NAD(P)H:quinone Oxidoreductase 1 Is Involved in AZ-1-induced Apoptotic Effects in Nasopharyngeal Carcinoma TW01 Cells.

BACKGROUND/AIM: Current NPC treatment methods have improved the 5-year survival rates of patients; however, some patients do not benefit from the treatments. Therefore, the existing treatment methods or new drugs must be developed to improve the patient's prognosis. NAD (P)H:quinone oxidoreductase 1 (NQO1), an electron reductase highly expressed in various cancers, can convert aziridinyl-substituted quinone-derived compound into an alkylating agent, resulting in cell apoptosis. Therefore, a di-aziridinyl-substituted quinone-derived compound, AZ-1, was designed previously. The present study investigated whether AZ-1 has anticancer activities in NPC cells and explored the underlying mechanism. MATERIALS AND METHODS: NPC-TW01 cells were used in the study, and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide, colony formation, terminal deoxynucleotidyl transferase dUTP nick end labeling, and immunoblotting assays were performed to assess the cell viability, cell survival, DNA fragmentation, and protein expression, respectively. RESULTS: The results show that AZ-1 significantly inhibited the viability and survival of NPC-TW01 cells. AZ-1 also induced the expression of cleaved PARP, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3, and triggered DNA fragmentation in NPC-TW01 cells. In addition, AZ-1 induced γH2AX expression, a DNA damage marker, in NPC-TW01 cells. Treatment with dicoumarol, an NQO1 activity inhibitor, not only reversed AZ-1-induced cell viability inhibition but also decreased AZ-1-induced expression of γH2AX, cleaved caspase-8, cleaved caspase-9, and cleaved caspase-3. CONCLUSION: NQO1 reverses AZ-1-triggered cell viability inhibition, DNA damage, and apoptosis. The findings of this study may provide a basis for the possible clinical application of AZ-1 in the treatment of NPC to improve the prognosis of patients with NPC.

The impact of COVID-19 pandemic on colorectal cancer patients: a single-center retrospective study.

BACKGROUND: Since December 2019, China has experienced a public health emergency from the coronavirus disease, which has become a pandemic and is impacting the care of cancer patients worldwide. This study evaluated the impact of the pandemic on colorectal cancer (CRC) patients at our center and aimed to share the lessons we learned with clinics currently experiencing this impact. METHODS: We retrospectively collected data on CRC patients admitted between January 1, 2020 and May 3, 2020; the control group comprised patients admitted between January 1, 2019 and May 3, 2019. RESULTS: During the pandemic, outpatient volumes decreased significantly, especially those of nonlocal and elderly patients, whereas the number of patients who received chemotherapy and surgery remained the same. During the pandemic, 710 CRC patients underwent curative resection. The proportion of patients who received laparoscopic surgeries was 49.4%, significantly higher than the 39.5% during the same period in 2019. The proportion of major complication during the pandemic was not significantly different from that of the control group. The mean hospital stay was significantly longer than that of the control group. CONCLUSIONS: CRC patients confirmed to be infection-free can receive routine treatment. Using online medical counseling and appropriate identification, treatment and follow-up can be effectively maintained. Adjuvant and palliative chemotherapy should not be discontinued. Endoscopic polypectomy, elective, palliative, and multidisciplinary surgeries can be postponed, while curative surgery should proceed as usual. For elderly CRC patients, endoscopic surgery and neoadjuvant radiotherapy are recommended.

Grade G2 Rectal Neuroendocrine Tumor Is Much More Invasive Compared With G1 Tumor.

