Intracorporeal versus extracorporeal anastomosis in laparoscopic right hemicolectomy for overweight colon cancer patients: a case-control study.

INTRODUCTION: Either extracorporeal anastomosis (EA) or intracorporeal anastomosis (IA) could be selected for digestive reconstruction in laparoscopic right hemicolectomy (LRH). However, whether LRH with IA is feasible and beneficial for overweight right-side colon cancer (RCC) is unclear. This study aims to investigate the feasibility and advantage of IA in LRH for overweight RCC. METHODS: Forty-eight consecutive overweight RCC patients undergoing LRH with IA were matched with 48 consecutive cases undergoing LRH with EA. Both clinical and surgical data were collected and analyzed. RESULTS: The incidence of postoperative complications was 20.8% (10/48) in the EA group and 14.6% (7/48) in the IA group respectively, with no statistical difference. Compared to the EA group, patients in the IA group revealed faster gas (40.2 + 7.8 h vs. 45.6 + 7.9 h, P = 0.001) and stool discharge (4.0 + 1.2 d vs. 4.5 + 1.1 d, P = 0.040), shorter assisted incision (5.3 + 1.3 cm vs. 7.5 + 1.2 cm, P = 0.000), and less analgesic used (3.3 + 1.3 d vs. 4.0 + 1.3 d, P = 0.012). There were no significant differences in operation time, blood loss, or postoperative hospital stays. In the IA group, the first one third of cases presented longer operation time (228.4 + 29.3 min) compared to the middle (191.0 + 35.0 min, P = 0.003) and the last one third of patients (182.2 + 20.7 min, P = 0.000). CONCLUSION: LRH with IA is feasible and safe for overweight RCC, with faster bowel function recovery and less pain. Accumulation of certain cases of LRH with IA will facilitate surgical procedures and reduce operation time.

Effect of Denonvilliers' Fascia Preservation Versus Resection During Laparoscopic Total Mesorectal Excision on Postoperative Urogenital Function of Male Rectal Cancer Patients: Initial Results of Chinese PUF-01 Randomized Clinical Trial.

OBJECTIVE: To compare the outcomes of laparoscopic total mesorectal excision (L-TME) with Denonvilliers' fascia (DVF) preservation versus resection on urogenital function of male patients with rectal cancer. BACKGROUND: The protective effect of DVF during L-TME on pelvic autonomic nerves and postoperative urogenital function remains controversial. METHODS: Between August 26, 2015 and July 18, 2019, 253 male patients with cT1-4 (T1-2 for anterior wall) N0-2M0 rectal cancer from 11 institutions were enrolled, and randomly assigned to L-TME with DVF preservation (Exp-group, n = 123) or resection procedures (Con-group, n = 130). Urinary function was assessed by residual urine volume, maximal flow rate, and International Prostate Symptom Score; sexual function was assessed by 5-item version of the International Index of Erectile Function (IIEF-5) and ejaculation grading. RESULTS: The Exp-group patients showed a lower urinary dysfunction rate (6.8% vs 25.4%, P = 0.003), higher maximal flow rate (16.25 ±â€Š8.02 vs 12.40 ±â€Š7.05 mL/s, P = 0.007), and lower International Prostate Symptom Score (6.55 ±â€Š5.86 vs 8.57 ±â€Š5.85, P = 0.026) than the Con-group patients at 2 weeks after surgery. The incidence of erectile dysfunction (IIEF-5 ≤ 11) at 12 months after surgery was lower in the Exp-group than in the Con-group (12.5% vs 34.2%, P = 0.023); Exp-group manifested superior IIEF-5 (16.63 ±â€Š6.28 vs 12.26 ±â€Š6.83, P = 0.018). The incidence of ejaculation dysfunction was lower in the Exp-group than in the Con-group at 12 months after surgery (10.0% vs 29.4%, P = 0.034). CONCLUSIONS: DVF preservation during L-TME revealed protective effects on postoperative urogenital function, and could be a better choice for male rectal cancer patients with specific staging and location. TRIAL REGISTRATION NUMBER: NCT02435758.

