Potential beneficial effects of long-term aspirin use on the prevalence of colorectal cancer: a population-based study of the US Nationwide Inpatient Sample.

PURPOSE: Whether long-term aspirin usage is associated with colorectal cancer (CRC) risk needs more evidence. The study evaluated the association between long-term aspirin use and prevalence of CRC in a large, nationally representative database. METHODS: Hospitalized patients aged ≥ 50 years during 2018 were identified in the United States (US) National Inpatient Sample (NIS). Patients without complete information of age, sex, race, income, and insurance status were excluded, as well as those with inflammatory bowel disease (IBD) or malignancies other than CRC. Propensity score matching (PSM) was applied to balance the characteristics between patients with and without long-term aspirin use. Logistic regressions were performed to determine the relationship between long-term aspirin use and the presence of CRC. CRC and aspirin use were identified through the administrative International Classification of Diseases (ICD) codes. RESULTS: Data from 3,490,226 patients were included, in which 688,018 (19.7%) had a record of long-term aspirin use. After 1:1 PSM, there remained 1,376,006 patients, representing 6,880,029 individuals in the US after weighting. After adjusting for confounders, long-term aspirin use was significantly associated with lower CRC odds (adjusted odds ratio [aOR] = 0.64, 95% confidence interval [CI] 0.62, 0.67). This association was not changed when stratified by age, sex, race, body mass index (BMI), and smoking. CONCLUSIONS: From a national inpatient dataset, US adults ≥ 50 years on long-term aspirin are less likely to have CRC, regardless of age, sex, race, BMI, and smoking status.

Outcomes of Robot-Assisted Versus Laparoscopic Surgery for Colorectal Cancer in Adults Aged 75 Years and Older: A Propensity Score-Matched Analysis of the US Nationwide Inpatient Sample.

BACKGROUND: Robot-assisted surgery has been increasingly adopted in colorectal cancer resection. OBJECTIVE: The study aimed to compare the inpatient outcomes of robot-assisted versus conventional laparoscopic colorectal cancer resection in patients aged 75 years and older. DESIGN: A retrospective, population-based study. SETTINGS: This study analyzed data from the United States Nationwide Inpatient Sample from 2005 to 2018. PATIENTS: Patients with colorectal cancer aged 75 years and older and who underwent robot-assisted or conventional laparoscopic resection. MAIN OUTCOME MEASURES: Postoperative complications, prolonged length of stay, and total hospital costs were assessed. RESULTS: Data from 14,108 patients were analyzed. After adjustment, any postoperative complications (adjusted OR = 0.87; 95% CI, 0.77-0.99; p = 0.030) and prolonged length of stay (adjusted OR = 0.78; 95% CI, 0.67-0.91; p = 0.001) were significantly less in the robotic than the laparoscopic group. In addition, robotic surgery was associated with significantly higher total hospital costs (26.06 USD greater cost; 95% CI, 21.35-30.77 USD; p < 0.001). LIMITATIONS: The analysis was limited by its retrospective and observational nature, potential coding errors, and the lack of intraoperative factors, such as operative time, laboratory measures, and information on surgeons' experience. CONCLUSIONS: In the United States, in patients with colorectal cancer aged 75 years and older who were undergoing tumor resections, compared to conventional laparoscopic surgery, robotic surgery is associated with better inpatient outcomes in terms of complication rate and risk of prolonged length of stay. This finding is especially true among patients with colon cancer. However, robotic surgery is associated with higher total hospital costs. See Video Abstract . RESULTADOS DE LA CIRUGA ASISTIDA POR ROBOT FRENTE A LA CIRUGA LAPAROSCPICA PARA EL CNCER COLORRECTAL EN ADULTOS AOS DE EDAD UN ANLISIS EMPAREJADO POR PUNTUACIN DE PROPENSIN DE LA MUESTRA NACIONAL DE PACIENTES HOSPITALIZADOS DE ESTADOS UNIDOS: ANTECEDENTES:La cirugía asistida por robot se ha adoptado cada vez más en la resección del cáncer colorrectal.OBJETIVO:El estudio tuvo como objetivo comparar los resultados hospitalarios de la resección del cáncer colorrectal asistida por robot versus la laparoscópica convencional en pacientes ≥ 75 años.DISEÑO:Estudio retrospectivo de base poblacional.AJUSTES:Este estudio analizó datos de la Muestra Nacional de Pacientes Hospitalizados de Estados Unidos de 2005 a 2018.PACIENTES:Pacientes con cáncer colorrectal ≥ 75 años y sometidos a resección laparoscópica convencional o asistida por robot.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron las complicaciones posoperatorias, la duración prolongada de la estancia hospitalaria y los costos hospitalarios totales.RESULTADOS:Se analizaron datos de 14.108 pacientes. Después del ajuste, cualquier complicación posoperatoria (aOR = 0,87; IC del 95 %: 0,77-0,99, p = 0,030) y duración prolongada de la estancia hospitalaria (aOR = 0,78; IC del 95 %: 0,67-0,91, p = 0,001) fueron significativamente menores en el grupo robótico que el grupo laparoscópico. Además, la cirugía robótica se asoció con costos hospitalarios totales significativamente mayores ($26,06 USD mayor costo; IC 95%: 21,35-30,77 USD, p < 0,001).LIMITACIONES:El análisis estuvo limitado por su naturaleza retrospectiva y observacional, posibles errores de codificación y la falta de factores intraoperatorios como el tiempo operatorio, medidas de laboratorio e información sobre la experiencia de los cirujanos.CONCLUSIONES:En Estados Unidos, los pacientes con cáncer colorrectal ≥ 75 años que se sometieron a resecciones tumorales, en comparación con la cirugía laparoscópica convencional, la cirugía robótica se asocia con mejores resultados hospitalarios en términos de tasa de complicaciones y riesgo de estadía prolongada, especialmente entre pacientes con cáncer de colon. Sin embargo, la cirugía robótica se asocia a costes hospitalarios totales más elevados. (Traducción-Yesenia Rojas-Khalil ).

