Meta-analysis of randomized controlled trials and individual patient data comparing minimally invasive with open oesophagectomy for cancer.

BACKGROUND: Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial. METHODS: A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects. RESULTS: Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P < 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P < 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P < 0.010). CONCLUSION: MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques. LAY SUMMARY: Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Dissection with LigaSure Impact™ versus conventional resection in pylorus-preserving partial pancreatoduodenectomy (DISSECT): a single-institution randomized controlled trial.

PURPOSE: In partial pancreatoduodenectomy, appropriate effective hemostasis during dissection is of major importance for procedural flow, operation time, and postoperative outcome. As ligation, clipping, or suturing of blood vessels is time-consuming and numerous instrument changes are required, the primary aim of this randomized controlled trial was to assess whether LigaSure Impact™ exhibits benefits over named conventional dissection techniques in patients undergoing pylorus-preserving partial pancreatoduodenectomy. METHODS: This single-institution, randomized, superiority trial was performed between September 27, 2009, and February 24, 2012. Patients undergoing pylorus-preserving partial pancreatoduodenectomy were allocated to the study arms in a 1:1 ratio based on an unstratified block randomization with random block sizes to receive either dissection with LigaSure Impact™ or conventional dissection. The primary endpoint was operation time. Secondary endpoints included peri- and postoperative morbidity and mortality, intraoperative blood loss, and length of hospital stay. To observe a time reduction of 40 min, 51 patients per arm were required. The primary analysis was the intention to treat. RESULTS: The mean operation time did not differ between the Ligasure Impact™ (308 min; SD: 56 min; range: 155-455 min) and the conventional dissection (318 min; SD: 90 min, range: 175-550 min) (p = 0.531). Moreover, LigaSure Impact™ dissection did not show significant advantages over conventional dissection in terms of peri- and postoperative morbidity and mortality, intraoperative blood loss, or length of hospital stay. CONCLUSIONS: The application of LigaSure Impact™ dissection in pylorus-preserving partial pancreatoduodenectomy does not increase effectiveness and safety of dissection. TRIAL REGISTRATION: DRKS00000166.

Endoscopic versus surgical treatment for infected necrotizing pancreatitis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To compare outcomes of endoscopic and surgical treatment for infected necrotizing pancreatitis (INP) based on results of randomized controlled trials (RCT). BACKGROUND: Treatment of INP has changed in the last two decades with adoption of interventional, endoscopic and minimally invasive surgical procedures for drainage and necrosectomy. However, this relies mostly on observational studies. METHODS: We performed a systematic review following Cochrane and PRISMA guidelines and AMSTAR-2 criteria and searched CENTRAL, Medline and Web of Science. Randomized controlled trails that compared an endoscopic treatment to a surgical treatment for patients with infected walled-off necrosis and included one of the main outcomes were eligible for inclusion. The main outcomes were mortality and new onset multiple organ failure. Prospero registration ID: CRD42019126033 RESULTS: Three RCTs with 190 patients were included. Intention to treat analysis showed no difference in mortality. However, patients in the endoscopic group had statistically significant lower odds of experiencing new onset multiple organ failure (odds ratio (OR) confidence interval [CI] 0.31 [0.10, 0.98]) and were statistically less likely to suffer from perforations of visceral organs or enterocutaneous fistulae (OR [CI] 0.31 [0.10, 0.93]), and pancreatic fistulae (OR [CI] 0.09 [0.03, 0.28]). Patients with endoscopic treatment had a statistically significant lower mean hospital stay (Mean difference [CI] - 7.86 days [- 14.49, - 1.22]). No differences in bleeding requiring intervention, incisional hernia, exocrine or endocrine insufficiency or ICU stay were apparent. Overall certainty of evidence was moderate. CONCLUSION: There seem to be possible benefits of endoscopic treatment procedure. Given the heterogenous procedures in the surgical group as well as the low amount of randomized evidence, further studies are needed to evaluate the combination of different approaches and appropriate timepoints for interventions.

Meta-analysis of α-blockade versus no blockade before adrenalectomy for phaeochromocytoma.

BACKGROUND: Preoperative α-blockade in phaeochromocytoma surgery is recommended by all guidelines to prevent intraoperative cardiocirculatory events. The aim of this meta-analysis was to assess the benefit of such preoperative treatment compared with no treatment before adrenalectomy for phaeochromocytoma. METHODS: A systematic literature search was undertaken in MEDLINE, Web of Science and CENTRAL without language restrictions. Randomized and non-randomized comparative studies investigating preoperative α-blockade in phaeochromocytoma surgery were included. Data on perioperative safety, effectiveness and outcomes were extracted. Pooled results were calculated as an odds ratio or mean difference with 95 per cent confidence interval. RESULTS: A total of four retrospective comparative studies were included investigating 603 patients undergoing phaeochromocytoma surgery. Mortality, cardiovascular complications, mean maximal intraoperative systolic and diastolic BP, and mean maximal intraoperative heart rate did not differ between patients with or without α-blockade. The certainty of the evidence was very low owing to the inferior quality of studies. CONCLUSION: This meta-analysis has shown a lack of evidence for preoperative α-blockade in surgery for phaeochromocytoma. RCTs are needed to evaluate whether preoperative α-blockade can be abandoned.

