Preoperative electroacupuncture versus sham electroacupuncture for the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer in China: a study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is a postoperative complication that can cause lingering recovery after colorectal resection and a heavy healthcare system burden. Acupuncture aims to prevent postoperative complications, reduce the duration of POI, help recovery and shorten hospital stays. We hypothesise that preoperative electroacupuncture (EA) can promote POI recovery under the enhanced recovery after surgery protocol after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 80 patients will be enrolled and randomly assigned to the EA or sham electroacupuncture (SA) group. The eligible patients will receive EA or SA for one session per day with treatment frequency starting on preoperative day 1 for four consecutive days. The primary outcome is the time to first defecation. The secondary outcomes include the time to first flatus, length of postoperative hospital stay, time to tolerability of semiliquid and solid food, postoperative nausea, vomiting, pain and extent of abdominal distention, time to first ambulation, preoperative anxiety, 30-day readmission rate, the usage of anaesthetics and analgesics during operation, length of postanaesthesia care unit stay. A mechanistic study by single-cell RNA sequencing in which postintervention normal intestinal tissue samples will be collected. The results of this study will provide evidence of the effects of acupuncture on POI and promote good clinical decision to millions of patients globally every year. ETHICS AND DISSEMINATION: This study has been approved by the ethical application of Beijing University of Chinese Medicine (2022BZYLL0401), Beijing Friendship Hospital Affiliated to Capital Medical University(2022-P2-368-02), Cancer Hospital Chinese Academy of Medical Science (23/175-3917), Huanxing Cancer Hospital (2023-002-02). The results will be published in a medical journal. In addition, we plan to present them at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300077633.

Preservation of left colic artery in laparoscopic colorectal operation: The benefit challenge.

BACKGROUND: During laparoscopic resection for colorectal cancer, there is controversy regarding whether the left colic artery (LCA) should be preserved at its origin. AIM: To investigate the prognostic significance of preservation of the LCA in colorectal cancer surgery. METHODS: Patients were divided into two groups. The high ligation (H-L) technique (refers to ligation performed 1 cm from the beginning of the inferior mesenteric artery) group consisted of 46 patients, and the low ligation (L-L) technique (refers to ligation performed below the initiation of the LCA) group consisted of 148 patients. Operative time, blood loss, lymph nodes with tumor invasion, postoperative complications and recovery time, recurrence rate, and 5-year survival rate were compared between the two groups. RESULTS: The average number of lymph nodes detected in postoperative pathological specimens was 17.4/person in the H-L group and 15.9/person in the L-L group. There were 20 patients (43%) with positive lymph nodes (lymph node metastasis) in the H-L group and 60 patients (41%) in the L-L group. No statistical differences were found between the groups. Complications occurred in 12 cases (26%) in the H-L group and in 26 cases (18%) in the L-L group. The incidences of postoperative anastomotic complications and functional urinary complications were significantly lower in the L-L group. The 5-year survival rates in H-L and L-L groups were 81.7% and 81.6%, respectively, and relapse-free survival rates were 74.3% and 77.1%, respectively. The two groups were similar statistically. CONCLUSION: Complete mesenteric resection combined with lymph node dissection around the inferior mesenteric artery root while preserving the LCA is a beneficial surgical approach during laparoscopic resection for colorectal cancer.

Electroacupuncture vs Sham Electroacupuncture in the Treatment of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer: A Multicenter, Randomized Clinical Trial.

