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Purpose: This study aimed to evaluate the clinicopathological and prognostic significance of preoperative serum creatine kinase (CK) levels in colorectal cancer., Methods: This study analyzed 1169 patients with colorectal cancer at stages 0 (n = 35), I (n = 301), II (n = 456), III (n = 339), and IV (n = 38). The CK cut-off value was 52 U/L to predict recurrence based on receiver operative characteristics curve. Clinicopathological factors were compared between the low (< 52 U/L) and high CK groups (≥ 52 U/L). The multivariate analysis evaluated relapse-free survival (RFS) and overall survival (OS) following CK status., Results: The female sex, elderly age (≥ 75), deep tumor (pT4), and carcinoembryonic antigen (+) were independently associated with low CK status. The recurrent rate was significantly higher in the low CK group than in the high CK group (19.1% vs. 11.7%, p < 0.001). Elderly age, pT4, pN (+), preoperative carbohydrate antigen (CA) 19-9 (+), and low CK status were independent risk factors for RFS. Elderly age, pT4, pN (+), preoperative CA19-9 (+), and low CK status were independent risk factors for OS., Conclusion: Preoperative low CK status was associated with deep tumors and was a poor prognostic factor in patients with colorectal cancer., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biosimilar(BS)drugs have recently been introduced owing to concerns with healthcare economics. In this report, we present a case in which a patient discontinued bevacizumab treatment following an allergic reaction to a BS formulation of bevacizumab but was able to safely continue treatment by switching to an original bevacizumab formulation in the late-line setting. The patient was a 66-year-old man diagnosed with unresectable colorectal cancer with synchronous multiple liver metastases. After primary tumor resection, chemotherapy including the original bevacizumab formulation was initiated. Allergic reactions to the BS formulation of bevacizumab occurred during the second-line treatment; however, in the late-line setting, switching back to the original bevacizumab formulation enabled the safe continuation of therapy. Overall, our case study suggests that switching of biologic agents may contribute to the ongoing management of chemotherapy.

Purpose: To compare the utility of preoperative immunonutritional parameter measures for predicting postoperative mortality following palliative surgery (PS) for malignant bowel obstruction (MBO) in patients with late-stage cancer., Methods: The subjects of this retrospective study were 83 late-stage cancer patients with MBO who underwent PS between January, 2005 and December, 2018, at a single institution in Japan. We compared the modified Glasgow prognostic score (mGPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for predicting postoperative mortality following PS in these patients., Results: The most prevalent cancer in the patients who underwent PS was colorectal cancer (54.2%), followed by gastric cancer (24.1%). Postoperative complications of Clavien-Dindo classification grade ≥ 2 developed in 32 (38.6%) patients and stoma-related complications developed in 26 (31.3%) patients. There were 15 (18.1%) patients with 60-day mortality, 22 (26.5%) with 90-day mortality, and 4 (4.8%) with 30-day mortality. Multivariable analysis identified only mGPS as being associated with 60-day mortality (odds ratio, 9.387; 95% confidence interval, 0.001-4.478; p = 0.049). The overall survival of patients with a mGPS score of 2 was significantly worse than that of those with a mGPS score of < 2 (p = 0.013)., Conclusions: These results suggest that the mGPS is a good predictor not only of 60-day mortality, but also of the overall survival of patients with late-stage cancer and MBO., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Objective: To elucidate tumor cell behavior associated with cancer stem cell (CSC) marker expression, the expression of CD133, CD44v9, and ALDH1A1, which are considered markers of CSCs, was examined in sporadic and ulcerative colitis (UC)-associated colorectal tumors., Methods: A total of 23 cases of sporadic colorectal cancer and 44 cases of adenoma were collected. Additionally, 22 cancer lesions and 38 dysplasia lesions were selected from 28 colectomy cases of UC with neoplastic lesions. Lesions were examined by immunohistochemistry using primary antibodies against CD133, CD44v9, ALDH1A1, Ki-67, cleaved-Caspase 3, and p53., Results: CD133, CD44v9, and ALDH1A1 showed higher expression in both sporadic and UC-associated tumors than in the normal mucosa. ALDH1A1 expression in sporadic cancer was higher in the right colon than in the left colon (p=0.0089). ALDH1A1 expression in UC-associated cancer was higher in those with longer disease duration than in those with shorter disease duration (p=0.019). The CD44v9+/CD133- region had fewer cleaved-Caspase 3 positive cells in both sporadic and UC-associated cancers. In sporadic cancer, CD133+/ALDH1A1+ regions had fewer apoptotic cells than CD133+/ALDH1A1- regions, while CD133+/ALDH1A1- regions were less proliferative than CD133+/ALDH1A1+ regions in UC-associated cancer., Conclusion: CD44+/CD133- regions were commonly associated with low apoptosis in sporadic and UC-associated cancers; thus, these were considered target areas for CSCs. Additionally, the combination of markers comprising CSCs may differ between sporadic and UC-associated cancers.

