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Competing Interests: Satoki Shichijo has received honoraria for lectures from Olympus, Boston Scientific Japan, EA Pharma, AstraZeneca, AI Medical Service, and Janssen Pharmaceutical. Yoji Takeuchi has received honoraria for lectures from Olympus, Boston Scientific Japan, Takeda Pharmaceutical, EA Pharma, Zeria Pharmaceutical, and Viatris. Noriya Uedo has received honoraria for lectures from Olympus, FUJIFILM, Boston Scientific Japan, Daiichi-Sankyo, Takeda Pharmaceutical, EA Pharma, Otsuka Pharmaceutical, AstraZeneca, Miyarisan Pharmaceutical, and AI Medical Service.

Introduction: Acute malignant large bowel obstruction (MBO) occurs in 8%-15% of colorectal cancer patients. Self-expandable metal stents (SEMS) have progressed from a palliative modality to use as bridge to surgery (BTS). We aimed to assess the safety and efficacy of SEMS for MBO in our institution., Methods: The data of patients undergoing SEMS insertion for MBO were reviewed. Technical success was defined as successful SEMS deployment across tumour without complications. Clinical success was defined as colonic decompression without requiring further surgical intervention. Rates of complications, median time to surgery, types of surgery and rates of recurrence were studied., Results: Seventy-nine patients underwent emergent SEMS placement from September 2013 to February 2020. Their mean age was 68.8 ± 13.8 years and 43 (54%) patients were male. Mean tumour length was 4.2 cm ± 2.2 cm; 89.9% of malignant strictures were located distal to the splenic flexure. Technical and clinical success was 94.9% and 98.7%, respectively. Perforation occurred in 5.1% of patients, with none having stent migration or bleeding. Fifty (63.3%) patients underwent SEMS insertion as BTS. Median time to surgery was 20 (range 6-57) days. Most (82%) patients underwent minimally invasive surgery. Primary anastomosis rate was 98%. Thirty-nine patients had follow-up beyond 1-year posttreatment (median 34 months). Local recurrence and distant metastasis were observed in 4 (10.3%) and 5 (12.8%) patients, respectively., Conclusion: Insertion of SEMS for acute MBO has high success rates and a good safety profile. Most patients in this audit underwent minimally invasive surgery and primary anastomosis after successful BTS.

Introduction: Computer-aided diagnosis (CADx) of polyp histology could support endoscopists in clinical decision-making. However, this has not been validated in a real-world setting., Methods: We performed a prospective, multicenter study comparing CADx and endoscopist predictions of polyp histology in real-time colonoscopy. Optical diagnosis based on visual inspection of polyps was made by experienced endoscopists. After this, the automated output from the CADx support tool was recorded. All imaged polyps were resected for histological assessment. Primary outcome was difference in diagnostic performance between CADx and endoscopist prediction of polyp histology. Subgroup analysis was performed for polyp size, bowel preparation, difficulty of location of the polyps, and endoscopist experience., Results: A total of 661 eligible polyps were resected in 320 patients aged ≥40 years between March 2021 and July 2022. CADx had an overall accuracy of 71.6% (95% confidence interval [CI] 68.0-75.0), compared with 75.2% (95% CI 71.7-78.4) for endoscopists ( P = 0.023). The sensitivity of CADx for neoplastic polyps was 61.8% (95% CI 56.9-66.5), compared with 70.3% (95% CI 65.7-74.7) for endoscopists ( P < 0.001). The interobserver agreement between CADx and endoscopist predictions of polyp histology was moderate (83.1% agreement, κ 0.661). When there was concordance between CADx and endoscopist predictions, the accuracy increased to 78.1%., Discussion: The overall diagnostic accuracy and sensitivity for neoplastic polyps was higher in experienced endoscopists compared with CADx predictions, with moderate interobserver agreement. Concordance in predictions increased this diagnostic accuracy. Further research is required to improve the performance of CADx and to establish its role in clinical practice., (Copyright © 2023 by The American College of Gastroenterology.)

