Integrated profiling identifies DXS253E as a potential prognostic marker in colorectal cancer.

BACKGROUND: Increasing evidence suggests that DXS253E is critical for cancer development and progression, but the function and potential mechanism of DXS253E in colorectal cancer (CRC) remain largely unknown. In this study, we evaluated the clinical significance and explored the underlying mechanism of DXS253E in CRC. METHODS: DXS253E expression in cancer tissues was investigated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The Kaplan-Meier plot was used to assess the prognosis of DXS253E. The cBioPortal, MethSurv, and Tumor Immune Estimation Resource (TIMER) databases were employed to analyze the mutation profile, methylation, and immune infiltration associated with DXS253E. The biological functions of DXS253E in CRC cells were determined by CCK-8 assay, plate cloning assay, Transwell assay, flow cytometry, lactate assay, western blot, and qRT-PCR. RESULTS: DXS253E was upregulated in CRC tissues and high DXS253E expression levels were correlated with poor survival in CRC patients. Our bioinformatics analyses showed that high DXS253E gene methylation levels were associated with the favorable prognosis of CRC patients. Furthermore, DXS253E levels were linked to the expression levels of several immunomodulatory genes and an abundance of immune cells. Mechanistically, the overexpression of DXS253E enhanced proliferation, migration, invasion, and the aerobic glycolysis of CRC cells through the AKT/mTOR pathway. CONCLUSIONS: We demonstrated that DXS253E functions as a potential role in CRC progression and may serve as an indicator of outcomes and a therapeutic target for regulating the AKT/mTOR pathway in CRC.

Risk factors and clinical significance of lower perigastric lymph node metastases in Siewert type II and III esophagogastric junction adenocarcinoma: a retrospective cohort study.

BACKGROUND: No consensus has been concluded with regarding to the scope of lymph node (LN) dissection for Siewert type II and III adenocarcinoma of the esophagogastric junction (AEG). This study aimed to explore risk factors for lower perigastric LN (LPLN) metastases (including no. 4d, 5, 6, and 12a LN stations) and analyze the indications for LPLN dissection. METHODS: In total, 302 consecutive patients with Siewert type II and III AEG who underwent total gastrectomy (TG) were enrolled. The logistic regression model was used to perform uni- and multivariate analyses of risk factors for LPLN metastases. Kaplan-Meier curves were used for survival analysis, and log-rank tests were used for group comparisons. Basing on the guidelines of Japanese Gastric Cancer Association, the LN metastases (LNM) as well as the efficiency index (EI) of each LN station was further evaluated. RESULTS: The independent risk factors for LPLN metastases in patients with Siewert type II and III AEG were distance from the esophagogastric junction (EGJ) to the distal end of the tumor (> 4.0 cm), preoperative carcinoembryonic antigen (CEA) ( +), pT4 stage, and HER-2 ( +). LPLN metastases was an independent risk factor for overall survival following TG. The LNM and EI of LPLN were 8.6% and 2.31%, respectively. The LNM of LPLN > 10% under the stratification of the distance from the EGJ to the distal end of the tumor (> 4.0 cm), pT4, preoperative CEA ( +), and HER-2 ( +) exhibited EI values of 3.55%, 2.09%, 2.51%, and 3.64%, respectively. CONCLUSIONS: LPLN metastases was a malignant factor for the prognosis of patients with Siewert type II and III AEG. For patients with preoperative CEA ( +), pT4 stage, HER-2 ( +), and the distance from the EGJ to the distal end of the tumor (> 4.0 cm), TG with LPLN dissection is prioritized for clinical recommendation.

Long-term outcomes of laparoscopic versus open distal gastrectomy for patients with advanced gastric cancer in North China: a multicenter randomized controlled trial.

