Controlling unmeasured confounders in non-randomized controlled studies is challenging. Negative control theory is based on the theoretical concept that the test result of negative controls must be negative. Setting appropriate negative control incorporates the specificity of association into population studies for the identification and control of unmeasured confounders. This paper explains the principles to control unmeasured confounders using negative control theory from a statistical perspective. A detailed introduction of derived methods based on negative control theory is also introduced, including adjusted standardized mortality ratio method, calibrating P-value method, generalized difference-in-difference model and double negative control method. The reasonable application of those derived methods is also comprehensively summarized based on representative case studies. Negative control is an important statistical design to identify, revise and control unmeasured confounders and a valuable method for comparative effectiveness research based on real-world data.
Humans ; Confounding Factors, Epidemiologic ; Research Design ; Comparative Effectiveness Research ; Bias

No abstract available.
Comparative Effectiveness Research

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra- or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.
Carcinoma, Hepatocellular ; diagnostic imaging ; therapy ; Chemoembolization, Therapeutic ; adverse effects ; instrumentation ; methods ; Comparative Effectiveness Research ; Drug Delivery Systems ; instrumentation ; methods ; Epirubicin ; administration & dosage ; therapeutic use ; Humans ; Liver Neoplasms ; Magnetic Resonance Imaging ; Microspheres ; Neoplasm Recurrence, Local ; Retrospective Studies ; Treatment Outcome

OBJECTIVETo investigate the safety, feasibility and long-term outcomes of laparoscopic complete mesocolic excision for the transverse colon cancer.

METHODSClinical data of 61 patients who underwent laparoscopic complete mesocolic excision for transverse colon cancer (transverse group) in our department from January 2011 to January 2014 were retrospectively analyzed, which were compared with those of 155 patients undergoing laparoscopic complete mesocolic excision for ascending colon cancer (ascending group) and 230 patients undergoing laparoscopic complete mesocolic excision for sigmoid colon cancer (sigmoid group). Differences in operative details, postoperative recovery, postoperative complications and long-term survival among 3 groups were evaluated.

RESULTSNo significant differences in the baseline information were found among 3 groups(all P>0.05). The average operative time was significantly longer in transverse group as compared to ascending group and sigmoid group [(192.1±58.7) min vs. (172.2±54.7) min and (169.1±53.6) min]( P<0.05), while the blood loss [(89.7±63.6) ml, (86.3±66.3) ml, (82.6±61.5) ml], conversion rate [3.3%(2/61), 2.6%(4/155), 2.2%(5/230)], number of harvested lymph node (13.0±4.7, 14.4±6.5, 13.4±5.6), time to flatus [(2.7±1.1) d, (2.6±1.1) d, (2.5±1.0) d], time to liquid diet [(3.0±1.7) d, (2.8±1.5) d, (2.7±1.4) d], incidence of postoperative complication(6.6%, 9.0%, 11.7%), and hospital stay [(11.6±5.8) d, (10.7±5.8) d, (10.6±5.7) d] among 3 groups were not significantly different (all P>0.05). A total of 436 patients received postoperative follow-up of median 36 (5 to 67) months. The overall 5-year survival rate was 73.1%, 73.7% and 74.8%, and the 5-year disease-free survival rate was 71.5%, 71.1% and 72.7% in transverse, ascending and sigmoid colon cancer groups respectively, whose differences were not significant among 3 groups (all P>0.05).

CONCLUSIONLaparoscopic complete mesocolic excision for transverse colon cancer is safe and feasible with slightly longer operation time, and has quite good long-term oncologic efficacy.

Colectomy ; methods ; Colon, Ascending ; surgery ; Colon, Sigmoid ; surgery ; Colon, Transverse ; surgery ; Colonic Neoplasms ; surgery ; Comparative Effectiveness Research ; Disease-Free Survival ; Humans ; Laparoscopy ; methods ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Mesocolon ; surgery ; Operative Time ; Postoperative Complications ; Postoperative Period ; Retrospective Studies ; Survival Rate ; Treatment Outcome

OBJECTIVETo compare the clinical efficacy of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancers.

