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Background/aim: Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme in tryptophan metabolism and plays an important role in immunosuppression. The effects of IDO1 on tumor invasion and metastasis have been studied in several types of malignancies. However, the role of IDO1 in these steps in colorectal cancer (CRC) has not been elucidated. Therefore, we aimed to investigate the effects of IDO1 on invasion, migration, and epithelial-mesenchymal transition (EMT) in CRC cells., Materials and Methods: All experiments were performed using the DLD-1 colon cancer cell line that expresses IDO1. We conducted a scratch wound healing assay and Boyden chamber assay to investigate the impact of IDO1 on DLD-1 cell migration and invasion, respectively, in the presence and absence of the IDO1 inhibitor L-1-methyl-tryptophan (L-1-MT). Additionally, western blotting was performed to analyze alterations in the expression of EMT-related markers caused by L-1-MT., Results: High expression of IDO1 was confirmed in the cytoplasm of DLD-1 by immunofluorescence staining. In the scratch wound healing assay, the invasion ability of DLD-1 cells decreased to 62% after treatment with L-1-MT at 1,000 μM for 24 h. In the Boyden chamber assay, the migration of DLD-1 cells was suppressed by 85% after treatment with L-1-MT at 2,500 μM for 24 h. L-1-MT treatment increased the expression level of E-cadherin and decreased the expression levels of vimentin, Snail, and Slug., Conclusion: IDO1 inhibition reduced the invasion and migration ability of IDO1-expressing DLD-1 colon cancer cells, which was accompanied by altered expression of EMT-related proteins. IDO1 could be a potential target for the treatment of advanced CRC., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The usefulness of robotic surgery compared to laparoscopic surgery for rectal cancer has been reported; however, few reports exist on robotic abdominoperineal resection (APR). The aim of this study was to compare the outcomes of robotic and laparoscopic surgery to determine their usefulness in patients with locally advanced rectal cancer who had undergone preoperative chemoradiotherapy (CRT)., Patients and Methods: This retrospective study included 43 patients with locally advanced rectal cancer who underwent preoperative CRT and robotic (22 patients) or laparoscopic APR (21 patients) between December 2012 and September 2022. We examined the short- and long-term outcomes in the robotic and laparoscopic groups., Results: The median follow-up durations were 36 and 48 months for the robotic and laparoscopic groups, respectively. No significant differences in operative time, intraoperative blood loss, or overall complication rates were observed. However, the incidence of organ/space surgical site infection (SSI) was significantly lower in the robotic surgery group than in the laparoscopic group (9.1% vs. 38.1%, p=0.034) and the 3-year overall survival rate was significantly higher in the robotic surgery group than in the laparoscopic group (95% vs. 67%, p=0.029)., Conclusion: Robotic APR was associated with a significantly lower rate of organ/space SSIs than the laparoscopic approach, indicating the usefulness of the robotic approach., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: In colorectal cancer cases, treatment strategies differ between those with regional and extra-regional lymph node metastases. The inferior mesenteric lymph nodes are categorized as regional lymph nodes, while the para-aortic lymph nodes are classified as extra-regional lymph nodes. Although inferior mesenteric and para-aortic lymph node metastases are both associated with a dismal prognosis, few prognostic comparisons have been conducted. The present study aimed to clarify the prognosis of inferior mesenteric and para-aortic lymph node metastases in rectal cancer., Patients and Methods: We retrospectively evaluated 71 patients with pathologically diagnosed rectosigmoid or rectal cancer with inferior mesenteric lymph node metastasis and 27 with pathologically diagnosed rectosigmoid or rectal cancer with para-aortic lymph node metastasis who underwent curative surgery. They were identified from the Japanese Study Group for Postoperative Follow-Up of Colorectal Cancer database. Overall survival, recurrence-free survival, and recurrence patterns were compared between the two groups., Results: The five-year recurrence-free survival