TIGIT promotes CD8+T cells exhaustion and predicts poor prognosis of colorectal cancer.

TIGIT is a lymphocyte surface receptor, which is mainly expressed on the surface of CD8+T cells. The role of TIGIT in colorectal cancer and its expression pattern in colorectal cancer infiltrating lymphocytes are still controversial. This study aimed at identifying the function of TIGIT in colorectal cancer. Patients with colorectal cancer showed significantly higher TIGIT+CD8+T cell infiltration in tumor tissues, metastases compared with paired PBMC and normal tissues through flow cytometry. TIGIT+CD8+T cells showed an exhausted phenotype and expressed low levels of killer cytokines IFN-γ, IL-2, TNF-α. In addition, more inhibitory receptors such as PD-1, LAG-3, and TIM-3 were expressed on the surface of TIGIT+CD8+T cells. TGF-ß1 could promote the expression of TIGIT and inhibit CD8+T cell function in vitro. Moreover, the accumulation of TIGIT+T cells in tumors was associated with advanced disease, predicted early recurrence, and reduced survival rates in colorectal cancer patients. Our results indicate that TIGIT can be a biological marker for the prognosis of colorectal cancer, and TIGIT can be used as a potential target for treatment.

Reconsideration of the Anterior Surgical Plane of Total Mesorectal Excision for Rectal Cancer.

INTRODUCTION: Previous studies on total mesorectal excision suggested dissection anterior to Denonvilliers' fascia, which might lead to intraoperative pelvic autonomic nerves injury and a high incidence of urogenital dysfunction. TECHNIQUE: We dissected 4 cases of cadavers, mainly focusing on anatomy of Denonvilliers' fascia, to study the relationship between Denonvilliers' fascia and rectum. In practice, instead of dissection 1 cm above peritoneal reflection, dissection of the peritoneum was performed at the lowest level of peritoneal reflection during laparoscopic resection for mid-low rectal cancer. RESULTS: The cadaveric study revealed that there were loose tissues between Denonvilliers' fascia and rectal specimen, thus a surgical plane posterior to Denonvilliers' fascia did exist. During laparoscopic resection for mid-low rectal cancer, some loose reticulate structures between Denonvilliers' fascia and proper fascia of rectum would present after dissection of peritoneum at the lowest level of peritoneal reflection. Then dissection within the surgical plane posterior to Denonvilliers' fascia became easy and feasible. In this plane, both the pelvic nerves and postoperative urogenital function could be well protected by Denonvilliers' fascia. CONCLUSIONS: The anterior surgical plane for total mesorectal excision should be reconsidered, and dissection posterior to Denonvilliers' fascia is feasible and practicable for patients without risk of positive anterior circumferential resection margin.

Preservation of Denonvilliers' fascia for nerve-sparing laparoscopic total mesorectal excision: A neuro-histological study.

Urogenital complications due to pelvic autonomic nerve damage frequently occur following rectal surgery. We investigated whether total mesorectal excision (TME) with preservation of the Denonvilliers' fascia (DVF) can effectively prevent the removal of pelvic autonomic nerves through microscopy. Twenty consecutive male patients with mid-low rectal cancer who received TME with preservation or resection of the Denonvilliers' fascia (P and R groups, respectively) were included. Serial transverse sections from surgical specimens were studied histologically. Nerve fibers at the surfaces of the mesorectum were counted. Clinical correlation between the amount of nerve fibers removed and post-operative sexual function was analyzed. Nerve fibers closely localized to the DVF in the R group displaying rich erectile activity (positive anti-nNOS immunostaining). At the anterior surface of the mesorectum, the mean numbers of nNOS-positive nerve fibers per specimen in the P group were significantly lower than the R group (3.0 ± 1.8 vs. 5.0 ± 2.3, P < 0.05). Compared to the R group, patients in the P group had higher IIEF scores and better erectile function at 3 and 6 months post-operatively. The DVF is a key risk zone for pelvic denervation during laparoscopic TME. Preservation of the DVF can prevent the removal of autonomic nerves and protect post-operative erectile function. Clin. Anat. 32:439-445, 2019. © 2019 Wiley Periodicals, Inc.

