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The surgical approaches and resection extent for rectal gastrointestinal stromal tumors (GISTs) are controversial due to the low incidence of this disease. A multicenter retrospective cohort study was conducted to compare the postoperative and oncologic outcomes of local excision (LE) and radical resection (RR) in patients with low rectal GIST. The medical records of rectal GIST patients from 11 large-scale medical centers in China (January 2000-December 2019) were reviewed. All patients were divided into either the LE group or the RR group. Propensity score matching (PSM) was conducted to reduce confounders. A total of 280 patients with low rectal GIST were enrolled. After PSM, 144 patients were included (72 in each group). The LE group showed a higher anal preservation rate (100.0% vs. 76.4%, P < 0.001), shorter operation time (77.1 ± 68.4 min vs. 159.1 ± 83.6 min, P < 0.001), fewer complications (8.3% vs. 22.2%, P = 0.021) and shorter postoperative hospital stay (4.9 ± 4.1 d vs. 10.7 ± 8.1 d, P < 0.001) than the RR group. There was no significant difference in recurrence-free survival (RFS) between the RR and LE groups among patients with tumors ≤2 cm (P = 0.220), and the RR group had a superior RFS than the LE group in patients with tumors >2 cm (P = 0.046). LE resulted in improved postoperative outcomes and comparable oncological safety with a low rectal GIST of ≤2 cm. However, for patients with a low rectal GIST of >2 cm, RR might be a more appropriate option with better RFS. [ABSTRACT FROM AUTHOR]

The application of endoscopic resection (ER) in gastric gastrointestinal stromal tumours (GIST) is controversial. We carried out a meta-analysis to compare the safety and efficiency of ER with laparoscopic resection (LR) in patients with gastric GISTs. We searched PubMed to identify studies comparing ER with LR in GIST. The outcomes focused on two areas: safety, including operation time, blood loss, length of hospital stay, time to flatus, time to liquid, time to soft diet, and postoperative complications; and efficiency, including positive margin, recurrence, and long-term survival. A total of 1292 patients from 12 studies were included in the meta-analysis. Patients undergoing ER had a shorter operation time (standardised mean difference [SMD] −1.48, 95% confidence interval [CI] −2.18 to −0.78) and shorter time to soft diet (SMD -1.02, 95% CI -1.52 to −0.52) than those undergoing LR. No significant differences were observed between the groups in terms of blood loss, length of hospital stay, time to flatus, time to liquid, and postoperative complications. ER was also associated with greater positive margins compared with LR (relative risk 6.32, 95% CI 1.41–28.26). There were no significant differences between ER and LR for recurrence and 5-year disease-free survival. The limited evidence suggests that ER is a more effective strategy for improving postoperative recovery without increasing the risk of surgery and recurrence in gastric GIST. However, close attention should be paid to margin status after ER. [ABSTRACT FROM AUTHOR]

The surgical and oncological outcome of extra-levator abdominoperineal excision (ELAPE) procedure remains unclear in low rectal cancer. A total of 194 cases of rectal cancer patients underwent ELAPE or conventional abdominoperineal excision (APE) procedure were analyzed in four hospitals' databases from January 2010 to December 2015. Clinicopathological data, overall survival (OS), disease free survival (DFS) and local recurrence free survival (LRFS) of patients were compared between two groups. The operation time spent in perineal phase was significantly shorter in the ELAPE group than that in conventional APE procedure (P < 0.001). There were more specimens with excellent or good quality in ELAPE group compared to conventional APE group (P = 0.033). Patients whom underwent ELAPE procedures showed significantly better OS, DFS and LRFS than those underwent conventional APE procedures. Patients with preoperative stage cT3∼T4 (P = 0.033, P = 0.008, P = 0,033), cN+ (P = 0.002, P < 0.001, P = 0.006) and pathological stage III-IV (P = 0.023, P = 0.008, P = 0.016) were associated with significant benefits from ELAPE procedure in terms of OS, DFS and LRFS. DFS differed significantly between two groups of patients whom got preoperative chemoradiation therapy (P = 0.009) or postoperative chemotherapy (P = 0.029). For patients of pathological stage IIII-IV without preoperative chemoradiation, ELAPE procedures resulted in statistically better OS (P = 0.018) and DFS (P = 0.030). ELAPE procedure was an independent risk factor of OS, DFS and LRFS in multivariate analysis. Low rectal cancer patients might benefit from ELAPE procedure on both surgical and oncological outcomes, especially in patients with relatively advanced tumors, inspite of the effects of pre-operative radio- and chemotherapy. [ABSTRACT FROM AUTHOR]

