Mechanical bowel preparation combined with oral antibiotics in colorectal cancer surgery: a nationwide population-based study.

BACKGROUND: The guidelines for reducing surgical site infection in colorectal surgery recommend mechanical bowel preparation with oral antibiotics; however, this recommendation remains controversial. This study aimed to reveal the effect of oral antibiotics combined with mechanical bowel preparation in colorectal surgery. METHODS: This study was a nationwide population-based retrospective study. Data between January 1, 2016, and December 31, 2018, from the Korean National Health Insurance Service database were analyzed. Patients who underwent elective colorectal cancer surgery were included. RESULTS: A total of 20,740 patients were finally included, comprising 14,554 (70.2%) who underwent mechanical bowel preparation alone and 6186 (29.8%) who underwent mechanical bowel preparation with oral antibiotics. The mechanical bowel preparation alone group was older than the mechanical bowel preparation with oral antibiotics group (65.7 ± 11.9 vs. 64.7 ± 11.8 years, p < 0.001). Rectal cancer patients and patients who underwent open surgery were more likely to receive mechanical bowel preparation with oral antibiotics. Patients who underwent mechanical bowel preparation with oral antibiotics demonstrated lower surgical-site infection rate (2.9% vs. 9.4%, p < 0.001), shorter hospital stay (11.7 ± 5.5 vs. 13.5 ± 7.3 days, p < 0.001), and lower medical cost (US$7414 ± 2762 vs. US$7791 ± 3235, p < 0.001) than those who underwent mechanical bowel preparation alone. The 30-day readmission rates and mortality were not significantly different. CONCLUSIONS: The use of mechanical bowel preparation with oral antibiotics reduces surgical site infection, hospital stay, and medical cost in colorectal cancer surgery.

Conservative treatment of uncomplicated right-sided diverticulitis: a systematic review and meta-analysis.

PURPOSE: Right-sided diverticulitis has different epidemiologic features compared to left-sided diverticulitis. However, data on the appropriate treatment of right-sided diverticulitis are lacking. This systematic review aimed to examine the outcomes of conservative treatment for uncomplicated right-sided diverticulitis. METHODS: MEDLINE, Embase, and the Cochrane Library were searched for articles published from January 1, 1990, to May 31, 2020. A total of 21 studies were included in the systematic review. We calculated proportions and 95% confidence intervals (CIs) to assess the outcomes of individual studies and pooled the results using a random effects model. RESULTS: A total of 2811 patients (59.1% men; mean and median age, 37-54 years) with right-sided diverticulitis were included. The pooled rate of treatment failure was 2.5% (95% CI 1.2-4.3%; p <0.01; I2 = 64.0%). The recurrence rate ranged from 0 to 26.9%, and the pooled recurrence rate was 10.9% (95% CI 8.1-14.1%; p <0.01; I2 = 78.2%). The pooled rate of complicated diverticulitis at recurrence was 4.4% (95% CI 1.4-9.0%; p = 0.84; I2 = 0%). The pooled rate of emergency surgery at recurrence was 9.0% (95% CI 4.6-14.7%; p = 0.12; I2 = 30.3%). CONCLUSIONS: Conservative treatment of uncomplicated right-sided diverticulitis results in a low rate of recurrence and complicated diverticulitis at recurrence. Based on these results, unnecessary surgery may be avoided and a new treatment paradigm for uncomplicated right-sided diverticulitis may be introduced.

Complications Following the Use of Biologic Mesh in Ileostomy Closure: A Retrospective, Comparative Study.

