microRNA-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation.

BACKGROUND: Epigenetic alterations contribute greatly to the development and progression of colorectal cancer, and effect of aberrant miR-622 expression is still controversial. This study aimed to discover miR-622 regulation in CRC proliferation. METHODS: miR-622 expression and prognosis were analyzed in clinical CRC samples from Nanfang Hospital. miR-622 regulation on cell cycle and tumor proliferation was discovered, and FOLR2 was screened as functional target of miR-622 using bioinformatics analysis, which was validated via dual luciferase assay and gain-of-function and loss-of-function experiments both in vitro and in vivo. RESULTS: miR-622 overexpression in CRC indicated unfavorable prognosis and it regulated cell cycle to promote tumor growth both in vitro and in vivo. FOLR2 is a specific, functional target of miR-622, which negatively correlates with signature genes in cell cycle process to promote CRC proliferation. CONCLUSIONS: miR-622 upregulates cell cycle process by targeting FOLR2 to promote CRC proliferation, proposing a novel mechanism and treatment target in CRC epigenetic regulation of miR-622.

Pharmacologic inhibition of IL11/STAT3 signaling increases MHC-I expression and T cell infiltration.

BACKGROUND: Recent studies have discovered an emerging role of IL11 in various colitis-associated cancers, suggesting that IL11 mainly promotes tumor cell survival and proliferation in regulating tumorigenesis. Herein we aimed to reveal a novel function of IL-11 through STAT3 signaling in regulating tumor immune evasion. METHODS: AOM/DSS model in Il11-/- and Apcmin/+/Il11-/- mice were used to detect tumor growth and CD8+ T infiltration. STAT1/3 phosphorylation and MHC-I, CXCL9, H2-K1 and H2-D1 expression were detected in MC38 cells and intestine organoids treated with/without recombinant IL11 to explore effect of IL11/STAT3 signaling, with IL11 mutein used to competitively inhibit IL11 and rescue inhibited STAT1 activation. Correlation between IL11 and CD8+ T infiltration was analyzed using TIMER2.0 website. IL11 expression and survival prognosis was analyzed in clinical data of patient cohort from Nanfang Hospital. RESULTS: IL11 is highly expressed in CRC and indicates unfavorable prognosis. IL11 knockout increased CD8+ T cell infiltration and reduced intestinal and colon formation. Tumors were significantly suppressed while MHC-I and CXCL9 expression for CD8+ T infiltration were remarkably increased in the tumor tissues of Apcmin/+/Il11-/- mice or Il11-/- mice induced by AOM/DSS. IL11/STAT3 signaling downregulated MHC-I and CXCL9 by inhibiting IFNγ-induced STAT1 phosphorylation. IL11 mutein competitively inhibit IL11 to upregulate CXCL9 and MHC-I in tumor and attenuated tumor growth. CONCLUSIONS: This study ascribes for a new immunomodulatory role for IL11 during tumor development that is amenable to anti-cytokine based therapy of colon cancer.

Short-term and long-term outcomes of single-incision plus one-port laparoscopic surgery for colorectal cancer: a propensity-matched cohort study with conventional laparoscopic surgery.

BACKGROUND: Single-incision plus one-port laparoscopic surgery (SILS + 1) has been demonstrated to be minimally invasive while possessing better cosmesis and less pain compared with conventional laparoscopic surgery (CLS). However, SILS + 1 as an alternative to CLS for colorectal cancer is still controversial. METHODS: A total of 1071 patients who underwent curative laparoscopic surgery for colon cancer between 2015 and 2018 were included. Of these patients, 258 SILS + 1 cases and 516 CLS cases were analyzed using propensity score matching. The baseline characteristics, surgical outcomes, pathologic findings and recovery course, morbidity and mortality within postoperative 30 days and 3-year disease-free and overall survival were compared. RESULTS: Baseline characteristics were balanced between the groups. The mean operating time was significantly shorter in SILS + 1 group, with less estimated blood loss. Tumor size, tumor differentiation, number of harvested lymph nodes, resection margin and pathologic T, N, TNM stage was similar between the groups. There was no significant difference in overall perioperative complications. Uni- and multivariate analyses revealed that SILS + 1 was not a risk factor for complications. Postoperatively, SILS + 1 group showed faster recovery than CLS group in terms of ambulation, bowel function, oral intake and discharge. The 3-year disease-free survival rates of SILS + 1 and CLS groups were 90.1% and 87.3%(p = 0.59), respectively and the 3-year overall survival rates were 93.3% vs. 89.8%(p = 0.172). DISCUSSION: Our study revealed that SILS + 1 is safe, feasible, oncologically efficient, and may be considered as a surgical option for selected patients with colorectal cancer.

