Pelvic Neoadjuvant Radiotherapy for Stage M1a Rectal Adenocarcinoma Patients Treated With Systemic Therapy Followed by Proctectomy and Metastasectomy: A Nationwide Retrospective Cohort Study.

BACKGROUND/AIM: The effect of pelvic neoadjuvant radiotherapy (nRT) for stage M1a rectal adenocarcinoma patients treated with systemic therapy followed by proctectomy and metastasectomy was scarcely investigated in the literatures. PATIENTS AND METHODS: The eligible rectal cancer patients diagnosed between 2011-2019 were identified via the Taiwan Cancer Registry. In the primary analysis, we used propensity score weighting to balance observable potential confounders and compared the hazard ratio (HR) of death for the nRT group vs. without RT group. We also compared the incidence of rectal cancer mortality (IRCM) and performed various supplementary analyses. RESULTS: Our primary analyses included 145 patients. nRT was associated with improved OS (HR=0.51, p=0.01). The numerical trends remained similar for IRCM and in supplementary analyses. CONCLUSION: nRT was associated with improved OS in our study population.

Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study.

OBJECTIVE: This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC). METHODS: This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48). RESULTS: Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the -intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported. CONCLUSION: Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months' follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.

Laparoscopic total pelvic peritonectomy for colorectal cancer pelvic carcinomatosis: a retrospective case series and photographic/videographic step-by-step guide.

BACKGROUND: Cytoreductive surgery (CRS) for colorectal cancer peritoneal carcinomatosis has been shown to prolong survival with acceptable morbidity rates. Total pelvic peritonectomy (TPP), or complete removal of all pelvic peritoneum, constitutes an important and technically challenging component of CRS. Here we report our experience and describe our technique of laparoscopic total pelvic peritonectomy (LTPP), using a photographic/videographic step-by-step guide. METHODS: All patients who underwent LTPP for pelvic carcinomatosis from a colorectal origin were included in the study. Only patients with peritoneal cancer index (PCI) score of ≤ 10 were selected for CRS with LTPP. Patients who had extra-abdominopelvic cavity metastases were excluded. The final decision to proceed with CRS was made following laparoscopic assessment. RESULTS: From January 2017 to December 2020, 15 consecutive patients underwent LTPP for colorectal cancer pelvic carcinomatosis. Median patient age and PCI score was 53 years (range 33-78) and 8 (range 3-10), respectively. Complete cytoreduction was achieved in all patients. Thirteen patients (87%) underwent concomitant hyperthermic intraperitoneal chemotherapy (HIPEC). The median operative duration was 748 min (interquartile range [IQR] 681-850). Median intra-operative blood loss and length of hospital stay was 100 ml (IQR 50-300) and 10 days (IQR 8-12), respectively. Five patients (33%) experienced 30-day post-operative morbidity, with one (6.7%) experiencing a higher grade (Clavien-Dindo IIIa) complication. Median follow-up duration was 13 months (IQR 3-19), during which four (27%) had systemic recurrence and one (6.7%) died after 15 months following peritoneal and systemic recurrences. CONCLUSION: LTPP is a feasible option for low-volume pelvic carcinomatosis from colorectal cancer, offering the benefits of a minimally invasive approach. Strict patient selection is essential, and the procedure should be converted if the PCI score cannot be assessed or complete cytoreduction cannot be achieved. Proficiency at laparoscopic pelvic surgery is mandatory for performing LTPP.

Noninferiority clinical trial comparing the bowel cleansing efficacy of sodium phosphate tablets (Quiklean®) with a polyethylene glycol/bisacodyl kit.

