KRAS, NRAS, BRAF signatures, and MMR status in colorectal cancer patients in North China.

We assessed the clinicopathological features and prognostic values of KRAS, NRAS, BRAF, and DNA mismatch repair status in colorectal cancer (CRC) to provide real-world data in developing countries. We enrolled 369 CRC patients and analyzed the correlation between RAS/BRAF mutation, mismatch repair status with clinicopathological features, and their prognostic roles. The mutation frequencies of KRAS, NRAS, and BRAF were 41.7%, 1.6%, and 3.8%, respectively. KRAS mutations and deficient mismatch repair (dMMR) status were associated with right-sided tumors, aggressive biological behaviors, and poor differentiation. BRAF (V600E) mutations are associated with well-differentiated and lymphovascular invasion. The dMMR status predominated in young and middle-aged patients and tumor node metastasis stage II patients. dMMR status predicted longer overall survival in all CRC patients. KRAS mutations indicated inferior overall survival in patients with CRC stage IV. Our study showed that KRAS mutations and dMMR status could be applied to CRC patients with different clinicopathological features.

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies.

BACKGROUND: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited. AIM: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy. METHODS: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle. RESULTS: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer. CONCLUSION: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

Single-cell profiling reveals differences between human classical adenocarcinoma and mucinous adenocarcinoma.

Colorectal cancer is a highly heterogeneous disease. Most colorectal cancers are classical adenocarcinoma, and mucinous adenocarcinoma is a unique histological subtype that is known to respond poorly to chemoradiotherapy. The difference in prognosis between mucinous adenocarcinoma and classical adenocarcinoma is controversial. Here, to gain insight into the differences between classical adenocarcinoma and mucinous adenocarcinoma, we analyse 7 surgical tumour samples from 4 classical adenocarcinoma and 3 mucinous adenocarcinoma patients by single-cell RNA sequencing. Our results indicate that mucinous adenocarcinoma cancer cells have goblet cell-like properties, and express high levels of goblet cell markers (REG4, SPINK4, FCGBP and MUC2) compared to classical adenocarcinoma cancer cells. TFF3 is essential for the transcriptional regulation of these molecules, and may cooperate with RPS4X to eventually lead to the mucinous adenocarcinoma mucus phenotype. The observed molecular characteristics may be critical in the specific biological behavior of mucinous adenocarcinoma.

MRI measurements predict major low anterior resection syndrome in rectal cancer patients.

PURPOSE: Current low anterior resection syndrome (LARS) score is lagging behind and only based on clinical symptoms patient described. Preoperative imaging indicators which can be used to predict LARS is unknown. We proposed preoperative MRI parameters for identifying major LARS. METHODS: Patients receiving curative restorative anterior resection from Sept. 2007 to Sept. 2015 were collected to complete LARS score (median 75.7 months since surgery). MRI measurements associated with LARS were tested, and a multivariate logistic model was conducted for predicting LARS. Receiver operating characteristic curve was used to evaluate the model. RESULTS: Two hundred fifty-five patients undergoing neoadjuvant chemoradiotherapy and 72 patients undergoing direct surgery were enrolled. The incidence of major LARS in NCRT group was significantly higher (53.3% vs.34.7%, P = 0.005). In patients with neoadjuvant chemoradiotherapy, the thickness of ARJ (TARJ), the distance between the tumor's lower edge and anal rectal joint (DTA), and sex were independent factors for predicting major LARS; ORs were 0.382 (95% CI, 0.198-0.740), 0.653 (95% CI, 0.565-0.756), and 0.935 (95% CI, 0.915-0.955). The AUC of the multivariable model was 0.842 (95% CI, 0.794-0.890). In patients with direct surgery, only DTA was the independent factor for predicting major LARS; OR was 0.958 (95% CI, 0.930-0.988). The AUC was 0.777 (95% CI: 0.630-0.925). CONCLUSIONS: Baseline MRI measurements have the potential to predict major LARS in rectal cancer, which will benefit the decision-making and improve patients' life quality.

Clinical Decision Support for High-Risk Stage II Colon Cancer: A Real-World Study of Treatment Concordance and Survival.

