadjuvant chemoradiotherapy combined with lateral lymph nodes dissection or not on the local recurrence of low to intermediate-stage II/III rectal cancer.

BACKGROUND: Currently, the treatment options for stage II/III rectal cancer with preoperative lateral lymph nodes (LLN) enlargement are highly controversial between East and West, and the indications for diagnosing suspiciously positive enlarged LLN are inconsistent both nationally and internationally. Oriental scholars (especially Japanese) consider the LLN as a regional disease, they consider that prophylactic lateral lymph nodes dissection (LLND), regardless of whether the LLN is enlarged or not, is considered necessary if the tumor is found beneath the peritoneal reflex and invades the muscle layer. Western scholars regard LLN as distant metastases, recommending neoadjuvant chemoradiotherapy (nCRT) in conjunction with total rectal mesenteric resection (TME). In recent years, it has been found that neither of the two standard treatment regimens, East and West, significantly improved local control of tumors in patients with LLN enlargement. In contrast, nCRT combined with LLND significantly lowers the local recurrence (LR) rate. It has also been suggested that combination therapy regimens do not improve patient prognosis but increase treatment-related complications. Therefore, the suitable therapeutic option for rectal cancer with an enlarged LLN needs to be further explored. AIM: Exploring appropriate treatment options for low to intermediate-stage II/III rectal cancer with LLN enlargement, as well as risk variables that may affect the LR in these patients with LLN enlarged. METHODS AND PATIENTS: In this research, we retrospectively analyzed 110 patients with locally advanced mid-low (low boundary of tumor is no more than 10 cm from the anus) rectal cancer who were treated at Harbin Medical University Cancer Hospital arranged from 2017.1 to 2020.6. These patients had received nCRT and TME, and their initial rectal nuclear magnetic resonance imaging (MRI) revealed an enlarged LLN (short axis of LLN, SA ≥ 5 mm). Of these, 40 patients underwent LLND, thus, 110 patients were grouped into two groups: nCRT+TME (LLND-, n = 70) and nCRT+TME + LLND (LLND+, n = 40), and their 3 years prognoses were compared. RESULTS: After a median follow-up of 49.0 months, the 3-year LR rate of the LLND- group was notably greater than the LLND+ group (22.8% vs. 7.5%, p = 0.04). However, there was no noteworthy difference in the 3-year progression-free survival (PFS, 70.5% vs. 77.5%, p > 0.05) rate or distant metastasis (DM) rate (20.0% vs. 17.5%, p > 0.05). Additionally, the LLND+ group experienced significantly more postoperative complications than the LLND- group (15.0% vs. 4.2%, p = 0.05). Subgroups analysis for the LLND- group revealed that patients with LLN short axis regression (ΔSA) > 35.9% after nCRT had significantly lower 3-year LR rate than patients with ΔSA ≤ 35.9% (9.1% vs. 35.1%, p = 0.01). Patients in the LLND- group with ΔSA > 35.9%, however, had comparable 3-year LR rate and DM rates to those in the LLND+ group. CONCLUSION: LLN is an independent indicator for prognosis among people with low to intermediate-stage II/III malignant rectal tumors. Patients with poor SA regression (ΔSA ≤ 35.9%) after nCRT have a greater risk of positive LLN and a more substantial LR, and nCRT combined with LLND reduced the LR rate significantly, but considerably prolonged operative time, surgical bleeding, and postoperative complications. Patients with better SA regression (ΔSA > 35.9%), however, have a lower possibility of LR and might not need LLN clearance, in these cases, nCRT+TME is advised.

Identification of differentially expressed genes associated with the enhancement of X-ray susceptibility by RITA in a hypopharyngeal squamous cell carcinoma cell line (FaDu).

