Controversies and consensus in transanal total mesorectal excision (taTME): Is it a valid choice for rectal cancer?

Transanal total mesorectal excision (taTME) is a novel approach to radical surgery for low rectal cancer. taTME is associated with the benefits of a higher rate of free distal resection margins (DRM) under direct visualization, better visualization of the mesorectal plane, and the feasibility of overcoming the restriction of the distal pelvis. Thus, it is increasingly used globally. In this review, we investigated whether taTME yields better short- and long-term outcomes than laparoscopic TME.

Effect of different reinforcement methods on anastomotic leakage prevention after laparoscopic double anastomosis.

BACKGROUND AND OBJECTIVES: To investigate the effects of different suture reinforcement methods for anastomotic leakage and other postoperative complications after the use of a laparoscopic double stapling technique (DST). METHODS: We collected the data of 124 patients who underwent laparoscopic radical resection of colorectal cancer from July 2017 to September 2018 at our institution. Patients were divided into three groups according to the suture reinforcement methods: intermittent, continuous suture reinforcement, and non-reinforcement (n = 41, 41, and 42, respectively). One-way analysis of variance, χ2 , Fisher's exact, and nonparametric tests were used for statistical analysis. RESULTS: Among the 124 patients, there were no statistically significant differences in operation times, intraoperative blood loss, postoperative hospital stays and recovery of bowel movement. Nine patients were diagnosed with anastomotic leakage (AL). The incidences of serious AL in the intermittent and continuous suture reinforcement groups were lower than that in the control group, with lower reoperation rate, shorter average lengths of stay and lower treatment costs of two experimental groups. CONCLUSION: Intermittent and continuous sutures after laparoscopic DST is effective, safe, and feasible on anastomotic leakage prevention. These procedures could be popularized in rectal surgery on patients with high risk of AL.

Staged laparoscopic management of locally advanced gastric cancer with outlet obstruction.

BACKGROUND: The prognosis of patients with locally advanced gastric cancer with outlet obstruction is poor. Gastrectomy with curative intent is often initially impossible or difficult. OBJECTIVE: We report our experience of curative distal gastrectomy after laparoscopic gastrojejunostomy and fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) chemotherapy to examine the feasibility and safety of this modified strategy for locally advanced gastric cancer with outlet obstruction, initially deemed unresectable. METHODS: Between October 2017 and June 2019, 15 patients diagnosed with locally advanced gastric cancer with outlet obstruction sequentially underwent gastrojejunostomy, received four cycles of FLOT chemotherapy, and underwent laparoscopic distal gastrectomy with curative intent (R0 resection + D2 lymphadenectomy). Clinical data were retrospectively collected and analyzed. RESULTS: R0 resection was possible in 12/15 patients, laparoscopically in 11, and one conversion to laparotomy was necessary. There was no perioperative mortality in the 12 patients. Pathologic evaluation of the resected specimens revealed that complete tumor grade regression 1a (TRG1a), TRG1b, TRG2, and TRG3 occurred in 3, 2, 4, and 3 patients, respectively. CONCLUSION: This case series showed that curative surgical resection was feasible as a staged approach for patients with locally advanced gastric cancer with outlet obstruction, after initial staged gastrojejunostomy and chemotherapy.

Comparative study of oncologic efficacy of cephalomedial to lateral dissection versus medial to lateral dissection in laparoscopic total mesorectal excision for rectal cancer: An RCT study.