Outcomes of robot-assisted versus laparoscopic surgery for colorectal cancer in morbidly obese patients: A propensity score-matched analysis of the US Nationwide Inpatient Sample.

BACKGROUND AND AIM: Morbid obesity is associated with poorer postoperative outcomes in colorectal cancer (CRC) patients. We aimed to evaluate short-term outcomes after robotic versus conventional laparoscopic CRC resection in morbidly obese patients. METHODS: This population-based, retrospective study extracted data from the US Nationwide Inpatient Sample during 2005-2018. Adults ≥ 20 years old, with morbid obesity and CRC, and undergoing robotic or laparoscopic resections were identified. Propensity score matching (PSM) was applied to minimize the confounding. Univariate and multivariable regression was conducted to evaluate the associations between outcomes and study variables. RESULTS: After PSM, 1296 patients remained. The risks of any postoperative complication (adjusted odds ratio [aOR] = 0.99, 95% confidence interval [CI]: 0.80, 1.22), prolonged length of stay (LOS) (aOR = 0.80, 95% CI: 0.63, 1.01), death (aOR = 0.57, 95% CI: 0.11, 3.10), or pneumonia (aOR = 1.13, 95% CI: 0.73, 1.77) were not significantly different between the two procedures after adjustment. Robotic surgery was significantly associated with greater hospital cost (aBeta = 26.26, 95% CI: 16.08, 36.45) than laparoscopic surgery. Stratified analyses revealed that, in patients with tumor located at the colon, robotic surgery was associated with lower risk of prolonged LOS (aOR = 0.72, 95% CI: 0.54, 0.95). CONCLUSIONS: In patients with morbid obesity, risks of postoperative complication, death, or pneumonia are not significantly different between robotic and laparoscopic CRC resection. Among patients with tumor located at the colon, robotic surgery is associated with lower risk of prolonged LOS. These findings fill the knowledge gap and provide useful information for clinicians on risk stratification and treatment choice.

Association between metabolic syndrome and colorectal cancer incidence and all-cause mortality: a hospital-based observational study.

