Prediction of Neoadjuvant Chemoradiotherapy Response in Rectal Cancer Patients Using Harmonized Radiomics of Multcenter 18F-FDG-PET Image.

We developed machine and deep learning models to predict chemoradiotherapy in rectal cancer using 18F-FDG PET images and harmonized image features extracted from 18F-FDG PET/CT images. Patients diagnosed with pathologic T-stage III rectal cancer with a tumor size > 2 cm were treated with neoadjuvant chemoradiotherapy. Patients with rectal cancer were divided into an internal dataset (n = 116) and an external dataset obtained from a separate institution (n = 40), which were used in the model. AUC was calculated to select image features associated with radiochemotherapy response. In the external test, the machine-learning signature extracted from 18F-FDG PET image features achieved the highest accuracy and AUC value of 0.875 and 0.896. The harmonized first-order radiomics model had a higher efficiency with accuracy and an AUC of 0.771 than the second-order model in the external test. The deep learning model using the balanced dataset showed an accuracy of 0.867 in the internal test but an accuracy of 0.557 in the external test. Deep-learning models using 18F-FDG PET images must be harmonized to demonstrate reproducibility with external data. Harmonized 18F-FDG PET image features as an element of machine learning could help predict chemoradiotherapy responses in external tests with reproducibility.

Clinical outcomes of locking polymeric clip for laparoscopic appendectomy in patients with appendicitis: a retrospective comparison with loop ligature.

PURPOSE: This study aimed to compare the clinical outcomes of laparoscopic appendectomy (LA) according to the method of appendiceal stump closure. METHODS: Patients who underwent LA for appendicitis between 2010 and 2020 were retrospectively reviewed. Patients were classified into locking polymeric clip (LPC) and loop ligature (LL) groups. Clinical outcomes were compared between the groups. RESULTS: LPC and LL were used in 188 (56.6%) and 144 patients (43.4%), respectively for appendiceal stump closure. No significant differences were observed in sex, age, comorbidities, and the severity of appendicitis between the groups. The median operative time was shorter in the LPC group than in the LL group (64.5 minutes vs. 71.5 minutes, P=0.027). The median hospital stay was longer in the LL group than in the LPC group (4 days vs. 3 days, P=0.020). Postoperative incidences of intraabdominal abscess and ileus were higher in the LL group than in the LPC group (4.2% vs. 1.1%, P=0.082 and 2.8% vs. 0%, P=0.035; respectively). The readmission rate was higher in the LL group than that in the LPC group (6.3% vs. 1.1%, P=0.012). CONCLUSION: Using LPC for appendiceal stump closure during LA for appendicitis was associated with lower postoperative complication rate, shorter operative time, and shorter hospital stay compared to the use of LL. Operative time above 60 minutes and the use of LL were identified as independent risk factors for postoperative complications in LA. Therefore, LPC could be considered a more favorable closure method than LL during LA for appendicitis.

A Patient-Derived Organoid-Based Radiosensitivity Model for the Prediction of Radiation Responses in Patients with Rectal Cancer.

Patient-derived tumor organoids closely resemble original patient tumors. We conducted this co-clinical trial with treatment-naive rectal cancer patients and matched patient-derived tumor organoids to determine whether a correlation exists between experimental results obtained after irradiation in patients and organoids. Between November 2017 and March 2020, we prospectively enrolled 33 patients who were diagnosed with mid-to-lower rectal adenocarcinoma based on endoscopic biopsy findings. We constructed a prediction model through a machine learning algorithm using clinical and experimental radioresponse data. Our data confirmed that patient-derived tumor organoids closely recapitulated original tumors, both pathophysiologically and genetically. Radiation responses in patients were positively correlated with those in patient-derived tumor organoids. Our machine learning-based prediction model showed excellent performance. In the prediction model for good responders trained using the random forest algorithm, the area under the curve, accuracy, and kappa value were 0.918, 81.5%, and 0.51, respectively. In the prediction model for poor responders, the area under the curve, accuracy, and kappa value were 0.971, 92.1%, and 0.75, respectively. Our patient-derived tumor organoid-based radiosensitivity model could lead to more advanced precision medicine for treating patients with rectal cancer.