BACKGROUND AND OBJECTIVES: We compared the 3-year overall survival between cephalomedial-to-lateral approach proctectomy (CEMP) and medial-to-lateral approach proctectomy (MAP) in patients undergoing laparoscopic total mesorectal excision for rectal cancer. The advantages of CEMP and the clinical value of No. 253 lymph nodes resection have not been objectively analyzed in literature. METHODS: This was a prospective, two-arm, multicenter, single-blinded, randomized trial. The primary endpoint was 3-year overall survival, and secondary endpoints included safety, feasibility, oncological radicality (including number of No. 253 lymph nodes harvested), short-term outcome, 3-year disease-free survival, rate of postoperative complications, mortality, and rate of recurrence. RESULTS: From May 2016 to July 2020, 506 patients were enrolled-256 in the CEMP group and 250 in the MAP group. Comparison of overall survival and disease-free survival showed that there was treatment benefit in the CEMP group (28.22 ± 12.12 vs. 27.44 ± 13.06, p = 0.485; 27.24 ± 12.01 vs. 26.42 ± 12.81; p = 0.457). More No. 253 lymph nodes were harvested in the CEMP group, and cases with positive No. 253 lymph nodes had worse prognosis in stage III. Surgical safety was equal for both approaches. CONCLUSIONS: Dissection of No. 253 lymph nodes may be important to improve clinical prognosis, but further studies with larger samples are needed to confirm this finding.

A modified uncut Roux-en-Y anastomosis in totally laparoscopic distal gastrectomy: preliminary results and initial experience.

OBJECTIVE: To investigate the safety and feasibility of totally laparoscopic uncut Roux-en-Y anastomosis in the distal gastrectomy with D2 dissection for gastric cancer. We also summarized the preliminary experience of totally laparoscopic uncut Roux-en-Y anastomosis. METHODS: A retrospective analysis was done in 51 cases of total laparoscopic uncut Roux-en-Y anastomosis in the distant gastrectomy with D2 dissection for gastric cancer in our hospital from September 2014 to December 2015. RESULTS: All of 51 cases underwent total laparoscopic uncut Roux-en-Y anastomosis. All the procedures were performed successfully. There were neither conversions to open surgery nor intraoperative complications in all 51 cases. In this study, the median operative time was 170 (135-210) min and the median time of anastomosis was 27 (24-41) min. The blood loss was 60 (30-110) ml. The time to flatus and length of postoperative hospital stay were 2 (1-3) days, and 8 (7-12) days, respectively. The mean lymph node harvest was 34 (18-49). One anastomotic bleeding occurred postoperatively which was cured by conservative treatment. No major postoperative complication occurred, such as anastomotic leak, anastomotic stenosis, and Roux stasis syndrome. After a short-term follow-up, no recanalization or reflux gastritis was encountered by endoscopy. CONCLUSION: The totally laparoscopic uncut Roux-en-Y anastomosis in distal gastrectomy with lymph node dissection for gastric cancer is safe and feasible, with a very low rate of recanalization and reflux gastritis.

Completely medial versus hybrid medial approach for laparoscopic complete mesocolic excision in right hemicolon cancer.

OBJECTIVE: To explore the feasibilities between operational approaches for laparoscopic complete mesocolic excision (CME) to right hemicolon cancer. METHODS: This prospective randomized controlled trial included patients admitted to a Shanghai minimally invasive surgical center to receive laparoscopic CME from September 2011 to January 2013 randomized into two groups: hybrid medial approach (HMA) and completely medial approach (CMA). The feasibilities and strategies of the two techniques were studied and compared. Furthermore, the operation time and vessel-related complications were designed to be the primary end points, and other operational findings, including the classification of the surgical plane and postoperative recovery, were designed to be the secondary end points for this study. RESULTS: After screening, 50 cases were allocated to the HMA group and 49 to the CMA group. Within the HMA group, there were 48 cases graded with mesocolic plane and 2 with intramesocolic plane. For the CMA group, there were 42 cases graded with mesocolic plane and seven with intramesocolic plane. The differences between the two were insignificant, as were the number of lymph nodes retrieved. The mean±standard deviation total operation time for the CMA group was 128.3 ± 36.4 min, which was significantly shorter than that for the HMA group, 142.6 ± 34.8 min. For the CMA group, the time involved in central vessel ligations and laparoscopic procedures was 58.5 %, 14.1 and 81.2 ± 23.5 min, respectively, which were shorter than the HMA group. The vessel-related complication rate was significantly higher in the HMA group. CONCLUSIONS: Laparoscopic CME via the total medial approach is technically feasible after the precise identification of the surgical planes and spaces for the right hemicolon. The procedure has a shorter operation time and fewer vessel-related complications.

