Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

Developing a Robotic Surgical Platform Is Beneficial to the Implementation of the ERAS Program for Colorectal Surgery: An Outcome and Learning Curve Analysis.

BACKGROUND: Robotic surgery and ERAS protocol care are both prominent developments and have each become global trends. However, the effects and learning curves of combining robotic surgery and ERAS care in colorectal resection have not yet been well validated. This study aimed to present our real-world experience and establish the learning curves necessary for the implementation of an ERAS program in minimally-invasive surgery for colorectal resection, while also evaluating the impact that the development of the robotic technique has on ERAS outcomes. METHODS: A total of 155 patients who received elective, minimally-invasive surgery, including laparoscopic and robotic surgery for colorectal resection, with ERAS care during the period June 2019 to September 2021 were included in this retrospective analysis. Patients were divided chronologically into five groups (31 cases per quintile). Patient demographics, tumor characteristics, perioperative data, ERAS compliance, and surgical outcomes were all compared among the quintiles. Learning curves were evaluated based on ERAS compliance and optimal recovery, which are composed of an absence of major complications, postoperative length of stay (LOS) of no more than five days, and no readmission within 30 days. A multivariable logistic regression model was used to assess factors associated with postoperative LOS. RESULTS: There were no statistically significant differences seen overall or between the quintile groups in regards to demographic and tumor characteristic parameters. A total of 79 patients (51%) received robotic surgery, with the ratio of robotic groups rising chronologically from zero in the first quintile to 90.3% in the fifth quintile (p < 0.001). The median compliance rate of total ERAS protocol was 83.3% overall, 72.2% in the first quintile and 83.3% in the 2nd-5th quintiles (p < 0.001). A total of 85 patients underwent optimal recovery after surgery, four patients in the first quintile, 11 patients in the second quintile, and 21, 24, 25 patients in the 3rd-5th quintiles respectively (p < 0.001). There were significant improvements from early to later groups upon postoperative LOS (p < 0.001). In addition, the surgical outcomes including first oral intake within 24 hours after surgery, time to first stool and early termination of intravenous fluid administration showed significant improvement among the quintiles. A multivariable logistic regression model demonstrated that robotic surgery was superior to laparoscopic surgery upon postoperative LOS (odds ratio = 5.029, 95% confidence interval [CI] = 1.321 to 19.142; p = 0.018). CONCLUSIONS: Our experience demonstrated that an effective implementation of the ERAS program in minimally-invasive colorectal surgery requires 31 patients to accomplish the higher compliance and requires more cases to reach the maturation phase for optimal recovery. We believe that developing a robotic platform would have no impact on the learning curve of ERAS implementation. Moreover, there is a beneficial effect on the postoperative length of surgery provided through the combination of ERAS care and robotic surgery for patients undergoing colorectal resection.

Perioperative optimization of Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease mainly affecting the gastrointestinal tract. With the increased availability of modalities in the last two decades, the treatment of CD has advanced remarkably. Although medical treatment is the mainstay of therapy, most patients require surgery during the course of their illness, especially those who experience complications. Nutritional optimization and ERAS implementation are crucial for patients with CD who require surgical intervention to reduce postoperative complications. The increased surgical risk was found to be associated with the use of corticosteroids, but the association of surgical risk with immunomodulators, biologic therapy, such as anti-TNF mediations, anti-integrin medications, and anti-IL 12/23 was low in certainty. Decisions about preoperative medication must be made on an individual case-dependent basis. Preoperative imaging studies can assist in the planning of appropriate surgical strategies and approaches. However, patients must be informed of any alterations to their treatment. In summary, the management of perioperative medications and surgery-related decision-making should be individualized and patient-centered based on a multidisciplinary approach.

Real-World Evidence of Effectiveness and Safety of Vedolizumab for Inflammatory Bowel Disease in Taiwan: A Prospective Nationwide Registry (VIOLET) Study.

