Objective:To evaluate whether additional radical surgery is necessary following non-curative endoscopic resection of early colorectal cancer.Method:Clinicopathological data in 104 patients following non-curative endoscopic resection of early colorectal coucer at the Department of General Surgery, Peking University First Hospital between Jan 2011 and Dec 2021.Results:Lymph node metastasis and/or residual cancer was found in 23 patients (22%), including 12 cases of lymph node metastasis, 7 cases of residual cancer and 4 patients with both residual cancer and lymph node metastasis. Univariate analysis indicated that vascular infiltration, positive vertical margin, and female gender were risk factors for lymph node metastasis. Risk factors for residual cancer were tumors ≥2 cm in size, negative lift sign, infiltration depth of ≥1 000 μm, and positive horizontal and vertical margins. Multivariate Logistic regression analysis revealed that vascular invasion, positive vertical margins, and being female were independent risk factors for lymph node metastasis, while positive vertical margins was independent risk factor for residual cancer. Salvage surgery lasted for a median of 184 (156-233) minutes, with an estimated blood loss of 50 (20-100) ml and an average postoperative hospital stay of 9 (8-11) days. Seven cases of Clavein-Dindo Ⅱ or higher complications were observed, including pulmonary embolism in 1 case , anastomotic leakage in one, lymphatic fistula in one, bowel obstruction in 2 cases and urinary tract infection in 2 cases.Conclusion:Salvage surgery is mandatory for early endoscopic non-curative resection of colorectal cancer.

Objective:By analyzing the clinical data of patients with primary duodenal adenocarcinoma (PDA), the risk factors affecting the postoperative prognosis of PDA patients were discussed.Methods:The clinical data of 191 patients diagnosed with PDA in Peking University First Hospital from Jan 2009 to Dec 2022 were collected. The survival rate was calculated and the survival curve was plotted by Kaplan-Meier method. Univariate analysis was performed by Log-Rank test, and multivariate analysis was performed by COX proportional hazards regression model to obtain independent risk factors.Results:The median age of onset in patients with PDA is 65 years old, and the most common symptoms are abdominal pain and abdominal distension. Prognostic analysis showed that the survival rates at 1, 3 and 5 years were 73.8%, 44.6%, and 23.0%. The analysis of Cox risk proportional regression model showed that preoperative CA19-9 level, depth of tumor invasion, degree of differentiation, TNM stage, and surgical mode were independent risk factors for the prognosis of PDA (all P<0.01). Conclusion:The overall incidence of PDA is low, but the prognosis is rather poor. Multvariable factors are associated with its prognosis and surgery is still the mainstay for hope of cure.

Myelodysplastic syndromes (MDS) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are bone marrow disorders characterized by cytopenias and progression to acute myeloid leukemia. Hypomethylating agents (HMAs) are Food and Drug Administration-approved therapies for MDS and MDS/MPN patients. HMAs have improved patients’ survival and quality of life when compared with other therapies. Although HMAs are effective in MDS and MDS/MPN patients, they are associated with significant toxicities that place a large burden on patients. Our goal is to develop a safer and more effective HMA from natural products. We previously reported that black raspberries (BRBs) have hypomethylating effects in the colon, blood, spleen, and bone marrow of mice. In addition, BRBs exert hypomethylating effects in patients with colorectal cancer and familial adenomatous polyposis. In the current study, we conducted a pilot clinical trial to evaluate the hypomethylating effects of BRBs in patients with low-risk MDS or MDS/MPN. Peripheral blood mononuclear cells (PBMCs) were isolated before and after three months of BRB intervention. CD45 + cells were isolated from PBMCs for methylation analysis using a reduced-representation bisulfite sequencing assay. Each patient served as their own matched control, with their measurements assessed before intervention providing a baseline for post-intervention results. Clinically, our data showed that BRBs were well-tolerated with no side effects. When methylation data was combined, BRBs significantly affected methylation levels of 477 promoter regions. Pathway analysis suggests that BRB-induced intragenic hypomethylation drives leukocyte differentiation. A randomized, placebo-controlled clinical trial of BRB use in low-risk MDS or MDS/ MPN patients is warranted.