Magnetic resonance imaging-based deep learning model to predict multiple firings in double-stapled colorectal anastomosis.

BACKGROUND: Multiple linear stapler firings during double stapling technique (DST) after laparoscopic low anterior resection (LAR) are associated with an increased risk of anastomotic leakage (AL). However, it is difficult to predict preoperatively the need for multiple linear stapler cartridges during DST anastomosis. AIM: To develop a deep learning model to predict multiple firings during DST anastomosis based on pelvic magnetic resonance imaging (MRI). METHODS: We collected 9476 MR images from 328 mid-low rectal cancer patients undergoing LAR with DST anastomosis, which were randomly divided into a training set (n = 260) and testing set (n = 68). Binary logistic regression was adopted to create a clinical model using six factors. The sequence of fast spin-echo T2-weighted MRI of the entire pelvis was segmented and analyzed. Pure-image and clinical-image integrated deep learning models were constructed using the mask region-based convolutional neural network segmentation tool and three-dimensional convolutional networks. Sensitivity, specificity, accuracy, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) was calculated for each model. RESULTS: The prevalence of ≥ 3 linear stapler cartridges was 17.7% (58/328). The prevalence of AL was statistically significantly higher in patients with ≥ 3 cartridges compared to those with ≤ 2 cartridges (25.0% vs 11.8%, P = 0.018). Preoperative carcinoembryonic antigen level > 5 ng/mL (OR = 2.11, 95%CI 1.08-4.12, P = 0.028) and tumor size ≥ 5 cm (OR = 3.57, 95%CI 1.61-7.89, P = 0.002) were recognized as independent risk factors for use of ≥ 3 linear stapler cartridges. Diagnostic performance was better with the integrated model (accuracy = 94.1%, PPV = 87.5%, and AUC = 0.88) compared with the clinical model (accuracy = 86.7%, PPV = 38.9%, and AUC = 0.72) and the image model (accuracy = 91.2%, PPV = 83.3%, and AUC = 0.81). CONCLUSION: MRI-based deep learning model can predict the use of ≥ 3 linear stapler cartridges during DST anastomosis in laparoscopic LAR surgery. This model might help determine the best anastomosis strategy by avoiding DST when there is a high probability of the need for ≥ 3 linear stapler cartridges.

Laparoscopic complete mesocolic excision (CME) with medial access for right-hemi colon cancer: feasibility and technical strategies.

OBJECTIVE: This study was designed to investigate the feasibility and technical strategies of laparoscopic complete mesocolic excision (CME) for right-hemi colon cancer. METHODS: The clinical and pathological findings of 64 patients with right-hemi colon cancer who underwent laparoscopic CME between March 2010 and September 2011 were collected retrospectively. Among them, 35 cases were eligible for the final analysis through various screening factors. The quality of surgery also was assessed by reviewing the recorded video obtained through the operations in terms of specimen anatomic planes and completeness of the excised mesocolon. RESULTS: Laparoscopic CME is focused on applying the concept of enveloped visceral and parietal planes during the operations. Laparoscopic approach proceeds with medial access where the dissection starts at ileocolic vessel before proceeds along with the superior mesenteric vessel. The access also emphasized en bloc resection of mesocolon without defections to the planes. Besides, lymph node resections at the root of ileocolic; right colic and middle colic vessels are necessary for ileocecum cancer. Cancers at the hepatic flexure requires further dissection of subpyloric lymph nodes and of greater omentum that is within 15 cm of the tumor and along the greater curvature. Thirty-five cases were evaluated as good plane. The median total number of central lymph nodes retrieved was 19 (range, 15-25) and central lymph node metastasis was found in 5 of all stage III cases. The median operation time was 2.6 h and the blood loss was 80 mL. The median time for passage of flatus and hospitalization were 2 and 12 days respectively. Complications were observed in three cases. CONCLUSIONS: CME is a novel concept for colon cancer surgery and might be a standard for the procedure. Laparoscopic CME with medial access is technically feasible and randomized trials are needed to evaluate its long-term outcomes.