BACKGROUND: This nationwide prospective registry study investigated the real-world effectiveness, safety, and persistence of vedolizumab (VDZ) in inflammatory bowel disease (IBD) patients in Taiwan. Disease relapse rates after VDZ discontinuation due to reimbursement restriction were assessed. METHODS: Data were collected prospectively (January 2018 to May 2020) from the Taiwan Society of IBD registry. RESULTS: Overall, 274 patients (147 ulcerative colitis [UC] patients, 127 Crohn's disease [CD] patients) were included. Among them, 70.7% with UC and 50.4% with CD were biologic-naïve. At 1 year, 76.0%, 58.0%, 35.0%, and 62.2% of UC patients and 57.1%, 71.4%, 33.3%, and 30.0% of CD patients achieved clinical response, clinical remission, steroid-free remission, and mucosal healing, respectively. All patients underwent hepatitis B and tuberculosis screening before initiating biologics, and prophylaxis was recommended when necessary. One hepatitis B carrier, without antiviral prophylaxis due to economic barriers, had hepatitis B reactivation during steroid tapering and increasing azathioprine dosage, which was controlled with an antiviral agent. No tuberculosis reactivation was noted. At 12 months, non-reimbursement-related treatment persistence rates were 94.0% and 82.5% in UC and CD patients, respectively. Moreover, 75.3% of IBD patients discontinued VDZ due to mandatory drug holiday. Relapse rates after VDZ discontinuation at 6 and 12 months were 36.7% and 64.3% in CD patients and 42.9% and 52.4% in UC patients, respectively. CONCLUSIONS: The findings demonstrated VDZ effectiveness in IBD patients in Taiwan, with high treatment persistence rates and favorable safety profiles. A substantial IBD relapse rate was observed in patients who had mandatory drug holiday.

Learning curve and surgical outcome of robotic assisted colorectal surgery with ERAS program.

This study analyzed learning curve and the surgical outcome of robotic assisted colorectal surgery with ERAS program. The study results serve as a reference for future robotic colorectal surgeon who applied ERAS in clinical practice. This was a retrospective case-control study to analyze the learning curve of 141 robotic assisted colorectal surgery (RAS) by Da Vinci Xi (Xi) system and compare the surgical outcomes with 147 conventional laparoscopic (LSC) surgery in the same team. Evaluation for maturation was performed by operation time and the CUSUM plot. Patients were recruited from 1st February 2019 to 9th January 2022; follow-up was conducted at 30 days, and the final follow-up was conducted on 9th February 2022. It both took 31 cases for colon and rectal robotic surgeries to reach the maturation phase. Teamwork maturation was achieved after 60 cases. In the maturation stage, RAS required a longer operation time (mean: colon: 249.5 ± 46.5 vs. 190.3 ± 57.3 p < 0.001; rectum 314.9 ± 59.6 vs. 223.6 ± 63.5 p < 0.001). After propensity score matching, robotic surgery with ERAS program resulted in significant shorter length of hospital stay (mean: colon: 5.5 ± 4.5 vs. 10.0 ± 11.9, p < 0.001; rectum: 5.4 ± 3.5 vs. 10.1 ± 7.0, p < 0.001), lower minor complication rate (colon: 6.0% vs 20.0%, p = 0.074 ; rectum: 11.1% vs 33.3%, p = 0.102), and no significant different major complication rate (colon: 2.0% vs 6.0%, p = 0.617; rectum: 7.4% cs 7.4%, p = 1.0) to conventional LSC. Learning curve for robotic assisted colorectal surgery takes 31 cases. Robotic surgery with ERAS program brings significant faster recovery and fewer complication rate compared to laparoscopy in colorectal surgery.

Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection.

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.

Tattooing or Metallic Clip Placement? A Review of the Outcome Surrounding Preoperative Localization Methods in Minimally Invasive Anterior Resection Performed at a Single Center.