Colonoscopy with endoscopic resection of detected colonic adenomas interrupts the adenoma-carcinoma sequence and reduces the incidence of colorectal cancer and cancer-related mortality. In the past decade, there have been significant developments in instruments and techniques for endoscopic polypectomy. Guidelines have been formulated by various professional bodies in Europe, Japan and the United States, but some of the recommendations differ between the various bodies. An expert professional workgroup under the auspices of the Academy of Medicine, Singapore, was set up to provide guidance on the endoscopic management of colonic polyps in Singapore. A total of 23 recommendations addressed the following issues: accurate description and diagnostic evaluation of detected polyps; techniques to reduce the risk of post-polypectomy bleeding and delayed perforation; the role of specific endoscopic resection techniques; the histopathological criteria for defining endoscopic cure; and the role of surveillance colonoscopy following curative resection., (Copyright: © Singapore Medical Association.)

Colonoscopy is the reference standard procedure for the prevention and diagnosis of colorectal cancer, which is a leading cause of cancer-related deaths in Singapore. Artificial intelligence systems are automated, objective and reproducible. Artificial intelligence-assisted colonoscopy has recently been introduced into clinical practice as a clinical decision support tool. This review article provides a summary of the current published data and discusses ongoing research and current clinical applications of artificial intelligence-assisted colonoscopy., (Copyright: © Singapore Medical Association.)

Introduction: Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD., Methods: We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed., Results: A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy., Conclusion: Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions., (Copyright: © Singapore Medical Association.)

Metadherin (MTDH) is a multifunctional oncogene involved in tumor cell migration and metastasis through regulating a number of oncogenic signaling pathways in various human malignancies. Previous studies have demonstrated that MTDH is overexpressed in human colorectal cancer (CRC) and associated with cancer progression and a poor prognosis. However, the underlying mechanisms remain largely unknown. The present study investigated the expression and role of MTDH in CRC cells as well as the underlying mechanism of this. Western blot analysis and quantitative polymerase chain reaction were conducted to determine protein and mRNA expression of MTDH in three human CRC cell lines. A short hairpin RNA (shRNA) targeting MTDH was introduced into CRC HCT116 cells to stably inhibit MTDH expression. A Cell Counting Kit‑8 assay, colony formation assay, Transwell assay and flow cytometry were used to investigate the effect of MTDH‑knockdown on cell proliferation, migration, apoptosis and cell cycle arrest. Western blotting was performed to examine the protein expression levels of cell growth‑ and apoptosis‑associated genes. The results demonstrated that MTDH was commonly expressed in CRC cell lines. MTDH silencing significantly suppressed cell growth, colony forming ability and migration while inducing the apoptosis of HCT116 cells. In addition, MTDH depletion induced S phase cell cycle arrest in HCT116 cells. Mechanistically, knockdown of MTDH markedly downregulated the expression of phosphorylated protein kinase B, c‑Myc, proliferating cell nuclear antigen and B‑cell lymphoma 2 (Bcl‑2) protein in HCT116 cells, and the expression of p53 and Bcl‑2‑associated X protein was significantly increased compared with the negative control shRNA group (P<0.05), suggesting that MTDH may function through the expression of numerous types of apoptosis‑associated and signaling channel proteins in CRC cells. Taken together, these data indicated that MTDH may serve as a biomarker and candidate therapeutic target for CRC.

Background & Aims: Rectal bleeding is associated with colorectal cancer. We characterized the evaluation of patients aged 40 years and older with rectal bleeding and identified characteristics associated with inadequate evaluation., Methods: We conducted a retrospective review of records of outpatient visits that contained reports of rectal bleeding for patients aged 40 years and older (N = 480). We studied whether patient characteristics affected whether or not they received a colonoscopy examination within 90 days of presentation with rectal bleeding. Patient characteristics included demographics; family history of colon cancer and polyps; and histories of screening colonoscopies, physical examinations, referrals to specialists at the index visit, and communication of laboratory results. Data were collected from medical records, and patient income levels were estimated based on Zip codes., Results: Nearly half of the patients presenting with rectal bleeding received colonoscopies (48.1%); 81.7% received the procedure within 90 days. A history of a colonoscopy examination was more likely to be reported in white patients compared with Hispanic or Asian patients (P = .012 and P = .006, respectively), and in high-income compared with low-income patients (P = .022). A family history was more likely to be documented among patients with private insurance than those with Medicaid or Medicare (P = .004). A rectal examination was performed more often for patients who were white or Asian, male, and with high or middle incomes, compared with those who were black, Hispanic, female, or with low incomes (P = .027). White patients were more likely to have their laboratory results communicated to them than black patients (P = .001)., Conclusions: Sex, race, ethnicity, patient income, and insurance status were associated with disparities in evaluation of rectal bleeding. There is a need to standardize the evaluation of patients with rectal bleeding., (Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to evaluate the learning curve of the laparoscopic approach for colorectal cancer and generate a focused training program for more junior surgeons., Subjects and Methods: This study analyzed data from 100 consecutive laparoscopic surgeries for colorectal cancer between January 2009 and July 2010. The learning curve was compared between the first 50 surgeries (study group 1) and the subsequent 50 surgeries (study group 2)., Results: Age, gender, mean body mass index, history of abdominal surgery, and tumor stage were not significantly different between the two study groups. Operative time decreased with increasing experience and reached a plateau after 23 patients. The operative time in study group 2 tended to be shorter than in study group 1 (P=.06). Other parameters including blood loss, average number of retrieved lymph nodes, conversion rate, and intraoperative complication rates were not different between the two study groups., Conclusions: More junior surgeons can be safely trained if they are exposed to a focused training program. Supervision by an experienced surgeon and considerable experiences in open colorectal surgery are assets for an accelerated learning curve.