FAM98A promotes resistance to 5-fluorouracil in colorectal cancer by suppressing ferroptosis.

BACKGROUND: FAM98A is a microtubule-associated protein involved in cell proliferation and migration, and is frequently dysregulated in epithelial cancers. But its role in the development of colorectal cancer (CRC) cancer remains unknown. METHODS: Immunohistochemical analysis was performed to examine the expression of FAM98A in CRC samples. We also investigated the effects of abnormal expression on the biological behavior of colorectal cancer cells both in vitro and in vivo. Immunoblotting and immunoprecipitation were used to screen FAM98A-related signalling pathways and downstream factors. RESULTS: FAM98A was upregulated in CRC tissues and CRC cell lines. Overexpression of FAM98A promoted cell proliferation and recovered 5-FU suppressed CRC cell proliferation both in vitro and in vivo. In addition, the Enhanced expression of FAM98A inhibited ferroptosis in CRC cells by activating the translation of xCT in stress granules (SGs). Furthermore, we identified that metformin could reverse FAM98A-mediated 5-FU resistance in CRC cells. CONCLUSIONS: Our results for the first time indicate that FAM98A plays a critical role in promoting CRC progression, which provides a novel target for clinical drug resistance of colorectal cancer. And metformin may sensitize 5-FU in the treatment of colorectal cancer.

Prognostic value and nomograms of proximal margin distance in gastric cancer with radical distal gastrectomy.

OBJECTIVE: The proximal margin (PM) distance for distal gastrectomy (DG) of gastric cancer (GC) remains controversial. This study investigated the prognostic value of PM distance for survival outcomes, and aimed to combine clinicopathologic variables associated with survival outcomes after DG with different PM distance for GC into a prediction nomogram. METHODS: Patients who underwent radical DG from June 2004 to June 2014 at Department of General Surgery, Nanfang Hospital, Southern Medical University were included. The first endpoints of the prognostic value of PM distance (assessed in 0.5 cm increments) for disease-free survival (DFS) and overall survival (OS) were assessed. Multivariate analysis by Cox proportional hazards regression was performed using the training set, and the nomogram was constructed, patients were chronologically assigned to the training set for dates from June 1, 2004 to January 30, 2012 (n=493) and to the validation set from February 1, 2012 to June 30, 2014 (n=211). RESULTS: Among 704 patients with pTNM stage I, pTNM stage II, T1-2, T3-4, N0, differentiated type, tumor size ≤5.0 cm, a PM of (2.1-5.0) cmvs. PM≤2.0 cm showed a statistically significant difference in DFS and OS, while a PM>5.0 cm was not associated with any further improvement in DFS and OSvs. a PM of 2.1-5.0 cm. In patients with pTNM stage III, N1, N2-3, undifferentiated type, tumor size >5.0 cm, the PM distance was not significantly correlated with DFS and OS between patients with a PM of (2.1-5.0) cm and a PM≤2 cm, or between patients with a PM >5.0 cm and a PM of (2.1-5.0) cm, so there were no significant differences across the three PM groups. In the training set, the C-indexes of DFS and OS, were 0.721 and 0.735, respectively, and in the validation set, the C-indexes of DFS and OS, were 0.752 and 0.751, respectively. CONCLUSIONS: It is necessary to obtain not less than 2.0 cm of PM distance in early-stage disease, while PM distance was not associated with long-term survival in later and more aggressive stages of disease because more advanced GC is a systemic disease. Different types of patients should be considered for removal of an individualized PM distance intra-operatively. We developed a universally applicable prediction model for accurately determining the 1-year, 3-year and 5-year DFS and OS of GC patients according to their preoperative clinicopathologic characteristics and PM distance.