BACKGROUND: For minimally invasive colorectal surgery, preoperative localization is a typical procedure. We here aimed to analyze compared 2 different localization methods in terms of short-term outcomes, like the operative outcome and postoperative complication rates based on real-world data. MATERIALS AND METHODS: This was a retrospective analysis study conducted at a medical center. We enrolled patients who were presented with colonic tumor between January 1, 2016, and December 31, 2019, and they had undergone laparoscopic anterior resection in a single institution. Data included patient characteristics, operative outcome, length of hospital stay, and postoperative complications. RESULTS: The preoperative localization group had a better resection margin (4 vs. 3 cm; P<0.001) and fewer procedures of intraoperative colonoscopy (4.67% vs. 18.22%; P=0.002). Lymph node harvest occurred more in patients with endoscopic tattooing procedures than with metallic clip procedures (25 vs. 20; P=0.031). No significant difference was found regarding postoperative complications and the length of hospital stay. CONCLUSIONS: Preoperative localization in a laparoscopic anterior resection led to better surgical planning and resection margin. The metallic clip placement was helpful in the preoperative localization and setting. The endoscopic tattooing method had a larger lymph node harvest and with fewer intraoperative colonoscopy.

Incidence and management of metabolic acidosis with sodium bicarbonate in the ICU: An international observational study.

BACKGROUND: Metabolic acidosis is a major complication of critical illness. However, its current epidemiology and its treatment with sodium bicarbonate given to correct metabolic acidosis in the ICU are poorly understood. METHOD: This was an international retrospective observational study in 18 ICUs in Australia, Japan, and Taiwan. Adult patients were consecutively screened, and those with early metabolic acidosis (pH < 7.3 and a Base Excess < -4 mEq/L, within 24-h of ICU admission) were included. Screening continued until 10 patients who received and 10 patients who did not receive sodium bicarbonate in the first 24 h (early bicarbonate therapy) were included at each site. The primary outcome was ICU mortality, and the association between sodium bicarbonate and the clinical outcomes were assessed using regression analysis with generalized linear mixed model. RESULTS: We screened 9437 patients. Of these, 1292 had early metabolic acidosis (14.0%). Early sodium bicarbonate was given to 18.0% (233/1292) of these patients. Dosing, physiological, and clinical outcome data were assessed in 360 patients. The median dose of sodium bicarbonate in the first 24 h was 110 mmol, which was not correlated with bodyweight or the severity of metabolic acidosis. Patients who received early sodium bicarbonate had higher APACHE III scores, lower pH, lower base excess, lower PaCO2, and a higher lactate and received higher doses of vasopressors. After adjusting for confounders, the early administration of sodium bicarbonate was associated with an adjusted odds ratio (aOR) of 0.85 (95% CI, 0.44 to 1.62) for ICU mortality. In patients with vasopressor dependency, early sodium bicarbonate was associated with higher mean arterial pressure at 6 h and an aOR of 0.52 (95% CI, 0.22 to 1.19) for ICU mortality. CONCLUSIONS: Early metabolic acidosis is common in critically ill patients. Early sodium bicarbonate is administered by clinicians to more severely ill patients but without correction for weight or acidosis severity. Bicarbonate therapy in acidotic vasopressor-dependent patients may be beneficial and warrants further investigation.

Real-world evidence of the safety and effectiveness of regorafenib in Taiwanese patients with metastatic colorectal cancer: CORRELATE Taiwan.

BACKGROUND/PURPOSE: This analysis reports safety and effectiveness data from the Taiwanese cohort of the CORRELATE study. METHODS: CORRELATE was a prospective, observational study to assess the safety and effectiveness of regorafenib for the treatment of metastatic colorectal cancer (CRC) in real-world clinical practice that was conducted in 13 different countries in Asia, Europe and Latin America. The primary endpoint of the study was incidence of all treatment-emergent AEs (TEAEs), and secondary endpoints included overall survival (OS), progression-free survival (PFS), and disease control rate (DCR). RESULTS: The global study population (N = 1037) included 128 Taiwanese patients with a median age of 64 years, median weight of 62.02 kg and 66.41% were male. Reduced initiating doses of regorafenib and dose interruptions were common in Taiwanese patients (71.87% and 50.00%, respectively). The safety profile of regorafenib was consistent with that seen in Asian patients in the clinical development trials, including the CORRECT and CONCUR studies, with hand-foot-skin reactions (HFSR) of any grade occurring in 33.59% of patients. Median OS was 11.64 months in the Taiwanese patients (95% confidence interval [CI], 8.36-13.82) and median PFS was 2.17 months (95% CI, 1.97-2.89). CONCLUSION: The safety and effectiveness of regorafenib in this real-world study was generally consistent with the known efficacy and safety profile in Asian patients in clinical trials. TRIAL REGISTRATION: NCT02042144.

