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Introduction: Scissor-type knives are spreading as safe devises in endoscopic submucosal dissection (ESD). We evaluated the efficacy of two kinds of scissor-type knives (Clutch Cutter: CC, Fujifilm Co. and SB Knife Jr2: SB, SB-KAWASUMI Laboratories. Inc.) in colorectal ESD., Methods: This single-center retrospective study analyzed 178 ESD cases treated with CC from January 2020 to August 2021 and 91 cases with SB from September 2021 to December 2023. The two groups were compared through propensity score matching. Therapeutic results, such as ESD procedure time, en bloc resection rate, perioperative bleeding frequency, and complications, were analyzed in each group. Risk factors for long ESD procedure time (≥ 90 min) were also examined., Results: After matching, 87 cases in each group were analyzed. There was no significant difference in the ESD procedure time (min, median [interquartile range]) between the CC and SB groups (54.0 [36.0-72.0] vs. 53.0 [39.0-72.0], p = 0.99). Additionally, there were no differences in the en bloc resection (100% vs. 100%, p = 1.00), perioperative perforation (1.1% vs. 1.1%, p = 1.00), or delayed bleeding (1.1% vs. 0.0%, p = 1.00). There was a significant difference in perioperative bleeding frequency (mean ± standard deviation: 1.8 ± 2.6 vs. 3.0 ± 3.5, p < 0.01). The significant risk factors (odds ratio [95% confidence interval]) for long ESD procedure time in patients treated with CC or SB were antiplatelet (7.51 [1.82-31.00]), large lesion size (1.08 [1.05-1.12]), severe fibrosis (24.30 [7.60-77.90]), and perioperative bleeding frequency (1.34 [1.14-1.56])., Conclusions: CC and SB in colorectal ESD enabled high en bloc resection and low complication rates. CC showed significantly less perioperative bleeding than SB., Competing Interests: Declarations Conflict of interest Naohisa Yoshida and Osamu Dohi received the grants for research from Fujifilm. Other authors did not have any conflict of interest. No funding was received for this study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: There are many reports that preoperative oral antibiotics (OAs) are effective in preventing surgical site infections (SSIs) in colorectal surgery. However, there is no consensus on the optimal dose of OAs. In this study, we investigated the efficacy of OAs in preventing SSIs and the possibility that OAs induce enterobacterial alteration in the intestinal tract., Method: We performed a retrospective cross-sectional analysis of 389 patients who underwent R0 resection and stoma creation for colorectal cancer in our department between 2009 and 2020. We focused on the incidence of peristomal candidiasis (PSC) as an indicator of enterobacterial alteration and used kanamycin (KM) and metronidazole (MNZ) as the OAs. A low-dose group received 1000 mg/day of both KM and MNZ, and a high-dose group received 2000 mg/day of both KM and MNZ., Results: SSI occurred in 60 of the 389 cases (15.4%). Regardless of stoma type, SSI was significantly more common in the non-OA group, while PSC was significantly less common. When examined by OA dose, the incidence of SSI was not significantly different between the low-dose and high-dose groups. However, PSC was significantly more common in the high-dose group than in the non-OA and low-dose groups. Analysis of bacterial and fungal levels in stool samples showed that bacterial levels after OAs were significantly lower than before OAs, while fungal levels increased., Conclusion: OAs significantly reduce SSI in colorectal cancer surgery. However, excess OAs were significantly associated with the occurrence of PSC without contributing to further reduction in SSI., (© 2023 Association of Coloproctology of Great Britain and Ireland.)

Early recurrence in patients with colorectal cancer (CRC) is associated with a poor prognosis. We aimed to identify circulating microRNAs that are biomarkers of early CRC recurrence and elucidate their functions. We identified miR-4442 as a candidate biomarker by microRNA array analysis comparing preoperative and postoperative plasma levels in patients with CRC, with and without recurrence. The association between preoperative plasma miR-4442 levels, clinicopathological features, and recurrence-free survival was analyzed in 108 patients with CRC after curative surgery. Furthermore, cell-function analyses were performed, and the involvement of miR-4442 in regulating epithelial-mesenchymal transition (EMT) was examined. Preoperatively plasma miR-4442 levels were associated with CRC recurrence and exhibited an incremental increase with earlier recurrence dates. Moreover, miR-4442 demonstrated high sensitivity and specificity as a potential biomarker for early CRC recurrence. The expression of miR-4442 in cancer tissues of patients with metastatic liver cancer from CRC was higher than in normal liver, CRC, and normal colorectal tissues. The overexpression of miR-4442 promoted the proliferative, migratory, and invasive activities of CRC cells, decreased levels of RBMS1 and E-cadherin, and increased levels of N-cadherin and Snail1. Plasma miR-4442 is a clinically useful biomarker for predicting the early recurrence of CRC. Furthermore, miR-4442 regulates EMT in CRC by directly targeting the messenger RNA of RBMS1 .

Background: Postoperative hepatobiliary enzyme abnormalities often present as postoperative liver dysfunction in patients with colorectal cancer. This study aimed to clarify the risk factors of postoperative liver dysfunction and its prognostic impact following colorectal cancer surgery., Methods: We retrospectively analyzed data from 360 consecutive patients who underwent radical resection for Stage I-IV colorectal cancer between 2015 and 2019. A subset of 249 patients with Stage III colorectal cancer were examined to assess the prognostic impact of liver dysfunction., Results: Forty-eight (13.3%) colorectal cancer patients (Stages I-IV) developed postoperative liver dysfunction (Common Terminology Criteria for Adverse Events version 5.0 CTCAE v5.0 ≥ Grade 2). Univariate and multivariate analyses identified the liver-to-spleen ratio on preoperative plain computed tomography (L/S ratio; P = 0.002, Odds ratio 2.66) as an independent risk factor for liver dysfunction. Patients with postoperative liver dysfunction showed significantly poorer disease-free survival than patients without liver dysfunction (P < 0.001). Univariate and multivariate analyses using Cox's proportional hazards model revealed that postoperative liver dysfunction independently was a poor prognostic factor (P = 0.001, Hazard ratio 2.75, 95% CI: 1.54-4.73)., Conclusions: Postoperative liver dysfunction was associated with poor long-term outcomes in patients with Stage III colorectal cancer. A low liver-to-spleen ratio on preoperative plain computed tomography images was an independent risk factor of postoperative liver dysfunction., (© 2023. The Author(s).)