BACKGROUND: Efficient bowel cleansing is essential for a successful colonoscopy, but the ideal cleansing agent, volume, and pharmaceutical dosage form have yet to be determined. Small-volume cleansers enhance patient compliance. AIM: To compare the bowel cleansing efficacy of 32-tablet sodium phosphate (Quiklean®) with 2-L polyethylene glycol (PEG)/bisacodyl (Klean-Prep/ Dulcolax®) under identical dietary recommendations. METHODS: This multicenter, randomized, parallel-group, noninferiority clinical trial enrolled 472 outpatients, randomized 456 subjects, and scheduled 442 subjects to undergo colonoscopy (Quiklean® = 222 and Klean-Prep/Dulcolax® = 220). After bowel preparation, a colonoscopist performed the colonoscopy with video recorded for rating. The primary efficacy endpoint was the bowel cleansing quality using the Aronchick Scale. The secondary endpoints were the bowel cleansing efficacy of three colon segments, tolerability and acceptability, safety using the Ottawa bowel preparation scale, questionnaires by subjects, and monitoring of adverse events. RESULTS: Success rates (Excellent + Good) of the bowel cleansing quality by Aronchick Scale were 98.6% (n = 205) and 97.6% (n = 204) in the Quiklean® and Klean-Prep/Dulcolax® groups, respectively. Quiklean® demonstrated noninferiority over Klean-Prep/Dulcolax® in colon cleansing efficacy. Quicken showed better tolerability and acceptability in the overall experience (was rated as excellent; 24.0% vs 17.2%; P = 0.0016) and the taste of the study preparation (was rated as excellent, 23.1% vs 13.4%; P < 0.0001) than Klean-Prep/Dulcolax®. Safety profiles did not differ between the two groups. Our data indicate that Quiklean® is an adequate, well-tolerated bowel cleansing preparation compared with the standard comparator Klean-Prep/Dulcolax®. CONCLUSION: Quiklean® is sodium phosphate tablets available on Taiwan's market for bowel preparation; it potentially offers patients an alternative to standard large-volume bowel preparation regimens and may, therefore, increase positive attitudes toward colonoscopies and participation rates.

Determination of the UGT1A1 polymorphism as guidance for irinotecan dose escalation in metastatic colorectal cancer treated with first-line bevacizumab and FOLFIRI (PURE FIST).

AIM: Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism plays a crucial role in the increased susceptibility of patients to irinotecan and its toxicity. This study is a multicenter, randomised clinical trial comparing the clinical outcomes and adverse events (AEs) in metastatic colorectal cancer (mCRC) patients treated with bevacizumab plus FOLFIRI with or without UGT1A1 genotyping and irinotecan dose escalation as the first-line therapy. METHODS: The control group received conventional biweekly FOLFIRI plus bevacizumab without UGT1A1 genotyping, whereas the study group received the same regimen with irinotecan dose escalation based on UGT1A1 genotyping. The primary end-point was progression-free survival (PFS), and secondary end-points were overall response rate (ORR), disease control rate (DCR), overall survival (OS), AEs and metastasectomy rate. RESULTS: Over a median follow-up of 26.0 months (IQR, 17.0-35.0 months), study group (n = 107) was superior to the control group (n = 106) in PFS, OS, ORR, DCR, and metastasectomy rate (all P < 0.05). Furthermore, there were no significant differences in AEs ≥ grade III between the two groups, even with the 1.36-fold increase in the relative dose intensity of irinotecan in the study group. Dose escalation of irinotecan, an independent factor of ORR (P < 0.001) and DCR (P = 0.006), improved PFS in mCRC patients with wild-type and mutant KRAS (P = 0.007 and P = 0.019, respectively). CONCLUSION: The current study revealed that mCRC patients, regardless of KRAS gene status, with UGT1A1 genotyping can tolerate escalated doses of irinotecan and potentially achieve a more favourable clinical outcome without significantly increased toxicities. CLINICAL TRIAL REGISTRATION: NCT02256800.

Long-term Oncologic Outcomes of Laparoscopic Anterior Resections for Cancer with Natural Orifice Versus Conventional Specimen Extraction: A Case-Control Study.