BACKGROUND: Metabolic syndrome (MetS) is a worldwide pandemic and complex disorder associated with colorectal cancer (CRC). This study aims to identify the influence of number of MetS components on CRC incidence and mortality, using a national, longitudinal dataset of hospital care in Taiwan. METHODS: Patient data from the Taiwan National Health Insurance Research Database (NHIRD) from 2001 to 2008 were extracted. Individuals with at least one inpatient diagnosis or 2 outpatient visits with any MetS component found within one year were identified and included. Subjects died within 12 months after the presence of MetS components or had any prior cancer were excluded. The study cohort were then divided into two groups: subjects who had more (i.e., 3 to 4) MetS components and those who had fewer (i.e., 1 to 2) MetS components. An 2:1 propensity score (PS) matching were performed to balance the baseline characteristics between the groups. Cox regression analyses were conducted to compare the CRC incidence and all-cause mortality at follow-up between subjects with more MetS components versus fewer components. RESULTS: After matching, a total of 119,843 subjects (78,274 with 1-2 and 41,569 with 3-4 MetS components) were analyzed. After adjusting for confounders, subjects with 3-4 MetS components had a significantly higher risk of CRC [adjusted hazard ratio (aHR), 1.28; 95% confidence interval (CI), 1.15-1.43, p < 0.001) and all-cause mortality (aHR, 1.13; 95% CI, 1.08-1.17, p < 0.001) than those with only 1-2 MetS components. In stratified analyses, the greatest increased risk of CRC incidence that 3-4 MetS components posed as compared to 1-2 MetS components was seen in subjects without CHD history (aHR, 1.41, 95% CI, 1.23-1.62, p < 0.001). In addition, 3-4 MetS components (vs. 1-2) led to greater all-cause mortality among the subjects < 65y, both genders, with or without CHD, subjects without CKD hisotry, both aspirin users and non-users, users of nonsteroidal anti-inflammatory drugs (NSAIDs), and users of statin. CONCLUSION: Compared with 1-2 components, subjects with 3-4 MetS components are at greater risk of CRC and death at follow-up. This study also demonstrates the risks for CRC and all-cause mortality in certain subgroups of individuals with 3-4 MetS components compared to 1-2 components. These findings may help clinicians on the CRC risk stratification according to individuals' characteristics, as well as to optimize the strategy of MetS surveillance and control in order to prevent CRC.

The impact of obesity on postoperative outcomes in colorectal cancer patients: a retrospective database study.

PURPOSE: Obesity is an independent risk factor for worse outcomes in various surgical settings. Whether obesity is a prognostic factor for postoperative morbidity and mortality of colorectal cancer (CRC) is inconclusive. This study aimed to determine the impact of obesity on short-term postoperative outcomes in CRC patients undergoing laparoscopic surgery. METHODS: Data of a total of 23,898 CRC patients aged ≥ 20 years and undergoing laparoscopic resection were extracted from the US National Inpatient Sample (NIS) database and analyzed. The study endpoints were in-hospital mortality, any postoperative complications, infection/sepsis, acute kidney injury (AKI), deep vein thrombosis (DVT)/pulmonary embolisms (PE), and extended hospital stay. Univariate and multivariate logistic regression analyses were performed to examine the associations between patients' obesity status (morbid obese: BMI > = 40 kg/m2; obese: BMI 30-39.9 kg/m2) and the study outcomes. RESULTS: In 23,898 CRC patients undergoing laparoscopic resection, the prevalence of obesity prevalence was 11.8%. After adjustment, the results revealed that morbid obesity was significantly associated with increased risk for in-hospital mortality (aOR = 2.06, 95%CI: 1.11-3.83), AKI (aOR = 1.78, 95%CI = 1.34-2.36), DVT/PE (aOR = 2.88, 95%CI = 1.70-4.88), and extended LOS (aOR = 1.21, 95%CI = 1.02-1.43), while non-morbid obesity was significantly associated with more DVT/PE (aOR = 2.12, 95%CI = 1.32-3.41) as compared with non-obesity. CONCLUSION: In patients with CRC undergoing laparoscopic surgery, morbid obesity is strongly associated with worse postoperative outcomes, including increased in-hospital mortality, postoperative AKI and DVT/PE, and extended LOS. The findings of the present study highlight the importance of obesity status in risk stratification for laparoscopic CRC surgery.

Risk factors of delayed hemorrhage after LigaSure hemorrhoidectomy.

BACKGROUND: As one of the most popular methods for treating hemorrhoidal diseases, hemorrhoidectomy with LigaSure devices has been proven to have less postoperative pain and has gained in popularity among surgeons. However, our previous study found higher incidence of delayed post-hemorrhoidectomy bleeding (DPHB) in patients who underwent LigaSure hemorrhoidectomy compared to those who underwent the traditional Ferguson's method. This follow-up study aimed to reveal the relationship between DPHB and the surgeon's experience. METHODS: This retrospective study included 437 consecutive patients with symptomatic grade II to IV hemorrhoids who received hemorrhoidectomy by LigaSure devices from March 2009 to December 2017. Twenty-two patients who experienced DPHB were analyzed to identify risk factors. Cumulative incidence of DPHB were calculated and visualized to assess the improvement of DPHB rate by time. RESULTS: All operations were performed by a single surgeon. The most common postoperative complication was constipation, followed by urinary retention. DPHB developed in 22 patients (5%). Multivariate analysis showed that the male sex was an independent risk factor for DPHB in patients who underwent hemorrhoidectomy with LigaSure devices. The cumulative incidence was initially higher (about 10%) in the earlier cases and stabilized at around 5% with more cases. The change in cumulative incidence indicated a lower complication rate as the surgeon's experience increased. CONCLUSION: Male sex is an independent risk factor for DHBP. The risk of DPHB is higher in patients undergoing hemorrhoidectomy with LigaSure in a surgeon's earlier cases, and decreases to a rate similar to that for the traditional hemorrhoidectomy once the surgeon becomes more familiar with the procedure and postoperative care.