Prophylactic placement of mesh in the abdominal wall during ileostomy closure can decrease the rate of hernia formation. However, few studies have evaluated the safety of biologic mesh in ileostomy closure. PURPOSE: This study aimed to investigate the safety of biologic mesh in ileostomy closure, specifically the need to remove the mesh due to infection. The rate of surgical site infection (SSI), incisional hernia, surgical site occurrence ([SSO] including seroma and hematoma), and wound pain between primary closure and mesh closure groups also were investigated. METHODS: Using a retrospective study design, data from all consecutive patients who underwent ileostomy closure from January 2015 to June 2016 at the Hanyang University Hospital, Seoul, Republic of Korea, were analyzed. Patients with stage IV colorectal cancer, who were older than 85 years, or who experienced intestinal perforation during the procedure were excluded. Demographic (age, sex, body mass index [BMI], underlying disease) and clinical characteristics as well as SSI, SSO, length of hospital stay, use of additional analgesics, white blood cell count, C-reactive protein, and visual analog scale (VAS) pain scores (noted on days 1, 3, 5, and 14) were abstracted and compared. Clinical and surgical variables were compared using the Mann-Whitney U test, the χ2-test, or Fisher's exact test, depending on the nature of the data. RESULTS: Of the 38 patients who underwent ileostomy closure, 33 (18 [54.5%] who received primary closure and 15 [45.5%] who received mesh closure) were included for analysis. Patient, surgical, and clinical characteristics were not significantly different, but the mean age of the primary closure group was significantly higher than that of the mesh closure group (71 ± 9 vs. 62 ± 10 years old; P = .014). The median follow-up duration was 25 months (interquartile range 18.0-31.5 months). Six (6) complications were observed in 5 patients in the primary closure group, and 8 complications in 5 patients were noted in the mesh closure group (27.8% vs. 33.3%; P = 1.000). None of the cases required removal of the biologic mesh due to mesh-related infectious complication. Two (2) SSIs occurred in the primary closure group (11.1% vs. 0%; P = .489). Three (3) patients experienced a postoperative incisional hernia (9.1%) - 1 in the primary closure group and 2 in the mesh closure group (5.6% vs. 13.3%; P = .579). No statistically significant differences in pain or length of hospitalization were noted. CONCLUSION: No mesh-related infectious complications required biologic mesh removal, and no significant differences were noted in SSI, incisional hernia, and wound pain between the primary closure and mesh closure groups. Although not significantly different, the higher rates of hernia and SSOs in the mesh group require further study.

Prognostic value of B-cell linker protein in colorectal cancer.

This study aimed to investigate the clinicopathological and prognostic impact of B-cell linker (BLNK) protein expression in colorectal cancer (CRC) as its function in CRC remains unexplored. We performed immunohistochemical staining for BLNK using tissue microarrays of 418 consecutive CRC samples; of these 10 were excluded due to inappropriate staining. The expression intensity and staining level was scored as 0-3 and 0-4, respectively, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying these two scores. BLNK expression was observed in 222 patients (54.4 %). Lymph node metastasis (p = 0.031), right colon cancer (p = 0.026), mucinous adenocarcinoma (p < 0.001), and perineural invasion (p = 0.049) were more frequently observed in the IRS 4-12 group than in the IRS 0-3 group. At the same cutoff point, the 5-year recurrence-free survival rate of the patients with stage III was significantly lower than that observed in IRS 4-12 group (74.8 % ± 4.2 % vs. 54.2 % ± 8.5 %, p = 0.003). Multivariate analysis revealed IRS 4-12 to be an independent risk factor for recurrence (Hazard ratio 2.346, 95 % confidence interval 1.348-4.085, p = 0.003). In conclusion, overexpression of BLNK protein is an independent risk factor for CRC recurrence.

Comprehensive Analysis of Somatic Mutations in Colorectal Cancer With Peritoneal Metastasis.