Short-term outcomes of single-incision plus one-port laparoscopic versus conventional laparoscopic surgery for rectosigmoid cancer: a randomized controlled trial.

OBJECTIVE: The objective of the study is to evaluate the short-term outcomes of single-incision plus one-port surgery (SILS + 1) compared with conventional laparoscopic surgery (CLS) for colonic cancer. BACKGROUND: At present, single-incision laparoscopic colectomy remains technically challenging. The use of SILS + 1 as an alternative has gained increasing attention; however, its safety and efficacy remain controversial. METHODS AND PATIENTS: Between April 2014 and July 2016, 198 patients with clinical stage T1-4aN0-2 M0 rectosigmoid cancer were enrolled. The participants were randomly assigned to either SILS + 1 (n = 99) or CLS (n = 99). The morbidity and mortality within 30 days, operative and pathologic outcomes, postoperative recovery course, inflammation and immune responses, and pain intensity were compared. RESULTS: There was no significant difference in overall complications between the two groups (17.2 vs. 16.3%, P = 1.000). The total operating time for the SILS + 1 group was significantly shorter (100.8 ± 30.4 vs. 116.6 ± 36.6, P = 0.002). Blood loss was significantly greater in the CLS group (20 vs. 50, P < 0.001). Thirteen patients (14%) in the CLS group required additional postoperative analgesics, which was significantly more than four patients in the SILS + 1 group. Notably, on postoperative day three, the visual analogue scale score of the CLS group was greater than that of the SILS + 1 group (1.3 ± 1.1 vs. 1.7 ± 1.3, P = 0.023). Tumor diameter, pathologic stage, length of the proximal and distal margins, and number of lymph nodes harvested were similar, other values were also similar between the two groups. CONCLUSION: Our findings suggest that SILS + 1 might be safe and feasible for rectosigmoid cancer when performed by experienced surgeons. It offers minimal invasiveness without compromising oncologic treatment principles. Trial Registration This trial was registered on ClinicalTrials.gov (NCT02117557).

Long-term outcomes of laparoscopy-assisted distal gastrectomy versus open distal gastrectomy for gastric cancer: a 10-year single-institution experience.

BACKGROUND: Laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer has been widely applied; however, its oncologic efficacy has yet been well established. The study aimed to compare the long-term oncologic outcomes of LADG versus open distal gastrectomy (ODG) on gastric cancer. METHODS: The clinicopathologic data of gastric cancer patients who underwent distal gastrectomy with curative intent from October 2004 through September 2014 were included and analyzed in a retrospective cohort. The last follow-up was September 2016. RESULTS: 769 eligible patients (LADG 414 vs. ODG 355) were included in the study. No significant difference was observed between the groups in 5-year DFS (LADG 61.2% vs. ODG 59.1%; p = 0.384) and OS rates (LADG 65.8% vs. ODG 66.3%; p = 0.750). During surgery, though LADG group had longer operating time, the blood loss was less than ODG group. LADG group had faster postoperative recovery course including shorter time to oral intake, ambulation, and discharge time. Postoperative complication rate within 30 days showed no significant difference between the groups (LADG 15.7% vs. ODG 13.0%; p = 0.281). Age over 65 years old, blood loss > 200 ml, postoperative complication, and advanced T and N stage were identified as independent risk factors for DFS and OS. CONCLUSIONS: LADG could yield similar oncologic outcomes compared with ODG in treating distal gastric cancer. However, the findings need to be further confirmed through ongoing prospective randomized controlled trials.

ImmunoScore Signature: A Prognostic and Predictive Tool in Gastric Cancer.