BACKGROUND: Although the short-term advantages of natural orifice specimen extraction are widely recognized, controversy exists concerning oncologic safety after laparoscopic surgery for colorectal cancer. OBJECTIVE: This study aimed to investigate the impact of natural orifice specimen extraction on local recurrence and long-term survival of patients undergoing colorectal cancer surgery. DESIGN: This is a propensity score-matched comparative study. SETTING: This study presents a single-center experience. PATIENTS: We retrospectively analyzed the records of patients who underwent curative laparoscopic anterior resection for American Joint Committee on Cancer stage I to III sigmoid or upper rectal cancer in 2011 to 2014, based on prospectively collected data. INTERVENTIONS: Oncologic outcomes were compared between patients undergoing natural orifice or conventional specimen extraction by minilaparotomy. Patients were matched 1:1 according to propensity scores calculated by logistic regression analysis with the following covariates: American Joint Committee on Cancer stage, tumor diameter, age, sex, BMI, and T stage. Cox proportional hazards regression analysis was performed to determine the impact on oncologic outcome. MAIN OUTCOME MEASURES: The primary outcomes measured were local recurrence and disease-free survival rates at 5 years. RESULTS: Of 392 eligible patients, 188 were matched (94 undergoing natural orifice specimen extraction and 94 undergoing conventional extraction by minilaparotomy). Median follow-up was 50.3 months. The cumulative local recurrence risk at 5 years was 2.3% and 3.5% (p = 0.632), whereas 5-year disease-free survival for all tumor stages combined was 87.3% and 82.0% (p = 0.383) in laparoscopic anterior resection with natural orifice specimen extraction and conventional extraction groups. T3 and T4 stages were the only variables independently associated with disease-free survival. LIMITATIONS: This study was limited because it focused on a single center, was a retrospective analysis, contained no long-term anorectal function testing, and had a small sample size. CONCLUSION: Long-term oncologic outcomes of patients undergoing laparoscopic anterior resection with natural orifice specimen extraction for sigmoid and upper rectal cancer do not differ from those undergoing conventional extraction. Thus, natural orifice specimen extraction could be a viable alternative to reduce abdominal wall insult in laparoscopic colorectal operations for malignancy in selected patients. See Video Abstract at http://links.lww.com/DCR/B241. RESULTADOS ONCOLÓGICOS A LARGO PLAZO DE RESECCIONES ANTERIORES LAPAROSCÓPICAS PARA CÁNCER A TRAVÉS DE ORIFICIO NATURAL FRENTE A EXTRACCIÓN CONVENCIONAL DEL ESPÉCIMEN: UN ESTUDIO DE CASOS Y CONTROLES: Si bien las ventajas a corto plazo de la extracción de especímenes por orificio natural son ampliamente reconocidas, existe controversia con respecto a la seguridad oncológica después de la cirugía laparoscópica para el cáncer colorrectal.Investigar el impacto de la extracción de especímenes por orificio natural en la recurrencia local y la supervivencia a largo plazo de pacientes sometidos a cirugía de cáncer colorrectal.Estudio comparativo con emparejamiento por puntuación de propensión.Experiencia en un centro único.Analizamos retrospectivamente los registros de pacientes que se sometieron a resección anterior laparoscópica curativa para cáncer sigmoideo o rectal superior AJCC en estadio I-III en 2011-2014, con base en datos recolectados prospectivamente.Los resultados oncológicos se compararon entre pacientes sometidos a extracción por orificio natural o convencional mediante minilaparotomía de especímenes. Los pacientes fueron emparejados 1:1 de acuerdo con los puntajes de propensión calculados por análisis de regresión logística con las siguientes covariables: estadio AJCC, diámetro del tumor, edad, sexo, índice de masa corporal y estadio T. Se realizó un análisis de regresión de riesgos proporcionales de Cox para determinar el impacto en el resultado oncológico.Recurrencia local y tasas de supervivencia libre de enfermedad a los 5 años.De 392 pacientes elegibles, 188 fueron emparejados (94 sometidos a extracción de espécimen por orificio natural y 94 a extracción convencional por minilaparotomía). La mediana de seguimiento fue de 50.3 meses. El riesgo cumulativo de recurrencia local a 5 años fue de 2.3% y 3.5% (p = 0.632), mientras que la supervivencia libre de enfermedad a 5 años para todas las etapas tumorales combinadas fue de 87.3% y 82.0% (p = 0.383) en los grupos de resección anterior laparoscópica con extracción de espécimen por orificio natural y extracción convencional, respectivamente. Las etapas T3 y T4 fueron las únicas variables asociadas independientemente con la supervivencia libre de enfermedad.Centro único, análisis retrospectivo, ausencia de pruebas de función anorrectal a largo plazo y tamaño de muestra pequeño.Los resultados oncológicos a largo plazo de los pacientes sometidos a resección anterior laparoscópica con extracción de espécimen por orificio natural para cáncer sigmoideo y rectal superior no difieren de los de aquellos sometidos a extracción convencional. Por lo tanto, la extracción de especímenes por orificio natural podría ser una alternativa viable para reducir el insulto a la pared abdominal en operaciones colorrectales laparoscópicas por malignidad en pacientes selectos. Consulte Video Resumen en http://links.lww.com/DCR/B241.

