前田 耕太郎

Objective: The treatment policy of colorectal cancer in elderly patients is controversial due to a lack of specific guidelines. To clarify the present management of colorectal cancer for aged patients, a questionnaire survey was conducted by the Japanese Society for Cancer of the Colon and Rectum. Methods: Questionnaire forms were sent to the 430 member institutions of the Japanese Society for Cancer of the Colon and Rectum. Results: The response rate of the surgical department to the questionnaire was 39%. Performance status was used for preoperative assessments, and electrocardiogram and ultrasonic cardiograms were conducted for cardiovascular evaluations in many institutions. The same extent of surgical procedures was often adopted for elderly and younger patients, and the frequency of a laparoscopic procedure was the same regardless of a patient's age. A simultaneous hepatectomy for hepatic metastasis was considered in one-third of institutions. In many institutions, intersphincteric resection for patients with possible sphincter-saving surgery was not considered for elderly patients with low rectal cancer. Conclusion: Japanese Society for Cancer of the Colon and Rectum member institutions often used the same surgical treatment strategies for both elderly and younger patients with the exception of performing intersphincteric resection.

To assess the working styles of men and women working as surgeons in Japan. In July, 2014, the Japan Surgical Society invited all their members (n = 29,861), through an internet campaign, to participate in a nationwide survey of surgeons. The items investigated in this descriptive study included demographic information and working styles, based on a questionnaire. In total, 6211 surgeons participated (response rate 20.8%, 5586 men and 625 women). The largest age stratum was 40-49 years for men and 30-39 years for women. Overall, respondents identified their labor contract, including salary and work hours, as the highest priority for improvement. Women with children were more likely to be part-time employees, work fewer hours, and take fewer house calls/on-calls than their male counterparts. Moreover, women of all ages earned a lower annual income than men, irrespective of whether they had children. Perception scores for discrimination related to work and promotion were significantly higher among women than men (p < 0.01 and p = 0.011, respectively). A significant difference in working style was observed between men and women working as surgeons in Japan.

Although hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) therapy are well-documented, few reports have compared different therapies in terms of HSR occurrence. In this study, we compared the frequency and pattern of HSRs to modified FOLFOX6 (mFOLFOX6; 5-fluorouracil, levofolinate calcium and L-OHP infusions) and XELOX (capecitabine and L-OHP) therapies, and sought to identify risk factors associated with HSRs. Patients who had received mFOLFOX6 or XELOX chemotherapeutic regimens for unresectable colon or rectal cancer or as adjuvant chemotherapy following colon cancer surgery between April 2012 and August 2015 were included. Potential correlation between treatment modalities (regimen, dosage and route of administration of L-OHP, and injection timing for dexamethasone administration) and HSRs was assessed. Among the 240 patients included in the study, 136 had received mFOLFOX6 therapy and 104 had received XELOX therapy. Although the frequency of HSRs did not differ between the two groups, incidence of HSRs in the first cycle was higher in the XELOX therapy group. Treatment method or cumulative dosage was not identified as a risk factor for HSR; however, the incidence of aegrade-2 HSR was higher in cases where the cumulative L-OHP dosage was ae600 mg/m(2) and in patients in whom dexamethasone was not co-infused with L-OHP. Although HSR rates were comparable among patients treated with mFOLFOX6 and XELOX, HSRs tended to occur more frequently during the first cycle of XELOX therapy as compared to that with mFOLFOX6 therapy. Our findings warrant careful assessment of aegrade-2 HSRs in patients who are prescribed cumulative L-OHP dosages of ae600 mg/m(2).