BACKGROUND: Laparoscopic distal gastrectomy (LDG) has become a common procedure for treating advanced gastric cancer (AGC) in China. However, there is uncertainty regarding its oncological outcomes compared to open distal gastrectomy (ODG). This study aims to compare the 3-year disease-free survival (DFS) rates among patients who underwent surgery for AGC in northern China. METHODS: A multicenter, non-inferiority, open-label, parallel, randomized clinical trial was conducted to evaluate patients with AGC who were eligible for distal gastrectomy at five tertiary hospitals in North China. In this trial, patients were randomly assigned preoperatively to receive either LDG or ODG in a 1:1 allocation ratio. The primary endpoint was postoperative morbidity and mortality within 30 days and the secondary endpoint was the 3-year DFS rate. This trial has been registered at ClinicalTrials.gov (Identifier: NCT02464215). RESULTS: A total of 446 patients were randomly allocated to LDG (n = 223) or ODG group (n = 223) between March 2014 and August 2017. After screening, a total of 214 patients underwent the open surgical approach, while 216 patients underwent laparoscopic surgery. The 3-year DFS rate was 85.9% for the LDG group and 84.72% for the ODG group, with no significant statistical difference (Hazard ratio 1.12; 95% CI 0.68-1.84, P = 0.65). Body mass index (BMI) < 25 kg/m2, advanced pathologic T4, and pathologic N2-3 category were confirmed as independent risk factors for DFS in the Cox regression. CONCLUSIONS: In comparison to ODG, LDG with D2 lymphadenectomy yielded similar outcomes in terms of 3-year DFS rates among patients diagnosed with AGC.

The safety and short-term effect of mixed approach in laparoscopic right hemicolectomy for right colon cancer compared with middle approach: a retrospective study.

PURPOSE: To investigate whether the mixed approach is a safe and advantageous way to operate laparoscopic right hemicolectomy. METHODS: A retrospective study was performed on 316 patients who underwent laparoscopic right hemicolectomy in our center. They were assigned to the middle approach group (n = 158) and the mixed approach group (n = 158) according to the surgical approaches. The baseline data like gender、age and body mass index as well as the intraoperative and postoperative conditions including operation time, blood loss, postoperative hospital stay and complications were analyzed. RESULTS: There were no significant differences in age, sex, BMI, ASA grade and tumor characteristics between the two groups. Compared with the middle approach group, the mixed approach group was significantly lower in terms of operation time (217.61 min vs 154.31 min, p < 0.001), intraoperative blood loss (73.8 ml vs 37.97 ml, p < 0.001) and postoperative drainage volume. There was no significant difference in the postoperative complications like postoperative anastomotic leakage, postoperative infection and postoperative intestinal obstruction. CONCLUSIONS: Compared with the middle approach, the mixed approach is a safe and advantageous way that can significantly shorten the operation time, reduce intraoperative bleeding and postoperative drainage volume, and does not prolong the length of hospital stay or increase the morbidity postoperative complications.

The validity of neoadjuvant chemotherapy with paclitaxel plus S-1 is not inferior to that of SOX regimen for locally advanced gastric cancer: an observational study.

BACKGROUND: Paclitaxel plus S-1(PTXS) has shown definite efficacy for advanced gastric cancer. However, the efficacy and safety of this regimen in neoadjuvant setting for locally advanced gastric cancer (LAGC) are unclear. This study aimed to compare the efficacy of neoadjuvant chemotherapy (NAC) PTXS and oxaliplatin plus S-1 (SOX) regime for patients with LAGC. METHODS: A total of 103 patients with LAGC (cT3/4NanyM0/x) who were treated with three cycles of neoadjuvant SOX regimen (n = 77) or PTXS regimen (n = 26) between 2011 and 2017 were enrolled in this study. NAC-related clinical response, pathological response, postoperative complication, and overall survival were analyzed between the groups. RESULTS: The baseline data did not differ significantly between both groups. After NAC, the disease control rate of the SOX group (94.8%) was comparable with that of the PTXS group (92.3%) (p = 0.641). Twenty-three cases (29.9%) in the SOX group and 10 cases (38.5%) in the PTX group got the descending stage with no statistical difference (p = 0.417). No significant differences were observed in the overall pathological response rate and the overall postoperative complication rate between the two groups (p > 0.05). There were also no differences between groups in terms of 5-year overall and disease-free survival (p > 0.05). CONCLUSIONS: The validity of NAC PTXS was not inferior to that of SOX regimen for locally advanced gastric cancer in terms of treatment response and overall survival. PTXS regimen could be expected to be ideal neoadjuvant chemotherapy for patients with LAGC and should be adopted for the test arm of a large randomized controlled trial.