Combined repeat laparoscopy and transanal endolumenal repair (hybrid approach) in the early management of postoperative colorectal anastomotic leaks: technique and outcomes.

BACKGROUND: Few clear recommendations exist for the management of colorectal anastomotic leaks, often based on surgeon preferences or institutional protocols. The primary goal was to evaluate the feasibility and safety of the combined laparoscopic and transanal (hybrid) approach to treat postoperative colorectal anastomotic leaks. The secondary goals included comparison of outcomes following early (< 5 days after initial resection) versus late (≥ 5 days) detection of leaks. MATERIALS AND METHODS: Sixteen hemodynamically stable patients, with anastomotic dehiscence < 50% of the circumference after laparoscopic anterior resection underwent repeat laparoscopy (lavage/drainage) and transanal endolumenal repair (7 low (< 5 cm from the anal verge) with an ordinary anoscope and 9 high (≥ 5 cm from the anal verge) with a transanal endoscopic operations (TEO®) platform). RESULTS: The median delay to detection and management was 4.5 days. The procedure was feasible in 13/16 patients (3 patients required conversion to laparotomy). Primary healing of the anastomosis was obtained in 14 patients (13 with the combined procedure, one after conversion). Two patients (1 early, 1 late) sustained persistent purulent discharge via their drain, but the repair healed secondarily. All patients requiring conversion to laparotomy (n = 3) or sustaining intra-operative complications (n = 3) were in the delayed group. No patients required further intervention or died. Protective stomas, created either at index surgery (n = 7) or at re-operation (n = 9), were closed in 14/16 patients within 6 months and no anastomotic sinus, persistent or recurrent fistula, was noted at 1-year follow-up. LIMITATIONS: This is a single-center study consisting of small sample size. CONCLUSIONS: Combined repeat laparoscopy and transanal endolumenal repair is feasible and safe, potentially reducing postoperative morbidity associated with repeat laparotomy and anastomotic leaks. Early detection and re-intervention are fundamental to success. Currently missing from the International Study Group of Rectal Cancer recommendations, laparoscopy and endolumenal repair could be added as a therapeutic option in Grade B.

Diversity and enterotype in gut bacterial community of adults in Taiwan.

