Dechuan Li

Detection of circulating tumor cells in peripheral blood of colorectal cancer patients without distant organ metastases.

PurposeRecently, the detection of circulating tumor cells (CTCs) in peripheral blood has become an important tool for the non-invasive assessment of micrometastases and to predict clinical outcome. The objective of this study was to investigate if the presence of CTCs in peripheral blood influences the prognosis in colorectal cancer (CRC) patients without distant organ metastases.MethodsThe GCC mRNA and CK20 mRNA levels in peripheral blood and the serum levels of CEA of 92 CRC patients without distant organ metastasis were analyzed by quantitative RT-PCR and ELISA, respectively. Its associations with overall survival (OS) and disease-free survival (DFS) rates were analyzed.ResultsUnivariate analyses showed that lower OS and DFS rates were significantly associated with GCC and CK20 mRNA levels, the presence of lymph node metastases, the presence of mesenteric root lymph node metastases, and the presence of tumor emboli in vessels (p < 0.05), but not with CEA levels. Multivariate analyses showed a significant association between 1) OS and GCC mRNA levels and differentiation types and 2) DFS and the presence of tumor emboli in the vessels. Kaplan-Meier curves showed that DFS was significantly associated with the presence of poorly differentiated cells, the presence of mesenteric root lymph node metastases having received prior chemotherapy, and the presence of tumor emboli in vessels.ConclusionThe detection of CTCs in peripheral blood may be useful for the prediction of clinical outcome in CRC patients without distant organ metastases.

Prognostic Role of Neutrophil-to-Lymphocyte Ratio in Locally Advanced Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

Background Increasing evidence suggests that cancer-associated inflammation is associated with poorer outcomes. The neutrophil-to-lymphocyte ratio (NLR), considered as a systemic inflammation marker, is thought to predict prognoses in colorectal cancer. In this study, we explored the association between the NLR and prognoses following neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC). Material/Methods From February 2002 to December 2012, a group of 202 patients diagnosed with LARC and receiving neoadjuvant CRT followed by radical surgery was included in our retrospective study. The associations between the pre-CRT NLR and clinicopathological characteristics, as well as the predictive value of pre-CRT NLR against survival outcomes, were analyzed. Results The average NLR was 2.7±1.5 (median 2.4, range 0.6–12.8). There were 63 (31.2%) patients with NLR ≥3.0, and 139 (68.8%) patients with NLR <3.0. Correlation analyses showed that no clinicopathological characteristics except age were associated with NLR. We did not find an association between NLR and survival outcomes. In multivariate Cox model analyses, the R1/R2 resection, lymph node ratio ≥0.1, and perineural/lymphovascular invasion were independently associated with worse disease-free survival and overall survival. Conclusions In our cohort, the NLR did not correlate with survival outcomes in LARC patients undergoing neoadjuvant CRT. The prognostic value of NLR should be validated in large-scale prospective studies.

Factors Predicting Difficulty of Laparoscopic Low Anterior Resection for Rectal Cancer with Total Mesorectal Excision and Double Stapling Technique

Background Laparoscopic sphincter-preserving low anterior resection for rectal cancer is a surgery demanding great skill. Immense efforts have been devoted to identifying factors that can predict operative difficulty, but the results are inconsistent. Objective Our study was conducted to screen patients’ factors to build models for predicting the operative difficulty using well controlled data. Method We retrospectively reviewed records of 199 consecutive patients who had rectal cancers 5–8 cm from the anal verge. All underwent laparoscopic sphincter-preserving low anterior resections with total mesorectal excision (TME) and double stapling technique (DST). Data of 155 patients from one surgeon were utilized to build models to predict standardized endpoints (operative time, blood loss) and postoperative morbidity. Data of 44 patients from other surgeons were used to test the predictability of the built models. Results Our results showed prior abdominal surgery, preoperative chemoradiotherapy, tumor distance to anal verge, interspinous distance, and BMI were predictors for the standardized operative times. Gender and tumor maximum diameter were related to the standardized blood loss. Temporary diversion and tumor diameter were predictors for postoperative morbidity. The model constructed for the operative time demonstrated excellent predictability for patients from different surgeons. Conclusions With a well-controlled patient population, we have built a predictable model to estimate operative difficulty. The standardized operative time will make it possible to significantly increase sample size and build more reliable models to predict operative difficulty for clinical use.