Effect of the transanal drainage tube on preventing anastomotic leakage after laparoscopic surgery for rectal cancer: a systematic review and meta-analysis.

PURPOSE: Anastomotic leakage (AL) is a common postoperative complication of rectal cancer, and transanal drainage tube (TDT) efficacy is still contentious. This study aimed to evaluate the TDT effect on AL prevention. METHODS: All relevant papers were searched by using a predefined search strategy (two randomized controlled trials (RCTs), one prospective study, and four retrospective studies). Meta-analysis was conducted to estimate AL and re-operation pooled rates. RESULTS: A total of 7 studies (1556 patients) were included: No significant statistic difference was found between two groups on AL rate (odds ratio (OR) 0.61, P = 0.11) and re-operation rate (OR 0.52, P = 0.10). For subgroup analysis, significant statistic difference was found between two groups on AL rate (OR 0.29, P = 0.002) and re-operation rate (OR 0.15, P = 0.04) in patients without neoadjuvant therapy. As for patients without diverting stoma, the AL rate (OR 0.35, P = 0.002) was significantly lower than that in patients without TDT. CONCLUSIONS: TDT may reduce AL morbidity and re-operation rate for patients without high risk of AL, but may be useless for those in high-risk situations.

Effect of lateral lymph nodes without malignant characteristics on the prognosis of patients with rectal cancer.

Background: Lateral lymph node (LLN) metastasis is a poor prognostic factor for rectal cancer patients. However, the effect of LLNs without malignant characteristics on the prognosis of rectal cancer patients has been uncertain. Methods: Consecutive patients who underwent laparoscopic-assisted low anterior resection were included. Patients with MRI-detected LLNs, but without malignant characteristics, were compared with patients with no MRI-detected LLNs. Results: The local recurrence rate was higher in the LLN-present group than in the LLN-absent group (9.8% vs 2.5%; p = 0.056). The overall survival of patients with no MRI-detected LLNs was significantly better than that of patients with MRI-detected LLNs (p = 0.021). Conclusion: The presence of LLNs, even without malignant features, may lead to worse local control and overall survival.

Lymph node metastasis in the pelvic sidewall of patients with rectal cancer is a serious disease that affects the patient's life expectancy. At present, the assessment of lateral lymph node (LLN) metastasis relies mainly on MRI. Currently, there is no consensus on whether small lymph nodes without malignant features detected by MRI affect patient prognosis. Therefore, the authors designed this study to compare the survival of patients with small LLNs detected by MRI with that of patients without LLNs. The authors found that the presence of LLNs, even without malignant features, may lead to worse local control and overall survival. Therefore, for patients with MRI-detected LLNs, LLN dissection should be conducted by experienced surgeons to improve patient prognosis.

Adjuvant chemotherapy is an additional option for locally advanced gastric cancer after radical gastrectomy with D2 lymphadenectomy: a retrospective control study.

BACKGROUND: This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. METHODS: We retrospectively identified 428 patients with stage II-III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7-8 cycles every 3 weeks or 10-12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4-6 cycles every 3 weeks or 6-9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. RESULTS: The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4-6/6-9 and 7-8/10-12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). CONCLUSIONS: To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4-6 cycles every 3 weeks or FOLFOX regimen for 6-9 cycles every 2 weeks might be a favorable option for patients with stage II-III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.

Risk factors of symptomatic anastomotic leakage and its impacts on a long-term survival after laparoscopic low anterior resection for rectal cancer: a retrospective single-center study.