Efficacy of neoadjuvant CapeOX/mFOLFOX6 without radiation for patients with baseline resectable mid-low locally advanced rectal cancer.

OBJECTIVES: Chemotherapy without radiation therapy for locally advanced rectal cancer (LARC) has attracted increasing attention, but the optimal schema remains controversial. In this study, we aimed to assess the efficacy and toxicity of neoadjuvant chemotherapy (nCT) of two regimens for patients with mid-low baseline resectable LARC. METHODS: A retrospective study was performed in 131 patients with baseline resectable LARC in a single center between April 2016 and August 2020. All patients received four cycles of neoadjuvant CapeOX or mFOLFOX6 before surgery. Clinical characteristics, pathological response, and survival status were then assessed. RESULTS: After a 1:1 propensity score matching, 96 patients were enrolled, including 48 receiving CapeOX and 48 receiving mFOLFOX6. The objective regression rates were 50.00% and 58.33%, and the pathological complete response rates were 6.25% and 8.33%, respectively, in the CapeOX and mFOLFOX6 groups. Patients who received mFOLFOX6 had a better tumor regression grade (TRG) than those who received CapeOX (P = 0.005). Patients in both groups had similar survival outcomes. CONCLUSIONS: The nCT has shown promising tumor response and survival outcomes, which can be a treatment option for baseline resectable LARC. For the two regimens, mFOLFOX6 provided better TRG than CapeOX, although no differences were observed in disease-free survival and OS.

Direct and indirect costs and long-term survival of laparoscopic anterior resection for rectal cancer.

BACKGROUND: Few studies evaluate the cost-effectiveness issues of laparoscopic anterior resection (LAR) for rectal cancer. This study evaluates direct and indirect costs of LAR and its long-term survival rate in rectal cancer patients. MATERIAL/METHODS: This prospective nonrandomized controlled trial included 2 endpoints (direct and indirect costs, and disease-free survival). From January 2003 to May 2005, rectal cancer patients admitted to our center were assigned to 2 groups: 87 patients underwent LAR (LAP), while 86 cases received open anterior resection (OPEN). The direct costs were prospectively evaluated. Main indirect cost is productivity loss. The data of direct costs, indirect costs, and the total costs were collected for the minimal cost analysis. RESULTS: Disease-free survival at 65 months in the LAP group and the OPEN group was 78.2% and 74.7%; there was no significant difference between the groups. Median direct costs were not significantly different between the LAP and the OPEN groups. Indirect costs of the LAP group were significantly lower than those of the OPEN group, while total costs were not significantly different. Cost percentage for operations, medications, and hospitalization were 75.90%, 11.28%, and 2.18% in the LAP group; while in the operation group, they were 54.50%, 29.09%, and 3.35%. CONCLUSIONS: Total economic budget for a patient receiving LAR was not significantly increased compared with the conservative method owing to its technical predominance, oncologic safety, as well as frequent bed turnover.

Long-term outcome of laparoscopic total mesorectal excision for middle and low rectal cancer.

This study aimed to assess the feasibility and long-term outcome of laparoscopic total mesorectal excision for middle and lower rectal cancer. Retrospective assessment was performed on 612 patients with middle and low rectal cancer in the surgery department of our hospital. Three-hundred and three patients underwent laparoscopic total mesorectal excision (LTME), and 309 patients underwent open TME (OTME). All the data regarding patient details, operative variables and the short- and long-term outcomes were collected and compared. The sphincter-preserving rates of the two groups were similar. The conversion rate in LTME was 2.31% (seven cases). Fourteen cases (6.67%) of protective diverting stoma were fashioned in the LTME group compared with 57 cases (26.64%) in the OTME group. The postoperative morbidity was the same in these two groups, while the postoperative period until bowel movement and hospital discharge was shorter in the LTME group (P < 0.01). The median follow-up period was 34 (6-81) months for the LTME group and 36 (6-81) months for the OTME group. Local recurrence rates, the five-year disease-free survival rate and the five-year overall survival rate showed no difference between the two groups. Laparoscopic surgery is feasible and safe in patients with middle and lower rectal cancer and can provide favorable short-term and long-term outcomes.

