OBJECTIVETo establish gemcitabine-resistant pancreatic cancer cell strain and study the role of thioredoxin reductase (TrxR) in drug-resistant process.

METHODSGemcitabine-resistant pancreatic cancer cell strain SW1990/GZ was induced by increasing drug dosage intermittently, then the changes of its biological features and the activity of TrxR were examined.

RESULTSStable drug-resistant SW1990/GZ cell strain was established by culturing with gemcitabine for 9 months. The morphology and growth characteristics of the cell strain changed remarkably. The cells shrunk and became rounder; its endoplasm expanded; granular substances increased; and the doubling-time was prolonged. Resistance of the cell line to gemcitabine, fluorouracil, adriamycin, and mitomycin significantly increased. The TrxR activity of the drug-resistant cells was increased markedly.

CONCLUSIONSW1990/GZ has certain multidrug resistance to some chemotherapy drugs, and TrxR plays a role in the drug-resistant process.

Antimetabolites, Antineoplastic ; pharmacology ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Pancreatic Neoplasms ; enzymology ; pathology ; Thioredoxin-Disulfide Reductase ; drug effects ; metabolism

OBJECTIVETo summarize clinical experience in the treatment of low rectal cancer with anterior perineal plane for ultra-low anterior resection of the rectum(APPEAR).

METHODSClinical and follow-up data of 26 patients with low rectal cancer undergoing the APPEAR operation in Department of General Surgery at Peking Union Medical College from September 2009 to August 2011 were retrospectively analyzed.

RESULTSThe 26 cases consisted of 19 male and 7 female patients with an average age of (63.4 ± 9.5) years. The average tumor distance from the anal verge was (4.6 ± 0.7) cm according to preoperative examinations. Fourteen patients received neoadjuvant radiochemotherapy before the operation. All the 26 patients had successful sphincter-preserving operations. The average operative time was (170 ± 21) min and the average intra-operative blood loss (140 ± 69) ml. Complications included one case of intraoperative injury to the rectal wall and 4 cases of postoperative perineal wound infection. Postoperative pathological examination showed well to moderately differentiated adenocarcinomas(n=10), moderately differentiated adenocarcinomas with partial mucinous adenocarcinomas (n=7), poorly differentiated adenocarcinoma(n=1), villous adenoma with high-grade intraepithelial neoplasia (n=1), and rectal villous adenoma(n=1). In 6 cases no residual tumor cells were detected in the surgical specimens. All the patients were followed-up for an average period of(11.4 ± 5.6) months. No impaired urinary function or tumor recurrence was observed during the follow-up. Eighteen patients had the transverse colon stoma closure six months after the operation. The average Wexner continence score was 5.5 after colostomy reversal surgery. The anorectal manometry tests showed that maximum squeeze pressure of the anal sphincter was(224.0 ± 59.3) mm Hg. The maximum resting pressure was (42.5 ± 11.8) mm Hg, and the maximum tolerable volume of the rectum was (120.0 ± 27.4) ml. Anorectal reflexes were present in all these patients.

CONCLUSIONThe APPEAR technique can be applied in the sphincter-preserving operations for low rectal cancer patients with satisfactory anal function.

Aged ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Perineum ; surgery ; Rectal Neoplasms ; surgery ; Rectum ; surgery ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of neoadjuvant radiotherapy alone versus chemoradiotherapy in patients with mid-low locally advanced rectal cancer.

METHODSData of 69 patients with advanced (stage T(3) or T(4)) rectal cancer, undergone neoadjuvant therapy in our hospital from October 1997 to October 2007, were analyzed retrospectively. Forty patients received preoperative radiotherapy (50 Gy in 25 fractions over 5 weeks) alone (RT group), and 29 patients received preoperative radiotherapy concomitant with 5-FU/leucovorin -based preoperative chemoradiotherapy (CRT group). Radical surgery was performed 4-6 weeks after radiation therapy by the rule of TME.

RESULTSAll the patients underwent operations, including 26 abdominoperineal resections, 27 anterior resections, 10 Parks operations and 6 Hartmann's procedures. The sphincter preservation rate was 47.5%(19/40) in RT group, and 62.1%(18/29) in CRT group(P>0.05). In pathological findings, tumor and nodal downstaging were observed in 12 patients of RT group (30.0%), and 17 of CRT group (58.6%)(P<0.05). In RT group, 3 patients (7.5%) showed pathological complete regression (pCR), and the overall response rate (CR plus PR) was 60%(24/40). In CRT group, 4(13.8%) showed pCR and the overall response rate was 79.3%(23/29). There was significant difference of the overall response rate between two groups. Three-year disease-free survival for all patients was 77.3%.