BACKGROUND: Postoperative symptomatic anastomotic leakage (AL) is a serious complication after low anterior resection (LAR) for rectal cancer. AL can potentially affect short-term patient outcomes and long-term prognosis. This study aimed to explore the risk factors and long-term survival of symptomatic AL after laparoscopic LAR for rectal cancer. METHODS: From May 2009 to May 2015, 298 consecutive patients who underwent laparoscopic LAR for rectal cancer with or without a defunctioning stoma were included in this study. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for symptomatic AL. Survival analysis was performed using Kaplan-Meier curves, and log-rank tests were used for group comparisons. RESULTS: Among the 298 patients enrolled in this study, symptomatic AL occurred in eight (2.7%) patients. The univariate analysis showed that age of ≤65 years (P = 0.048), neoadjuvant therapy (P = 0.095), distance from the anal verge (P = 0.078), duration of operation (P = 0.001), and pathological tumor (T) category (P = 0.004) were associated with symptomatic AL. The multivariate analysis demonstrated that prolonged duration of operation (P = 0.010) was an independent risk factor for symptomatic AL after laparoscopic LAR for rectal cancer. No statistically significant differences were observed in the 3-year (P = 0.785) and 5-year (P = 0.979) overall survival rates. CONCLUSIONS: A prolonged duration of operation increased the risk of symptomatic AL after laparoscopic LAR for rectal cancer. An impact of symptomatic AL on a long-term survival was not observed in this study; however, further studies are required. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry ( ChiCTR2000033413 ) on May 31, 2020.

Influence of tumor location on short- and long-term outcomes after laparoscopic surgery for rectal cancer: a propensity score matched cohort study.

BACKGROUND: This study aimed to evaluate the short- and long-term outcomes after laparoscopic resection for low rectal cancer (LRC) compared with mid/high rectal cancer (M/HRC). METHODS: Patients with rectal cancer undergoing laparoscopic resection with curative intent were retrospectively reviewed between 2009 and 2015. After matched 1:1 by using propensity score analysis, perioperative and oncological outcomes were compared between LRC and M/HRC groups. Multivariate analysis was performed to identify independent factors of overall survival (OS) and disease-free survival (DFS). RESULTS: Of 373 patients who met the criteria for inclusion, 198 patients were matched for the analysis. Laparoscopic surgery for LRC required longer operative time (P<0.001) and more blood loss volume (P = 0.015) compared with M/HRC, and the LRC group tended to have a higher incidence of postoperative complications (16.2% vs. 8.1%, P = 0.082). There was no significant difference in local recurrence between the two groups (9.1% vs. 4.0%, P = 0.251), whereas distant metastasis was inclined to be more frequent in LRC patients compared with M/HRC (21.2% vs. 12.1%, P = 0.086). The LRC group showed significantly inferior 5-year OS (77.0% vs. 86.4%, P = 0.033) and DFS (71.2% vs. 86.2%, P = 0.017) compared with the M/HRC group. Multivariate analysis indicated that tumor location was an independent predictor of DFS (HR = 2.305, 95% CI 1.203-4.417, P = 0.012). CONCLUSION: Tumor location of the rectal cancer significantly affected the clinical and oncological outcomes after laparoscopic surgery, and it was an independent predictor of DFS.

Short-term surgical outcomes of laparoscopy-assisted versus open D2 distal gastrectomy for locally advanced gastric cancer in North China: a multicenter randomized controlled trial.

