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Objective:To investigate anticoagulant effects of mechanical methods in obese patients undergoing laparoscopic sleeve gastrectomy (LSG).Methods:In this prospective study, 54 obese patients receiving LSG were enrolled . All patients were given post-op mechanical methods for thrombogenic interventions. BMI and the operation-related factors were recorded. Venous blood specimens were taken from each patient before surgery, at the end of pneumoperitoneum (i.e., 0 h after surgery), at 24 hours after surgery for prothrombin time (PT) and activated partial thromboplastin time (APTT), fibrinogen (FIB) and D-dimer (D-D).Results:All 54 obese patients successfully underwent LSG. No severe complications were observed. Before operation, the mean BMI was (43.49±8.29) kg/m 2. DVT-2600 device was applied in all patients for 3 consecutive days after surgery. The PT values increased at 0 h, 24 h after surgery [(12.4±1.2) s, (12.4±0.8) s vs. (11.2±0.8) s, P=0, 0]. The APTT values at 0 h, 24 h after surgery decreased [(29.7±3.6) s, (29.0±3.1) s vs.(31.2±3.3) s, P=0.020, 0.001]. However, the D-D values increased at 0 h,24 h after operation [(213±143) ng/ml ,(445±237) ng/ml vs. (85±108) ng/ml, P=0, 0]. All patients were followed up for 1 month, and no thrombosis -related complications were observed. Conclusion:Mechanical methods for obese patients after LSG can help decrease the risk of deep venous thrombosis.
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Objective:To evaluate the application of Moorehead-Ardelt Ⅱ questionnaire (MA Ⅱ) in assessment of the quality of life (QOL) among obese patients after bariatric surgery.Methods:One hundred and five patients with obesity were enrolled, the weight, body mass index (BMI), comorbidities and MA Ⅱ scores before and after operation were counted. The difference between the QOL of pre- and post-operation was analyzed.Results:All the patients completed the questionnaire. The Cronbach α coefficient of the questionnaire was higher than 0.7. The post-operational scores of 6 items were significantly higher than that of pre-operation. ( P<0.001). The proportion of "poor" and "very poor" QOL in the pre-operational patients was 43.8%, compared with 0 in the post-operative patients;the proportion of "good" and "very good" QOL in the pre-operatve patients was 4.7%, compared to 86.7% in the post-operative patients ( χ2=146.863, P<0.001). Conclusions:MA Ⅱ questionnaire is a professional, easy oprated tool for assessment of QOL associated with obesity.
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Objective:To understand the demand of young doctors for scientific research in Beijing and explore possible strategies for improving scientific research ability.Methods:Data were collected by review the hospital′s scientific research management documents, questionnaire survey and department interview and obstacles for further analysis of the research demand of young doctors in the hospital.Results:According to the survey, the main reasons for conducting scientific research are: promotion of professional titles and busy clinical duties; Young doctors are in great demand and obstacles for scientific research.Conclusions:Based on the demand of young doctors, suggestions proposed including optimizing policy guidance and hospital fund support, developing scientific research technology platform and strengthening communication training to promote the scientific research ability of young doctors in hospitals.
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Objective:To study the clinical effect of liposuction combined with lymphatico-venous anastomosis for treatment of breast cancer-related lymphedema(BCRL).Methods:From Nov 2015 to Nov 2017, 111 patients with BCRL admitted to the Department of Lymphatic Surgery at Beijing Shijitan Hospital were enrolled. The rank-sum test was used for statistical analysis. The frequencies of erysipelas episodes before and after combined surgeries were compared.Results:The mean upper limb circumference significantly decreased at 7 days[0.2 cm (-0.8, 1.1)], at follow-up[0.2 cm(-0.4, 1.0)]compared with that of preoperation[5.0 cm(4.1, 6.9)]( P<0.05). The mean upper limb volume significantly decreased at day 7[26 ml(-120, 155)], at follow-up[37 ml(-66, 165)]compared with preoperation[786 ml(632, 1 200)]( P<0.05). The incidence of erysipelas of the affected limbs significantly decreased after treatment. Furthermore, the softness and the feeling of heaviness of the affected limbs significantly improved after the combined procedures(all P<0.05). Conclusion:Liposuction combined with lymphatico-venous anastomosis is an effective method for the treatment of breast cancer-related lymphedema.
