The effects of preoperative intestinal dysbacteriosis on postoperative recovery in colorectal cancer surgery: a prospective cohort study.

BACKGROUND: Accumulating evidence suggests a critical role of intestinal dysbacteriosis in surgical site infections and anastomotic leakage after abdominal surgery. However, a direct correlation between pre-existing dysbacteriosis and postoperative infectious complications has not yet been established clinically. METHODS: A total of 353 consecutive patients who underwent colorectal cancer (CRC) surgery were enrolled. Gram-stained faecal smears were tested at admission and the first defecation after surgery. Intestinal dysbacteriosis was graded into three groups: normal or slightly decreased intestinal microflora (grade 1), moderate dysbacteriosis (grade 2), and severe dysbacteriosis (grade 3). Clinical outcomes were postoperative infections and anastomotic leakage within 30 days after surgery. RESULTS: At the preoperative assessment, 268 (75.9%) patients had normal or slightly decreased intestinal microflora, 58 (16.4%) patients had moderate dysbacteriosis, and 27 (7.6%) patients had severe dysbacteriosis. The patients with preoperative dysbacteriosis had a higher rate of early postoperative diarrhoea (grade 2: OR = 4.53, 95% CI 2.28-9.00, grade 3: OR = 4.52, 95% CI 1.81-11.31), total complications (grade 3 40.7% vs. grade 2 25.9% vs. grade 1 12.7%, P < 0.001), and anastomotic leakage (grade 3 11.1% vs. grade 2 5.2% vs. grade 1 1.5%, P = 0.002). An interaction effect among preoperative dysbacteriosis and early postoperative diarrhoea on total complications was observed in rectal cancer patients (P for interaction = 0.007). CONCLUSIONS: An imbalance of the intestinal microbiome exists in a considerable proportion of CRC patients before surgery. Preoperative dysbacteriosis is associated with higher rates of early postoperative diarrhoea, which further correlates with infectious complications and anastomotic leakage. However, the contribution of preoperative dysbacteriosis to the occurrence of anastomotic leakage needs to be clarified in further studies. Trial registration ChiCTR, ChiCTR1800018755. Registered 8 October 2018-Retrospectively registered, http://www.chictr.org.cn/ChiCTR1800018755 .

Prognosis of synchronous colorectal carcinoma compared to solitary colorectal carcinoma: a matched pair analysis.

BACKGROUND: Synchronous colorectal carcinoma (CRC) is a specific and rare type of colorectal malignancy. The data on the impact of synchronous CRC are controversial. This study aimed to compare the characteristics and prognosis between synchronous CRC and solitary CRC. PATIENTS AND METHODS: 252 patients who underwent surgery between October 2009 and June 2013 with synchronous CRC (n = 126) or solitary CRC (n = 126) were included. The patients were matched according to age, sex, American Society of Anesthesiologists score, BMI, cancer grade, tumor location, and tumor stage. The short-term outcomes included the length of hospital stay, complications, and 30-day mortality. Long-term endpoints were overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). RESULTS: The median follow-up duration for all patients were 42.5 months. The incidence of synchronous CRC was high than in older and male patients as well as in mucinous adenocarcinoma containing signet-ring cell carcinoma, tumor deposit, and polypus. The length of hospital stay after surgery was longer for synchronous CRC than solitary CRC (median: 10 vs. 4 days, P = 0.033). In multivariate analysis, synchronous CRC was an independent prognostic factor associated with poor OS (hazard ratio: 2.355, 95% confidence interval: 1.322-4.195, P = 0.004), DFS (hazard ratio: 2.079, 95% confidence interval: 1.261-3.429, P = 0.004), and CSS (hazard ratio: 2.429, 95% confidence interval: 1.313-4.493, P = 0.005). CONCLUSION: The clinical and pathological features exhibit differences between synchronous CRC and solitary CRC and the prognosis of patients with synchronous CRC was poorer than those with solitary CRC.

Outcomes of open, laparoscopic, and hand-assisted laparoscopic surgeries in elderly patients with right colon cancers: A case-control study.