BACKGROUND: Although laparoscopic surgery has been recommended as an optional therapy for patients with early gastric cancer, whether patients with locally advanced gastric cancer (AGC) could benefit from laparoscopy-assisted distal gastrectomy (LADG) with D2 lymphadenectomy remains elusive due to a lack of comprehensive clinical data. To evaluate the efficacy of LADG, we conducted a multi-institutional randomized controlled trial to compare laparoscopy-assisted versus open distal gastrectomy (ODG) for AGC in North China. METHODS: In this RCT, after patients were enrolled according to the eligibility criteria, they were preoperatively assigned to LADG or ODG arm randomly with a 1:1 allocation ratio. The primary endpoint was the morbidity and mortality within 30 postoperative days to evaluate the surgical safety of LADG. The secondary endpoint was 3-year disease-free survival. This trial was registered at ClinicalTrial.gov as NCT02464215. RESULTS: Between March 2014 and August 2017, a total of 446 patients with cT2-4aN0-3M0 (AJCC 7th staging system) were enrolled. Of these, 222 patients underwent LADG and 220 patients underwent ODG were included in the modified intention-to-treat analysis. The compliance rate of D2 lymph node dissection was identical between the LADG and ODG arms (99.5%, P = 1.000). No significant difference was observed regarding the overall postoperative complication rate in two groups (LADG 13.1%, ODG 17.7%, P = 0.174). No operation-related death occurred in both arms. CONCLUSIONS: This trial confirmed that LADG performed by credentialed surgeons was safe and feasible for patients with AGC compared with conventional ODG.

Prognostic factors for patients with stage II colon cancer: results of a prospective study.

PURPOSE: Many studies revealed that the recurrence rate of stage II colon cancer was up to 25­40 %. Regrettably, the risk factors for recurrence of stage II colon cancer remain ambiguous. So, we conducted this study to identify the clinicopathological factors associated with prognosis of stage II colon cancer. METHODS: We enrolled 452 stage II colon cancer patients who underwent radical resection at Peking University Cancer Hospital between January 2007 and December 2010, and 162 patients who received adjuvant treatment were excluded. RESULTS: The 5-year recurrence rate and overall survival of this cohort were 19.3 (56/290) and 75.9 % (220/290), respectively. In univariate analysis, the following variables were significantly associated with tumor recurrence:male patients (P<0.001), tumor size >5 cm (P=0.048), and preoperative carcinoembryonic antigen (CEA) level ≥ 5 ng/ml (P=0.004); the following factors were significantly associated with adverse 5-year overall survival:male patients (P<0.001), age ≥60 years old (P=0.004), less than 12 lymph nodes (P=0.006), and preoperative CEA level ≥5 ng/ml (P=0.011). In multivariate analysis,the preoperative CEA level ≥5 ng/ml (P=0.003) and male (P<0.001) were adverse variables significantly associated with tumor recurrence, and the preoperative CEA level ≥ 5 ng/ml (P=0.016), male (P<0.001), and age ≥60 years old (P=0.008) were independent prognostic factors for the 5-year overall survival rate, respectively. CONCLUSIONS: The preoperative CEA level ≥5 ng/ml and male were undesirable factors significantly associated with tumor recurrence. The preoperative CEA level ≥5 ng/ml, male, and age ≥60 years old were adverse factors significantly associated with poor prognosis.

Validation of the Memorial Sloan-Kettering Cancer Center Nomogram to Predict Overall Survival After Curative Colectomy in a Chinese Colon Cancer Population.

BACKGROUND: Colon cancer nomogram designed by Memorial Sloan-Kettering Cancer Center (MSKCC) is an online prediction tool to predict overall survival for individual patient after curative resection. However, this model was never externally validated. We evaluated the accuracy of this nomogram in an independent external Chinese cohort. METHODS: Clinical data from 1005 patients who underwent primary curative-intent surgery at Peking University Cancer Hospital & Institute between 1996 and 2008 were used for external validation. Clinicopathologic characteristics and the performance of the MSKCC nomogram for prediction of overall survival were evaluated for 985 patients with complete data by using concordance index (C-index) and calibration plot. RESULTS: The C-index for the MSKCC nomogram was 0.71 in the Chinese cohort, compared with 0.67 for American Joint Committee on Cancer (AJCC) stage (P < .0001). This suggests that the nomogram discriminates overall survival better than AJCC staging system. Calibration plot showed a good calibration of the nomogram in the validation cohort. Furthermore, the MSKCC nomogram prediction illustrated the heterogeneity for survival of Chinese patients within each AJCC stage. CONCLUSIONS: The MSKCC nomogram for colon cancer provides more accurate survival predictions than the AJCC staging system when applied to an external Chinese cohort. The MSKCC nomogram improved individualized prediction of survival and may aid in more accurate patient counseling, selection of various treatment options, and follow-up scheduling.