METHODSFrom January 2015 to March 2016, intra-operative and postoperative follow-up data of 30 patients with middle-low rectal cancers who underwent robotic radical resection(robot group) and 32 patients with middle-low rectal cancers who underwent laparoscopic radical resection (laparoscopy group)n in our department were retrospectively collected. The distance from cancer to anal margin was less than 10 cm in both two groups and advanced rectal cancers were confirmed by preoperative colonoscopy biopsy. Associated data were compared between two groups.

RESULTSThere were 13 males and 17 females in robot group with age of 27 to 85 (mean 59.7) years, disease course of 3 to 12 (mean 6.2) months and clinical stage T2-3N0-1. There were 16 males and 16 females in laparoscopic group with age of 32 to 79 (mean 60.3) years, disease course of 2 to 10(mean 5.9) months and clinical stage T2-3N0-1. The baseline data of two groups were not significantly different (all P>0.05). All the patients in two groups completed operations successfully without conversion to open operation. Compared with laparoscopic group, the blood loss was less [(100.3±43.7) ml vs. (150.3±68.2) ml, t=3.413, P=0.001], the first flatus time [(49.3±12.4) h vs. (58.6±12.5) h, t=2.838, P=0.006] and urinary catheter removal time [(3.0±0.7) d vs. (4.8±0.9) d, t=5.491, P=0.000] were shorter, while the operation time [(217.3±57.8) min vs. (187.9±23.1) min, t=2.772, P=0.009] was longer in robot group. No cancer tissue was observed in resection margin of two groups. Number of harvested lymph node per case (15.2±7.4 vs. 13.9±4.9, t=-0.764, P=0.448), distance from anal margin to tumor distal edge [(7±3) cm vs. (6.5±3) cm, t=-1.952, P=0.056] and postoperative hospital stay [(13.6±1.3) d vs. (13.8±1.8) d, t=0.925, P=0.359] were not significantly different between two groups. No serious complications occurred in two groups during intra-operative and postoperative period. During following up of 3 to 12 (average 8.7) months, 1 case of anastomotic fistula occurred in each group and was cured by conservative treatment without significant difference [3.3%(1/30) vs. 3.1%(1/32), P=1.000]. No sexual dysfunction was found in either groups. Two cases in laparoscopic group presented relapse and metastasis, but no recurrence and metastasis was observed in robot group. There was no death in two groups.

CONCLUSIONRobotic radical surgery in the treatment of middle-low rectal cancers is safe and effective with the advantages of less trauma, less bleeding, rapid recovery of intestinal function and urinary function.

Adult ; Aged ; Blood Loss, Surgical ; Comparative Effectiveness Research ; Defecation ; Digestive System Surgical Procedures ; adverse effects ; methods ; Female ; Fistula ; etiology ; surgery ; Humans ; Laparoscopy ; adverse effects ; Length of Stay ; Lymph Node Excision ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Operative Time ; Postoperative Period ; Recovery of Function ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Robotic Surgical Procedures ; adverse effects ; Treatment Outcome ; Urination

OBJECTIVETo evaluate the efficacy of bowel plication combined with early enteral nutrition (EEN) in the enhanced recovery after surgery(ERAS) of jejunal atresia (JA) neonates.

METHODSBetween January 2005 and January 2014, 58 neonates with JA underwent surgical treatment in Children's Hospital of Nanjing Medical University. Their clinical data, including operation procedures, ages, birth weight, concomitant diseases, age at surgery, hospital stay, total parenteral nutrition (TPN), postoperative intestinal function recovery (the time to the first oral feeding and the time to oral feeding volume reaching 150 ml·kg·d), complications and reoperation, were retrospectively analyzed.

