Intestinal SURF4 is essential for apolipoprotein transport and lipoprotein secretion.

OBJECTIVE: Lipoprotein assembly and secretion in the small intestine are critical for dietary fat absorption. Surfeit locus protein 4 (SURF4) serves as a cargo receptor, facilitating the cellular transport of multiple proteins and mediating hepatic lipid secretion in vivo. However, its involvement in intestinal lipid secretion is not fully understood. In this study, we investigated the role of SURF4 in intestinal lipid absorption. METHODS: We generated intestine-specific Surf4 knockout mice and characterized the phenotypes. Additionally, we investigated the underlying mechanisms of SURF4 in intestinal lipid secretion using proteomics and cellular models. RESULTS: We unveiled that SURF4 is indispensable for apolipoprotein transport and lipoprotein secretion. Intestine-specific Surf4 knockout mice exhibited ectopic lipid deposition in the small intestine and hypolipidemia. Deletion of SURF4 impeded the transport of apolipoprotein A1 (ApoA1), proline-rich acidic protein 1 (PRAP1), and apolipoprotein B48 (ApoB48) and hindered the assembly and secretion of chylomicrons and high-density lipoproteins. CONCLUSIONS: SURF4 emerges as a pivotal regulator of intestinal lipid absorption via mediating the secretion of ApoA1, PRAP1 and ApoB48.

Analysis of textbook outcomes for ampullary carcinoma patients following pancreaticoduodenectomy.

BACKGROUND: Textbook outcomes (TOs) have been used to assess the quality of surgical treatment for many digestive tumours but not ampullary carcinoma (AC). AIM: To discuss the factors associated with achieving a TO and further explore the prognostic value of a TO for AC patients undergoing curative pancreaticoduodenectomy (PD). METHODS: Patients who underwent PD at the China National Cancer Center between 1998 and 2020 were identified. A TO was defined by R0 resection, examination of ≥ 12 Lymph nodes, no prolonged hospitalization, no intensive care unit treatment, no postoperative complications, and no 30-day readmission or mortality. Cox regression analysis was used to identify the prognostic value of a TO for overall survival (OS) and recurrence-free survival (RFS). Logistic regression was used to identify predictors of a TO. The rate of a TO and of each indicator were compared in patients who underwent surgery before and after 2010. RESULTS: Ultimately, only 24.3% of 272 AC patients achieved a TO. A TO was independently associated with improved OS [hazard ratio (HR): 0.443, 95% confidence interval (95%CI): 0.276-0.711, P = 0.001] and RFS (HR: 0.379, 95%CI: 0.228-0.629, P < 0.001) in the Cox regression analysis. Factors independently associated with a TO included a year of surgery between 2010 and 2020 (OR: 4.549, 95%CI: 2.064-10.028, P < 0.001) and N1 stage disease (OR: 2.251, 95%CI: 1.023-4.954, P = 0.044). In addition, the TO rate was significantly higher in patients who underwent surgery after 2010 (P < 0.001) than in those who underwent surgery before 2010. CONCLUSION: Only approximately a quarter (24.3%) of AC patients achieved a TO following PD. A TO was independently related to favourable oncological outcomes in AC and should be considered as an outcome measure for the quality of surgery. Further multicentre research is warranted to better elucidate its impact.

Novel prognostic score based on the preoperative total bilirubin-albumin ratio and fibrinogen-albumin ratio in ampullary adenocarcinoma.

BACKGROUND: The preoperative total bilirubin-albumin ratio (TBAR) and fibrinogen-albumin ratio (FAR) have been proven to be valuable prognostic factors in various cancers. AIM: To detect the prognostic value of TBAR and FAR in ampullary adenocarcinoma (AC) patients who underwent curative pancreaticoduodenectomy. METHODS: AC patients who underwent curative pancreaticoduodenectomy in the National Cancer Center of China between 1998 and 2020 were retrospectively reviewed. The prognostic cutoff values of TBAR and FAR were determined through the best survival separation model. Then, a novel prognostic score combining TBAR and FAR was calculated and validated through the logistic regression analysis and Cox regression analysis. RESULTS: A total of 188 AC patients were enrolled in the current study. The best cutoff values of TBAR and FAR for predicting overall survival were 1.7943 and 0.1329, respectively. AC patients were divided into a TBAR-low group (score = 0) vs a TBAR-high group (score = 1) and a FAR-low group (score = 0) vs a FAR-high group (score = 1). The total score was calculated as a novel prognostic factor. Multivariable logistic regression analysis revealed that a high score was an independent protective factor for recurrence [score = 1 vs score = 0: Odds ratio (OR) = 0.517, P = 0.046; score = 2 vs score = 0 OR = 0.236, P = 0.038]. In addition, multivariable survival analysis also demonstrated that a high score was an independent protective factor in AC patients (score = 2 vs score = 0: Hazard ratio = 0.230, P = 0.046). CONCLUSION: A novel prognostic score based on preoperative TBAR and FAR has been demonstrated to have good predictive power in AC patients who underwent curative pancreaticoduodenectomy. However, more studies with larger samples are needed to validate this conclusion.