Implication of FDG-PET/CT without synchronous colonic lesion in patients with stenotic left-sided colorectal cancer.

Although 18-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is useful for detecting synchronous colorectal cancer (CRC) in stenotic CRC, long-term outcomes of patients without synchronous FDG-avid lesions are not well reported. We investigated postoperative colonoscopy results in patients with left-sided stenosing CRC without synchronous FDG-avid lesions. In this retrospective review, 754 patients with left-sided CRC without synchronous FDG-avid lesions on preoperative 18F-FDG PET/CT were divided into two groups based on the completeness of preoperative colonoscopy. Propensity score matching was performed to balance baseline characteristics. Results of postoperative colonoscopy were compared in both the unmatched and matched cohorts. At 1 and 5 years after surgery, the cumulative risk of advanced adenoma (AA) or carcinoma (CA) in all patients, risk of CA, and additional surgical risk were 1.8% and 10.1%, 0.1% and 0.4%, and 0% and 0.5%, respectively. In both cohorts, the AA risk was significantly higher in the incomplete colonoscopy group. However, the risk of CA showed no between-group difference in the matched cohort. Additional surgical risk did not differ between the two groups. Thus, the finding of negative FDG-avid lesions in the proximal colon in addition to the target CRC ensures the absence of additional lesions warranting surgical plan changes.

The Impact of Primary Tumor Resection on Survival in Asymptomatic Colorectal Cancer Patients With Unresectable Metastases.

PURPOSE: This study was conducted to evaluate the effectiveness of primary tumor resection (PTR) in asymptomatic colorectal cancer (CRC) patients with unresectable metastases using the inverse probability of treatment weighting (IPTW) method to minimize selection bias. METHODS: We selected 146 patients diagnosed with stage IV CRC with unresectable metastasis between 2001 and 2018 from our institutional database. In a multivariate logistic regression model using the patients' baseline covariates associated with PTR, we applied the IPTW method based on a propensity score and performed a weighted Cox proportional regression analysis to estimate survival according to PTR. RESULTS: Upfront PTR was performed in 98 patients, and no significant differences in baseline factors were detected. The upweighted median survival of the PTR group was 18 months and that of the non-PTR group was 15 months (P = 0.15). After applying the IPTW, the PTR was still insignificant in the univariate Cox regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.5-1.21). However, in the multivariate weighted Cox regression with adjustment for other covariates, the PTR showed a significantly decreased risk of cancer-related death (HR, 0.61; 95% CI, 0.40-0.94). CONCLUSION: In this study, we showed that asymptomatic CRC patients with unresectable metastases could gain a survival benefit from upfront PTR by analysis with the IPTW method. However, randomized controlled trials are mandatory.

Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient­derived organoids.

Enhancing the radioresponsiveness of colorectal cancer (CRC) is essential for local control and prognosis. However, consequent damage to surrounding healthy cells can lead to treatment failure. We hypothesized that short­chain fatty acids (SCFAs) could act as radiosensitizers for cancer cells, allowing the administration of a lower and safer dose of radiation. To test this hypothesis, the responses of three­dimensional­cultured organoids, derived from CRC patients, to radiotherapy, as well as the effects of combined radiotherapy with the SCFAs butyrate, propionate and acetate as candidate radiosensitizers, were evaluated via reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and organoid viability assay. Of the three SCFAs tested, only butyrate suppressed the proliferation of the organoids. Moreover, butyrate significantly enhanced radiation­induced cell death and enhanced treatment effects compared with administration of radiation alone. The radiation­butyrate combination reduced the proportion of Ki­67 (proliferation marker)­positive cells and decreased the number of S phase cells via FOXO3A. Meanwhile, 3/8 CRC organoids were found to be non­responsive to butyrate with lower expression levels of FOXO3A compared with the responsive cases. Notably, butyrate did not increase radiation­induced cell death and improved regeneration capacity after irradiation in normal organoids. These results suggest that butyrate could enhance the efficacy of radiotherapy while protecting the normal mucosa, thus highlighting a potential strategy for minimizing the associated toxicity of radiotherapy.