Background: The coronavirus disease 2019 (COVID-19) pandemic has rapidly and dramatically influenced healthcare across Japan. However, the influence of the COVID-19 pandemic on the number of newly diagnosed cancer, surgical treatment, and diagnostic examination for cancer types have not been completely investigated all over Japan. This study aimed to analyze the number of cases before and during the COVID-19 pandemic., Methods: This retrospective study was a survey that asked to provide the number of cases diagnosed with gastric, colorectal, lung, breast, and cervical cancer between January 2019 and December 2020. The survey was sent to tertiary healthcare hospitals, including national cancer institutions, university hospitals, and general hospitals, all over Japan. Data obtained from 105 of 486 surveyed hospitals were evaluated, and the number of cases in each quarter in 2020 was compared with that in the equivalent quarter in 2019., Results: In the second quarter (Q2), significant reductions were observed in the median number of newly diagnosed cases from 2019 to 2020: gastric cancer, 26.7% (43 vs. 32, p <  0.001); colorectal cancer, 17.9% (52 vs. 40, p <  0.001); lung cancer, 12.3% (53.5 vs. 47, p <  0.001); and breast cancer, 13.1% (43 vs. 35.5, p <  0.001). A significant reduction of 11.4% (9 vs. 8, p = 0.03) was observed in the third quarter (Q3) for cervical cancer. In Q2, the number of cases decreased by 30.9% (25 vs. 15, p <  0.001) for stage I gastric cancer, by 27.3% (12 vs. 9, p <  0.001) for stage I colorectal cancer, and by 17.6% (13 vs. 10, p <  0.001) for stage II breast cancer. The magnitude of reduction was significant for the localized stages of gastric, colorectal, and breast cancer according to diagnostic examinations in Q2 and surgical and endoscopic treatment in Q3 rather than that for lung or cervical cancer., Conclusions: COVID-19 has prolonged collateral effects on cancer care, including examination, diagnosis, and surgery, with significant effects on gastric cancer, followed by colorectal, lung, breast, and cervical cancer in Japan., (© 2022. The Author(s).)

Various heterogeneous nuclear ribonucleoproteins (hnRNPs) have been reported to be associated with cancer cell growth. However, it remains unclear whether hnRNP G-T, which is specifically expressed in the testis, is expressed in tumor cells, and whether hnRNP G-T expressed in colorectal cancer (CRC) cells is associated with tumor progression. We herein report that hnRNP G-T promoted cancer cell growth and stabilized mRNA of ZDHHC11 in CRC. The cell growth was inhibited by transfection of siRNA of hnRNP G-T in cancer cells, but not in non-cancerous epithelial cells. The tumor promotive effect of hnRNP G-T was confirmed in an HCT116 transplanted mouse model. RT-PCR and western blotting indicated the augmentation of hnRNP G-T in CRC in comparison to non-cancerous cells. The downregulation of hnRNP G-T inhibited cancer cell growth and promoted apoptosis in CRC. A transcriptome analysis combined with immunoprecipitation revealed that hnRNP G-T stabilized 174 mRNAs, including ZDHHC11 mRNA. The cell growth was also suppressed by the transfection of siRNA of ZDHHC11 and the mRNA and the protein expression were decreased by the transfection of siRNA of hnRNP G-T. These results suggested that hnRNP G-T promotes the cell growth of CRC by regulating the mRNA of ZDHHC11. Therefore, hnRNP G-T will be highlighted as an effective therapeutic target with less adverse effects in CRC therapy., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: The clinical significance ofmiR-4257 in patients with colorectal cancer (CRC) remains unclear. Here, we investigated the usefulness of measuring miR-4257 levels in the plasma and cancer tissues of patients with CRC, and the function of miR-4257 in CRC cell lines., Materials and Methods: miR-4257 levels were measured in the plasma and cancer tissues of patients with CRC using quantitative polymerase chain reaction. The relationships between miR-4257 level and clinicopathological features were examined. Proliferation, transwell, wound healing, and adhesion assays were performed using a miR-4257 mimic and inflammatory cytokines., Results: Relapse-free survival was significantly lower in patients with high miR-4257 levels in the plasma and cancer tissue (p<0.001 andp=0.016, respectively). High miR-4257 expression was an independent predictive factor for recurrence (p=0.017 and p=0.028). Addition of inflammatory cytokines to CRC and normal cell lines increased the expression of miR-4257 in the cell lines and cell culture medium. Over-expression of miR-4257 in CRC cells increased malignancy, while over-expression in normal cells increased adhesion to CRC cells. The addition of inflammatory cytokines to normal cell lines enhanced adhesion to CRC cell lines., Conclusion: miR-4257 level in plasma and cancer tissues is a biomarker of disease recurrence in patients with CRC. Moreover, miR-4257 promoted tumour growth and was associated with cancer-induced inflammation., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The significance of the duration of the recurrence-free survival after curative resection for colorectal cancer remains unclear. The purpose was to reveal the association between time to recurrence after surgery and the survival after recurrence., Methods: Patients with stage II and III colorectal cancer who underwent curative resection between 2007 and 2015 were retrospectively reviewed (n = 645). Patients with recurrence after surgery (n = 133) were divided into 2 groups: early recurrence (within 13 months after surgery, n = 63) and late recurrence (more than 13 months after surgery, n = 70). The overall survival after recurrence and clinicopathological features were compared between early recurrence, late recurrence, and without recurrence groups., Results: The overall survival after recurrence was significantly shorter in patients with early recurrence occurring at less than 13 months (hazard ratio: 1.70, p = 0.03). A high preoperative CA19-9 level (odds ratio [OR]: 2.38, p = 0.03), venous invasion (OR: 2.26, p = 0.03), and the absence of adjuvant chemotherapy (OR: 2.08, p = 0.04) were independently correlated with early recurrence., Conclusion: Early recurrence was associated with a poor prognosis after recurrence. Venous invasion correlated with early recurrence. Adjuvant chemotherapy may reduce the risk of early recurrence. These results indicate the importance of prudent surveillance and the aggressive application of adjuvant chemotherapy., (© 2021. Springer Nature Singapore Pte Ltd.)

Background: Oligometastasis, the presence of a small number of resectable metastatic tumors, usually has favorable outcomes. Here we examined whether the novel oligometastatic score (OLGS), which divides the number of colorectal liver metastases (CRLMs) by the time from colorectal resection to liver recurrence, better predicts CRLM patient survival than the commonly used clinical risk score., Methods: A total of 143 patients who underwent curative hepatectomy for CRLMs between 2007 and 2018 were analyzed. We investigated their clinical characteristics and outcomes using OLGS., Results: Of the 143 CRLM patients, 70 had synchronous CRLMs and 73 had metachronous CRLMs. Patients with metachronous CRLMs were divided into OLGS-low (n = 59) and OLGS-high (n = 14) subgroups. The 5-year overall survival (OS) rates after hepatectomy differed significantly between the subgroups (p < .001). In the multivariate Cox model, a high OLGS was an independent predictor of 5-year OS (p < .001), and the hazard ratio (HR) of the OLGS-high group (HR = 7.171) was higher than that of the high clinical risk score group (HR = 4.337)., Conclusion: The OLGS, a simple and handy scoring system, better predicts the 5-year OS of patients with CRLMs after hepatectomy and warrants prospective validation., (© 2021 Wiley Periodicals LLC.)