Objective: To explore the relationship between gamma-synuclein gene expression and CpG island demethylation in colorectal cancer(CRC), and the relationship between the demethylation and clinicopathological factors of CRC., Methods: The expression of gamma-synuclein mRNA was examined in 30 pairs of tumor tissues and tumor-matched non-neoplastic adjacent tissues(NNAT) by RT-PCR. CRC cell lines including COLO205, LoVo, and SW480 were used and treated with a demethylating agent, 5-aza-2'-deoxycytidine(5-aza-C). Before and after the treatment, the expression of gamma-synuclein mRNA in the cells was determined by RT-PCR, and bisulfite sequencing PCR was also used to analyze methylation status of CpG island. The methylation status of gamma-synuclein was then examined in 67 CRC samples and 30 NNAT samples by nested methylation-specific PCR (NMSP) and real time methylation-specific PCR(real-time MSP). The relationship between the demethylation of gamma-synuclein in CRC and clinicopathological factors was analyzed., Results: The mean gamma-synuclein mRNA expression was 0.66+/-0.34 in CRC samples, which was much higher than 0.45+/-0.26 in NNAT samples(P=0.011). 5-aza-C could induce expression and demethylation of gamma-synuclein in COLO205, LoVo and SW480 cells. gamma-Synuclein gene was demethylated in 80.0%(24/30) of the CRC samples and 50.0%(15/30) of the NNAT samples. The demethylated status of gamma-synuclein was much higher in CRC samples than that in NNAT samples(P=0.030), and was significantly correlated with clinical stage, lymph node involvement, and distant metastasis of CRC(P<0.05)., Conclusion: The upregulation of gamma-synuclein expression in CRC is primarily attributed to the demethylation of CpG island, which may be used as a marker for prognosis.

Objectives: To investigate the impact of previous abdominal operations on the outcome of laparoscopic colorectal cancer surgery and to evaluate the feasibility and safety of laparoscopic reoperation in treatment for colorectal cancer., Methods: According to the statistical standards, 653 consecutive patients treated from March 2002 and March 2009 were enrolled in this study. The patients were divided into three groups: upper abdominal surgery group (n = 48), middle-lower abdominal surgery group (n = 110) and non-previous abdominal surgery group (n = 495). Demographic, pathoanatomical and surgical data were compared among the three groups., Results: There was no significant differences in demographic, pathoanatomical data and post-operative complications among the three groups. Compared with the other two groups, middle-lower abdominal surgery subgroup had a higher intra-operative conversion rate due to intra-abdominal adhesion (4.2%, 11.8% and 3.8% in upper abdominal surgery group, middle-lower abdominal surgery group and non-previous abdominal surgery group, respectively). And no significant differences was found in operating time [(132 ± 36), (141 ± 42), (132 ± 36) min], intra-operation blood loss [(58 ± 50), (81 ± 99), (57 ± 57) ml], blood transfusion rate (6.3%, 10.9%, 7.9%), low sphincter-preserving surgery rate (47.1%, 44.7%, 55.2%), time of first flatus passage [(2.5 ± 1.4), (2.9 +/- 1.7), (2.5 ± 2.1) d], fasting time [(5 ± 4), (5 ± 4), (4 ± 3) d], hospital stay [(17 ± 9), (15 ± 8), (16 ± 10) d] between the three groups., Conclusions: The history of previous abdominal operations should not be regarded as a contraindication for laparoscopic colorectal cancer reoperation. The laparoscopic reoperation for colorectal cancer is safe and feasible.