CONCLUSIONFor patients with locally advanced rectal cancer, neoadjuvant chemoradiotherapy provides higher sphincter preservation rate, overall response rate and better down-staging as compared to radiotherapy alone.

Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm Staging ; Radiotherapy, Adjuvant ; methods ; Rectal Neoplasms ; pathology ; radiotherapy ; therapy ; Retrospective Studies

OBJECTIVETo compare the application of transanal endoscopic microsurgery (TEM) technique with Mason's operation in the treatment of early rectal cancer.

METHODSPatients with early rectal cancer were divided into two groups according to different surgical procedures they underwent during different period. Patients in Mason Group underwent Mason's operations during the period from January 2000 to March 2006; and in TEM Group were managed with TEM procedures from April 2006 to July 2011. There were 21 patients in TEM Group and 26 patients in Mason Group. No statistically significant difference was found between the two groups in terms of patient's age, gender, preoperative TNM staging, and tumor diameter. In comparison with Mason Group, TEM Group had a longer distance of the tumor from the anal verge. The safety, postoperative complications, patients' postoperative recovery, and the oncological outcomes of 2 groups were compared with each other.

RESULTSNo perioperative death occurred in the two groups. The TEM Group had notably shorter operating time ((67 ± 24) minutes) and lesser intra-operative blood loss ((9 ± 6) ml) than Mason Group (t = 3.526 and 7.078, P < 0.05). The time of the postoperative bed rest, the urinary drainage, the recovery of oral intake, and the hospital stay in TEM Group were (1.3 ± 0.5) days, (1.2 ± 0.4) days, (1.5 ± 0.5) days, and (4.3 ± 1.6) days, respectively, and all were prominently shorter than those of Mason group (t = 4.925 - 14.640, P < 0.05). Patients in TEM group were followed up for an average of 36.5 months with one patient being lost, while patients in Mason group were followed up for an average of 81.6 months. The difference between the two groups in terms of short-term accumulated survival (94.8% vs. 96.3%) showed no statistical significance (P > 0.05).

CONCLUSIONTEM technique is a favorable minimally invasive procedure associated with satisfactory oncological outcomes in the treatment of early rectal cancer.

Adult ; Aged ; Anal Canal ; surgery ; Female ; Humans ; Male ; Microsurgery ; methods ; Middle Aged ; Minimally Invasive Surgical Procedures ; methods ; Rectal Neoplasms ; surgery

OBJECTIVETo compare the outcomes of right hemicolectomy performed either by the hand-assisted laparoscopic(HALS) or conventional laparoscopic surgery(LAS).

METHODSNinety-five patients undergoing HALS(n=47) from March 2002 to November 2006 or by LAS (n=48) from January 2007 to December 2009 were retrospectively studied. All the operations were performed by the same surgical team. Patient safety, postoperative recovery, complications, oncologic outcomes, medical expenses, and the follow-up results were compared between the two groups.

RESULTSNo severe complications or perioperative deaths were oberved. There were significant differences between the two groups in terms of intraoperative bleeding, operative time, and length of incision(all P<0.05). However, the conversion rate, intraoperative injuries, time to first bowel movement, postoperative bed-rest time, hospital stay, time to first oral intake, and the number of patients requiring postoperative analgesia were comparable between the two groups(P>0.05). Length of surgical specimen was (25.6±9.9) cm in the HALS group and was (26.8±7.9) cm in the LAS group, the diffenence was not statistically significant(P<0.05). The mean number of lymph nodes retrieved in HALS group was 18.2±12.1, which was significantly lower than that in LAS group(24.1±9.3, P<0.05). The medical expense of the LAS group was (28 049.8±7576.1) RMB, which was significantly higher than that of the HALS group(21 132.7±5323.4) RMB(P<0.05). A follow-up rate of 93.7% was achieved in the HALS group with 3 patients lost to follow-up. The follow-up duration ranged from 45.4 to 101.9 months with a median of 66.7 months. In LAS group, the follow-up rate was 96% with 2 patients lost to follow-up and the follow-up duration ranged from 12.4 to 45.7 months with a median of 21.6 months. There was no significant difference in 3-year disease-free survival(91.3% vs. 87.9%, P>0.05) between the two groups.

CONCLUSIONHALS and LAS can achieve similar minimal invasiveness efficacy and oncologic outcomes for right hemicolectomy.