BACKGROUND: To analyze for genetic mutations which may presage peritoneal metastasis by using targeted next-generation sequencing (NGS). MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded primary tumor specimens were obtained from 10 patients with small obstructing colorectal cancer and peritoneal metastasis (group A) and five with large non-obstructing colorectal cancer and no recurrence (group B). DNA was extracted for the sequencing of 409 cancer genes. The distribution of genetic mutations was compared between the two groups to find genetic mutations related to peritoneal metastasis. RESULTS: When the samples were sorted based on similarity of gene expression by hierarchical clustering analysis, the samples were well divided between the two study groups. Mutations in AT-rich interactive domain-containing protein 1A (ARID1A), polycystic kidney and hepatic disease 1 (PKHD1), ubiquitin-protein ligase E3 component n-recognin 5 (UBR5), paired box 5 (PAX5), tumor protein p53 (TP53), additional sex combs like 1 (ASXL1) and androgen receptor (AR) genes were detected more frequently in group A. CONCLUSION: A number of somatic mutations presumed to be relevant to colorectal cancer with peritoneal metastasis were identified in our study by NGS.

The usefulness of the status of extranodal tumor extension as a factor that can predict the recurrence of stage III colorectal cancer.

Background: Extranodal tumor extension (ENTE) is considered a poor prognostic factor in colorectal cancer (CRC). This study aimed to investigate the risk factors for recurrence according to ENTE status in stage III CRC. Methods: We retrospectively evaluated 169 consecutive stage III CRC patients. All patients underwent a curative resection between 2005 and 2010. The presence or absence of ENTE was assessed in the resected lymph nodes. Results: ENTE was observed in 65 (38.5%). Recurrence occurred in 38 patients (22.5%) and was more frequent (p = .041) in the ENTE (+) group. Disease-free survival (p = .016) was significantly shorter in the ENTE (+) group than in the ENTE (-) group. In a univariable analysis, recurrence was associated with vascular invasion (p = .006), perforation (p = .024) in the ENTE (-) group and perforation (p = .048) in the ENTE (+) group. In a Cox's regression test, vascular invasion (p = .014) and the higher ratio of metastatic lymph nodes/total removed lymph nodes (MLN/TLN) (0.009) in the ENTE (-) group and perforation (p = .025) in the ENTE (+) group were independent risk factors of recurrence. Conclusions: Vascular invasion and the higher ratio of MLN/TLN in ENTE (-) patients and perforation in ENTE (+) patients were independent risk factors of recurrence.

Cyclooxygenase-2 Expression Is a Predictive Marker for Late Recurrence in Colorectal Cancer.

INTRODUCTION: Cyclooxygenase-2 (COX-2) expression is elevated in colorectal cancer (CRC). However, data about the relation between COX-2 expression and the impact on the biologic behavior of recurrent disease are inconclusive as yet. The aim of this study is to investigate the relationship between the status of COX-2 expression in the primary CRC and the characteristics of recurrence after curative resection of stage I to III CRC. MATERIALS AND METHODS: Ninety-eight patients with recurrence in 376 CRC patients, who underwent curative surgery between January 1991 and August 2001, were retrospectively assessed. Immunohistochemical staining, performed for the presence of COX-2 on tissue microarrays, was analyzed. RESULTS: Forty-six patients showed elevated COX-2 expression, and 52 patients did not. The mean time to recurrence was significantly longer in the positive group than in the negative group (34.1 months ± 30.0 versus 21.9 months ± 17.4; P = 0.019). Positive COX-2 expression was correlated with late recurrence (>3 years after surgery) [43.5% versus 13.5%; P = 0.001]. In multivariate analysis, COX-2 expression was an independent factor associated with late recurrence (OR 4.656; 95% CI, 1.696 to 12.779; P = 0.003). Recurrence pattern and postrecurrence survival were not different between the two groups. CONCLUSIONS: Elevated COX-2 expression in itself is not a prognostic factor, but COX-2 expression in tumor tissue may be an independent predictive marker of late recurrence for patients with stage I to III CRC.

Higher visceral fat area/subcutaneous fat area ratio measured by computed tomography is associated with recurrence and poor survival in patients with mid and low rectal cancers.