Objective To establish predicting models of surgical complications in elderly colorectal cancer patients. Background Surgical complications are usually critical and lethal in the elderly patients. However, none of the current models are specifically designed to predict surgical complications in elderly colorectal cancer patients. Methods Details of 1008 cases of elderly colorectal cancer patients (age ≥ 65) were collected retrospectively from January 1998 to December 2013. Seventy-six clinicopathological variables which might affect postoperative complications in elderly patients were recorded. Multivariate stepwise logistic regression analysis was used to develop the risk model equations. The performance of the developed model was evaluated by measures of calibration (Hosmer-Lemeshow test) and discrimination (the area under the receiver-operator characteristic curve, AUC). Results The AUC of our established Surgical Complication Score for Elderly Colorectal Cancer patients (SCSECC) model was 0.743 (sensitivity, 82.1%; specificity, 78.3%). There was no significant discrepancy between observed and predicted incidence rates of surgical complications (AUC, 0.820; P = .812). The Surgical Site Infection Score for Elderly Colorectal Cancer patients (SSISECC) model showed significantly better prediction power compared to the National Nosocomial Infections Surveillance index (NNIS) (AUC, 0.732; P ˂ 0.001) and Efficacy of Nosocomial Infection Control index (SENIC) (AUC; 0.686; P˂0.001) models. Conclusions The SCSECC and SSISECC models show good prediction power for postoperative surgical complication morbidity and surgical site infection in elderly colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Kindlin-2 has been confirmed as an essential element of bidirectional integrin signaling. In recent years, the relationship between Kindlin-2 expression and cancers has been a focus of interest. However, the relationship between Kindlin-2 expression in gastric cancer and tumor invasion, metastasis, and the outcome of patients have not been studied. Methods: Kindlin-2 expression at protein and RNA levels were detected by Western blot and real-time polymerase chain reaction in 40 pairs of gastric cancer samples. In addition, the correlations between Kindlin-2 expression and clinicopathologic factors as well as the prognosis of the patients were analyzed. Multivariate Cox regression was used to study the effect of Kindlin-2 expression on overall and progression-free survival. Results: We found that Kindlin-2 was up-regulated both at RNA (P = .027) and protein levels (P = .014) in gastric cancer tissues. Tumor samples with high Kindlin-2 expression (Kindlin-2/β-actin:tumor tissue/paraneoplastic tissue, ≥2) was observed in 55% of the patients. Moreover, Kindlin-2 expression had a significant positive correlation with tumor stromal invasion (P = .014), lymph node metastasis (P = .007), and TNM stage (P = .014). Patients with high Kindlin-2 expression had significantly poorer overall survival (P = .012) and progression-free survival (P = .012). High Kindlin-2 expression was an independent risk factor of progression-free survival (hazard ratio, 5.2; 95% confidence interval, 1.1–3.3; P = .032). Conclusions: Kindlin-2 may play an important role in the development of gastric cancer and it is a potential factor that could be used to evaluate the outcome of gastric cancer. Kindlin-2 may shed new light on evaluating the prognosis and targeted therapy of gastric cancer. [Copyright &y& Elsevier]

Keywords: Gastric GIST; Meta-analysis; Endoscopic resection; Laparoscopic resection EN Gastric GIST Meta-analysis Endoscopic resection Laparoscopic resection 1560 1560 1 07/23/20 20200801 NES 200801 To the Editor, We welcome the opportunity to reply to Dr Peiwen Li et al.'s comment on our study. However, current consensus did not consider R1 resection as tumour rupture, which means R1 resection is not an independent prognostic factor for recurrence [[2]]. [Extracted from the article]