BACKGROUND: Gastrointestinal microbiota, particularly gut microbiota, is associated with human health. The biodiversity of gut microbiota is affected by ethnicities and environmental factors such as dietary habits or medicine intake, and three enterotypes of the human gut microbiome were announced in 2011. These enterotypes are not significantly correlated with gender, age, or body weight but are influenced by long-term dietary habits. However, to date, only two enterotypes (predominantly consisting of Bacteroides and Prevotella) have shown these characteristics in previous research; the third enterotype remains ambiguous. Understanding the enterotypes can improve the knowledge of the relationship between microbiota and human health. RESULTS: We obtained 181 human fecal samples from adults in Taiwan. Microbiota compositions were analyzed using next-generation sequencing (NGS) technology, which is a culture-independent method of constructing microbial community profiles by sequencing 16S ribosomal DNA (rDNA). In these samples, 17,675,898 sequencing reads were sequenced, and on average, 215 operational taxonomic units (OTUs) were identified for each sample. In this study, the major bacteria in the enterotypes identified from the fecal samples were Bacteroides, Prevotella, and Enterobacteriaceae, and their correlation with dietary habits was confirmed. A microbial interaction network in the gut was observed on the basis of the amount of short-chain fatty acids, pH value of the intestine, and composition of the bacterial community (enterotypes). Finally, a decision tree was derived to provide a predictive model for the three enterotypes. The accuracies of this model in training and independent testing sets were 97.2 and 84.0%, respectively. CONCLUSIONS: We used NGS technology to characterize the microbiota and constructed a predictive model. The most significant finding was that Enterobacteriaceae, the predominant subtype, could be a new subtype of enterotypes in the Asian population.

Natural Orifice Specimen Extraction With Single Stapling Colorectal Anastomosis for Laparoscopic Anterior Resection: Feasibility, Outcomes, and Technical Considerations.

BACKGROUND: Double and triple stapling techniques to close the rectal stump in laparoscopic anterior resection are fraught with technical drawbacks that could possibly be avoided with the use of the single stapling technique. However, little is known of its safety in laparoscopic surgery or outcomes when combined with natural orifice specimen extraction. OBJECTIVE: This study aims to analyze the feasibility and the operative and immediate postoperative outcomes of single-stapled anastomosis and natural orifice specimen extraction with conventional techniques. It intends to evaluate technical variations related to colon, mesentery, and pelvic anatomy characteristics. DESIGN AND PATIENTS: A consecutive series of 188 patients underwent elective surgery for benign or malignant lesions between 10 and 40 cm from the anal verge, 5 cm or less in diameter on radiological examination, stage T1 to T3, Nx, M0, with 2 different methods of rectal stump closure (pursestring vs linear-stapled closure) associated with single or double stapling and per anus vs conventional specimen extraction. SETTING: This study was conducted at China Medical University Hospital, Taiwan, a tertiary referral center, between January 2012 and April 2015. MAIN OUTCOME MEASURES: The main outcomes measured are feasibility and operative and immediate postoperative outcomes. RESULTS: Single-stapled resection with natural orifice specimen extraction was feasible in 94% patients with an 11% perioperative morbidity rate. The patients required statistically significantly less analgesia, had earlier return of bowel movements, and shorter hospital stay, whereas there was no statistically significant difference in the overall readmission rate and overall morbidity, including anastomotic leakage. LIMITATIONS: This was a single-center, retrospective case-matched study. CONCLUSION: Anatomic variations (short colon and short mesentery) can be managed adequately with intracorporeal anvil head fixation. The single stapling technique is feasible and as safe as conventional double stapling techniques, although it is technically more demanding. The transanal endoscopic operation platform can be useful when the rectal stump is long.

Efficacy, Tolerability, and Biomarker Analyses of Once-Every-2-Weeks Cetuximab Plus First-Line FOLFOX or FOLFIRI in Patients With KRAS or All RAS Wild-Type Metastatic Colorectal Cancer: The Phase 2 APEC Study.