Impact of perioperative blood transfusion on oncological outcomes in ampullary carcinoma patients underwent pancreaticoduodenectomy.

BACKGROUND: The effect of perioperative blood transfusion (PBT) on the prognosis of ampullary carcinoma (AC) is still debated. AIM: To explore the impact of PBT on short-term safety and long-term survival in AC patients who underwent pancreaticoduodenectomy. METHODS: A total of 257 patients with AC who underwent pancreaticoduodenectomy between 1998 and 2020 in the Cancer Hospital, Chinese Academy of Medical Sciences, were retrospectively analyzed. We used Cox proportional hazard regression to identify prognostic factors of overall survival (OS) and recurrence-free survival (RFS) and the Kaplan-Meier method to analyze survival information. RESULTS: A total of 144 (56%) of 257 patients received PBT. The PBT group and nonperioperative blood transfusion group showed no significant differences in demographics. Patients who received transfusion had a comparable incidence of postoperative complications with patients who did not. Univariable and multivariable Cox proportional hazard regression analyses indicated that transfusion was not an independent predictor of OS or RFS. We performed Kaplan-Meier analysis according to subgroups of T stage, and subgroup analysis indicated that PBT might be associated with worse OS (P < 0.05) but not RFS in AC of stage T1. CONCLUSION: We found that PBT might be associated with decreased OS in early AC, but more validation is needed. The reasonable use of transfusion might be helpful to improve OS.

Laparoscopic endoscopic cooperative surgery for the duodenal neuroendocrine tumor: a single-center case series (How I Do It).

BACKGROUND: Duodenal neuroendocrine tumors (D-NETs) are uncommon. The surgical treatment for D-NETs was in debate. Laparoscopic and endoscopic cooperative surgery (LECS) is a promising approach for treating gastrointestinal tumors. The study aimed to evaluate the feasibility and safety of LECS for D-NETs. Meanwhile, the authors described the details of the LECS technique. METHODS: All patients diagnosed with D-NETs underwent LECS between September 2018 and April 2022 were retrospectively reviewed. The endoscopic procedures were performed with endoscopic full-thickness resection. The defect was manually closed under the surveillance of the laparoscopy. RESULTS: A total of seven patients were enrolled, including three men and four women. The median age was 58 years (ranging from 39-65). Four tumors were located in the bulb and three in the second portion. All cases were diagnosed as NET with grade G1. The tumor depth was pT1 in two cases and pT2 in five cases. The median specimen size and the tumor size were 22 mm (ranging from 10-30) and 8.0 mm (ranging from 2.3-13.0), respectively. En-bloc resection and curative resection rates are 100 and 85.7%, respectively. There were no severe complications. Until 1 June 2022, there was no recurrence. The median follow-up was 9.5 months (range, 1.4-45.1). CONCLUSIONS: LECS with endoscopic full-thickness resection is a reliable surgical procedure. The minimally invasive advantages of LECS enable more individualized treatment options for a specific group. Limited by the length of observation, the long-term performance of LECS for D-NETs requires additional investigation.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

[Prognosis and Related Factors of Patients with Pathological Complete Response after Neoadjuvant Therapy for Gastric Cancer].