rates of patients with inferior mesenteric and para-aortic lymph node metastases were 31.2 and 28.1%, respectively (p=0.37), and the five-year overall survival rates were 43.1 and 39.6%, respectively (p=0.60). Furthermore, the survival curves of the two groups almost overlapped for both recurrence-free survival and overall survival rates. Recurrence patterns did not significantly differ between the two groups., Conclusion: In rectal cancer, the prognosis of inferior mesenteric lymph node metastasis is similar to that of para-aortic lymph node metastasis. Inferior mesenteric lymph node metastasis has a poor prognostic impact on rectal cancer., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Cancer cells evade apoptosis in colorectal cancer (CRC); however, overlap between apoptosis and poor prognosis marker proteins in the invasive front of tumors has not been reported. Here, we aimed to clarify the relationship between apoptosis, apoptosis-related protein expression, and prognosis in the central and invasive front regions of CRC using tissue microarrays., Patients and Methods: Data of 207 patients with pathological stage 3 CRC, who underwent radical surgery between October 2010 and November 2014, were retrospectively reviewed. We assessed apoptosis using M30 CytoDEATH, CD163, and p53 immunostaining in tumor sections in the center and invasive front using tissue microarrays and correlated the results with the survival outcomes., Results: M30 CytoDEATH staining was negative; 134 cases (64.7%) were apoptosis-negative in the center and 103 (49.8%) were apoptosis-negative at the invasive front. CD163 positivity was observed in 16 cases (7.8%) in the center and in 36 cases (17.6%) at the invasive front; p53 positivity was observed in 33 (15.9%) and 64 (30.9%) cases in the center and invasive front, respectively. CD163 and p53 expression was not associated with survival outcomes; however, the apoptosis-negative group at the invasive front had significantly poorer survival outcomes (overall survival: p=0.044, relapse-free survival: p=0.001). We identified cases with a poor prognosis by combining apoptosis and CD163 expression., Conclusion: A lower apoptosis percentage at the invasive front is associated with a poorer prognosis. CRC cases with a poor prognosis can be identified by evaluating apoptosis and CD163 expression in the invasive front., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Even though epithelial-mesenchymal transition markers in primary tumors are identified as a helpful indicator of cancer metastasis and prognosis, their expression in lymph node metastases (LNMs) remains poorly described. We aimed to investigate the difference between snail family transcriptional repressor 1 (SNAI1) and E-cadherin expression in primary tumors and LNMs, and how it affects prognosis., Patients and Methods: From 2010 to 2014, 127 patients who underwent radical surgery for stage III colonic adenocarcinoma without preoperative treatment were retrospectively reviewed for SNAI1 and E-cadherin expression in primary tumors and LNMs., Results: High SNAI1 expression was found in 76% and 70% of primary tumors and LNMs, respectively, and low E-cadherin expression was found in 73% and 84%, respectively. High expression of SNAI1 in LNMs significantly correlated with poor overall and relapse-free survival rates. Even though the rate of liver metastasis at 5 years was similar for the groups with high and low SNAI1 expression in LNMs, the incidence in the group with low SNAI1 expression in the second year was higher than that in the first year (33% vs. 17%), whilst in the group with high SNAI1 expression, the incidence in the first year was higher than in the second year (71% vs. 29%). The rate of recurrence of lung metastasis was significantly lower when SNAI1 expression in LNMs was low (p=0.031)., Conclusion: Low expression of SNAI1 in LNMs of colonic adenocarcinoma may indicate delayed recurrence in the liver and lung., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In recent years, it has become clear that, in addition to normal cytokines, phospholipid mediators play an important role in the development, growth, infiltration, and metastasis of cancer and in the cancer microenvironment. A phospholipid analysis method using tandem mass spectrometry (LC-MS/MS) with high detection sensitivity has enabled quantification of phospholipids, even when using a very small sample. To date, we had applied