GOLPH3 predicts survival of colorectal cancer patients treated with 5-fluorouracil-based adjuvant chemotherapy.

BACKGROUND: Golgi phosphoprotein 3 (GOLPH3) has been validated as a potent oncogene involved in the progression of many types of solid tumors, and its overexpression is associated with poor clinical outcome in many cancers. However, it is still unknown the association of GOLPH3 expression with the prognosis of colorectal cancer (CRC) patients who received 5-fluorouracil (5-FU)-based adjuvant chemotherapy. METHODS: The expression of GOLPH3 was determined by qRT-PCR and immunohistochemistry in colorectal tissues from CRC patients treated with 5-FU based adjuvant chemotherapy after surgery. The association of GOLPH3 with clinicopathologic features and prognosis was analysed. The effects of GOLPH3 on 5-FU sensitivity were examined in CRC cell lines. RESULTS: GOLPH3 expression was elevated in CRC tissues compared with matched adjacent noncancerous tissues. Kaplan-Meier survival curves indicated that high GOLPH3 expression was significantly associated with prolonged disease-free survival (DFS, P = 0.002) and overall survival (OS, P = 0.011) in patients who received 5-FU-based adjuvant chemotherapy. Moreover, multivariate analysis showed that GOLPH3 expression was an independent prognostic factor for DFS in CRC patients treated with 5-FU-based chemotherapy (HR, 0.468; 95%CI, 0.222-0.987; P = 0.046). In vitro, overexpression of GOLPH3 facilitated the 5-FU chemosensitivity in CRC cells; while siRNA-mediated knockdown of GOLPH3 reduced the sensitivity of CRC cells to 5-FU-induced apoptosis. CONCLUSIONS: Our results suggest that GOLPH3 is associated with prognosis in CRC patients treated with postoperative 5-FU-based adjuvant chemotherapy, and may serve as a potential indicator to predict 5-FU chemosensitivity.

Extent of Lymphadenectomy for Surgical Management of Right-Sided Colon Cancer: The Randomized Phase III RELARC Trial.

PURPOSE: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer, although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. METHODS: This multicenter, open-label, randomized controlled trial (ClinicalTrials.gov identifier: NCT02619942) was performed across 17 hospitals in China. Patients diagnosed with stage T2-T4aNanyM0 or TanyN + M0 right-sided colon cancer were randomly assigned (1:1) to undergo either CME or D2 dissection during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). RESULTS: Between January 11, 2016, and December 26, 2019, 1,072 patients were randomly assigned (536 patients to CME and 536 patients to D2 dissection). In total, 995 patients (median age 61 years, 59% male) were included in the primary analysis (CME [n = 495] v D2 dissection [n = 500]). No significant differences were found between the groups in 3-year DFS (hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.02]; P = .06; 86.1% in the CME group v 81.9% in the D2 group) or in 3-year OS (HR, 0.70 [95% CI, 0.43 to 1.16]; P = .17; 94.7% in the CME group v 92.6% in the D2 group). CONCLUSION: This trial failed to find evidence of superior DFS outcome for CME compared with standard D2 lymph node dissection in primary surgical excision of right-sided colon cancer. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement.

microRNAs and ceRNAs: RNA networks in pathogenesis of cancer.

microRNAs (miRNAs) are a class of endogenous, single-stranded non-coding RNAs of 20-23 nucleotides in length, functioning as negative regulators of gene expression at the post-transcriptional level. The dysregulation of miRNAs has been demonstrated to play critical roles in tumorigenesis, either through inhibiting tumor suppressor genes or activating oncogenes inappropriately. Besides their promising clinical applications in cancer diagnosis and treatment, recent studies have uncovered that miRNAs could act as a regulatory language, through which messenger RNAs, transcribed pseudogenes, and long noncoding RNAs crosstalk with each other and form a novel regulatory network. RNA transcripts involved in this network have been termed as competing endogenous RNAs (ceRNAs), since they influence each other's level by competing for the same pool of miRNAs through miRNA response elements (MREs) on their target transcripts. The discovery of miRNA-ceRNA network not only provides the possibility of an additional level of post-transcriptional regulation, but also dictates a reassessment of the existing regulatory pathways involved in cancer initiation and progression.