BACKGROUND: To compare clinicopathologic feature of rectal neuroendocrine tumor (NET) grade G1 with G2 NET. METHODS: Six hundred-one cases of rectal G1 and G2 NETs diagnosed in our center were analyzed. RESULTS: Of 601 cases of rectal NET, 515 cases were with grade G1 and 86 cases were with grade G2. Median tumor size was 0.7 cm. Compared with G1 NET, G2 tumors were with significantly larger tumor size (0.8 vs 2.2 cm, p < 0.001), less percentages of patients with tumors confined to submucosa (92.6 vs 42.8%, p < 0.001), more frequent presence of microvascular invasion (MVI) (3.6 vs 16.9%, p < 0.001) or peri-neural invasion (PNI) (2.0 vs 24.1%, p < 0.001). Incidence of lymph node and distant metastasis was 5.2 and 2.1% in G1 NET compared with 44.2 and 31.4% in G2 tumor, respectively (p < 0.001). For tumors sized 1-2 cm and confined to submucosa, incidence of lymph node metastasis was 6.1% for G1 NET compared with 21.1% for G2 NET. Status of MVI/PNI was predictive of lymph node metastasis for G2 tumor rather than G1 NET in this subgroup. CONCLUSIONS: Rectal G2 NET was much more invasive with significantly elevated prevalence of lymph node metastasis compared with G1 tumor.

Comparison of long-term outcomes between Lynch sydrome and sporadic colorectal cancer: a propensity score matching analysis.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. Comparison of prognosis between LS and sporadic CRC (SCRC) were rare, with conflicting results. This study aimed to compare the long-term outcomes between patients with LS and SCRC. METHODS: Between June 2008 and September 2018, a total of 47 patients were diagnosed with LS by genetic testing at Fudan University Shanghai Cancer Center. A 1:2 propensity score matching was performed to obtain homogeneous cohorts from SCRC group. Thereafter, 94 SCRC patients were enrolled as control group. All of enrolled patients received curative surgeries and standardized postoperative monitoring. The long-term survival rates between the two groups were compared, and the prognostic factors were also analyzed. RESULTS: The 5-year overall survival rate of LS group was 97.6%, which was significantly higher than of 82.6% for SCRC group (χ2 = 4.745, p = 0.029). The 5-year recurrence free survival rate showed no significant differences between the two groups (78.0% for LS group vs. 70.6% for SCRC patients; χ2 = 1.260, p = 0.262). The 5-year tumor free survival rates in LS group was 62.1% for LS patients, which were significantly lower than of 70.6% for SCRC group (χ2 = 4.258, p = 0.039). Subgroup analysis of recurrent patients show that the LS group had longer overall survival than the SCRC group after combined chemotherapy. By multivariate analysis, we found that tumor recurrence of primary CRC [Risk ratio (95% (confidence interval): 48.917(9.866-242.539); p < 0.001] and late TNM staging [Risk ratio (95% (confidence interval): 2.968(1.478-5.964); p = 0.002] were independent risk factors for OS. CONCLUSION: LS patients have better long-term survival prognosis than SCRC patients, even though the two groups have statistically comparable recurrence free survival. Combined chemotherapy is an effective treatment for LS patients who developed primary CRC recurrence. Standardized postoperative monitoring for LS patients may enable detection of metachronous tumors at earlier stages, which was a guarantee of a favorable prognosis despite lower tumor free survival.

Clinicopathologic features and prognostic value of KRAS, NRAS and BRAF mutations and DNA mismatch repair status: A single-center retrospective study of 1,834 Chinese patients with Stage I-IV colorectal cancer.

Mutations of KRAS, NRAS, BRAF and DNA mismatch repair (MMR) status have become an important part of the assessment of patients with colorectal cancer (CRC), while respective clinicopathologic features and prognostic significance in specific stages and related detection strategies remain unclear. We retrospectively analyzed clinicopathologic features and prognosis of 1,834 patients with Stage I-IV colorectal adenocarcinoma. Mutations in KRAS, NRAS and BRAF and DNA MMR status were determined. The mutation rates of KRAS, NRAS and BRAF were 46.4, 3.2 and 3.5%, respectively, and the mismatch repair gene deletion (dMMR) rate was 5.6%. In a multivariate analysis, female, advanced age, tumor type histology, mucinous carcinoma and positive tumor deposits were associated with a high KRAS mutation rate. A high BRAF mutation rate was associated with female, poor differentiation, lymphovascular invasion and positive tumor deposits. Factors associated with high dMMR rates included low age, large tumor size, poor differentiation, Stages I-III. Tumor site was independently associated with KRAS mutation, BRAF mutation and dMMR. KRAS and BRAF mutations were independent risk factors for shorter overall survival (OS) in Stage IV tumors but not in Stage I-III tumors. NRAS mutation was an independent risk factor for shorter OS in Stage I-II tumors. dMMR was independently associated with longer OS in Stage III tumors.