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Objectives To investigate the efficacy of laparoscopic sleeve gastrectomy (LSG)for patients of type 2 diabetes mellitus (T2DM).Methods Between Jun 2013 and Jun 2017,39 T2DM patients were enrolled in this study and underwent LSG.The clinical data of all patients were collected.The fasting plasma glucose (FPG),glycosylated hemoglobin (HbAl c),C-peptide,fasting insulin (FINS),glucagon-like peptide-1 (GLP-1) as well as BMI of all patients were measured before and at 1,6 months after surgery.Results All patients underwent LSG surgery successfully.The mean levels of FPG,HbAlc,C-peptide,FINS and BMI of all patients decreased at 6 months after surgery respectively compared to those before surgery [(6.4 ± 1.2) mmol/L vs.(9.6 ± 2.3) mmol/L,t =9.455,P =0.000;(6.0 ± 0.7) ％ vs.(7.5 ±1.0)％,t=10.538,P=0.000;(2.7±2.2)ng/ml vs.(4.0±2.6) ng/ml,t=3.491,P=0.001;(9.2 ±6.3) μIU/L vs.(15.5 ±11.1) μIU/L,t=4.902,P=0.000;(32.0 ±6.1) kg/m2 vs.(41.0 ± 7.5) kg/m2,t =10.826,P =0.000],however the mean GLP-1 of all patients increased after surgery compared to that before surgery [(4.0 ± 2.1) pmol/L vs.(3.1 ± 2.2) pmol/L,t =-4.242,P =0.000].At 6 months after surgery,32 patients achieved complete remission of T2DM,5 patients gained partial remission of T2DM and 2 patients got no remission of T2DM.Conclusions LSG is effective for obesity patients as well as patients suffering from T2DM.
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Objective To compare laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy for the treatment of obese patients with type 2 diabetes mellitus.Methods A retrospective analysis of T2DM patients with LRYGB (28 cases) and LSG (35 cases) was enrolled from Jan 2010 to Jun 2013.Results The indicator such as BMI,fasting glucose,fasting insulin,HbA1c,and insulin resistance were significantly lower in 1 year,3 years and 5 years after operation [LRYGB group:(37.3 ±3.7) kg/m2 to (32.3 ± 3.4) kg/m2 to (28.8 ± 3.0) kg/m2 to (25.5 ± 2.8) kg/m2,t =13.670,15.499,21.710,P=0.000,0.000,0.000;(8.2 ± 1.8) mmol/L to (6.0 ± 1.3) mmol/L to (5.2 ±0.9) mmol/L to (4.7±0.5) mmol/L,t =6.664,8.723,10.282,P=0.000,0.000,0.000;(32.2±17.0) μ IU/ml to (16.1 ± 12.1) μIU/ml to (8.6 ±5.2) μ IU/ml to (5.2 ±2.8) μIU/ml,t =7.453,8.218,8.687,P =0.000,0.000,0.000;(7.4％ ±0.6％) to (6.2％ ±0.7％) to (5.7％ ±0.7％) to (5.1％ ±0.6％),t =11.362,18.771,21.186,P=0.000,0.000,0.000;(12.0±7.3) to (4.6±4.3) to (2.1 ±1.7) to (1.1 ±0.7),t =6.455,7.667,8.050,P=0.000,0.000,0.000;LSG group:(39.2±5.2) kg/m2 to (34.1 ±4.5) kg/m2to (29.3±4.0) kg/m2to (25.1 ±2.3) kg/m2,t=11.676,13.680,19.161,P=0.000,0.000,0.000;(8.0±2.9) mmol/L to (5.8±1.5) mmol/L to (5.1 ±0.9) mmol/L to (4.6 ±0.5) mmoL/L,t=5.467,6.921,7.741,P=0.000,0.000,0.000;(29.1 ±25.2) μIU/ml to (16.4±10.6) μ IU/ml to (8.8±5.5) μ IU/ml to (5.5 ±2.0) μIU/ml,t =3.512,5.232,5.702,P=0.001,0.000,0.000;(7.7％ ±1.3％) to (6.3％ ±0.6％) to (5.8％ ±0.6％) to (5.2％ ±0.6％),t=8.001,10.106,11.922,P =0.000,0.000,0.000;(9.8 ±9.6) to (3.9 ±2.2) to (1.9 ±1.0) to (1.1 ± 0.4),t =3.733,4.972,5.404,P =0.001,0.000,0.000].There was no significant difference between the two groups in 1 year,3 year and 5 year post-operation (DM remission:71％ to 69％,89％ to 80％,93％ to 89％) (P ＞ 0.05).Conclusion LRYGB and LSG have the same long-term efficacy for T2DM patients.