Background: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53)., Methods: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer., Results: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 μg/mL (range < 0.02-29.2 μg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 μg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer., Conclusions: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Background: The clinical impact of monitoring serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen in patients with colorectal cancer has not been fully evaluated., Methods: A total of 420 surgically treated stage II/III colorectal cancer patients were retrospectively analyzed. Among them, 101 patients developed disease recurrence. The prognostic impact of preoperative and recurrence levels of serum p53 antibodies, carbohydrate antigen19-9, and carcinoembryonic antigen status was evaluated., Results: Although preoperative carcinoembryonic antigen- and carbohydrate antigen19-9-positive status was significantly associated with recurrence, preoperative serum p53 antibody levels were not. Among two marker combinations, carcinoembryonic antigen + serum p53 antibodies showed the highest positive rate at recurrence. Although carcinoembryonic antigen and carbohydrate antigen19-9 frequently converted from preoperative-negative status to positive status at recurrence, serum p53 antibodies converted to positive status in only one patient. Carcinoembryonic antigen- and carbohydrate antigen19-9-positive status were significant prognostic factors for overall survival after recurrence, but the presence of serum p53 antibodies at recurrence was not., Conclusions: Postoperative serum p53 antibody status should only be followed in patients with preoperative-positive status. Carcinoembryonic antigen and carbohydrate antigen19-9 should be followed even in preoperative-negative patients. Unlike carcinoembryonic antigen- and carbohydrate antigen19-9-positive status, serum p53 antibody-positive status as recurrence was not a poor prognostic indicator.

Background: In Japan, R0 resection has been recommended for colorectal cancer patients with peritoneal metastases confined to the adjacent peritoneum and those with a few metastases to the distant peritoneum. R0 resection for M1c disease has drawn attention in Western countries and is currently considered an acceptable therapeutic option in the US National Comprehensive Cancer Network guidelines. However, clinical factors that affect the choice of R0 resection are unknown., Methods: This multicenter, prospective, observational study was conducted by the Japanese Society for Cancer of the Colon and Rectum. Colorectal cancer patients with synchronous peritoneal metastases were enrolled at 28 institutions in Japan from October 2012 to December 2016. To determine factors affecting R0 resection and R1 resection with intended R0 resection, stepwise logistic regression analyses were performed on clinical factors including age, sex, performance status (PS), body mass index, peritoneal cancer index (PCI) score, presence of ascites, presence of distant metastases, and primary tumor site., Results: R0/R1 resection was performed in 36 (31/5; 25%) of 146 patients. No distant metastases [odds ratio (OR) 52.9; 95% confidence interval (CI) 13.3-210.1; p < 0.0001], low PCI score (1-6) (OR 20.0; 95% CI 4.8-83.4; p < 0.0001), and high PS (0) (OR 2.40; 95% CI 0.66-8.68; p = 0.18) were independent factors affecting R0/R1 resection. PCI score and PS were also independent factors affecting R0/R1 resection in M1c patients without non-peritoneal distant metastases (n = 59)., Conclusion: Distant metastases, PCI score, and PS are three factors which affect R0 resection for M1c disease.