Type of adjuvant chemotherapy and treatment frequency in survival outcome of patients with colorectal liver metastases who underwent liver metastasectomy: an 8-year cohort study in Taiwan.

PURPOSE: The role of adjuvant chemotherapy (ACT) in treating patients who have colorectal liver metastases (CLM) and undergo liver metastasectomy (LMS) is unclear in this patient population. We aimed to compare the mortality of patients receiving different ACT (i.e., oxaliplatin-based, irinotecan-based, and 5-fluorouracil-only (5FU)) and different treatment frequencies. METHODS: We included 2583 patients with CLM who underwent LMS (including synchronous LMS [SLMS] and metachronous LMS [MLMS]) in this retrospective cohort study. We used Cox proportional hazard model to obtain hazard ratios (HRs) for mortality. The reference group was 5FU-only ACT when comparing ACT type and the reference group was treatment for ≤ 3 times when comparing ACT frequency. RESULTS: In SLMS patients, oxaliplatin-based ACT (HR = 0.78) and receiving ACT for ≥ 4 times (4-6 times, HR = 0.61; 7-9 times, HR = 0.69; 10-12 times, HR = 0.66) were associated with lower risk of mortality. In MLMS patients, oxaliplatin-based ACT (HR = 0.52), irinotecan-based ACT (HR = 0.64), and receiving ACT for 10-12 times (HR = 0.65) were associated with lower risk of mortality. CONCLUSIONS: In SLMS and MLMS patients, patients who received oxaliplatin-based ACT were more likely to survive than patients who received 5FU-only ACT. In MLMS patients, patients who received irinotecan-based ACT were also more likely to survive than those who received 5FU-only ACT. We recommend a course of at least four to six times of ACT after LMS in this patient population.

High serum folate might have a potential dual effect on risk of colorectal cancer.

BACKGROUND & AIMS: The possible dual role of serum folate in the development and progression of colorectal cancer (CRC) has not been well established in human studies. This study investigated the association between serum folate and the risk of CRC in subjects with CRC or colorectal adenomatous polyps (AP, a precursor of CRC), and healthy subjects. METHODS: This study has a case-control design. Two hundred and thirty-seven men and 171 women were recruited with 156 subjects in the CRC group, 70 subjects in the AP group and 182 healthy subjects in the control group. RESULTS: The risk of CRC was significantly increased in the third (OR, 3.46; 95% CI, 1.16-10.34) and fourth (OR, 4.86; 95% CI, 1.42-16.58) quartiles of serum folate concentration after adjusting for potential confounders among subjects with AP or CRC. Furthermore, serum folate concentration had no significant effect on the risk of CRC among subjects in the control and CRC groups. CONCLUSIONS: Higher serum folate concentration was significantly correlated with increased CRC risk in subjects with AP, while serum folate had no effect on CRC risk in healthy controls. Serum folate might possess potential dual modulatory effects on the risk of CRC.

The metabolic syndrome is associated with an increased risk of colorectal polyps independent of plasma homocysteine.

BACKGROUND/AIMS: The links between the metabolic syndrome and homocysteine in relation to the risk of colorectal polyps are not understood. The purpose of this study was to investigate the association between the metabolic syndrome and homocysteine and further analyze the relationship between these two factors and the risk of colorectal polyps. METHODS: This was a case-control study. A total of 135 participants with colorectal polyps (cases) and 110 participants without polyps (controls) were recruited. RESULTS: There were 59 participants with the metabolic syndrome in the case group and 36 participants with the metabolic syndrome in the control group. The metabolic syndrome and its individual components, except for serum triglycerides, and homocysteine were associated with the risk of colorectal polyps. When the association of the metabolic syndrome and homocysteine with the risk of colorectal polyps was simultaneously considered, the association between homocysteine and the risk of colorectal polyps disappeared, but waist circumference, systolic and diastolic blood pressure, high-density lipoprotein cholesterol, and the metabolic syndrome itself were still significant risk factors for the development of colorectal polyps. CONCLUSION: Although the metabolic syndrome and plasma homocysteine were individually related to the risk of colorectal polyps, the metabolic syndrome was a major contributing factor in relation to the risk of colorectal polyps independent of plasma homocysteine.