OBJECTIVE: We postulated that the ImmunoScore (IS) could markedly improve the prediction of postsurgical survival and chemotherapeutic benefits in gastric cancer (GC). SUMMARY BACKGROUND DATA: A prediction model for GC patients was developed using data from 879 consecutive patients. METHODS: The expression of 27 immune features was detected in 251 specimens by using immunohistochemistry, and a 5-feature-based ISGC was then constructed using the LASSO Cox regression model. Testing and validation cohorts were included to validate the model. RESULTS: Using the LASSO model, we established an ISGC classifier based on 5 features: CD3invasive margin (IM), CD3center of tumor (CT), CD8IM, CD45ROCT, and CD66bIM. Significant differences were found between the high-ISGC and low-ISGC patients in the training cohort in 5-year disease-free survival (45.0% vs. 4.4%, respectively; P <0.001) and 5-year overall survival (48.8% vs. 6.7%, respectively; P <0.001). Multivariate analysis revealed that the ISGC classifier was an independent prognostic factor. A combination of ISGC and tumor, node, and metastasis (TNM) had better prognostic value than TNM stage alone. Further analysis revealed that stage II and III GC patients with high-ISGC exhibited a favorable response to adjuvant chemotherapy. Finally, we constructed 2 nomograms to predict which patients with stages II and III GC might benefit from adjuvant chemotherapy after surgery. CONCLUSIONS: The ISGC classifier could effectively predict recurrence and survival of GC, and complemented the prognostic value of the TNM staging system. Moreover, the ISGC might be a useful predictive tool to identify stage II and III GC patients who would benefit from adjuvant chemotherapy.

Reduced Port Laparoscopic Distal Gastrectomy with D2 Lymphadenectomy.

BACKGROUND: Reduced port laparoscopic surgery (RPLS), as a more minimally invasive treatment alternative to conventional laparoscopic surgery (CLS), has been increasing in recent years. 1 With the accumulation of surgical experience and improvements in surgical techniques, the indication of RPLS has been gradually extended from benign diseases to malignant tumors, including gastric cancer. 2-4 However, due to the lack of counteraction and triangulation, lymphadenectomy during reduced port laparoscopic gastrectomy (RPLG) for gastric cancer was considered challenging. In this study, we report our experience performing RPLG with D2 lymphadenectomy for distal gastric cancer. METHODS: A disposable, single-incision, multiport, laparoscopic surgery trocar was used through a 3-cm incision at the umbilicus for the laparoscopist and surgeon's right hand. One 12-mm trocar was inserted at the upper-right quadrant for the surgeon's left hand. Distal gastrectomy with D2 lymphadenectomy was performed in the same manner with CLS. 5 After extracting the resected specimen through the umbilicus incision, intracorporeal Roux-en-Y or B-II gastrojejunostomy was used for reconstruction. RESULTS: RPLG with D2 lymphadenectomy was performed on five patients from April 2017 to June 2017. No intraoperative event requiring conversion to CLS or open surgery occurred. No postoperative complication was observed. The median operating time and blood loss was 166 min and 50 ml. The mean number of retrieved lymph nodes was 32.7. Postoperatively, the mean time to first flatus, soft intake, and hospital stay was 2.6, 3.5, and 6.7 days respectively. CONCLUSIONS: RPLG with D2 lymphadenectomy might be safe and feasible in selected patients.

Laparoscopy-assisted colectomy as an Oncologically safe alternative for patients with stage T4 Colon Cancer: a propensity-matched cohort study.