this MS technology to colorectal cancer tissue. Therefore, in this study, this mass spectrometry technique was applied to ulcerative colitis (UC) and UC-related colorectal cancer, and an analysis was conducted with the aim of clarifying which lysophospholipids specifically change in each type of tissue., Materials and Methods: UC-associated colorectal cancer tissue and UC mucosa were collected from surgical specimens of colitic cancer (n=3). Cancerous and non-cancerous tissues were collected from surgical specimens from patients with sporadic colorectal cancer (n=11). After extraction from these tissues, the amounts of lysophospholipids were quantified by LC-MS/MS. In addition, lysophosphatidylserine (LPS) and lysophosphatidylinositol (LPI) were quantified for each molecular species of fatty acids., Results: Compared to normal mucosa, LPI was increased 3.8-fold (p<0.001) and LPS 3.5-fold (p<0.001) in UC-related colorectal cancer. Molecular species of LPI which were increased in UC-related colorectal cancer were 18:0 (p=0.001), 16:0 (p=0.03) and 20:4 (p=0.004), and of LPS were 18:0 (p<0.001) and 22:6 (p=0.014)., Conclusion: Lysophospholipids increased in colorectal cancer and in UC-associated colorectal cancer. In particular, LPI may have contributed significantly to colitis-associated carcinogenesis., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: CD133 and hypoxia-inducible factor 1α (HIF-1α) have been reported to be affected by chemoradiotherapy (CRT), but the combinatorial assessment of these markers for prognosis after CRT has not been fully investigated. Therefore, we aimed to predict recurrence and prognosis in patients with rectal cancer by assessing changes in the expression of both CD133 and HIF-1α after CRT., Materials and Methods: CD133 and HIF-1α expression was evaluated by immunohistochemistry in surgical specimens from 243 patients with advanced low rectal cancer who received CRT followed by curative resection., Results: The positivity rate of CD133 expression showed increase with increased HIF-1α expression. The combination of these two markers showed that the CD133(+)HIF-1α(-) group exhibited a markedly shorter relapse-free survival (p=0.007), higher liver recurrence (p=0.004), and higher local recurrence (p=0.006)., Conclusion: CD133(+)HIF-1α(-) expression after CRT is a promising marker to predict recurrence in rectal cancer., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to determine the effectiveness of surgical site infection (SSI) prevention approaches in rectal cancer surgery., Patients and Methods: A total of 1,408 patients who underwent elective rectal cancer surgery between 1995 and 2017 were reviewed. Patients were divided into three groups: control group (group A, n=245), SSI prevention intervention group (group B, n=516), and laparoscopic or robotic surgery group (group C, n=647). The groups were compared in terms of SSI and anastomotic leakage (AL) incidences, and risk factors for SSI were investigated., Results: The overall SSI and AL rates were 19.4% and 3.6%, respectively. These rates were significantly lower in Group C (9.3%, 1.7%), compared to Groups A (40.0%, 6.1%) and B (22.5%, 3.5%). Abdominoperineal resection, open surgery, operation time, intraoperative bleeding, lack of absorbable sutures, lack of mechanical bowel preparation, and lack of oral antibiotics were independently associated with SSI., Conclusion: SSI reduction after rectal cancer surgery was achieved through various intervention strategies., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The inferior mesenteric arteries (IMA) are occluded in some colorectal cancer patients. This study evaluated the impact of IMA occlusion on the calibre of collateral arteries., Patients and Methods: As an IMA obstruction model, 20 patients who underwent abdominal aortic aneurysm surgery, with ligated, excluded, or embolised IMA, were enrolled. Changes in the calibre of the left colic arteries (LCAs) and marginal arteries after surgeries were evaluated., Results: The cross-sectional area of the LCA significantly increased after surgery (4.34 mm 2 vs. 6.34 mm 2 , p=0.0009) and that of the marginal artery did not change significantly (2.69 mm 2 vs. 3.01 mm 2 , p=0.33)., Conclusion: The calibre of the LCA increased after IMA occlusion. The descending branch of the LCA should be confirmed preoperatively to preserve blood flow during a low tie procedure., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: This study aimed to develop a new pathological finding, namely, invasion front grade and verify its clinical usefulness., Materials and Methods: We re-examined haematoxylin-eosin-stained specimens in 162 stage II-III colorectal cancer patients who underwent radical resection. We assessed the desmoplastic reaction, Klintrup grade, and poorly differentiated cluster. These three findings were combined to form the invasion front grade (good prognosis group; Grade A, poor prognosis group; Grade B), and its reproducibility and prognostic stratification ability were statistically analysed., Results: Invasion front grade was Grade A in 116 cases and Grade B in 46 cases, and its kappa coefficient was 0.81 for interobserver and 0.74 for intraobserver variability. The 3-year recurrence-free survival rates of Grade A and Grade B were 90.4% and 55.9%. Multivariate analysis showed that invasion front grade was an independent prognostic factor., Conclusion: Invasion front grade is useful as a prognostic stratification factor for stage II-III colorectal cancer., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Lysophosphatidylinositol (LPI) is a subspecies of the lysophospholipid mediators produced when phospholipase hydrolyzes membrane phosphatidylinositol. Previously, we used mass spectrometry-based lipidomics to demonstrate that LPI is selectively elevated in colorectal cancer (CRC) tissues. Here, we hypothesized that the expression levels of the LPI biosynthetic enzyme and LPI receptor - DDHD domain containing 1 (DDHD1) and G protein-coupled receptor 55 (GPR55), respectively - may be correlated with malignant potential, and we evaluated their roles in the context of CRC., Materials and Methods: Colorectal specimens from 92 CRC patients underwent DDHD1 and GPR55 immunolabeling. Correlation between protein expression levels and clinicopathological variables was examined., Results: Depth of tumor invasion was positively correlated with DDHD1 expression. Regardless of the degree of invasion depth, GPR55 was highly expressed in CRC tissues. Neither DDHD1 nor GPR55 expression levels were associated with disease-free survival., Conclusion: DDHD1 expression is associated with depth of tumor invasion in CRC tissues and may be involved in tumor progression., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: It remains unclear whether rectal cancers down-staged by preoperative chemoradiotherapy (CRT) have similar prognoses to those of the same stage without preoperative CRT. We compared prognoses of pT1 rectal cancer patients stratified by preoperative CRT., Patients and Methods: We retrieved data of patients with pathological T1 rectal cancer between 2003 and 2020. Patients were divided into the "ypT1 group" who received preoperative CRT following surgery and the "pT1 group" who underwent surgery alone. Factors associated with relapse-free survival (RFS) were investigated., Results: Among 86 patients, ypT1 and pT1 groups comprised 18 and 68 patients, respectively. There was no significant difference in RFS between the groups (p=0.19). Tumor location within 5 cm from the anal verge was associated with recurrence (hazard ratio: 0.13, p=0.034)., Conclusion: The prognosis of patients with ypT1 rectal cancer was similar to that of patients with pT1. Low tumor location was a poor prognostic factor., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The clinical significance of surgery for secondary small intestinal non-Hodgkin's lymphomas (NHL) remains unknown. This study aimed to investigate the efficacy of resection for both primary and secondary small intestinal NHL., Patients and Methods: Twenty patients with small intestinal lymphoma who underwent surgical resection at our Institute between 2009 and 2017 were retrospectively evaluated. The clinicopathological and surgery-related factors were reviewed. We also analyzed their surgical outcomes such as postoperative complications, perforation rate, and overall survival (OS)., Results: In total, 13 (65%) and 7 (35%) patients had primary and secondary lymphomas, respectively. A total of 70% of patients were diagnosed with aggressive-type lymphomas. A total of 15 (75%) patients had Lugano system stage IV. Only one (5%) patient experienced postoperative grade II deep vein thrombosis and pulmonary embolism. The 3-year OS rate after surgery was 59.6%., Conclusion: Surgical resection prior to chemotherapy is a feasible and safe therapeutic strategy