Objective: To compare the outcomes of laparoscopic colorectal surgery in elderly (> or = 70 years) and younger(< 70 years) patients, and to evaluate the safety of laparoscopic colorectal surgery in elderly., Methods: From Aug. 2007 to Dec. 2007, 25 patients with colorectal cancer undergone laparoscopic colorectal surgery were studied prospectively. Ten patients aged 70 years or older(Elder Group), and 15 patients less than 70 years(Younger Group). The parameters of perioperative hemodynamics, blood chemistry, and intraabdominal organs perfusion were recorded periodically during operation and compared between the two groups., Results: Elder group had a higher ASA degree(P<0.01). Mean age, height, weight, the classification of the disease, operative time, blood loss and complication were not significantly different between the two groups. The HCO(3) value and PaCO(2) value increased significantly intraoperatively, while the pH value decreased significantly. These parameters returned to basal line at the end of operation, with the decreased electrolytes, especially the kaliopenia and hypocalcemia. The CVP increased significantly at the beginning of operation and after fluid expansion, and decreased postoperatively. Gastric mucosal pH(pHi) decreased when the operation began. The partial pressure of gastric mucosa(PgCO(2)) increased significantly at the end of operation. Other parameters of hemodynamics including HR, CI, and SI were not significantly different during operation. The CVP of elder group was higher than that of younger group at 5 min after the beginning of the operation, while the MAP of elder group was lower than that of younger at 15 min after the end of the operation. Other parameters of hemodynamics including oxygenation, perfusion, and blood chemistry were not significantly different., Conclusions: For laparoscopic colorectal surgery, no significant adverse response attributes to elderly patients. The compensation capacity of the elderly is lower. With the reasonable anesthesia administration, the adverse response can be controlled effectively.

Ethnopharmacological Relevance: Ganoderma, known as Lingzhi or Reishi, has been traditionally administered throughout Asia for centuries as a cancer treatment and for other medicinal purposes., Aim of the Study: To investigate the inhibitory activity and explore the molecular mechanisms of anti-tumor effect on colorectal cancer cells in vitro and in vivo as well as to test the side effects of Ganoderma tsugae., Materials and Methods: Methanol fraction was obtained from dried fruiting bodies of Ganoderma. TLC and HPLC were performed to differentiate and confirm the identification of different species as well as to quantify the bioactive molecules in methanol extracts of Ganoderma species. MTT and Trypan blue exclusion assay as well as tumorigenesis study were used to assess the anti-tumor effect in vitro and in vivo. Using flow cytometry and Western Blots, we examined further the molecular mechanisms of anti-tumor effect. Finally, biochemical and hematological profiles and pathological examinations were used to evaluate the safety., Results: The Ganoderma tsugae extracts inhibit colorectal cancer cell proliferation caused by accumulating cells in G(2)/M phase, and it may be through downregulation of cyclin A and B1 and upregulation of p21 and p27. Tumorigenesis study in nude mice revealed the extracts caused tumor shrinkage. Additionally, safety assay showed Ganoderma tsugae extracts caused no significant side effects in an animal model., Conclusions: This study provides molecular evidence that Ganoderma tsugae extracts exert anti-tumor effects both in vitro and in vivo on colorectal adenocarcinoma cells by inducing G(2)/M cell cycle arrest. More importantly, no significant physiological changes resulting from treatment with Ganoderma tsugae extracts were observed in the animal model. Therefore, these data provide new insights into the possible therapeutic use of Ganoderma tsugae for treating colorectal cancer.