Preoperative chemoradiotherapy with oxaliplatin and tegafur-uracil in locally advanced rectal cancer: pathologic complete response rate and preliminary results of overall and disease-free survival in a single institute in Taiwan.

BACKGROUND: We conducted a Phase II study of biweekly oxaliplatin plus oral tegafur-uracil in the preoperative chemoradiotherapy (CRT) for locally advanced resectable mid-to-lower rectal cancer in our hospital, to evaluate the feasibility of this drug combination in tumor pathologic response, acute toxicity, local control, disease-free survival (DFS), overall survival (OS), and time to distant metastasis in an Asian cohort. METHODS: Twenty patients with histopathologically confirmed rectal cancer (Stage II-III) were enrolled in the study. Radiotherapy of 50 Gy was delivered in 25 fractions of 2 Gy, one fraction/day, five fractions/week, for 5 weeks. Oxaliplatin 55 mg/m(2) was administered intravenously for 60 minutes on Day 1 every 2 weeks, and tegafur-uracil 350 mg/m(2) was given orally everyday during the whole radiotherapy course, including holidays. Surgery was scheduled 6 weeks after completion of the preoperative chemoradiotherapy. The primary endpoint was to determine the pathologic complete response (pCR) rate after this neoadjuvant chemoradiotherapy. The secondary endpoint was to determine the treatment-related toxicity profile, local control, DFS, OS, and time to metastasis. RESULTS: All patients underwent a complete course of preoperative chemoradiotherapy. There was no local recurrence during the study period. The complete resection rate was 20/20 (100%) and the close resection margin rate was 3/20 (15%). The pCR rate was 8/20 (40%). During chemoradiotherapy, the most frequent toxicity was diarrhea 9/20 (45% of patients, grade 2 in 3/20, 15%). There were no grade 3 or higher hematologic or non-hematologic events or treatment-related deaths. The 3-year OS and DFS rates were 94.1% and 78.6%, respectively. CONCLUSION: Preoperative chemoradiotherapy with oxaliplatin and tegafur-uracil was well-tolerated and achieved an excellent pCR in our patients with locally advanced mid-to-lower rectal cancer.

High homocysteine is associated with increased risk of colorectal cancer independently of oxidative stress and antioxidant capacities.

BACKGROUND & AIMS: Increased homocysteine concentration and oxidative stress and decreased antioxidant capacities are thought to affect carcinogenesis. However, the associations of homocysteine, cysteine, pyridoxal 5'-phosphate (PLP) and folate with oxidative stress and antioxidant capacities in patients with colorectal cancer are unclear. The purpose of this study was to determine the associations of homocysteine, cysteine, PLP and folate with oxidative stress indicators and antioxidant capacities, and to further analyze their relationships with respect to risk for colorectal cancer. METHODS: One hundred and sixty-eight subjects with colorectal cancer (cases) and 188 healthy subjects (controls) were recruited. RESULTS: There were no significant associations of homocysteine, cysteine and folate with oxidative stress indicators and antioxidant capacities in cases; however, PLP positively correlated with glutathione S-transferase activities after adjusting for potential confounders in cases. Subjects with higher plasma homocysteine concentration exhibited significantly increased risk of colorectal cancer with or without adjustment for potential confounders. The associations of cysteine, PLP and folate with the risk of colorectal cancer were not observed when potential confounders were adjusted. CONCLUSIONS: Increased homocysteine was strongly associated with the risk of colorectal cancer independently of oxidative stress indicators and antioxidant capacities. However, cysteine, PLP and folate were not found to be related to oxidative stress, antioxidant capacities and the risk of colorectal cancer.