BACKGROUND: In patients with KRAS wild-type (wt) metastatic colorectal cancer (mCRC), outcomes with first-line chemotherapies are improved by adding weekly cetuximab. The APEC study investigated first-line once-every-2-weeks cetuximab plus chemotherapy for patients with KRAS wt mCRC; additional biomarker subgroups were also analyzed. PATIENTS AND METHODS: APEC was a nonrandomized phase 2 trial conducted in the Asia-Pacific region. Patients (n = 289) received once-every-2-weeks cetuximab with investigator's choice of chemotherapy (FOLFOX or FOLFIRI). The primary end point was best confirmed overall response rate (BORR); progression-free survival (PFS) and overall survival (OS) were secondary end points. Early tumor shrinkage (ETS) and depth of response (DpR) were also evaluated. RESULTS: In the KRAS wt population, BORR was 58.8%, median PFS 11.1 months, and median OS 26.8 months. Expanded RAS mutational analysis revealed that patients with RAS wt mCRC had better outcomes (BORR = 64.7%; median PFS = 13.0 months; median OS = 28.4 months). The data suggest that ETS and DpR may be associated with survival outcomes in the RAS wt population. Although this study was not designed to formally assess differences in outcome between treatment subgroups, efficacy results appeared similar for patients treated with FOLFOX and FOLFIRI. There were no new safety findings; in particular, grade 3/4 skin reactions were within clinical expectations. CONCLUSION: The observed activity and safety profile is similar to that reported in prior first-line pivotal studies involving weekly cetuximab, suggesting once-every-2-weeks cetuximab is effective and tolerable as first-line therapy and may represent an alternative to weekly administration.

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 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.

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.

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.

EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 as potential prognostic markers for postoperative Taiwanese colorectal cancer patients.

Undetected micrometastasis may play a key role in the early relapse of colorectal cancer (CRC) patients. The aim of this study was to detect circulating tumor cells (CTCs) for predicting early relapse of CRC patients by a weighted enzymatic chip array (WEnCA) and analyze 15 candidate genes associated with CRC carcinogenesis. The genes of 105 postoperative CRC patients were analyzed by membrane array and direct sequencing. We constructed a WEnCA platform including five prognosis-related genes and analyzed the detection rate of WEnCA for CTCs in 30 clinically confirmed CRC relapse patients. Postoperative relapse was significantly correlated with gene overexpression, including EVI2B (p=0.001, OR=4.622), ATP2A2 (p=0.006, OR=4.688), S100B (p=0.001, OR=11.521), TM4SF3 (p=0.001, OR=6.756), and OLFM4 (p=0.008, OR=3.545). Using WEnCA (weighting score of each gene: 5 to EVI2B, 5 to ATP2A2, 12 to S100B, 7 to TM4SF3, and 4 to OLFM4), we could detect CTCs presenting these genotypes in relapsed CRC patients. The sensitivity, specificity, and accuracy were 94.7%, 93.5%, and 97%, respectively. The results of the present study suggest that EVI2B, ATP2A2, S100B, TM4SF3, and OLFM4 could be potential prognostic markers for CRC patients.

Overexpression of S100B, TM4SF4, and OLFM4 genes is correlated with liver metastasis in Taiwanese colorectal cancer patients.

Distant metastasis of colorectal cancer (CRC) occurs mainly in the liver and is the major cause of death. This study explored the overexpression of liver metastasis-associated mRNAs in human CRC by using a well-established, weighted enzymatic chip array platform. Analysis of 10 CRC tissue specimens compared with their normal adjacent tissues revealed that ATP2A2, ELAVL4, hTERT, KCTD2, MUC1, OLFM4, S100B, and TM4SF4 genes were upregulated (gene expression ratio of cancer tissue to paired normal tissue was >2) by microarray and bioinformatics analysis. A gene chip including eight candidate genes was constructed to investigate the circulating tumor cells in blood specimens of 103 preoperative CRC patients and further validated by reverse transcriptase-polymerase chain reaction. Liver metastasis was significantly correlated with overexpression of S100B (p=0.001, OR=9.217), TM4SF3 (p=0.011, OR=4.385), and OLFM4 (p=0.015, OR=3.438). These results suggest that S100B, TM4SF3, and OLFM4 overexpression may affect metastatic behavior of tumor cells in Taiwanese CRC patients.