Background: Surgical management of malignant bowel obstruction carries with high morbidity and mortality. Placement of a trans-anal decompression tube (TDT) has traditionally been used for malignant bowel obstruction as a bridge to surgery. Recently, colonic metallic stent (CMS) as a bridge to surgery for malignant bowel obstruction, particularly left-sided malignant large bowel obstruction (LMLBO) caused by colorectal cancer, has been reported to be both a safe and feasible option. The aim of this retrospective study is to evaluate the clinical effects of CMS for LMLBO as a bridge to surgery compared to TDT., Methods: Between January 2000 and December 2015, we retrospectively evaluated outcomes of 59 patients with LMLBO. We compared the outcomes of 26 patients with CMS for LMLBO between 2013 and 2015 (CMS group) with those of 33 patients managed with TDT between 2003 and 2011 (TDT group) by the historical study. LMLBO was defined as a large bowel obstruction due to a colorectal cancer that was diagnosed by computed tomography and required emergent decompression., Results: All patients in the CMS group were successfully decompressed (p = 0.03) and could initiate oral intake after the procedure (p <  0.01). Outcomes in the CMS group were superior to the TDT group in the following areas: duration of tube placement (p <  0.01), surgical approach (p <  0.01), operation time (p <  0.01), number of resected lymph nodes (p <  0.001), and rate of curative resection (p <  0.01). However, no significant differences were found in the overall postoperative complication rate (p = 0.151), surgical site infection rate (p = 0.685), hospital length of stay (p = 0.502), and the need for permanent ostomy (p = 0.745). The 3-year overall survival rate of patients in the CMS and TDT groups was 73.0% and 80.9%, respectively, and this was not significant (p = 0.423)., Conclusions: Treatment with CMS for patients with LMLBO as a bridge to surgery is safe and demonstrated higher rates of resumption of solid food intake and temporary discharge prior to elective surgery compared to TDT. Oncological outcomes during mid-term were equivalent.

Background: Although serum p53 autoantibodies (s-p53-Abs) are induced even in the early stages of colorectal cancer, their positive rate is only approximately 20%. Therefore, we assessed the possibility of using other serum autoantibodies to increase the positive rates for detecting colorectal cancer., Methods: Autoantibodies against 17 tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, NY-ESO-1, p90, Sui1, HSP40, CyclinB1, HCC-22-5, c-myc, PrxVI, VEGF, HCA25a, p62, and Annexin II) were evaluated in 279 patients with colorectal cancer and 74 healthy controls. Cutoff values were fixed at mean + 3 standard deviations of serum titers in healthy controls., Results: Autoantibodies with the highest positive rates were p53 (20%), RalA (14%), HSP70 (12%), and Galectin1 (11%). Combination assays using multiple autoantibodies increased the positive rates based on the number of autoantibodies used. Positive rates of 56, 62, 66, 71, and 73% were obtained with 6, 9, 11, 14, and 17 antibodies, respectively, for the overall disease. Moreover, these autoantibodies showed relatively high positive rates even during stage 0/I disease (55 and 70% with 6 and 17 antibodies, respectively)., Conclusion: The measurement of set of 17 autoantibodies allowed autoantibody profiling in patients with colorectal cancer. The combination assay of six tumor antigens (p53, RalA, HSP70, Galectin1, KM-HN-1, and NY-ESO-1) achieved a positive rate of 56%. Such high positive rates will be helpful for detecting colorectal cancer regardless of tumor stages.

When a medical provider(medical personnel)becomes a medical receiver(patient), does the consciousness about chemotherapy change ? If yes, what is the main reason ? In this study, we conducted a questionnaire on the consciousness of doctors and pharmacologists engaged in chemotherapy for gastric and/or colorectal cancer. The number of questionnaires collected was 83 and 92 for gastric and colorectal cancer, respectively. In adjuvant chemotherapy, 5%and 4%do not want to receive any chemotherapy for gastric and colorectal cancer if they are patients. The main reasons are binding hours, side effects, and no wish for life extension. About 11%and 9%change their consciousness regarding chemotherapy according to whether they are care providers or receivers. The main reasons are medical perspective and their sense of duty. In chemotherapy for advanced cancer, 6% and 5% of gastric and colorectal cancer patients, do not want to receive any chemotherapy. The main reasons are low expectations for being cured, binding hours, and no wish for life extension. Further, 21%and 14%wish to have limited chemotherapy. As regards consciousness on chemotherapy, 26% and 18% reported changes according to whether they are providers or receivers. The main reasons are medical perspective and their sense of duty. As for the purpose of chemotherapy for advanced gastric and colorectal cancer, 96% and 43% answered prolonging life and relief, respectively. The proportion of persons who answered complete cure is statistically higher in colorectal(32%)than in gastric cancer(18%). The most common answer for an adverse event they want to avoid if they are patients is peripheral neuropathy. These results clearly demonstrate that a considerable proportion of medical personnel hold a negative attitude against or are reluctant to receiving chemotherapy, especially for advanced gastric and colorectal cancer. It is of great importance to make use of these results in clinical practice.

