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.

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.

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.

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.

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.

Pharmacoeconomic analysis of capecitabine versus 5-fluorouracil/leucovorin as adjuvant therapy for stage III colon cancer in Taiwan.

OBJECTIVES: To assess the cost-effectiveness of oral capecitabine compared with intravenous bolus 5-fluorouracil/leucovorin (5-FU/LV) in the adjuvant treatment of stage III colon cancer in Taiwan from payer (Bureau of National Health Insurance [BNHI]) perspectives. METHODS: A health state-transition model was developed to estimate the incremental costs and effectiveness of capecitabine versus 5-FU/LV. The time horizons studied were: treatment duration (24 weeks) plus 36 months, 48 months, 60 months, 120 months, and lifetime. Costs were expressed in Taiwanese new dollars (NT$). Clinical outcomes, medical resource use, and utilities were extracted from published sources. Unit costs were estimated from BNHI fee schedules, published sources, and local expert opinion. Outcomes and future costs were discounted at 3%. Cost-effectiveness was expressed as cost per quality-adjusted life-month (QALM). The effects of uncertainty were explored through a one-way sensitivity analysis. RESULTS: For the 24-week time period, drug acquisition costs were higher for capecitabine than 5-FU/LV (NT$114,405 vs. NT$4,904 per patient); however, these were offset by the higher administration costs of 5-FU/LV (NT$2,573 vs. NT$204,201 per patient). Overall direct costs for the 24-week treatment period were less with capecitabine than 5-FU/LV (NT$129,327 vs. NT$233,873 per patient). Cost savings with capecitabine were also evident when longer time horizons were considered. Over a lifetime, the projected survival benefit for capecitabine was 7 QALMs. CONCLUSIONS: From the perspectives of the BNHI and society in Taiwan, capecitabine not only saves costs but also improves health outcomes compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer.

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.

Enhancing detection of circulating tumor cells with activating KRAS oncogene in patients with colorectal cancer by weighted chemiluminescent membrane array method.

BACKGROUND: In 2008, the National Comprehensive Cancer Network suggested conducting a KRAS mutations test in metastatic colorectal cancer (mCRC) patients prior to administering therapy that uses anti-epidermal growth factor receptor (EGFR) monoclonal antibody. However, tests of KRAS mutations have been limited when traditional molecular techniques, such as polymerase chain reaction (PCR) combined direct sequencing, are used to obtain and analyze patients' cancer tissues. If the primary tumor or metastatic tissues of patients with mCRC is unavailable, then such analysis will not be feasible. Our laboratory has successfully established a colorimetric membrane array analysis platform that could detect activating KRAS mutations from the peripheral blood of patients with various malignancies. METHODS: The current research aims to improve the above-mentioned technique not only by using chemiluminescence detection to replace color development, but also to add scores weighted according to the relevance of each gene to activating KRAS mutations. RESULTS: Our results show that the described weighted chemiluminescent membrane array (WCHMA) can detect circulating tumor cells (CTCs) harboring activating KRAS mutations in the peripheral blood in CRC. The sensitivity, specificity, and accuracy were 90.2, 94.9, and 93.5%, respectively, and the detection limitation was three colon tumor cells per millimeter of blood. The current study would significantly improve the detection sensitivity and accuracy over that of our previously designed membrane array method. CONCLUSIONS: These findings also highlight the need to prompt further prospective studies on more cases of CRC to further establish the clinical relevance of activating KRAS mutation detection from peripheral blood in anti- EGFR-based chemotherapy that uses activating KRAS detection chips and the WCHMA analysis method.

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.

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.

Neoadjuvant concurrent chemoradiotherapy in treating locally advanced rectal cancer.

BACKGROUND: Colorectal cancer is a common cancer and a major cause of morbidity and mortality worldwide. Middle to lower rectal cancer, a challenge for surgeons, is problematic. Neoadjuvant concurrent chemoradiotherapy (CCRT), introduced in the last decade, leads the local control of advanced rectal cancer to a high percentage of R0 resection (margin negative under microscopic examination) and a low recurrence rate. METHODS: From January 2005 to June 2007, 46 patients with locally advanced rectal cancer who received neoadjuvant CCRT were included. Factors including disease-free survival time, overall survival time, local recurrence, metastasis, and postoperative complications were evaluated retrospectively. Response was defined according to Mandard's classification, in which TRG1 is no residual tumor and TRG2-3 is 50-100% tumor shrinkage. RESULTS: In this series, 3 patients who did not receive post-CCRT curative resection were excluded. The remaining 43 patients (22 males, 21 females) had received curative surgery and were included. Thirty-four patients had tumor shrinkage, and the response rate was 79% (Mandard's classification: TRG1-TRG3). The median follow-up time was longer than 1.5 years. Patients who responded to CCRT had lower local recurrence rates (5.9% vs. 55.6%; p = 0.002) and a greater curative resection rate (97.1% vs. 66.7%; p = 0.024). The complication rates of both groups were similar. CONCLUSION: Neoadjuvant CCRT gives locally advanced rectal cancer patients a more favorable result, with acceptable toxicity.