Purpose We devised a simple dichotomous classification system and showed sufficient reproducibility to indicate treatment strategies for peritoneal metastasis of colorectal cancer. Methods We included 67 patients with peritoneal metastasis of colorectal cancer and classified them according to the largest lesion size, number of lesions and number of regional peritoneal metastases. The oncological data were recorded and compared. Results According to the univariate analyses, the prognoses were significantly better in patients with <= 3 disseminated lesions than in those with >= 4, and in patients with disseminated lesions in only one region than in those with >= 2 lesions. A multivariate analysis showed that primary tumor resection and the presence of peritoneal metastases in only one region were favorable factors for the patient survival. Patients with disseminated lesions in only one region (localized group) and those with nonlocalized lesions had three-year survival rates of 45.6 and 12.2 %, respectively. Finally, primary tumor resection improved the prognoses in both the localized and nonlocalized groups. Conclusions Colorectal cancer patients were categorized into localized and nonlocalized groups according to the number of regions with peritoneal metastasis, and significant prognostic associations were demonstrated. Subsequent analyses of the oncological data suggested that primary tumor resection contributes to an improved prognosis in all patients with synchronous peritoneal metastases.

Purposes This study prospectively assessed the sexual and urinary functions, as well as factors influencing these functions, in patients who underwent open or robotic surgery for rectal cancer. Methods Forty-five consecutive male patients who underwent rectal resection for rectal cancer were prospectively enrolled in this study. Their sexual and urinary functions were assessed through self-administered questionnaires comprising the International Index of Erectile Function (IIEF; sexual function) and the International Prostate Symptom Score (IPSS; urinary function) before and at 3, 6, and 12 months after surgery. Results Fifteen patients who underwent robotic surgery and 22 who underwent open surgery were finally analyzed in this study. The total IIEF score and the individual score items did not change at 3, 6 or, 12 months after open or robotic surgery compared with the preoperative values. However, a univariate analysis revealed that age affected the urinary function 12 months after surgery, while both univariate and multivariate analyses revealed that postoperative complications affected the sexual function 12 months after surgery. Conclusions In this non-randomized comparison, the postoperative sexual and urinary functions were comparable between patients who underwent open rectal surgery and those who underwent robotic rectal surgery. Postoperative complications were a risk factor for sexual dysfunction, while age was a risk factor for urinary dysfunction.

Background/Aims: Peritoneal metastasis (PM) is a wellknown predictor of poor prognosis. This study aims at identifying factors affecting recurrence and prognosis after R0 resection for colorectal cancer (CRC) with synchronous PM. Methods: A multi-institutional, retrospective analysis of 172 patients with R0 surgery for CRC with PM was conducted. Clinicopathological variables were analyzed for their significance in contributing toward recurrence and prognosis. Results: Lymph node (LN) metastasis was an independent factor affecting recurrence as indicated by logistic regression analyses. The following factors were independent predictors of poor prognostic using the Cox proportional hazard model: LN metastasis, no postoperative adjuvant chemotherapy, five or fewer dissected LNs, and preoperative high serum carbohydrate antigen 19-9 levels. Of the patients undergoing postoperative adjuvant chemotherapy, no significant differences were observed in recurrence rate and disease-free interval between those with intensive adjuvant chemotherapy and those with non-intensive chemotherapy. After R0 surgery for PM, 90 patients (76.3%) experienced recurrence by 18 months, and hematogenous recurrence occurred significantly more often than peritoneal recurrence. Conclusion: Harvesting of more than 5 LNs and administration of postoperative adjuvant chemotherapy after R0 surgery are recommended for prognosis improvement. Intensive follow-up should be performed within 18 months after R0 surgery for CRC with synchronous PM. (C) 2016 S. Karger AG, Basel