Standard treatment of colorectal cancer (CRC) improves the prognosis of CRC patients, but it is still intractable to control the progression of metastatic CRC. Immune microenvironment and immunotherapies of CRC have received extensive attention in recent years, but present immunotherapies of CRC have mainly focused on T cells and therapeutic response is only observed in a small proportion of patients. Innate immune cells are the first-line of defense in the development of malignancies. Natural killer (NK) cells, NKT cells and γδT cells are three types of innate cells of lymphoid origin and show cytotoxicity against various tumor cells including CRC. Besides, in the development of CRC, they can also be inhibited or express regulatory type, promoting tumor progression. Researches about anti-tumorigenic and pro-tumorigenic mechanisms of these cells are ongoing and regulation of these cells is also being unearthed. Meanwhile, immunotherapies using these cells more or less have shown efficacy in animal models and some of them are under exploration in clinical trials. This review provides an overview of intrinsic properties of NK cell, NKT cell and γδT cell, and summarizes current related promising treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Whether extended lymphadenectomy for right colon cancer leads to increased perioperative complications or improves survival is still controversial. This trial aimed to compare the efficacy and safety of complete mesocolic excision (CME) versus D2 dissection in laparoscopic right hemicolectomy for patients with right colon cancer. This article reports the early safety results from the trial.Methods: This randomised, controlled, phase 3, superiority, trial was done at 17 hospitals in nine provinces of China. Eligible patients were aged 18-75 years with histologically confirmed primary adenocarcinoma located between the caecum and the right third of the transverse colon, without evidence of distant metastases. Central randomisation was done by means of the Clinical Information Management-Central Randomisation System via block randomisation (block size of four). Patients were randomly assigned (1:1) to CME or D2 dissection during laparoscopic right colectomy. Central lymph nodes were dissected in the CME but not in the D2 procedure. Neither investigators nor patients were masked to their group assignment but the quality control committee were masked to group assignment. The primary endpoint was 3-year disease-free survival, but the data for this endpoint are not yet mature; thus, only the secondary outcomes-intraoperative surgical complications and postoperative complications within 30 days of surgery, graded according to the Clavien-Dindo classification, mortality (death from any cause within 30 days of surgery), and central lymph node metastasis rate in the CME group only-are reported in this Article. This early analysis of safety was preplanned. The outcomes were analysed according to a modified intention-to-treat principle (excluding patients who no longer met inclusion criteria after surgery or who did not have surgery). This study is registered with ClinicalTrials.gov, NCT02619942. Study recruitment is complete, and follow-up is ongoing.Findings: Between Jan 11, 2016, and Dec 26, 2019, 1072 patients were enrolled and randomly assigned. After exclusion of 77 patients, 995 patients were included in the modified intention-to-treat population (495 in the CME group and 500 in the D2 dissection group). The postoperative surgical complication rate was 20% (97 of 495 patients) in the CME group versus 22% (109 of 500 patients) in the D2 group (difference, -2·2% [95% CI -7·2 to 2·8]; p=0·39); the frequency of Clavien-Dindo grade I-II complications were similar between groups (91 [18%] vs 92 [18%], difference, -0·0% [95% CI -4·8 to 4·8]; p=1·0) but Clavien-Dindo grade III-IV complications were significantly less frequent in the CME group than in the D2 group (six [1%] vs 17 [3%], -2·2% [-4·1 to -0·3]; p=0·022); no deaths occurred in either group. Of the intraoperative complications, vascular injury was significantly more common in the CME group than in the D2 group (15 [3%] vs six [1%], difference, 1·8 [95% CI 0·04 to 3·6]; p=0·045). Metastases in the central lymph nodes were detected in 13 (3%) of 394 patients who underwent central lymph node biopsy in the CME group; no patient had isolated metastases to central lymph nodes.Interpretation: Although the CME procedure might increase the risk of intraoperative vascular injury, it generally seems to be safe and feasible for experienced surgeons.Funding: The Capital Characteristic Clinical Project of Beijing and the Chinese Academy of Medical Sciences. [ABSTRACT FROM AUTHOR]