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The paper introduced the discipline evaluation and discipline development of the hospital and the outcomes of these efforts. These include the management at the discipline level through establishing key disciplines;building discipline platforms to facilitate the development of scientific research; promoting the cultivation of scientific research atmosphere and capacity; and the perfection of scientific research inventive mechanism to promote long-term and dynamic management of disciplines. These efforts empowered scientific and effective construction of hospital disciplines.
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Objective To explore the morbidity of surgery in connection with laparoscopic sleeve gastrectomy (LSG) and its effect on obese T2DM.Methods 106 obese T2DM patientes undergoing LSG were divided into 2 groups in group 125 patients did not have oversewing the staple line and group 281 patients had the staple line oversewn in order to reduce bleeding.Results The differences in intraoperative blood loss (35 ± 15) ml vs.(28 ± 18) ml,postoperative recovery time (2.4 ± 0.9) d vs.(2.3 ± 0.9) d,time to taking liquid food (4.7 ± 1.0) d vs.(4.6 ± 1.0) d between two groups were not significant.There were no significant difference of complication between 2 groups (x2 =3.271,P =0.071).Comparing before surgery to 6 month after surgery,the BMI in group 1,was from (39 ± 5) to (29 ±4) kg/m2;in group 2,from (40 ±6) to (31 ±5) kg/m2,FPG in group 1,from (8.4 ± 1.4) to (6.4 ±1.2) mmol/L;in group 2,from (8.2 ± 2.0) to (6.8 ± 1.5) mmol/L,2 hour post-meal blood sugar [group 1,(13.2±4.1) to (9.6±3.2) mmol/L;group 2,(12.2±3.2) to (10.6±2.8) mmol/L] and HbAlc (group 1,7.2％ ±1.2％ to5.5％ ±1.1％;group 2,7.1％ ±1.1％ to 5.9％ ±1.2％) decreased significantly in both groups (P ＜ 0.01).There was 72 (68％) remission cases of T2DM in 106 patients,there were no significant differences of T2DM remission and BMI between 2 groups at 6 months after surgery (P =0.617).Conclusions LSG leads to significant weight loss and T2DM control.
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Objective To investigate the effect of FTO gene on laparoscopic Roux-en-Y gastric bypass for type 2 diabetes.Methods From Jan 2014 to 2015 Jun,32 T2DM patients received LRYGB in Beijing Shijitan Hospital.According to single nucleotide polymorphism of FTO rs9939609 gene,patients were divided into TF genotype (20 cases),and AT/AA genotype (12 cases).Results Following the degression of BMI from (36.4 ±3.3) kg/m2 to (28.1 ±2.8) kg/m2,fasting blood glucose and HbA1c in group A significantly improved [(8.9 ± 1.6) mmol/L vs.(5.6 ± 1.2) mmol/L,t =8.274,P =0.000;(8.5％ ± 1.9％) vs.(6.2％ ± 0.8％),t =5.032,P =0.000].Following the degression of BMI from (39.5 ±5.6) kg/m2 to (29.7 ± 5.1) kg/m2,fasting blood glucose and HbA1c in group B significantly improved [(10.8 ± 2.8) mmol/L vs.(4.9 ± 0.6) mmol/L,t =7.589,P =0.000;(9.0％ ± 1.8％) vs.(6.1％ ±0.9％),t =5.324,P =0.000].Insulin resistance index in both groups significantly improved [(12.6±10.7) vs.(4.9±5.6),t=5.402,P=0.000;(16.0±5.6) vs.(1.7±1.3),t=9.025,P=0.000].Fasting blood glucose and the insulin resistance index in group B patients was significantly lower than that in group A patients (P ＜ 0.05).Conclusion T2DM patients with FTO rs9939609 gene phenotype AT/AA have better prognosis than those with TT in postoperative diabetes improvement.