Recent evidence suggests that gamma-synuclein is abnormally expressed in a high percentage of tumor tissues of diversified cancer types, but rarely expressed in tumor-matched non-neoplastic adjacent tissues (NNAT). The molecular mechanism of CpG island demethylation may underlie aberrant gamma-synuclein expression. To fully understand the roles of aberrant gamma-synuclein expression and demethylation in the development of colorectal cancer (CRC), we examined the expression and methylation status of gamma-synuclein in 67 CRC samples, 30 NNAT samples, and five CRC cell lines as well. By using reverse transcription-polymerase chain reaction (RT-PCR), western blot, and immunohistochemistry analyses, gamma-synuclein expression was detected in both HT-29 and HCT116 cells, and was much higher in CRC samples than in NNAT samples (P < 0.05). The demethylating agent, 5-aza-2 cent-deoxycytidine, can induce re-expression of gamma-synuclein in COLO205, LoVo, and SW480 cells. Unmethylated gamma-synuclein alleles were detected in HT-29, HCT116, and LoVo cells by nested methylation-specific PCR, and the demethylated status of gamma-synuclein was much higher in CRC samples than in NNAT samples by real-time quantitative methylation-specific PCR (P < 0.05). The results of genomic bisulfite DNA sequencing further confirmed that the aberrant gamma-synuclein expression in CRC was primarily attributed to the demethylation of CpG island. The protein expression and demethylation status of gamma-synuclein in 67 CRC samples correlated with clinical stage, lymph node involvement, and distant metastasis. These findings suggest an involvement of aberrant gamma-synuclein expression and demethylation in progression of CRC, especially in advanced stages.

Objective: To study the expression of vascular endothelial growth factor (VEGF) and metastin in colorectal carcinoma and their association with the clinicopathological features of the malignancy., Methods: VEGF and metastin expressions were examined immunohistochemically with SP method in 70 specimens of human colorectal carcinoma tissues and adjacent normal tissues., Results: VEGF protein overexpression was detected in 48.6% (34/70)of the colorectal carcinoma tissues but in none of the adjacent normal tissues (P<0.01), and for metastin, the overexpression rate was 28.6% (20/70) in the colorectal carcinoma tissues and 70.0% (49/70) in the normal tissues (P<0.01). The expression of both VEGF and metastin was related to the histological grades, infiltration depth, TNM stage and lymph node metastasis of the tumor (P<0.01 and P<0.05, respectively)., Conclusion: Immunohistochemical detection of VEGF and metastin can be of value in assessment of the malignancy and in prognostic evaluation of colorectal carcinoma.

Background/aims: Vascular endothelial growth factor C (VEGF-C) and vascular endothelial growth factor D (VEGF-D) are potent lymphangiogenic and angiogenetic mediators in many kinds of tumors. However, the exact impacts of VEGF-C and VEGF-D on the prognosis of colorectal cancer (CRC) remain elusive. The aims of this study were to demonstrate the expression of VEGF-C and VEGF-D and to correlate their expression levels with clinicopathological factors and long-term survival in patients with CRC., Patients and Methods: Between January 1996 and January 1998, 69 patients with pathologically confirmed CRC who received routine follow-up at the Ruijin Hospital were included in this study. VEGF-C and VEGF-D protein expression and microvessel density of 69 surgical specimens were assessed by immunohistochemistry, with 20 samples of normal colorectal tissues as controls. All patients were followed up for 108 months or until death. The Immunohistochemical stains were quantified and analyzed by means of a Zeiss Axioplan 2 imaging analysis system., Results: The protein expression of VEGF-C and VEGF-D in tumor tissues was much higher than that in normal colorectal tissues (p < 0.01). The VEGF-C expression significantly correlated with lymph node metastasis (p = 0.011) and clinical stages of CRC (p < 0.01). The VEGF-D expression correlated with patient ages (p = 0.013), depth of tumor invasion (p = 0.013), and lymph node metastasis (p = 0.028). The expression of VEGF-C and VEGF-D was significantly correlated with the microvessel density. Both overall survival and disease-free survival at 108 months were significantly lower in the CRC patients with a high VEGF-C and/or a high VEGF-D expression, and the patients with a high expression of both VEGF-C and VEGF-D had the shortest overall survival and disease-free survival when compared with other patients., Conclusion: The VEGF-C or VEGF-D expression was significantly correlated with lymph node metastasis and long-term prognosis and could be applied as prognostic markers in CRC., (Copyright 2007 S. Karger AG, Basel.)