A bridging study of INTRIGUE study to assess the efficacy and safety of ripretinib versus sunitinib as second-line treatment in Chinese GIST patients. This was a phase 2, multicenter, randomized, open-label study in China. GIST patients previously treated with imatinib were randomized (1:1) to receive ripretinib 150 mg once daily (QD) by continuous dosing in 42-day cycles or sunitinib 50 mg QD in 42-day cycles (four weeks on/two weeks off). Primary endpoint was progression-free survival (PFS) by independent radiological review (IRR). Between 6 December 2020 and 15 September 2021, 108 patients were randomized to receive ripretinib (n = 54) or sunitinib (n = 54) (all-patient [AP] intention-to-treat [ITT] population). Seventy patients had primary KIT exon 11 mutations (ripretinib, n = 35; sunitinib, n = 35; Ex11 ITT population). By data cut-off (20 July 2022), in AP ITT population, PFS by IRR was comparable between ripretinib and sunitinib arms (HR 0·99, 95 % CI 0·57, 1·69; nominal p = 0·92; median PFS [mPFS] 10·3 vs 8·3 months). In Ex11 ITT population, PFS by IRR was longer for ripretinib than sunitinib (HR 0·46, 95 % CI 0·23, 0·92; nominal p = 0·03; mPFS not reached in ripretinib arm and 4·9 months in sunitinib arm). Fewer patients experienced grade 3/4 treatment-related treatment-emergent adverse events with ripretinib (17%) versus sunitinib (56%). Ripretinib demonstrated similar efficacy and a favorable safety profile versus sunitinib as second-line treatment in Chinese GIST patients. Furthermore, ripretinib provided greater clinically meaningful benefit versus sunitinib in patients with KIT exon 11 mutation. • 2nd-line treatment of GIST in China: ripretinib has similar efficacy as sunitinib. • Ripretinib demonstrated a more favorable safety profile versus sunitinib. • KIT exon 11 mutation patient: greater clinically meaningful benefit with ripretinib. [ABSTRACT FROM AUTHOR]

To investigate the expression of chromosome 6 open reading frame 15 (C6orf15) in colon cancer and its effects on clinicopathological features and prognosis. Using the transcriptome and clinical data of colon cancer and normal tissues in The Cancer Genome Atlas (TCGA) database, the expression of C6orf15 mRNA in colon cancer samples and its relationship with clinicopathological characteristics and prognosis were explored. The expression level of C6orf15 protein in 23 colon cancer tissues was detected by immunohistochemistry (IHC). The possible mechanism of C6orf15 involved in the occurrence and development of colon cancer was explored by gene set enrichment analysis (GSEA). Compared with normal tissues, C6orf15 was highly expressed in colon cancer (1.207 ± 0.694 vs 0.276 ± 0.166, t = 8.281, P < 0.01). The expression level of C6orf15 was associated with tumor invasion depth (χ2 = 8.30, P = 0.04), lymph node metastasis (χ2 = 36.97, P < 0.001), distant metastasis (χ2 = 8.69, P = 0.003) and pathological stage (χ2 = 34.17, P < 0.001). High expression of C6orf15 was associated with poor prognosis (χ2 = 6.43, P < 0.05). The results of GSEA showed that C6orf15 promotes the occurrence and development of colon cancer by promoting the ECM receptor interaction pathway, Hedgehog signaling pathway and Wnt signaling pathway. Immunohistochemical results showed that the expression of C6orf15 protein in colon cancer tissues was correlated with the depth of invasion (P = 0.023) and lymph node metastasis (P = 0.048). C6orf15 is highly expressed in colon cancer tissue and is related to adverse pathological features and poor prognosis of colon cancer. It is involved in multiple oncogenic signaling pathways and may serve as a prognostic marker of colon cancer. [ABSTRACT FROM AUTHOR]

Objective: To investigate the capability of a radiomics model, which was designed to identify histopathologic growth pattern (HGP) of colorectal liver metastases (CRLMs) based on contrast-enhanced multidetector computed tomography (ceMDCT), to predict early response and 1-year progression free survival (PFS) in patients treated with bevacizumab-containing chemotherapy.Methods: Patients with unresectable CRLMs who were treated with bevacizumab-containing chemotherapy were included in this multicenter retrospective study. For each target lesion, the radiomics-diagnosed HGP (RAD_HGP) of desmoplastic (D) pattern or replacement (R) pattern was determined. Logistic regression and receiver operating characteristic (ROC) curves were used to assess lesion- and patient-based responses according to morphologic response criteria. One-year PFS was calculated using Kaplan-Meier curves. Hazard ratios for 1-year PFS were obtained through Cox proportional hazard regression analysis.Results: Among 119 study patients, 206 D pattern and 140 R pattern lesions were identified. In patients with multiple lesions, 52 had D pattern, 31 had R pattern, and 36 had mixed (D + R) pattern. The area under the curve value for RAD_HGP in predicting early response was 0.707 for lesion-based analysis and 0.720 for patient-based analysis. Patients with D pattern had a significantly longer PFS than patients with R pattern or mixed pattern (P < 0.001). RAD_HGP was the only independent predictor of 1-year PFS.Conclusions: HGP diagnosed using a radiomics model could be used as an effective predictor of PFS for patients with CRLMs treated with bevacizumab-containing chemotherapy. [ABSTRACT FROM AUTHOR]