Background: Colonoscopy is the gold standard for detecting earlier stages of CRC, although screening of patients is difficult because of invasiveness, low compliance and procedural health risks. Therefore, the need for new screening methods for CRC is rising. Previous studies have demonstrated the diagnostic ability of serum BAs; however, the results have been inconsistent. In this study, we conducted a comprehensive analysis of serum BAs from patients with CRC and verified their diagnostic ability to detect CRC., Methods: A total of 56 CRC patients ( n  = 14 each of stages I-IV), 59 patients with colonic adenoma and 60 healthy controls were included. Age and sex were matched for each group. Serum BA compositions were measured by LC-MS/MS and serum concentration of 30 types of BAs were analysed by discriminant analysis with multidimensional scaling method., Results: Free CA, 3epi-DCA&CDCA, 3-dehydro CA, GCA and TCA were extracted as principal component (PC) 1 and free 3-dehydroDCA as PC 2 by canonical discriminant function coefficients. The verification of discriminability using cross-validation method revealed that the correct classification rate was 66.3% for original data and 52.6% for cross-validation data., Conclusions: A combined analysis using comprehensive serum BA concentration can be an efficient method for screening CRC.

Background/aim: The self-expanding metallic stent (SEMS) has recently been used for obstructive colorectal cancer (OCRC), and reports of its use are increasing. However, the long-term results of OCRC after using SEMS remain unclear. This study investigated the characteristics of SEMS compared to trans-anal tube (TAT) and clarified the long-term results and efficacy of SEMS for OCRC., Patients and Methods: We analyzed 48 patients who required SEMS or TAT for emergent decompression of OCRC and underwent resection for OCRC between 2007 and 2019. The perioperative factors and long-term results in the two groups were evaluated., Results: Patients with OCRC were divided into the SEMS (n=23) and the TAT group (n=25). No significant differences were seen in background factors, complications and the 5-year overall survival after surgery (p=0.3500) between the two groups. The clinical success of decompression (p=0.0072), oral intake (p<0.0001) and change in serum albumin (p<0.0001) from decompression to surgery were significantly better in the SEMS compares to the TAT group., Conclusion: The long-term outcomes in the SEMS group were not significantly different than in the TAT group, and nutritional status was better in patients with SEMS, suggesting that SEMS is very effective and may be the first-line treatment of OCRC., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to investigate the impact of the inferior mesenteric artery (IMA) lymph node metastasis [IMALN (+)] on prognosis in left-sided colorectal cancer (LCRC)., Patients and Methods: A total of 285 patients with stage III LCRC and 118 patients with stage IV LCRC who underwent resection of primary tumor between 2005 and 2016 were included., Results: IMALN (+) patients (n=10) had worse overall survival (OS) than patients without IMA lymph node metastasis [IMALN (-); n=275] in stage III LCRC (p=0.007). Multivariate analysis revealed that IMALN (+) was a prognostic factor in stage III LCRC (OS, HR=3.09, p=0.043). Conversely, there was no difference between the OS of IMALN (+) and stage IV LCRC with distant lymph node metastasis only [stage IV LCRC (LYM); n=21; p=0.434]., Conclusion: The prognosis of IMALN (+) was worse than that of IMALN (-); it was similar to that of stage IV LCRC (LYM)., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Clinical significance of plasma urothelial carcinoma associated 1 (UCA1) in patients with colorectal cancer (CRC) remains unclear. This study investigated the usefulness of plasma UCA1 as a biomarker in patients with CRC., Materials and Methods: UCA1 levels were measured in the plasma and tissue from patients with CRC by quantitative polymerase chain reaction. Relationships between plasma UCA1 and clinicopathological features were examined., Results: Plasma UCA1 levels were significantly lower in patients with CRC than in healthy volunteers. UCA1 expression in B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutant CRC tissue was also lower than that in non-cancerous tissue, although it was higher in CRC with wild-type BRAF. In right-sided CRC, a lower plasma UCA1 level was associated with pT4 and BRAF mutation. In contrast, in left-sided CRC, higher plasma UCA1 was associated with pT4 and pStage 3b-4., Conclusion: Plasma UCA1 is a useful biomarker for CRC detection and predicting clinicopathological features, particularly BRAF mutation.

RNA regulation mediating RNA-binding proteins (RBPs) have been shown to be related to the maintenance of homeostasis as well as cancer progression. However, the tumor-associated functions as well as the detailed mechanisms underlying the anti-tumor effects of most RBPs have yet to be explored. We herein report that the phosphorylated heterogeneous ribonucleoprotein (hnRNP) A0 promotes mitosis through the RAS-associated protein 3 GTPase-activating protein catalytic subunit 1 (RAB3GAP1)-Zeste white 10 interactor (ZWINT1) cascade. The downregulation assay of 20 representative hnRNPs, a major family of RNA-binding proteins, in colorectal cancer cells revealed that hnRNPA0 is a strong regulator of cancer cell growth. The tumor promotive function of hnRNPA0 was confirmed in gastrointestinal cancer cells, including pancreatic, esophageal, and gastric cancer cells, but not in non-cancerous cells. Flow cytometry and Western blotting analyses revealed that hnRNPA0 inhibited the apoptosis through the maintenance of G2/M phase promotion in colorectal cancer cells. A comprehensive analysis of mRNAs regulated by hnRNP A0 and immunostaining revealed that mitotic events were regulated by the hnRNPA0-RAB3GAP1 mRNA-mediated ZWINT-1 stabilization in colorectal cancer cells, but not in non-tumorous cells. The interaction of hnRNP A0 with mRNAs was dramatically changed by the deactivation of its phosphorylation site in cancer cells, but not in non-tumorous cells. Therefore, the tumor-specific biological functions characterized by the abnormal phosphorylation of RBPs are considered to be an attractive target for tumor treatment.

