Status for clinically complete remission rectal cancer after concomitant chemo-radiotherapy in Taiwan.

Treatment for Rectal cancer changed after the induction of concomitant chemo-radiotherapy, CCRT. Complete remission of the tumor leads to debate of the necessity of surgical intervention. We evaluate the treatment outcome to know if operation is beneficial to these patients. Patients received long course concomitant chemo-radiotherapy for advanced rectal cancer between 2004 and 2013 in Taiwan were enrolled. Total 2780 patients diagnosed advanced rectal cancer were enrolled. In these patients, 2578 received surgical intervention and 202 were in wait and see for complete remission tumor. Higher local recurrence rate was found with wait and see group (8.9% vs. 2.7%). Also, better overall survival, disease free survival and local recurrence free survival were seen with the surgical intervention group. Surgical intervention may be benefit for some misdiagnosed completed response to CCRT.

Sebacoyl Dinalbuphine Ester Extended-release Injection for Long-acting Analgesia: A Multicenter, Randomized, Double-Blind, And Placebo-controlled Study in Hemorrhoidectomy Patients.

OBJECTIVES: This study was conducted to evaluate the safety and efficacy of single sebacoyl dinalbuphine ester (SDE) injection (150 mg/2 mL) when administered intramuscularly to patients who underwent hemorrhoidectomy for postoperative long-acting analgesia. METHODS: A total of 221 patients scheduled for hemorrhoidectomy from 6 centers in Taiwan were randomly divided into SDE group and placebo group, and received the treatment, vehicle or SDE, 1 day before the surgery. Visual analogue scale (VAS) was recorded up to 7 to 10 days. Pain intensity using VAS AUC through 48 hours after surgery was calculated as the primary efficacy endpoint. RESULTS: Area under the curve of VAS pain intensity scores (VAS AUC) through 48 hours after hemorrhoidectomy was significantly less in SDE group than those in placebo group (209.93 vs. 253.53). VAS AUC from the end of surgical procedure to day 7 was also significantly different between SDE and placebo group (630.79 vs. 749.94). SDE group consumed significantly less amount of other analgesics, such as PCA ketorolac and oral ketorolac. Median time from the end of surgery to the first use of pain relief medication was also shortened in the placebo group than in the SDE group. Most adverse events were assessed as mild and tolerable in both groups. DISCUSSION: SDE injection demonstrated an extended analgesia effect, with a statistically significant reduction in pain intensity through 48 hours and 7 days after hemorrhoidectomy.

Early prediction by 18F-FDG PET/CT for progression-free survival and overall survival in patients with metastatic colorectal cancer receiving third-line cetuximab-based therapy.

OBJECTIVE: In metastatic colorectal cancer (mCRC) with wild-type K-ras, cetuximab-based regimen is an option for third-line therapy. The objective of this study was to assess if early response evaluation by 18F-FDG PET/CT can predict progression-free survival (PFS) and overall survival (OS) in these patients. PATIENTS AND METHODS: Patients with mCRC going to receive third-line cetuximab-based therapy were enrolled. 18F-FDG PET/CT studies were arranged at baseline and at the ends of the first and fourth weeks of therapy. Treatment response was evaluated with 2 methods: method 1 based on PET response criteria in solid tumors 1.0 and method 2 based on the assumption that an increase in peak tumor metabolism implies nonresponse. Progression-free survival was counted to tumor progression based on the Response Evaluation Criteria in Solid Tumors 1.1 or death. The predictive powers for PFS and OS were analyzed using the Kaplan-Meier method and the log-rank test. RESULTS: Twenty-seven patients were eligible with a median PFS of 5.8 months and a median OS of 9.1 months. Method 2 predicts PFS (P = 0.001) and OS (P < 0.001) at the end of the first week, whereas method 1 does not. Both methods predict PFS and OS at the end of the fourth week. CONCLUSIONS: Early response evaluation by 18F-FDG PET/CT predicts PFS and OS in patients with mCRC receiving third-line cetuximab-based therapy. Early therapeutic change may be possible for nonresponsive patients after 1 week of treatment.

