Health-related quality of life and cost comparison of adjuvant capecitabine versus 5-fluorouracil/leucovorin in stage III colorectal cancer patients.

PURPOSE: The purpose of this study was to compare health-related quality of life (HRQoL) and costs associated with 2 adjuvant chemotherapy regimens [capecitabine-based therapy versus 5-fluorouracil/leucovorin (5-FU/LV)-based therapy] in stage III colorectal cancer patients. METHODS: We conducted a prospective, open-label, observational, multicenter study from July 2008 to July 2011. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires was used to assess HRQoL before, during, and after treatment. The direct and indirect costs of adjuvant treatment were estimated from a specially prepared questionnaire, the National Health Insurance Research Database, and other published sources. We used propensity scoring to match samples between groups and performed multivariate analyses to adjust for differences in patient demographics and clinical characteristics. RESULTS: A total of 497 patients were enrolled, and 356 completed the surveys. Following propensity score matching, 239 patients were included in the analysis (122 in the capecitabine-based group, 117 in the 5-FU/LV-based group). Global HRQoL scores did not differ significantly between the two groups. However, compared to patients in the 5-FU/LV-based group, patients in the capecitabine-based group had less nausea and vomiting (mid-term, P = 0.024; final, P = 0.013), appetite loss (mid-term, P < 0.0001; final, P = 0.001), and fewer side effects from chemotherapy (mid-term, P = 0.017). In addition, the monthly cost of capecitabine-based therapy was lower than those of 5-FU/LV-based therapy [NT$31,895.46 (US$1063.18) vs. NT$79,159.24 (US$2638.64) per patient]. CONCLUSIONS: Capecitabine is a reasonable alternative and cost-effective treatment option under current conditions for patients with stage III colorectal cancer.

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.

Comparison of treatment results between surgery alone, preoperative short-course radiotherapy, or long-course concurrent chemoradiotherapy in locally advanced rectal cancer.

BACKGROUND: The aim of this study is to compare the results between surgery alone, preoperative radiotherapy (RT), or preoperative concurrent chemoradiotherapy (CCRT) followed by surgery in the treatment of locally advanced rectal cancer in Asian patients. METHODS: This study included 151 consecutive patients with clinical T3, T4 or node-positive rectal cancer from Jan. 2005 to Dec. 2007. Eighty-six patients underwent total mesorectal excision (TME) alone, 28 patients received preoperative RT (25 Gy in 5 fractions) followed by TME in 1 week, and 37 patients received preoperative CCRT (50.4 Gy in 28 fractions) followed by TME in 4-6 weeks. RESULTS: The 3-year loco-regional recurrence (LRR), distant metastasis, overall and disease-free survival rates are comparable among Surgery, RT and CCRT groups. By multivariate analysis, pT4, distal margin <2 cm, the ratio of positive lymph nodes to totally dissected lymph nodes ≥ 0.2, and non-R0 resection were significant factors for LRR. In subgroup analysis, TME alone produced comparable LRR to RT or CCRT (3.3 vs.. 4.8%) for favorable patients (0-1 risk factors). For unfavorable patients (2 or more risk factors), the LRR rose to 37% in patients receiving surgery alone as compared with 15% in the RT or CCRT patients. CONCLUSIONS: Preoperative RT or CCRT followed by TME produced good local control in favorable and unfavorable patients with locally advanced rectal cancer. If preoperative RT or CCRT is not given, TME alone has a high incidence of local recurrence in unfavorable patients with 2 or more risk factors.

Metastatic lymph node ratio is a more precise predictor of prognosis than number of lymph node metastases in stage III colon cancer.

OBJECTIVE: The objective of this study is to assess the value of metastatic lymph node ratio (LNR) in predicting disease-free survival (DFS) in patients with stage III adenocarcinoma of the colon. MATERIALS AND METHODS: From 1995 to 2003 inclusively, a total of 624 patients featuring stage III adenocarcinoma of the colon underwent curative resection. Of the 624 patients, an adequate number of lymph nodes (n > or = 12) had been harvested in 490 patients. These patients were stratified into LNR groups 1 (LNR < or = 0.4), 2 (0.4 < LNR < or = 0.7), and 3 (LNR > 0.7). Kaplan-Meier survival curve and log-rank test were used to evaluate the prognostic value of LNR. A Cox regression model was used for multivariate analyses. RESULTS: The 5-year DFS rate was 66.7% for patients with LNR1, 35.1% for those with LNR2, and 0% for patients with LNR3 (p < 0.0001). In T3/4LNR1 patients (n = 411), there was no difference in survival between those with N1 stage and those with N2 stage. Cox proportional hazards regression analysis revealed that N stage (number of positive lymph nodes) was not a significant factor when LNR was taken into consideration. CONCLUSIONS: LNR is a more precise predictor of 5-year DFS than number of positive lymph nodes (N stage) in patients with stage III colon cancer.