Background: Systemic inflammatory response is strongly linked to among cancer development, progression and poor prognosis. The aim of this study was to clarify the impact of postoperative serum C-reactive protein (CRP) levels on the prognoses of patients with colorectal cancer (CRC)., Methods: A total of 467 patients with stage I-III CRC who underwent curative surgery were retrospectively analyzed. To precisely evaluate the effect of postoperative inflammatory status on prognosis in CRC patients, we excluded patients with postoperative complication or elevated preoperative CRP level (CRP > 1.0 mg/dL). Patients were divided into two groups based on their highest post-resection CRP levels (max CRP): the low CRP group (LCG; < 9.0 mg/dL, n = 385) and high CRP group (HCG; ≥ 9.0 mg/dL, n = 82). Furthermore, the effect of inflammation on malignant potential of CRC cells was evaluated using in vitro peritoneal dissemination model., Results: HCG patients showed significantly worse recurrence-free survival (RFS) than LCG patients (p = 0.012). Multivariate analysis revealed that a higher max CRP was an independent prognostic factor for RFS (HR: 2.07, 95% CI 1.04-3.96, p = 0.038). Concerning the risk factors for high max CRP level, multivariate analysis revealed that older age (p < 0.001), male sex (p < 0.001), higher BMI (p = 0.005), right-sided colorectal cancer (p = 0.008), and longer operative time (p = 0.007) were independent risk factors. A higher max CRP was also significantly associated with peritoneal recurrence (p < 0.001). Additionally, recombinant cytokines enhanced the adhesive ability of CRC cells to mesothelial cell in vitro (p < 0.05)., Conclusions: Postoperative inflammation may be a possible mechanism portending the poor prognosis of CRC patients.

Background: Colorectal cancer (CRC) is one of the most predominant types of cancer, and it is the fourth most common cause of cancer-related death and it is important to diagnose CRC in early stage to decrease the mortality by CRC. In our previous study, we identified a combination of five peptides as a biomarker candidate to diagnose CRC by BLOTCHIP ® -MS analysis using a set of healthy control subjects and CRC patients (stage II-IV). The aim of the present study was to validate the serum biomarker peptides reported in our previous study using a second cohort and to establish their potential usefulness in CRC diagnosis., Methods: A total of 56 patients with CRC (n = 14 each of stages I-IV), 60 healthy controls, and 60 patients with colonic adenoma were included in this study. The five peptides were extracted and analyzed by selected reaction monitoring using ProtoKey ® Colorectal Cancer Risk Test Kit (Protosera, Inc., Amagasaki, Japan)., Results: The results clearly showed that the four CRC groups, stages I-IV, could be sufficiently discriminated from the control group and colonic polyp group. This five-peptide set could identify CRC at each stage compared to the control population in this validation cohort, including those with early-stage disease. The AUC values for each stage of CRC compared to the control population were 0.779, 0.946, 0.852, and 0.973 for stages I, II, III, and IV, respectively., Conclusions: In this case-control validation study, we confirmed high diagnostic performance for CRC using five peptides that were identified in our previous study as serum biomarker candidates for the detection of CRC.

Natural killer (NK) cells exhibit strong cytotoxic activity against tumor cells without prior sensitization, and have the potential to exert antibody-dependent cellular cytotoxicity (ADCC). In this clinical trial, we examined the safety and efficacy of the use of NK cells, generated using a novel expansion system, in combination with IgG1 antibodies for the treatment of advanced gastric or colorectal cancers. Treatment consisted of trastuzumab- or cetuximab-based chemotherapy, plus adoptive NK cell therapy. For administration of expanded NK cells, dose escalation with a sequential 3 + 3 design was performed in three steps, at doses of 0.5 × 10 9 , 1.0 × 10 9 , and 2.0 × 10 9 cells/injection (N = 9). After 3 days of IgG1 antibody administration, patients were infused with expanded NK cells three times at triweekly intervals. NK cell populations expanded with our system were confirmed as being enriched in NK cells (median 92.9%) with high expression of NKG2D (97.6%) and CD16 (69.6%). The combination therapy was very well tolerated with no severe adverse events. Among six evaluable patients, four presented stable disease (SD) and two presented progressive disease. Of the four SD patients, three showed an overall decrease in tumor size after combination therapy. Immune monitoring suggested that combination therapy enhanced whole blood IFN-γ production and reduced peripheral regulatory T cells (Tregs). In conclusion, this phase I trial provides evidence of good tolerability, induction of Th1 immune responses, and preliminary anti-tumor activity for this combination therapy, in patients with advanced gastric and colorectal cancer that have received previous therapy., (© 2018 UICC.)

Purpose: Linked color imaging (LCI) by laser endoscopy is a novel narrow band light observation. In this study, we analyzed the efficacy of LCI for improving the various featured colorectal polyp's visibility utilizing a subjective endoscopist's visibility scoring and objective color difference (CD) value., Methods: We retrospectively reviewed two pictures both with white light (WL) and LCI for 54 consecutive neoplastic polyps 2-20 mm in size. All pictures were evaluated by four endoscopists according to a published polyp visibility score from four (excellent visibility) to one (poor visibility). Additionally, we calculated CD value between each polyp and surrounding mucosa in LCI and WL using an original software., Results: The mean polyp visibility scores of LCI (3.11 ± 1.05) were significantly higher than those of WL (2.50 ± 1.09, P < 0.001). The ratio of an endoscopist's poor visibility (polyp visibility scores 1 and 2) was significantly lower in LCI (27.9%) than WL (55.6%, P < 0.001). With respect to the CD analysis, the CD value of LCI was significantly higher than that of WL (33.3 ± 13.9 vs. 20.7 ± 13.6, P < 0.001). In a subgroup analysis, the polyp visibility scores and CD values of LCI about 24 diminutive polyps (≤5 mm) were higher than those of WL (3.29 ± 0.99 vs. 2.12 ± 0.99, P < 0.001; 31.6 ± 12.8 vs. 14.7 ± 7.6, P < 0.001). Additionally, the polyp visibility scores and CD values of LCI for polyps with any location, size, histology, and morphology were significantly higher than those of WL., Conclusions: LCI improved the various featured polyp's visibility compared to WL in both polyp visibility scores and CD value.