Objective:To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC).Methods:A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ 2 test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results:A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n=28), posterior pelvic exenteration ( n=32), and total pelvic exenteration ( n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P=0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions:The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

Objective:To evaluate the factors affecting the degree of radical resection and the prognosis of patients with locally recurrent rectal cancer (LRRC).Methods:A retrospective case-control study was performed. Clinical data of 111 patients with LRRC undergoing operation at the General Surgery Department of Peking University First Hospital from January 2009 to August 2019 were analyzed retrospectively. The "Peking University First Hospital F typing" was performed according to the preoperative images of the pelvic involvement. The pelvis was assigned into four directions: the front wall, lateral sides of the pelvic wall and the sacrum. According to the degree of pelvic wall involvement, F typing included F0 type (no involvement of the pelvic wall, the cancer only involved the adjacent organs or invaded conteriorly the urinary tract, genital organs or small intestine), F1 type (cancer involved the pelvic wall in one direction, such as the sacrum, or one side of the pelvic wall), F2 type (cancer involved the pelvic wall in two directions) and F3 type (cancer involved the pelvic wall in three directions). Case inclusion criteria: (1) LRRC was confirmed by imaging and pathological examination of samples (puncture or endoscopic biopsy); (2) complete clinical and follow-up data; (3) informed consent of patient. Those with dysfunction of heart, lung, etc., intolerance of operation, F3 type indicated by image, and distant metastasis were excluded. The degree of radical resection was evaluated according to the postoperative pathological results. Patients were followed up every 12 months and related examinations were arranged. The univariate analysis of radical resection was performed by χ 2 test, and the multivariate analysis was performed by logistic methods. The survival rate was calculated by Kaplan-Meier method and the survival curve was drawn. The survival rate was compared by log-rank test. Cox proportional hazards model was used to analyze the factors affecting the prognosis of patients with LRRC. Results:A total of 111 patients were included in this study. Of 111 patients, 59 were male and 52 were female; recurrent age of 36 cases was ≥ 65 years old; CEA level of 48 cases was ≥15 μg/L. According to the "Peking University First Hospital F typing", 70 cases were F0 type, 38 F1 type and 3 F2 type. Surgical procedures were abdominoperineal resection ( n=28), posterior pelvic exenteration ( n=32), and total pelvic exenteration ( n=51, including 1 case of TPE combined with sacrectomy). According to the postoperative pathological results, R0, R1 and R2 resections were 83, 20 and 8 cases, respectively. Univariate analysis showed that the degree of radical resection was associated with the secondary surgical procedure, F typing and lymph node metastasis (all P<0.05). Multivariate analysis showed that F typing (F1-F2) was an independent risk factor for non- R0 resection (OR=37.256, 95%CI:8.572 to 161.912, P<0.001). The morbidity of operative complications was 22.5% (25/111); the perioperative mortality was 1.8% (2/111); the local recurrence rate after the second operation was 37.8% (42/111). The 3- and 5-year overall survival rates were 41.2% and 21.9% respectively. The 3-year survival rates of patients with and without postoperative chemotherapy were 52.7% and 32.4% respectively ( P=0.005). The 3-year survival rates of patients with lower (<15 μg/L) and higher CEA level (≥15 μg/L) were 52.9% and 24.3% respectively ( P<0.001). The 3-year survival rates of patients with R0, R1 and R2 resection were 49.8%, 21.3% and 8.5% respectively ( P=0.002). The 3-year survival rates of patients with F0, F1 and F2 type were 52.7%, 22.0% and 0 respectively ( P<0.001). Cox analysis confirmed that the degree of radical resection (HR=2.088, 95%CI:1.095 to 3.979, P=0.025), the CEA level before the secondary operation (HR=1.857, 95%CI:1.157 to 2.980, P=0.010) and postoperative chemotherapy (HR=1.826, 95%CI:1.137 to 2.934, P=0.013) were independent factors affecting the prognosis. Conclusions:The indication of LRRC surgical treatments must be strictly limited. Evaluation of the fixation site to the pelvic wall is helpful for improving the rate of R0 resection. Lower preoperative CEA level, radical resection and postoperative chemotherapy are protective factors of prolonged overall survival time of patients with LRRC.