Objective To investigate the related factors of pathological complete response(pCR)of patients with gastric cancer treated by neoadjuvant therapy and resection,and to analyze the risk factors of prognosis. Methods The clinical and pathological data of 490 patients with gastric cancer who received neoadjuvant therapy followed by radical gastrectomy from January to December in 2008 were retrospectively analyzed.Univariate and multivariate analyses were performed to identify the risk factors affecting pCR and prognosis. Results Among the 490 patients,41 achieved pCR,and the overall pCR rate was 8.3%(41/490).The pCR rate was 16.0% in the neoadjuvant chemoradiation group and 6.4% in the neoadjuvant chemotherapy group.The results of multivariate analysis showed that neoadjuvant chemoradiation(OR=4.401,95% CI=2.023-9.574,P<0.001)and preoperative therapeutic response as partial response(OR=40.492,95% CI=5.366-305.572,P<0.001)were independent predictors of pCR after neoadjuvant therapy.Multivariate analysis of prognosis showed that poorly differentiated tumor(HR=1.809,95% CI=1.104-2.964,P=0.019),gastric cardia-fundus-body tumor(HR=2.025,95% CI=1.497-2.739,P<0.001),≤15 intraoperative dissected lymph nodes(HR=1.482,95% CI=1.059-2.073,P=0.022),and postoperative complications(HR=1.625,95% CI=1.156-2.285,P=0.005)were independent risk factors for prognosis,while pCR(HR=0.153,95% CI=0.048-0.484,P=0.001)and postoperative adjuvant chemotherapy(HR=0.589,95% CI=0.421-0.823,P<0.001)were independent protective factors of prognosis. Conclusions Patients who achieved pCR after neoadjuvant therapy for locally advanced gastric cancer might have promising long-term survival,and pCR is an independent predictor for overall survival.Compared with chemotherapy alone,preoperative chemoradiotherapy can significantly improve the pCR rate of patients with locally advanced gastric cancer.

Long non-coding RNA Igf2as controls hepatocellular carcinoma progression through the ERK/MAPK signaling pathway.

Long non-coding RNAs (lncRNAs) serve an important role in numerous human diseases, including cancer. Abnormal expression of lncRNAs has been associated with a number of tumor types; however, the underlying mechanisms through which lncRNA functions have yet to be elucidated. The present study primarily focuses on insulin-like growth factor 2 antisense 1 (Igf2as), a lncRNA reported to be differentially expressed in hepatocellular carcinoma (HCC). Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the level of Igf2as in HCC cells and tissues. Flow cytometry was used to determine the level of cell apoptosis following Igf2as suppression and western blot analysis was used to identify altered protein expression levels. The results demonstrated that Igf2as was upregulated in HCC cells and tissues, and that the inhibition of Igf2as using a targeted small interfering RNA (si-Igf2as), significantly decreased cell proliferation and increased apoptosis. Western blot analysis identified that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway was inhibited in cells transfected with si-Igf2as. In addition, cell migration was markedly reduced by the knockdown of Igf2as. These results suggest that lncRNA Igf2as may control hepatocellular progression primarily through the regulation of the ERK/MAPK signaling pathway.

A nomogram to predict lymph node metastasis in patients with early gastric cancer.

BACKGROUND: Lymph node status is crucial to determining treatment for early gastric cancer (EGC). We aim to establish a nomogram to predict the possibility of lymph node metastasis (LNM) in EGC patients. METHODS: Medical records of 952 EGC patients with curative resection, from 2002 to 2014, were retrospectively retrieved. Univariate and multivariate analysis were performed to examine risk factors associated with LNM. A nomogram for predicting LNM was established and internally validated. RESULTS: Five variables significantly associated with LNM were included in our model, these are sex (Odd ratio [OR] = 1.961, 95% confidence index [CI], 1.334 to 2.883; P = 0.001), depth of tumor (OR = 2.875, 95% CI, 1.872 to 4.414; P = 0.000), tumor size (OR = 1.986, 95% CI, 1.265 to 3.118; P = 0.003), histology type (OR = 2.926, 95% CI, 1.854 to 4.617; P = 0.000) and lymphovascular invasion (OR = 4.967, 95% CI, 2.996 to 8.235; P = 0.000). The discrimination of the prediction model was 0.786. CONCLUSIONS: A nomogram for predicting lymph node metastasis in patients with early gastric cancer was successfully established, which was superior to the absolute endoscopic submucosal dissection (ESD) indication in terms of the clinical performance.

A nomogram for predicting the likelihood of lymph node metastasis in early gastric signet ring cell carcinoma: A single center retrospective analysis with external validation.

Treatment algorithm has not been established for early gastric cancer with signet ring cell carcinoma (SRC), which has a reported low rate of lymph node metastasis (LNM) similar to differentiated cancer. A cohort of 256 patients with early gastric SRC at our center between January 2002 and December 2015 were retrospectively reviewed. Multivariate logistic regression analysis was used to determine the independent factors of LNM. A nomogram for predicting LNM was constructed and internally validated. Additional external validation was performed using the database from Cancer Institute Ariake Hospital in Tokyo (n = 1273). Clinical performance of the model was assessed by decision analysis of curve. The overall LNM incidence was 12.9% (33/256). The multivariate logistic model identified sex, tumor size, and LVI as covariates associated with LNM. Subsequently, a nomogram consisted of sex, tumor size, and depth of invasion was established. The model showed qualified discrimination ability both in internal validation (area under curve, 0.801; 95% confidence interval [CI], 0.729-0.873) and in external dataset (area under curve, 0.707; 95% CI, 0.657-0.758). Based on the nomogram, treatment algorithm for early gastric SRC was proposed to assist clinicians in making better decisions. We developed a nomogram predicting risk of LNM for early gastric SRC, which should be helpful for patient counseling and surgical decision-making.