PURPOSE: Obesity is thought to influence postoperative complications and recurrence of mid and low rectal cancer (MLRC) because of intraoperative technical difficulties. However, few reports have described the relationship between obesity indices and the clinical outcomes of MLRC. This study aimed to investigate the association between visceral obesity on computed tomography (CT) and oncolofical outcomes after surgery for MLRC and identify the obesity index that most accurately reflects clinical outcomes. METHODS: We investigated 125 patients who underwent curative resection for MLRC between 2004 and 2010. Visceral fat area (VFA) was defined as the umbilicus-level intra-abdominal adipose tissue area measured by CT. Body mass index (BMI), total fat area, VFA, subcutaneous fat area (SFA) and VFA/SFA ratio (V/S ratio) were analysed. RESULTS: The median follow-up time was 60.3 months (range, 38.2-122.6 months). Recurrence was detected in 28 (22.4%) patients. Among the various obesity indices, recurrence was significantly associated with V/S ratio only (1.02 ± 0.45 versus 0.86 ± 0.34; P = 0.046). Stage, preoperative carcinoembryonic antigen level, V/S ratio, lymphatic invasion and perineural invasion were significantly associated with recurrence on univariate analysis, while only V/S ratio (P = 0.019; 95% confidence interval, 1.22 to 9.09) was significantly associated with recurrence on multivariate analysis. Disease-free and overall survival of the obese group (V/S ratio > 1.0) were shorter than those of the non-obese group. CONCLUSIONS: V/S ratio is the optimal obesity index for predicting stage I-III MLRC recurrence.

Loss of Wnt7a expression correlates with tumor progression and poor prognosis in colorectal carcinoma.

Wnt7a is a known tumor suppressor gene in non-small cell lung cancer that regulates normal cellular proliferation and differentiation. The purpose of this study was to investigate the clinicopathologic significance of Wnt7a expression in colorectal adenocarcinoma. Wnt7a expression was immunohistochemically examined in 46 normal colorectal tissues, 47 tubular adenomas, 393 adenocarcinomas, and 93 lymph node metastases. Wnt7a was expressed in the cytoplasm. Loss of Wnt7a expression was more frequent in adenocarcinoma and lymph node metastasis compared to that in normal and tubular adenoma (P < 0.001). Wnt7a expression was inversely correlated with tumor size (P = 0.026), gross type (P = 0.008), differentiation (P = 0.009), vascular invasion (P = 0.038), tumor deposit (P = 0.007), tumor invasion (T category) (P = 0.003), lymph node metastasis (N category) (P < 0.001), and AJCC stage (P < 0.001). There was a significant correlation between loss of Wnt7a expression and overall survival and disease-free survival (P < 0.001 and P = 0.001, respectively) on univariable analysis. On multivariable analysis, loss of Wnt7a expression was an independent prognostic factor for both overall and disease-free survival (P = 0.002 and P = 0.047, respectively). Loss of Wnt7a expression may contribute to the carcinogenesis and tumor progression of colorectal adenocarcinoma and may be a new prognostic marker of colorectal adenocarcinoma.

Loss of APAF-1 expression is associated with early recurrence in stage I, II, and III colorectal cancer.

PURPOSE: Apoptotic protease activating factor-1 (APAF-1) is a key regulator in the mitochondrial apoptotic pathway and an important diagnostic and therapeutic biomarker. Loss of APAF-1 expression has been observed in various tumors including colorectal cancer. The aim of our study was to evaluate the relationship between loss of APAF-1 expression and early recurrence of stage I-III colorectal cancer. METHODS: We investigated 165 out of 492 patients who had undergone curative resection for colorectal cancer between 1991 and 2001. Sixty-one patients (37.0 %) had early recurrence within 1 year after surgery. Tissue microarrays were used for immunohistochemical detection of APAF-1. RESULTS: The mean age of patients with recurrence was 58 years (range, 24-85); 88 (53.3 %, 88/165) were male. APAF-1 was expressed in 32 (19.4 %, 32/165) cases and was not expressed in 133 (80.6 %, 133/165). In univariate analysis, early recurrence significantly correlated with loss of APAF-1 expression (p = 0.017), tumor stage (p = 0.005), N category (p = 0.001), and lymphatic invasion (p = 0.008). In a logistic regression model, loss of APAF-1 expression (p = 0.015, 95 % CI = 1.280-10.063) and N category (p = 0.001, 95 % CI = 0.004-0.739) proved to be independent risk factors associated with early recurrence. In patients with lymph node metastasis, early recurrence was more frequent in the APAF-1-negative group than in the APAF-1-positive group (46.2 % (54/117) vs. 22.2 % (6/27), p = 0.023). CONCLUSIONS: Loss of APAF-1 expression is associated with early recurrence in stage I-III colorectal cancer, suggesting that APAF-1 may have clinical value as a predictive marker of early recurrence.

