Advances in three-dimensional tumor models for colorectal cancer / 中华肿瘤杂志

Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models. The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance, while the latter are limited by the slow growth, low engraftment successful rate, and high cost. In recent years, in vitro three-dimensional (3D) tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors. In addition, they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors, which have become a powerful tool for investigating the tumor mechanism, drug screening, and personalized cancer treatment. 3D tumor model technologies such as spheroids, organoids, and microfluidic devices are maturing. Application of new technologies such as co-culture, 3D bioprinting, and air-liquid interface has further improved the clinical relevance of the models. Some models recapitulate the tumor microenvironment, and some can even reconstitute endogenous immune components and microvasculature. In recent years, some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks, giving full play to the advantages of the two technologies, and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors. So far, the above technologies have been widely applied in the field of colorectal cancer research. Our research team is currently studying upon the application of patient-derived tumor cell-like clusters, a self-assembly 3D tumor model, in guiding the selection of postoperative chemotherapy regimens for colorectal cancer. A high modeling success rate and satisfactory results in the drug screening experiments have been achieved. There is no doubt that with the advancement of related technologies, 3D tumor models will play an increasingly important role in the research and clinical practice of colorectal cancer.

Analysis of intestinal microbial diversity in Leopoldamys edwardsi based on illumina sequencing technique / 中华预防医学杂志

To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and β diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.

Preventive and therapeutic effects of rhEGF gel on radiation-induced oral mucositis:A clinical observation / 医学研究生学报

Objective Few studies are reported on the prevention and management of oral mucositis(OM) induced by post-operative radiotherapy in patients with oral cavity cancer.This study aimed to investigate the therateutic effect of the recombinant human epidermal growth factor(rhEGF) gel on radiation-induced OM. Methods Sixty-eight cases of radiation-induced OM after surgery for oral cavity cancer were randomly divided into an experimental and a control group of equal number,the former treated with rhEGF gel while the latter with borax mouthwash. Comparisons were made between the two groups of patients in the severity of oral cavity mucous membrane injury,the intensity of radiation-induced oral pain,the in-cidence of oral cavity infection, and the duration of radiotherapy. Results At 3 weeks of radiotherapy,the patients of the experimental group showed mainly mild and moderate OM while the controls chiefly moderate and severe OM,and at 6 weeks,the former exhibited mainly moderate while the latter chiefly severe OM, with statistically significant differences in the incidence rate between the two groups (P<0.01). The experimental group, compared with the controls, had a significantly higher incidence rate of grade-Ⅰ radiation-induced pain (47.1% vs 20.6%,P<0.01),but lower rates of grade-Ⅱ(17.6% vs 32.4%,P<0.01) and grade-Ⅲpain(2.9% vs 20.6%,P<0.01).The rates of oral infection and antibiotics medication were remarkably lower in the experimental group than in the controls(23.5% vs 38.2% and 11.8% vs 26.5%,P<0.05),and the duration of radiotherapy was markedly shorter in the former than in the latter ([42.37±3.14] d vs [48.47±4.39] d, P<0.05). Conclusion The rhEGF gel can significantly reduce the severity of radiation-induced oral mucositis,improve its symptoms,and shorten the time of postoperative radiotherapy for patients with oral cavity cancer.

The reversal of antineoplastic drug resistance in cancer cells by β-elemene / 癌症

Multidrug resistance (MDR), defined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, significantly limits the efficacy of antitumor drugs. A major mechanism that mediates MDR in cancer is the overexpression of adenosine triphosphate (ATP)-binding cassette transporters. These transporters bind to their respective substrates and catalyze their efflux from cancer cells, thereby lowering the intracellular concentrations of the substrates and thus attenuating or even abolishing their efficacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen-activated protein kinase pathway. In this review, we discuss the mechanisms by which β-elemene, a compound extracted from Rhizoma zedoariae that has clinical antitumor efficacy, overcomes drug resistance in cancer.