An increasing proportion of patients aged more than 70 years old are suffering from colorectal cancers. This study aimed to compare the short- and long-terms outcomes between open surgery (OS) or conventional laparoscopic surgery (LS) and hand-assisted laparoscopic surgery (HALS) in treatment of these elderly patients with right colon cancers.We retrospectively reviewed patients who underwent right colon resections for cancers in our institution between June, 2009 and December, 2014. Short- and long-terms outcomes including surgical endpoints, postsurgical recovery data, postoperative morbidity and mortality, overall survival and disease-free survival were compared among OS, LS, and HALS groups. All data were analyzed by SPSS 22.0.Finally, 69 consecutive patients (OS = 26, LS = 24, HALS = 19) with right colon cancers were included in the analysis. Compared with OS, HALS was associated with less time to first anus exhaust (P = .013), first liquid diet (P = .045), and first soft diet (P = .036). Meanwhile, there were significant less operative time (P = .0027), blood loss (P < .001), and less time to first liquid diet (P = .009) in HALS, compared with LS. In regards to long-term outcomes, there were no significant differences in overall survival and disease-free survival among the 3 groups.Compared with OS or LS, HALS may be more favorable in the treatment of elderly right colon cancers with decreased surgical time and postoperative recovery, and comparable cancer-specific survivals.

Lymph node ratio is an independent prognostic factor for rectal cancer after neoadjuvant therapy: A meta-analysis.

OBJECTIVE: With neoadjuvant therapy increasingly used in advanced rectal cancer, the lymph node ratio (LNR) has been strongly considered to indicate cancer-specific survival in recent years, and a comprehensive evaluation of a large number of studies is deficient. The objective of our study is to pool enough eligible studies to assess the relationship between LNR and prognosis of advanced rectal cancer after neoadjuvant therapy. METHODS: A systematic search was done in the PubMed and EmBase databases (through 1 March 2017) that reported LNR in colorectal cancer after neoadjuvant therapy. The first two authors independently conducted the study selection and data extraction. All statistical analyses were conducted using STATA 13.0 (College Station, Texas). RESULTS: Thirteen studies with 4023 participants were included in the meta-analysis, and all were published after 2011. A high LNR was assessed to be a predictor of poor overall survival in rectal cancer after neoadjuvant therapy (HR: 2.94, 95% CI:1.97 to 3.91, P < 0.001). Similarly, a high LNR was related to poor disease-free survival (HR: 2.83, 95% CI: 1.82 to 3.85, P < 0.001). With respect to recurrence, the HRs of 3.25, 1.93, and 2.11 also showed a strong relationship between high LNR and poor local, distant, and total recurrences. CONCLUSIONS: Our present study demonstrates that a high LNR can predict poor survival in advanced rectal cancer. We suggest well-designed clinical trials to prospectively assess LNR as an independent predictor of rectal cancer survival.

A novel hand-assisted laparoscopic versus conventional laparoscopic right hemicolectomy for right colon cancer: study protocol for a randomized controlled trial.

BACKGROUND: Although conventional laparoscopic and hand-assisted laparoscopic surgery for colorectal cancer is widely used today, there remain many technical challenges especially for right colon cancer in obese patients. Herein, we develop a novel hand-assisted laparoscopic surgery (HALS) with complete mesocolic excision (CME), D3 lymphadenectomy, and a total "no-touch" isolation technique (HALS-CME) in right hemicolectomy to overcome these issues. According to previous clinic practice, this novel procedure is not only feasible and safe but has several technical merits. However, the feasibility, short-term minimally invasive virtues, long-term oncological superiority, and potential total "no-touch" isolation technique benefits of HALS-CME should be confirmed by a prospective randomized controlled trial. METHODS/DESIGN: This is a single-center, open-label, noninferiority, randomized controlled trial. Eligible participants will be randomly assigned to the HALS-CME group or to the laparoscopic surgery with CME, D3 lymphadenectomy, and total "no-touch" isolation technique (LAP-CME) group, or to conventional laparoscopic surgery with CME and D3 lymphadenectomy (cLAP) group at a 1:1:1 ratio using a centralized randomization list. Primary endpoints include safety, efficacy, and being oncologically clear, and 3-year disease-free, progression-free, and overall survival. Second endpoints include operative outcomes (operation time, blood loss, and incision length), pathologic evaluation (grading the plane of surgery, length of proximal and distal resection margins, distance between the tumor and the central arterial high tie, distance between the nearest bowel wall and the same high tie, area of mesentery resected, width of the chain of lymph-adipose tissue, length of the central lymph-adipose chain, number of harvested lymph nodes), and postoperative outcomes (pain intensity, postoperative inflammatory and immune responses, postoperative recovery). DISCUSSION: This trial will provide valuable clinical evidence for the feasibility, safety, and potential total "no-touch" isolation technique benefits of HALS-CME for right hemicolectomy. The hypothesis is that HALS-CME is feasible for the radical D3 resection of right colon cancer and offers short-term safety and long-term oncological superiority compared with conventional laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02625272 . Registered on 8 December 2015.