for small intestinal NHL., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: To date, there is no clear understanding whether preoperative long-course chemoradiotherapy combined with surgery for rectal cancer is detrimental to anorectal function. The purpose of this study was to clarify the influence of preoperative chemoradiotherapy and surgery for middle and lower rectal cancer on postoperative anorectal function., Patients and Methods: Data of 113 patients with middle or lower rectal cancer treated with preoperative chemoradiotherapy plus surgery or surgery alone between January 2013 and December 2016 were analyzed. A total of 84 and 29 patients underwent low anterior resection and intersphincteric resection, respectively. In patients with T3 or deeper and with any N stage cancer below peritoneal reflection, surgery plus lateral lymph node dissection or preoperative radiation (total: 50.4 Gy/28 fractions) to the pelvis with chemoradiotherapy plus surgery was treated. Anorectal function was assessed prior to treatment and 6 and 12 months postoperatively. Specifically, maximum resting pressure and maximum squeezing pressures were measured. The Wexner score was recorded prior to treatment and 12 months postoperatively., Results: maximum resting pressure and maximum squeezing pressure decreased post-surgery in both groups. Maximum resting pressure and maximum squeezing pressure at 12 months and the Wexner score at 12 months post-surgery were comparable among patients treated with chemoradiotherapy plus surgery and those treated with surgery alone., Conclusion: Preoperative chemoradiotherapy did not clearly impair postoperative anorectal function in patients who underwent low anterior resection and intersphincteric resection., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Mitochondria are energy-producing organelles, and dysfunction in these organelles causes various types of disease. Although several studies have identified mutations in nuclear DNA that are associated with the etiology of ulcerative colitis (UC), information regarding mitochondrial DNA (mtDNA) in UC is limited. This study aimed to investigate the mitochondrial DNA polymorphism underlying the etiology of UC and UC-associated colorectal cancer., Materials and Methods: Next-generation sequencing was performed to assess mitochondrial DNA mutations in 12 patients with UC-associated cancer. The mtDNA mutations in the non-neoplastic mucosa, tumor tissues, and healthy controls were compared., Results: The incidence of mutations of nicotinamide adenine dinucleotide phosphate ubiquinone oxidase subunit, ATP synthetase, and tRNA was higher in non-neoplastic mucosa in those with UC compared with the healthy controls. However, no statistically significant differences were observed in mutations between the tumor tissues and non-neoplastic mucosa in UC., Conclusion: Significant mutations in mtDNA were observed in the non-neoplastic mucosa of patients with UC-associated cancer., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We aimed to investigate the molecular features of synchronous colorectal cancer (CRC)., Materials and Methods: Out of 1,262 patients with CRC, 130 lesions in 59 patients with synchronous CRC were retrospectively analyzed. Microsatellite, v-Ki-Ras2 Kristen rat sarcoma viral oncogene homolog (KRAS), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), tumor protein 53 (TP53) and β-catenin status were evaluated and compared between synchronous CRC lesions in each patient., Results: The subtypes of instability, BRAF and β-catenin subtypes was significant but low. Patients with discordant KRAS and TP53 were not concordant between lesions in the same patient, and concordance of microsatellite KRAS/BRAF subtypes comprised 50.8% of those with synchronous CRC. The rate of patients with lesions containing both mutL homolog 1 (MLH1) methylation and microsatellite stable status was 66.7% in those with synchronous CRC, with at least one lesion with high microsatellite instability., Conclusion: The present study on synchronous CRC demonstrated a low concordance of molecular subtypes between lesions in the same patient. A molecular analysis of metastatic lesions is warranted for molecular targeted therapy of metastatic synchronous CRC., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Aim: This study aimed to clarify the difference in the clinicopathological and prognostic features between synchronous colorectal