Laparoscopic resection for rectal cancer and cholecystectomy for patient with situs inversus totalis.

Situs inversus totalis (SIT) is a rare congenital anomaly presenting with complete transposition of thoracic and abdominal viscera. Laparoscopic surgery for either rectal cancer or gallbladder diseases with SIT is rarely reported in the literature. A 39-year-old woman was admitted to hospital owing to rectal cancer. She was diagnosed with SIT by performing radiography and abdominal computed tomography scan as a routine preoperative investigation. We performed laparoscopic resection for rectal cancer successfully in spite of technical difficulties caused by abnormal anatomy. One year later, she was diagnosed with cholecysticpolyp, and we performed laparoscopic cholecystectomy for her uneventfully. With this case, we believe that performance by an experienced laparoscopic surgeon, either laparoscopic resection for rectal cancer or cholecystectomy with SIT is safe and feasible.

Laparoscopic lysis of the ligament of treitz for superior mesenteric artery syndrome.

BACKGROUND: Superior mesenteric artery (SMA) syndrome (SMAS) is a rare condition caused by compression of the third portion of the duodenum by the SMA. The effect of the laparoscopic management of SMAS remains poorly understood. This study aimed to investigate the feasibility and effect of the laparoscopic management for SMAS. METHODS: We retrospectively reviewed 19 cases of SMAS who underwent surgical interventions in The Third Affiliated Hospital of Sun Yat-sen University between June 2006 and October 2013, consisting of 8 cases of duodenojejunostomy (DJ) and 11 cases of laparoscopic lysis of the ligament of Treitz (LL-LOT). A telephone survey was conducted to collect the follow-up status. RESULTS: Either DJ or LL-LOT was performed smoothly. The median operative time of the laparoscopic procedure and DJ was 56 and 95 min, respectively. Median blood loss was 10 versus 35 ml. Median postoperative hospital stays in both were 8 days. Ten cases of the laparoscopic group recovered uneventfully, while 1 case still presented symptoms of abdominal distention. Upper gastrointestinal fluoroscopy showed marked 'to-and-fro' peristalsis. An additional DJ was performed 35 days later to resolve her symptoms. CONCLUSIONS: LL-LOT is simple, feasible, minimally invasive and effective for SMAS with no severe duodenum 'to-and-fro' peristalsis.

[Laparoscopic versus open mesh rectopexy for total rectal prolapse].

OBJECTIVE: To evaluate the efficacy and safety of laparoscopic versus open mesh rectopexy for total rectal prolapse. METHODS: A retrospective review was conducted for 34 patients undergoing laparoscopic versus open mesh rectopexy for total rectal prolapse between January 2006 and December 2013. RESULTS: Laparoscopic rectopexy (n = 15) and open surgery (n = 19) were performed. Two groups were matched with regards to age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score. Mortality was zero in each group. There were insignificant inter-group differences in operative duration, postoperative complication, rate of long-term recurrence and improvement of incontinence and constipation. Perioperative blood loss, time to first flatus and hospital stay were significantly shorter in laparoscopic rectopexy group. CONCLUSIONS: Laparoscopic mesh rectopexy is as safe and efficient as open rectopexy. And both are suitable for senile patients. Long-term outcomes are similar for two groups, but laparoscopic group has better short-term outcome.

[A comparative study of the laparoscopic appearance and anatomy of the autonomic nervous in normal males].

