First experience with robotic pancreatoduodenectomy in Singapore

INTRODUCTIONRecent studies reported that laparoscopic pancreatoduodenectomy (LPD) is associated with superior perioperative outcomes compared to the open approach. However, concerns have been raised about the safety of LPD, especially during the learning phase. Robotic pancreatoduodenectomy (RPD) has been reported to be associated with a shorter learning curve compared to LPD. We herein present our initial experience with RPD.METHODSA retrospective review of a single-institution prospective robotic hepatopancreaticobiliary (HPB) surgery database of 70 patients identified seven consecutive RPDs performed by a single surgeon in 2016–2017. These were matched at a 1:2 ratio with 14 open pancreatoduodenectomies (OPDs) selected from 77 consecutive pancreatoduodenectomies performed by the same surgeon between 2011 and 2017.RESULTSSeven patients underwent RPD, of which five were hybrid procedures with open reconstruction. There were no open conversions. Median operative time was 710.0 (range 560.0–930.0) minutes. Two major morbidities (> Grade 2) occurred: one gastrojejunostomy bleed requiring endoscopic haemostasis and one delayed gastric emptying requiring feeding tube placement. There were no pancreatic fistulas, reoperations or 90-day/in-hospital mortalities in the RPD group. Comparison between RPD and OPD demonstrated that RPD was associated with a significantly longer operative time. Compared to open surgery, there was no significant difference in estimated blood loss, blood transfusion, postoperative stay, pancreatic fistula rates, morbidity and mortality rates, R0 resection rates, and lymph node harvest rates.CONCLUSIONOur initial experience demonstrates that RPD is feasible and safe in selected patients. It can be safely adopted without any compromise in patient outcomes compared to the open approach.     

False-negative and False-positive Errors in Abdominal Pain Evaluation Failure to Diagnose Acute Appendicitis and Unnecessary Surgery

OBJECTIVES: To test the hypothesis that physician errors (failure to diagnose appendicitis at initial evaluation) correlate with adverse outcome. The authors also postulated that physician errors would correlate with delays in surgery, delays in surgery would correlate with adverse outcomes, and physician errors would occur on patients with atypical presentations. METHODS: This was a retrospective two-arm observational cohort study at 12 acute care hospitals: 1) consecutive patients who had an appendectomy for appendicitis and 2) consecutive emergency department abdominal pain patients. Outcome measures were adverse events (perforation, abscess) and physician diagnostic performance (false-positive decisions, false-negative decisions). RESULTS: The appendectomy arm of the study included 1, 026 patients with 110 (10.5%) false-positive decisions (range by hospital 4.7% to 19.5%). Of the 916 patients with appendicitis, 170 (18.6%) false-negative decisions were made (range by hospital 10.6% to 27.8%). Patients who had false-negative decisions had increased risks of perforation (r = 0.59, p = 0.058) and of abscess formation (r = 0.81, p = 0.002). For admitted patients, when the inhospital delay before surgery was >20 hours, the risk of perforation was increased [2.9 odds ratio (OR) 95% CI = 1.8 to 4.8]. The amount of delay from initial physician evaluation until surgery varied with physician diagnostic performance: 7.0 hours (95% CI = 6.7 to 7.4) if the initial physician made the diagnosis, 72.4 hours (95% CI = 51.2 to 93.7) if the initial office physician missed the diagnosis, and 63.1 hours (95% CI = 47.9 to 78.4) if the initial emergency physician missed the diagnosis. Patients whose diagnosis was initially missed by the physician had fewer signs and symptoms of appendicitis than patients whose diagnosis was made initially [appendicitis score 2.0 (95% CI = 1.6 to 2.3) vs 6.5 (95% CI = 6.4 to 6.7)]. Older patients (>41 years old) had more false-negative decisions and a higher risk of perforation or abscess (3.5 OR 95% CI = 2.4 to 5.1). False-positive decisions were made for patients who had signs and symptoms similar to those of appendicitis patients [appendicitis score 5.7 (95% CI = 5.2 to 6.1) vs 6.5 (95% CI = 6.4 to 6.7)]. Female patients had an increased risk of false-positive surgery (2.3 OR 95% CI = 1.5 to 3.4). The abdominal pain arm of the study included 1,118 consecutive patients submitted by eight hospitals, with 44 patients having appendicitis. Hospitals with observation units compared with hospitals without observation units had a higher "rule out appendicitis" evaluation rate [33.7% (95% CI = 27 to 38) vs 24.7% (95% CI = 23 to 27)] and a similar hospital admission rate (27.6% vs 24.7%, p = NS). There was a lower miss-diagnosis rate (15.1% vs 19.4%, p = NS power 0.02), lower perforation rate (19.0% vs 20.6%, p = NS power 0.05), and lower abscess rate (5.6% vs 6.9%, p = NS power 0.06), but these did not reach statistical significance. CONCLUSIONS: Errors in physician diagnostic decisions correlated with patient clinical findings, i.e., the missed diagnoses were on appendicitis patients with few clinical findings and unnecessary surgeries were on non-appendicitis patients with clinical findings similar to those of patients with appendicitis. Adverse events (perforation, abscess formation) correlated with physician false-negative decisions.     