Visceral Obesity Predicts Fewer Lymph Node Metastases and Better Overall Survival in Colon Cancer.

BACKGROUND: The relationship between visceral obesity and colon cancer outcome has not been well studied. The goal of this study was to determine the impact of visceral obesity on lymph node (LN) metastasis and overall survival (OS) in colon cancer. MATERIALS AND METHODS: Metastatic LN ratio (MLR) was defined as the number of involved nodes by tumor divided by the total number of resected LNs. Visceral (VFA) and subcutaneous fat areas (SFA) were determined by measuring abdominal fat volume distribution via CT scan, and visceral obesity was defined as a VFA to total fat area ratio (V/T) > 0.29. RESULTS: In a multivariate analysis among 186 patients, there were inverse associations between V/T and MLR (OR = 0.413, 95% CI = 0.216-0.789, P = 0.007). Furthermore, patients with visceral obesity tended to have significantly better OS than patients with non-visceral obesity. CONCLUSIONS: Higher V/T ratios which indicate referring to visceral obesity was significantly associated with decreased MLR and better OS for CRC.

Immunohistochemical expression of dual-specificity protein phosphatase 4 in patients with colorectal adenocarcinoma.

The role of dual-specificity protein phosphatase 4 (DUSP4) appears to vary with the type of malignant tumors and is still controversial. The purpose of our study was to clarify the exact role of DUSP4 expression in colorectal adenocarcinoma. We constructed tissue microarrays and investigated DUSP4 expression by immunohistochemistry. DUSP4 was more frequently expressed in adenocarcinomas and lymph node/distant metastases compared to that in normal colorectal tissues and tubular adenomas (P < 0.001). Mean DUSP4 expression score was significantly higher in malignant tumors than in benign lesions (P < 0.001). DUSP4 expression was significantly correlated with older age (P = 0.017), male gender (P = 0.036), larger tumor size (P = 0.014), nonmucinous tumor type (P = 0.023), and higher T stage (P = 0.040). Kaplan-Meier survival curves revealed a significant effect of DUSP4 expression on both overall survival and disease-free survival in AJCC stage I (P = 0.008 and P = 0.003, resp., log-rank test) and male gender (P = 0.017 and P = 0.049, resp., log-rank test). DUSP4 protein is frequently upregulated in colorectal adenocarcinoma and may play an important role in carcinogenesis and cancer progression and may be a marker of adverse prognosis.

The use of indocyanine green fluorescence to assess anastomotic perfusion during robotic assisted laparoscopic rectal surgery.

BACKGROUND: Decreased blood perfusion at an intestinal anastomosis may contribute to postoperative anastomotic leak (AL) resulting in substantial morbidity and mortality. Near-infrared (NIR) laparoscopy in conjunction with indocyanine green (ICG) allows for visualization of the microcirculation before formation of the anastomosis, thereby allowing the surgeon to choose the point of transection at an optimally perfused area. METHODS: This is a retrospective case-control analysis examining the effectiveness of NIR + ICG in reducing the rate of AL after low anterior resection (LAR) for rectal cancer. Records of patients undergoing robot-assisted LAR for rectal cancer with and without ICG were analyzed for the years 2011 and 2012. RESULTS: Among the 40 patients who underwent robotic LAR, NIR + ICG was used in 16 cases (41 %). Male patients accounted for the majority of cases in both groups (74 %). The median level of the anastomosis was 3.5 cm in the NIR + ICG group and 5.5 cm in the control group. There was no difference in the use of diverting ileostomy. In 3 patients (19 %), the use of NIR + ICG resulted in revision of the proximal bowel (colonic) transection point before formation of the anastomosis. The distal transection point was never revised. The rate of AL in the NIR + ICG group was 6 % versus 18 % in control group. CONCLUSIONS: ICG fluorescence may play a role in anastomotic tissue perfusion assessment and affect the AL rate. Larger prospective studies are needed to further validate this novel technology.