• The expression of TDO2 in colorectal cancer is higher than that in normal tissues. • Invasion and migration of colorectal cancer cells may be affected by the TDO2. • TDO2 may be an indicator of poor prognosis of colorectal cancer. • The expression of Kyn pathway enzymes may have a potential relationship with increased AhR activity. The aim of this study was to explore the expression levels and biological significance of TDO2 in colorectal cancer (CRC). First, we explored the potential oncogenic roles of TDO2 across 33 tumors based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Second, we evaluated TDO2 protein expression in 55 CRC tissue samples and 30 cDNA samples by immunohistochemistry and qPCR. Third, we investigated the effect of TDO2 on CRC cells by cell proliferation, wound healing, invasion, and colony formation assays. Finally, we determined the protein that is most closely associated with TDO2 via bioinformatics analysis, enriched the key pathways, and verified them. The expression level of TDO2 was found to be associated with the tumor clinical stage in CRC. A high expression of TDO2 was associated with a poor outcome in CRC patients. Inhibition of TDO2 expression by RNAi in LoVo and HCT116 cell lines significantly reduced the proliferation, migration, and invasion abilities as well as colony formation abilities of cells. Further, knockdown of TDO2 expression induced inactivation of the TDO2–KYNU–AhR signaling pathway. The results suggest that TDO2 plays an important role in the progression of CRC. Accordingly, TDO2 is a potential therapeutic target in CRC. [ABSTRACT FROM AUTHOR]

Purpose: To develop a radiomic nomogram to predict disease-free survival (DFS) in patients with colon cancer.Methods: We retrospectively identified 302 patients with stage III colon cancer and 269 patients with stage II colon cancer who had undergone multidetector computed tomography (MDCT) and radical resection between January 2009 and December 2015. Patients were divided into a training cohort (n = 322) and an external validation cohort (n = 249). Radiomic features were extracted from MDCT images, and a radiomic signature was built as to predict DFS. A radiomic nomogram integrating the radiomic signature and clinicopathologic characteristics was developed using multivariable logistic regression. The nomogram was evaluated with regard to calibration, discrimination, and clinical utility.Results: The radiomic signature was an independent prognostic factor for DFS in the training cohort (HR = 1.102; 95 % CI: 1.052-1.156; P < 0.001) and the external validation cohort (HR = 1.157; 95 % CI: 1.030-1.301; P = 0.014). The radiomic signature-based nomogram was more effective at predicting DFS than either the TNM staging system or a clinicopathologic nomogram. The C-indices of the radiomic nomogram and TNM staging system were 0.780 (95 % CI: 0.734-0.847) and 0.738 (0.687-0.784) respectively. The radiomic signature-based nomogram demonstrated good fitness (shown by calibration curves) and clinical usefulness (shown by decision curve analysis).Conclusion: A radiomic signature derived from MDCT images can effectively predict DFS in patients with stage II and III colon cancer and could be used as a supplement for risk stratification. [ABSTRACT FROM AUTHOR]

To study the relationship between the expression of SATB2 in colonic adenocarcinoma and clinicopathological factors, and its role in the identification of ovarian digestive system metastatic adenocarcinoma. Immunohistochemistry was used to analyze the expression of SATB2 in 130 cases of colon adenocarcinoma, 46 cases of gastric adenocarcinoma, 47 cases of pancreatic ductal adenocarcinoma, 22 cases of cholangiocarcinoma, 53 cases of ovarian mucinous adenocarcinoma, and 38 cases of ovarian metastasis of colorectal carcinoma. Data was analyzed using SPSS 16.0 statistical software. The positive expression rate of SATB2 in 130 cases of colon adenocarcinoma was 73.85% (96/130). The expression rate of SATB2 was significantly higher in well -moderately differentiated colon adenocarcinoma than in poorly differentiated adenocarcinoma (p<0.05); the expression rate was significantly higher in cases without tumor deposits than in cases with tumor deposits (p<0.05). The positive expression rate of SATB2 in ovarian metastases of colorectal adenocarcinoma was 81.58% (31/38). No positive expression of SATB2 was observed in other cancers. Loss of expression of SATB2 is associated with poor differentiation of primary colon cancer and the formation of tumor deposits. SATB2 provides an ideal diagnostic marker for clinical surgeons to choose the right treatment plan. [ABSTRACT FROM AUTHOR]