BACKGROUND: Routine creation of a diverting stoma (DS) in every patient who undergoes low anterior resection (LAR) remains controversial. We aimed to investigate the effect of DS on symptomatic anastomotic leakage (AL) after LAR. STUDY DESIGN: Patients with rectal cancer within 10 cm from the anal verge were eligible for this prospective, multicenter, cohort study (UMIN-CTR, number 000004017). Propensity score matching (PSM) was used to compare groups of patients with and without DS. RESULTS: One thousand fourteen consecutive patients were registered, of whom 936 patients who underwent LAR were analyzed. Before PSM, the overall rate of symptomatic AL was 13.2% (52 of 394) in patients with DS vs 12.7% (69 of 542) in cases without DS (p = 0.84). Symptomatic AL requiring re-laparotomy occurred in 4.7% (44 of 936) of all patients, occurring in 1.0% (4 of 394) of patients with DS vs 7.4% (40 of 542) of patients without DS (p < 0.001). After PSM, the 2 groups were nearly balanced, and the incidence rates of symptomatic AL in patients with and without DS were 10.9% and 15.8% (p = 0.26). The incidences of AL requiring re-laparotomy in patients with and without DS were 0.6% and 9.1% (p < 0.001). Multivariate analysis identified male sex (p < 0.001; odds ratio [OR] 3.2; 95% confidence interval [CI] 1.8 to 5.7) and tumor size (p < 0.001; OR 1.2; 95% CI 1.1 to 1.4) as independent risk factors of symptomatic AL. CONCLUSIONS: Diverting stoma did not have a significant relationship with symptomatic AL before and after PSM. However, DS does seem to mitigate the consequences of leakage, reducing the need for urgent abdominal reoperation. ((C) 2015 by the American College of Surgeons)

Background: Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%-20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found that the pH of a solution of dexamethasone and oxaliplatin was less than 7.4, and that hypersensitivity to oxaliplatin could have been prevented by coinfusion of dexamethasone. We aimed to evaluate the effectiveness of coinfusion of dexamethasone and oxaliplatin to prevent oxaliplatin-induced hypersensitivity reactions. Patients and methods: The AVOID trial was a prospective, multicenter, open-label, singlearm Phase II trial conducted from January to September 2013. The study included 73 patients who received capecitabine plus oxaliplatin (XELOX) or XELOX plus bevacizumab therapy for colorectal cancer. In all patients, oxaliplatin was administered in combination with dexamethasone. The primary outcome measure was the presence of hypersensitivity reactions. Results: Hypersensitivity reactions occurred in three patients (4.1%); all three experienced a cutaneous reaction (grade 1 erythema). None of the 73 patients developed respiratory symptoms, ocular symptoms, or anaphylaxis. Grade 3 or higher hemotoxicity occurred in 13.7% of the patients and grade 3 or higher nonhematological toxicity occurred in 13.7%. The response rate to treatment was 64.4%. Conclusion: The coinfusion of dexamethasone and oxaliplatin effectively reduced oxaliplatin-induced hypersensitivity reactions in patients with colorectal cancer. This approach should be considered for all patients treated with oxaliplatin, allowing treatment to be completed as planned.

Local excision is increasingly performed for "early stage'' rectal cancer in the US; however, local recurrence after local excision has become a controversial issue in Western countries. Local recurrence is considered to originate based on the type of tumor and procedure performed, and in surgical margin-positive cases. This review focuses on the inclusion criteria of "early" rectal cancers for local excision from the Western and Japanese points of view. "Early" rectal cancer is defined as T1 cancer in the rectum. Only the tumor grade and depth of invasion are the "high risk" factors which can be evaluated before treatment. T1 cancers with sm1 or submucosal invasion <1,000 mu m are considered to be "low risk" tumors with less than 3.2 % nodal involvement, and are considered to be candidates for local excision as the sole curative surgery. Tumors with a poor tumor grade should be excluded from local excision. Digital examination, endoscopy or proctoscopy with biopsy, a barium enema study and endorectal ultrasonography are useful for identifying "low risk" or excluding "high risk" factors pre-operatively for a comprehensive diagnosis. The selection of an initial local treatment modality is also considered to be important according to the analysis of the nodal involvement rate after initial local treatment and after radical surgery.

A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC). From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI. A total of 195 patients with UC who underwent colorectal surgery were enrolled. SSI was diagnosed in 38 (19.5 %) patients, in the form of incisional infection in 23 (11.8 %), organ/space infection in 16 (8.2 %), and both in 1 (0.5 %). There were no significant risk factors associated with an increased risk of development of incisional SSI. An American Society of Anesthesiologists physical status of a parts per thousand yen 3 was indicated as the only significant risk factor for organ/space SSI (P = 0.02) compared with other factors, such as a neutrophil count of > 100 x 10(2)/mm(3), albumin level of < 3.5 g/dl, perioperative packed red blood cell transfusion, fair or poor colonic cleanliness, and therapeutic use of antibiotics. Poor general physical status was the significant independent risk factor for organ/space SSI in patients with UC in Japan.