Differential short-term outcomes of laparoscopic resection in colon and rectal cancer patients aged 80 and older: an analysis of Nationwide Inpatient Sample.

BACKGROUND: Approximately, 22.6% of colorectal cancer surgeries were performed on patients aged 80 or over. The present study aimed to evaluate the use of laparoscopic resection and its short-term surgical outcomes in patients who were aged 80 and older and diagnosed with colon cancer or rectal cancer in parallel. METHODS: In this retrospective population-based study, colon and rectal cancer patients ≥ 80 years undergoing laparoscopic resection or open resection were identified from the United States National Inpatient Sample (2005-2014). Primary outcomes were postoperative complication and in-hospital mortality. Logistic regression analyses were performed to assess the short-term effectiveness of laparoscopic and open resection. RESULTS: In this study, 40,451 colon cancer patients and 1117 rectal cancer patients were included. Multivariate analysis revealed that laparoscopic resection was significantly associated with lower risks for developing postoperative complications (aOR = 0.67; 95%, CI 0.64-0.71) and in-hospital mortality (aOR = 0.37; 95% CI 0.32-0.43) compared to open resection in colon cancer patients. For rectal cancer patients, multivariate analysis indicated that laparoscopic resection was significantly associated with a lower risk of developing postoperative complications (aOR = 0.41; 95% CI 0.32-0.52) but was not associated with in-hospital mortality. CONCLUSION: Compared to open resection, laparoscopic resection has better or similar short-term surgical outcomes in colon and rectal cancer patients ≥ 80 years.

Laparoscopic versus Open Surgery for Diverticulitis: A Systematic Review and Meta-Analysis.

BACKGROUND/AIMS: The study aimed to perform a meta-analysis comparing laparoscopic and open surgery for diverticulitis. METHODS: Studies comparing the outcomes of laparoscopic surgery versus open surgery for diverticulitis that reported quantitative data were included. Outcome measures were mortality and morbidity rates and length of hospital stay. RESULTS: Four randomized controlled trials - 3 prospective and 21 retrospective - were included in the analysis. The total numbers of patients ranged from 5 to 14,562 in the laparoscopic groups and from 4 to 110,172 in the open surgery groups, and the mean patient age ranged from 38.9 to 78 years. Overall analysis revealed that laparoscopic surgery was associated with lower mortality (pooled OR 0.40, 95% CI 0.25-0.63, p < 0.001) and a lower overall morbidity rate (pooled OR 0.65, 95% CI 0.51-0.82, p < 0.001) than open surgery. Laparoscopic surgery was associated with a higher anastomotic bleeding rate, but lower rates of ileus, anastomotic leakage, small bowel obstruction, wound infection, fascial dehiscence and intra-abdominal abscesses. Length of hospital stay was less with laparoscopic surgery. CONCLUSIONS: The current meta-analysis supports the use of laparoscopy for the treatment of diverticulitis. The results, however, should be interpreted with caution.

Amphiregulin Upregulation in Visfatin-Stimulated Colorectal Cancer Cells Reduces Sensitivity to 5-Fluororacil Cytotoxicity.

Colorectal cancer (CRC) has become a prevalent and deadly malignancy over the years. Drug resistance remains a major challenge in CRC treatment, significantly affecting patient survival rates. Obesity is a key risk factor for CRC development, and accumulating evidence indicates that increased secretion of adipokines, including Visfatin, under obese conditions contributes to the development of resistance in CRC to various therapeutic methods. Amphiregulin (AREG) is a member of the epidermal growth factor (EGF) family, which activates the EGF receptor (EGFR), influencing multiple tumorigenic characteristics of cancers. Abnormal expression levels of AREG in cancer cells have been associated with resistance to anti-EGFR therapy in patients. However, it remains unclear whether this abnormal expression also impacts CRC resistance to other chemotherapeutic drugs. The aim of this study is to examine whether AREG expression levels could be affected in CRC cells under Visfatin stimulation, thereby initiating the development of resistance to 5-fluororacil (5-FU). Through our results, we found that Visfatin indeed increases AREG expression, reducing the sensitivity of HCT-116 CRC cells to 5-FU cytotoxicity. Moreover, AREG upregulation is regulated by STAT3-CREB transcription factors activated by JNK1/2 and p38 signaling. This study highlights the significant role of AREG upregulation in CRC cells in initiating chemotherapeutic resistance to 5-FU under Visfatin stimulation. These findings provide a deeper understanding of drug resistance development in CRC under obese conditions and offer new insights into the correlation between an abnormal increase in AREG levels and the development of 5-FU-resistance in CRC cells, which should be considered in future clinical applications.