cancer (CRC) and solitary CRC., Materials and Methods: A retrospective analysis was conducted in patients with synchronous and solitary CRC., Results: A total of 92 (7.1%) out of 1,295 consecutive patients had synchronous CRC. Mucinous adenocarcinoma was more frequent in patients with synchronous CRC than in those with solitary CRC (13.0% vs. 3.7%; p<0.001). The 5-year relapse-free survival (RFS) rate was poorer in patients with synchronous CRC than in those with solitary CRC (65.3% vs. 75.1%; p=0.035), which was contrived by the multivariate analysis (hazard ratio=1.52(HR); p=0.039)., Conclusion: Patients with synchronous CRC had a poorer RFS than those with solitary CRC; thus, patients with synchronous CRC might require more intensive care than those with solitary CRC in follow-up., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Several risk factors for recurrence have been identified in stage II colorectal cancer. However, in contrast to stage III, the benefits of adjuvant chemotherapy for these patients remain controversial. We hypothesized that the different impacts of chemotherapy may be due to different patterns of recurrence between these stages. The aim of this study was to characterize recurrence in high-risk stage II colorectal cancer (CRC) in comparison with stage III., Patients and Methods: A total of 442 patients with curatively resected stage III and high-risk stage II CRCs were evaluated. The recurrence site and frequency were compared between these stages. The risk factors of recurrence by site were identified using multivariate analyses., Results: During the follow-up (median: 6.4 years), 31% of stage III and 13% of high-risk stage II patients manifested recurrence. Recurrence in the liver, lung, and distant lymph nodes was significantly more frequent in stage III (18%, 12%, 11%) than in high-risk stage II (7%, 6%, 3%). Stage III was independently associated with recurrence in these organs. In contrast, the rate of peritoneal recurrence was 5% in both stages., Conclusion: Clinicians should be aware that high-risk stage II CRC has a similar risk of postoperative recurrence in the peritoneum to Stage III CRC., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The revised Bethesda guidelines (rBG) are generally used for screening of Lynch syndrome, and few researchers have investigated the associations between microsatellite instability (MSI) status and each item of the rBG., Patients and Methods: This retrospective study included patients with colorectal cancer who were classified into those fulfilling the rBG (Bethesda group) and those not (control group). The breakdown of each item in the rBG and predictors of high MSI (MSI-H) were determined in the Bethesda group., Results: Of 809 consecutive patients, 161 (19.9%) were found to fulfil the rBG criteria. As a predictor of MSI-H, items 2 or 5 of the rBG showed a sensitivity of 93.3%. Item 5 and right-sided tumour location were independent predictors of MSI-H in patients fulfilling the rBG (odds ratio(OR)=4.49 and 25.1; p=0.0260 and <0.0001, respectively)., Conclusion: Item 5 of the rBG and right-sided tumour location are significant predictors of MSI-H., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Hypoxia offers resistance to therapy in human solid tumors. The aim of the study was to investigate whether SN-38, the active metabolite of irinotecan, acts as a radiosensitizer through inhibition of hypoxia-inducible factor (HIF)-1α in the human colorectal cancer (CRC) cells., Materials and Methods: HT29 and SW480 cells were cultured with SN-38 (0-4 μM) immediately after irradiation (0-8 Gy). HIF-1α expression was assessed using flow-cytometry and western blot analysis. Cell proliferation was evaluated by the calcein assay. Apoptosis and cell cycle were determined by flow-cytometry., Results: Radiation up-regulated HIF-1α, and SN-38 inhibited the radiation-induced HIF-1α. The combination of radiation and SN-38 inhibited cell proliferation more than radiation alone; treatment with SN-38 after radiation exposure did not increase the number of apoptotic cells, whereas, it enhanced the S and G 2 /M cell-cycle arrest and decreased the population of cells in G 1 Conclusion: SN-38 inhibits the radiation-induced up-regulation of HIF-1α and acts as a radiosensitizer by inducing cell-cycle arrest in CRC cells., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The expression of doublecortin-like kinase 1 (DCLK1) has been