Clinicopathological characteristics and treatment outcome of resectable gastric cancer patients with small para-aortic lymph node.

Background: Resectable gastric cancer (GC) patients with small para-aortic lymph node (smaller than 10mm in diameter, sPAN) were seldom reported, and existing guidelines did not provide definite treatment recommendation for them. Methods: A total of 667 consecutive resectable GC patients were enrolled. 98 patients were in the sPAN group, and 569 patients without enlarged para-aortic lymph node were in the nPAN group. Standard D2 lymphadenectomy was performed. Neoadjuvant and adjuvant chemotherapy were administrated according to the cTNM and pTNM stage, respectively. Clinicopathological features and prognosis were compared between these two groups. Results: The median size of sPAN was 6 (range, 2-9) mm and the distribution was prevalent in No. 16b1. cN stage (p=0.001) was significantly related to the presence of sPAN. sPAN was both independent risk factor for OS (p=0.031) and RFS (p=0.046) of all patients. The prognosis of patients with sPAN was significantly worse than that of patients with nPAN (OS: p=0.008; RFS: p=0.007). Preoperative CEA and CA19-9 were independent risk factors for prognosis of patients with sPAN. Furthermore, patients in the sPAN group with normal CEA and CA19-9 exhibited acceptable prognosis (5-year OS: 67%; RFS: 64%), while those with elevated CEA or CA19-9 suffered significantly poorer prognosis (5-year OS: 17%; RFS: 17%) than patients in the nPAN group (5-year OS: 64%; RFS 62%) (both p < 0.05). Conclusions: Standard D2 lymphadenectomy should be considered a valid approach for GC patients with sPAN associate to normal preoperative CEA and CA19-9 levels. Patients with sPAN associated to elevated CEA or CA19-9 levels could benefit from a multimodal approach: neoadjuvant chemotherapy; radical surgery with D2 plus lymph nodal dissection extended to No. 16 station.

Long-term health-related quality of life in patients with gastric cancer after total or distal gastrectomy: a propensity score-matched cohort study.

BACKGROUND: Surgical resection remains the cornerstone of treatment for locally advanced gastric cancer (LAGC) and is accompanied by potential deterioration in patients' health-related quality of life (HRQOL). As an important indicator of the psychosocial burden, HRQOL has become an essential endpoint to evaluate the efficacy and impact of cancer treatment. We examined longitudinal changes in HRQOL among patients with LAGC receiving total gastrectomy (TG) or distal gastrectomy (DG) over time. MATERIALS AND METHODS: The patients in this study were from a prospective observational study (NCT04408859) conducted during 2018-2022. We used the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and the stomach module questionnaire to evaluate HRQOL at baseline and at postoperative months 1, 3, 6, and 12. We used linear mixed models to analyze longitudinal changes in HRQOL between groups and correlations with follow-up time. RESULTS: A total of 219 patients were included. After propensity score matching, 186 patients were ultimately analyzed. Compared with the DG group, patients in the TG group reported significantly poorer global health status, physical functioning, and role functioning and more severe fatigue, insomnia, appetite loss, pain, and financial problems. Gastric-specific symptoms, dysphagia, chest and abdominal pain, reflux, restricted eating, and anxiety were more common and severe in the TG group. Most scales showed deterioration at months 1 and 3 after surgery, with gradual recovery thereafter, except the scales for global health status, pain, chest and abdominal pain, and reflux, which improved continually compared with baseline. TG was associated with worsening in at least six HRQOL domains for each measure after baseline, compared with DG. CONCLUSIONS: In contrast with DG, TG had an adverse impact on postoperative HRQOL scales in patients with LAGC. Different HRQOL scales had various recovery trajectories after surgery. Effects of the gastrectomy scope on patients' HRQOL should be considered together with sound oncology principles.