RESULTSAccording to the surgical procedures, the 58 neonates were divided into three groups: control group(18 cases, undergoing atretic segments resection and primary anastomosis), bowel plication group(19 cases, undergoing bowel plication after atretic segments resection and primary anastomosis) and bowel plication combined with EEN group (21 cases, undergoing bowel plication combined with EEN). No significant differences of ages, birth weight, age at operation, and concomitant diseases were found among 3 groups (all P>0.05). The time of hospital stay, the time to the first oral feeding, the time to oral feeding volume reaching 150 ml·kg·d, and the time of TPN in bowel plication group were significantly shorter than those of control group [(19.3±4.4) d vs. (22.7±3.1) d, t=2.696, P=0.011; (9.8±3.3) d vs. (12.5±3.0) d, t=2.630, P=0.013; (18.5±4.1) d vs. (21.5±2.5) d, t=2.726, P=0.011; (13.1±2.9) d vs. (15.0±2.3) d, t=2.219, P=0.033]. However, above parameters of bowel plication combined with EEN group were significantly shorter than those of bowel plication group [(15.3±3.5) d vs. (19.3±4.4), t=4.120, P=0.003; (7.7±2.2) d vs. (9.8±3.3) d, t=2.428, P=0.020; (14.8±2.5) d vs. (18.5±4.1) d, t=3.752, P=0.001; (9.5±3.0) vs. (13.1±2.9) d, t=4.370, P=0.000].

CONCLUSIONThe bowel plication combined with EEN contributes to the early use of intestinal function, shorten the time to the first oral feeding, and reduces the use of TPN, which can improve the recovery of jejunal atresia neonates.

Anastomosis, Surgical ; Comparative Effectiveness Research ; Defecation ; Digestive System Surgical Procedures ; methods ; Enteral Nutrition ; methods ; Humans ; Infant, Newborn ; Intestinal Atresia ; rehabilitation ; surgery ; Jejunum ; abnormalities ; surgery ; Length of Stay ; Parenteral Nutrition, Total ; Postoperative Period ; Retrospective Studies

OBJECTIVETo evaluate the technical advantages of 3D laparoscopic and 2D laparoscopic surgery for gastrointestinal tumors.

METHODSClinical data of gastrointestinal cancer patients undergoing 3D laparoscopic or 2D laparoscopic surgery from January 2015 to January 2017 in our department were retrospectively analyzed These patients included 93 gastric cancer cases undergoing laparoscopic radical resection (total gastrectomy, 48 cases in 3D group, 45 cases in 2D group), 45 rectal cancer cases undergoing radical resection combined with lateral lymph node dissection (27 cases in 3D group, 18 cases in 2D group) and 76 right colon cancer cases undergoing radical resection (37 cases in 3D group, 39 cases in 2D group). The enrolled criteria of cases were 18-80 years old and diagnosed as advanced gastric or colorectal cancer by pathological examination. Patients with preoperative distant metastasis, severe heart or lung diseases who were not suitable for laparoscopic surgery, combined organ resection and conversion to open surgery were excluded. The choice of surgical procedure was determined by the discussion between patients and surgeon. Operations were performed by the same surgical team. Total operation time, complex operation time (deep lymph node dissection time, endoscopic intestinal anastomosis time), number of harvested lymph node, number of times in wrong grasp (accurate grasp for the same site needs to position for two times or more) and intraoperative bleeding were compared between 3D group and 2D group.

RESULTSThere were no significant differences in baseline data between 3D group and 2D group. All the patients completed laparoscopic radical operation successfully without conversion to open surgery. In patients with gastric cancer, compared with 2D group, the total operation time was shorter [(185±25) min vs. (190±27) min, P<0.05]; dissection time of No.10 and 11d lymph node [(40±8) min vs. (55±12)min, P<0.05], and No.7, 8, 9 and 12 lymph node [(30±6) min vs. (41±9) min, P<0.05] was shorter; the number of times in wrong grasp (5±2 vs. 11±2, P<0.05) was less in 3D group. In patients with rectal cancer, compared with group 2D, 3D group had shorter time of lateral lymph node dissection [(27±6) min vs. (35±9) min, P<0.05] and laparoscopic anastomosis [(45±7) min vs. (58±11) min, P<0.05]; less number of times in wrong grasp (4±2 vs. 13±2, P<0.05]. In patients with right colon cancer, 3D group had shorter laparoscopic anastomosis time [(38±7) min vs. (44±5) min, P<0.05] and less number of times in wrong grasp (5±1 vs. 13±3, P<0.05] as compared to 2D group.

CONCLUSION3D laparoscopic surgery for gastrointestinal tumors, compared with 2D laparoscopic technology has significant advantages, which can improve the spatial location and depth of operation, decrease the difficulty of fine operation, and shorten the operation time.