Long noncoding RNA LINC01234 silencing exerts an anti-oncogenic effect in esophageal cancer cells through microRNA-193a-5p-mediated CCNE1 downregulation.

BACKGROUND: Long non-coding RNAs (lncRNAs) are transcribed pervasively in the genome and act to regulate chromatin remodeling and gene expression. Dysregulated lncRNA expression has been reported in many cancers, but the role of lncRNAs in esophageal cancer (EC) has so far remained poorly understood. In this study, we aimed to understand the effect of lncRNA LINC01234 on EC development through competitively binding to microRNA-193a-5p (miR-193a-5p). METHODS: The Gene Expression Omnibus (GEO) database was used for microarray-based EC expression profiling. Gain- and loss-of-function analyses were carried out in human EC-derived Eca-109 and EC9706 cells. Expression analyses of miR-193a-5p, LINC01234, CCNE1, caspase-3, p21, Bax, cyclinD1 and Bcl-2 were performed using RT-qPCR and Western blotting. Cell proliferation, colony formation and apoptosis analyses were carried out using MTT, Hoechst 33258 and flow cytometry assays. A xenograft EC model in nude mice was used to evaluate in vivo tumor growth and CCNE1 expression. RESULTS: Microarray-based analyses revealed that LINC01234 expression was increased in primary EC samples, whereas that of miR-193a-5p was decreased. We found that CCNE1 was a target of miR-193a-5p and that LINC01234, in turn, sponges miR-193a-5p. After treatment with si-LINC01234 or miR-193a-5p mimic, EC cells (Eca-109 and EC9706) exhibited cyclinD1 and Bcl-2 downregulation, and caspase-3, p21, Bax and cleaved caspase-3 upregulation. LINC01234 silencing or miR-193a-5p upregulation resulted in decreased proliferation and colony formation, and increased apoptosis of EC cells. In addition, LINC01234 silencing or miR-193a-5p upregulation resulted in reduced in vivo EC tumor growth and CCNE1 expression in nude mice. CONCLUSIONS: We found that silencing of LINC01234 suppresses EC development by inhibiting CCNE1 through competitively binding to miR-193a-5p, which suggests that LINC01234 may represent a novel target for EC therapy.

Long-term Outcomes of Laparoscopy-assisted Gastrectomy for T4a Advanced Gastric Cancer: A Single-center Retrospective Study.

BACKGROUND: Laparoscopy-assisted gastrectomy (LAG) has been proven to be feasible and oncologically safe for early gastric cancer. Despite the rapid increase in the number of LAG cases, there are few reports on the long-term outcomes of T4a (serosalinvasion) gastric cancer after LAG. The aim of the present study was to evaluate the long-term clinical outcomes in patients with stage T4a gastric cancer after laparoscopic gastrectomy. MATERIALS AND METHODS: A total of 578 patients with gastric cancer were treated with LAG between February 2004 and December 2014. Among these patients, 224 patients were pathologically confirmed with T4a advanced gastric cancer. The clinical and follow-up data were retrospectively analyzed, the survival rates were estimated using the Kaplan-Meier method, and the risk factors for overall and disease-free survival (DFS) were evaluated by Cox regression. RESULTS: Among these 224 patients, 129 patients were above 60 years old, and the male-to-female ratio was 157:67. Furthermore, among these patients, 125 patients received laparoscopy-assisted distal gastrectomy, whereas 99 patients received laparoscopy-assisted total gastrectomy. Forty (17.90%) patients experienced postoperative complications according to the Clavien-Dindo classification. Median follow-up time was 32 months. Recurrence was observed in 99 (44.20%) patients. The cumulative 5-year overall survival (OS) and DFS rates were 47.20% and 43.60%, respectively. The 5-year OS and DFS rates were 72.50% and 70.00% for stage N0, 57.00% and 53.90% for stage N1, 41.60% and 37.00% for stage N2, and 23.30% and 21.30% for stage N3, respectively. In the univariate analysis, tumor size, tumor location, N stage and metastatic lymph node ratio (MLR) were correlated with OS and DFS. The MLR was identified as an independent predictor for OS (P<0.05; hazard ratio=1.828; 95% confidence interval, 1.353-2.469) and DFS (P<0.05; hazard ratio=1.197; 95% confidence interval, 0.945-1.516). CONCLUSIONS: The long-term outcomes of LAG for T4a (M0) gastric cancer were acceptable, compared with previous reports. Therefore, this treatment could be considered as an alternative operative approach for T4a gastric cancer. The MLR was an independent predictor for OS and DFS.