Do inflammatory markers predict prognosis in patients with synchronous colorectal cancer?

Systematic inflammatory response markers are considered as the most informative prognostic factors in many types of cancer. However, in synchronous colorectal cancer (synCRC), the prognostic value of inflammatory markers, including prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (d-NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), had rarely been evaluated. Thus, this present study reviewed our consecutive patients with synCRC to investigate the prognostic value of those factors.The primary endpoint was overall survival (OS), and disease-free survival (DFS) was considered as the secondary endpoint. Receiver-operating characteristic curve analysis was conducted to determine optimal cutoff levels for the 5 markers. Kaplan-Meier survival curves and Cox proportional hazards models were applied to assess the relationship between OS, DFS, and inflammatory markers.In total, 114 patients with pathologically confirmed synCRC at initial diagnosis were identified among 5742 patients who underwent surgery for colorectal cancer from October 2009 to May 2013. In the multivariate analysis, elevated postoperative NLR (≥10.50) was confirmed as an independent prognostic factor for 3-year OS (P = .001; hazard ratio [HR] 4.123, 95% confidence interval [CI] 1.750-9.567) and DFS (P = .001; HR 3.342, 95% CI 1.619-6.898). In addition, for 3-year OS, both tumor grade and pN stage were confirmed as independent prognostic factors. And pN stage was confirmed as an independent prognostic factor for 3-year DFS.In conclusion, this study identified elevated postoperative NLR is associated with a poor prognosis in patients with synCRC underwent surgery resection, and the NLR provides improved accuracy for predicting clinical outcomes to stratify patients into different risk categories.

Malignant ascites-derived exosomes promote proliferation and induce carcinoma-associated fibroblasts transition in peritoneal mesothelial cells.

Malignant ascites-derived exosomes have been demonstrated to participate in tumor metastasis. In peritoneal metastasis, normal mesothelial cells (MCs) can be converted into carcinoma-associated fibroblasts (CAFs) by mesothelial-mesenchymal transition (MMT). Herein, we evaluated the effect of malignant ascites-derived exosomes on peritoneal MCs in vitro and in vivo experiments to determine whether exosomes could educate MCs and contribute to peritoneal metastasis.Under the treatment of ascites-derived exosomes, peritoneal MCs showed increased ability to proliferate and migrate. Expression of CAFs specific proteins markers in MCs, including fibroblast activation protein (FAP), alpha-smooth muscle actin (α-SMA), and fibronectin, were increased after treatment of exosomes. In clinical samples test, TGF-ß1 was found to be overexpressed in both malignant ascites and malignant ascites-derived exosomes, and the high volume of TGF-ß1 may be responsible for peritoneum fibrosis. In addition, exosomes can increase xenograft tumor growth by suppressing the inhibitive ability on tumor cells by MCs. Besides, CAFs specific proteins markers including FAP, α-SMA, and vimentin were increased in clinical peritoneal biopsies. The immunohistochemical staining for mice tumor biopsies also revealed increased expression of fibronectin and FAP, along with decreased expression of E-cadherin and VCAM-1 after exosomes treatment.Thus, malignant ascites-derived exosomes may be of importance in the development of peritoneal metastasis by facilitating MCs to proliferate and convert into CAFs by TGF-ß1 induced MMT.

Hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision and central vascular ligation: a novel technique for right colon cancer.