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Objective To compare the effects of laparoscopic Roux-en-Y gastric bypass (LRYGB) for the treatment of type 2 diabetes mellitus (T2DM) patients in various obesity degree.Methods A total of 36 T2DM patients undergoing LRYGB were enrolled in this study in our hospital from June 2012 to June 2014.The patients were divided into BMI ≥ 32.5 kg/m2 group (n =13) and 27.5 kg/m2 ≤ BMI ＜ 32.5 kg/m2 group (n =23) based on BMI.Results In group 1,following the degression of BMI from (37.7±3.6) kg/m2 to (29.1 ±3.5) kg/m2 at 12 months after surgery,fasting blood glucose of group 1 decreased from (7.8 ± 1.6)mmol/L to (5.2 ±1.0)mmol/L (t =5.796,P =0.000),and HbA1c decreased from 7.3％ ±0.7％ to 6.1％ ± 1.0％ (t =5.589,P =0.000);and following the degression of BMI from(30.0 ± 1.6) kg/m2 to (25.8 ± 3.2) kg/m2,fasting blood glucose of group 2 decreased from (8.9 ± 1.7) mmol/L to (6.1 ± 1.5) mmol/L (t =6.577,P =0.000),and HbA 1 c decreased from 7.8 ％ ± 1.8％ to 6.4％ ± 1.0％ (t =4.257,P =0.000).Though Homa-IR of two groups was significantly improved after surgery (t =6.415,4.135;P =0.000,0.000),there was no difference to Homa-β (t =1.007,-0.155;P =0.334,0.878).Complete remission ratio of BMI ≥ 32.5 kg/m2 group was not significantly different with 27.5 kg/m2 ≤ BMI ＜ 32.5 kg/m2 group.Conclusion LRYGB is effective for the treatment of type 2 diabetes patients despite preoperative various obesity degree.
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Objective To explore the application of different approaches in single lateral endoscopic thyroidectomy.Methods Ninety one patients with single lateral thyroid nodule who underwent endoscopic thyroidectomy were divided randomly into bilateral axillo-breast approach group (n =45) and transaxillary approach group (n =46).The clinical data and cosmetic outcomes were compared.Results Procedures were successfully performed in 86 patients with no conversion to open surgery,5 patients in transaxillary group were excluded because of the malignant frozen pathology.The total operation time of transaxillary approach group was (61.6 ± 4.9) min,significantly shorter than that of the bilateral axillo-breast approach approach (90.0 ± 6.5) min,P ＜ 0.05.There was no significant difference in time of subcutaneous tunnel construction,muscles disposal,lateral dissection,lower pole resection,parathyroid identification,thyroid lobe resection and bleeding volume between two groups (P ＞ 0.05),while the time of work space creation,upper pole resection in transaxillary approach was significantly shorter than that in the bilateral axillo-breast approach (P ＜ 0.05).All patients of both groups were satisfied with cosmetic results.Conclusions The operation time in transaxillary approach group was shorter than that in bilateral axillo-breast approach group for the single lateral thyroid nodule,but the operation was more difficuh.
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SUMMARY To summarize the experience of managing substernal goiter by totally endoscopic procedure and evaluate the curative effect , we analysed eight patients diagnosed as substernal goiter type Ⅰ and treated with totally endoscopic technique via central routing approach during March 2011 to June 2013 in Beijing Shijitan Hospital retrospectively .The feasibility , safety and curative effect of this surgical tech-nique were estimated .All the cases were successfully operated with the totally endoscopic procedure , and the pathological result showed that 6 were goiter and the other 2 were minimal papillary carcinoma .None of the patients suffered from any complication , and the median follow up time was 6 months ( 1 -28 months) .The totally endoscopic technique is a feasible , safe and cosmic one for managing substernal goiter type Ⅰ.