Background: Although colorectal cancer (CRC) is one of the most common causes of cancer mortality, early-stage detection improves survival rates dramatically. Because cancer impacts important metabolic pathways, the alteration of metabolite levels as a potential biomarker of early-stage cancer has been the focus of many studies. Here, we used CE-TOFMS, a novel and promising method with small injection volume and high resolution, to separate and detect ionic compounds based on the different migration rates of charged metabolites in order to detect metabolic biomarkers in patients with CRC., Methods: A total of 56 patients with CRC (n = 14 each of Stages I-IV), 60 healthy controls, and 59 patients with colonic adenoma were included in this study. Metabolome analysis was conducted by CE-TOFMS on serum samples of patients and controls using the Advanced Scan package (Human Metabolome Technologies)., Results: We obtained 334 metabolites in the serum, of which 139 were identified as known substances. Among these 139 known metabolites, 16 were correlated with CRC stage by upregulation and 44 by downregulation, with benzoic acid (r = -0.649, t = 11.653, p = 6.07599E-24), octanoic acid (r = 0.557, t = 9.183, p = 7.9557E-17), decanoic acid (r = 0.539, t = 8.749, p = 1.24352E-15), and histidine (r = -0.513, t = 8.194, p = 3.90224E-14) exhibiting significant correlation., Conclusions: To the best of our knowledge, this is the first report to determine the correlation between serum metabolites and CRC stage using CE-TOFMS. Our results show that benzoic acid exhibited excellent diagnostic power and could potentially serve as a novel disease biomarker for CRC diagnosis.

Background: The benefits of narrow band imaging (NBI) in colorectal polyp detection remain questionable. Previous NBI has poorer brightness and resolution than white light (WL). However, recently these factors were improved by the new-generation video processor system (EVIS LUCERA ELITE) in comparison with the previous system (EVIS LUCERA SPECTRUM). The aim of this study was to investigate whether NBI with EVIS LUCERA ELITE could improve the visibility of colorectal polyps compared to WL., Methods: We analyzed prospectively 240 colorectal polyps (group 1: ELITE with CF-HQ290 scope, 80 polyps; group 2: ELITE with PCF-Q260AZI scope, 80 polyps; group 3: SPECTRUM with PCF-Q260AZI scope, 80 polyps) whose videos were recorded using NBI and WL at Kyoto Prefectural University of Medicine. The videos were evaluated in a randomized order by three experts and three non-experts. Each polyp was assigned a polyp visibility score from 4 (excellent visibility) to 1 (poor visibility). The polyp visibility scores in each mode and their relationship to the clinical characteristics were analyzed., Results: The mean polyp visibility scores of NBI with ELITE system were significantly higher than those of WL (ELITE with CF-HQ290: 3.14 ± 0.87 vs. 2.75 ± 0.98, p < 0.0001, ELITE with PCF-Q260AZI: 3.03 ± 0.92 vs. 2.83 ± 0.93, p = 0.0006). Conversely, the mean polyp visibility score of NBI using SPECTRUM system with PCF-Q260AZI was significantly lower than WL (2.75 ± 1.06 vs. 3.05 ± 0.92, p < 0.0001)., Conclusions: Our study showed that NBI using EVIS LUCERA ELITE improved polyp visibility.

Background/aim: Tumor biomarkers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9), are used to screen and monitor tumor recurrence in patients with colorectal cancer (CRC). 5-Aminolevulinic acid (5-ALA) is used in photodynamic diagnosis and therapy. Porphyrins produced by tumor cells are excreted in the urine after 5-ALA administration. In this study, we evaluated the use of porphyrins as novel tumor markers in urine samples from patients with CRC., Patients and Methods: Porphyrin metabolite concentrations were measured in urine samples of 33 patients with CRC, 16 patients with benign disease and 8 healthy adults, after 5-ALA administration., Results: The porphyrin metabolite concentrations were significantly increased in the CRC group compared to the control group, while in CRC patients, the porphyrin metabolite concentrations in urine were significantly decreased after surgery., Conclusion: These results suggest that the measurement of porphyrin metabolites in urine may potentially serve as a new screening and recurrence marker for CRC., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Aim: Tolerability, adverse events, and long-term outcomes were compared and analyzed between patients receiving oral anticancer agent-based adjuvant chemotherapy regimen (PO group) and those receiving combination adjuvant chemotherapy with oxaliplatin (OX group), after curative resection of colorectal cancer at our Department., Patients and Methods: The subjects included in the study were 169 patients with stage III colorectal cancer who underwent curative resection and received postoperative adjuvant chemotherapy between June 2007 and October 2014. Fifty-three patients were included in the OX group, while 116 patients were included in PO group., Results: No significant difference was observed in treatment completion rates. No significant difference in either the overall or relapse-free survival rates was observed between the two groups., Conclusion: Oxaliplatin has been shown to improve therapeutic outcomes after curative resection of colorectal cancer. Even compared to oral anticancer agents, oxaliplatin appears to be equal in tolerability and treatment completion rate., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

While the progress of chemotherapy and molecular targeted therapy has improved the outcome of colorectal cancer patients, the mortality of colon cancer remains high, indicating the need to develop novel therapeutic targets for improving the outcome of colon cancer. Heterogeneous ribonucleoprotein A1 (hnRNP A1) is highly expressed in colorectal cancer and its expression correlates with malignant transformation. In this study, we performed a microarray analysis with the RNA immunoprecipitation (RNA-IP) method and identified hnRNP A1-interacting miRs, including miR-26a and -584, in a colorectal cancer cell line, SW620. A SRB assay revealed the tumor suppressive effect of miR-26a and -584, and the tumor suppressive effect of these miRs was diminished by the downregulation of hnRNP A1. The combined method of a transcriptome analysis and RNA-IP revealed hnRNP A1-interacting mRNAs, including cyclin dependent kinase 6 (CDK6). A Western blot analysis revealed the downregulation of CDK6 in miR-26a and -584 overexpression cells, as well as hnRNP A1 knockdown cells. The binding assay indicated that the binding of hnRNP A1-CDK6 mRNA was reduced by transfection of miR-26a and -584. The expression of cleaved caspase-3 was induced in miR-26a and -584 overexpression cells. These data indicate that miR-26a and -584 inhibit the binding of hnRNP A1-CDK6 mRNA and induce colorectal cancer cell apoptosis., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Although the efficacy of adjuvant chemotherapy with oxaliplatin for colorectal cancer patients has been established, the tolerability of this regimen is rarely reported in Japan. The aim of this study was to clarify the tolerability of adjuvant oxaliplatin-based regimen for Japanese patients with colorectal cancer., Methods: This study included 158 advanced colorectal cancer patients who consecutively underwent a surgical procedure at our hospital and received adjuvant chemotherapy. Completion rate and adverse events were monitored in this study., Results: Among the 158 patients, 44 received oxaliplatin-based chemotherapy and the remaining received chemotherapy without oxaliplatin. The use of oxaliplatin was significantly correlated with more cases of adverse events such as myelosuppression (p<0.001) and peripheral neurotoxicity (p=0.005), which lead to dose reduction (p<0.001) or drug withdrawal (p<0.001). However, the completion rate did not significantly differ between the 2 groups. The median relative dose intensity (RDI) was 85.7%, which means that the oxaliplatin-based regimen is feasible. As for recurrence-free survival, no significant differences were observed between the 2 groups., Conclusion: This study demonstrates that adjuvant chemotherapy with oxaliplatin is tolerable by colorectal cancer patients in Japan.