A randomized, double-blind, placebo-controlled trial of a Chinese herbal Sophora flower formula in patients with symptomatic haemorrhoids: a preliminary study.

Dried flowers and buds of Sophora japonica (Huaihua) are used in China, Japan and Korea for treating haematemesis and bleeding haemorrhoids. This study compared the clinical safety and efficacy of a Sophora flower formula with a placebo for the conservative treatment of symptomatic haemorrhoids. The study was a prospective, double-blind, randomized placebo-controlled trial. The clinical effective rate, symptom score and the incidence of important clinical events were used as observation indices to evaluate the effect of the Sophora flower formula. The results showed that after 7 days of treatment, improvement was observed in 87.0% of the patients' major symptoms in the Sophora flower formula group compared with 81.8% of those in the placebo group. After 14 days, 78.2% patients in the Sophora flower formula group were asymptomatic, whereas 40.9% of those in the placebo group exhibited residual symptoms. However, the difference between both groups was not statistically significant. As the bowel habits of the patients improved and as the patients took sitz baths, their symptoms improved drastically, regardless of the use of the Sophora flower formula. These findings indicate that the traditional Chinese Sophora flower formula is clinically safe; however, its effects on haemorrhoids need to be studied in a larger sample size and with different dosages. The present study results may be a potential clinical reference for physicians prescribing medications for patients with symptomatic haemorrhoids.

A new method for post Genome-Wide Association Study (GWAS) analysis of colorectal cancer in Taiwan.

Recently, single nucleotide polymorphisms (SNPs) located in specific loci or genes have been identified associated with susceptibility to colorectal cancer (CRC) in Genome-Wide Association Studies (GWAS). However, in different ethnicities and regions, the genetic variations and the environmental factors can widely vary. Therefore, here we propose a post-GWAS analysis method to investigate the CRC susceptibility SNPs in Taiwan by conducting a replication analysis and bioinformatics analysis. One hundred and forty-four significant SNPs from published GWAS results were collected by a literature survey, and two hundred and eighteen CRC samples and 385 normal samples were collected for post-GWAS analysis. Finally, twenty-six significant SNPs were identified and reported as associated with susceptibility to colorectal cancer, other cancers, obesity, and celiac disease in a previous GWAS study. Functional analysis results of 26 SNPs indicate that most biological processes identified are involved in regulating immune responses and apoptosis. In addition, an efficient prediction model was constructed by applying Jackknife feature selection and ANOVA testing. As compared to another risk prediction model of CRC for European Caucasians population, which performs 0.616 of AUC by using 54 SNPs, the proposed model shows good performance in predicting CRC risk within the Taiwanese population, i.e., 0.724 AUC by using 16 SNPs. We believe that the proposed risk prediction model is highly promising for predicting CRC risk within the Taiwanese population. In addition, the functional analysis results could be helpful to explore the potential associated regulatory mechanisms that may be involved in CRC development.

Clinical experience in 89 consecutive cases of chronic radiation enterocolitis.

BACKGROUND: Pelvic irradiation has been a popular therapy modality for cervical cancer for many years, and its usage in rectal cancer and prostate cancer cases is on the rise. However, it is associated with significant side effects. In this study, we compared the different characteristics of surgical and nonsurgical patients who were treated for radiation enterocolitis, the treatment results, posttreatment quality of life (QOL), nutrition status, and predisposing factors for surgery. METHODS: From 1985 to 2009, the records of a total of 89 patients with chronic radiation enterocolitis in our hospital were retrospectively reviewed for demographic data, operative data and long-term treatment results. Posttreatment QOL and nutrition status were also recorded. Univariate and multivariate analyses were performed to identify the independent predicting factors associated with surgical intervention. Characteristics of surgical and nonsurgical patients were compared. RESULTS: Radiotherapy before 1995, concomitant radiation uropathy and smoking were independent predictive factors for surgery. Surgical and nonsurgical cases had similar Kaplan-Meier curves. Although the recurrence rate of radiation enterocolitis was much higher for the surgical group (p = 0.031), both groups had similar QOL score (median: 8 vs.7; p = 0.709), serum albumin level (3.29 g/dL vs. 3.16 g/dL; p = 0.095), and body mass index (20.19 vs. 19.86; p = 0.603). CONCLUSIONS: We confirmed that as compared with recently developed innovative techniques, early primitive radiotherapy techniques were associated with more severe radiotherapy complications that required surgery. Smoking may enhance patients' vulnerability to severe radiation injury. Surgery for radiation-induced intestinal obstruction, intestinal fistula and perforation is warranted because QOL, serum albumin level and body mass index were similar between the surgical and nonsurgical groups.