BACKGROUND: It is still controversial whether laparoscopy-assisted colectomy (LAC) is suitable for patients with stage T4 colon cancer. This study aimed to compare the short- and long-term outcomes of LAC and open colectomy (OC) for patients with pathologic T4 colon cancer. METHODS: Data of eligible patients with colon cancer in our institution from March 2004 to September 2014 were retrospectively reviewed. The patients were followed up to September 2016. Propensity score matching was performed to control the bias. RESULTS: Two hundred and forty two patients were selected by propensity score matching, with 121 patients in the LAC group and 121 in the OC group. Mean operating time and rate of intraoperative blood transfusion were similar between two groups. In LAC group, shorter time to first flatus and first liquid intake were observed in patients with pT4b stage disease, but not for patients with pT4a stage disease. Less blood loss and shorter length of postoperative hospital stay were examined in LAC group, including pT4a and pT4b stages. Conversion was required in 9.1% (11 out of 121) cases. DFS and OS were similar between LAC and OC groups. The 5-year DFS rate was 64.2% for pT4a stage and 35.5% for pT4b stage in LAC group, and 62.9% and 33.7% in OC group for pT4a (p = 0.374) and pT4b (p = 0.385) stage respectively. For 5-year OS rates, two groups did not differ in pT4a stage (LAC 69.2% vs. OC 66.0%, p = 0.151) and pT4b stage (LAC 37.5% vs. OC 38.1%, p = 0.510). CONCLUSIONS: Laparoscopic colectomy appears to be safe for selected patients with pT4 colon cancer in centres with expertise in minimally invasive surgery.

Multidimensional analyses of the learning curve for single-incision plus one port laparoscopic surgery for sigmoid colon and upper rectal cancer.

BACKGROUND AND OBJECTIVES: Single-incision plus one port surgery (SILS + 1) provides the advantages of being minimally invasive and easier to perform than pure single-incision laparoscopic surgery. The aim of this study was to investigate the learning curve (LC) for SILS + 1 for sigmoid colon and upper rectal cancer. METHOD: From November 2012 to May 2014, a series of 85 consecutive patients underwent selective SLIS + 1 for sigmoid colon and upper rectal cancer performed by a single surgeon at Nanfang Hospital. The LC for SILS + 1 was evaluated using cumulative sum control chart (CUSUM) and risk-adjusted CUSUM methods. Data for all the perioperative variables and pathologic results among the phases were compared. RESULTS: The LC had three phases: phase 1 (cases 1-13) was the initial learning period; phase 2 (cases 14-44) was the learning plateau period; and phase 3 (cases 45-85) was the competent period. The differences in total operating time among the three phases were significant. The number of harvested lymph nodes increased along with increases in the surgeon's experience. CONCLUSIONS: For experienced CLS surgeons, the learning process reached the plateau period after the 13th case, and technical competence was achieved after the 44th case.

Short-term outcomes of intracorporeal esophagojejunostomy using the transorally inserted anvil versus extracorporeal circular anastomosis during laparoscopic total gastrectomy for gastric cancer: a propensity score matching analysis.

BACKGROUND: To assess the short-term outcomes of intracorporeal Roux-en-Y esophagojejunostomy using the transorally inserted anvil (OrVil) compared with extracorporeal circular Roux-en-Y anastomosis during laparoscopic total gastrectomy (LTG) for gastric cancer. METHODS: From January 2011-April 2014, a total of 165 consecutive patients with gastric cancer underwent either intracorporeal Roux-en-Y esophagojejunostomy (n = 25) using the Orvil or extracorporeal circular anastomosis (n = 140) during LTG. After generating propensity scores with six covariates, including gender, age, body mass index (BMI), Eastern Cooperative Oncology Group performance status, tumor location, and tumor size, 25 patients undergoing the OrVil method (intracorporeal group) were one-to-one matched with 25 patients undergoing the extracorporeal method (extracorporeal group). The short-term outcomes were compared between the two groups. RESULTS: Both groups were balanced regarding baseline variables. The total operative time was not significantly different between the two groups (216.5 ± 24.9 min versus 224.0 ± 30.5 min, P = 0.344), whereas either the duration of anvil insertion (9.9 ± 2.4 min versus 12.9 ± 2.0 min, P < 0.001) or reconstruction completion (44.4 ± 9.4 min versus 50.1 ± 5.4 min, P = 0.012) in the intracorporeal group was less. The mean length of minilaparotomy in the intracorporeal group was shorter (5.6 ± 0.4 cm versus 7.2 ± 1.7 cm, P < 0.001). No significant differences were observed in intraoperative complication rate, estimated blood loss, length of proximal margin, or postoperative recovery course (including the time to first flatus, liquid resumption, liquid, and soft diet) between the two groups. No patients suffered from anastomosis-related complications. The overall morbidity rates of 28.0% in the intracorporeal group and 32.0% in the extracorporeal group were comparable (P = 0.758). CONCLUSIONS: Intracorporeal Roux-en-Y esophagojejunostomy using the transorally inserted anvil system may be a safe procedure during LTG for gastric cancer. However, a longer follow-up in a well-designed randomized controlled trial is necessary to more thoroughly evaluate this technique.