Short- and long-term outcomes of intracorporeal versus extracorporeal ileocolic anastomosis in laparoscopic right hemicolectomy for colon cancer.

BACKGROUND: We assessed the short- and long-term outcomes of intracorporeal ileocolic anastomosis (IA) in laparoscopic right hemicolectomy for colon cancer compared with extracorporeal anastomosis (EA). METHODS: A retrospective chart review of 86 consecutive patients who underwent laparoscopic right hemicolectomy for colon cancer from March 2005 to June 2010 was performed. RESULTS: There were 51 and 35 patients who underwent intracorporeal and extracorporeal anastomosis, respectively. The two groups were demographically comparable. The conversion rate to open surgery was 8.6 % in the EA group, but none in the IA group (p = 0.064). There was no significant difference in operative time, estimated blood loss, complications (intra-abdominal abscess, anastomotic leak, ileus, and wound infection), and length of hospital stay between the groups. There was no perioperative mortality in both groups. There was no significant difference in median number of retrieved lymph node. The overall survival and the disease-free survival at 3 years were not different between the groups. CONCLUSIONS: Compared with the extracorporeal anastomosis technique, intracorporeal ileocolic anastomosis produces comparable short- and long-term outcomes in laparoscopic right hemicolectomy for colon cancer.

Single-dose antibiotic prophylaxis is effective enough in colorectal surgery.

BACKGROUND: The aim of this study was to investigate the hypothesis that prevention of surgical site infection (SSI) is equally effective when patients receive single-dose (SD) or three-dose antibiotic prophylaxis with second-generation cephalosporin and metronidazole in elective colorectal surgery. METHODS: Ninety-three patients were enrolled from May 2009 to November 2010. The SD group received only one preoperative prophylactic intravenous dose and the three-dose or multiple-dose (MD) group received one preoperative prophylactic and two additional post-operative doses of second-generation cephalosporin and metronidazole. The incidence of infectious complications (SSI of the incision site and organ/space) was compared in the two groups. RESULTS: The overall post-operative infection rate did not differ between the two groups (16.7% in the SD versus 13.3% in the MD, P = 0.653). The incidence of SSI of the incision site and organ/space also did not differ between the groups (6.3% (3/48) versus 4.4% (2/45), P = 0.700; 4.2% versus 6.7%, P = 0.593, respectively). The number of antibiotics administered was not an independent risk factor for SSIs in multivariable analysis. CONCLUSIONS: SD antibiotic prophylaxis with second-generation cephalosporin and metronidazole is equivalent to a three-dose prophylaxis for preventing SSI in elective colorectal surgery. But further study would be needed to clarify this because of the small number of participants.

Clinicopathological significance of CADM4 expression, and its correlation with expression of E-cadherin and Ki-67 in colorectal adenocarcinomas.