海马区星形胶质细胞培养上清液体外诱导人脂肪基质细胞向神经元样细胞的分化

目的:观察海马区星形胶质细胞培养上清液能否在体外诱导人脂肪基质细胞向神经元样细胞分化。方法:实验于2004-10/2005-06在华北煤炭医学院中心实验室完成。在无菌条件下从Wistar乳鼠分离出海马组织,从分离的海马组织中获得星形胶质细胞,并收集其培养上清液。取外科手术获得的人腹部皮下脂肪组织进行人脂肪基质细胞的原代培养。30例患者均知情同意。取第3代人脂肪基质细胞接种到培养孔中,预先放置无菌盖玻片的24孔培养板,制备细胞爬片或者接种到培养瓶中,细胞生长达50%～60%融合时,去除培养液,换为海马区星形胶质细胞培养上清诱导液进行诱导,对照组培养液为无血清培养基。倒置相差显微镜下连续观察细胞生长情况和形态变化,应用免疫细胞化学、鉴定神经前体细胞的特异性标志神经巢蛋白、神经细胞的特异性标志神经元特异性烯醇化酶、微管联合蛋白2和神经胶质细胞的特异性标志胶质纤维酸性蛋白的表达。结果:①诱导培养第3天,部分人脂肪基质细胞开始变形,从原先的细长梭状细胞变成神经元样细胞,可见细胞伸出突起,多为双极或多极细胞。②刚分离接种的人脂肪基质细胞镜下呈圆形,悬浮状态,接种后24h内贴壁,并开始伸展,多呈梭形。1周后细胞融合成单层,排列出现方向性,但有少量圆形及卵圆形细胞混杂生长。③第4,5代人脂肪基质细胞在诱导48h后形态即开始发生变化,扁平的胞体较预诱导后逐渐回缩,向外伸出突起,72h后扁平的胞浆向胞核收缩,突起继续延长,以后随时间进展,具有典型神经细胞形态特点的细胞数量逐渐增多,形成双极或多极细胞。④免疫细胞化学检测人脂肪基质细胞诱导5d后发现有(10.5±3.7)%神经巢蛋白、(38.4±5.2)%胶质纤维酸性蛋白、(15.7±2.3)%神经元特异性烯醇化酶表达,未见微管联合蛋白2的表达。结论:海马区星形胶质细胞培养上清液可以在体外诱导人脂肪基质细胞向神经元样细胞方向分化。     

Thrombosis in inflammatory bowel disease: clinical setting, procoagulant profile and factor V Leiden