investigated in cancer; however not in precancerous adenomatous polyps., Materials and Methods: Immunohistological expression of DCLK1 was evaluated in various grades of adenomas, cancerous polyps, and hyperplastic polyps in resected human tissue specimens., Results: Ninety-two specimens were positive for DCLK1 and 134 were negative. Cancerous polyps showed a high DCLK1 positivity rate compared to adenomas (68.4% vs. 36.8%; p<0.01). The rate of DCLK1 positivity was not significantly different among the three grades of adenomas (mild, moderate, and severe). DCLK1 was highly positive in advanced adenomas than low risk adenomas (49.6% vs. 29.3%; p<0.01)., Conclusion: The expression of DCLK1 was found in low-grade adenomas and increased with worsening severity of dysplasia. DCLK1 expression was highly observed in advanced adenomas, which had a clinically higher malignant potential., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Although systemic chemotherapy has been improved, peritoneal carcinomatosis remains a factor of poor prognosis in patients with colorectal cancer. In order to achieve a higher drug concentration in the peritoneal cavity, intraperitoneal chemotherapy has been performed. However, the optimal regimen for intraperitoneal chemotherapy has not been determined. In this review of intraperitoneal chemotherapy for colorectal cancer, we summarize regimens of hyperthermic intraperitoneal chemotherapy (HIPEC) and other intraperitoneal chemotherapy modalities, such as early postoperative intraperitoneal chemotherapy (EPIC) and sequential postoperative intraperitoneal chemotherapy (SPIC). Mitomycin C and oxaliplatin are the most common chemotherapeutic agents used for HIPEC. Some combination therapies such as those involving bevacizumab, H 2 O 2 , and amifostine have potential to increase HIPEC efficacy. 5-Fluorouracil is used mainly for EPIC and SPIC. Some new agents such as paclitaxel, melphalan, and various nanoparticles have been developed. These novel chemotherapeutic agents may achieve clinical implementation in the future., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Patients with ulcerative colitis (UC) are at risk of UC-associated colorectal cancer (CRC); however, little is known about genetic alterations occurring during UC carcinogenesis. We examined mutational changes in patients with colitic cancer and the features that differed between the carcinogenesis of UC and sporadic CRC., Material and Methods: Specimens were obtained from the non-neoplastic mucosa and cancer cells of 12 patients with colitic cancer. The mutational rate of oncogenes in colitic cancer was analyzed and compared to that of oncogenes in sporadic CRC., Results: We observed a lower mutation rate in adenomatous polyposis coli (APC) (16.7%(2/12) vs. 75.9%(161/212), respectively, p=0.0001) and KRAS (16.7%(2/12) vs. 42% (89/212), respectively, p=0.04) in colitic cancer than in sporadic CRC. With respect to cadherin 1 (CDH1) and fibroblast growth factor receptor 2 (FGFR2), the mutational rates for non-neoplastic colorectal mucosa were similar to those in sporadic CRC., Conclusion: We demonstrated that mutational rates for APC and KRAS differ between colitic cancer and sporadic CRC. Furthermore, we revealed that CDH1 and FGFR2 become mutated at an earlier stage in colitic carcinogenesis than in sporadic CRC., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Intersphincteric resection (ISR) aims to preserve anal function in patients with very low rectal tumors. Here, we analyzed patients who underwent neoadjuvant imatinib therapy followed by ISR for low rectal gastrointestinal stromal tumors (GISTs)., Patients and Methods: We retrospectively analyzed patients with low rectal GISTs who underwent neoadjuvant imatinib therapy and ISR between January 2013 and December 2015 at the University of Tokyo hospital., Results: The study included 4 men and 1 woman, with a median age of 67 years (range=45-67). All patients received 400 mg of neoadjuvant imatinib once daily for the median duration of 4 months (range=3-12). Microscopically, R0 resection was performed in 4 patients, and R1, in 1 patient. There was 1 recurrence event during the median follow-up duration of 35 months., Conclusion: Neoadjuvant imatinib therapy and ISR for low rectal GISTs is a challenging, but promising, alternative to achieve complete resection margins and preserve anal function., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)