Neutrophil to Lymphocyte Ratio: A Predictive Marker for Treatment Outcomes in Patients With Rectal Cancer Who Underwent Neoadjuvant Chemoradiation Followed by Surgery.

PURPOSE: In this study, we investigated the role of neutrophil to lymphocyte ratio (NLR) as a predictor of tumor response and as a prognostic factor in patients with rectal cancer who had undergone curative surgery after neoadjuvant chemoradiation therapy (nCRT). METHODS: Between January 2009 and July 2016, we collected 140 consecutive patients who had undergone curative intent surgery after nCRT due to rectal adenocarcinoma. We obtained the pre- and post-nCRT NLR by dividing the neutrophil count by the lymphocyte count. The cutoff value was obtained using receiver operating characteristic analysis for tumor response and using maximally selected rank analysis for recurrence-free survival (RFS). The relationship among NLR, tumor response, and RFS was assessed by adjusting the possible clinico-pathological confounding factors. RESULTS: The possibility of pathologic complete response (pCR) was significantly decreased in high pre- (>2.77) and postnCRT NLR (>3.23) in univariate regression analysis. In multivariate analysis, high post-nCRT NLR was an independent negative predictive factor for pCR (adjusted odds ratio, 0.365; 95% confidence interval [CI], 0.145-0.918). The 5-year RFS of all patients was 74.6% during the median 37 months of follow-up. Patients with higher pre- (>2.66) and post-nCRT NLR (>5.21) showed lower 5-year RFS rates (53.1 vs. 83.3%, P = 0.006) (69.2 vs. 75.7%, P = 0.054). In multivariate Cox analysis, high pre-nCRT NLR was an independent poor prognostic factor for RFS (adjusted hazard ratio, 2.300; 95% CI, 1.061-4.985). CONCLUSION: Elevated NLR was a negative predictive marker for pCR and was independently associated with decreased RFS. For confirmation, a large-scale study with appropriate controls is needed.

Detection of Methylated SEPT9 in Korean Colorectal Cancer Patients: Comparison with Previous Studies.

BACKGROUND: This study aimed to investigate the detection of methylated Septin 9 (mSEPT9) in Korean patients with colorectal cancer (CRC) and compare the results with those of previous studies. METHODS: A total of 127 plasma samples (111 patients with untreated CRC, 5 patients with adenomas, and 11 CRC patients treated with concurrent chemoradiotherapy before surgery) were collected. mSEPT9 was measured qualitatively with the Abbott RealTime ms9 Colorectal Cancer Assay. RESULTS: mSEPT9 was detected in 44 of 111 (39.6%) cases of untreated CRC but was not detected in the adenoma cases. The difference in the sensitivity of mSEPT9 among patients with adenomas and those with each stage of untreated CRC was statistically significant (Dukes' staging, p = 0.002 and TNM staging, p = 0.008). The sensitivity of mSEPT9 for each of the stages (I - IV) of untreated CRC patients were 20.7%, 54.1%, 36.6%, and 75.0%, respectively. The positive mSEPT9 results in untreated CRC patients reverted to negative in 19 of 21 patients (90.5%) after treatment. CONCLUSIONS: Compared to previous studies, the overall sensitivity of mSEPT9 was lower, but similar patterns were found in the sensitivities for each stage. Additionally, mSEPT9 appeared to have potential as a monitoring tool for CRC.

Protein arginine methyltransferase 5 is implicated in the aggressiveness of human hepatocellular carcinoma and controls the invasive activity of cancer cells.