Background/aims: KRAS mutation is an important prognostic factor for patients with metastatic colorectal cancer receiving anti-epidermal growth factor receptor therapy. However, the influence of KRAS mutation on the response to mFOLFOX6 ± bevacizumab remains unclear., Methodology: We retrospectively analyzed 49 patients who received modified FOLFOX6 (mFOLFOX6) ± bevacizumab as first-line therapy. Genetic analysis showed that 30 patients had wild-type (WT) KRAS and 19 patients hadKRAS mutations (MT). These two groups were compared with regard to the response rate (RR), progression-free survival (PFS), and overall survival (OS)., Results: The RR was not significantly different between the WT and MT groups, but PFS and OS were significantly better in the WT group than the MT group (PFS: 11.8 months vs. 8.7 months, p<0.01; OS: 37.8 months vs. 29.3 months, p<0.0385). A similar analysis of 27 patients who were treated with mFOLFOX6 + bevacizumab showed a better prognosis for WT patients. Multivariate analysis also revealed that KRAS mutation was an independent factor with a significant relation to PFS., Conclusions: These results suggest that KRAS mutation may be a useful prognostic marker for patients with metastatic colorectal cancer receiving mFOLFOX6 ± bevacizumab therapy, especially for patients treated with mFOLFOX6 + bevacizumab.

Background: Peritoneal metastasis is well-known as a poor prognostic factor in patients with colorectal cancer. It is important to improve the prognosis of patients with colorectal cancer and synchronous peritoneal metastasis. This study aimed to clarify the factors affecting R0 resection and the prognosis of colorectal cancer patients with synchronous peritoneal metastasis., Methods: We investigated the data of patients with stage IV colorectal cancer between 1991 and 2007 in 16 hospitals that were members of the Japanese Society for Cancer of the Colon and Rectum., Results: Of the 564 colorectal cancer patients with synchronous peritoneal metastases, 341 also had hematogenous metastases. The 5-year overall survival rates in patients with and without R0 resection were 32.4 and 4.7 %, respectively. A Cox proportional hazards model showed that histologic type of poorly differentiated adenocarcinoma, regional lymph node metastasis, liver metastasis, chemotherapy after surgery, R0 resection, the Japanese classification of peritoneal metastasis, and the size of peritoneal metastases were independent prognostic factors. Of the 564 patients, 28.4 % had R0 resection. The Japanese classification of peritoneal metastasis (P1-P2, p = 0.0024) and absence of hematogenous metastases (p < 0.0001) were associated with R0 resection., Conclusions: P1-P2 peritoneal metastasis and the absence of hematogenous metastasis were the most favorable factors benefiting from synchronous resection of peritoneal metastasis. In addition, chemotherapy after surgery was essential.

Down-regulation of hMSH3 is associated with elevated microsatellite alterations at selected tetranucleotide repeats and low levels of microsatellite instability in colorectal cancer (CRC). However, the mechanism that down-regulates hMSH3 in CRC is not known. In this study, a significant association between over-expression of glucose transporter 1, a marker for hypoxia, and down-regulation of hMSH3 in CRC tissues was observed. Therefore, we examined the effect of hypoxia on the expression of hMSH3 in human cell lines. When cells with wild type p53 (wt-p53) were exposed to hypoxia, rapid down-regulation of both hMSH2 and hMSH3 occurred. In contrast, when null or mutated p53 (null/mut-p53) cells were exposed to hypoxia, only hMSH3 was down-regulated, and at slower rate than wt-p53 cells. Using a reporter assay, we found that disruption of the two putative hypoxia response elements (HREs) located within the promoter region of the hMSH3 abrogated the suppressive effect of hypoxia on reporter activity regardless of p53 status. In an EMSA, two different forms of HIF-1α complexes that specifically bind to these HREs were detected. A larger complex containing HIF-1α predominantly bound to the HREs in hypoxic null/mut-p53 cells whereas a smaller complex predominated in wt-p53 cells. Finally, HIF-1α knockdown by siRNA significantly inhibited down-regulation of hMSH3 by hypoxia in both wt-p53 and mut-p53 cells. Taken together, our results suggest that the binding of HIF-1α complexes to HRE sites is necessary for down-regulation of hMSH3 in both wt-p53 and mut-p53 cells., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Metastasis to the abdominal wall including port sites after laparoscopic surgery for colorectal cancer is rare. Resection of metastatic lesions may lead to greater survival benefit if the abdominal wall metastasis is the only manifestation of recurrent disease. A 57-year-old man, who underwent laparoscopic surgery for advanced mucinous adenocarcinoma of the cecum 6 years prior, developed a nodule in the surgical wound at the lower right abdomen. Although tumor markers were within normal limits, the metastasis to the abdominal wall and abdominal cavity from the previous cecal cancer was suspected. An abdominal computed tomography scan did not provide detective evidence of metastasis. (18)F-fluorodeoxyglucose positron emission/computed tomography ((18)F-FDG PET/CT) was therefore performed, which demonstrated increased (18)F-fluorodeoxyglucose uptake (maximum standardized uptake value: 3.1) in the small abdominal wall nodule alone. Histopathological examination of the resected nodule confirmed the diagnosis of metastatic mucinous adenocarcinoma. Prognosis of intestinal mucinous adenocarcinoma is reported to be poorer than that of non-mucinous adenocarcinoma. In conclusion, this case suggests an important role of (18)F-FDG PET/CT in early diagnosis and decision-making regarding therapy for recurrent disease in cases where a firm diagnosis of recurrent colorectal cancer is difficult to make., (© 2011 Funahashi et al; licensee BioMed Central Ltd.)