Background: Fujifilm developed blue laser imaging (BLI) via a laser light source with a narrow-band light observation function. It has a brighter BLI bright mode for tumor detection., Objective: To investigate whether the BLI bright mode can improve the visibility of colorectal polyps compared with white light (WL)., Design: We studied 100 colorectal polyps (protruding, 42; flat, 58; size, 2-20 mm) and recorded videos of the polyps by using the BLI bright mode and WL at Kyoto Prefectural University of Medicine and Fukuoka Chikushi University Hospital. The videos were evaluated by 4 expert endoscopists and 4 nonexperts. Each endoscopist evaluated the videos in a randomized order. Each polyp was assigned a visibility score from 4 (excellent visibility) to 1 (poor visibility)., Setting: Japanese academic units., Main Outcome Measurements: The visibility scores in each mode and their relationship to the clinical characteristics were analyzed., Results: The mean visibility scores of the BLI bright mode were significantly higher than those of WL for both experts and nonexperts (experts, 3.10 ± 0.95 vs 2.90 ± 1.09; P = .00013; nonexperts, 3.04 ± 0.94 vs 2.78 ± 1.03; P < .0001). For all nonexperts, the visibility scores of the BLI bright mode were significantly higher than those of WL; however, these scores were significantly higher in only 2 experts. For experts, the mean visibility scores of the BLI bright mode was significantly higher than those of WL for flat polyps, neoplastic polyps, and polyps located on the left side of the colon and the rectum., Limitations: Small sample size and review of videos., Conclusions: Our study showed that polyps were more easily visible with the BLI bright mode compared with WL. (, Clinical Trial Registration Number: UMIN000013770.)., (Copyright © 2015 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aim: Generally, colorectal endoscopic submucosal dissection (ESD) cannot be carried out with severe lens cloudiness. We examined the occurrence of lens cloudiness during ESD as well as the efficacy of a novel cleaner for it., Methods: This study was a prospective study compared to historical control. First, we analyzed 103 ESD cases using standard cleaner at the Kyoto Prefectural University of Medicine in 2012. Relationship between lens cloudiness and clinical characteristics of lesions was analyzed. Lens cloudiness was recorded as grade 0 (clear) to grade 2 (very unclear). Then, we recruited 92 consecutive patients who underwent colorectal ESD using the novel cleaner from August 2013 to July 2014. The cleaner was applied on top of the lens before procedure and ability to prevent lens cloudiness was tested. Additionally, the novel cleaner was injected from endoscopic channel into a space created by endoscopic hood and colonic wall in seven cases with grade 1 or 2 of lens cloudiness and the ability to clean lens cloudiness inside the colon was tested., Results: Rate of severe lens cloudiness was 8.7%. Multivariate analysis showed that severe lens cloudiness was related with severe submucosal fatty tissue (P < 0.001). The novel cleaner had significantly less cloudiness cases compared to the standard cleaner (14.1% vs 33.0%, P = 0.002). Additionally, the novel cleaner enabled us to clean lens cloudiness in all seven cases., Conclusion: Lens cloudiness during ESD was associated with submucosal fatty tissue. Effective lens cleaner should be used to prevent and clean lens cloudiness., (© 2015 The Authors. Digestive Endoscopy © 2015 Japan Gastroenterological Endoscopy Society.)

Purpose: We examined the clinical data of patients treated with oxaliplatin to determine the risk factors of oxaliplatin-related hypersensitivity reaction (HSR). In addition, we evaluated the efficacy of rechallenging patients with HSRs with oxaliplatin using prophylactic agents or desensitization procedures., Methods: This study consisted of 162 patients with colorectal cancer (88 men and 74 women) who were treated consecutively at the outpatient chemotherapy department at University Hospital, Kyoto Prefectural University of Medicine. Patients underwent chemotherapy, including oxaliplatin, between March 2006 and June 2012. We analyzed the patients' clinical backgrounds (eg, age, sex, performance status, disease stage, and allergic history) to uncover any connections to the development of HSR to oxaliplatin. In addition, we rechallenged 10 patients who had oxaliplatin-related HSR using prophylactic agents or desensitization procedures., Findings: Of 162 patients, 28 (17.2%) developed oxaliplatin-related HSRs (16, 2, 9 and 1 patient had grade 1, 2, 3, and 4 HSRs, respectively). The total cumulative dose of oxaliplatin at the onset of the HSR was 301 to 1126 mg/m(2) (median, 582 mg/m(2)), and the first reactions developed in these patients after 5 to 17 infusions of oxaliplatin (median, 8 infusions). Logistic regression analysis indicated that sex (male: odds ratio = 3.624; 95% CI, 1.181-11.122; P = 0.024) and eosinophil count in peripheral blood (odds ratio = 35.118; 95% CI, 1.058-1166.007; P = 0.046) were independent variables for oxaliplatin-related HSRs. Rechallenging patients with prophylactic agents was successful in 2 (28.6%) of 7 patients who successfully completed their treatment. On the other hand, all 3 patients rechallenged with oxaliplatin using a desensitization protocol successfully completed their treatment without new HSRs., Implications: In this retrospective study, we observed that being male and having higher counts of peripheral eosinophil could be predictors for HSR to oxaliplatin. In addition, this study confirms that oxaliplatin desensitization protocol allows patients who developed HSRs to continue with their treatment. However, the optimum desensitization protocol for oxaliplatin administration in terms of tolerability and efficacy needs to be defined., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)

Background: Peritoneal lavage with distilled water has been performed during colorectal cancer surgery. This study investigated the cytocidal effects of hypotonic shock in vitro and in vivo in colorectal cancer cells., Methods: Three human colorectal cancer cell lines, DLD1, HT29, and CACO2, were exposed to distilled water, and morphological changes were observed under a differential interference contrast microscope connected to a high-speed digital video camera. Cell volume changes were assessed using a high-resolution flow cytometer. Re-incubation experiments were performed to investigate the cytocidal effects of distilled water. In the in vivo experiment, cancer cells after hypotonic shock were injected intraperitoneally into mice and the degree of established peritoneal metastasis was subsequently evaluated. The effects of the blockade of Cl(-) channels on these cells during hypotonic shock were also analyzed., Results: Morphological observations revealed a rapid cell swelling followed by cell rupture. Measurements of cell volume changes showed that mild hypotonic shock induced regulatory volume decrease (RVD) while severe hypotonic shock broke cells into fragments. Re-incubation experiments demonstrated the cytocidal effects of hypotonicity. In vivo experiments revealed the absence of peritoneal dissemination in mice in the distilled water group, and its presence in all mice in the control group. The blockade of Cl(-) channels increased cell volume by inhibiting RVD and enhanced cytocidal effects during mild hypotonic shock., Conclusions: These results clearly support the efficacy of peritoneal lavage with distilled water during colorectal cancer surgery and suggest that regulating of Cl(-) transport may enhance the cytocidal effects of hypotonic shock.