Prognostic significance of the number of tumors and aggressive surgical approach in colorectal cancer hepatic metastasis.

BACKGROUND: Although liver resection (LR) for colorectal cancer (CRC) hepatic metastasis is the best strategy to improve patient outcomes, there are considerable concerns regarding the recurrence of CRC after LR. In this study, we investigated the prognostic indicators associated with CRC recurrence after LR for hepatic metastasis. METHODS: This is a retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and December 2012. The clinicopathological features and outcome parameters affecting prognosis were analyzed. RESULTS: A total of 332 LRs with curative intent were performed in 278 patients, of whom 168 (60.4%) experienced CRC recurrence after the first LR, and 206 of the 332 LRs (62.0%) developed CRC recurrence. A preoperative serum carcinoembryonic antigen level greater than 100 ng/mL and four or more metastatic tumor nodules were independent prognostic factors for CRC recurrence after LR. The disease-free survival rate after LR was significantly associated with the number of metastatic nodules. The patients who underwent surgical resection for recurrent CRC had favorable outcomes, with a five-year overall survival rate of 65.2%. CONCLUSION: The number of metastatic tumors significantly affects the outcomes of patients who undergo LR for CRC hepatic metastasis, indicating that a novel therapeutic strategy for patients at high risk may be required. However, favorable long-term outcomes are achievable through aggressive treatment with surgical resection of the recurrent CRC.

Cannabinoid receptor 1 disturbance of PPARγ2 augments hyperglycemia induction of mesangial inflammation and fibrosis in renal glomeruli.

UNLABELLED: Intensive fibrosis in the glomerular microenvironment is a prominent feature of diabetic nephropathy. Cannabinoid receptor 1 (CB1R) reportedly mediates diabetes-induced renal injury. However, studies on the molecular events underlying CB1R promotion of renal dysfunction are limited. This study is undertaken to investigate whether CB1R signaling via Ras or PPARγ pathway regulates mesangial fibrosis in diabetic kidneys. In streptozotocin-induced diabetic rats, hyperglycemia induced glomerular hypertrophy and fibrosis in association with increased IL-1ß, fibronectin, and CB1R expressions and reduced PPARγ2 signaling. CB1R transgenic mice gained kidney weight, and renal glomeruli strongly displayed IL-1ß and fibrotic matrices. Disruption of CB1R by antisense oligonucleotides or inverse agonist AM251 restored PPARγ2 signaling and reduced the promotional effects of hyperglycemia on the expression of fibrogenic transcription factor c-Jun, inflammation regulator SOCS3, proinflammatory cytokines, and accumulation of fibrotic matrix. PPARγ agonist rosiglitazone reduced the hyperglycemia-mediated enhancement of CB1R signaling, inflammation, and glomerular fibrosis in diabetic animals. In vitro, CB1R antagonism restored PPARγ2 action and reduced the promotional effects of high glucose on Ras, ERK, c-Jun, SOCS3 signaling, IL-1ß, and fibronectin expression in renal mesangial cells. Activation of PPARγ2 reduced the high glucose-induced CB1R expression in mesangial cells. Taken together, CB1R signaling contributes to the hyperglycemia disturbance of PPARγ2 signaling and increases inflammatory cytokine secretion and fibrotic matrix deposition in renal glomeruli. CB1R mediates the hyperglycemia-induced inflammation and fibrosis in mesangial cells by regulating Ras, ERK, and PPARγ2 signaling. CB1R blockade has a therapeutic potential to reduce the deleterious actions of hyperglycemia on renal glomerular integrity. KEY MESSAGE: Hyperglycemia increases glomerular fibrosis, inflammation, and CB1R signaling. CB1R signaling promotes fibrosis and inflammation of renal tissue. Loss of CB1R function alleviates diabetes-mediated renal deterioration. PPARγ agonist decreases CB1R expression in diabetic renal glomeruli. Ras and ERK mediated CB1R promotion of fibrosis matrix deposition in mesangial cells.

Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6.

Multipotent mesenchymal stem cells (MSCs) have been isolated from several tumors and are implicated to play critical roles to increase malignant cell growth, invasion and metastasis. Here, we show that the MSC-like cells were isolated from human colon cancer tissues. These isolated hCC-MSCs (human colon cancer-derived mesenchymal stem cells) shared similar characteristic features with bone marrow-derived MSCs, which include cell morphology, surface antigens and specific gene expression. Additionally, the hCC-MSCs could differentiate into osteocytes or adipocytes under appropriate culture conditions. The conditioned medium collected from the cultured hCC-MSCs was shown to enhance the migration and invasive activity of HCT-116 colon cancer cells in vitro. Besides, transplantation of HCT-116 cells along with hCC-MSCs in nude mice increased the tumor growth and metastasis. Further study revealed that IL-6 present in the hCC-MSC-conditioned medium sufficiently induced the levels of Notch-1 and CD44 in HCT-116 and HT-29 cells, which contribute to enhance tumorigenic activity of HCT-116 and HT-29 cells. By using immunohistochemical staining, the intense co-expression of IL-6, Notch-1 and CD44 was predominantly detected in human colon cancer tissues. Taken together, our findings suggest the importance of the IL-6/Notch-1/CD44 signaling axis in the interaction between hCC-MSCs and colon cancer cells.

An open-label safety study of first-line bevacizumab in combination with standard chemotherapy in Chinese patients with metastatic colorectal cancer treated in an expanded access program in Taiwan.

OBJECTIVE: An increased risk of serious adverse effects related to bevacizumab has been observed in many Western studies for metastatic colorectal cancer. To evaluate the safety of bevacizumab in Chinese patients, a safety study was conducted in Taiwan. METHODS: Bevacizumab was provided by the Expanded Access Program in combination with first-line chemotherapy per investigator's choice. The primary objective is the safety profile, particularly the targeted adverse events such as proteinuria, bowel perforation, hypertension, wound healing complication, thromboembolism and bleeding. The second objectives include time to disease progression and overall survival time. Patients with major surgical procedure performed within the 28 days of bevacizumab were excluded from this study. RESULTS: Forty patients were eligible for intent-to-treat analysis. The overall rate of objective response and disease control was 55.2 and 81.6%. The median time to disease progression and overall survival were 11.9 and 22.9 months. The actuarial 2-year survival was 46.6%. Regarding toxicity, 7 subjects (17.5%) had serious adverse effects related to study treatment. None of the patients in this cohort had arterial thrombotic events and bowel perforation. CONCLUSIONS: Bevacizumab demonstrates a similar activity and safety profile in Chinese patients. Life-threatening bowel complications were avoided in this study by excluding patients with major surgery within the first 28 days.

Anorectal melanoma: review of 22 consecutive cases.

BACKGROUND/AIMS: To evaluate outcome and prognostic factors of patients with anorectal melanoma. METHODOLOGY: Twenty-two consecutive patients with anorectal melanoma received operation from 1993 through 2011 were reviewed. The definitions of stage I, II and III are local disease, locoregional lymphadenopathy and metastatic disease, respectively. RESULTS: The patients included 8 men and 14 women, aged from 36 to 83 years (mean, 58.4 years). At the end of the follow-up period, 19 patients died of disease and only 3 patients were alive with disease. Only two patients were alive longer than 5 years after operation. For stage I and II tumors that underwent clinical curative resection (n=17), stage II (p=0.04), tumor size >3 cm (p=0.008) and invasion depth to muscle (p=0.021) all showed poorer prognosis in overall survival. Though wide local excision (WLE) were performed in the patients with earlier tumors, there was no statistical difference in overall (p=0.063) and disease-free survival (p=0.333) between WLE and radical surgery. Furthermore, patients with WLE had more chance of local recurrence than radical surgery (6/7 vs. 3/10, p=0.050). Four salvage radical operations could be performed after local recurrence in WLE group. CONCLUSIONS: WLE increases the chance of local recurrence more than radical surgery. Care should be taken to avoid microseeding during performed WLE.