Anastomosis, Surgical ; methods ; statistics & numerical data ; Colectomy ; methods ; statistics & numerical data ; Comparative Effectiveness Research ; Female ; Gastrectomy ; methods ; statistics & numerical data ; Humans ; Intestines ; surgery ; Laparoscopy ; methods ; statistics & numerical data ; Lymph Node Excision ; methods ; statistics & numerical data ; Lymph Nodes ; surgery ; Male ; Operative Time ; Rectal Neoplasms ; surgery ; Retrospective Studies ; Stomach Neoplasms ; surgery

OBJECTIVETo explore the application of three-stitch preventive transverse colostomy in anterior resection of low rectal cancer.

METHODFrom May 2015 to March 2016, 70 consecutive low rectal cancer patients undergoing anterior resection and preventive transverse colostomy in our department were recruited in this prospective study. According to the random number table method, 70 patients were divided into three-stitch transverse colostomy group(observation group, n=35) and traditional transverse colostomy group(control group, n=35). Procedure of three-stitch preventive transverse colostomy was as follows: firstly, at the upper 1/3 incision 0.5-1.0 cm distance from the skin, 7# silk was used to suture from outside to inside, then the needle belt line went through the transverse edge of the mesangial avascular zone. At the lower 1/3 incision 0.5-1.0 cm distance from the skin, 7# silk was used to suture from inside to outside, then silk went through the transverse edge of the mesangial avascular zone again and was ligatured. Finally, in the upper and lower ends of the stoma, 7# silk was used to suture and fix transverse seromuscular layer and the skin. The operation time and morbidity of postoperative complications associated with colostomy were compared between two groups.

RESULTSThere were no significant differences in baseline data between the two groups(all P>0.05). The operative time of observation group was shorter than that of control group [(3.2±1.3) min vs. (15.5±3.4) min, P<0.05]. Incidences of colostomy skin-mucous separation, dermatitis, stoma rebound were significantly lower in observation group [5.7%(2/35) vs. 34.3%(12/35), P=0.007; 8.6%(3/35) vs. 31.4%(11/35), P=0.036; 0 vs. 17.1%(6/35), P=0.025, respectively], while incidences of parastomal hernia and stoma prolapse in two groups were similar (both P>0.05).

CONCLUSIONCompared with traditional transverse colostomy method, the three-stitch preventive transverse colostomy has more operating advantages and can reduce postoperative complications associated with colostomy.

Colostomy ; adverse effects ; methods ; Comparative Effectiveness Research ; Humans ; Operative Time ; Postoperative Complications ; epidemiology ; Prospective Studies ; Rectal Neoplasms ; surgery ; Surgical Stomas ; adverse effects ; Suture Techniques ; adverse effects ; instrumentation ; Sutures ; Treatment Outcome

OBJECTIVETo systematically assess the safety and efficacy of hand-assisted laparoscopic distal gastrectomy (HALG) versus open distal gastrectomy (ODG) for gastric cancer.

METHODSChinese or English literature regarding comparison of HALG and ODG were collected by searching in databases (such as PubMed, Cochrane Library, CNKI, Wanfang database) between January 1996 and September 2016. The data of operative time, incision length, blood loss, number of harvested lymph nodes, time to flatus, hospital stay, postoperative complication morbidity and long-term outcomes were compared between the two procedures. Then funnel plot was used to evaluate publication bias and sensitivity analysis was used to evaluate the stability of the results. All these data analyses were performed using the Meta for or Meta package of R version 3.3.1.