BACKGROUND: Next generation sequencing and bio-informatic analyses were conducted to investigate the mechanism of reactivation of p53 and induction of tumor cell apoptosis (RITA)-enhancing X-ray susceptibility in FaDu cells. MATERIALS AND METHODS: The cDNA was isolated from FaDu cells treated with 0 X-ray, 8 Gy X-ray, or 8 Gy X-ray + RITA. Then, cDNA libraries were created and sequenced using next generation sequencing, and each assay was repeated twice. Subsequently, differentially expressed genes (DEGs) were identified using Cuffdiff in Cufflinks and their functions were predicted by pathway enrichment analyses. Genes that were constantly up- or down-regulated in 8 Gy X-ray-treated FaDu cells and 8 Gy X-ray + RITA-treated FaDu cells were obtained as RITA genes. Afterward, the protein-protein interaction (PPI) relationships were obtained from the STRING database and a PPI network was constructed using Cytoscape. Furthermore, ClueGO was used for pathway enrichment analysis of genes in the PPI network. RESULTS: Total 2,040 and 297 DEGs were identified in FaDu cells treated with 8 Gy X-ray or 8 Gy X-ray + RITA, respectively. PARP3 and NEIL1 were enriched in base excision repair, and CDK1 was enriched in p53 signaling pathway. RFC2 and EZH2 were identified as RITA genes. In the PPI network, many interaction relationships were identified (e.g., RFC2-CDK1, EZH2-CDK1 and PARP3-EZH2). ClueGO analysis showed that RFC2 and EZH2 were related to cell cycle. CONCLUSIONS: RFC2, EZH2, CDK1, PARP3 and NEIL1 may be associated, and together enhance the susceptibility of FaDu cells treated with RITA to the deleterious effects of X-ray.

Rare Metastatic Embryonal Carcinoma Resembling Lymphoma: A Case Report

BACKGROUND: Embryonal carcinoma is a rare tissue type in germ cell tumors. According to our literature review, metastatic embryonal carcinoma misdiagnosed as lymphoma because of its high similarity to lymphoma is extremely rare and has not been reported yet. CASE PRESENTATION: A 46-year-old middle adulthood male presented with unexplained fever, night sweats, abdominal distension for 3 months, and weight loss of around 7kg during almost 6 months, which is extremely similar to lymphoma from the clinical features and imaging examinations. After a clear diagnosis, the case not only obtained the opportunity of surgery but was also exempted from radiotherapy. The treatment effect was good. We report a case of rare metastatic embryonal carcinoma, which can provide insight into the diagnosis and treatment of embryonal carcinoma. CONCLUSION: Metastatic embryonal carcinoma of abdominal lymph nodes can be highly similar to lymphoma; the diagnosis can only be based on clinical manifestations and imaging examination but also combined with patient history, tumor markers and biochemical examination. However, the final diagnosis depends on pathological biopsy.

Association studies of ERCC1 polymorphisms with lung cancer susceptibility: a systematic review and meta-analysis.

BACKGROUND: Excision repair cross-complimentary group 1 (ERCC1) is an essential component of the nucleotide excision repair system that is responsible for repairing damaged DNA. Functional genetic variations in the ERCC1 gene may alter DNA repair capacity and modulate cancer risk. The putative roles of ERCC1 gene polymorphisms in lung cancer susceptibility have been widely investigated. However, the results remain controversial. OBJECTIVES: An updated meta-analysis was conducted to explore whether lung cancer risk could be attributed to the following ERCC1 polymorphisms: rs11615 (T>C), rs3212986 (C>A), rs3212961 (A>C), rs3212948 (G>C), rs2298881 (C>A). METHODS: Several major databases (MEDLINE, EMBASE and Scopus) and the Chinese Biomedical database were searched for eligible studies. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to measure the strength of associations. RESULTS: Sixteen studies with 10,106 cases and 13,238 controls were included in this meta-analysis. Pooled ORs from 11 eligible studies (8,215 cases vs. 11,402 controls) suggested a significant association of ERCC1 rs11615 with increased risk for lung cancer (homozygous: CC versus TT, OR = 1.24, 95% CI: 1.04-1.48, P = 0.02). However, such an association was disproportionately driven by a single study. Removal of that study led to null association. Moreover, initial analyses suggested that ERCC1 rs11615 exerts a more profound effect on the susceptibility of non-smokers to lung cancer than that of smokers. Moreover, no statistically significant association was found between remaining ERCC1 polymorphisms of interest and lung cancer risk, except for rs3212948 variation (heterozygous: CG vs.GG, OR = 0.78, 95% CI: 0.67-0.90, P = 0.001; dominant: CG/CC vs.GG, OR = 0.79, 95% CI: 0.69-0.91, P = 0.001). CONCLUSION: Overall, this meta-analysis suggests that ERCC1 rs3212948 G>C, but not others, is a lung cancer risk-associated polymorphism. Carefully designed studies with large sample size involving different ethnicity, smoking status, and cancer types are needed to validate these findings.