Importance: Despite the adoption of the optimized Enhanced Recovery After Surgery (ERAS) protocol, postoperative ileus (POI) severely impairs recovery after colorectal resection and increases the burden on the health care system. Objective: To assess the efficacy of electroacupuncture (EA) in reducing the duration of POI with the ERAS protocol. Design, Setting, and Participants: This multicenter, randomized, sham-controlled trial was conducted in China from October 12, 2020, through October 17, 2021. There was a 1:1 allocation using the dynamic block random method, and analyses were by intention to treat. Patients 18 years or older undergoing laparoscopic resection of colorectal cancer for the first time were randomly assigned to treatment group by a central system. Interventions: Patients were randomly assigned to 4 sessions of EA or sham electroacupuncture (SA) after surgery. All patients were treated within the ERAS protocol. Main Outcomes and Measures: The primary outcome was the time to first defecation. Secondary outcomes included other patient-reported outcome measures, length of postoperative hospital stay, readmission rate within 30 days, and incidence of postoperative complications and adverse events. Results: A total of 249 patients were randomly assigned to treatment groups. After the exclusion of 1 patient because of a diagnosis of intestinal tuberculosis, 248 patients (mean [SD] age, 60.2 [11.4] years; 153 men [61.7%]) were included in the analyses. The median (IQR) time to first defecation was 76.4 (67.6-96.8) hours in the EA group and 90.0 (73.6-100.3) hours in the SA group (mean difference, -8.76; 95% CI, -15.80 to -1.73; P = .003). In the EA group compared with the SA group, the time to first flatus (median [IQR], 44.3 [37.0-58.2] hours vs 58.9 [48.2-67.4] hours; P < .001) and the tolerability of semiliquid diet (median [IQR], 105.8 [87.0-120.3] hours vs 116.5 [92.0-137.0] hours; P = .01) and solid food (median [IQR], 181.8 [149.5-211.4] hours vs 190.3 [165.0-228.5] hours; P = .01) were significantly decreased. Prolonged POI occurred in 13 of 125 patients (10%) in the EA group vs 25 of 123 patients (20%) in the SA group (risk ratio [RR], 0.51; 95% CI, 0.27-0.95; P = .03). Other secondary outcomes were not different between groups. There were no severe adverse events. Conclusions and Relevance: Results of this randomized clinical trial demonstrated that in patients undergoing laparoscopic surgery for colorectal cancer with the ERAS protocol, EA shortened the duration of POI and decreased the risk for prolonged POI compared with SA. EA may be considered as an adjunct to the ERAS protocol to promote gastrointestinal function recovery and prevent prolonged POI after surgery. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038444.

Electroacupuncture versus sham electroacupuncture in the treatment of postoperative ileus after laparoscopic surgery for colorectal cancer: study protocol for a multicentre, randomised, sham-controlled trial.

INTRODUCTION: Postoperative ileus (POI) is an inevitable complication of almost all abdominal surgeries, which results in prolonged hospitalisation and increased healthcare costs. Various treatment strategies have been developed for POI but with limited success. Electroacupuncture (EA) might be a potential therapy for POI. However, evidence from rigorous trials that evaluated the effectiveness of EA for POI is limited. Thus, the aim of this study was to examine whether EA can safely reduce the time to the first defecation after laparoscopic surgery in patients with POI. METHODS AND ANALYSIS: This multicentre randomised sham-controlled trial will be conducted in four hospitals in China. A total of 248 eligible participants with colorectal cancer who will undergo laparoscopic surgery will be randomly allocated to an EA group and a sham EA group in a 1:1 ratio. Treatment will be performed starting on postoperative day 1 and continued for four consecutive days, once per day. If the participant is discharged within 4 days after surgery, the treatment will cease on the day of discharge. The primary outcome will be the time to first defecation. The secondary outcome measures will include time to first flatus, tolerability of semiliquid and solid food, length of postoperative hospital stay, postoperative nausea and vomiting, abdominal distension, postoperative pain, postoperative analgesic, time to first ambulation, blinding assessment, credibility and expectancy and readmission rate. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of Beijing University of Chinese Medicine (number 2020BZHYLL0116) and the institutional review board of each hospital. The results will be disseminated through peer-reviewed publications. This study protocol (V.3.0, 6 March 2020) involves human participants and was approved by the ethics committees of Beijing University of Chinese Medicine (number 2020BZHYLL0116), Beijing Friendship Hospital Affiliated to Capital Medical University (number 2020-P2-069-01), Beijing Chao-Yang Hospital Affiliated to Capital Medical University (number 2020-3-11-2), National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (number 20/163-2359), and the Affiliated Hospital of Qingdao University (number QYFYKYLL711311920). The participants gave informed consent to participate in the study before taking part. TRIAL REGISTRATION NUMBER: ChiCTR2000038444.

Transanal total mesorectal excision for rectal cancer: a multicentric cohort study.