Objectives: To examine the value of multi-slice spiral CT angiography (MSCTA) in the analysis of anatomical variation and structural classification of right colon vessels. Methods: From August 2015 to August 2017, 198 patients (96 of whom underwent laparoscopic radical resection of right colon cancer) at Department of General surgery of Peking University First Hospital were retrospectively collected, and the results of abdominal enhanced CT scan were collected and three-dimensional reconstruction of blood vessels was performed. There were 104 males and 94 females. The age was 64(27) years (M(Q_R), range: 19 to 87 years). Right gastroepiploic vein, anterior superior pancreaticoduodenal vein, right colonic vein (RCV), superior right colonic vein, ileocolon artery or vein (ICA or ICV), middle colon artery or vein (MCA or MCV) and Henle trunk were observed and recorded respectively. The anatomical relationship between the positions of blood vessels, the length of Henle trunk and surgical trunk were measured. Results: ICV and ICA were the most constant anatomic structures. The ICV/ICA of all patients came directly from SMV/SMA, 36.9% (73/198) ICV going in front of SMV and 63.1% (125/198) behind SMV. 72.2% (143/198) of the patients had RCV imported into Henle trunk and the rest into SMV. Middle colonic vein (MCV) could be observed in 81.3% (161/198) of the cases. 81.4% (131/161) of MCV were imported into SMV, 16.8% (27/161) into Henle trunk, 1.2% (2/161) into the first jejunal vein and 0.6% (1/161) into the splenic vein. Henle trunk was divided into 4 types, among which the occurrence probability of gastric node and pancreatic trunk was the highest. The dry length of Henle trunk was (0.82±0.39) cm (range: 0.37 to 1.68 cm). The length of surgical trunk was (2.54±0.83) cm (range: 1.57 to 3.95 cm). Accuracy of MSCTA results was 96.9%(93/96). Conclusions Anatomical variation of blood vessels in the right colon is common. Abdominal CT angiography can accurately determine the anatomical structure of the blood vessels in the right colon.

OBJECTIVETo investigate the clinicopathological features and prognosis of colorectal synchronous multiple primary cancer(SMPC).

METHODSFrom January 2008 to June 2011, 51 patients diagnosed with colorectal SMPC underwent surgery at Department of General Surgery of Peking University First Hospital. Their clinicopathological features, diagnosis, treatment and prognosis were summarized and analyzed. SMPC was diagnosed according to the following criteria: each tumor must have a definite pathologic picture of malignancy; metastasis or recurrence from another colorectal cancer was excluded; tumors must be distinctly separated by at least 5 cm of all intact bowel wall from each other; SMPC has abnormal cells between tumor and normal mucosa and abnormal gland of transitional zone; each cancer is infiltrating carcinoma except the carcinoma in situ; all the cancers are detected at the same time or within 6 months. Multiple primary colorectal cancer originated from familial colonic polyposis or ulcerative colitis was excluded.