OBJECTIVE: To further understand the anatomical basis of pelvic autonomic nerve preservation. METHODS: Autopsy of five adult male donated cadavers was performed. Meanwhile, ten videos of laparoscopic total mesorectal excision for male mid-low rectal cancer admitted from January to June 2012 were observed and studied. Anatomical features of pelvic autonomic nerve were compared between autopsy and laparoscopic appearance. RESULTS: Autopsy observations indicated that:the abdominal aortic plexus was situated upon the sides and front of the aorta, between the origins of the superior and inferior mesenteric arteries. The superior hypogastric plexus was a plexus of nerves situated on the the bifurcation of the abdominal aorta to sacrum; after incision of sacrum fascia was done cling to the sacrum; the pelvic splanchnic nerves and sacral splanchnic nerves were demonstrated; pelvic splanchnic nerves were splanchnic nerves that arised from ventral rami of the second, third, and often the fourth sacral nerves to provide preganglionic parasympathetic innervation to the hindgut;sacral splanchnic nerves providing postganglionic fibers, emerged from the sympathetic trunk, were then joined by the pelvic splanchnic nerves to form the inferior hypogastric plexuses which were placed lateral to the rectum.Laparoscopic observations showed that:abdominal aortic plexus and superior hypogastric plexus were unclear; at the level of sacroiliac joint, the hypogastric nerve began where the superior hypogastric plexus split into a right and left plexus, situated under the loose connective tissue, and continued inferiorly on its corresponding side of the body at the level of the 3rd sacral vertebra;left hypogastric nerve was closed to posterior of mesorectum;denonvilliers fascia was thin, reflective fascial structure, and easily removed together with mesorectum excision because of anterior loose structure. CONCLUSIONS: Ligation of the inferior mesenteric artery at its origin is safe.Excessive dissection of the connective tissue covering the surface of the aorta should be avoided to protect the abdominal aortic plexus.Sharp dissection performed by pursuing the outer surface of the mesorectum maintaining the integrity of mesorectum, could avoid the superior hypogastric plexus and hypogastric nerves injury posteriorly, and protect the inferior hypogastric plexues while cutting lateral ligament laterally. The integrity of Denonvilliers fascia during anterior resection of rectum should be confirmed to avoid urogenitalis aparatus branches damage.

Nanodrug modified with engineered cell membrane targets CDKs to activate aPD-L1 immunotherapy against liver metastasis of immune-desert colon cancer.

Immunotherapy based on the PD-1/PD-L1 axis blockade has no benefit for patients diagnosed with colon cancer liver metastasis (CCLM) for the microsatellite stable/proficient mismatch repair (MSS/pMMR)) subtype, which is known as an immune-desert cancer featuring poor immunogenicity and insufficient CD8+ T cell infiltration in the tumor microenvironment. Here, a multifunctional nanodrug carrying a cyclin-dependent kinase (CDK)1/2/5/9 inhibitor and PD-L1 antibody is prepared to boost the immune checkpoint blockade (ICB)-based immunotherapy against MSS/pMMR CCLM via reversing the immunosuppressive tumor microenvironment. To enhance the MSS/pMMR CCLM-targeting efficacy, we modify the nanodrug with PD-L1 knockout cell membrane of this colon cancer subtype. First, CDKs inhibitor delivered by nanodrug down-regulates phosphorylated retinoblastoma and phosphorylated RNA polymerase II and meanwhile arrests the G2/M cell cycle in CCLM to promote immunogenic signal release, stimulate dendritic cell maturation, and enhance CD8+ T cell infiltration. Moreover, CDKi suppresses the secretion of immunosuppressive cytokines in tumor-associated myeloid cells sensitizing ICB therapy in CCLM. Notably, the great efficacy to activate immune responses is demonstrated in the patient-derived xenograft model and the patient-derived organoid model as well, revealing a clinical application potential. Overall, our study represents a promising therapeutic approach for targeting liver metastasis, remolding the tumor immune microenvironment (TIME), and enhancing the response of MSS/pMMR CCLM to boost ICB immunotherapy.

[Surgical treatment for endoscopically unresectable polyps of colon and rectum].