Unlabelled: We report 5 cases of colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) oxaliplatin after systemic infusion chemotherapy failure. Patients with unresectable CRLM and history of systemic chemotherapy failure were treated with HAI oxaliplatin (L-OHP 100 mg/body, 2 hours) combined with intravenous (iv) levofolinate calcium (175 mg/body, 2 hours) and iv bolus 5-FU (500 mg/body) every 2 weeks., Result: An average age was 58 years. All patients had previously received FOLFOX. Lung metastases had already existence before HAI oxaliplatin in 4 patients. A median of 10 treatments were administered (range 5-14). Serum level of CEA was decreased in 4 cases. In 2 patients, lung metastasis developed while a PR was obtained in the liver metastasis. Progress disease (PD) was confirmed in other 3 patients. No major toxicity was presented. The median time to progression free survival was 3.0 months and the median overall survival was 7.1 months., Conclusion: HAI oxaliplatin might be beneficial as a salvage therapy for CRLM without extrahepatic metastasis, which demonstrated an acceptable tolerability and maintenance of QOL.

Most tumors of patients with Lynch syndrome and a fraction of sporadic colorectal cancers (CRCs) exhibit high levels of microsatellite instability (MSI) at mono- and dinucleotide repeat loci. A different type of instability, elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been found in non-colonic cancers. Our previous study demonstrated that EMAST is common in sporadic CRC. Here, we focused on the relationships between EMAST and other genomic instability parameters or clinicopathological features in an unselected series of 88 sporadic CRCs. Of the tumors in the sample, 4 (4.5%) were MSI-high (MSI-H), 9 (10.2%) were MSI-low (MSI-L) and 75 (85.2%) were microsatellite stable. EMAST status was determined using 7 EMAST markers. Fifty-three (60.2%) tumors without MSI-H showed instability at >or=1 EMAST loci. All 4 MSI-H tumors showed instability at several EMAST loci. Instability profiles of MSI-H tumors at EMAST loci were more complex than those of non-MSI-H tumors. A tendency of positive association was observed between MSI-L and EMAST (P=0.023). The frequency of loss of heterozygosity (LOH) for the 14 loci in EMAST-positive tumors was significantly higher than negative tumors (P=0.048). Among the clinicopathological parameters, only tumor location at the distal colon was associated with EMAST-negative tumors (P=0.0084, one-tailed). A relatively higher frequency of well-differentiated adenocarcinomas was observed in EMAST tumors as opposed to non-EMAST tumors, though the survival rate was similar. These results suggest that overlapping mechanisms that cause MSI-L, EMAST and LOH in CRCs may exist.

Metastasis to the regional lymph nodes is an important prognostic factor in colorectal cancer, and nodal evaluation is essential for accurate staging. In colorectal cancer, the aim of evaluating sentinel lymph nodes (SLNs) is the selection of patients for adjuvant therapy and the detection of aberrant lymphatic drainage patterns, leading to modification of the initial therapeutic plan. In a review of the literature, tracer, technique, tumor-related factors (location and size of tumor, T stage, status of lymph node metastasis), neoadjuvant chemoradiation therapy, and body mass index were important factors in the accurate diagnosis of SLNs in colorectal cancer. In recent multicenter SLN trials, ultrastaging has been possible in 10-38% of NO colon cancer patients. Most recently, the trial conducted by Bilchik et al., which investigated the prognostic significance of micrometastases in SLNs in colon cancer patients, found that all NO colon cancer patients with recurrence had positive SLN findings after reverse transcriptase-polymerase chain reaction (RT-PCR)-ultrastaging, whereas none of those with negative SLN findings in immunohistologic staining had recurrence, and there was only a significant correlation between recurrence and molecular markers in RT-PCR. However, further prospective multicenter trials are warranted to evaluate the ultimate clinical relevance of SLN diagnosis in colorectal cancer including anal cancer.