To establish the efficiency of bowel ligatures in colon cancer surgery, focusing on the extent to which exfoliated cancer cells are shed in the colonic lumen during sigmoidectomy. Twenty consecutive patients who underwent sigmoidectomy for sigmoid colon cancer were prospectively randomized into two groups: the "ligatures group", in which bowel ligatures were placed, 3, 5, 10 cm from the tumor proximally and distally before dissection; and the "no ligatures group", in which the corresponding sites were ligated only immediately before taking the specimen out. Each colonic segment ligated was irrigated with saline and samples were sent for blind cytological examination. Cancer cells were found in the colonic segment where the tumor was located, in 18 of 20 samples. The frequency of free cancer cells decreased from 50 to 0 % (p < 0.04) in the distal 3-5 cm colonic segment and from 80 to 20 % (p < 0.03) in the proximal colonic segment after performing bowel ligatures. Free cancer cells were confirmed in 1 of 10 samples at both colonic segments 5-10 cm from the tumor, even after bowel ligatures. Intraluminal exfoliated cancer cells could be eliminated by placing bowel ligatures during sigmoidectomy. Measures should be considered to eliminate exfoliated cancer cells during colectomy, even after placing bowel ligatures.

Oxaliplatin is currently approved for patients with metastatic colorectal cancer (mCRC). Its uptake and consequent cytotoxicity is determined by the levels of organic cation transporter 2 (OCT2). In addition, tumor budding (TB) is associated with high malignant potential. However, the impact of the levels of OCT2 and TB on clinicopathological findings and the prognosis of mCRC patients treated with oxaliplatin-based chemotherapy remains unclear. Here, 80 mCRC patients were retrospectively assessed. Immunohistochemistry was performed to determine the levels of OCT2 and TB. High levels of OCT2 (47/80, 59%) were detected at the invasion front and were associated with depth of invasion (P=0.03), whereas high levels of TB (40/80, 50%) were associated with extensive lymphatic invasion (P=0.03). In univariate analysis, high OCT2 levels were significantly correlated with longer progression-free survival (PFS) (P=0.02) whereas high TB levels were associated with shorter PFS (P=0.01). In combined analysis, patients with 2 favorable factors (high OCT2/low TB) had longer PFS than those with 1 (P=0.03) or 0 (P<0.001) favorable factors. Multivariate analysis confirmed that the OCT2 level (P=0.007), TB level (P=0.004), and combined OCT2/TB status (P=0.001) were independent predictors for PFS. These results suggest that high levels of OCT2 indicate severe invasion, but also better prognosis in mCRC patients treated with oxaliplatin-based chemotherapy, possibly because of its role in oxaliplatin susceptibility. Combined analysis of OCT2 and TB status may guide the selection of patients for successful oxaliplatin-based chemotherapy.

Although metastatic colorectal cancer (mCRC) is commonly treated with 5-fluorouracil (5-FU)/leucovorin/ oxaliplatin (FOLFOX), their response to FOLFOX varies, and no biomarkers predictive of treatment outcome have been validated. Organic anion transporter 2 (OAT2) and organic cation transporter 2 (OCT2) are critical determinants in uptake of 5-FU and oxaliplatin, respectively. In this study, we evaluated whether OAT2 and OCT2 levels can predict effectiveness of FOLFOX-based therapy. We retrospectively assessed 90 patients with mCRC who were treated with first-line FOLFOX with or without bevacizumab. We immunohistochemically determined OAT2 and OCT2 expression levels at invasion fronts of their tumors and correlated the levels to clinicopathological parameters, including objective tumor response (OTR) and progression-free survival (PFS). High expression of OAT2 (OAT2(High)) and OCT2 (OCT2(High)) were detected in 36% and 60% of the tumors, respectively. OCT2(High) was significantly associated with invasion depth (P = 0.03), whereas OAT2(High) was not associated with any clinicopathological parameters. In univariate analysis, OAT2(High) was significantly correlated with good OTR (P = 0.02), and OCT2(High) with long PFS (P = 0.03). Multivariate analyses showed that OAT2(High) and OCT2(High), respectively, were the sole independent predictors of good OTR (P = 0.02) and long PFS (P = 0.03). We found that patients with OAT2(High)/OCT2(High) showed the best treatment outcomes (good OTR and long PFS) with significantly higher frequency than patients with other expression patterns (P = 0.003). OAT2(High)/OCT2(High) status was also the only independent predictive factor in multivariate analysis. This study suggests that OAT2(High) and OCT2(High) are important independent predictors of good outcomes in FOLFOX-treated mCRC.