Sacral nerve stimulation is more effective than optimal medical therapy for severe fecal incontinence: a randomized, controlled study.

PURPOSE: This randomized study was designed to compare the effect of sacral neuromodulation with optimal medical therapy in patients with severe fecal incontinence. METHODS: Patients (aged 39-86 years) with severe fecal incontinence were randomized to have sacral nerve stimulation (SNS group; n = 60) or best supportive therapy (control; n = 60), which consisted of pelvic floor exercises, bulking agent, and dietary manipulation. Full assessment included endoanal ultrasound, anorectal physiology, two-week bowel diary, and fecal incontinence quality of life index. The follow-up duration was 12 months. RESULTS: The sacral nerve stimulation group was similar to the control group with regard to gender (F:M = 11:1 vs. 14:1) and age (mean, 63.9 vs. 63 years). The incidence of a defect of < or = 120 degrees of the external anal sphincter and pudendal neuropathy was similar between the groups. Trial screening improved incontinent episodes by more than 50 percent in 54 patients (90 percent). Full-stage sacral nerve stimulation was performed in 53 of these 54 "successful" patients. There were no septic complications. With sacral nerve stimulation, mean incontinent episodes per week decreased from 9.5 to 3.1 (P < 0.0001) and mean incontinent days per week from 3.3 to 1 (P < 0.0001). Perfect continence was accomplished in 25 patients (47.2 percent). In the sacral nerve stimulation group, there was a significant (P < 0.0001) improvement in fecal incontinence quality of life index in all four domains. By contrast, there was no significant improvement in fecal continence and the fecal incontinence quality of life scores in the control group. CONCLUSIONS: Sacral neuromodulation significantly improved the outcome in patients with severe fecal incontinence compared with the control group undergoing optimal medical therapy.

Performing handsewn coloanal anastomosis with the pursestring suture anoscope.

The pursestring suture anoscope, originally developed for the procedure for rectal prolapse and hemorrhoids, has been successfully used when performing coloanal anastomosis. The use of this tool for handsewn coloanal anastomosis can achieve relatively atraumatic results to the patient. It is a suitable and handy tool that makes handsewn transanal colonanal anastomosis simple and easy to perform.

Measurement of physical activity in cancer survivors: a validity study.

PURPOSE: The purpose of the study was to validate the Taiwanese version of the Physical Activity Scale for the Elderly (PASE-T) and to assess physical activity in Taiwanese cancer survivors. METHODS: One hundred twenty-seven cancer survivors participated in this study. Instruments consisted of the PASE-T, the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T), Karnofsky performance status (KPS), and actigraph. Reliability was assessed by calculating the test-retest reliability. The validity was assessed by the content validity, criterion-related validity, convergent validity, and known-group validity. RESULTS: The test-retest reliability of PASE-T was 0.90 over a 2-week interval, based on a sample of 30 patients. The content validity index was very acceptable at 0.91. Convergent validity was demonstrated by its significant association with MDASI-T scores (symptom severity: r = -0.23, p = 0.001; symptom interference: r = -0.21, p = 0.001) and KPS scores (r = 0.59, p < 0.001). Criterion-related validity was established by a significant relationship to the actigraph total counts per minute (r = 0.64, p < 0.001). Known-group validity was established by its ability to detect significant differences according to a patient's performance status. Moreover, KPS (ß = 0.37), fatigue (ß = -0.32), and age (ß = -0.20) were significant predictors of physical activity (R(2) = 0.46). CONCLUSIONS: The PASE-T is a reliable and valid instrument for measurement of physical activity among cancer survivors in Taiwan. IMPLICATION FOR CANCER SURVIVORS: This scale could be a useful measure of physical activity in cancer survivors and subsequently facilitate the quality of oncology care.

Effectiveness of a novel herbal agent MB-6 as a potential adjunct to 5-fluoracil-based chemotherapy in colorectal cancer.