Background/aims: Although aggressive resection is recommended for the treatment of resectable liver metastasis of colorectal cancer, recurrences often develop in the remaining liver. In our department, perioperative chemotherapy was introduced for the treatment of colorectal cancer associated with resectable synchronous liver metastasis. The results of this treatment are reported herein. The study population was 20 patients (9 men, 11 women) with colorectal cancer associated with resectable synchronous liver metastasis whose data were collected between April 2009 and September 2012., Methodology: The patients received chemotherapy (mFOLFOX6 or XELOX + bevacizumab) for 3 months each before and after hepatectomy following resection of the primary lesion., Results: Preoperative chemotherapy yielded a response rate of 66.7%, and no serious postoperative complications were noted. Although recurrence was found in 9 patients after treatment, 4 have so far remained cancer-free after re-resection. Thus, re-resection of the recurrent lesion resulted in patients maintaining cancer-free status for a prolonged period., Conclusions: The use of perioperative chemotherapy in patients with colorectal cancer associated with resectable synchronous liver metastasis may improve outcomes after hepatectomy.

A precise diagnosis of peritoneal dissemination is necessary to determine the appropriate treatment strategy for colorectal cancer. However, small peritoneal dissemination is difficult to diagnose. 5-aminolevulinic acid (5-ALA) is an intermediate substrate of heme metabolism. The administration of 5-ALA to cancer patients results in tumor-specific accumulation of protoporphyrin IX (PpIX), which emits red fluorescence with blue light irradiation. We evaluated the usefulness of photodynamic diagnosis (PDD) using 5-ALA to detect the peritoneal dissemination of colorectal cancer. EGFP-tagged HT-29 cells were injected into the peritoneal cavity of BALB/c nude mice. After 2 weeks, the mice were given 5-ALA hydrochloride, and metastatic nodules in the omentum were observed with white light and fluorescence images. Twelve colorectal cancer patients suspected to have serosal invasion according to preoperative computed tomography (CT) were enrolled in this study. 5-ALA (15-20 mg per kg body weight) was administered orally to the patients 3 h before surgery. The abdominal cavity was observed under white light and fluorescence. Fluorescence images were analyzed with image analysis software (ImageJ 1.45s, National Institutes of Health, Bethesda, MD, USA). The mice developed peritoneal disseminations. The observed 5-ALA-induced red fluorescence was consistent with the EGFP fluorescent-positive nodules. Peritoneal dissemination was observed with conventional white light imaging in 8 patients. All nodules suspected as being peritoneal dissemination lesions by white light observation were similarly detected by ALA-induced fluorescence. In 1 patient, a small, flat lesion that was missed under white light observation was detected by ALA-induced fluorescence; the lesion was pathologically diagnosed as peritoneal metastasis. In the quantitative fluorescence image analysis, the red/(red + green + blue) ratio was higher in the metastatic nodules compared to the non-metastatic sites of the abdominal wall, fat and liver. We demonstrated better diagnostic accuracy using 5-ALA-PDD compared to conventional laparoscopy in patients with colorectal cancer. 5-ALA-PDD is a promising candidate method for diagnosing peritoneal dissemination of colorectal cancer.

Survivin is a component of the chromosomal passenger complex (CPC) that is essential for accurate chromosome segregation. Interfering with the function of Survivin in mitosis leads to chromosome segregation errors and defective cytokinesis. Survivin contains a Baculovirus IAP Repeat (BIR) and therefore was originally classified as inhibitor of apopotosis protein (IAP), yet its role in apoptosis after cellular stress remains largely unknown. We demonstrate here, that Survivin predominantly suppresses anoikis, a form of programmed cell death induced by loss of cellular adhesion to extracellular matrix. Interestingly, cells ectopically overexpressing EGFP-Survivin showed after loss of cell-matrix-interaction a decreased expression of IκB-α. Subsequent subcellular protein fractionation and immunoprecipitation experiments revealed that XIAP interacts with detergent-soluble Survivin which is known to cooperatively activate NF-κB signaling. Examination of the expression levels of detergent soluble Survivin in colorectal cancer cell lines and in colorectal cancerous tissues revealed that detergent soluble cytoplasmic Survivin levels correlated inversely with anoikis susceptibility in colorectal cancer. Therefore, the detergent soluble cytoplasmic Survivin might be a promising predictive biomarker for lymph node and distant metastases of colorectal cancer. We conclude that an anti-apoptotic function of detergent-soluble Survivin in interphase cells experiencing anoikis is mediated at least via XIAP/IκB-α/NF-κB signaling.

Purpose: Flexible spectral imaging color enhancement (FICE), or image-enhanced endoscopy, can enhance visualization of surface and vascular patterns of colorectal polyps. Resolution of FICE has recently been improved. We evaluated diagnostic accuracy for neoplastic and non-neoplastic colorectal polyp differentiation with detection of surface patterns by FICE without magnification., Methods: Retrospective analysis of 151 colorectal polyps evaluated by FICE without magnification was performed. Neoplastic surface patterns were defined as tubular and oval pit. We aimed to determine sensitivity, specificity, positive and negative predictive values (PPV and NPV), and accuracy in correlating diagnosis by FICE without magnification with histology. Moreover, findings were compared to those of white-light endoscopy (WL) and chromoendoscopy (CHR)., Results: Of the 151 colorectal polyps, 95 were identified as neoplastic and 56 were identified as non-neoplastic. FICE without magnification had a sensitivity of 89.4%, specificity of 89.2%, PPV of 93.4%, NPV of 83.3%, and accuracy of 89.4%. The accuracy of FICE value was higher than that of WL (sensitivity of 74.7%, specificity of 73.2%, PPV of 82.5%, NPV of 63.0%, and accuracy of 74.1%) and was worse than that of CHR (sensitivity of 96.8%, specificity of 89.2%, PPV of 93.9%, NPV of 96.1%, and accuracy of 94.7%). Imaging evaluation was validated by inter-/intra-observer measurements, demonstrating consistent results., Conclusions: The detection of surface patterns by FICE without magnification is useful for differential diagnosis of colorectal polyps. We believe that FICE without magnification is more convenient and easier method than CHR.