Simultaneous laparoscopy-assisted low anterior resection and distal gastrectomy for synchronous carcinoma of rectum and stomach.

Laparoscopic resection of rectal cancer or gastric cancer has been advocated for the benefits of a reduced morbidity, a shorter treatment time, and similar outcomes. However, simultaneous laparoscopy-assisted low anterior resection and distal gastrectomy for synchronous carcinoma of rectum and stomach are rarely documented in literature. Endoscopic examination revealed a synchronous carcinoma of rectum and stomach in a 55-year-old male patient with rectal bleeding and epigastric discomfort. He underwent a simultaneous laparoscopy-assisted low anterior resection and distal gastrectomy with regional lymph nodes dissected. The operation time was 270 min and the estimated blood loss was 120 mL. The patient required parenteral analgesia for less than 24 h. Flatus was passed on postoperative day 3, and a solid diet was resumed on postoperative day 7. He was discharged on postoperative day 13. With the advances in laparoscopic technology and experience, simultaneous resection is an attractive alternative to a synchronous gastrointestinal cancer.

Molecular characterization of a stress-induced NAC gene, GhSNAC3, from Gossypium hirsutum.

NAC genes, specific to plants, play important roles in plant development as well as in response to biotic and abiotic stresses. Here, a novel gene encoding a NAC domain, named as GhSNAC3, was isolated from upland cotton (Gossypium hirsutum L.). Sequence analyses showed that GhSNAC3 encodes a protein of 346 amino acids with an estimated molecular mass of 38.4 kDa and pI of 8.87. Transient localization assays in onion epidermal cells confirmed GhSNAC3 is a nuclear protein. Transactivation studies using a yeast system revealed that GhSNAC3 functions as a transcription activator. Quantitative real-time polymerase chain reaction analysis indicated that GhSNAC3 was induced by high salinity, drought and abscisic acid treatments. We overexpressed GhSNAC3 in tobacco by using Agrobacterium-mediated transformation. Transgenic lines produced longer primary roots and more fresh weight under salt and drought stresses as compared to wild-type plants. Collectively, our results indicated that overexpression of GhSNAC3 in tobacco can enhance drought and salt tolerances.

[Experience of laparoscopic salvage surgery for locally recurrent rectal cancer].

OBJECTIVE: To investigate the feasibility of the laparoscopic salvage surgery for locally recurrent rectal cancer. METHODS: Seven cases with recurrent rectal carcinoma treated by laparoscopic salvage surgery from February 2004 to July 2005 were retrospectively analyzed. Among them, four were males and 3 females, and the median age was 60 years (range 37-74). Three cases of recurrence were after conventional anterior resection, 2 after laparoscopic-assist anterior resection, 1 after laparoscopic-assist Parks' procedure, and 1 with pars sacral fistula after per-sacral-local resection for three times. Image examination (CT scanning) was taken preoperatively to evaluate the locally recurrence and exclude the distant metastases. The laparoscopic-assist procedure with or without a hand-assist technique was used in this study. RESULTS: Six cases with the recurrent lesion of central type were treated by salvage surgical procedure as follows: 3 laparoscopic-assist anterior resection, 1 laparoscopic-assist abdominoperineal resection, 1 laparoscopic-assist posterior exenteration, and 1 laparoscopic-assist proctocolectomy with a terminal ileum stoma. All of them were R0 resection confirmed by postoperative pathological examination. The other one with the lesion of combination type was treated with the procedure of laparoscopic-assist sigmoid colostomy. A hand-assist technique was used in 2 cases. The mean operation time, bleeding and hospital day was (211 +/- 13) min, (200 +/- 91) ml, and (15 +/- 10) d, respectively. No conversion and complication occurred. CONCLUSION: Laparoscopic salvage surgery for locally recurrent rectal cancer is safe and feasible when taken by experienced laparoscopic colorectal surgeon to the cases with the recurrent lesion of central type.