Natural products, such as fermented soybeans, have been used to treat various physical conditions, including cancer. MB-6 is a botanical preparation composed of fermented soybean extract, green tea extract, Antrodia camphorata mycelia, spirulina, grape seed extract, and curcumin extract. Based on this, we hypothesized that MB-6 would increase the effectiveness of chemotherapy in patients with colon cancer. In a rodent study, MB-6, in combination with leucovorin/5-fluorouracil chemotherapy, increased the survival rate and life span of colon cancer tumor-bearing BALB/c mice as compared with treatment with chemotherapy alone. In a proof-of-concept clinical study, 72 patients with metastatic colorectal cancer were randomized to receive leucovorin, 5-fluorouracil, and oxaliplatin in combination with either MB-6 or placebo for 16 weeks. The primary outcome was the best overall response, and secondary outcomes included progression-free survival, overall survival, and adverse effects. Up to 77 weeks after treatment, there was follow-up with the patients. No significant difference in the best overall response rate and overall survival was observed between the 2 groups. Patients in the MB-6 group had a significantly lower disease progression rate than patients in the placebo group, during the study period (0.0% vs 15.8%, P = .026). The placebo group had a significantly higher incidence of adverse events at least grade 4 compared with the MB-6 group (28.9% vs 2.9%, respectively, P = .004) and a significantly higher occurrence of increased serum creatinine compared with the MB-6 group (29% vs 5.9%, P = .014). MB-6 is a promising botanical supplement that may increase the effectiveness of chemotherapy in patients with metastatic colorectal cancer.

A postmarketing surveillance study on erbitux (cetuximab) in patients with metastatic colorectal cancer refractory to irinotecan-containing treatment.

OBJECTIVE: This postmarketing surveillance study evaluated the safety and efficacy of cetuximab therapy in patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer (mCRC) in Taiwan. METHODS: Patients with EGFR-expressing mCRC who had failed prior irinotecan-based chemotherapy and were receiving cetuximab therapy were monitored for treatment efficacy and safety from the time of first infusion until 28 days after the last infusion regardless of the reasons fordiscontinuation. The study followed 269 patients for approximately 2 years. RESULTS: No unexpected adverse events associated with cetuximab therapy were reported, and most events were grade 1 or 2. The most common drug-related adverse events of any grade were rash (21.6%) and dermatitis acneiform (4.8%). Reported grade 3/4 events were rash (4.5%), dermatitis acneiform (0.4%), and diarrhea (0.4%). Cetuximab treatment for patients receiving second-/third-line (177 patients) or above therapy (92 patients) was associated with a median progression-free survival time of 3.37 and 3.90 months, respectively, and a median overall survival time of 17.6 and 21.1 months, respectively. The response rates for the second-/third-line treatment and fourth-line or above cetuximab treatment groups were similar (21.5% vs 17.4%; P = 0.428). CONCLUSION: Cetuximab showed no unexpected safety findings and was efficacious in treating patients with EGFR-expressing mCRC in community practice in Taiwan.

Role of peroxiredoxin I in rectal cancer and related to p53 status.

BACKGROUND: Neoadjuvant chemoradiotherapy is widely accepted for the treatment of localized rectal cancer. Although peroxiredoxin I (PrxI) and p53 have been implicated in carcinogenesis and cancer treatment, the role of PrxI and its interaction with p53 in the prognosis and treatment response of rectal cancer remain relatively unstudied. METHODS AND MATERIALS: In the present study, we examined the levels of PrxI and p53 in rectal cancer patients using membrane arrays and compared them with normal population samples. To demonstrate the biologic changes after manipulation of PrxI expression, we established stable transfectants of HCT-116 (wild-type p53) and HT-29 (mutant p53) cells with a PrxI silencing vector. The predictive capacities of PrxI and p53 were also assessed by relating the immunohistochemical staining of a retrospective series of rectal cancer cases to the clinical outcome. RESULTS: The membrane array and immunochemical staining data showed that PrxI, but not p53, was significantly associated with the tumor burden. Our immunochemistry findings further indicated that PrxI positivity was linked to a poor response to neoadjuvant therapy and worse survival. In cellular and animal experiments, the inhibition of PrxI significantly decreased tumor growth and sensitized the tumor to irradiation, as indicated by a lower capacity to scavenge reactive oxygen species and more extensive DNA damage. The p53 status might have contributed to the difference between HCT-116 and HT-29 after knockdown of PrxI. CONCLUSION: According to our data, the level of PrxI combined with the p53 status is relevant to the prognosis and the treatment response. We suggested that PrxI might be a new biomarker for rectal cancer.

Calvatia lilacina protein-extract induces apoptosis through glutathione depletion in human colorectal carcinoma cells.