Concurrent chemoradiotherapy in the treatment of locally recurrent rectal cancer.

BACKGROUND/AIMS: Long course concurrent chemoradiotherapy provides potential tumor downstaging. When local recurrent rectal cancer without distant metastases is diagnosed, a potentially curative resection can be performed. The aim of this study was to assess the outcome of concurrent chemoradiotherapy in treating isolated local recurrent rectal cancer. METHODOLOGY: Patients (n=102) with isolated local recurrent rectal cancer within the pelvis were scheduled for concurrent chemoradiotherapy, consisting of pelvic irradiation with a total dose of 50.4 Gy in 28 fractions. Chemotherapy was administered concurrently and included 85 mg/m2 oxaliplatin by venous infusion over 2 h on day 1, followed by 1,200 mg*m-2*day-1 of continuous venous infusion for 2 days. This regimen was repeated every 2 weeks for 6 cycles. The overall survival rate, responses, disease-free interval and toxicities were assessed. RESULTS: A total of 96 patients completed planned concurrent chemoradiation. Complete clinical responses were found in 13 of the 96 patients (14%), partial responses in 59 (61%), stable disease in 21 (22%) and disease progression in 3 (3%). The overall survival and disease-free survival rates in all the 96 patients were 45% and 14%, respectively. CONCLUSIONS: The treatment of locally recurrent rectal cancer is complicated. Concurrent chemoradiation can increase disease-free survival and overall survival by increasing complete resection rate of locally recurrent tumors and even complete response of the tumors. Ongoing treatment strategies aim to enhance response rates and to accurately assess the extent of local recurrent tumor response to concurrent chemoradiation.

Impact of chemotherapy-related prognostic factors on long-term survival in patients with stage III colorectal cancer after curative resection.

BACKGROUND: This retrospective study evaluated the prognostic factors of chemotherapy in stage III colorectal cancer after curative resection. METHODS: From 1996 to 2001, 1,054 patients with primary single colorectal cancer underwent curative resection. Seven hundred sixteen patients received various 5-fluorouracil (FU)-based adjuvant chemotherapy regimens, including oral and intravenous treatments. The chemotherapy-related parameters examined included therapeutic duration, frequency, route of administration, composition of combination therapies, and postoperative time interval from the operation to the start of chemotherapy. RESULTS: The therapeutic duration and postoperative time interval of starting therapy were independent prognostic factors, in addition to clinicopathological factors. The 8-year cancer-specific/overall survival rates in patients who received chemotherapy for >4 months (63.0/58.6%) were significantly higher than the rates in patients who received no chemotherapy (56.7/37.7%, P < 0.01) and those who remained on chemotherapy for 1-4 months (49.4/41.9%, P < 0.05). The 8-year cancer-specific/overall survival rates in patients who waited 1-5 weeks after surgery to receive chemotherapy (62.9/58.5%) were significantly higher versus rates in those who did not receive chemotherapy (56.7/37.7%) and those who did not receive chemotherapy until >5 weeks after surgery (52.3/45.9%) (both P < 0.05). Survival rates did not differ between patients who did not undergo chemotherapy, those for whom chemotherapy lasted 1-4 months, and patients who did not receive chemotherapy until >5 weeks after surgery. CONCLUSIONS: The appropriate duration of therapy and early chemotherapy after surgery were 2 of the most important factors in eradicating occult cancer and effecting long-term survival benefits in patients with stage III colorectal cancer.

Role of body mass index in colon cancer patients in Taiwan.