RESULTSA total of 7 studies with 835 patients (323 cases in HALG group and 512 cases in ODG group) were included. Compared with ODG, HALG had a longer operative time (WMD=28.93 minutes, 95%CI=9.59 to 48.28, Z=2.93, P=0.000), a shorter incision length (WMD=-10.31 cm, 95%CI=-14.01 to -6.62, Z=-5.47, P=0.000), less blood loss (WMD=-140.08 ml, 95%CI=-215.07 to -65.09, Z=-3.66, P=0.000), faster gastrointestinal recovery (WMD=-1.23 days, 95%CI=-1.89 to -0.56, Z=-3.62, P=0.000), shorter postoperative hospital stay (WMD=-3.24 days, 95%CI=-5.47 to -1.02, Z=-2.85, P=0.000). In subgroup analysis, 3 studies published before 2013 vs. 4 studies published afterwards, the number of harvested lymph nodes (WMD=-0.78, 95%CI=-2.05 to 0.50, Z=-1.19, P=0.235) and postoperative complication morbidity (RR=1.02, 95%CI=0.43 to 2.44, Z=0.05, P=0.961) did not differ significantly between two groups. Compared with ODG, the RR(95%CI) of ileus of HALG was 0.43 (0.07 to 2.82), but the difference was not statistically significant (P=0.383). One study reported the 5-year overall survival rates of HALG and ODG were 81.0% vs 67.5%, and the tumor recurrence rates were 7.1% vs 22%, respectively, but the differences were not statistically significant(all P>0.05). Sensitivity analysis showed that the above results were stable. The funnel plots of the lymph nodes and postoperative complication morbidity did not present significant publication bias.

CONCLUSIONSHALG has the advantages of minimal invasiveness such as shorter incision length and quicker recovery. Furthermore, the short-term efficacy of HALG is similar to conventional open surgery. However, the long-term efficacy is lack of support from multicenter long-term follow-up results.

Blood Loss, Surgical ; statistics & numerical data ; Comparative Effectiveness Research ; Gastrectomy ; methods ; Hand-Assisted Laparoscopy ; adverse effects ; Humans ; Length of Stay ; statistics & numerical data ; Lymph Node Excision ; statistics & numerical data ; Neoplasm Recurrence, Local ; epidemiology ; Operative Time ; Postoperative Complications ; epidemiology ; Postoperative Period ; Recovery of Function ; Stomach Neoplasms ; mortality ; surgery ; Survival Rate ; Time ; Treatment Outcome

OBJECTIVETo compared the clinical efficacy of laparoscopic repair (LR) versus open repair (OR) for perforated peptic ulcers.

METHODSFrom January 2010 to June 2014, in Shanghai Tongji Hospital, 119 patients who were diagnosed as perforated peptic ulcers and planned to receive operation were prospectively enrolled. Patients were randomly divided into LR (58 patients) and OR(61 patients) group by computer. Intra-operative and postoperative parameters were compared between two groups. This study was registered as a randomized controlled trial by the China Clinical Trials Registry (registration No.ChiCTR-TRC-11001607).

RESULTSThere was no significant difference in baseline data between two groups (all P>0.05). No significant differences of operation time, morbidity of postoperative complication, mortality, reoperation probability, decompression time, fluid diet recovery time and hospitalization cost were found between two groups (all P>0.05). As compared to OR group, LR group required less postoperative fentanyl [(0.74±0.33) mg vs. (1.04±0.39) mg, t=-4.519, P=0.000] and had shorter hospital stay [median 7(5 to 9) days vs. 8(7 to 10) days, U=-2.090, P=0.001]. In LR group, 3 patients(5.2%) had leakage in perforation site after surgery. One case received laparotomy on the second day after surgery for diffuse peritonitis. The other two received conservative treatment (total parenteral nutrition and enteral nutrition). There was no recurrence of perforation in OR group. One patient of each group died of multiple organ dysfunction syndrome (MODS) 22 days after surgery.

CONCLUSIONLR may be preferable for treating perforated peptic ulcers than OR, however preventive measures during LR should be taken to avoid postopertive leak in perforation site.

China ; Comparative Effectiveness Research ; Digestive System Surgical Procedures ; adverse effects ; methods ; Enteral Nutrition ; Female ; Fentanyl ; Humans ; Laparoscopy ; adverse effects ; rehabilitation ; Laparotomy ; Length of Stay ; statistics & numerical data ; Male ; Multiple Organ Failure ; epidemiology ; Operative Time ; Pain, Postoperative ; drug therapy ; epidemiology ; Parenteral Nutrition, Total ; Peptic Ulcer Perforation ; rehabilitation ; surgery ; Peritonitis ; therapy ; Postoperative Complications ; epidemiology ; therapy ; Postoperative Period ; Prospective Studies ; Recurrence ; Reoperation ; Treatment Outcome