Patients with inflammatory bowel disease have an increased frequency of thromboembolism, and microvascular thrombosis has been proposed as a contributory pathogenic factor. The mechanism of enhanced procoagulant activity is not understood. We examined the clinical setting of thromboembolic events in 52 patients with Crohn's disease or ulcerative colitis, and assessed the procoagulant laboratory profile, including Factor V Leiden, in a subset of 20 patients to identify procoagulant risk factors. Patients who developed thrombosis tended to be young; 60% of thrombotic events occurred in patients under 50 years. Multiple thromboembolic episodes occurred in 13% and unusual sites of thrombosis (e.g. intracardiac, cerebral, inominate veins) in 11%. No risk factor was identifiable in 52% of cases and two-thirds of thromboses occurred in an out-patient setting. The mortality rate was 8%. Evidence for inflammatory disease activity was found in only 45% of patients with ulcerative colitis at the time of the thromboembolic event, in contrast to 89% of those with Crohn's disease. Assays for specific coagulation defects were negative in all cases tested (protein S, C were normal in 17/17; anti-thrombin III, anti-phospholipid antibodies and activated protein C resistance were negative in 20/20, and only 1/20 patients was found to be heterozygous for Factor V leiden. Thrombosis in inflammatory bowel disease is important because it occurs in a young population, often in unusual sites, and has a high mortality. The development of thrombosis is related to active inflammatory disease in most patients with Crohn's disease but apparently not in those with ulcerative colitis. Since approximately half of the patients had no other identifiable risk factor, there remains a substantial group of patients with IBD who develop thrombosis for unknown reasons.      

Association of FADS2 rs174575 gene polymorphism and insulin resistance in type 2 diabetes mellitus

BackgroundMany risk factors contribute to the pathogenesis of diabetes. Gene and lifestyle factors are considered to be the major contributors. A dietary pattern is attributed to be one of the lifestyle risk factors favoring diabetes. The present study aims to find an association between fatty acid desaturase (FADS) gene polymorphism and glycemic profile in type 2 diabetes mellitus (T2DM).MethodologyA total of 429 subjects were included in the study on the basis of inclusion and exclusion criteria, of which 213 and 216 subjects were diabetic and control, respectively. Body mass index was calculated. Fasting plasma glucose, glycated hemoglobin (HbA1c) and insulin were measured using commercially available kits. rs174575 of FADS2 was selected based on previous publications and identified using the dbSNP database. To compare the biochemical parameters with the genotype, the following three models were used: additive model (CC vs CG vs GG), dominant model (CC + CG vs GG), and recessive model (CC vs CG + GG).Results and DiscussionFBS, HbA1c, insulin, HOMA-IR, and HOMA-B exhibited a high and statistically significant difference between subjects and controls. The three models exhibited a statistically significant difference between FBS, HOMA-IR, and HOMA- B (p<0.05).ConclusionThe distribution of rs174575 genotype differed significantly between the subjects and controls in the present study. The study revealed that genetic variation in FADS2 is an additional facet to consider while studying the risk factors of T2DM.     

Influence of clinical status on the association between plasma total and unbound bilirubin and death or adverse neurodevelopmental outcomes in extremely low birth weight infants

Objectives: To assess the influence of clinical status on the association between total plasma bilirubin and unbound bilirubin on death or adverse neurodevelopmental outcomes at 18–22 months corrected age in extremely low birth weight infants. Method: Total plasma bilirubin and unbound bilirubin were measured in 1101 extremely low birth weight infants at 5 ± 1 days of age. Clinical criteria were used to classify infants as clinically stable or unstable. Survivors were examined at 18–22 months corrected age by certified examiners. Outcome variables were death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death prior to follow‐up. For all outcomes, the interaction between bilirubin variables and clinical status was assessed in logistic regression analyses adjusted for multiple risk factors. Results: Regardless of clinical status, an increasing level of unbound bilirubin was associated with higher rates of death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss and death before follow‐up. Total plasma bilirubin values were directly associated with death or neurodevelopmental impairment, death or cerebral palsy, death or hearing loss, and death before follow‐up in unstable infants, but not in stable infants. An inverse association between total plasma bilirubin and death or cerebral palsy was found in stable infants. Conclusions: In extremely low birth weight infants, clinical status at 5 days of age affects the association between total plasma bilirubin and death or adverse neurodevelopmental outcomes at 18–22 months of corrected age. An increasing level of UB is associated a higher risk of death or adverse neurodevelopmental outcomes regardless of clinical status. Increasing levels of total plasma bilirubin are directly associated with increasing risk of death or adverse neurodevelopmental outcomes in unstable, but not in stable infants.