Protein arginine methyltransferase 5 (PRMT5) is a protein that catalyzes transfer of methyl groups to the arginine residues of proteins and is involved in diverse cellular and biological responses. While the participation of PRMT5 in cancer progression has been increasingly documented, its association with the invasive phenotype currently remains poorly understood. In the present study, we revealed that PRMT5 is overexpressed in human hepatocellular carcinoma (HCC) and in colon cancer and its depletion leads to the suppression of cell invasive activity via the reduction of the expression of MMP-2. Real-time quantitative RT-PCR analysis of 120 HCC patient tissues revealed the overexpression of PRMT5 in HCC and the association of PRMT5 with aggressive clinicopathological parameters, such as poorer differentiation (P=0.004), more frequent hepatic vein invasion (P=0.019), larger tumor size (P=0.011) and higher α-fetoprotein levels (P=0.020). Similarly to the data obtained with HCC, overexpression of PRMT5 was also displayed in colon cancer tissues, compared to matched non-tumor regions. Consistent with the significant association of the overexpression of PRMT5 with hepatic vein invasion in patient specimens, PRMT5 depletion via siRNA transfection led to a marked reduction in the invasion rate in both HCC and colon cancer cells. Reduced invasion associated with PRMT5 depletion was accompanied by a decrease in the expression of MMP-2. Collectively, our results indicated that PRMT5 overexpression in HCC and colon cancer cells contributed to their acquisition of aggressive characteristics, such as invasiveness, thus presenting a promising therapeutic target for the treatment of these diseases.

Association between Metformin Use and Survival in Nonmetastatic Rectal Cancer Treated with a Curative Resection: A Nationwide Population Study.

PURPOSE: Metformin is associated with an anticancer effect. However, the effects of metformin in rectal cancer are controversial. This study investigated the impact of metformin on the survival of patients with diabetes mellitus and nonmetastatic rectal cancer who underwent curative surgery. MATERIALS AND METHODS: The database was provided by the Korea Center Cancer Registry and National Health Insurance Service of the Republic of Korea. A cohort of patients with newly diagnosed rectal cancer between 2005 and 2011 was identified. Drug exposure was defined as receiving the oral hypoglycemic agent for at least 90 days over the period from 6 months before the initial diagnosis of rectal cancer to the last follow-up. RESULTS: A total of 4,503 patients were prescribed oral hypoglycemic agents and classified as the diabetic group, of which 3,694 patients received metformin for at least 90 days. Unadjusted analyses showed a significantly higher overall survival (hazard ratio, 0.596; 95% confidence interval, 0.506 to 0.702) and rectal cancer-specific survival (hazard ratio, 0.621; 95% confidence interval, 0.507 to 0.760) in the metformin group than in the nonmetformin group. The adjusted overall survival (hazard ratio, 0.631; 95% confidence interval, 0.527 to 0.755) and cancer-specific survival (hazard ratio, 0.598; 95% confidence interval, 0.479 to 0.746) in the group with a medication possession ratio of 80% or greater was significantly higher than in the group with a medication possession ratio of less than 80%. CONCLUSION: Metformin use is associated with overall and cancer-specific survival in diabetic patients with a nonmetastatic rectal cancer treated with a curative resection.

Is the Location of the Tumor Another Prognostic Factor for Patients With Colon Cancer?

PURPOSE: In this study, we investigated both the characteristics of right colon cancer (RTCC) in comparison with those of left colon cancer (LTCC) and the impact of the location of the colon cancer on the prognosis. METHODS: We retrospectively analyzed the cases of 974 patients with nonmetastatic colon cancer who had undergone surgery with a curative intent from January 2001 to December 2011. RTCC was defined as a tumor located proximal to the splenic flexure. The characteristics of RTCC cancer were investigated by using descriptive analyses, and their impacts on the prognosis were assessed by using a Cox multivariate regression. RESULTS: Compared to LTCC, RTCC showed a female-dominant feature, and an undifferentiated pathology was more frequently observed. The number of lymph nodes retrieved from patients with RTCC was significantly higher than that retrieved from patients with LTCC. During 75 months of follow-up, peritoneal recurrence was more common in patients with RTCC than it was in patients with LTCC, and among the patients with stage III colon cancer, the disease-free and the overall survival rates were significantly worse in patients with RTCC. After adjustments with the other prognostic factors associated with colon cancer had been made, a tumor located at the right colon was found to be independently associated with poor prognosis. CONCLUSION: RTCC showed unique clinicopathologic features and was associated with a poorer prognosis.

Stereotactic body radiotherapy for oligometastases confined to the para-aortic region: clinical outcomes and the significance of radiotherapy field and dose.

