1.Establishment of a prediction model for capecitabine chemotherapy-related hepatotoxicity in colorectal cancer patients based on metabonomics
Zeshuai LIN ; Jiani CHEN ; Houshan YAO ; Mingming LI ; Jia YAO
Academic Journal of Naval Medical University 2025;46(1):40-47
Objective To identify potential biomarkers and establish a prediction model for chemotherapy-related hepatotoxicity susceptibility based on plasma endogenous metabolites of colorectal cancer(CRC)patients before chemotherapy.Methods The plasma samples of 50 CRC patients before capecitabine chemotherapy and the records of their chemotherapy-related hepatotoxicity during the follow-up were collected.An ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS)was used to perform untargeted metabolomic analysis.Based on bioinformatics analysis,differential analysis,correlation analysis,and random forest were used to screen for hepatotoxicity-related plasma endogenous metabolites.All samples were randomly assigned(7∶3)to training set or test set.A multivariate logistic regression model was established to predict the hepatotoxicity of capecitabine chemotherapy based on the training set data.The prediction effects of the model in the training,test and entire sets were evaluated by receiver operating characteristic(ROC)curve analysis.Results The endogenous metabolites related to hepatotoxicity in the plasma of CRC patients before chemotherapy were mainly lipid endogenous metabolites.A series of potentially important predictive biomarkers for hepatotoxicity susceptibility were identified,including sphingamine-1-phosphate,ceramide,galactose,arachidonic acid,tyrosine,biliverdin,myristic acid,phosphatidylcholine(35∶1),phosphatidylethanolamine(36∶1),and hexadecanoic acid.The area under curve values of the prediction model based on the above biomarkers in the training,test and entire sets were 0.946(95%confidence interval[CI]0.842-1.000),0.920(95%CI 0.720-1.000),and 0.912(95%CI 0.810-0.982),respectively.Conclusion The endogenous metabolites in the plasma of CRC patients before chemotherapy can effectively predict the hepatotoxicity of capecitabine chemotherapy.These hepatotoxicity biomarkers indicate that susceptible patients have characteristics related to lipid metabolism disorders.
2.Preliminary application study of robot-assisted pelvic exenteration in the treatment of low locally advanced or recurrent rectal cancer
Yu TAO ; Yunsheng CHAI ; Junnan CHEN ; Huan PENG ; Yi WANG ; Jian ZHANG ; Houshan YAO
Chinese Journal of Gastrointestinal Surgery 2025;28(8):895-901
Objective:To explore the feasibility and preliminary clinical experience of robot-assisted pelvic exenteration (PE) in the treatment of locally advanced (LARC) and recurrent (LRRC) rectal cancer.Method:A descriptive case series research method was adopted. Inclusion criteria included: (1) Age 18-80 years old; (2) Preoperative puncture biopsy performed through endoscopy, and a pathological diagnosis of rectal malignant tumor; (3) Preoperative imaging examinations confirming locally advanced (cT4b stage) or locally recurrent rectal cancer, with tumor location in the pelvic cavity; (4) Physical condition: ECOG score ≤1 point, and radical resection being feasible after assessment. The data for five patients with LARC or LRRC who underwent pelvic exenteration (PE) using the da Vinci robotic surgical system in the Department of Anorectal Surgery, the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from January, 2024 to January, 2025 were collected retrospectively. The mean age was (46.8±7.7) years, with 3 males and 2 females, who comprised 2 cases of LARC and 3 cases of LRRC. Two patients received preoperative radiotherapy, and 4 patients received preoperative chemotherapy. The average body mass index was (21.5±2.7) kg/m2. According to the American Society of Anesthesiologists (ASA) classification, 2 cases were grade II and 3 cases were grade III.Results:All patients with LARC or LRRC successfully underwent robot-assisted PE. The average operation time was (496.4±139.5) minutes; the average intraoperative blood loss was (72.0±29.5) ml; the average postoperative exhaust time was (50.0 ±13.6) hours; and the average postoperative defecation time was(64.2±15.3) hours. Mean early postoperative VAS pain scores was (3.6±1.5) points. Three patients underwent primary intestinal anastomosis, and 2 patients underwent colonic single-lumen ostomy. All 5 patients underwent urinary system reconstruction, among which 2 underwent ureterovesical reimplantation, 1 underwent percutaneous ureterostomy, 1 underwent ileal conduit replacement of bladder, and 1 underwent direct bladder suture. After surgery, except for 1 case of pelvic infection with effusion (Clavien-Dindo grade IIIa), there were no obvious postoperative complications. Postoperative pathological results showed that all patients achieved R0 resection, including 1 case of T4a stage and 4 cases of T4b stage (all involving urogenital organs or tissues), and 3 cases of N0 stage and 2 cases of N1 stage, with a maximum tumor diameter of (4.7±1.9) cm. The median postoperative follow-up time was 11 (range 7 to 17) months, and no patient experienced local recurrence.Conclusion:The above short-term preliminary results of robot-assisted PE in the treatment of LARC or LRRC within the pelvic cavity indicate that it is both safe and feasible.