Purpose Continuous treatment with FOLFOX therapy is associated with peripheral nerve toxicity, and to improve this inconvenient side effect various methods of administration are being investigated. A regimen of intermittent oxaliplatin administration by continuous infusion therapy, i.e., modified FOLFOX7 (mFOLFOX7) + bevacizumab, was designed with the goal of alleviating severe peripheral nerve disorders and hematological toxicity. A phase II clinical study was conducted to evaluate the efficacy and safety of this regimen. Methods Previously untreated patients were assigned to mFOLFOX7 (oxaliplatin 85 mg/m(2), levofolinate [l-LV] 200 mg/m(2), 5-fluorouracil [5-FU] 2400 mg/m(2)) + bevacizumab (5 mg/kg) administered every 2 weeks for 8 cycles, maintenance without oxaliplatin for 8 cycles, and reintroduction of mFOLFOX7 + bevacizumab for 8 cycles or until disease progression. Progression free survival (PFS) following the first dose (PFS 1) and following reintroduction of oxaliplatin (PFS 2) were used as indices for assessing the efficacy of intermittent administration. Results Fifty-two patients were enrolled, with median age of 64 years (range, 36-74). Median PFS 1 was 11.8 months (95 % confidence interval [CI], 9.5 to 13.7), median time to treatment failure was 10.3 months (95 % CI, 5.6 to 12.1), percentage of patients with neutropenia of grade 3 or higher was 7.8 %, and percentage with peripheral nerve disorders was 3.9 %. Response rate was 50 %, and 84.4 % of patients who started modified simplified LV5FU2 + bevacizumab were reintroduced to oxaliplatin. Conclusion By excluding 5-FU bolus administration and administering bevacizumab continuously the mFOLFOX7 + bevacizumab regimen with preplanned withdrawal of oxaliplatin showed high tolerability and prevented severe peripheral neuropathy and neutropenia without reducing efficacy.

BACKGROUND: Recurrence of Crohn's disease usually occurs at anastomotic sites. OBJECTIVE: A new anastomosis technique (Kono-S anastomosis) designed to minimize anastomotic restenosis was compared with conventional anastomoses. DESIGN AND SETTINGS: The Kono-S anastomosis technique was first used for Crohn's disease in 2003 at the Asahikawa Medical University Hospital. The resection is accomplished by transecting the bowel with a linear cutter so that the mesentery side is located in the center of the stump. Both stumps are sutured to create a supporting column to maintain the diameter and dimension of the anastomosis. Longitudinal enterotomies are made at the antimesenteric sides of the 2 segments of intestine. The side-to-side antimesenteric anastomosis is then performed in transverse fashion. The medical records and follow-up details of all patients undergoing this procedure were reviewed. PATIENTS: From 2003 to 2009, 69 patients with Crohn's disease who underwent Kono-S anastomosis (group S) were compared with 73 historical patients with Crohn's disease who underwent conventional anastomosis (group C) from 1993 to 2003. MAIN OUTCOME MEASURES: A Kaplan-Meier analysis of the follow-up data on surgical recurrence at the anastomosis was performed. The endoscopic recurrence score at the anastomosis was calculated. RESULTS: The median endoscopic recurrence score in group S was significantly lower than that in group C (2.6 vs 3.4; P = .008). The Kaplan-Meier analysis showed a lesser probability of anastomotic surgical recurrence in the S group at 5 years (0% vs 15%; P = .0013). The absence of postoperative infliximab did not affect the restenosis rate in group S. LIMITATIONS: This study was limited by its historical retrospective nature. CONCLUSION: The Kono-S anastomosis appears to be effective in preventing anastomotic surgical recurrence in Crohn's disease.