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ObjectiveTo evaluate treatment of type 2 diabetes mellitus (T2DM) by laparoscopic Roux-en-Y gastric bypass (LRYGB) using different amastomoses. MethodsTwenty one T2DM patients were divided into two groups:transoral EEA (OrVil) and Endo-GIA according to ways of gastrointestinal anatomosis andunderwentLRYGB. Clinicaldataincluding outcomeof operation, complications,preoperative and postoperative oral glucose tolerance test (OGTT),Homa-IR,Homa-β,blood lipid and nutrition status were analyzed.ResultsLRYGB procedures were successfully performed in all the 21 patients with no conversion to open surgery.The difference of intraoperative blood loss,postoperative recovery time between two groups was not significant.The mean operation time in OrVil group ( 126 ± 29 )mins was shorter than that in Endo-GIA group ( 156 ± 28 ) mins ( P ＜ 0.05 ),but at the same time,the mean expenditure was higher. Evaluated on three months after operation,the T2DM cure rate was 78％,and effective rate was 100％ in OrVil goup and those were 83％,100％ respectively in Endo-GIA group.No postoperative malnutrition, anemia or severe complication occurred.ConclusionsThe efficiency of laparoscopic Roux-en-Y gastric bypass using different amastomoses was same in the treatment of type 2 diabetes mellitus.The operation time was shorter in OrVil group but the expenditure was higher.
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Objective To sunmarize the clinical experience of emergency laparoscopic choledocholithotomy plus T-tube drainage for acute calculous cholangitis.Methods We retrospectively analyzed the clinical data of 98 cases with acute calculous cholangitis undergoing emergency laparoscopic choledocholithotomy between Mar 2007 to Jul 2011 at our hospital.Results In this study,93 cases with definite diagnosis of acute calculous cholangitis underwent at their acute stage totally laparoscopic choledocholithotomy and T-tube drainage,2 cases received laparoscopic transeystic common bile duct exploration and 3 cases were treated with primary closure of the common bile duct following laparoscopic common bile duct exploration and intra-bile duct stent.All procedures were successful without conversion to open surgery.The average of the operative time and the hospital stay was 96 minutes and 12 days respectively.The major complications included residual stones in 8 cases,bile leakage in 4 cases and intraperitoneal bleeding in I case.All were cured by conservative therapy.Conclusions For most patients of acute calculous cholangitis,emergency T-tube drainage after laparoscopic chuledocholithotomy is safe and effective.
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Objective To investigate the technical difficulties and the avoidance of complications in delayed laparoscopic cholecystectomy (LC) for acute cholecystitis (AC).MethodsThe results of LC carried out on 133 consecutive patients with AC between February 2004 and August 2008 were retrospectively studied.The outcomes were compared between patients who received LC for AC within 72 hours (the early group) and those after 72 hours (the delayed group).There were 34 patients in the early group and 99 in the delayed group.During LC,Calot's triangle was carefully dissected,and the relationship of the cystic duct to the CBD and common hepatic duct was clearly identified.Retrograde cholecystectomy in 2 patients was used when the Calot's triangle was poorly identified.Laparoscopic subtotal cholecystectomy was carried out in 4 patients whose inflammation or fibrosis precluded dissection of the Calot's triangle.ResultsThere was no conversion to open cholecystectomy,biliary tract injury,biliary leak,or any other intraoperative or postoperative complications.There was no 30day readmission in the 2 groups.Patients who received delayed LC had a significantly longer operation time [(44.1±5.32) vs (66.4±3.05)rnin,P＜0.01].There was no significant difference in wound infection rates in the 2 groups (1/34 2.94 ％ vs 2/99 2.02 ％,P＞0.05).ConclusionsDelayed LC was as feasible and safe as early LC in the treatment of AC.Delayed LC was technically more demanding than early LC.
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Objective To evaluate some key steps influencing success rate in process of totally laparoscopic extraperitoneal herniorrhaphy(TEPH). Methods Between October 2006 and May 2009,we performed totally laparoscopic extraperitoneal herniorrhaphy in 98 patients with like procedures and under the same condition. Results The critical procedures of the operation are related to the establishment of the extraperitoneal cleavage. We used one-way anova analysis. The operation time in different peritoneal burst sites have no significant difference (P > 0. 05), but the operation time in different burst periods have significant difference(P <0. 05). The timing at which the burst occurs significantly influence the length of operation, while the rapture sites don't influence the operation time. The conversion rate was higher and operation time was longer between the cases with the rapture occurrence in early period and in mid and late period. Postoperatively 98 patients were followed up. The follow-up rate was 100%. The median follow-up time was 18 months. Three patients complained local discomfort one month after operation, which subsided after 2 months. There was no recurrence or chronic pain case. Conclusion The burst of the peritoneum during the process of establishing extraperitoneal cleavage significantly influences the success rate of TEPH.