OBJECTIVE: To explore the characteristics and risks of cancer in endoscopically unresectable polyps and compare the surgical outcomes of different operations. METHODS: A retrospective review of 40 patients undergoing surgical operations for polyps unresectable at colonoscopy between August 2006 and July 2012 from Department of Gastrointestinal Surgery was performed. The follow-up period was 3 to 72 months (median: 24.5 months). RESULTS: The rate of endoscopically unresectable polyps with invasive cancer was 67.5% (27/40). And it was significantly influenced by patient age and number of polyps (both P < 0.01). Perioperative volume of blood loss ((86 ± 58) ml vs (44 ± 32) ml, P = 0.0066), time to first flatus ((2.7 ± 1.3) d vs (1.7 ± 0.6) d, P = 0.0018), incidence of complication (2 cases vs 0, P = 0.0365) and hospital stay ((11.2 ± 1.0) d vs (15.0 ± 5.0) d, P = 0.0164) were significantly different between open colectomy and laparoscopic group. And the long-term survival outcomes were similar in both groups (90.9% (10/11) vs 100.0% (27/27), 90.9% (10/11) vs 96.3% (26/27), both P > 0.05). CONCLUSIONS: Endoscopically unresectable polyps of colon and rectum have high malignancy rate. Polyps in elderly patients and multiple polyps are more likely to develop invasive cancer. Long-term outcomes are similar between open colectomy and laparoscopic colectomy groups, but laparoscopic group has better short-term outcomes. For endoscopically unresectable polyps, laparoscopic colectomy may be the first choice.

New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Erratum: CM082 Enhances the Efficacy of Chemotherapeutic Drugs by Inhibiting the Drug Efflux Function of ABCG2.

[This corrects the article DOI: 10.1016/j.omto.2019.12.007.].

Preservation versus resection of Denonvilliers' fascia in total mesorectal excision for male rectal cancer: follow-up analysis of the randomized PUF-01 trial.

Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers' fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Synchronous Colorectal Liver Metastases considering Infectious Complications: Simultaneous or Delayed Surgery?

Background: Simultaneous or delayed surgery for synchronous colorectal liver metastases is performed in the clinic; which method is better is still up for debate. In particular, infectious complications are rarely compared. This study aims to investigate the differences between simultaneous and delayed surgery for synchronous colorectal liver metastases by comparing infectious complications and prognosis. Methods: Firstly, the patients' information from a single institution's database was retrospectively analyzed. Then the patients were divided into a simultaneous group and a delayed group according to synchronous colorectal liver metastases. Analyzing the postoperative complications within 30 days, the progression-free survival, and the overall survival in the two groups. Results: The simultaneous group had a higher neo-adjuvant chemotherapy rate (42.0% VS. 16.0% in the delayed group, P < 0.05) and laparoscopic surgery rate (89.8% VS. 72.0% in the delayed group, P < 0.05) than the delayed group. Moreover, the simultaneous group had a higher liver-related infection rate (17.0 VS. 0.0% in the delayed group, P < 0.05). Conclusion: Although there was no difference in survival rate between delayed and simultaneous surgeries, the delayed surgery have fewer liver-related infections compared with the simultaneous surgery in synchronous colorectal liver metastases patients. Delayed surgery could be a better treatment method for synchronous colorectal liver metastases patients.

Tumor-associated macrophage-specific CD155 contributes to M2-phenotype transition, immunosuppression, and tumor progression in colorectal cancer.

BACKGROUND: Onco-immunogenic molecule CD155 is overexpressed in various tumor microenvironments (TME) including in colorectal cancer (CRC). Tumor-associated macrophages (TAMs) are the most abundant immune cells in CRC TME and play a vital role in CRC progression and metastasis. Most studies have focused on investigating the role of CRC cell-specific CD155 on CRC progression, while the contribution of TAMs-specific CD155 is still unknown. Here, we sought to investigate the expression pattern of CD155 in CRC TAMs and its role in tumor immunity and progression. METHODS: CD155 expression patterns in CRC TAMs and macrophages in paratumor or adjacent normal tissue were analyzed in 50 patients with CRC using flow cytometry and in 141 patients with CRC using immunohistochemistry. The correlation of CD155 expression level in TAMs with M1 and M2 phenotypic transition was analyzed. The role of macrophage-specific CD155 in CRC progression and tumor immune response was investigated in vitro and in vivo. We further analyzed the effect of CRC cells on the regulation of CD155 expression in macrophages. RESULTS: CRC TAMs from clinical samples showed robustly higher expression of CD155 than macrophages from paratumor and adjacent normal tissues. The CD155 expression level was higher in TAMs of CRC at III/IV stages compared with the I/II stages and was negatively associated with the survival of patients with CRC. CD155+ TAMs showed an M2 phenotype and higher expression of interleukin (IL)-10 and transforming growth factor (TGF)-ß. CD155+ macrophages promoted CRC cell migration, invasion, and tumor growth supporting the findings from the clinical tissue analysis. This effect was mainly regulated by TGF-ß-induced STAT3 activation-mediated release of matrix metalloproteinases (MMP)2 and MMP9 in CRC cells. CD155-/- bone marrow transplantation in wild-type mice, as well as CD155- macrophages treatment, promoted the antitumor immune response in the mice ectopic CRC model. Additionally, CRC cells released IL-4 to trigger CD155 expression in macrophages indicating the regulatory role of CRC cells in the development of CD155+ TAMs. CONCLUSIONS: These findings indicated that CD155+ TAMs are responsible for the M2-phenotype transition, immunosuppression, and tumor progression in CRC. The specific localization of CD155+ TAMs in CRC tissue could turn into a potential therapeutic target for CRC treatment.