BACKGROUND: Transanal total mesorectal excision (taTME) has recently emerged as a promising novel surgical procedure for rectal cancer. It is believed to hold the potential advantage of providing better access to mobilize the distal rectum and achieving better pathologic results. This study aimed to evaluate the feasibility of taTME for rectal cancer and summarize the preliminary experience in 10 Chinese hospitals. METHODS: A total of 211 patients were enrolled in this study. Variables for evaluation of safety, feasibility, and oncologic outcomes were retrospectively collected and analysed. RESULTS: The median distance between the tumor and the anal verge was 5.9 cm (range, 1.5-12 cm). The median operating time was 280 min (range, 70-600 min) and the median estimated intra-operative blood loss was 50 mL (range, 10-1,500 mL). The overall rate of complication was 27.9%. Among the 211 patients, 175 (82.9%) had complete TME and 33 (15.6%) had near complete TME. The circumferential resection margin was negative in 97.7% of patients. The patients were followed for a median of 35 months (range, 2-86 months). There was 7.6% (16) mortality, 6.2% (13) had local recurrence, and 12.8% (27) had systemic recurrence. Kaplan-Meier survival analysis showed that 1-, 2-, and 3-year disease-free survival rates were 94.8%, 89.3%, and 80.2%, respectively, and 1-, 2-, and 3-year OS rates were 97.4%, 95.7%, and 92.9%, respectively. CONCLUSIONS: Although limited by its retrospective nature, taTME was safe and feasible in selected patients. Future work with rigorous data recording is warranted.

Utility of circulating tumor cells in stage II colorectal cancer patients undergoing curative resection.

BACKGROUND: The aim of this study was to determine whether circulating tumor cells (CTCs) have utility as a prognostic biomarker in stage II colorectal cancer (CRC), as well as a biomarker for the selection of patients for adjuvant chemotherapy. METHODS: CTCs were detected in peripheral blood samples obtained from 73 stage II CRC patients, using a negative enrichment and immune-fluorescence in situ hybridization (imFISH) staining method. The follow-up time ranged from 3.5 to 35.9 months, and the clinic-pathologic characteristics and recurrence free survival (RFS) were collected and analyzed. RESULTS: Seventy-three stage II CRC patients were included in this study. The positive rate of CTCs was 65.8% in all patients, 87.5% in recurrent patients and 59.6% in no recurrence patients. The mean RFS was 30.6 months for all patients, 28.7 months for CTC-positive patients and 34.0 months for CTC-negative patients (P=0.043). The mean RFS of CTC-positive and CTC-negative patients with adjuvant chemotherapy were not reached, and those without adjuvant chemotherapy were 27.7 and 33.4 months, respectively. CONCLUSIONS: The level of CTCs may be an effective prognostic factor to predict RFS in stage II CRC patients, and has potential in selecting stage II CRC patients for adjuvant chemotherapy.

Circulating tumor DNA detectable in early- and late-stage colorectal cancer patients.

Characterization, diagnosis, and treatment of colorectal cancers (CRC) is difficult due to limited biopsy information, impracticality of repeated biopsies, and cancer biomarker fallibility. Circulating tumor DNA (ctDNA) has recently been investigated as a non-invasive way to gain representative gene mutations in tumors, in addition to monitoring disease progression and response to treatment. We analyzed ctDNA mutations and concentrations in 47 early- and late-stage CRC patients using a targetted sequencing approach using a panel that covers 50 cancer-related genes. ctDNA mutations in 37 genes were identified in 93.6% of the patients (n=47). The results showed that TP53, PIK3CA, APC, and EGFR were the most frequently mutated genes. Stage IV patients had significantly higher ctDNA concentration than Stage I patients, and increased ctDNA concentration correlated with increased tumor size. Additionally, ctDNA detection was found to be a greater predictor of disease when compared with five known commonly used tumor biomarkers. The present study supports the use of ctDNA as a liquid biopsy to gain clinical tumor information that may facilitate early diagnosis and treatment and improve CRC patient prognosis.

[Feasibility and Safety of Enhanced Recovery after Surgery for Elderly Patients with Colorectal Cancer].