Up-regulation of lncRNA SNHG1 indicates poor prognosis and promotes cell proliferation and metastasis of colorectal cancer by activation of the Wnt/β-catenin signaling pathway

Recently, the lncRNA small nucleolar RNA host gene (SNHG1) has been exhibited to be upregulated, which plays a crucial role in the development and prognosis of several cancers. However, the role of the biology and clinical significance of SNHG1 in the tumorigenesis of colorectal cancer (CRC) has rarely been reported. In this work, we firstly found that SNHG1 expression levels were upregulated aberrantly in colorectal cancer tissues and colorectal cancer cell lines. By Kaplan-Meier survival analysis, patients with high SNHG1 expression level had poorer overall survival (OS) and progression-free survival (PFS) than those with low SNHG1 expression. In multivariate analysis, increased SNHG1 expression was proved to be an independent unfavorable prognostic indicator for CRC. In vitro experiments revealed that SNHG1 silencing inhibited the growth and metastasis and induced apoptosis of CRC cell lines. Finally, we found that SNHG1 may induce the activation of the WNT/β-catenin pathway through regulating β-catenin expression and transcription factor-4 (TCF-4), cyclin D1 and MMP-9. Altogether, our findings demonstrated that lncRNA SNHG1, was high expressed in colorectal cancer tissues and may serve as a tumor oncogene through regulating WNT/β-catenin signal pathway, which provided a candidate diagnostic biomarker and a promising therapeutic target for patients with CRC.

Preparation, characterization, and in vivo study of Rhein Solid Lipid Nanoparticles for oral delivery

In this study, rhein‐SLNs were successfully produced by hot homogenization followed by ultrasonication. Precirol ATO5 in which rhein exhibited higher partition coefficient was selected for preparation of SLNs. In the dynamic light scattering, the rhein‐SLNs showed a smaller size with a mean value of 120.8 ± 7.9 nm and with zeta potential of −16.9 ± 2.3 mV. SLNs exhibited a good stability during the period of 2 months. The SLNs indicated faster drug release with a burst release within 2 hr and followed by a sustained release with a biphasic drug‐release pattern. Comparing with the same concentration (free drug), the cellular cytotoxicity of rhein‐loaded SLNs increased significantly at the same incubation condition. In vivo, the AUC0‐t of rhein in the form of SLNs was significantly increased and was 2.06‐fold that of suspensions group. The results showed an increased oral absorption and improved the oral bioavailability of rhein by the formulation of SLNs.

Comparison of hand-assisted laparoscopic surgery using tissue fusion devices and open resection for treatment of rectosigmoid carcinoma.

Modern tissue fusion devices used in hand-assisted laparoscopic surgery (HALS), a method of combining endoscopic surgery with tactile sensation, can minimize surgical trauma and hospitalization times beyond both conventional laparoscopy and open surgery. The outcomes of HALS using tissue fusion devices and conventional open surgery for curative resection of rectosigmoid carcinoma were compared. A total of 78 (45 males, 33 females; mean age, 57.2±11.7 y) rectosigmoid carcinoma patients underwent HALS surgery (HALS group) and 78 age-matched, sex-matched, and tumor status–matched rectosigmoid carcinoma patients (control group) underwent open resection between June 2008 and June 2010. In the HALS and control groups, abdominal incision length, intraoperative blood loss, procedure time, postoperative abdominal drainage, time to first flatus (bowel function return), length of hospital stay, morbidity, mortality, and pathology were assessed. Procedure times were similar in both groups (142.37±42.09 vs. 137.56±36.24 min). However, length of abdominal incision (5.14±0.47 vs. 13.17±2.41 cm), intraoperative blood loss (125.96±75.58 vs. 142.56±65.37 mL), need for postoperative analgesia, bowel function return (68.01±22.64 vs. 79.77±19.94 h), and postoperative hospital stay (6.47±1.73 vs. 7.73±1.71 d) were all significantly improved in the HALS group. At a median follow-up of 26 months, no significant differences in anastomotic recurrence were observed between groups (1 case/each group). Thus, the HALS approach for curative resection of rectosigmoid carcinoma was found to be similarly safe and effective compared with open resection. Furthermore, HALS may improve postoperative recovery and reduce hospitalization times.

Endoscopic extraperitoneal radical prostatectomy after radical resection of pT1-pT2 rectal cancer: a report of thirty cases

Introduction Endoscopic extraperitoneal radical prostatectomy (EERPE) has gained popularity for the treatment of localized prostate cancer. However, prior complex lower abdominal or pelvic surgery can complicate subsequent EERPE. To date, there have been few reports on patients who underwent EERPE after radical resection of pT1-pT2 rectal cancer. Aim To present our experience with EERPE in patients after radical resection of pT1-pT2 rectal carcinoma and introduce a simple and effective way to create an extraperitoneal working space. Material and methods Thirty patients after radical resection of pT1-pT2 rectal carcinoma were treated with EERPE for biopsy-proven localized prostate cancer. Operation time, estimated blood loss, conversion to open surgery rate, transfusion rate and transurethral catheter time were recorded. Meanwhile, functional outcome (continence and potency) and oncological outcome were reviewed. Results The average operative time was 168 min. Mean blood loss was 195 ml. There was no need for conversion to open surgery or transfusion. The catheter was removed on postoperative day (POD) 7.8. After a mean follow-up time of 53.1 months, 3 patients had a prostate-specific antigen level relapse over 0.1 ng/ml. At the follow-up time, 26 patients were completely continent, and 4 needed 1–2 pads/day. Of the 6 patients who underwent neurovascular bundle preservation, none have experienced return of erections at the last follow-up time. Conclusions Endoscopic extraperitoneal radical prostatectomy after radical resection of rectal carcinoma appears promising, with feasibility in experienced hands. The operative data, postoperative urinary incontinence and oncological outcomes appear encouraging, but the rate of erectile dysfunction seems to be disappointing.