This paper reports that a novel protein extract isolated from Calvatia lilacina (CL) can induce cell death against four types of human colorectal cancer cells. Importantly, CL was shown to be free of apoptotic effects against normal rat liver cells. We have also identified that CL-induced glutathione (GSH) depletion is the major contributor responsible for the apoptotic cell death induction of SW 480 cells, as evidenced by the observation that exogenously added N-acetylcysteine (NAC), or GSH, but not vitamin C, could offer a near complete protection of CL-treated cells against apoptotic cell death. Furthermore, the participation of reactive oxygen species (ROS) evoked a drop in the transmembrane potential (Delta Psi(m)) in the CL-induced apoptotic cell death. This observation can only be deemed as a minor pathway due to the fact that cyclosporine A (CyA) could only partially rescue the CL-treated cells from apoptotic cell death. Likewise, despite the fact that CL could induce the upregulation of Bax, its knockdown via siRNA (48 h) failed to completely mitigate apoptotic cell death, indicating that its role in this apoptotic process was insignificant. To further explore the possible underlying mechanism associated with CL-induced GSH depletion, we proceeded to determine the effect of CL on the cellular gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme responsible for GSH biosynthesis, and demonstrated that indeed gamma-GCS could be repressed by CL. Taken together, we report here for the first time that the anticancer effect of CL on human colorectal cancer cells is mediated through GSH depletion mechanism rather than a ROS-mediated killing process. This functional attribute of CL can thus provide the basis for the strategic design of a treatment of colorectal cancer.

Laparoscopic- vs. hand-assisted ultralow anterior resection: a prospective study.

PURPOSE: A standard laparoscopic-assisted operation can be conducted with colorectal anastomosis performed after extraction of specimen and insertion of a pursestring via a small left iliac fossa or suprapubic incision, or completed via hand-assisted laparoscopic technique with a 7-cm to 8-cm suprapubic incision. This study compares the short-term outcomes of either technique. METHODS: Sixty-three consecutive patients undergoing laparoscopic-assisted ultralow anterior resection or total mesorectal excision for rectal cancer were examined. The laparoscopic-assisted group (n = 31) had standard laparoscopic-assisted resection, whereas the hand-assisted laparoscopic group (n = 32) had a 7-cm to 8-cm suprapubic incision to allow an open colorectal anastomosis. In patients who were obese or have had multiple abdominal surgeries, the hand-assisted approach was generally favored. All patients had a diverting ileostomy. RESULTS: There was no conversion in either group. Mean operating time was significantly longer in the laparoscopic-assisted group (188.2 vs. 169.8 minutes; P < 0.0001). Mean duration for narcotic analgesia (1.65 vs. 3.38 days, P < 0.0001), mean time to flatus (1.97 vs. 3.19 days, P < 0.0001), and mean duration of intravenous hydration (2.45 vs. 3.88 days, P < 0.0001) were longer in the hand-assisted laparoscopic group. However, the mean length of hospital stay (5.8 vs. 5.9 days, P = 0.379) was similar. There was no major surgical complication in either group; chest infection, wound infection, and thrombophlebitis were similar between the laparoscopic-assisted group and the hand-assisted laparoscopic group. Adequacy of specimen harvest (distal tumor margins, P = 0.995; circumferential resection margin, P = 0.946; number of lymph nodes, P = 0.845) was similar. CONCLUSIONS: Although both laparoscopic-assisted and hand-assisted laparoscopic surgeries are safe and feasible for ultralow anterior resection, the hand-assisted technique significantly shortens operating time.

Stapled hemorrhoidopexy for prolapsed hemorrhoids in patients with liver cirrhosis; a preliminary outcome for 8-case experience.

PURPOSE: To investigate the efficacy and safety of stapled hemorrhoidopexy in treating prolapsed hemorrhoids in patients with liver cirrhosis. PATIENTS AND METHODS: Eight consecutive cases of patients with prolapsed hemorrhoids comorbid with liver cirrhosis, who had intractable response to other interventions, were enrolled in this retrospective study between January 2002 and June 2006 at our institute. Six patients (75%) had Child-Pugh class A liver cirrhosis, whereas only two patients (25%) had class B disease. Rectal varices were identified in three patients (37.5%), and esophageal varices were identified in six patients (75%). Concurrent rectal and esophageal varices existed in three patients (37.5%). The patients underwent stapled hemorrhoidopexy with Proximate PPH-03 in a lithotomy position under spinal/intravenous general anesthesia. RESULTS: There was no procedure-related mortality or major complications except hemorrhage. Two patients (25%) were complicated with postoperative staple-line bleeding, which was managed with conservative treatment without reoperation. There were no leading symptoms of relapsing during a follow-up period of at least 6 months. CONCLUSIONS: This study may prove that stapled hemorrhoidopexy is a feasible and safe approach for prolapsed hemorrhoids concurrent with liver cirrhosis.