RESULTSThese 51 colorectal SMPC patients accounted for 3.5% of 1 452 colorectal cancer patients in the same period at our hospital, with 32 males and 19 females, and mean age of (63±13)(29 to 82) years. Of 51 cases, 46(90.2%) had 2 original carcinoma, 3(5.9%) had 3 original carcinoma and 2(3.9%) had 4 carcinoma; 23(45.1%) complicated with colon polyps, 4(7.8%) complicated with malignancy outside the colorectum. In TNM staging, 7(13.7%), 15(29.4%), 24(47.1%) and 5(9.8%) patients were stage I(, II(, III( and IIII( respectively. Among 51 patients undergoing surgery by different procedures, 16 were subtotal colon resection, 8 were extended right colon resection, 5 were extended left hemicolon resection, 8 were right hemicolon resection plus Dixon procedure, 10 were Dixon, and 4 were right hemicolon resection plus sigmoid colon resection. Adjuvant chemotherapy and support treatment were given according to the condition after operation. A total of 105 tumors were found, including 25(23.8%) tumors in sigmoid colon, 24(22.9%) in rectum, 22(21.0%) in ascending colon and 4 in organs outside the colorectum. Tubular adenocarcinoma (86/105, 81.9%) was the main pathological type in these colorectal SMPC patients. During the follow-up of median 43.5 months, 10 cases presented local recurrence and 6 cases had liver metastasis. Multivariable analysis showed that ≤65 years old (OR=22.757, 95%CI: 1.562-331.543, P=0.002),undifferentiated carcinoma or mucous adenocarcinoma (OR=27.174, 95%CI: 2.834-260.512, P=0.004), stage III(-IIII( (OR=29.626, 95%CI: 3.216-272.884, P=0.003) were independent risk factors of postoperative 5-year recurrence and metastasis, but the number of SMPC lesions and the surgical method were not associated with postoperative 5-year recurrence and metastasis (P=0.564, P=0.513). The 3-year and 5-year survival rates of colorectal SMPC patients were 76.5% and 64.7%.

CONCLUSIONTwo-original carcinoma is the most common in colorectal SMPC patients, which mainly distributes in sigmoid colon and rectum. Postoperative monitoring should be strengthened for those patients with younger age, poor pathological types and advanced staging to prevent recurrence and metastasis.

Objective: To investigate the risk factors and computed tomography (CT) diagnostic accuracy of anastomotic leakage after resection of rectal cancer (Dixon) . Methods: This retrospective study was conducted in Peking University First Hospital from January 2013 to June 2015. A cohort of 452 patients with rectal cancer was enrolled in the study. All the patients underwent anterior resection. The relationship between clinical-pathological data (including sex, age, body mass index (BMI) , presence of diabetes, hypohemoglobin (Hb < 90 g/L) , hypoalbuminemia (Alb < 35 g/L) , the distance from the lower edge of the tumors to the anus, tumor diameter, tumor differentiation, tumor TNM stage, neoadjuvant therapy status, ligation of the left colonic artery (LCA) , preventive colostomy, and anastomotic leakage was analyzed retrospectively. Univariate analysis using χ² test and multivariate analysis by using the Ordered Classification Arguments Logistic regression model. Results: Of all the cases, 281 and 171 patients were men and women, respectively. The median age was 64 years (range, 18-88 years) . Forty-seven patients (10.4%) were diagnosed with anastomotic leakage, and the median diagnostic time of anastomotic leakage was 6.5 days (range, 3-31 days) . One patient with anastomotic leakage died because of respiratory failure within 1 month postoperatively; 11 patients underwent salvage colostomy performed 2-34 days (median, 7 days) after the first surgery. All the 11 patients underwent colostomy closure within 2 years. The other 35 patients recovered by antibiotic and peritoneal lavage treatment. The mean length of postoperative hospital stay in patients without anastomotic leakage was 8.4±2.4 days, which was significantly shorter than that in patients with anastomotic leakage (34.6±15.7 days) , and the difference was statistically significant (t = 24.127, P = 0.008) . The results of the univariate analysis showed that BMI≥28 kg/m² (χ² = 7.550, P = 0.000) , diabetes mellitus (χ² = 5.055, P = 0.025) , Hb < 90 g/L preoperatively (χ² = 5.718, P = 0.017) , Alb < 35 g/L preoperatively (χ² = 8.096, P = 0.004) , distance of < 6 cm from the lower edge of the tumors to the anus (χ² = 8.205, P = 0.004) and LCA ligation (χ² = 16.540, P = 0.000) were risk factors for the occurrence of anastomotic leakage. Multivariate analysis showed that BMI≥28 kg/m² (OR = 1.758, 95%CI: 1.265-2.454, P = 0.021) , distance of < 6 cm from the lower edge of the tumors to the anus (OR=1.530, 95%CI: 1.035-2.117, P = 0.037) , LCA ligation (OR = 1.551, 95%CI: 1.035-2.131, P = 0.042) were independent risk factors for anastomotic leakage. The CT diagnostic sensitivity of anastomotic leakage was 91.2% (31/34) . The false positive rate of CT for diagnosing anastomotic leakage was zero 7 days after the Dixon procedure. Conclusion Important factors, including BMI of patients, LCA ligation, and the distance from the lower edge of the tumors to the anus are related with anastomotic leakage. The individual treatments should be considered based on the patient′s clinical condition. CT was recommended 7 days postoperatively when anastomotic leakage was highly suspected.