An automatically contamination-avoiding technique for intracorporeal esophagojejunostomy using a transorally inserted anvil during laparoscopic total gastrectomy for gastric cancer.

BACKGROUND: Intracorporeal Roux-en-Y esophagojejunostomy during laparoscopic total gastrectomy for gastric cancer remains a challenging manipulation due to the uncontrolled direction of the jejunal side or unintended embedded tissues, although several methods have been introduced. In this study, we simplified the procedure based on a surgical string fixing technique using a transorally inserted anvil (OrVil™; Covidien Ltd., Mansfield, MA, USA). METHODS: From March 2012 to September 2013, 14 consecutive patients underwent simplified intracorporeal Roux-en-Y esophagojejunostomy using OrVil™ during laparoscopic total gastrectomy for gastric cancer at our hospital. Clinicopathologic characteristics and surgical outcomes of these patients were retrospectively analyzed. RESULTS: All of the procedures were successful completed with no complication or conversion to open surgery. The mean overall operative time was 193.8 ± 41.8 min, whereas the mean reconstruction time was 32.6 ± 4.6 min. The mean estimated blood loss was 105.7 ± 65.4 ml. The mean diameter of anastomosis measured by upper gastrointestinal contrast X-ray test at 1 month after operation was 2.3 cm. During a median follow-up period of 12 months, neither local recurrence nor anastomosis-related morbidity was observed. CONCLUSIONS: Our preliminary results suggested that this automatically contamination-avoiding technique based on a surgical-string-fixing strategy using OrVil™ during laparoscopic total gastrectomy for gastric cancer might be feasible and safe and provide a simple solution for intracorporeal Roux-en-Y esophagojejunostomy.

Glycemic changes after gastrectomy in non-morbidly obese patients with gastric cancer and diabetes.

BACKGROUND/AIMS: To evaluate the glycemic changes after gastrectomy in non-morbidly obese patients with gastric cancer (GC) and type 2 diabetes mellitus (T2DM). METHODOLOGY: Between December 2011 and June 2014, we included 46 patients with gastric cancer and T2DM of a body mass index (BMI) < 30 kg/m2, who underwent gastrectomy in our center. The comparisons of FPGs in specific periods were performed according to age, extent of gastrectomy, reconstruction type, preoperative triglyceride (TG) level and so on. RESULTS: The non-morbidly obese patients experienced an improvement of glycemic control. T2DM resolution happened 3 weeks after surgery. FPG decreased significantly after postoperative day 21 compared to preoperative FPG. 32 patients experienced DM improvement after postoperative day 21. The age and relatively lower preoperative TG patients, who underwent total gastrectomy (P<0.001) or duodenal bypass reconstruction (Billroth II, Roux-en-Y gastrojejunostomy, or Roux-en-Y esophagojejunostomy, P=0.009) appeared to have a better glycemic control. CONCLUSIONS: Our finding observed through this simulation model suggested that non-morbidly obese patients may also benefit from metabolic surgery for glycemic control, associated with age, extent of gastrectomy, reconstruction type, and preoperative triglyceride level.