A Retrospective Single-Arm Cohort Study in a Single Center of Radiofrequency Ablation in Treatment of Chronic Radiation Proctitis.

BACKGROUND: Chronic radiation proctitis (CRP) may develop in patients within months to years after undergoing pelvic radiotherapy. Numerous treatment modalities are available to achieve hemostasis in CRP, but the optimal treatment remains controversial. We report our clinical experience and long-term outcomes using radiofrequency ablation (RFA) in patients with CRP. METHODS: We retrospectively reviewed patients who underwent RFA for CRP at Kaohsiung Chang Gung Memorial Hospital between October 2015 and March 2021. The patient characteristics, endoscopic findings, and clinical outcomes were collected and analyzed. RESULTS: 35 total patients were enrolled in the study. The mean age was 70.5 ± 12.4 years. All patients sustained repeated rectal bleeding before RFA, and 15 of 35 patients needed blood transfusion. Bleeding cessation was achieved in all patients. Mean follow-up time was 18.6 months (ranging from 2 to 52 months). The hemoglobin (Hb) levels at 6 months after RFA revealed significant improvement from 11.0 ± 2.3 to 11.8 ± 1.9 g/dL (p = 0.048). The rectal telangiectasia density (RTD) scores also showed significant improvement from 2.96 ± 0.2 to 0.85 ± 0.7 (p < 0.0001). In conclusion, RFA treatment is safe and effective in controlling rectal bleeding in CRP without serious complications and can be considered as a first-line or alternative endoscopic treatment for patients with CRP.

High Red Cell Distribution Width Is Associated with Worse Prognosis in Early Colorectal Cancer after Curative Resection: A Propensity-Matched Analysis.

The red blood cell distribution width (RDW) is a simple and widely available parameter obtained from a complete blood cell count test and is usually used in the analysis of anemia. Recently, studies have discovered the association between RDW and the host inflammatory response of cancer patients. We aimed to determine the prognostic value of RDW in colorectal cancer (CRC) patients. 5315 total patients with stage I-II CRC from the Chang Gung Memorial Hospital between 2001 and 2018 were enrolled. The study cohort was divided into two groups using RDW = 13.8 as the cutoff value as determined by receiver operating curve. High RDW had worse overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS), and was also independently related to older age, more advanced tumor stage, lower albumin level, lower hemoglobin level, and more co-morbidities including diabetes, hypertension, and chronic kidney disease. We performed a propensity-score matched analysis to balance the heterogeneity between the two groups and to reduce the influence of confounding factors that may have compromised the prognosis. High RDW remained a negative predictor of OS (HR = 1.49, 95% CI: 1.25-1.78), as well as DFS and CSS. In conclusion, this is the first report using propensity matching to demonstrate the relationship between RDW and the prognosis of early-stage CRC patients.

Fermented Ginger Extract in Natural Deep Eutectic Solvent Enhances Cytotoxicity by Inhibiting NF-κB Mediated CXC Chemokine Receptor 4 Expression in Oxaliplatin-Resistant Human Colorectal Cancer Cells.