AIM: To determine the effect of body mass index (BMI) on the characteristics and overall outcome of colon cancer in Taiwan. METHODS: From January 1995 to July 2003, 2138 patients with colon cancer were enrolled in this study. BMI categories (in kg/m²) were established according to the classification of the Department of Health of Taiwan. Postoperative morbidities and mortality, and survival analysis including overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were compared across the BMI categories. RESULTS: There were 164 (7.7%) underweight (BMI < 18.5 kg/m²), 1109 (51.9%) normal-weight (BMI = 18.5-23.9 kg/m²), 550 (25.7%) overweight (BMI = 24.0-26.9 kg/m²), and 315 (14.7%) obese (BMI ≥ 27 kg/m²) patients. Being female, apparently anemic, hypoalbuminemic, and having body weight loss was more likely among underweight patients than among the other patients (P < 0.001). Underweight patients had higher mortality rate (P = 0.007) and lower OS (P < 0.001) and DFS (P = 0.002) than the other patients. OS and DFS did not differ significantly between normal-weight, overweight, and obese patients, while CSS did not differ significantly with the BMI category. CONCLUSION: In Taiwan, BMI does not significantly affect colon-CSS. Underweight patients had a higher rate of surgical mortality and a worse OS and DFS than the other patients. Obesity does not predict a worse survival.

Does body mass index impact the number of LNs harvested and influence long-term survival rate in patients with stage III colon cancer?

BACKGROUND: The aim of this study is to evaluate whether different body mass index (BMI) values affect lymph node (LN) retrieval and whether such variations influence long-term survival in Asian patients. METHOD: From January 1995 to July 2003, 645 stage III colon cancer patients were enrolled in our study. Patients were stratified into four groups: Obese (BMI ≧ 27 kg/m(2)), overweight (24 ≤ BMI < 27 kg/m(2)), normal (18.5 ≤ BMI < 24 kg/m(2)), and underweight (BMI < 18.5 kg/m(2)). RESULTS: Mean BMI in the cohort was 23.3 kg/m(2). Mean number of LNs harvested was 23.1, 19.5, 19.8 and 28.1 in the normal, overweight, obese and underweight groups, respectively. There was a significant difference in the mean number of LNs harvested when comparing the overweight and underweight groups to the normal group (p = 0.013 and p = 0.04, respectively). Females were overrepresented in the underweight group (p = 0.011), and patients who had proximal colon cancers were more frequently underweight (p = 0.018). The mean number of LNs harvested varied by cases of right hemicolectomy (p = 0.009) and proximal cancer location (p = 0.009) for different BMI groups. Multivariate analysis showed that underweight, proximal colon cancer, well- or moderately differentiated adenocarcinoma and stage IIIC cancer were significant variables for adequate LN recovery. BMI was not significantly associated with relapse-free survival (p = 0.523) or overall survival (p = 0.127). CONCLUSION: BMI is associated with LN harvest but is not an independent variable in stage III colon cancer survival.

Proteomic analysis of the effects of baicalein on colorectal cancer cells.

Baicalein is the flavonoids with multiple pharmacological activities. The aim of our study was to investigate the effects of baicalein on colorectal cancer (CRC) and to recognize the targets of baicalein treatment. To better understand baicalein's target, proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to elucidate proteins differential display. Results from this study investigate that baicalein treatment of CRC cells results in reduced cell proliferation. As a result, differential protein displays between baicalein-treated and untreated CRC were determined and validated. There were 11 differentially expressed proteins between baicalein-treated and untreated CRC. Furthermore, we demonstrate that baicalein inhibits cancer cell proliferation and reduced reactive oxygen species (ROS) by up-regulating the levels of peroxiredoxin-6 (PRDX6). Knockdown of PRDX6 in baicalein-treated CRC cells by specific small interfering RNA resulted in ROS production and proliferation, opposite of the baicalein treatment scenario as indicated by cell cycle distribution. These results illustrate that baicalein up-regulates the expression of PRDX6, which attenuates the generation of ROS and inhibits the growth of CRC cells, whereas baicalein treatment have no effect on normal epithelial cells.