[Expression and single nucleotide polymorphisms of kallikrein 10 in colorectal cancer].

OBJECTIVE: To demonstrate expression and single nucleotide polymorphisms (SNP) of human kallikrein 10 (KLK 10) in colorectal cancer (CRC) and to correlate the KLK 10 expression level with clinicopathological factors of CRC. METHODS: KLK 10 expression in 63 cases of tumoral and nontumoral colorectal tissues at the mRNA and protein levels were evaluated by quantitative real-time RT-PCR (qRT) and Western blot methods. KLK 10 protein was localized by immunohistochemistry. The KLK 10 genomic DNA from 16 cases of paired normal and cancerous colorectal tissues was PCR-amplified and examined for SNP by direct sequencing. RESULTS: The KLK 10 mRNA expression was detected by qRT in 61 of 63 (97%) CRC specimens. The KLK 10 expression was much higher in tumor tissue than in the corresponding normal mucosal tissue at the mRNA and protein levels. The KLK 10 mRNA expression level significantly correlated with the lymphatic invasion (P < 0.05) and clinical stage of CRC (P < 0.05). No mutations or polymorphisms were detected in exon 1, 2 and 5 of KLK 10 gene in CRC. A SNP in codon 50 of exon 3, GCC (alanine) to TCC (serine) was identified. The genetic changes of exon 4 were located at codon 106 [GGC (glycine) to GGA (glycine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and codon 149 [CCG (proline) to CTG (leucine)]. All these SNP were identical in tumor as well as the corresponding normal tissue DNA from the same individuals. CONCLUSIONS: The KLK 10 expression is up-regulated in CRC and higher expression of KLK 10 closely correlate with advanced disease stage, which predicts a poorer prognosis, however, further follow-up study is needed.

Effects and possible anti-tumor immunity of electrochemotherapy with bleomycin on human colon cancer xenografts in nude mice.

AIM: To evaluate the anti-tumor effects and possible involvement of anti-tumor immunity of electrochemotherapy (ECT) employing electroporation and bleomycin in human colon cancer xenografts in nude mice, and to establish the experimental basis for clinical application of ECT. METHODS: Forty nude mice, inoculated subcutaneously human colon cancer cell line LoVo for 3 wk, were allocated randomly into four groups: B+E+ (ECT), B+E- (administration of bleomycin alone), B-E+ (administration of electric pulses alone), and B-E- (no treatment). Tumor volumes were measured daily. The animals were killed on the 7th d, the weights of xenografts were measured, and histologies of tumors were evaluated. Cytotoxicity of spleen natural killer (NK) and lymphokine-activated killer (LAK) cells was then assessed by lactic dehydrogenase release assay. RESULTS: The mean tumor volume of group B+E+ was statistically different from the other three groups after the treatment (F = 36.80, P<0.01). There was one case of complete response, seven cases of partial response (PR) in group B+E+, one case of PR in group B+E- and group B-E+ respectively, and no response was observed in group B-E-. The difference of response between group B+E+ and the other three groups was statistically significant (chi2 = 25.67, P<0.01). Histologically, extensive necrosis of tumor cells with considerable vascular damage and inflammatory cells infiltration were observed in group B+E+. There was no statistical difference between the cytotoxicity of NK and LAK cells in the four treatment groups. CONCLUSION: ECT significantly enhances the chemosensitivity and effects of chemotherapy in human colon cancer xenografts in nude mice, and could be a kind of novel treatment modality for human colon cancer. The generation of T-cell-dependent, tumor-specific immunity might be involved in the process of ECT.

[Application of urinary nucleosides in the diagnosis and surgical monitoring of colorectal cancer].