A negative-doughnut distal resection margin less than 5 mm does not affect prognosis in rectal cancer.

AIM: Many issues relating to the distal margin of anterior resection of the rectum still exist. We aimed to investigate whether negative distal resection margin (DRM) and positive DRM in the main specimen with negative doughnut has equivalent prognosis in patients with rectal cancer. METHODS: We included 287 patients with rectal cancer, including 69 cases with positive margins and 218 cases with negative margins, all of whom underwent regular follow-up. Survival rate was calculated using Kaplan-Meier survival analysis, while the log-rank test was used to determine statistical difference. Prognostic factors were found using the Cox regression model. RESULTS: There was no significant difference in clinicopathological features between the two groups with the exception of tumor location. Positive findings in the DRM with negative findings in the doughnut resection do not affect the overall survival, local recurrence, or distant metastasis. Factors relating to resection margin, such as the length of resection, negative, or positive findings, were not found to be prognostic. CONCLUSION: Given postoperative pathology results with positive DRM but negative findings in the doughnut resection, a second surgery was not necessary. Instead, adjuvant radiochemotherapy and close follow-up will suffice.

The Prognostic Value of Preoperative Serum CEA and CA19-9 Values in Stage I-III Colorectal Cancer.

BACKGROUND/AIMS: There is disagreement about the prognostic value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) in patients who have stage I-III colorectal cancer. Therefore, we investigated the relationship between preoperative serum CEA and CA19-9 levels and clinical outcome in patients with this disease. METHODOLOGY: The study included 724 patients who had received radical resection for stage I-III colorectal cancer in Fudan University Shanghai Cancer Center. We retrospectively investigated the relationship between patients' characteristics and survival, using univariate and multivariate analyses. In multivariate analysis, factors found significant in the univariate analysis were compared with patients' outcomes. RESULTS: In univariate analysis, differentiation (P < 0.001), depth of invasion (P < 0.001), number of lymph node metastases (P < 0.001), and elevated levels of CEA (P < 0.001) and CA19-9 (P < 0.001) were closely correlated with patients' survival. In multivariate analysis, the number of lymph node metastases (P < 0.001), preoperative CA19-9 (P = 0.015) and CEA (P = 0.028) values, differentiation (p = 0.040) and depth of invasion (p = 0.039) were independent prognostic factors for survival. CONCLUSIONS: Preoperative CA19-9 and CEA have independent prognostic values in stage I-III colorectal cancer. Elevation of and both CEA and CA19-9 values predicted the worst outcome.

[Prospective study on the use of nickel-titanium temperature-dependent memory-shape device (CAR27) for anastomosis after colorectal surgery].

OBJECTIVE: To prospectively evaluate the safety and efficacy of nickel- titanium temperature-dependent memory-shape device(CAR27) for colorectal anastomosis. METHODS: Sixty colorectal cancer patients were randomly divided into two groups and received colorectal anastomosis with CAR27 or traditional stapling device. Complications, bowel function return, and the extrusion of anastomosis ring were prospectively monitored. RESULTS: Both CAR27 and stapler group had one case of anastomotic leakage. Other complications such as stricture or obstruction were not found. Time for anastomosis of the two groups were (10.1±1.2) minutes and (11.2±2.1) minutes respectively. Time to first flatus was(3.2±1.2) days and (3.5±1.4) days respectively. Time to food intake resumption was (4.0±1.4) days and (4.3±1.3) days respectively. The differences above between the two groups were not statistically significant(P>0.05). The ring was expelled with stool within 7-16 days. The two groups were similar in operative time and the return of bowel function. CONCLUSION: CAR27 is safe and simple for colorectal anastomosis.