Aged ; Colectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Laparoscopy ; methods ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the safety and efficacy of prophylactic single antibiotic administration in selective open colorectal surgery.

METHODSTwo hundred and seventy-five patients undergoing selective open colorectal surgery in the Peking Union Medical College Hospital from October 2009 to October 2011 were retrospectively reviewed. Prophylatic single antibiotic administration was used by intravenous infusion 30-60 min before incision. No antibiotics would be given after operation if there was no surgical site infection(SSI). According to the incidence of postoperative SSI, unexplained use of antibiotics, anastomotic leakage and distant-site infection, the clinical outcome was assessed to be prophylactic success, prophylactic failure or distant-site infection, respectively.

RESULTSThere was no intraoperative or postoperative antibiotics related drug anaphylaxis in all the 275 patients. By prophylactic single antibiotic administration, there were prophylactic success in 243 patients(88.4%,243/275), prophylactic failure in 23(8.4%,23/275), distant-site infection in 9(3.3%,9/275). In the 23 patients with failed prophylaxis, there were SSI in 13(4.7%,13/275) patients, postoperative use of broad-spectrum antibiotics for unexplained fever in 2(0.7%,2/275), postoperative anastomotic leakage in 8(3.6%,8/222).

CONCLUSIONProphylactic single antibiotic administration in selective open colorectal surgery is safe and effective.

Anti-Bacterial Agents ; therapeutic use ; Antibiotic Prophylaxis ; Colorectal Surgery ; Humans ; Incidence ; Retrospective Studies ; Surgical Wound Infection ; epidemiology ; prevention & control

OBJECTIVETo investigate the impact of the drug resistance on the radioresistance in human pancreatic cancer cell lines.

METHODSThree drug resistant pancreatic cancer cell sublines induced by fluorouracil (5-FU), adriamycin (ADM) and gemcitabine respectively, SW1990/FU, SW1990/ADM and SW1990/Gz, were tested for the cell cycle and radio-sensitivity with flow cytometry and clonogenic assay.

RESULTSCompared with SW1990, the cell cycle assay indicated higher G(0)/G(1) period percentage in SW1990/FU and SW1990/Gz, but the G(2)/M period percentage decreased; SW1990/FU had the same while SW1990/Gz had lower S period percentage. SW1990/ADM almost had a similar cell cycle with SW1990. Clonogenic assay showed both SW1990/FU and SW1990/Gz had greater survival fraction (SF(2)) than SW1990, but SW1990/ADM had seemingly similar SF(2) as SW1990.

CONCLUSIONDrug resistant pancreatic cancer cell lines have reduced G(2)/M period percentage and increased radioresistance.

Antineoplastic Agents ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Deoxycytidine ; analogs & derivatives ; pharmacology ; Doxorubicin ; pharmacology ; Drug Resistance, Neoplasm ; drug effects ; genetics ; Fluorouracil ; pharmacology ; Humans ; Pancreatic Neoplasms ; pathology ; Radiation Tolerance ; drug effects

OBJECTIVELaparoscopic colorectal surgery is a skill-dependent procedure. The present study aims to analyze the learning curve of a properly trained surgeon, with basic laparoscopic techniques, to become skillful in performing laparoscopic colorectal operations.

METHODSA series of non-selective, consecutive 189 cases of laparoscopic colorectal surgery were accomplished, from December 2009 to February 2012, by one surgeon with years of skilled technique in laparoscopic cholecystectomy, rich experience in assisting laparoscopic colorectal surgery, and experience of approximately 180 procedures of gastric and colorectal surgery annually. 170 out of 189 procedures were radical operations for colorectal neoplasma, including right colectomies in 28 cases, left colectomies in 5 cases, sigmoidectomies in 28 cases, high Dixon procedures in 45 cases, low Dixon (total mesorectal excision, TME) procedures in 41 cases and Miles procedure in 23 cases. 19 other patients underwent combined procedures for multi-primary tumors or inflammatory enteritis. All these procedures were analyzed according to time span (the earlier half and later half) in respect to length of surgery, intraoperative blood loss, number of lymph nodes retrieved, intraoperative events and postoperative complications.