Identifying the E2F3-MEX3A-KLF4 signaling axis that sustains cancer cells in undifferentiated and proliferative state.

Rationale: Dysregulation of signaling that governs self-renewal and differentiation of intestinal stem cells (ISCs) is a major cause of colorectal cancer (CRC) initiation and progression. Methods: qRT-PCR, western blotting, in situ hybridization, immunohistochemistry and immunofluorescence assays were used to detect the expression levels of MEX3A, KLF4 and E2F3 in CRC tissues. The biological functions of MEX3A were studied using Mex3a knockout (KO) and intestinal epithelium specific conditional knockout (cKO) mice, AOM-DSS mouse colorectal tumor model, Apc floxed mouse tumor model and intestinal and tumor organoids. Transcriptomic RNA sequencing (RNA-seq), RNA crosslinking immunoprecipitation (CLIP) and luciferase reporter assays were performed to explore the molecular mechanisms of MEX3A. Results: RNA-binding protein MEX3A, a specific ISC marker gene, becomes ectopically upregulated upon CRC and its levels negatively correlate with patient survival prognosis. MEX3A functions as an oncoprotein that retains cancer cells in undifferentiated and proliferative status and it enhances their radioresistance to DNA damage. Mechanistically, a rate limiting factor of cellular proliferation E2F3 induces MEX3A, which in turn activates WNT pathway by directly suppressing expression of its pro-differentiation transcription factor KLF4. Knockdown of MEX3A with siRNA or addition of KLF4 agonist significantly suppressed tumor growth both by increasing differentiation status of cancer cells and by suppressing their proliferation. Conclusions: It identifies E2F3-MEX3A-KLF4 axis as an essential coordinator of cancer stem cell self-renewal and differentiation, representing a potent new druggable target for cancer differentiation therapy.

Laparoscopic versus open appendectomy for acute appendicitis: a metaanalysis.

BACKGROUND: Currently, laparoscopic appendectomy (LA) provides a safe and effective alternative to open appendectomy (OA), but its use remains controversial. This study aimed to evaluate the efficiency and safety of LA through a metaanalysis. METHODS: Randomized controlled trials (RCTs) comparing LA and OA published between January 1992 and February 2010 were included in this study. Strict literature appraisal and data extraction were carried out independently by two reviewers. A metaanalysis then was performed to evaluate operative time, hospital cost, postoperative complications, length of analgesia, bowel function recovery, day liquid diet began, hospital stay, and return to work and normal activity. RESULTS: The metaanalysis comprised 25 RCTs involving 4,694 patients (2,220 LA and 2,474 OA cases). No significant differences were found between the LA and OA groups in terms of age, gender, body mass index (BMI), or type of appendiceal inflammation. Compared with OA, LA showed advantages of fewer postoperative complications (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.55-0.98; p = 0.04), less pain (length of analgesia: weighted mean difference [WMD], -0.53; 95% CI, -0.91 to -0.15; p = 0.007), earlier start of liquid diet (WMD, -0.51; 95% CI, -0.75 to -0.28; p < 0.0001), shorter hospital stay (WMD, -0.68; 95% CI, -1.02 to -0.35; p < 0.0001), and earlier return to work (WMD, -3.09; 95% CI, -5.22 to -0.97; p = 0.004) and normal activity (WMD, -4.73; 95% CI, -6.54 to -2.92; p < 0.00001), but a comparable hospital cost (WMD of LA/OA ratio, 0.11; 95% CI, -0.18 to 0.40; p = 0.47) and a longer operative time (WMD, 10.71; 95% CI, 6.76-14.66; p < 0.00001). CONCLUSION: Despite the longer operative time, LA results in less postoperative pain, faster postoperative rehabilitation, a shorter hospital stay, and fewer postoperative complications than OA. Therefore, LA is worth recommending as an effective and safe procedure for acute appendicitis.