Acquiring laparoscopic skill for colorectal surgery: based on the experience of a colorectal surgeon / 中华外科杂志

<p><b>OBJECTIVE</b>Laparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations.</p><p><b>METHODS</b>A series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications.</p><p><b>RESULTS</b>For radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase.</p><p><b>CONCLUSIONS</b>For a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.</p>

Impact of neoadjuvant chemoradiation on perineal wound healing after abdominoperineal resection for lower rectal cancer / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of neoadjuvant chemoradiation on perineal wound healing following abdominoperineal resection(APR) for lower rectal cancer.</p><p><b>METHODS</b>Data of 93 patients who underwent APR for low rectal cancer between January 2005 and January 2009 in Peking Union Medical College Hospital were reviewed, including patients who received neoadjuvant chemoradiation (n=29) and those undergoing surgery alone(n=64). Perineal wound healing was the primary outcome measurement. Condition of wound healing was classified as good, moderate, and poor and was compared between the two groups.</p><p><b>RESULTS</b>Twenty nine patients in the neoadjuvant group received preoperative regional radiation(50 Gy, 25 fractions/5 weeks) with synchronous FOLFOX4 chemotherapy(fluorouracil and oxaliplatin). In the neoadjuvant group, wound healing after APR was good in 18 patients(62.1%), moderate in 6(20.7%), and poor in 5(17.2%). In patients who had surgery alone, wound healing after APR was good in 41 patients(64.1%), moderate in 15(23.4%), and poor in 8(12.5%). There was no significant difference in the incidence of wound infection(poor wound healing)between the two groups(P=0.773).</p><p><b>CONCLUSION</b>Neoadjuvant chemoradiation therapy is not associated with increased perineal wound infection following abdominoperineal resection for low rectal cancer.</p>

Management of the perineal wounds after abdominoperineal resection: simple drainage only or with continuous irrigation? / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the effects of presacral irrigation and simple drainage on the perineal wound healing in patients after abdominoperineal resection (APR).</p><p><b>METHODS</b>From October 2004 to August 2009, patients with rectal cancer, ulcerative colitis or rectal gastrointestinal stromal tumor, who underwent APR or proctocolectomy, were randomized into two arms: simple drainage group (n = 37) and continuous irrigation (n = 37). Patients randomized to arm B received simple drainage only to presacral space; while those patients in arm A received continuous irrigation in addition to simple drainage. Perineal wound healing was taken as endpoint of this study. Major complication was defined as wound dehiscence or wound infection that the perineal wound should be reopened for drainage. Minor complication was defined as delayed healing wound with seroma or hematoma.</p><p><b>RESULTS</b>A total of 74 patients were enrolled in present study, with 37 patients in each arm, and there were 12 cases and 10 cases who received preoperative radiation therapy, respectively. In the arm A, 2 patients developed major complications, 3 patients incurred with minor complications and 32 patients got primary healing of the perineal wounds. In arm B, 8 patients suffered major complications, 3 patients incurred with minor complications and 26 patients got primary healing of the perineal wounds. The incidence of major complication was significantly lower in arm A (5.4% vs.21.6%, P = 0.042). Patients received preoperative radiation therapy had significantly higher rate of minor complications than patients underwent surgery only (18.2% vs. 3.9%, P = 0.039).</p><p><b>CONCLUSIONS</b>Simple drainage with continuous irrigation of the presacral space, in patients with abdominoperineal resection or proctocolectomy, could significantly lower the incidence of major complication and improve wound healing for perineal wound when compared with simple drainage only. Preoperative radiation therapy tends to increase the incidence of minor complications.</p>

Impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To study the impact of neoadjuvant therapy on lymph nodes retrieval in locally advanced mid-low rectal carcinoma.</p><p><b>METHODS</b>Data collected from 120 patients with locally advanced mid-low rectal cancer (T2-4 and/or N1-2M0) treated from January 2005 to June 2008 was investigated. The patients were divided into two groups: the study group (n=54) was treated with neoadjuvant therapy (preoperative radiation with a total dosage of 50 Gy and synchronous 5-Fu-based chemotherapy) followed by radical tumor resection 4-6 weeks after;the control group (n=66) underwent primary surgery without neoadjuvant therapy. The clinical stage was evaluated before and after neoadjuvant therapy. The total lymph nodes yields, as well as the tumor-positive lymph nodes of each resected specimen was compared between the two groups statistically.</p><p><b>RESULTS</b>Clinical downstage was achieved in 30 cases (56%) in study group after neoadjuvant therapy. The number of total lymph nodes and positive lymph nodes harvested from each resected specimen in the control group were 14+/-7 and 2.2+/-3.7, meanwhile those were 9+/-6 and 0.7+/-2.4 in study group, which were all significantly lower than those in control group (P<0.01).</p><p><b>CONCLUSIONS</b>Preoperative radiotherapy combined with chemotherapy can downstage the tumor and reduce the retrieval rate of total lymph nodes and positive lymph nodes in locally advanced rectal cancer. It is necessary to retrieve as many lymph nodes as possible for it has some prognostic significance for the patients.</p>