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Objective To study prognostic factors after surgical resection for distal bile duct cancer. Methods A retrospective muhicenter clinical analysis,including Beijing Shijitan Hospital,Peking University People's Hospital and Peking University First Hospital,was made for 103 patients of distal bile duct cancer receiving surgical resection from 1995 to 2009.Potential clinicopathological prognostic factors were examined bv univariate and multivariate survival analysis. Results The 1.3 and 5 years overall survival rate was 72%,41%and 25% respectively (median survival time,24.13 months).Univariate analysis revealed operative modality,lymph node status,surgical margin and TNM stage as significant factors influencing postoperative survival.Positive surgical margin,lymph node metastasis and TNM stage were significant independent predictors of poor prognosis by a Cox proportional hazards regression model. Condusions Surgical margin margin,lymph node metastasis and TNM stage were the most important prognostic factors for bile duct carcinoma after resection.Radical pancreaticoduodenectomy was the choice of therapy for distal bile duct carcinoma.
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Objective To summarize the experience of totally endoscopic thyroidectomy (TET) in treating differentiated thyroid carcinoma and to evaluate its feasibility, safety and the therapeutic result.Methods The clinical data of 25 cases of thyroid carcinoma treated with TET via the areola of breast or by axillary approach from November 2004 to July 2009 in our hospital were retrospectively analyzed.Result TET procedures were successfully performed in all 25 cases. Postoperative pathology confirmed that 23 cases were of papillary cancer and the other 2 were follicle cancer. Lobectomy and subtotal thyroidectomy were performed in 11and 14 cases respectively. In 7 cases additional lymph node dissection was performed.All the cases were followed-up, ranging from 5 to 58 months, with a median of 28 months. No recurrence was found during this period. There was no morbidity nor major complications and patients were all satisfied with the cosmetic effect. Conclusion Totally endoscopic thyroidectomy (TET) is curative, safe and cosmetic therapy for differentiated thyroid carcinoma.
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Objective To evaluate the effectiveness and safety of open tension-free hernioplasty and two kind of laparoscopic hernia repair for the treatment of primary unilateral inguinal hernia. Methods Patients suffering from primary unilateral inguinal hernia were randomly divided into 3 groups to undergoopen operation with mesh-plug and patch or transabdominal preperitoneal hernioplasty (TAPP) or totally extraperitoneal hernioplasty (ZEP). Results From February 2006 to February 2009, a total of 164patients were divided into 3 groups, with 62 undergoing open tension-free mesh-plug hernia repair, 50receiving TAPP and 52 receiving TEP. Postoperative patients were then followed up for a period of(16±8)months. The average operating time for the patients in the open mesh repair group was significantly shorter compared to the other two groups (P＜0.01 ). The cost in the open mesh repair group was also significantly lower than the other two groups (P＜0.01). The pain scores in open mesh group were significantly higher than those in the other two groups (P＜0.01). The hospital stay and the recovery time were both significantly longer in the open mesh repair group (P＜0.01) compared to the other two groups. No major complications and recurrence was found in neither groups. Conclusions Open tension-free mesh-plug hernia repair, TAPP and TEP are all safe and effective for the treatment for patients with primary unilateral inguinal hernia. TAPP and TEP are superior to open tension-free mesh-plug hernia repair as these two procedures involve less postoperative pain and fast recovery.
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Objective To discuss the operative difficulties and management in laparoscopic thyroidectomy.Method The clinical data of 169 cases undergoing laparoscopic thyroidectomy were retrospectively analyzed.Result Among 169 cases,only 2 cases were switched to open surgery.Among the other 167 cases local thyroidectomy for thyroid adenoma Was performed in 37 cases,one side subtotal thyroidectomy in 63 cases,two side subtotal thyroidectomy in 42 cases,laparoscopic subtotal thyroideetomy was done in 20 cases for Grave's disease,and radical thyroidectomy was undeRaken in 5 cases of thyroid carcinoma.Postoperatively fat colliquation occurred in 2 cases,pneumohypoderma,skin bruise and temporary vocal dullness or hoarsness in 1 each case.There was no postoperative recurrent laryngeal nerve injury,nor that of the parathyroid gland. Conclusions Laparoscopie thyroidectomy has its own intraoperative difficulties. Accurate operative skills and careful perioperative management can decrease the occurrence of complications.