Local recurrence after laparoscopic resection of T3 rectal cancer without preoperative chemoradiation and a risk group analysis: an Asian collaborative study.

Risk factors for local recurrence and indication for preoperative radiation therapy have not been well evaluated for patients undergoing laparoscopic rectal cancer operation. From 1998 to 2004, 497 T3 rectal cancer patients with tumor located within 12 cm from the anal verge who had undergone laparoscopic surgery without preoperative radiation therapy by eight experienced laparoscopic surgeons in four Asian countries were reviewed retrospectively for the incidence of local recurrence and related factors. The median follow-up was 29.0 months (range, 6.0 to 92.3), and 31 cases of local recurrence were observed during the follow-up period (6 anastomosis site, 6 perineum, 17 pelvic wall, and 2 unclassified). The estimated local recurrence rates at 24 and 60 months were 5.42 and 9.41%, respectively. Patient's gender, tumor location, lymph node metastasis, and tumor perforation were independent factors for local recurrence by multivariate analysis. The local recurrence rate was comparable to previous studies using conventional open surgery with preoperative chemoradiation, except for a subgroup of male patients with the tumor located within 7 cm from the anal verge. The indication for preoperative radiation therapy would be different from those who will undergo conventional open surgery, and further evaluation of the benefits of preoperative radiation therapy is required for those with low risk tumor.

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.

Laparoscopic-assisted operation for familial adenomatous polyposis patients-two case reports.

OBJECTIVE: We describe herein the results of 2 laparoscopic operations to treat patients with familial adenomatous polyposis (FAP). METHODS: Two female FAP patients, aged 32 and 29 years old, were treated with restorative proctocolectomy and total colectomy with ileorectal anastomosis (hand-assisted laparoscopic surgery), respectively. RESULTS: The operative time was 360 minutes for the restorative proctocolectomy and 150 minutes for the total colectomy with ileorectal anastomosis. The blood loss was 500 cc for the restorative proctocolectomy and minimal for the total colectomy patient. The return of bowel movements took 3 days for each patient, and no complication occurred. Patients were discharged on the 15th and 7th postoperative days. CONCLUSION: A laparoscopic approach for restorative proctocolectomy or total colectomy with ileorectal anastomosis is safe and technically feasible, and provides good cosmesis.

Laparoscopic coloanal anastomosis for low rectal cancer.

OBJECTIVES: Low anterior resection with hand-sutured coloanal anastomosis for low rectal cancer is technically feasible, and it does not compromise oncologic results. We describe herein the effectiveness of the operation in treating low rectal cancer by a laparoscopic approach followed by intraanal canal dissection. METHODS: From February 1999 to October 1999, we used a laparoscopic procedure to divide the inferior mesenteric vessels and to dissect downward into the pelvic cavity as low as possible. A purse-string suture 1-cm distal to the lower margin of the tumor was secured and transection of the rectum was performed circumferentially via the anal canal near the dentate line. The specimen was removed by the pull-through method and coloanal anastomosis was completed with hand suture. A protective loop ileostomy was fashioned. RESULTS: We operated on 8 patients (4 males) with low tumor localization (average 4-cm above the dentate line). The age ranged from 45 to 83 years, with a median age of 64. The average operation time was 210 minutes (150 to 360 minutes), and the average blood loss was 250 cc (minimal to 750 cc). No operative mortalities occurred, but 2 patients had minor anastomotic slough complications. The average hospital stay was 13 days (7 to 26 days). The postoperative pathologic stage was T2N0M0 in 4 patients, T3N0M0 in 2 patients, T2N1M0 in 1 patient, and T3N2M0 in 1 patient. No local recurrence or distant metastasis occurred during the median 14 months (12 to 20 months) of follow-up. CONCLUSION: Laparoscopic coloanal anastomosis combined with intraanal canal dissection is safe and technically feasible. The oncologic results seem not to be compromised, but need further evaluation.