Immunohistochemical study of vascular endothelial growth factor (VEGF) and matrilysin (MMP-7) in T1 adenocarcinoma of the colon and rectum to predict lymph node metastases or distant metastases.

BACKGROUND/AIMS: Predicting the lymph node metastatic or distant metastatic potential of T1 adenocarcinoma of the colon and rectum remains a major challenge. We investigated the role of the expressions of tumor matrilysin (MMP-7), VEGF-C and VEGF-A in predicting these metastatic potentials. METHODOLOGY: Single T1 adenocarcinomas were examined and pathological tumor factors were reviewed. Immunohistochemical staining of VEGF and MMP-7 was performed and the metastatic potential was defined on the basis of the presence of lymph nodes in the specimen or the identification of other distant metastasis during follow-up examinations. RESULTS: There was little correlation between the IHC staining results of VEGF-A, VEGF-C and MMP-7 in the same specimen (kappa<0.1). After a 61-month median follow-up (2-131 months), 17 (11.8%) tumors showed metastatic potential, including 14 lymph node metastases and 3 distant metastases. The tumors showing high levels of MMP-7 expression had higher metastatic potentials than those with low expression (19.1% vs. 8.2%, respectively; p=0.057). Overexpression of MMP-7 generally indicated an inferior overall survival (p=0.09). In analysis of the traditional pathological tumor factors, only lymphovascular invasion showed significance in predicting metastatic potential (p=0.04). CONCLUSIONS: Overexpression of MMP-7 generally indicated a higher metastatic potential and inferior overall survival. Lymphovascular invasion was a significant risk factor for lymph node metastasis.

Preoperative carcinoembryonic antigen elevation in colorectal cancer.

UNLABELLED: BACKGROUND /AIMS: The aim of this study was to calculate the prevalence of elevated carcinoembryonic antigen (CEA) among colorectal cancer (CRC) patients and to evaluate the prognostic value of preoperative serum CEA levels in them. METHODOLOGY: Between 1995 and 2005, 8,861 consecutive patients were enrolled from a prospective database. CEA =5ng/mL was defined as elevated CEA. RESULTS: In the multivariate analysis, elevated preoperative CEA correlated with higher ages, circumferential tumors, colon tumors, large tumors, liver metastasis and high-stage (AJCC) tumors. After a 44-month median follow-up, elevated CEA was found to be an independent prognostic factor (odds ratio = 1.61) for overall survival in all 4 stages of the disease. The survival among patients with stage I tumors and elevated CEA (5-year survival rate = 74.7%) was not greater than that among patients with stage II tumors and no CEA elevation (5-year survival rate = 80.8%). CONCLUSIONS: Elevated preoperative CEA correlated with a higher age, circumferential tumors, colon tumors, large tumors, liver metastasis, and high-stage (AJCC) tumors. Elevated preoperative CEA indicates a potential poor prognosis even in early stage tumors. This poorer prognosis in the patients with stage I tumors and elevated preoperative CEA was not cancer specific.

Long-term survival benefits of adjuvant chemotherapy by decreasing incidence of tumor recurrence without delaying relapse in stage III colorectal cancer.