AIMS: Cell adhesion molecule 4 (CADM4) is a novel tumour suppressor. The purpose of this study was to investigate the correlation between its expression and the expression of E-cadherin and Ki-67 in colorectal adenocarcinomas, as well as its effect on patient survival. METHODS: We evaluated CADM4 expression in tissue microarrays of 513 colorectal adenocarcinomas by immunohistochemistry. RESULTS: CADM4 was highly expressed in 210 of the 513 colorectal adenocarcinomas; expression was reduced in 185 cases and absent in the remaining cases. Loss of CADM4 expression was correlated with larger tumour size (6.2±2.1 cm vs 5.3±2.0 cm, p<0.001), mucinous tumour type (61.5% vs 20.9%, p<0.001), lymph node metastasis (31.4% vs 20.9%, p=0.022), higher Dukes stage (25.5% vs 19.6%, p=0.044), poorer differentiation (38.5% vs 18.8%, p<0.001), absence of E-cadherin expression (28.5% vs 16.0%, p=0.007) and presence of Ki-67 expression (27.3% vs 12.3%, p<0.001). In univariable Cox regression analysis, absence of CADM4 expression was associated with poorer overall survival (HR 0.712; 95% CI 0.512 to 0.989, p=0.042) and disease-free survival (HR 0.732; 95% CI 0.546 to 0.981, p=0.037). In multivariate analysis with the Cox proportional hazards model, CADM4 expression was not an independent prognostic factor of overall survival (HR 0.726; 95% CI 0.516 to 1.021, p=0.066) and disease-free survival (HR 0.762; 95% CI 0.563 to 1.033, p=0.080). CONCLUSIONS: Loss of CADM4 expression is relatively frequent in colorectal adenocarcinomas and may play an important role in cancer progression and patient survival.

Smad4 may help to identify a subset of colorectal cancer patients with early recurrence after curative therapy.

BACKGROUND/AIMS: Loss of Smad4 function is associated with the acquisition of advanced colorectal cancer phenotypes. We investigated the role of Smad4 as a prognostic marker after curative therapy. METHODOLOGY: Four hundred and twenty nine consecutive colorectal cancers were analyzed by tissue microarray-based immunohistochemical assay. RESULTS: Smad4 protein was expressed in 61.5% (24/39), 53.1% (77/145), 41.3% (78/189) and 34.8% (16/46) of stage I, II, III and IV cancers, respectively. Lymphovascular invasion and lymph node metastasis were strongly correlated with the loss of Smad4 expression (p<0.0001 and p=0.002, respectively). Disease-free survival did not differ between Smad4-positive and Smad4-negative cancers. In stage III disease, time to recurrence after curative therapy was shorter in the Smad4-negative than in the Smad4- positive cancers (20.1±15.1 vs. 34.6 ± 34.1 months, p=0.035). CONCLUSIONS: Smad4 protein is of no value in predicting recurrence after curative therapy in colorectal cancer, but it may be helpful in identifying a subset of patients with early recurrence after curative therapy.

Clinicopathologic significance of GLUT1 expression and its correlation with Apaf-1 in colorectal adenocarcinomas.

AIM: To investigate the role of glucose transporter 1 (GLUT1) expression in colorectal carcinogenesis and evaluate the correlation with clinicopathological parameters and apoptosis-activating factor-1 (Apaf-1) expression in colorectal adenocarcinomas. METHODS: We used tissue microarrays consisting of 26 normal mucosa, 50 adenomas, 515 adenocarcinomas, and 127 metastatic lesions. Medical records were reviewed and clinicopathological analysis was performed. RESULTS: GLUT1 expression was absent in normal mucosa and low or moderately apparent in 19 cases (38.0%) of 50 adenomas. However, GLUT1 expression was detected in 423 (82.1%) of 515 adenocarcinomas and in 96 (75.6%) of 127 metastatic lesions. GLUT1 expression was significantly correlated with female gender (P = 0.009), non-mucinous tumor type (P = 0.045), poorer differentiation (P = 0.001), lymph node metastasis (P < 0.001), higher AJCC and Dukes stage (P < 0.001 and P < 0.001, respectively). There was a significant inverse correlation between GLUT1 expression and Apaf-1 expression (P = 0.001). In univariate survival analysis, patients with GLUT1 expression demonstrated poor overall survival and disease-free survival (P = 0.047 and P = 0.021, respectively, log-rank test). CONCLUSION: GLUT1 expression was frequently increased in adenocarcinomas and metastatic lesions. GLUT1 expression was significantly correlated with poorer clinicopathologic phenotypes and survival of patients with colorectal adenocarcinomas.