We retrospectively reviewed 88 patients with oligometases in the para-aortic region from any controlled primary tumor site who were treated with stereotactic body radiotherapy (SBRT). The 5-year local control, disease-free survival, and overall survival rates were 83%, 31%, and 41%, respectively. A 90% tumor-control probability was predicted at a biological effective dose of 90 Gy. Severe gastrointestinal toxicities (grade ≥3) were observed in 2 of 88 patients (1%). The results of this study are limited by the retrospective nature of the study but could serve as the background and rationale for future prospective trials on SBRT-based treatment for oligometastses.

Prognostic value of 18F-FDG uptake by regional lymph nodes on pretreatment PET/CT in patients with resectable colorectal cancer.

PURPOSE: We evaluated the ability of pretreatment (18)F-FDG uptake by regional lymph nodes to predict the survival of patients with resectable colorectal cancer. METHODS: The records of 78 patients with AJCC stage III colorectal cancer (pathologically confirmed node-positive disease without evidence of distant metastasis) treated with surgery and adjuvant chemotherapy were retrospectively reviewed. The maximum standardized uptake values of the primary tumor (SUVp) and regional lymph nodes (SUVn) were measured by pretreatment (18)F-FDG PET/CT. The ROC curve analyses and the Cox proportional hazard model were used to analyze whether SUVp, SUVn, and clinicopathologic parameters could predict disease-free survival. RESULTS: Although there were no significant differences between the median SUVp in the event group and that in the non-event group, the median SUVn was significantly higher in the event group (1.7) than in the non-event group (0.8, p = 0.023). Based on the ROC curve analysis, SUVn predicted the event for disease-free survival (AUC = 0.668, p = 0.02) with the optimal criterion, sensitivity, specificity, and accuracy of > 1.2, 71%, 63%, and 65%, respectively. However, SUVp did not predict disease-free survival (AUC = 0.570, p = 0.349). Univariate analysis revealed that SUVn (p = 0.011) and venous invasion (p = 0.016) were associated with disease-free survival, but pathologic N stage was not (p = 0.09). By multivariate analysis, only SUVn > 1.2 independently shortened the disease-free survival (relative risk, 2.97; 95% CI, 1.14-7.74, p = 0.026). CONCLUSION: SUVn before surgery may be a useful prognostic marker in patients with AJCC stage III colorectal cancer.

Is microsatellite instability really a good prognostic factor of colorectal cancer?

PURPOSE: The aim of this study was to investigate the clinicopathologic features of and the prognosis for colorectal cancers (CRCs) with microsatellite instabilities (MSIs). METHODS: Between 2006 and 2009, genotyping was performed on 245 patients with stage II/III CRCs to establish the MSI status. The clinicopathologic differences and the prognostic value of MSI were analyzed. The median follow-up period was 38 months (range, 7-68 months). RESULTS: Of the total 245 patients, 20 (8.2%) had MSI-high (H) and 225 (91.8%) had MSI-low (L) or stable (S) CRCs. Adjuvant chemotherapies were performed on 101 stage II (87.8%) and 107 stage III patients (82.3%). Patients with MSI-H CRCs more frequently had a family history of colon cancer (10% vs. 2.7%, P = 0.003), more frequently had a cancer located at the proximal colon (90.0% vs. 19.1%, P < 0.0001), and more often showed a mucinous phenotype or poor differentiation (35.0% vs. 7.1%, P = 0.001). Despite less frequent lymph node metastasis (25% vs. 55.6%, P = 0.01), the number of retrieved lymph nodes was higher (26.3 ± 13.1 vs. 20.7 ± 1.2, P = 0.04) in the MSI-H group. The overall survival and the disease-free survival (DFS) did not differ with respect to MSI status. However, in the stage II subgroup, the DFS for patients with MSI-H CRCs was significantly worse (72.2% vs. 90.7%, P = 0.03). The multivariate analysis performed on this subgroup revealed that MSI-H was an independent poor prognostic factor (adjusted hazard ratio, 4.0; 95% confidence interval, 1.0-15.6, P = 0.046). CONCLUSION: MSI-H CRCs had distinct clinicopathologic features, and MSI-H was an independent poor prognostic factor in stage II CRCs. Considering the majority of stage II patients were administrated adjuvant chemotherapy, the efficacy of adjuvant chemotherapy for treating MSI CRCs might be different from that for treating MSI-L/S tumors.