BACKGROUNDS AND AIMS: To elucidate the survival benefits of adjuvant chemotherapy by decreasing incidence or by delaying time of tumor recurrence, we reported the long-term results of a nonrandomized prospective study comparing the adjuvant chemotherapy to no chemotherapy in stage III colorectal cancer. PATIENTS: From 1991 to 1995, 463 patients with stage III colorectal cancer were divided to three groups which were no chemotherapy, weekly chemotherapy, and monthly chemotherapy (5-FU plus levamisole). RESULTS: The recurrent incidence was significantly decreased in patients with chemotherapy (47.8% vs. 63.9% of no chemotherapy, P = 0.001), resulting into better survival. The 10-year cancer-specific and overall survival rates of patients with chemotherapy vs. no chemotherapy were 52.1% vs. 37.8% and 46.9% vs. 29.9%, respectively (P < 0.001). Weekly chemotherapy had better survival than monthly chemotherapy (P < 0.05). There was no significant difference in recurrent time or types between the patients with and without chemotherapy. The percentages of patients with recurrence happened within 3 years were 85.2% and 84.6% of those with and without chemotherapy, respectively. Patients with advanced stage of T4b invasion depth, N2, and central node invasion had no significant survival benefits by adjuvant chemotherapy. CONCLUSIONS: Long-term survival benefits achieved by adjuvant chemotherapy is through decreasing recurrent incidence, not through postponing tumor recurrent time. That means adjuvant chemotherapy indeed cures some patients by eradicating occult tumor. In adjuvant setting, more powerful regimen for eradicating occult tumor is the keystone to improve long-term survival of stage III colorectal cancer.

Effect of preoperative neutrophil-lymphocyte ratio on the surgical outcomes of stage II colon cancer patients who do not receive adjuvant chemotherapy.

BACKGROUND AND AIMS: Selection of appropriate stage II colon cancer patients for adjuvant chemotherapy is critical for improving survival outcome. With the aim of identifying more high risk factors for stage II colon cancer, this study aimed to determine whether the neutrophil-lymphocyte ratio (NLR) is a predictor of surgical outcomes in patients with stage II colon cancer who do not receive adjuvant chemotherapy. MATERIALS AND METHODS: We enrolled 1,040 stage II colon cancer patients who had undergone colectomy at a single institution between January 1995 and December 2005 and did not receive adjuvant chemotherapy. RESULTS: Of these 1,040 patients, 785 (75.5%) patients had a normal NLR and 255 (24.5%) had an elevated NLR. Those with an elevated NLR included patients ≥65 years, T4b cancer, carcinoembryonic antigen ≥5 ng/mL, and tumor obstruction or perforation. Patients with an elevated NLR had a significantly worse overall survival (OS) and worse disease-free survival (DFS) than did patients with a normal NLR. Cox regression analysis revealed that elevated NLR was an independent predictor of OS (P=0.012) but not DFS (P=0.255). CONCLUSION: An elevated NLR is an independent predictor of OS but not DFS in stage II colon cancer patients who did not receive adjuvant chemotherapy. Preoperative NLR measurement in stage II colon cancer patients may be a simple method for identifying patients with a poor prognosis who can be enrolled in further trials of adjuvant chemotherapy.

Surgical resection of locally advanced primary transverse colon cancer--not a worse outcome in stage II tumor.

BACKGROUND AND AIMS: In locally advanced primary transverse colon cancer, a tumor may cause perforation or invade adjacent organs. Extensive resection is the best choice of treatment, but such procedures must be weighed against the potential survival benefits. This study was performed to identify the clinicopathological features and treatment outcomes of such tumors. MATERIALS AND METHODS: We retrospectively reviewed the database of the Colorectal Cancer Registry of Chang Gung Memorial Hospital between February 1995 and December 2005. Patients with colon cancer sited between the hepatic and splenic flexure that involved an adjacent organ without distant metastasis were defined as having locally advanced transverse colon cancer. RESULTS: A total of 827 patients who underwent surgery for transverse primary colon cancer were enrolled in the study. Stage II and stage III colon cancer were diagnosed in 548 patients. Thirty-two (5.8%) patients were diagnosed with locally advanced tumors. Multivariate analysis revealed that stage III, preoperative carcinoembryonic antigen ≥5 ng/mL, a tumor with perforation or obstruction, and the presence of a locally advanced tumor were significant prognostic factors for both overall and cancer-specific survival. Postoperative morbidity rates differed significantly between the locally advanced and non-locally advanced tumor groups (22.7% vs. 12.3%, P < 0.01). No significant overall survival difference was observed among the stage II transverse colon tumors (P = 0.21). CONCLUSION: Surgical resection of locally advanced transverse colon tumors resulted in a higher morbidity and mortality than that of non-locally advanced tumors, but the benefit of extensive surgery in the case of locally advanced tumors cannot be underestimated. Furthermore, this benefit is more pronounced in the case of stage II tumors.