Background and Aim: Recent evidence suggests that the human kallikrein 10 (KLK10) gene is differentially regulated in endocrine-related tumors and has potential as diagnostic and/or prognostic marker; however, KLK10 expression has never been investigated in gastrointestinal cancers. The aims of this study were to demonstrate expression and single nucleotide polymorphisms of KLK10 in colorectal cancer (CRC) and gastric cancer (GC), and to correlate the relative KLK10 expression level with clinicopathological factors of CRC and GC., Methods: Between March 2004 and January 2005, 63 patients with histologically confirmed CRC and 36 with GC were recruited into the study. Using quantitative real-time (qRT) RT-PCR and Western blot, KLK10 expression in tumor and non-tumor colorectal and gastric tissues was determined at the mRNA and protein levels. KLK10 protein was localized by immunohistochemistry. The KLK10 genomic DNA from 16 cases of paired normal/cancerous colorectal tissues was PCR-amplified and examined for single nucleotide polymorphisms by direct sequencing., Results: KLK10 mRNA expression was detected by qRT in 61 of 63 (96.8%) CRC specimens and in all GC specimens. KLK10 expression was much higher in tumor tissue than in the corresponding normal mucosal tissue at the mRNA and protein levels (P<0.01). The KLK10 mRNA expression level significantly correlated with lymphatic invasion (P=0.034) and clinical stage of CRC (P=0.025). The KLK10 mRNA expression level significantly correlated with the depth of GC invasion (P=0.018), clinical stage (P=0.045), patient sex (P=0.027) and Lauren type of gastric cancer (P=0.028). No mutations or polymorphisms were detected in exon 1, 2 and 5 of KLK10 gene in CRC. Single nucleotide polymorphisms were identified in codon 50 of exon 3, GCC (alanine) to TCC (serine). The genetic changes of exon 4 were located at codon 106 [GGC (glysine) to GGA (glysine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and codon 149 [CCG (proline) to CTG (leucine)]. All were identical in tumor and corresponding normal tissue DNA from the same individuals., Conclusion: KLK10 expression is up-regulated in CRC and GC and higher expression of KLK10 closely correlates with advanced disease stage, which predicts a poorer prognosis; however, further follow-up study is needed.

Objective: To compare the systemic and local inflammatory response after laparoscopic and conventional surgery for colorectal carcinoma., Methods: From April 2004 to August 2004, 51 colorectal cancer patients undergoing laparoscopic (n=25) and conventional open (n=26) colorectal resection were enrolled in the study. The general clinical data,and inflammatory response were compared between the two groups., Results: There were no significant differences in age, sex, pre-operative levels of haemoglobin and albumin, Dukes stage and surgical procedure between the two groups (P > 0.05). Laparoscopic surgery had more advantages over conventional open surgery such as incision, operating time, recovery time of bowel function, and hospitalization. On postoperative day (POD) 1, WBC count [(7.30+/- 2.62)x10(9)/L], and the serum levels of IL-10 [(19.46+/- 3.31)pg/ml] and C-reactive protein (CRP) [(2.76+/- 2.17)mg/dl] were significantly lower in laparoscopic group than those in conventional group (P< 0.05), but there were no differences on POD 4 between the two groups (P > 0.05). There were no significant differences in the volume of peritoneal drainage fluid, and levels of IL-10, TNF and CRP in it on POD 1 between the two groups, but the volume of peritoneal drainage fluid decreased significantly from POD 2, and the level of IL-10 in it was significantly lower on POD 4 in laparoscopic group than that in conventional group., Conclusions: In early stage after operation,intra- peritoneal inflammatory response caused by laparoscopic surgery is similar to that by conventional open surgery, but systemic inflammatory response is slighter than that by conventional open surgery for colorectal carcinoma.

Background and Aims: Elderly patients have a high incidence of colorectal cancer, which may be associated with increased morbidity and mortality due to complex comorbidity and diminished cardiopulmonary reserves. The aims of this study were to compare the outcomes of laparoscopic colorectal cancer surgery with those observed in traditional open surgery in patients aged over 70 years., Methods: Between January 2003 and October 2004, 51 patients aged over 70 years with colorectal cancer, who underwent laparoscopic surgery (LAP group), were evaluated and compared with 102 controls (also over 70 years old) treated by traditional open surgery (OPEN group) in the same period. All patients were evaluated with respect to the American Society of Anesthesiologists (ASA) classification, surgery-related complications, and postoperative recovery., Results: No surgery-related death was observed in the LAP group, whereas two deaths occurred in the OPEN group for severe post-operative pulmonary infection and anastomotic leak, respectively. No pneumoperitoneum-related complications were observed in the LAP group; 2 (3.9%) patients required conversion to open surgery, because of the unexpectedly bulky tumor and severe adhesions in the abdominal cavity. With the increase in patients' age, increased ASA classification was observed. No significant differences were observed in gender, Dukes' staging or types of procedures between LAP and OPEN groups. The overall morbidity in the LAP group was significantly less than that of the OPEN group [17.6% (9/51) vs 37.3% (38/102), p=0.013]. Mean blood loss, time to flatus passage, and time to semi-liquid diet in the LAP group were significantly shorter than those of the OPEN group (90.7+/-49.9 vs 150.3+/-108.7 ml, 2.4+/-1.2 vs 3.5+/-2.9 d, 5.0+/-1.8 vs 5.9+/-1.2 d, respectively, p<0.05). No significant differences were observed in terms of mean operation time or hospital stay between LAP and OPEN groups., Conclusion: Laparoscopic colorectal cancer surgery in elderly patients with colon cancer has clinically significant advantages over traditional open surgery, and appears to be the ideal surgical choice for the elderly.