We evaluated the effect of hepatic arterial infusion (HAI) chemotherapy for liver metastases from colorectal cancer. A total of 65 patients received HAI chemotherapy. The chemotherapy regimen consisted of weekly 5-FU (1, 500 mg/body) or 5-FU (400 mg/mm2) and /-LV (200 mg/mm2). The survival and response rates were assessed according to RECIST. Median survival time with HAI chemotherapy was 13.5 months, 5-year survival rate 8% and response rates 55%. There was no evidence of myelosuppression, and HAI could be continued for a long time even for poor PS patients. There were no differences in survival time between synchronous, metachronous and postoperative metachronous liver metastases. In the patients who underwent curative hepatectomy after HAI chemotherapy, the 5-year survival rate was 21%, which was better than in patients with HAI chemotherapy alone. HAI chemotherapy could thus be an option for unresectable liver metastases, which could be well tolerated.

Hepatic resection for colorectal metastases was performed for 188 patients. Overall survival rates after the first hepatectomy are 41.4% and 32.7% for 5 and 10 years, respectively. The survival rate of 116 cases with unilobar hepatic metastases (H1) is significantly higher than those of 48 cases with two to four bilobar metastases (H2) and 24 cases with more than four (H3), respectively. However, the differences between the survival rates from H1 with multiple metastases, H2, and H3 are not significant, even though the H3 group has no 10-year survivors. The 5-year survival rates after the second hepatectomy (30 patients) and the resection of the lung (26 patients) are 30.3% and 35.2%, respectively, in this series. In those patients, the 5-year survival rates from the first metastasectomy are 43.4% and 50.3%, respectively. There are 14 5-year survivors with multiple metastases and 8 of those patients underwent multiple surgeries. There are 13 patients with three or more repeat resections of the liver and/or lung. The 5-year survival rates of the patients from the first and third metastasectomy are 53.9% and 22.5%, respectively. Repeat operations for the liver and the lung contribute to the improving prognosis.

Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelia] cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.

Background: Our previous analyses on the expression of thymidylate synthase (TS) and p16(INK4a) in colorectal cancer patients administered 5-fluorouracil (5-FU) pre-operatively demonstrated that a high level of TS expression was a predictor of 5-FU resistance, and that the combination of a low level of TS expression and induction of p16(INK4a) after chemotherapy implicated chemosensitivity. The present study aimed to assess the relationship between the biological behavior of advanced colorectal cancer treated post-operatively by 5-FU-based chemotherapy and the expression of TS and p16(INK4a) in primary tumors. Methods: Formalin-fixed, paraffin-embedded specimens from 132 colorectal cancers (Dukes' B, 36 cases; Dukes' C, 60 cases; and Dukes' D, 36 cases) treated by 5-FU post-operatively were immunostained for TS and p16(INK4a). Antigenicities were suitably retrieved. Results: Primary tumors expressing high levels of TS in the Dukes' C group showed a significantly shorter recurrence-free interval (RFI) (P = 0.0002). The overall survival (OS) was shorter in high TS expressors than in low TS expressors (P = 0.001). A high level of TS expression also correlated with advanced Dukes' staging and the severity of nodal metastasis (Dukes' B versus Dukes' D, P = 0.001; Dukes' C versus Dukes' D, P = 0.008; N0 versus N2, P = 0.002; N1 versus N2, P = 0.03). p16(INK4a) expression was not correlated with the prognosis or clinicopathological features. Conclusions: Appropriate immunohistochemical evaluation is essentially important. We suggest that, in the Dukes' C group, a 5-FU-based regimen can be chosen as a first-line chemotherapy for low TS expressors. TS-high cancer should be treated with anti-cancer agents acting through different mechanisms. Further research should be conducted on applying TS immunostaining to the treatment strategy.