Role of peritoneal lavage cytology and prediction of prognosis and peritoneal recurrence after curative surgery for colorectal cancer.

PURPOSE: In colorectal cancer, the role of detecting free malignant cells from peritoneal lavage is currently unclear. In this study, we investigated the positive rate of free malignant cells in peritoneal lavage fluid and their predictive value for prognosis and peritoneal recurrence after a curative resection. METHODS: From October 2009 to December 2011, in a prospective manner, we performed cytologic examinations of peritoneal lavage fluid obtained just after the abdominal incision from 145 patients who underwent curative surgery for colorectal cancer. We used proportional hazard regression models to analyze the predictive role of positive cytology for peritoneal recurrence and survival. RESULTS: Among total 145 patients, six patients (4.1%) showed positive cytology. During the median follow-up of 32 months (range, 8-49 months), 27 patients (18.6%) developed recurrence. Among them, 5 patients (3.4%) showed peritoneal carcinomatosis. In the multivariate analysis, positive cytology was an independent predictive factor for peritoneal recurrence (hazard ratio [HR], 136.5; 95% confidence interval [CI], 12.2-1,531.9; P < 0.0001) and an independent poor prognostic factor for overall survival (HR, 11.4; 95% CI, 1.8-72.0; P = 0.009) and for disease-free survival (HR, 11.1; 95% CI, 3.4-35.8; P < 0.0001). CONCLUSION: Positive cytology of peritoneal fluid was significantly associated with peritoneal recurrence and worse survival in patients undergoing curative surgery for colorectal cancer. Peritoneal cytology might be a useful tool for selecting patients who need intraperitoneal or systemic chemotherapy.

Immunogenicity of influenza vaccine in colorectal cancer patients.

PURPOSE: Although influenza is regarded as a major cause of morbidity and mortality in immunocompromised patients, vaccine coverage remains poor. We evaluated the immunogenicity of influenza vaccines in colorectal cancer patients. MATERIALS AND METHODS: In this study, 40 colorectal cancer patients who received an influenza vaccine at the Korea Cancer Center Hospital during the 2009-2010 and 2010-2011 influenza seasons were analyzed. The blood samples were collected at prevaccination and 30 days post vaccination, and antibody titers were measured using the hemagglutination-inhibition tests. RESULTS: In the 2009-2011 season, the seroprotection rate for H1N1 (94.7%) was significantly higher than that for H3N2 (42.1%) and B (47.3%). The seroconversion rate was 52.6%, 26.3%, and 36.8% for H1N1, H3N2, and B, respectively. Fold increase of geometric mean titer (MFI) was 3.86, 1.49, and 3.33 for H1N1, H3N2, and B, respectively. In the 2010-2011 season, the seroprotection rate for H1N1 (57.1%) was significantly higher than that for H3N2 (52.4%) and B (38.1%). The seroconversion rate was 52.4%, 47.6% and 33.3% for H1N1, H3N2, and B, respectively. MFI was 12.29, 3.62 and 4.27 for H1N1, H3N2, and B, respectively. CONCLUSION: Our study cohort showed an acceptable immune response to an influenza vaccine without significant adverse effects, supporting the recommendation for annual influenza vaccination in colorectal cancer patients.

Incidence and risk factors of parastomal hernia.