RESULTSFor radical right colectomy, the D2 dissection conducted in the earlier phase (n = 8) had the similar length of surgery, more blood loss and less LN retrieval, compared with the D3 dissection conducted in recent phase (n = 20). The earlier performed high Dixon procedures (n = 22) consumed longer time than the later procedures (n = 23) consumed, but with similar blood loss and LN retrieval. Low Dixon (TME) procedures showed significant differences in length of surgery and blood loss relative to time span. Recently performed simoidectomy and Miles procedures showed a trend of shorter time consumed compared with earlier performed procedures. Conversion ratio to open surgery was 1.05%. Adverse effects occurred in 8 cases of surgeries, including intestinal injury (3/189), insufficient distal margin (2/189), intraoperative bleeding (2/189) and vaginal injury (1/76). There was no operative death. Chief complications included urinary retention 5.82%, ileus 4.76%, anastomotic leak 4.24%, perineal infection 23.08% (6/26), wound dehiscence 2.65%, gastrointestinal bleeding 1.59%, peritoneal infection 1.06%. Surgery for distal rectum tended to have more complications, such as urinary retention, anastomotic leak and perineal infection. The later performed low Dixon procedures produced insignificantly fewer anastomotic leaks than those in the earlier phase.

CONCLUSIONSFor a trained surgeon with basic laparoscopic techniques, there are at least 15 - 25 cases of different procedures needed for him/her to become skilled to perform laparoscopic surgery. The learning curve should also depend on the annual number of colorectal surgeries.

Aged ; Colonic Diseases ; surgery ; Colorectal Neoplasms ; surgery ; Colorectal Surgery ; methods ; Female ; Humans ; Laparoscopy ; methods ; Learning Curve ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Treatment Outcome

Objective To evaluate the prognostic value of the log odds of positive lymph nodes (LODDS) in stage 3 colorectal cancer (CRC) patients who have undergone curative resection. Methods We performed a retrospective review of 175 stage 3 CRC patients who underwent curative resection in Peking Union Medical College Hospital from 2005 to 2012. Patients were categorized respectively according to the AJCC/UICC N grade,the metastatic lymph node ratio (LNR),and the ratio of their LODDS. The relationship between the N grade,LNR,LODDS,and overall survival (OS) rates were assessed.Results The five-year disease-free survival (DFS) was significantly different among stage 3 CRC patients in different N grade (Χ(2)=33.1,P=0.000),LNR (Χ(2)=14.3,P=0.001),and LODDS (Χ(2)=14.9,P=0.001). Univariate analysis showed that TNM stage (Χ(2)=27.0,P=0.000),cancerous node(Χ(2)=3.6,P=0.040),N grade (Χ(2)=33.1,P=0.000),LNR (Χ(2)=14.3,P=0.001),and LODDS (Χ(2)=30.4,P=0.000) were related to OS. Multivariate analysis indicated that TNM stage (HR:1.84,95%CI:1.59～6.29,P=0.001) and LODDS classification (HR:1.34,95%CI:1.01～1.80,P=0.047) were independent prognostic factors for OS in stage 3 CRC patients. Conclusion LODDS is a good prognostic indicator in stage 3 CRC patients who have undergone curative resection.
Colorectal Neoplasms ; diagnosis ; pathology ; Disease-Free Survival ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; diagnosis ; Multivariate Analysis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Survival Rate

OBJECTIVE: To explore the effect of modified Bacon coloanal anastomosis in transanal total mesorectal excision(TaTME).METHODS: The clinical data of 8 patients with low rectal cancer treated with TaTME from January 2016 to January 2019 in the division of colorectal surgery of department of general surgery of Peking Union Medical College Hospital were retrospectively analyzed. Laparoscopic assisted modified Bacon coloanal anastomosis was used during operation. The incidence of postoperative complications including anastomotic leakage was observed and the anal function was evaluated.RESULTS: All 8 patients underwent operation successfully. The distance from the inferior margin of the tumor to the anal verge was(4.8 ±0.4) cm. The number of retrieved lymph nodes in postoperative pathological examination was(12.9±2.5). The mean time of first operation was(140.8±8.6) min, and the Second stage operation time was(39.1±9.6) min. The median time between the two operations was 19(13, 20) days, and the median hospital stay was22(17, 24) days. The median follow-up time was 16(4, 36) months. No anastomotic leakage occurred and the anal function was good after operation. Six patients had uncontrollable anal exhaust after operation, and two patients had occasional mucous or watery fecal incontinence after operation, but they were less than once a month. They could be improved by dietary structure adjustment and external sanitary pads.CONCLUSION: Laparoscopic-assisted modified Bacon operation in TaTME avoids anastomotic leakage, and reduces the incidence of anal incontinence after operation.However, the hospital stay is prolonged.