Low preoperative serum albumin in colon cancer: a risk factor for poor outcome.

OBJECTIVE: The number of colon cancer patients is increasing worldwide. Malnutrition and comorbidities are frequently associated with these patients. The relationships between the preoperative malnutrition and the outcomes of colon cancer patients are unclear; this study aimed to clarify these issues. METHODS: A total of 3,849 consecutive colon cancer patients were enrolled in an analysis of short-term outcomes and 2,529 patients were included in an analysis of the long-term outcomes. These patients were divided into the hypoalbuminemic and normal groups according to the definition of hypoalbuminemia (serum albumin < 35 g/L). RESULTS: Advanced age, female gender, abnormal CEA levels, right colon or large tumors, mucinous adenocarcinoma, poor differentiation, stage II cancer, TNM advancing T stage, old cardiovascular accident, diabetes, and liver cirrhosis were more likely to be associated with hypoalbuminemia. Hypoalbuminemic patients had a higher rate of postoperative mortality and morbidity, including complications related to wounds, lungs, the urinary system, and anastomosis. The 5-year overall survival rates of patients with normal albumin and hypoalbuminemia were 78.0% and 60.0%, respectively (P < 0.0001), and the 5-year relapse-free survival rates were 78.9% and 73.5%, respectively (P = 0.0042). In a multivariate analysis, the albumin level was also significantly correlated with 5-year overall survival (<35 vs. ≥ 35, HR 1.75; 95% CI 1.49-2.08) and 5-year relapse-free survival (<35 vs. ≥ 35, HR 1.28; 95% CI 1.04-1.56). CONCLUSIONS: Hypoalbuminemia is a predictor of poor surgical outcomes of colon cancer and is a poor prognosis factor for long-term survival of colon cancer after curative operation.

Outcomes of resection for colorectal cancer hepatic metastases stratified by evolving eras of treatment.

BACKGROUND AND PURPOSE: The outcomes and management of colorectal cancer (CRC) hepatic metastasis have undergone many evolutionary changes. In this study, we aimed to analyze the outcomes of patients with CRC hepatic metastasis in terms of the era of treatment. METHODS: We conducted a retrospective review of 279 patients who underwent liver resection (LR) for CRC hepatic metastases. The prognoses of patients treated pre-2003 (era 1) and post-2003 (era 2) were examined. RESULTS: Of the patients included in the study, 210 (75.3%) had CRC recurrence after LR. There was a significant difference in the ratio of CRC recurrence between the 2 eras (82.0% in era 1 vs. 69.5% in era 2; p = 0.008). Analysis of recurrence-free and overall survival rates also showed that the patient outcome was significantly better in the post-2003 era than in the pre-2003 era. Further analysis showed that a significantly higher percentage of patients in era 2 had received modern chemotherapeutic regimens including irinotecan and oxaliplatin, while patients in era 1 were mainly administered fluorouracil and leucovorin for adjuvant chemotherapy. Among patients with CRC recurrence, a significant ratio of those in era 2 underwent surgical resection for recurrent lesions, and these patients had a better survival curve than did patients without resection (34.1% vs. 2.2% for 5-year survival; p < 0.0001). CONCLUSION: The incidence of CRC recurrence after LR for hepatic metastasis remains very high. However, the management and outcomes of patients with CRC hepatic metastasis have greatly improved with time, suggesting that the current use of aggressive multimodality treatments including surgical resection combined with modern chemotherapeutic regimens effectively prolongs the life expectancy of these patients.