Objective To evaluate the feasibility and safety of enhanced recovery after surgery (ERAS) in elderly patients with colorectal cancer (CRC).Methods A retrospective analysis was conducted on 230 CRC patients undergoing ERAS from January 2017 to January 2018. These subjects included 120 young patients (<70 years) and 110 elderly patients (≥70 years).The rates of ERAS compliance,anastomotic leakage,re-operation,and re-hospitalization,the mortality,and the average hospital stay were compared between these two groups.Results The elderly group had significantly higher incidences including diabetes (20.9% vs. 10.8%,P=0.045),heart disease (24.5% vs. 11.7%,P=0.039),respiratory diseases (20.0% vs. 10.0%,P=0.041),and hypertension (26.4% vs. 15.0%,P=0.035) than the young group. However,these two groups were not statistically significant in terms of ERAS compliance rate (79% in the young group vs. 74% in the elderly group,P=0.574),incidence of anastomotic leakage (2.5% vs. 1.8%,P=1.000),re-operation rate (1.7% vs. 2.7%,P=0.672),re-hospitalization rate (2.5% vs. 4.5%,P=0.484),mortality rate within 30 days after operation (1.7% vs. 2.7%,P=0.672). The average hospital stay was 5 days in the young group and 7 days in the elderly group (P=0.000).Conclusions Although the elderly patients tend to have poor general status,their ERAS compliance rate and main treatment indicators including incidence of anastomotic leakage,re-operation rate,re-hospitalization rate,and mortality rate within 30 days after surgery are not different from young patients. Thus,the ERAS program is safe and feasible for elderly CRC patients.

Laparoscopic-assisted Transanal Total Mesorectal Excision for Middle-Low Rectal Carcinoma: A Clinical Study of 19 Cases.

AIM: To explore the safety, feasibility and short-term outcomes of laparoscopic-assisted transanal total mesorectal excision (La-TaTME) of middle-low rectal carcinoma. MATERIALS AND METHODS: This retrospective research collected and analyzed the clinical data of 19 patients diagnosed with middle and low rectal carcinoma who underwent La-TaTME from August 2015 to February 2017. RESULTS: No case was converted to laparotomy. In none of the enrolled cases, did the circumferential resection margin test positive by histopathology examination. Also, there was no detected residual tumor at the proximal and distal resection margins. The rate of postoperative morbidity was 15.8% (Clavien-Dindo grade 2). During the follow-up period, no local recurrence or metastasis was observed. CONCLUSION: La-TaTME is a safe alternative to standard laparoscopic TME in middle-low rectal carcinoma when operated by an experienced colorectal surgeon. However, large-scaled randomized multi-centered comparative trials are still needed to further test its oncological effectiveness.

Heparin-functionalized Pluronic nanoparticles to enhance the antitumor efficacy of sorafenib in gastric cancers.

In this study, chitosan/heparin immobilized delivery system was developed for the delivery of sorafenib in gastric cancers. The SRF NP was nanosized with spherical outfit and present in the amorphous form. The SRF NP exhibited a sustained release of drug at pH 7.4 conditions and enhanced drug released at pH 5.5 conditions. Flow cytometer analysis showed that cellular uptake of NP increased two-fold after 4h of incubation compared to 1h incubation. The SRF NP showed superior anticancer effect compared to that of free SRF in BGC-823 cancer cells. SRF NP induced a remarkable apoptosis of cancer cells consistent with the cytotoxicity assay. Approximately, ∼ 50% of cell fractions were observed in early apoptosis phase with ∼ 15% of cells in the late apoptosis stage. Consistently, SRF NP exhibited a strong band for caspase-3 and P-53 than compared to free SRF in MGC-823 cancer cells. Importantly, SRF NP showed superior anticancer effect in xenograft tumor model making it a promising delivery vehicle in the treatment of gastric cancers.

Oligonucleotide microarray identifies genes differentially expressed during tumorigenesis of DMBA-induced pancreatic cancer in rats.

The extremely dismal prognosis of pancreatic cancer (PC) is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA)-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes) were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.

[Evaluation of RCAS1 as serum tumor marker for pancreatic cancer].