Pelvic exenteration for men with locally advanced rectal cancer: a morbidity analysis of complicated cases.

BACKGROUND: The role of pelvic exenteration in locally advanced rectal cancer (LARC) has not been clearly defined. This procedure carries a mortality rate of approximately 10%. The challenges during pelvic surgery are different between men and women. The morbidity in men with LARC who received pelvic exenteration was analyzed. METHODS: Medical records of men with LARC undergoing total pelvic exenteration or supralevator pelvic exenteration from January 1991 to December 2007 were retrospectively reviewed. RESULTS: A total of 23 cases were included in the analysis. Thirteen patients had primary cancer; 10 had recurrent cancer. Microscopically clear surgical margins were obtained in 14 patients (60.9%). Sixteen patients (69.6%) experienced major or minor postoperative complications. The overall in-hospital mortality rate was 8.7%. Ten patients (43.5%) died within 1 year after surgery. All 10 patients with early mortality experienced refractory complications and repeated surgeries. The longest survival of patients with margin involvement was 25 months. The correlation between involved surgical margins and 1-year mortality was statistically significant (p = 0.001). CONCLUSION: Resection margins with tumor involvement after pelvic exenteration is associated with poor prognosis and early mortality in men with locally advanced rectal cancer.

Recurrence of radiation enterocolitis within 1 year is predictive of 5-year mortality in surgical cases of radiation enterocolitis: our 18-year experience in a single center.

BACKGROUND: Pelvic irradiation is commonly used in the treatment of pelvic malignancies. Chronic radiation enterocolitis is the most serious complication resulting from such treatment, and it frequently requires surgery. The prognosis for patients after surgery remains ill-defined. We conducted a retrospective study to identify risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis. METHODS: From 1985 to 2009, a total of 89 patients were diagnosed as having chronic radiation enterocolitis in Taichung Veterans General Hospital. The chart records of 35 surgical and 54 nonsurgical patients were reviewed. A total of 21 candidate risk factors were selected from (1) those related to rapid disease progression (recurrence within 1 year, reoperation within 1 year, short latency), (2) those mentioned in published series (diabetes mellitus, history of smoking, history of abdominopelvic surgery), and (3) other risk factors that might adversely affect outcomes (older age, higher radiation dosage, longer latency period). Factors with p < 0.1 in univariate analysis were subjected to multivariate analysis to identify those that were independent risk factors. RESULTS: Surgical patients were significantly older (65.09 vs. 61.61 years, p = 0.011), had a longer latency period (17.08 vs. 8.09 months, p = 0.037), and were associated with a higher percentage of radiation uropathy (54.28 vs. 12.96%, p < 0.0001) than nonsurgical patients. There was no difference in radiation dosage between surgical and nonsurgical cases (p = 0.152). Recurrence of radiation enterocolitis within 1 year following surgery (p = 0.022), older age (p = 0.002), and uncured cancer (p = 0.001) were identified as independent risk factors for poor overall survival after surgery. All patients (100%) who had recurrent radiation enterocolitis within 1 year of surgery died within 5 years of recurrence. CONCLUSIONS: The surgical cases were older, had a longer latency period, and had a higher percentage of radiation uropathy .Recurrence of radiation enterocolitis within 1 year after surgery, older age, and uncured cancer were independent risk factors associated with mortality for patients who received surgery for chronic radiation enterocolitis.