Risk Factors for Lymph Node Metastasis in Early Gastric Cancer with Signet Ring Cell Carcinoma.

BACKGROUND: Gastrectomy was reported to be an excessive approach for early gastric cancer with signet ring cell carcinoma. This study was conducted to explore the feasibility of endoscopic submucosal dissection for early gastric with signet ring cell carcinoma. METHODS: Data from 1067 patients who underwent gastrectomy for early gastric cancer were collected retrospectively. The association between the clinicopathological factors and the lymph node metastasis was analyzed by univariate and multivariate logistic regression analyses. RESULTS: Lymph node metastasis was confirmed in 17.2 % (184/1067) of patients. Meanwhile, the incidence of lymph node metastasis with each histology type was 13.1 % (26/198), 9.8 % (34/347), and 23.8 % (124/522) for signet ring cell carcinoma, differentiated carcinomas, and undifferentiated carcinomas, respectively. Signet ring cell carcinoma occurs more in women and young patients, with a higher predominance for mucosa. Various factors-including sex, tumor size, depth of tumor, and lymphovascular invasion-were found to be associated with lymph node metastasis for signet ring cell carcinoma (P < 0.05). Multivariate analysis revealed that tumor size (7.489, 95 % CI 2.025-27.701) and lymphovascular invasion (18.434, 95 % CI 3.256-104.359) were independent risk factors for lymph node metastasis (P < 0.05). Further analysis reveals there was no positive lymph node in patients with signet ring cell carcinoma when tumor confined to mucosa, size ≤2 cm and without lymphovascular invasion and ulceration. CONCLUSIONS: Given the low risk of lymph node involvement, we recommend that endoscopic submucosal dissection be safely applied for early gastric signet ring cell carcinoma when tumor confined to mucosa, size ≤2 cm, and without lymphovascular invasion and ulceration.

[SNCG expression and clinical significance in colorectal cancer liver metastasis].

OBJECTIVE: To investigate the expression of SNCG in colorectal cancer with liver metastasis and its clinical significance. METHODS: Surgical specimens were collected from 217 colorectal cancer patients with complete clinical and follow up data between January 1999 and December 2003. There were 113 cases with liver metastasis and 104 without liver metastasis. SNCG expression was identified by immunohistochemistry. Association of SNCG expression with clinicopathologic factors and prognosis of colorectal cancer was accessed. RESULTS: The positive rate of SNCG in colorectal cancer with and without liver metastasis was 68.1% and 27.9%, respectively, and the difference was statistically significant(P<0.05). Logistic regression analysis showed that SNCG expression was an independent factor associated with the presence of liver metastasis(OR=8.29, 95%CI: 3.37-20.37, P<0.01). In synchronous colorectal liver metastasis, the median survival time of SNCG-negative and SNCG-positive was 12.6 months and 8.2 months, respectively(Log Rank, P<0.05). Multivariate Cox analysis showed that SNCG expression was an independent prognostic factor for colorectal cancer with synchronous liver metastasis(RR=1.97, 95%CI:1.10-3.53, P<0.05). CONCLUSIONS: High expression of SNCG is present in the tumor tissue in patients with liver metastasis from colorectal cancer. SNCG may be used as a predictive biomarker for colorectal liver metastases and is an important prognostic factor in patients with liver metastasis from colorectal cancer.

Diagnosis of colon cancer with Fourier transform infrared spectroscopy on the malignant colon tissue samples.

BACKGROUND: Fourier transform infrared spectroscopy (FT-IR) combined with chemometrics discriminant analysis technology could improve diagnosis. The present study aimed to evaluate the effects of FT-IR on malignant colon tissue samples in diagnosis of colon cancer. METHODS: Principal component analysis (PCA) and support vector machine classification were used to discriminate FT-IR spectra from malignant and normal tissue. Colon tissues samples from 85 patients were used to demonstrate the procedure. RESULTS: For this set of colon spectral data, the sensitivity and specificity of the support vector machine (SVM) classification were found both higher than 90%. CONCLUSIONS: FT-IR provided important information about cancerous tissue, which could be used to discriminate malignant from normal tissues. The combination of PCA and SVM classification indicated that FT-IR has a potential clinical application in diagnosis of colon cancer.