Oncologic outcomes of laparoscopy-assisted gastrectomy for advanced gastric cancer: a large-scale multicenter retrospective cohort study from China.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been indicated to be safe, feasible, and oncologically efficacious for the treatment of early gastric cancer by both retrospective and prospective studies. Although some reports have demonstrated that LAG was also a safe and technically feasible procedure for advanced gastric cancer (AGC), its oncologic outcomes have not yet been confirmed in a multicenter, large-scale study. The aim of this study was to evaluate the oncologic outcomes of LAG for AGC on a multicenter basis in China. METHODS: Data of 1,184 consecutive patients with locally AGC who underwent LAG with curative intent between February 2003 and December 2009 were collected from the Chinese Laparoscopic Gastrointestinal Surgery Study group database and retrospectively analyzed. Survival rates were estimated by the Kaplan-Meier method. Risk factors for recurrence and survival were evaluated by Cox regression models. RESULTS: Postoperatively, 121 patients (10.2%) experienced complications, and 1 patient died (0.1%). Median follow-up was 12 months. Recurrence was observed in 185 patients (16.7%), including hematogenous (31 patients), peritoneal (52), locoregional (25), distant lymph node (LN) (8), mixed (63), and uncertain (6) recurrences. The cumulative 3-year overall survival and disease-free survival rates were 75.3 and 69.0%, respectively. The 3-year overall survival and disease-free survival rates were 89.7 and 88.9% for stage I tumors, 85.0 and 77.0 % for stage II, 60.5 and 59.3% for stage III. Independent risk factors for recurrence were tumor size > 40 mm, intraoperative blood transfusion, and advanced tumor stage. For survival, age > 65 years, tumor size > 40 mm, and advanced tumor stage were independent risk factors. CONCLUSIONS: In addition to being safe and technically feasible, LAG for locally AGC could also yield acceptable short-term oncologic outcomes.

Functional evaluation of pure natural edible Ferment: protective function on ulcerative colitis.

Purpose: To investigate the therapeutic efficiency of a novel drink termed "Ferment" in cases of ulcerative colitis (UC) and its influence on the gut microbiota. Method: In this study, we developed a complex of mixed fruit juice and lactic acid bacteria referred to as Ferment. Ferment was fed to mice for 35 days, before inducing UC with Dextran Sulfate Sodium Salt. We subsequently investigated the gut microbiome composition using 16S rRNA sequencing. Result: After Ferment treatment, mouse body weight increased, and animals displayed less diarrhea, reduced frequency of bloody stools, and reduced inflammation in the colon. Beneficial bacteria belonging to Ileibacterium, Akkermansia, and Prevotellacea were enriched in the gut after Ferment treatment, while detrimental organisms including Erysipelatoclostridium, Dubosiella, and Alistipes were reduced. Conclusion: These data place Ferment as a promising dietary candidate for enhancing immunity and protecting against UC.

[The safety and long-term survival after laparoscopic surgery versus open surgery for colon cancer].

OBJECTIVE: To evaluate the short-term outcomes and 5-year recurrence, overall survival, and disease-free survival of laparoscopic assisted surgery for colon cancer. METHODS: The clinical and pathologic data were compared between the patients who underwent colectomy during March 2003 to July 2008 and assigned in laparoscopic group (n = 92) and open group (n = 285) according the surgical approach. The 5-year overall survival, disease-free survival, and recurrence rate were analyzed for all patients who were followed-up for more than 36 months in either of the groups. RESULTS: The laparoscopic colectomy was associated with manifested less blood loss (50(50) ml) (Z = -8.292, P < 0.01), early return of bowel function (the evacuation time was (3.0 ± 1.0) days, and the meal time after operation was (4.0 ± 1.3) days) (t = -6.475 and -4.871, P < 0.01), and longer length (cm) of distal resection margin ((10 ± 4) cm vs. (9 ± 4) cm, t = 3.527, P = 0.000). The 5-year overall survival of the laparoscopic group and the open group were 63.6% and 61.8% respectively. The 5-year disease-free survival of the I-III stage patients in the laparoscopic group and the open group were 69.5% and 65.5% respectively, and the local recurrence were 8.7% and 13.6% (all P > 0.05). CONCLUSION: The laparoscopic colectomy for colon cancer is safe in short-term clinical results and non-inferior to the open colectomy in long-term oncological outcomes.