Background and Aim: Endoscopic mucosal resection (EMR) is the standard procedure for colorectal tumors. High mucosal elevation by submucosal injection is important for definite en bloc resection and the prevention of perforation. Hyaluronic acid (HA) is a reportedly useful injection solution for high and long-lasting mucosal elevation, but the ideal HA concentration for optimization of mucosal elevation maintenance, injection pressure, and cost is unknown. In the present study, we assessed the appropriate concentration of HA for EMR., Methods: A resected porcine colon and esophagus were used. The injection solutions examined were 0.9% normal saline (NS) and four concentrations of an 800-KDa HA preparation (0.4%, 0.2%, 0.13%, and 0.1%). Each solution (2 mL) was injected into the submucosa; injection pressure was calculated, and elevation was measured. The durations of mucosal elevation and EMR were additionally assessed in the living minipig colon., Results: In the resected porcine colon, the mucosal elevation was measured 0, 2, 4, and 6 min after the submucosal injection. All concentrations of HA solution maintained greater mucosal elevation at all times than NS (P < 0.05). An almost similar result was obtained in the resected porcine esophagus. The injection pressure correlated with the HA concentration. In the living minipig colon, mucosal elevation diminished 2 min after the submucosal injection with NS, but was maintained 2 min after injection with 0.4%, 0.2%, and 0.13% HA. The average duration of EMR was 139 s., Conclusions: Mucosal elevation by HA was greater than that by NS in resected and living animal models. We recommend 0.13% HA for maintaining mucosal elevation, injection pressure, and cost., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is an image-enhanced endoscopy that captures the surface and vascular patterns of colorectal tumors. We evaluated and compared FICE magnification to narrow-band imaging (NBI) magnification., Methods: Flexible spectral imaging color enhancement or NBI magnification was performed to the visualize surface and vascular patterns of colorectal tumors, classified into 4 types: Type A, Type B, Type C1/C2, and Type C3, as previously reported. A total of 235 colorectal tumors were examined. The correlations between classifications found by FICE or NBI magnification and histopathological diagnoses were examined. Image evaluation was validated by assessing inter-observer and intra-observer agreements on examinations., Results: Twenty-eight hyperplastic polyps (HPs), 115 tubular adenomas (TAs), 72 mucosal and slightly invaded submucosal cancers (M-sSM), and 20 massively invaded submucosal cancers (mSM) were diagnosed. By FICE magnification, HP and TA were observed in 93.3 and 6.7% of Type A (15 lesions), respectively. TA, M-sSM, and HP were observed in 82.6, 15.4, and 2.0% of Type B (52 lesions),respectively. M-sSM, TA, and mSM were observed in 50.0,46.0, and 4.0% of Type C1/2 (50 lesions), respectively.mSMs were observed in all 7 Type C3 lesions. In diagnosing mSM in Type C3, the sensitivity and specificity of FICE magnification were 77.7 and 100%, respectively, compared to those of NBI, at 63.6 and 99.0%, respectively. Imaging evaluation was validated accurately by intra- and intraobserver measurements showing consistent results., Conclusions: The classification of colorectal tumors by FICE magnification correlated well with the histopathological diagnoses, similar to findings for NBI magnification. FICE magnification can be evaluated accurately with the same diagnostic classifications as those used for NBI magnification.

Background: Endoscopic submucosal dissection (ESD) has been reported to be effective for the en bloc resection of large colorectal tumors. Our study investigated whether ESD was suitable for elderly people with large colorectal tumors in terms of its invasiveness., Patients and Methods: We studied 119 colorectal tumors that were treated with ESD at Kyoto Prefectural University of Medicine or Nara City Hospital between 2006 and 2009. We classified each patient as either elderly, i.e., more than 75 years old, or non-elderly, i.e., less than 75 years old. Thirty-two of the cases were classified as elderly. Performance status, tumor size, operation time, rate of en bloc resection, histopathological diagnosis, complications, and hospital stay after ESD were analyzed retrospectively in both groups., Results: In the elderly group, the average tumor size was 32.6 mm; the average operation time, 96 min; the rate of en bloc resection, 81.2%; the rate of perforation, 3.1%; and hospital stay after ESD, 5.1 days. Histopathological diagnosis for 16 tumors was adenoma; for 13, carcinoma with invasion into the mucosa; and for three, carcinoma with invasion into the submucosa. There were no statistical differences between the two groups in any of these data. The case with perforation was treated conservatively without urgent surgery in the elderly group., Conclusions: ESD for colorectal tumors resulted in favorable rates of en bloc resection in elderly people. Perforation occurred in elderly people, but these patients were cured with conservative treatment. ESD is a safe and minimally invasive treatment for elderly people with colorectal tumors.

Background and Aims: Although an increasing number of early colorectal cancers (CRC) have been curatively treated by endoscopy, there have been no definitive criteria to decide the effectiveness of such therapy. We retrospectively analyzed clinicopathological factors to establish criteria for curative endoscopic treatment of early CRC., Methods: First, risk factors of lymph node metastasis were analyzed in 171 patients who received surgery with postoperative histology of CRC submucosal invasion. The resultant new criteria were evaluated in another 60 patients who experienced endoscopic resection of CRC and surgery according to the current criteria most often used in Japan., Results: In the first substudy, lymph node metastasis was present in 18 of 171 patients (10.5%). Lymphatic permeation, sprouting and infiltrative growth of cancer cells were identified as histological factors significantly related to lymph node metastasis, and observed in much higher rates when the depth of submucosal invasion was beyond 1,500 micron. The minimum depth with positive lymph nodes was 1,075 micron. In the second group of 60 patients, lymph node metastasis was recorded in none of nine patients who met our new criteria of complete endoscopic treatment: submucosal invasion below 1,500 micron in depth, and no lymphatic permeation, sprouting or infiltrative growth pattern on tumor histology. Lymph node metastasis was positive in three of the other cases who did not meet our new criteria., Conclusions: The present study showed that endoscopic treatment of early CRC may be considered complete when submucosal invasion beyond 1,500 micron, lymphatic permeation, sprouting, and infiltrating growth are all denied.

Three patients with colorectal cancer and pulmonary metastasis who had previously undergone surgical treatment, were treated by combination chemotherapy with CDDP and 5-FU regimen, but the growth of the metastatic tumor could not be controlled finally. Thus, a new strategy of combination chemotherapy using 5'-DFUR and MMC were investigated in these cases, and resulted in suppressing the tumor growth successfully without admission. The procedure for treating pulmonary metastasis of colorectal cancer has not been established clearly. This new regimen may play an important role from the standpoint of not only its effectiveness against tumor growth but also the quality of life of patients.