BACKGROUND: Prognostic and pathologic risk factors typically guide clinicians and patients in their choice of surveillance or adjuvant chemotherapy when managing high-risk stage II colon cancer. However, variations in treatment and outcomes in patients with stage II colon cancer remain. OBJECTIVE: This study aimed to assess the survival benefits of treatments concordant with suggested therapeutic options from Watson for Oncology, a clinical decision support system. DESIGN: This is a retrospective observational study of concordance between actual treatment and Watson for Oncology therapeutic options. SETTING: This study was conducted at a top-tier cancer center in China. PATIENTS: Postoperative treatment data were retrieved from the electronic health records of 306 patients with high-risk stage II colon adenocarcinoma. MAIN OUTCOME MEASURES: The primary outcomes measured were the treatment patterns plus 3- and 5-year overall and disease-free survival for concordant and nonconcordant cases. RESULTS: Overall concordance was 90%. Most nonconcordant care resulted from adjuvant chemotherapy use (rather than surveillance) in patients with high-level microsatellite instability and ≥70 years old. No difference in overall survival (p = 0.56) or disease-free survival (p = 0.19) was observed between concordance groups. Patients receiving adjuvant chemotherapy had significantly higher 5-year overall survival than those undergoing surveillance (94% vs 84%, p = 0.01). LIMITATIONS: This study was limited by the use of retrospective cases drawn from patients presenting for surgery, the lack of complete follow-up data for 58% of patients who could not be included in the analysis, and a survival analysis that assumes no unmeasured correlation between survival and censoring. CONCLUSIONS: Watson for Oncology produced therapeutic options highly concordant with human decisions at a top-tier cancer center in China. Treatment patterns suggest that Watson for Oncology may be able to guide clinicians to minimize overtreatment of patients with high-risk stage II colon cancer with chemotherapy. Survival analyses suggest the need for further investigation to specifically assess the association between surveillance, single-agent and multiagent chemotherapy, and survival outcomes in this population. See Video Abstract at http://links.lww.com/DCR/B291. APOYO A LA DECISIÓN CLÍNICA DEL CÁNCER DE COLON EN ESTADIO II DE ALTO RIESGO: UN ESTUDIO DEL MUNDO REAL SOBRE LA CONCORDANCIA DEL TRATAMIENTO Y LA SUPERVIVENCIA: Los factores de riesgo pronósticos y patológicos generalmente guían a los médicos y pacientes en su elección de vigilancia o quimioterapia adyuvante cuando se trata el cáncer de colon en estadio II de alto riesgo. Sin embargo, las variaciones en el tratamiento y los resultados en pacientes con cáncer de colon en estadio II permanecen.Evaluar los beneficios de supervivencia de los tratamientos concordantes con las opciones terapéuticas sugeridas por "Watson for Oncology" (Watson para la oncología), un sistema de apoyo a la decisión clínica.Estudio observacional retrospectivo de concordancia entre el tratamiento real y las opciones terapéuticas de Watson para oncología.Un centro oncológico de primer nivel en China.Datos de tratamiento postoperatorio de registros de salud electrónicos de 306 pacientes con adenocarcinoma de colon en estadio II de alto riesgo.Patrones de tratamiento más supervivencia global y libre de enfermedad a 3 y 5 años para casos concordantes y no concordantes.La concordancia general fue del 90%. La mayoría de la atención no concordante resultó del uso de quimioterapia adyuvante (en lugar de vigilancia) en pacientes de alto nivel con inestabilidad de microsatélites y pacientes ≥70 años. No se observaron diferencias en la supervivencia global (p = 0,56) o la supervivencia libre de enfermedad (p = 0,19) entre los grupos de concordancia. Los pacientes que recibieron quimioterapia adyuvante tuvieron una supervivencia global a los 5 años significativamente más alta que los que fueron sometidos a vigilancia (94% frente a 84%, p = 0,01).Uso de casos retrospectivos extraídos de pacientes que se presentan para cirugía, falta de datos de seguimiento completos para el 58% de los pacientes que no pudieron ser incluidos en el análisis, y análisis de supervivencia que asume que no exite una correlación no medida entre supervivencia y censura.Watson para Oncología produjo opciones terapéuticas altamente concordantes con las decisiones humanas en un centro oncológico de primer nivel en China. Los patrones de tratamiento sugieren que Watson para Oncología puede guiar a los médicos para minimizar el sobretratamiento de pacientes con cáncer de colon en estadio II de alto riesgo con quimioterapia. Los análisis de supervivencia sugieren la necesidad de realizar mas investigaciónes para evaluar específicamente la asociación entre la vigilancia, la quimioterapia con uno solo o múltiples agentes y los resultados de supervivencia en esta población. Consulte Video Resumen en http://links.lww.com/DCR/B291. (Traducción-Dr. Gonzalo Hagerman).

[Prospective study of gracilis muscle repair of complex rectovaginal fistula and rectourethral fistula].