OBJECTIVE: To evaluate the effect of receptor-binding cancer antigen expressed on SiSO cells (RCAS1) as serum tumor marker on the diagnosis of pancreatic cancer. METHODS: Receiver-operating characteristics (ROC) curve methods were used to assay the serum content of RCAS1, CA19-9 and CA242 in 46 patients with pancreatic cancer, 18 patients and 20 normal tissues of chronic pancreatitis detected by enzyme linked immunosorbent assay (ELISA), and the results were analyzed by statistics methods. The expressions of RCAS1 protein were analyzed by immunohistochemical method in 32 patients with pancreatic cancer, 10 patients with chronic pancreatitis and 6 cases of normal pancreatic specimens. RESULTS: The serum levels of RCAS1, CA19-9 and CA242 in pancreatic cancer were higher than that in chronic pancreatitis respectively (P < 0.01). The area under curve of RCAS1, CA19-9 and CA242 were 0.826, 0.804 and 0.737, respectively. Subgroup analysis indicated that the RCAS1 and CA19-9 levels of pancreatic cancer patients without obstructive jaundice were lower than those for patients with obstructive jaundice (P < 0.01). CA19-9 levels of patients with resectable pancreatic cancer were lower than those with unresectable pancreatic cancer (P < 0.01). Immunohistochemistry showed that the expression rates of RCAS1 in pancreatic cancer and chronic pancreatitis were 87.5% and 40.0%, respectively (P < 0.05). CONCLUSIONS: In diagnosis of pancreatic cancer, the clinical value of RCAS1 is available. And the combination test of RCAS1 and CA19-9 have clinical value to evaluate if the pancreatic cancer can be resected before operation.

Combined detection of serum tumor markers for differential diagnosis of solid lesions located at the pancreatic head.

BACKGROUND: The differential diagnosis of solid lesions located at the pancreatic head is very important for choosing therapies and setting up surgical tactics. This study was designed to evaluate the clinical significance of combined measurement of multiple serum tumor markers and the application of the receiver-operating characteristic (ROC) curves in the differential diagnosis of solid lesions located at the pancreatic head. METHODS: The serum levels of CA19-9, CA242, CA50 and carcinoembryonic antigen (CEA) in 112 patients with carcinoma of the pancreatic head and 38 patients with focal chronic pancreatitis in the pancreatic head were measured with ELISA. The sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of the four serum tumor markers were calculated. The ROC curves for the four serum tumor markers were constructed and the area under the curve (AUC) was calculated. RESULTS: The AUCs of CA19-9, CA242, CA50 and CEA were 0.805, 0.749, 0.738 and 0.705; the PLRs were 1.91, 3.43, 5.09 and 5.46; and the NLRs were 0.41, 0.56, 0.59 and 0.71, respectively. Combined measurements increased the diagnostic specificity, and parallel combined testing increased the diagnostic sensitivity. CONCLUSIONS: Combined measurement of serum tumor markers CA19-9, CA242, CA50 and CEA is valuable in differential diagnosis of solid lesions located at the pancreatic head, and CA19-9 has the best diagnostic ability. Combined measurements can increase the specificity of diagnosis. Evaluation with the ROC curve is better than the sensitivity or specificity alone and the results are more integrated and objective.

[Immuno-proteomic screening of human pancreatic cancer associated membrane antigens for early diagnosis].

OBJECTIVE: To screen and identify the immunogenic membrane antigens in human pancreatic cancer for early diagnosis. METHODS: Membrane protein was extracted from pancreatic cancer cell lines and separated by using 2-DE. One of the two parallel 2-DE gels went for staining while the other underwent immunoblot. Serum IgG, which was purified from clinically collected sera of pancreatic cancer patients, was used as the primary antibodies for the immunoblot. Positive dots of immunoblot were identified by MALDI-TOF mass spectrometry and PMF matching, and then evaluated by bio-informatics methods. The candidate membrane antigens were further validated respectively in cell lines and tissues by RT-PCR and immunohistochemistry. RESULTS: The immunoblot of mixed membrane protein with serum IgG from cancer patients showed eight positive dots. These dots were identified with MALDI and PMF as: VDAC-1, VDAC-2, CHCHD3, SLP-2 and TOM40. RT-PCR showed that these membrane antigens were expressed in several pancreatic cancer cell lines. Immunohistochemistry showed prominent SLP-2 over expression in cancer tissue. CONCLUSIONS: VDAC-1, VDAC-2, CHCHD3, SLP-2, and TOM40 are the new candidate immunogenic membrane antigens of pancreatic cancer. These membrane antigens can be subsequently tested in high dangerous population for early diagnosis of pancreatic cancer.