Ginger extracts have been shown to have health-promoting pharmacological activity and beneficial effects, including antioxidant and anticancer properties. The extraction of ginger by natural deep eutectic solvents (NaDES) has been shown to enhance bioactivity, but the cytotoxicity of NaDES extracts needs to be further determined. Signaling through the CXC chemokine receptor 4 (CXCR4) expressed on colorectal cancer (CRC) cells has a pivotal role in tumor cell chemosensitivity. Oxaliplatin is a third-generation platinum compound used as an effective chemotherapeutic drug for CRC treatment. However, whether ginger extract and oxaliplatin could induce a synergistic cytotoxic effect in oxaliplatin-resistant CRC cells through modulating CXCR4 expression is not known. In this study, oxaliplatin-resistant HCT-116 (HCT-116/R) cells were generated first. Ginger was extracted using the NaDES mixture betaine/lactate/water (1:2:2.5). Lactobacillus reuteri fermentation of NaDES-ginger extract increased the total polyphenol content (12.42 mg gallic acid/g in non-fermented NaDES-ginger extract and 23.66 mg gallic acid/g in fermented NaDES-ginger extract). It also increased the antioxidant activity by about 20−30% compared to non-fermented NaDES-ginger extract. In addition, it achieved low cytotoxicity to normal colonic mucosal cells and enhanced the anticancer effect on HCT-116/R cells. On the other hand, the inhibition of NF-κB activation by fermented NaDES-ginger extract significantly decreased the CXCR4 expression (p < 0.05) in HCT-116/R cells. The inactivation of NF-κB by pharmacological inhibitor pyrrolidine dithiocarbamate further enhanced the fermented NaDES-ginger extract-reduced CXCR4 expression levels (p < 0.05). Moreover, fermented NaDES-ginger extract could synergistically increase the cytotoxicity of oxaliplatin by inhibiting CXCR4 expression and inactivating NF-κB, resulting in HCT-116/R cell death. These findings demonstrate that fermented NaDES-ginger extract reduces the NF-kB-mediated activation of CXCR4 and enhances oxaliplatin-induced cytotoxicity in oxaliplatin-resistant CRC cells.

Inhibition of NLRP3 by Fermented Quercetin Decreases Resistin-Induced Chemoresistance to 5-Fluorouracil in Human Colorectal Cancer Cells.

The drug resistance of colorectal cancer (CRC) cells against 5-fluorouracil (5-FU) therapy is a major challenge to successful cancer treatment. While previous studies have proposed several 5-FU resistance mechanisms, the effects of the adipokines on cancer cells remain unclear. Thus, this study investigated the effect of resistin on 5-FU-treated CRC cell lines. The upregulation of NLRP3 can regulate the inflammatory responses in cancer cells and then enhance cancer progression. This study investigated the expression level and the function of NLRP3 on 5-FU-induced cytotoxicity in CRC cells and found that resistin-induced ERK activation and increased NLRP3 expression in CRC HCT-116 and DLD-1 cells were mediated by Toll-like receptor 4 (TLR4). The inhibition of TLR4 and ERK by pharmacological inhibitors attenuated the resistin-induced NLRP3 mRNA and protein levels. In contrast, the knockdown of NLRP3 enhanced the cytotoxic effects of 5-FU. Furthermore, quercetin is an effective chemopreventive compound. This study showed that quercetin fermented by Lactobacillus could exhibit low cytotoxicity on normal mucosa cells and improve the function of inhibiting CRC cells. The treatment of CRC cells with fermented quercetin increased the cytotoxicity and enhanced cell death in the presence of resistin. In this study, fermented quercetin induced the cytotoxicity and cell death of 5-FU in resistin-treated CRC cells, which is associated with the downregulation of NLRP3 expression and ERK phosphorylation. These results indicate the role of NLRP3 in the development of drug resistance to 5-FU in CRC cells. Elucidating the mechanism regarding the cytotoxicity effect of quercetin may provide another vision for the development of a chemotherapy strategy for CRC in the future.

Colorectal Cancer Risk in Patients with Hemorrhoids: A 10-Year Population-Based Retrospective Cohort Study.

Colorectal cancer (CRC) is a common disease and one of the leading causes of cancer deaths worldwide. This retrospective cohort study evaluated the risk of developing CRC in people with hemorrhoids. Using Taiwan's National Health Insurance Research Database, we established three sets of retrospective study cohorts with and without hemorrhoids. The first set of cohorts were matched by sex and age, the second set of cohorts were matched by propensity score without including colonoscopies, and the third set of cohorts were matched by propensity score with colonoscopies, colorectal adenomas, and appendectomies included. In the second set of cohorts, 36,864 persons with hemorrhoids that were diagnosed from 2000 to 2010 and a comparison cohort, with the same size and matched by propensity score, were established and followed up to the end of 2011 to assess the incidence and Cox proportional regression-measured hazard ratio (HR) of CRC. The overall incidence rate of CRC was 2.39 times greater in the hemorrhoid cohort than it was in the comparison cohort (1.29 vs. 0.54 per 1000 person-years), with a multivariable model measured adjusted HR of 2.18 (95% CI = 1.78-2.67) after controlling for sex, age, and comorbidity. Further analysis on the CRC incidence rates among colorectal sites revealed higher incidence rates at the rectum and sigmoid than at other sites, with adjusted HRs 2.20 (95% CI = 1.48-3.28) and 1.79 (95% CI = 1.06-3.02), respectively. The overall incidence rates of both cohorts were similar in the first and second sets of cohorts, whereas the rate was lower in the third set of hemorrhoid cohorts than in the respective comparison cohorts, probably because of overmatching. Our findings suggest that patients with hemorrhoids were at an elevated risk of developing CRC. Colonoscopy may be strongly suggested for identifying CRC among those with hemorrhoids, especially if they have received a positive fecal occult blood test result.