OBJECTIVE: To assess the efficacy and experience of gracilis muscle transposition for complex rectovaginal fistula (RVF) and rectourethral fistula (RUF). METHODS: Nineteen patients underwent gracilis muscle transposition for complex RVF and RUF from May 2009 to November 2011 in the Beijing Shijitan Hospital and the clinical data were prospectively collected. The success rate and complications were recorded. SF-36 quality of life score, Wexner fecal incontinence score, and female sexual function score before surgery and 6 months after surgery were recorded. RESULTS: In 19 patients, there were 8 males (RUF) and 11 females (RUF). The times of failed attempt repair preoperatively ranged from 0-3 (mean, 1.0). The diameter of the fistula ranged from 0.5-3.0 cm (mean, 1.6), and all fistulas located above the sphincter. The operative time ranged from 145-400 minutes (median, 240). The postoperative hospital stay ranged from 10-39 days (median 21). Early postoperative complications included thigh pain and numbness in 2 cases, leg numbness in 2 cases. No long-term complications were noticed. The follow-up period ranged from 6-35 months (median, 18). The gracilis muscle transposition had a healing rate of 94.7% (18/19). As compared with the preoperative level, Wexner score decreased from 10.0±8.8 to 2.9±5.8, and the continence function improved significantly (P=0.002). Sexual function score of 11 female patients increased from 1.0±1.8 to 4.0±4.0, and the sexual function had a significant improvement after surgery (P=0.022). SF-36 quality of life scores improved significantly (P<0.001). CONCLUSIONS: Gracilis muscle transposition for complex rectovaginal fistula and rectourethral fistula has high success rate with mild and rare complications.

[Study on subtype of human papillomavirus infection among aged 25 - 54 reproductive women in Beijing from 2006 to 2008].

OBJECTIVE: To investigate subtype of HPV infection among women at age of 25 to 54 years in Beijing. METHODS: From Sept. 2006 to Dec. 2008, 5552 reproductive women at age of 25 to 54 years classified into each 5-year as group were screened. Each participant completed a questionnaire and a sample of exfoliated cervical cells for liquid-based cytology and HPV subtype gene testing was performed. RESULTS: The overall prevalence of HPV was 6.68% (371/5552). High-risk HPV and Low-risk HPV prevalence were 5.76% (320/5552) and 2.00% (111/5552), respectively. The most common HPV types were HPV16 (2.61%, 145/5552), HPV58 (0.97%, 54/5552), HPV33 (0.85%, 47/5552), HPV43 (0.74%, 41/5552) and HPV56 (0.70%, 39/5552). There were two peaks of HPV prevalence: groups of 30 - 34 years and 40 - 44 years. CONCLUSION: The most common HPV subtypes in Beijing were HPV 16, 58, 33 and 43 and HPV prevalence showed a bi-modal age-specific curve.

[Epidemiological study of high risk human papillomavirus infection in 25 to 54 years old married women in Beijing.].

OBJECTIVE: To investigate high risk human papillomavirus (HR-HPV) prevalence among married women in Beijing and to study the high risk factors. METHODS: During March 2007 to September 2008, a total of 6185 married women sampled from 137 communities in 12 districts were screened by HR-HPV DNA test and cytological test. The interview was carried out with unified questionnaires. The database was set up and twice entered in EpiData 3.0. After checked up, the data were analyzed in SPSS 15.0. RESULTS: (1) The HR-HPV infection rate was 9.89%. The HR-HPV infection rate of the city zone, the suburb and the exurb were 9.34%, 10.51% and 9.51% (P > 0.05). The HR-HPV infection rate of the native and the outlander were 9.53%, 11.30% (P < 0.05). (2) The age distribution of HR-HPV infection was that the rate was around 10% among 25 to 44 age groups, which was the highest (11.21%) in 30 to 34 age group; then the rate was descended as the age raising, the rate of 50 to 54 age group was the lowest (7.78%). (3) Multiple logistic regression showed that the related risk factors of HR-HPV infection mainly included 1000 RMB and above of family income per person per month, possessing more than 1 sexual partner of her husband, outlander and high levels of education. (4) The prevalence of cervical intraepithelial neoplasia (CIN) in HR-HPV positive group was significantly higher than that in HR-HPV negative group (29.76% vs 3.32%, P < 0.01). CONCLUSIONS: (1) The HR-HPV infection rate among aged 25 to 54 years was 9.9% and there was no significant difference in area distribution. (2) The high risk population which should strengthen screening was the married bearing-age women with high level of family income, outlander, high levels of education and her husband possessing more than 1 sexual partner. (3) HR-HPV infection is the main risk factor for CIN and cervical cancer, while does not provide a causal relationship with them. The high risk population should be checked regularly to understand the development of HR-HPV infection and CIN incidence.

Decentralized impulsive control for a class of uncertain interconnected systems.

A great deal of stabilization criteria has been obtained from study of stabilizing interconnected systems. The results obtained are usually based on continuous systems by state feedback. In this paper, decentralized impulsive control is presented to stabilize a class of uncertain interconnected systems based on Lyapunov theory. The system under consideration involves parameter uncertainties and unknown nonlinear interactions among subsystems. Some new criteria of stabilization under impulsive control are established. Two numerical examples are offered to prove the effectiveness and practicality of the proposed method.