OBJECTIVE: To evaluate the value of urinary normal and modified nucleosides in diagnosis and surgical monitoring of colorectal cancer (CRC). METHODS: Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were included in this study. Spontaneous urine samples were collected 1 d before and 8 d after surgery and 14 kinds of urinary nucleosides in the samples were determined by reversed-phase high-performance liquid chromatography (RP-HPLC) method. Another 62 healthy volunteers were also enrolled as controls. The routine clinical tumor markers, including serum CEA, CA199, CA125 and AFP levels of CRC patients were evaluated by electrochemical-luminescence immunoassay simultaneously. RESULTS: The mean levels of pseudouridine (Pseu), adenosine (A), cytidine (C), 1-methyladenosine (m1A), 1-methylinosine (m1I), 3-methyluridine + 5-methyluridine (mU), 2,2-methylguanosine (m22G), inosine (I), 1-methylguanosine (m1G), N4-acetylcytidine (ac4C), N6-methyladenosine (m6A) among 14 kinds of determined urinary nucleosides in CRC group were much higher than those of controls (P < 0.05). Based on principal component analysis, 76.9% of CRC patients were correctly identified, which was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%) (P < 0.01). ROC curve analysis of m1G, and Pseu showed good sensitivity-specificity profiles to CRC. Two classification equations, Y(normal) = -3.009 + 0.0272 x Pseu + 4.918 x m1G and Y(CRC) = -8.057 + 0.0667 x Pseu + 8.258 x m1G, were established by Bayes stepwise discriminate analysis for predicting carcinogenesis of CRC. The elevated levels of Pseu, C, U (uridine), m1A, m1I, m1G, ac4C, A, m22G dramatically decreased after curative resection of 40 cases of CRC. And our data also showed that the preoperative levels of Pseu, m1G, m1A and m22G were positively related with tumor size and the preoperative levels of m1A, m22G and ac4C were positively related with Duke's staging of CRC (P < 0.05). CONCLUSIONS: Normal and modified urinary nucleosides may become additional tumor markers which are feasible in the clinical setting and will prove helpful in the diagnosis, management and follow-up of CRC, and Pseu and m1G may be more promising for clinical application.

Endoscopic management for the assessment and treatment of anastomotic bleeding in laparoscopic anterior resection for rectal cancer.

OBJECTIVE: To evaluate the impact of routine intraoperative endoscopy (IOE) on postoperative anastomotic bleeding of laparoscopic anterior resection (LAR) for rectal cancer, and to investigate the value of the IOE in terms of prevention and treatment of postoperative anastomotic bleeding. METHODS: Medical records of the 279 cases of LAR from January 2006 to December 2011 were retrospectively analyzed, of which postoperative anastomotic bleeding occurred in 18. Univariate analysis was taken to determine the possible influencing factors of the bleeding. Then related influencing factors were put into the multivariate logistic regression analysis to ultimately determine the independent influencing factors of anastomotic bleeding. The efficacy of treatments to the anastomotic bleeding was also evaluated. RESULTS: The incidence of anastomotic bleeding after LAR is 6.5% (18/279).The rates of anastomotic bleeding in lower tumor location group and upper tumor location group were 9.2% (16/173) and 1.9% (2/106), respectively, as in intraoperative colonoscopy and nonintraoperative colonoscopy group were 3.3% (5/151), and 10.2% (13/128), respectively. Comparing the location of the tumor, the coefficient of regression and relative risk value for lower tumor were 1.564 and 4.776. Comparing the intraoperative colonoscopy and nonintraoperative colonoscopy group, the value for intraoperative colonoscopy group were -1.085 and 0.338. Sex, age, tumor stage, pathologic type, and preventive ileostomy had no relevance with the anastomotic bleeding. In 18 cases of the anastomotic bleeding, 7 received conservative treatments, 9 underwent endoscopic treatment, and 2 underwent reoperation. All the 18 cases had reached hemostasis. CONCLUSION: IOE is an independent protective factor of anastomotic bleeding after LAR. Endoscopic hemostasis is recommended for an anastomotic bleeding after LAR for rectal cancer with a stapling technique.