Path Analysis of the Impact of Obesity on Postoperative Outcomes in Colorectal Cancer Patients: A Population-Based Study.

BACKGROUND: Obesity is adversely affecting perioperative outcomes; however, long-term outcomes do not appear to be affected by excess body weight (the obesity paradox). The purpose of this study is to examine the association between obesity and surgical outcomes in patients with colorectal cancer (CRC) using data from the United States National Inpatient Sample (NIS). METHODS: Patients ≥20 years old diagnosed with CRC who received surgery were identified in the 2004-2014 NIS database. Patients who were obese (ICD-9-CM code: 278.0) were matched with controls (non-obese) in a 1:4 ratio for age, sex, and severity of CRC (metastasis vs. no metastasis). Linear regression and path analysis were used to compare outcomes between obese and non-obese patients. A total of 107,067 patients (53,376 males, 53,691 females) were included in the analysis, and 7.86% were obese. RESULTS: The rates of postoperative infection, shock, bleeding, wound disruption, and digestive system complications were significantly different between the obese and non-obese groups. The obesity group had increased incidence of postoperative infection by 1.9% (∂P/∂X = 0.019), shock by 0.25% (∂P/∂X = 0.0025), postoperative bleeding by 0.5% (∂P/∂X = 0.005), wound disruption by 0.6% (∂P/∂X = 0.006), and digestive system complications by 1.35% (∂P/∂X = 0.0135). Path analysis showed that obesity group had higher in-hospital mortality through mentioned above five complications by 66.65 × 10-5%, length of hospital stay by 0.32 days, and total hospital charges by 2384 US dollars. CONCLUSIONS: Obesity increases the risk of postoperative complications in patients with CRC undergoing surgery. It also increased in-hospital mortality, length of hospital stay, and total hospital charges. Therefore, patients with obesity might require a higher level of preoperative interventions and complications monitoring to improve outcomes.

6-Shogaol Antagonizes the Adipocyte-Conditioned Medium-Initiated 5-Fluorouracil Resistance in Human Colorectal Cancer Cells through Controlling the SREBP-1 Level.

The resistance of colorectal cancer (CRC) to chemotherapy, e.g., 5-fluorouracil (5-FU), is an impediment to successful cancer treatment. Although many mechanisms have been proposed to explain the occurrence of resistance, little is known concerning the role of the adipocyte-containing microenvironment of CRC. Accumulating data have proposed that the combined therapy of clinical drugs with ginger derivatives, e.g., 6-shogaol, might improve resistance development. In the present study, we examined the effect of adipocyte-conditioned medium (ACM) on 5-FU-treated CRC cells (human DLD-1 and SW480 cells) and further examined the possible antagonized role of 6-shogaol in this situation. It was shown that the level of sterol-regulatory element-binding protein-1 (SREBP-1), a critical transcription factor involved in lipid synthesis and metabolism, would be upregulated through Akt and p70S6K signaling pathways while CRC cells are cultured in ACM, which subsequently decreases the cell sensitivity to 5-FU cytotoxicity. Moreover, our results also demonstrated the antagonized role of 6-shogaol in attenuating the ACM effects on CRC cells through activating AMPK signaling. Overall, the present study elucidated the role of adipocyte-containing microenvironment in 5-FU resistance development of CRC through controlling the SREBP-1 level and further enhanced the concept of clinical application of 6-shogaol and AMPK signaling in CRC therapy.

Visfatin and Resveratrol Differentially Regulate the Expression of Thymidylate Synthase to Control the Sensitivity of Human Colorectal Cancer Cells to Capecitabine Cytotoxicity.