Laparoscopic distal gastrectomy with D2 dissection for advanced gastric cancer.

The successful application of the laparoscopic distal gastrectomy with D2 dissection for gastric cancer requires adequate understanding of the anatomic characteristics of peripancreatic and intrathecal spaces, the role of pancreas and vascular bifurcation as the surgical landmarks, as well as the variations of gastric vascular anatomy. The standardized surgical procedures based on distribution of regional lymph node should be clarified.

ASCL2 induces an immune excluded microenvironment by activating cancer-associated fibroblasts in microsatellite stable colorectal cancer.

Proficient mismatch repair or microsatellite stable (pMMR/MSS) colorectal cancers (CRCs) are vastly outnumbered by deficient mismatch repair or microsatellite instability-high (dMMR/MSI-H) tumors and lack a response to immune checkpoint inhibitors (ICIs). In this study, we reported two distinct expression patterns of ASCL2 in pMMR/MSS and dMMR/MSI-H CRCs. ASCL2 is overexpressed in pMMR/MSS CRCs and maintains a stemness phenotype, accompanied by a lower density of tumor-infiltrating lymphocytes (TILs) than those in dMMR/MSI CRCs. In addition, coadministration of anti-PD-L1 antibodies facilitated T cell infiltration and provoked strong antitumor immunity and tumor regression in the MC38/shASCL2 mouse CRC model. Furthermore, overexpression of ASCL2 was associated with increased TGFB levels, which stimulate local Cancer-associated fibroblasts (CAFs) activation, inducing an immune-excluded microenvironment. Consistently, mice with deletion of Ascl2 specifically in the intestine (Villin-Cre+, Ascl2 flox/flox, named Ascl2 CKO) revealed fewer activated CAFs and higher proportions of infiltrating CD8+ T cells; We further intercrossed Ascl2 CKO with ApcMin/+ model suggesting that Ascl2-deficient expression in intestinal represented an immune infiltrating environment associated with a good prognosis. Together, our findings indicated ASCL2 induces an immune excluded microenvironment by activating CAFs through transcriptionally activating TGFB, and targeting ASCL2 combined with ICIs could present a therapeutic opportunity for MSS CRCs.

Effect of single-incision plus one port laparoscopic surgery assisted with enhanced recovery after surgery on colorectal cancer: study protocol for a single-arm trial.

BACKGROUND: Studies have proved that the enhanced recovery after surgery (ERAS) protocol can significantly improve the recovery course of patients during the perioperative period. The application of minimally invasive surgery is a critical component of ERAS protocol. Single-incision plus one port laparoscopic surgery (SILS plus one) could achieve further minimally invasive surgical results than conventional laparoscopic surgery (CLS). The objective of this trial is to evaluate the safety and feasibility of SILS plus one with ERAS protocol in colorectal cancer. METHODS: This is a prospective, single-center, open-label, single-arm trial. A total of 120 eligible patients with colorectal cancer will receive SILS plus one followed by the ERAS management during the perioperative period. The primary endpoint is postoperative hospital stay. The secondary endpoints include rehabilitative rate of the fourth postoperative day, postoperative medical cost, postoperative pain score, postoperative recovery indexes, inflammatory immune response indexes, compliance with ERAS measures, 6 min postoperative walking test (6MWT), hospital readmissions, and early postoperative complications. DISCUSSION: This trial will be the first to evaluate the short-term outcomes of SILS plus one assisted with ERAS protocol for patients with colorectal cancer and will provide valuable clinical evidence on the benefit of the combination of these two techniques, hopefully, to provide patients with more safe, economic, feasible, and rapid surgery and perioperative strategies. TRIAL REGISTRATION: Clinical Trial Registry, NCT0426829. Registered February 15, 2020 (https://clinicaltrials.gov/ct2/show/NCT04268290).