Serum and peritoneal biomarkers for the early prediction of symptomatic anastomotic leakage in patients following laparoscopic low anterior resection: A single-center prospective cohort study.

BACKGROUND: Anastomotic leakage (AL) is one of the common complications after rectal cancer surgery. This study aimed to evaluate the combination of biomarkers for the early prediction of symptomatic AL after surgery. METHODS: A prospective cohort study evaluated the serum and peritoneal biomarkers of patients who underwent laparoscopic low anterior resection (Lap LAR) from November 1, 2021, to May 1, 2022. Multivariate-penalized logistic regression was performed to explore the independent biomarker with a P-value <.1, and receiver operating characteristic (ROC) curve was used to analyze the area under the curve (AUC), sensitivity, and specificity of the independent biomarkers. A predictive model for symptomatic AL was built based on the independent biomarkers and was visualized with a nomogram. The calibration curve with the concordance index (c-index) was further applied to evaluate the efficacy of the predictive model. RESULTS: A total of 157 patients were included in this study, and 7 (4.5%) were diagnosed with symptomatic AL. C-reactive protein/album ratio (CAR) on postoperative day 1 and systemic immune-inflammation index (SII) and peritoneal interleukin-6 (IL-6) on postoperative day 3 were proven to be independent predictors for the early prediction of symptomatic AL. The optimal cutoff values of CAR, SII, and peritoneal IL-6 were 1.04, 916.99, and 26430.09 pg/ml, respectively. Finally, the nomogram, including these predictors, was established, and the c-index of this nomogram was 0.812, indicating that the nomogram could be used for potential clinical reference. CONCLUSION: The combination of CAR, SII, and peritoneal IL-6 might contribute to the early prediction of symptomatic AL in patients following Lap LAR. Given the limitations of this study and the emergence of other novel biomarkers, multicenter prospective studies are worthy of further exploration.

Oncological results in rectal cancer patients with a subcentimetre distal margin after laparoscopic-assisted sphincter-preserving surgery.

BACKGROUND: Distal resection margin (DRM) is closely associated with sphincter-preserving surgery and oncological safety for patients with mid-low rectal cancers. However, the optimal DRM has not been determined. METHODS: Data of 378 rectal cancer patients who underwent laparoscopic-assisted sphincter-preserving surgery from 2009 to 2015 were retrospectively analysed. Patients were divided into two groups based on DRM: ≤1 cm (n = 74) and >1 cm (n = 304). To minimize the differences between the two groups, propensity-score matching on baseline features was performed. RESULTS: Before propensity-score matching, no significant differences in 5-year disease-free survival (DFS) (92.8% versus 81.3%, P = 0.128) and 5-year overall survival (OS) (83.7% versus 82.2%, P = 0.892) were observed in patients with DRMs of ≤1 cm (n = 74) and >1 cm (n = 304), respectively. After propensity-score matching (1:1), there were also no significant differences in DFS (88.1% versus 78.2%, P = 0.162) and OS (84.5% versus 84.9%, P = 0.420) between the DRM of ≤1 cm group (n = 65) and >1 cm group (n = 65), respectively. A total of 44 patients received preoperative chemoradiotherapy (CRT). In this cohort, the 5-year local recurrence (LR) rates (P = 0.118) and the 5-year DFS rates (P = 0.298) were not significantly different between the two groups. A total of 334 patients received surgery without neoadjuvant CRT. There were also no significant differences in the 5-year LR rates (P = 0.150) and 5-year DFS rates (P = 0.172) between the two groups. CONCLUSIONS: When aiming to achieve at least a 1-2 cm distal clinical resection margin, a histological resection margin of <1 cm on the DRM gave equivalent clinical outcomes to a DRM of >1 cm.