Colorectal cancer (CRC) is a highly lethal malignant cancer. Capecitabine, a 5-fluororacil (5-FU) derivate, is its first-line drug, but the resistance of CRC to capecitabine is still the most challenging factor for curing patients. It has been suggested that thymidylate synthase (TYMS) level might affect the capecitabine efficacy in CRC patients, but the mechanism still needs more elucidation. Obesity is a risk factor for CRC. Recently, a correlation between serum visfatin, an obesity-elicited adipokine, and CRC development has been found. Thus, the aim of present study is to examine the visfatin capacity in TYMS expression and in the development of capecitabine resistance of CRC. Moreover, an attractive natural component, i.e., resveratrol, has been proposed in anticancer therapy and has hence been examined in the present study to see its potential capacity in the alleviation of CRC resistance. Our results found that visfatin significantly reduces the CRC sensitivity to capecitabine by controlling the TYMS expression via p38 signaling and Sp1 transcription factor. Moreover, resveratrol could significantly alleviate the visfatin effect on capecitabine-treated CRC cells. These results provided new insights to understand the capecitabine susceptibility of CRC under a visfatin-containing environment and a possible therapeutic application of resveratrol in CRC patients with obesity.

The Impact of Comorbid Diabetes on Short-Term Postoperative Outcomes in Stage I/II Colon Cancer Patients Undergoing Open Colectomy.

PURPOSE: This study aimed at evaluating the impact of comorbid diabetes on short-term postoperative outcomes in patients with stage I/II colon cancer after open colectomy. METHODS: The data were extracted from the National Inpatient Sample database (2005-2010). Short-term surgical outcomes included in-hospital mortality, postoperative complications, and hospital length of stay. RESULTS: A total of 49,064 stage I/II colon cancer patients undergoing open surgery were included, with a mean age of 70.35 years. Of them, 21.94% had comorbid diabetes. Multivariable analyses revealed that comorbid diabetes was significantly associated with a lower risk of in-hospital mortality and postoperative complications. Compared to patients without diabetes, patients with uncomplicated diabetes had lower percentages of in-hospital mortality and postoperative complications, but patients with complicated diabetes had a higher percentage of postoperative complications. In addition, patients with diabetes only, but not patients with diabetes and hypertension only, had a lower percentage of in-hospital mortality than patients without any comorbidity. CONCLUSION: The present results suggested the protective effects of uncomplicated diabetes on short-term surgical outcomes in stage I/II colon cancer patients after open colectomy. Further studies are warranted to confirm these unexpected findings and investigate the possible underlying mechanisms.

Short-term postoperative outcomes of colorectal cancer among patients with chronic liver disease: a national population-based study.

OBJECTIVE: Patients with colorectal carcinoma (CRC) with pre-existing chronic liver disease (CLD) had a significantly higher 30-day mortality after CRC surgery compared with healthy controls. This study investigated the factors associated with postoperative complications and in-hospital mortality in patients with CRC with coexisting CLD (excluding cirrhosis) who underwent colorectal surgery. DESIGN: A retrospective, observational, population-based study. SETTING: Data were sourced from the National Inpatient Sample database, a part of the Healthcare Cost and Utilisation Project. PARTICIPANTS: This study analysed 7463 inpatients with CRC who underwent colorectal surgery on admission between 2005 and 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint of this study was the prevalence of postoperative complications, and the secondary endpoint was in-hospital mortality. RESULTS: In the CLD group, 36.27% of patients had chronic hepatitis C, 28.36% had non-alcoholic fatty liver disease and 31.19% had other types of CLD. The median hospital stay was 7.0 (5.0-10.0) days in patients with no postoperative complications vs 17.0 (10.0-26.0) days, 8.0 (6.0-12.0) days, 8.0 (6.0-17.0) days, 9.0 (8.0-14.0) days and 10.5 (7.0-17.0) days for patients with postoperative infection, postoperative bleeding, cardiac arrest/heart failure, respiratory complications and digestive complications, respectively (all p<0.05). The presence of CLD was significantly associated with higher risk of postoperative bleeding (adjusted OR (aOR)=1.64, 95% CI 1.15 to 2.34, p=0.007). The presence of CLD (aOR=1.98, 95% CI 1.39 to 2.82, p<0.001) and length of hospital stay (aOR=1.06, 95% CI 1.04 to 1.08, p<0.001) were significantly associated with higher risk of in-hospital mortality. However, hyperlipidaemia was associated with a significantly lower risk of mortality (aOR=0.46, 95% CI 0.28 to 0.75, p=0.002). CONCLUSIONS: Postoperative complications prolonged the length of hospital stay. The presence of CLD and hyperlipidaemia were important factors impacting postoperative complications and in-hospital mortality in patients with CRC with underlying CLD.