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.

Background: Up to now, there is still no ideal tumor marker in early diagnosis and effective monitoring, especially for surgical resection of colorectal cancer (CRC). The aim of the present study was to evaluate the application of urinary normal and modified nucleosides in diagnosis and surgery monitoring of CRC., Methods: Between October 2002 and July 2003, 52 consecutive patients with pathological confirmed CRC were enrolled. Spontaneous urine samples were collected 1 day before surgery and on day 8 postoperatively, and 14 urinary nucleosides were determined by reverse-phase high-performance liquid chromatography (RP-HPLC). Another 62 healthy people were also studied as control. The clinical routine tumor markers, serum carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, and alpha-fetoprotein (AFP) of CRC patients, were correspondingly evaluated by electrochemiluminescent immunoassay., Results: The levels of 11 out of 14 of the determined urinary nucleosides in the CRC group were much higher than those of normal controls. Through the principal component analysis of these 14 nucleosides, 76.9% of CRC patients were correctly classified. The sensitivity of this analysis was much higher than that of CEA (38.5%), CA199 (40.4%), CA125 (15.4%), and AFP (17.3%; P < 0.01). Receiver operating characteristic (ROC) curve analysis of 1-methylguanosine (m1G) and pseudouridine (Pseu) showed good sensitivity-specificity profiles of the diagnosis of CRC. The elevated levels of the nine nucleosides significantly decreased after curative resection of 40 CRC cases. The data also showed that the preoperative levels of some nucleosides were positively related with tumor size and Dukes staging of CRC., Conclusion: The evaluation of normal and modified urinary nucleosides might become novel tumor markers, which will be facilitated in the clinical setting and helpful in the diagnosis, management and follow up of CRC. Pseu and m1G may be more promising for clinical use and be worthy of further studies in the near future.

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.

While HER2/neu receptor tyrosine kinase is involved in various malignancies, studies on colorectal adenocarcinoma (CRC) remain controversial. To try to clarify the role played by HER2/neu in CRC, sixty-seven CRC patients in Taiwan were analyzed. For this analysis, we used normalized dual-color fluorescence in situ hybridization (FISH) and Photoshop-aided immunohistochemistry (IHC) between cancers and their autologous non-neoplastic epithelia. The results revealed that HER2/neu status was unrelated to age, sex, location and positive-nodal percentage. Intramucosal carcinomas had earlier HER2/neu protein upregulation than regional stromal invasion within Dukes' A, and had a gene level that had not risen yet. Both gene gains and protein increases were significant in later stages in regards to volumetric progression and nodal-metastatic Dukes' stage. Overall, there were 1.53-fold (gene) and 1.81-fold (protein) increases from non-neoplastic enterocytes to CRCs. The upregulating directions of gene (88%) and protein (88%) presented symmetric agreement. Most CRCs exhibited low to intermediate levels of HER2/neu overexpression with double-minute gene amplicons and cytosolic HER2/neu proteins. Normalized FISH and IHC showed high cubic-regression correlation, especially in Dukes' C. According to the correlation curve, the points with IHC index >2.41 and FISH ratio >1.22 defined the area where gene-amplification-dependent HER2/neu overexpression was present. Eleven (16%) patients had values above the cut-off point (IHC = 2.41 and FISH = 1.22), including 7 (10%) cases in cytosolic and 4 (6%) cases in membranous HER2/neu overexpressions. The results suggest that HER2/neu plays a crucial role in CRC tumorigenicity with gene-amplification-independent transcriptional activations early in the carcinogenesis, and gene-amplification-dependent overexpression later in the advanced stages. This indicates that HER2/neu can be a good biological marker for selecting patients that may improve under therapies that employ adequate HER2/neu-targeting strategies.