Factors Influencing Difficulty of Laparoscopic Abdominoperineal Resection for Ultra-Low Rectal Cancer.

Purpose: Our current study was conducted to identify patients’ anatomic, pathologic, and clinical factors to predict difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. Materials and Methods: Records of 117 consecutive patients with rectal cancer 2 to 5 cm from the anal verge were retrospectively reviewed. Using univariate and multivariate linear or logistic regression models, standardized operative time and blood loss, as well as postoperative morbidity were utilized as endpoints to screen patients’ multiple variables to predict operative difficulty. Results: Multivariate linear regression analysis showed body mass index (BMI) (estimate=0.07, P=0.0056), interspinous distance (estimate=−0.02, P=0.0011), tumor distance from anal verge (estimate=−0.17, P=0.0355), prior abdominal surgery (estimate=0.51, P=0.0180), preoperative chemoradiotherapy (estimate=0.67, P=0.0146), and concurrent diseases (hypertension and/or diabetes mellitus) (estimate=0.49, P=0.0122) are predictors for standardized operative time. Age (estimate=0.02, P=0.0208) and concurrent diseases (estimate=0.43, P=0.0476) were factors related to standardized blood loss. BMI (estimate=0.15, P=0.0472) was the only predictor for postoperative morbidity based on logistic regression analysis. Conclusions: Age, BMI, interspinous distance, tumor distance from anal verge, prior abdominal surgery, preoperative chemoradiotherapy, and concurrent diseases influence the difficulty of performing laparoscopic abdominoperineal resection for ultra-low rectal cancer. Standardized operative time allows researchers to amass samples by pooling data from all published studies, thus building reliable models to predict operative difficulty for clinical use.

Expression of guanylyl cyclase C in tissue samples and the circulation of rectal cancer patients

Guanylyl cyclase C (GCC) is a transmembrane surface receptor restricted to intestinal epithelial cells, from the duodenum to the rectum. We compared GCC expression in tumors and normal rectal tissues, and investigated the relation between GCC expression and metastasis and long-term survival of rectal cancer patients. Based on the UICC classification, 42 rectal cancer patients in this study were classified as stage I, 48 patients as stage II, and 90 patients as stage III. Overexpression of GCC was observed in 80 rectal tumors as compared to matched normal tissues, where no strong staining of GCC was observed. An association between GCC mRNA in the circulation and tumor emboli in vessels, CK20 mRNA, distant organ metastasis, and survival status was observed in 100 rectal cancer patients. Univariate Cox regression analysis indicated that tumor emboli in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC mRNA correlated with 5-year disease-free survival (DFS); while lymph node metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall survival (OS). In a multivariate Cox regression model, GCC mRNA level and mesenteric root lymph node metastasis associated with DFS, while GCC mRNA levels associated with OS. Quantification of GCC expression in circulation is a valuable biomarker for assessing tumor burden and predicting outcome in rectal cancer patients.

Comparison of perioperative outcomes between laparoscopic and open surgery for mid-low rectal cancer with total mesorectal excision following neoadjuvant chemoradiotherapy

OBJECTIVE The objective of our study was to determine the feasibility and safety of laparoscopic total mesorectal excision (TME) for mid-low rectal cancer following neoadjuvant chemoradiotherapy (nCRT). METHODS We retrospectively reviewed the records of 172 patients with locally advanced rectal cancer who underwent laparoscopic (n = 75) or conventional open (n = 97) surgery with TME following nCRT from June 2009 to October 2015. Perioperative outcomes and related clinical variables were collected and statistically analyzed. RESULTS Our results showed that patients who underwent laparoscopic surgery had significantly less blood loss and shorter time to pass first flatus and to start a liquid diet compared to those on open surgery. However, other perioperative outcomes, including operative times, postoperative morbidity rates, number of lymph nodes harvested, and sphincter preservation rates, were not significantly different between the two groups. After controlling for surgical approaches, we found that age, gender, tumor stages, and tumor distance to anal verge were significantly correlated with operative times in both groups. Likewise, age, body mass index, tumor T stages, and tumor distance to anal verge were predictors for postoperative morbidity in both groups. CONCLUSIONS We concluded that laparoscopic TME following nCRT is feasible and safe for patients with mid-low rectal cancer. Furthermore, tumor distance to anal verge and age are two important determinants of both operative times and postoperative morbidity, regardless of surgical option.