BACKGROUND: It can be difficult to locate the superior mesenteric vein and dissect around middle colic vessels during laparoscopic right hemicolectomy with complete mesocolon excision due to a high rate of vascular variations in the superior mesenteric vessels. Therefore, we report a modified technique for hand-assisted laparoscopic right hemicolectomy with complete mesocolic excision and central vascular ligation, which addresses these two problems. METHODS: Thirty-one consecutive patients with right colon cancer underwent this procedure from March 2014 to August 2015. Extracorporeally, the transverse colon and distal ileum were excised with a transumbilical hand-port incision, and the distal part of the superior mesenteric vein was identified. Intracorporeally, with the assistance of the surgeon's left hand inserted through the incision, D3-lymphadenectomy with central vascular ligation was performed, and the colon with the tumor, which had no blood supply, was removed. Patients' demographic data and intraoperative, postoperative and pathological characteristics were examined. RESULTS: The median operative time was 130.0 (range 115-180) minutes. The median blood loss was 45.0 (range 20-300) milliliters. The median length of the hand-port incision was 7.3 (range 6.0-8.2) centimeters. The median numbers of lymph nodes and central lymph nodes was 34.0 (range 18-91) and 13.0 (range 3-28), respectively. Five (16.1%) of 31 patients had positive central lymph nodes. Specimen morphometric quantitation was as follows: the median distances from the tumor and nearest bowel wall to the high tie were 10.5 (range 5.0-15.0) and 8.0 (range 6.0-12.0) centimeters, respectively; the median resected area of the mesentery was 200.0 (range 96.0-300.0) square centimeters; the median width of the chain of lymph-adipose tissue at the central lymph nodes area was 2.0 (range 0.8-8.0) centimeters; and the median length of the central lymph-adipose chain was 19.0 (range 3.0-26.0) centimeters. CONCLUSIONS: Our procedure confers technical advantages and is feasible for treatment of right colon cancer.

Prognostic role of the lymphocyte-to-monocyte ratio in patients undergoing resection for nonmetastatic rectal cancer.

Lymphocyte-to-monocyte ratio (LMR) was associated with survival benefit in some types of cancer. The relationship between LMR and rectal cancer has not been investigated. We conducted a retrospective cohort study to assess the prognostic significance of LMR in patients with nonmetastatic rectal cancer. Patients with rectal cancer who underwent potentially curative resection between January 2009 and December 2013 were enrolled. The LMR was calculated from preoperative blood test by dividing the absolute lymphocyte counts by the absolute monocyte counts. The optimal cut-off value for LMR was calculated as the median value. On the basis of the cut-off value, patients were divided into 2 groups: low group and high group. A total of 543 patients with rectal cancer were eligible for this study. The median follow-up time for all patients was 55 months (range 6-85 months). The cut-off value of LMR was 5.13 and patients were divided into 2 groups: low group (LMR < 5.13) and high group (LMR ≥ 5.13). In the univariate and multivariate analysis, the LMR was not significantly associated with overall survival (OS) [hazard ratio (HR): 1.034, 95% confidence intervals (CIs): 0.682-1.566, P = 0.876]. When disease-free survival (DFS) was compared, univariate and multivariate analysis also indicated that the LMR was not significantly associated with DFS (HR: 0.988, 95% CI: 0.671-1.453, P = 0.950). In addition, in the subgroup analysis by tumor-node-metastasis stage, there existed no significance between LMR and OS and DFS. Although as an easy access and highly efficient laboratorial inflammatory marker, LMR cannot predict the prognosis of nonmetastatic rectal cancer patients.

[The Comparison Between Extraction Methods of Exosomes From Ascites of Colorectal Cancer].

OBJECTIVE: To compare the two different methods to isolate the exosome from the ascites of colorectal cancer (CRC) patient and find the efficient one. METHODS: Exosome from the ascites of CRC patient were isolated by two different methods: density gradient exosome isolation (DG-Exo) and Exo-Quick isolation, and followed by identification with transmission electron microscopy observation and Western blot analysis. And then, Nanodrop was used for protein quantification. RESULTS: Exosome were isolated by both of the two methods. The protein concentration of the exosome isolated by the Exo-Quick isolation were higher than that of DG-Exo. CONCLUSION: Exo-Quick isolation can obtain higher purity and more complete exosome from the ascites.