PURPOSE: Among the various stoma complications, the parastomal hernia (PSH) is the most common. Prevention of PSH is very important to improve the quality of life and to prevent further serious complications. The aim of this study was to analyze the incidence and the risk factors of PSH. METHODS: From January 2002 and October 2008, we retrospectively reviewed 165 patients who underwent an end colostomy. As a routine oncologic follow-up, abdomino-pelvic computed tomography was used to examine the occurrence of the PSH. The associations of age, sex, body mass index (BMI), history of steroid use and comorbidities to the development of the PSH were analyzed. The median duration of the follow-up was 36 months (0 to 99 months). RESULTS: During follow-up, 50 patients developed a PSH and the 5-year cumulative incidence rate of a PSH, obtained by using the Kaplan-Meier method, was 37.8%. In the multivariate COX analysis, female gender (hazard ratio [HR], 3.29; 95% confidence interval [CI], 1.77 to 6.11; P < 0.0001), age over 60 years (HR, 2.37; 95% CI, 1.26 to 4.46; P = 0.01), BMI more than 25 kg/m(2) (HR, 1.8; 95% CI, 1.02 to 3.16; P = 0.04), and hypertension (HR, 2.08; 95% CI, 1.14 to 3.81; P = 0.02) were all independent risk factors for the development of a PSH. CONCLUSION: The 5-year incidence rate of a PSH was 37.8%. The significant risk factors of a PSH were as follows: female gender, age over 60 years, BMI more than 25 kg/m(2), and hypertension. Using a prophylactic mesh during colostomy formation might be advisable when the patients have these factors.

High dose stereotactic body radiotherapy using three fractions for colorectal oligometastases.

BACKGROUND AND OBJECTIVES: This study evaluated the treatment result of high dose stereotactic body radiation therapy (SBRT) for colorectal oligometastases. METHODS: Between 2003 and 2009, 41 patients with 50 lesions confined to one organ from colorectal cancer (CRC) and treated with high dose SBRT ≥45 Gy were retrospectively reviewed. Lymph nodes (LNs) (18 patients) were the most frequent sites followed in order by lung (12) and liver (11). SBRT doses ranged from 45 to 60 Gy in three fractions (median 48 Gy). The cumulative gross tumor volume (GTV) ranged from 2 to 123 ml (median 13 ml). RESULTS: The median follow-up period from the SBRT date was 28 months (range, 6-65 months). The 3-year local control and overall survival rates were 64 and 60%, and the respective 5-year rates were 57 and 38%. Cumulative GTV and SBRT dose were statistically significant prognostic factors for local control. The grade 3 or 4 complications occurred in three patients (7%). CONCLUSIONS: High dose SBRT for colorectal oligometastases was found to produce results comparable with surgical series. To improve local control, dose higher than 48 Gy are recommend when possible, but further study will be required to define the optimal normal tissue constraints and acceptable toxicity.

Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer.

PURPOSE: Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. METHODS: The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. RESULTS: Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR ≤ 0.25 group was 92.9% (P = 0.03). CONCLUSION: The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer.

Effectiveness of Adjuvant Chemotherapy with 5-FU/Leucovorin and Prognosis in Stage II Colon Cancer.

PURPOSE: The aims of this study were to investigate the survival results and the prognostic factors of adjuvant chemotherapy in stage II colon cancer in the sparsity of Korean data. METHODS: From 1993 to 2006, 363 curatively resected pathologic stage II colon cancer patients were enrolled. Six cycles of adjuvant chemotherapy was performed: intravenous bolus 5-fluorouracil (5-FU) 500 mg/m(2) with leucovorin 20 mg/m2 for 2 hours daily for 5 days, followed by a 3-week resting period (n = 308). Fifty-five patients received only curative surgery. A high risk of recurrence was defined as the presence of one or more of the following factors: T4 tumor, lympho-vascular invasion, perineural invasion, perforation, obstruction, retrieved lymph node < 12, and poorly differention. The median follow-up period was 68 months (1 to 205 months). RESULTS: The five-year overall survival (OS) rate was 90.1%, and the five-year disease-free survival (DFS) rate was 84.7%. Among high-risk patients, the OS and the DFS rates of the treatment group were significantly higher than those of the non-treatment group (OS: 90.6% vs. 69.1%, P < 0.0001; DFS: 85.9% vs. 54.1%, P < 0.0001). Among low-risk patients, the survival results of the treatment group were also significantly superior (OS: 97.7% vs. 88.2%, P < 0.0001; DFS: 93.0% vs. 80.0%, P = 0.001). In the multivariate analysis, adjuvant chemotherapy was a significantly favorable prognostic factor for overall survival (hazard ratio, 0.41; 95% confidence interval, 0.22 to 0.75; P = 0.004). CONCLUSION: In our population, adjuvant chemotherapy showed superior survival to curative surgery alone and significantly reduced the risk of death. A nationwide multicenter randomized trial is needed.