In this study, we established a rapid and efficient HPLC method to determine the accumulation of Huperzine A and Huperzine B in the fermentation broth of endophytic fungus Colletotrichum gloesporioides from Huperzia serrate. The chloroform extracts of fermentation broth were dissolved in methanol and filtered before injection for HPLC analysis. The analysis was performed on an Agilent Eclipse plus-C18 column (250 mm×4.6 mm, 5 μm) by isocratic elution. The mobile phase was 0.015 mol/L ammonium acetate-methanol (70:30, V/V), the flow rate was 1 mL/min and the detection wavelength was set at 308 nm. Huperzine A and Huperzine B could be well separated within 25 min. Good linearity of Huperzine A was found in the range of 1.50-48.00 μg/mL (r=0.999 5), and that of huperzine B was in 0.25-7.50 μg/mL (r=0.999 7). The average recoveries of Huperzine A and Huperzine B were 106.83% and 108.06%, respectively (RSD=3.34%, 3.60%). The results demonstrate that this method can detect the content of huperzine A and huperzine B in fermentation broth simply, rapidly, accurately and in good reproducibility. Under the optimized conditions, the accumulated content of huperzine A and huperzine B were measured from the sixth to the fifteenth day. Huperzine A and Huperzine B reached the highest (12.417 0 μg/mL and 4.660 3 μg/mL, respectively) at the fourteenth and eighth days. The analysis methodology could contribute to the future study of huperzine A and huperzine B biosynthesis in C. gloeosporioides, consequently facilitate the development of new drug resources.

The clinical application of novel chemotherapeutic drugs including oral 5-FU and targeted drugs and preoperatively accurate imaging grading has brought challenges to the indication criteria developed by NCCN and ESMO for neoadjuvant chemoradiotherapy in locally advanced rectal cancer (LARC). Extended hotspots have focused on the effectiveness of using capecitabine instead of fluorouracil infusion, the combination of multiple drugs and the feasibility of using neoadjuvant chemotherapy instead of neoadjuvant chemoradiotherapy for selective patients. Traditionally, the evaluation of the effect of neoadjuvant therapy has been based on the effect on the pathological complete remission (pCR) rate. However, current studies recommend the disease-free survival (DFS) as a more important outcome. Besides, seeking for effective biomarkers as predictive markers for neoadjuvant therapies or as prognostic markers remains a hotspot in the field of neoadjuvant chemoradiotherapy. The "watch and wait" approach refers to taking a close follow-up strategy instead of direct operation for patients achieving clinically complete remission (cCR) after neoadjuvant therapy. However, there is no unified evaluation criteria and time point for the evaluation of cCR following neoadjuvant therapy. Therefore, there remain a lot of controversies regarding the clinical application of neoadjuvant chemoradiotherapy in LARC. In this manuscript, research progress in the indication for neoadjuvant therapy, improvement in the neoadjuvant therapeutic schedule, advancement of the efficacy evaluation criteria of neoadjuvant therapy, the "watch and wait" approach and other hot topics is summarized to provide references for clinical practice.
Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; therapeutic use ; Chemoradiotherapy ; Fluorouracil ; therapeutic use ; Humans ; Neoadjuvant Therapy ; Neoplasm Staging ; Rectal Neoplasms ; therapy ; Treatment Outcome