We report 27 cases of liver metastases treated with transarterial chemoembolization (TACE) with CPT-11, DSM, and mitomycin C (CPT-DSM therapy). In the 27 patients with liver metastases from colorectal cancer, CPT-DSM therapy was performed 47 times. All of these patients were a contra indication of hepatectomy. We compared a tumor marker before and after the treatment, and measured a serum level of SN-38, which is an active substance of CPT-11 and resolved from CPT-11. Although the level of CPT-11 was wearing off after CPT-DSM therapy, the peak of SN-38 level delayed 1 hour after the infusion. The CEA and CA19-9 levels were decreased to 54.2% and to 45.1% of the level before the treatment, respectively. Nine of the partial response and stable disease patients underwent surgery. The response rate was 59%. A 3-year survival rate was 20%. These results suggest that CPT-DSM therapy is one of the most effective anticancer agents. This TACE can be a feasible therapy for colorectal liver metastases as the first-line therapy.

We measured TS and DPD activities in 40 patients with colorectal cancer who had undergone surgical reduction in our department between May 1997 and April 1998, including 26 patients with preoperative UFT (450 mg/body/day) chemotherapy for 2 weeks, and evaluated the clinical significance of TS and DPD activities as predictive factors of UFT sensitivity. TS activity was collated with histological type from a clinical pathological examination (p = 0.0103). Also, the tendency for TS activity to become high with the stage was observed. According to the evaluation of pathological response, histological effectiveness greater than grade 2 was noted in 7.7%. The apoptosis index (AI) in tumors with preoperative UFT chemotherapy was higher than those without such treatment, which showed a higher correlation with DPD activity of tumor tissue than TS activity (p = 0.0465). Recurrence was seen in 7 cases (lung metastasis: 2, liver metastasis: 4, and local recurrence: 1) in the preoperative chemotherapy group. TS activity was high in all patients with recurrence. TS showed significantly high activity in patients with recurrence compared with the non-recurrence (p = 0.0034) patients. Therefore, these results suggested that activity of both TS and DPD was a key factor for anti-tumor effectiveness of UFT. In particular, TS activity was an important predictive factor for effectiveness of UFT in recurrences.

We report a case in which low-dose CPT-11 chemotherapy was effective for metastatic liver tumor of sigmoid colon cancer. A 49-year-old male with metastatic liver tumor, who had undergone sigmoidectomy with D2 lymphadenectomy, was treated by low-dose CPT-11 chemotherapy (CPT-11 30 mg/m2 x 3 days, every 2 weeks). After 7 courses of this chemotherapy, CT and ultrasound examinations showed a reduction of tumor size in the liver. This chemotherapy also showed no high grade toxicities. Therefore, low-dose CPT-11 chemotherapy seems to be effective for metastatic colorectal cancer, and safe in view of toxicities.

Background and Aim: The rate of ulcerative colitis (UC)‐related colorectal cancer (colitis‐associated carcinoma) is increasing. Estrogen receptor (ER) beta expression has been studied separately in patients with sporadic colorectal cancer and those with colitis‐associated carcinoma. However, no study has compared the expression in both of these cancer types. The present study aimed to evaluate the relationship between colitis‐associated carcinoma and ERs and assess whether the expression of ER beta influences cell proliferation. Methods: This study included 45 surgically operated colitis‐associated carcinomas, 43 high‐grade dysplasias, 34 low‐grade dysplasias, 36 sporadic colorectal cancers, 44 high‐grade adenomas, and 34 low‐grade adenomas. ER beta expression was evaluated with immunohistochemistry. Results: Colitis‐associated carcinoma showed significantly lower ER beta immunoexpression than sporadic colorectal lesions and high‐ and low‐grade dysplasia. In seven colitis‐associated carcinoma harboring both intensity score 3 (strong immunoexpression) and score 1 (weak immunoexpression) areas, the correlation among ER beta intensity, Ki‐67, and p21 labeling index was assessed; an area with an ER beta intensity score of 3 showed a higher Ki‐67 labeling index than that with score 1. In four out of the seven lesions, p21 labeling index was higher in the area of ER beta score 1 than in that of ER beta score 3. Conclusions: The data suggest that ER beta expression is an accelerating factor in colorectal tumors. This association may be lower in colitis‐associated carcinoma than in sporadic colorectal cancer. [ABSTRACT FROM AUTHOR]