Case Report: Cetuximab in Combination With Chemotherapy for the Treatment of Multifocal Hepatic Metastases From Colorectal Cancer Guided by Genetic Tests.

Hepatic metastases were reported in up to 70% of colorectal cancer patients, among which multifocal hepatic metastasis represents one of the complications that lead to poor prognosis. The majority of the patients carrying multifocal hepatic metastases required pharmaceutical treatments to reduce the tumor size prior to surgical resection. However, the clinical responses to pharmaceutical agents were difficult to predict due to the heterogeneous nature of the multifocal tumors. Here, we report a case with multifocal hepatic metastases from colorectal cancer that was resistant to the primary chemotherapy and Bevacizumab plus chemotherapy, but responded to the combined therapy of Cetuximab and FOLFOX. Genetic tests had revealed that the tumor was highly metastatic due to the mutations of the WNT signaling pathway, and the metastatic tumors might be sensitive to Cetuximab. Consistent with the molecular characterizations, the metastatic tumors continue to emerge after chemotherapy, and rapidly relapsed in great numbers after liver resection. However, the combined therapy of Cetuximab and FOLFOX guided by the genetic tests significantly reduced the size and number of metastatic tumors. To conclude, deciphering the mutation profiles of multifocal metastatic tumors may guide the determination of treatment tactics, which may benefit the patients with non-resectable advanced carcinoma.

SPT6 recruits SND1 to co-activate human telomerase reverse transcriptase to promote colon cancer progression.

Human telomerase reverse transcriptase (hTERT) plays an extremely important role in cancer initiation and development, including colorectal cancer (CRC). However, the precise upstream regulatory mechanisms of hTERT in different cancer types remain poorly understood. Here, we uncovered the candidate transcriptional factor of hTERT in CRC and explored its role and the corresponding molecular mechanisms in regulating hTERT expression and CRC survival with an aim of developing mechanism-based combinational targeting therapy. The possible binding proteins at the hTERT promoter were uncovered using pull-down/mass spectrometry analysis. The regulation of SPT6 on hTERT expression and CRC survival was evaluated in human CRC cell lines and mouse models. Mechanistic studies focusing on the synergy between SPT6 and staphylococcal nuclease and Tudor domain containing 1 (SND1) in controlling hTERT expression and CRC progression were conducted also in the above two levels. The expression correlation and clinical significance of SPT6, SND1, and hTERT were investigated in tumor tissues from murine models and patients with CRC in situ. SPT6 was identified as a possible transcriptional factor to bind to the hTERT promoter. SPT6 knockdown decreased the activity of hTERT promoter, downregulated the protein expression level of hTERT, suppressed proliferation, invasion, and stem-like properties, promoted apoptosis induction, and enhanced chemotherapeutic drug sensitivity in vitro. SPT6 silencing also led to the delay of tumor growth and metastasis in mice carrying xenografts of human-derived colon cancer cells. Mechanistically, SND1 interacted with SPT6 to co-control hTERT expression and CRC cell proliferation, stemness, and growth in vitro and in vivo. SPT6, SND1, and hTERT were highly expressed simultaneously in CRC tissues, both from the murine model and patients with CRC in situ, and pairwise expression among these three factors showed a significant positive correlation. In brief, our research demonstrated that SPT6 synergized with SND1 to promote CRC development by targeting hTERT and put forward that inhibiting the SPT6-SND1-hTERT axis may create a therapeutic vulnerability in CRC.