3.Preliminary application study of robot-assisted pelvic exenteration in the treatment of low locally advanced or recurrent rectal cancer
Yu TAO ; Yunsheng CHAI ; Junnan CHEN ; Huan PENG ; Yi WANG ; Jian ZHANG ; Houshan YAO
Chinese Journal of Gastrointestinal Surgery 2025;28(8):895-901
Objective:To explore the feasibility and preliminary clinical experience of robot-assisted pelvic exenteration (PE) in the treatment of locally advanced (LARC) and recurrent (LRRC) rectal cancer.Method:A descriptive case series research method was adopted. Inclusion criteria included: (1) Age 18-80 years old; (2) Preoperative puncture biopsy performed through endoscopy, and a pathological diagnosis of rectal malignant tumor; (3) Preoperative imaging examinations confirming locally advanced (cT4b stage) or locally recurrent rectal cancer, with tumor location in the pelvic cavity; (4) Physical condition: ECOG score ≤1 point, and radical resection being feasible after assessment. The data for five patients with LARC or LRRC who underwent pelvic exenteration (PE) using the da Vinci robotic surgical system in the Department of Anorectal Surgery, the Second Affiliated Hospital of Naval Medical University (Shanghai Changzheng Hospital) from January, 2024 to January, 2025 were collected retrospectively. The mean age was (46.8±7.7) years, with 3 males and 2 females, who comprised 2 cases of LARC and 3 cases of LRRC. Two patients received preoperative radiotherapy, and 4 patients received preoperative chemotherapy. The average body mass index was (21.5±2.7) kg/m2. According to the American Society of Anesthesiologists (ASA) classification, 2 cases were grade II and 3 cases were grade III.Results:All patients with LARC or LRRC successfully underwent robot-assisted PE. The average operation time was (496.4±139.5) minutes; the average intraoperative blood loss was (72.0±29.5) ml; the average postoperative exhaust time was (50.0 ±13.6) hours; and the average postoperative defecation time was(64.2±15.3) hours. Mean early postoperative VAS pain scores was (3.6±1.5) points. Three patients underwent primary intestinal anastomosis, and 2 patients underwent colonic single-lumen ostomy. All 5 patients underwent urinary system reconstruction, among which 2 underwent ureterovesical reimplantation, 1 underwent percutaneous ureterostomy, 1 underwent ileal conduit replacement of bladder, and 1 underwent direct bladder suture. After surgery, except for 1 case of pelvic infection with effusion (Clavien-Dindo grade IIIa), there were no obvious postoperative complications. Postoperative pathological results showed that all patients achieved R0 resection, including 1 case of T4a stage and 4 cases of T4b stage (all involving urogenital organs or tissues), and 3 cases of N0 stage and 2 cases of N1 stage, with a maximum tumor diameter of (4.7±1.9) cm. The median postoperative follow-up time was 11 (range 7 to 17) months, and no patient experienced local recurrence.Conclusion:The above short-term preliminary results of robot-assisted PE in the treatment of LARC or LRRC within the pelvic cavity indicate that it is both safe and feasible.
4.Clinical significance of hepatocyte nuclear factor 4αin rectal cancer and its relationship with prognosis
Juan WANG ; Weiping JI ; Houshan YAO ; Liangzhe WANG ; Zhiqian HU
Journal of International Oncology 2014;(9):704-708
Objective To investigate the clinical significance of hepatocyte nuclear factor 4α(HNF4α)in rectal cancer and its relationship with prognosis.Methods Real-time PCR was designed to detect the expression of HNF4αon mRNA level and the immunohistochemistry was used to determine the expression of HNF4αon protein level in rectal cancer tissue.The relationship between HNF4αexpression and clinical characteristics was also analysed.The Kaplan-Meier method was used for univariate analysis and a Cox proportional hazards regression model was performed for multivariate analysis.Results HNF4αwas low expressed both on mRNA (t=6.092,P<0.001)and protein level (χ2 =15.230,P<0.001)in rectal cancer tissue.HNF4αexpression on protein level was related with the clinical stage (χ2 =48.311,P<0.001),depth of invasion (χ2 =23.911,P<0.001),histological differentiation (χ2 =20.787,P<0.001),lymph node metastasis (χ2 =39.064,P<0.001)and distant metastasis (χ2 =5.146,P=0.04),while age and gender were not relevant.The cumulative 3-year overall survival of patients with low HNF4αexpression (43.8%)was much worse than the patients with high HNF4αexpression (95 .5%),and the difference was statistically sig-nificant (P<0.001).Univariate analysis revealed that HNF4αexpression (χ2 =28.778,P<0.001),differ-entiation (χ2 =26.680,P<0.001 ),clinical stage (χ2 =32.702,P<0.001 ),depth of invasion (χ2 =6.226,P=0.013),lymph node invasion (χ2 =15.270,P<0.001)and distant metastasis (χ2 =21.817, P<0.001)were statistically significant worse predictors for rectal cancer,whereas age and gender were not rel-evant.The multivariate Cox proportional hazard analysis revealed that HNF4αlow expression (RR=6.084, P=0.028)was independent prognostic markers for 3-year overall survival in the patients with rectal cancer. Conclusion HNF4αwas closely related to the tumorigenesis and progression of rectal cancer,which is an independent prognostic marker for rectal cancer,and which may be an effective target for the therapy of rectal cancer.
5.Application of ' three phases and seven steps' case-based learning in surgical teaching
Houshan YAO ; Antang LIU ; Lei JIANG ; Yongfei GUO ; Hongliang SHEN
Chinese Journal of Medical Education Research 2013;(5):481-483
In view of the characteristics of the learning curve for medical students,the ' three phases and seven steps' case-based learning model was designed and implemented by Changzheng Hospital,the Second Military Medical University.This model was carried out in the theoretical study stage,the first round of internship and the second round of internship.Cases of single diseases,multiple diseases involving variant systems and a variety of diseases involving different department were enrolled for analysis and discussion.Implementation of each case study was divided in seven procedures:determining learning objective and choosing typical case,studying case and raising questions,panel discussions and establishment of common problems,looking up for information to answer questions and preparing report slide,large group discussions,summary and evaluation.'Three phases and seven steps' case based learning model ensure the width and depth of basic medical knowledge learned by the students.With the practice of this model,the basic medical knowledge was constructed systemically and comprehensively by medical students.Students' abilities of problem-analyzing and problem-solving as well as clinical research were developed.This model was effective according to our practice and was worth spreading out.

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