ANTECEDENTES: Todas las guías recomiendan el bloqueo alfa preoperatorio en la cirugía del feocromocitoma para prevenir eventos cardiocirculatorios intraoperatorios. El objetivo de este metaanálisis fue evaluar el beneficio de dicho tratamiento preoperatorio antes de la adrenalectomía por feocromocitoma en comparación con ningún tratamiento. MÉTODOS: Se realizó una búsqueda sistemática de la literatura en MEDLINE, Web of Science y CENTRAL sin restricciones de idioma. Se incluyeron estudios comparativos aleatorizados y no aleatorizados que investigaron el bloqueo alfa preoperatorio en la cirugía del feocromocitoma. Se extrajeron los datos en relación a la seguridad perioperatoria, la efectividad y los resultados. Los resultados agrupados se mostraron como razón de oportunidades (odds ratio, OR) o diferencia de medias (MD) con el correspondiente i.c. del 95%. RESULTADOS: Se incluyeron un total de cuatro estudios comparativos retrospectivos que analizaron a 603 pacientes sometidos a cirugía del feocromocitoma. La mortalidad, las complicaciones cardiovasculares, la media del valor máximo de la presión arterial sistólica y diastólica intraoperatoria y la media del valor máximo de la frecuencia cardíaca intraoperatoria no difirieron entre pacientes con o sin bloqueo. La certeza de la evidencia fue muy baja debido a la baja calidad de los estudios. CONCLUSIÓN: Este metaanálisis demuestra la falta de evidencia del bloqueo alfa preoperatorio en la cirugía del feocromocitoma. Se necesitan ensayos controlados aleatorizados para evaluar si se puede abandonar el bloqueo alfa preoperatorio.

Learning Curves of Laparoscopic Roux-en-Y Gastric Bypass and Sleeve Gastrectomy in Bariatric Surgery: a Systematic Review and Introduction of a Standardization.

BACKGROUND: The most commonly performed bariatric procedures are laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (LSG). Impact of learning curves on operative outcome has been well shown, but the necessary learning curves have not been clearly defined. This study provides a systematic review of the literature and proposes a standardization of phases of learning curves for RYGB and LSG. METHODS: A systematic literature search was performed using PubMed, Web of Science, and CENTRAL databases. All studies specifying a number or range of approaches to characterize the learning curve for RYGB and LSG were selected. RESULTS: A total of 28 publications related to learning curves for 27,770 performed bariatric surgeries were included. Parameters used to determine the learning curve were operative time, complications, conversions, length of stay, and blood loss. Learning curve range was 30-500 (RYGB) and 30-200 operations (LSG) according to different definitions and respective phases of learning curves. Learning phases described the number of procedures necessary to achieve predefined skill levels, such as competency, proficiency, and mastery. CONCLUSIONS: Definitions of learning curves for bariatric surgery are heterogeneous. Introduction of the three skill phases competency, proficiency, and mastery is proposed to provide a standardized definition using multiple outcome variables to enable better comparison in the future. These levels are reached after 30-70, 70-150, and up to 500 RYGB, and after 30-50, 60-100, and 100-200 LSG. Training curricula, previous laparoscopic experience, and high procedure volume are hallmarks for successful outcomes during the learning curve.

[Evidence-based perioperative medicine]. / Evidenzbasierte perioperative Medizin.

Perioperative medical interventions are an integral part of modern surgical management. In addition to the main manual aspects of surgical interventions, surgeons must also be familiar with preoperative and postoperative medical interventions. This ranges from the indications for perioperative anticoagulation, handling of drainage, adjusting the perioperative analgesia, prescribing an antibiotic prophylaxis to deciding whether a preoperative bowel preparation is necessary. Therefore, this article exemplifies some areas in perioperative medicine. Based on the best available evidence, it should always be critically assessed whether these perioperative interventions really contribute to the success of the treatment.

Systematic review of the quantity and quality of randomized clinical trials in pancreatic surgery.

BACKGROUND: RCTs are considered the reference standard in clinical research. However, surgical RCTs pose specific challenges and therefore numbers have been lower than those for randomized trials of medical interventions. In addition, surgical trials have often been associated with poor methodological quality. The objective of this study was to evaluate the evolution of quantity and quality of RCTs in pancreatic surgery and to identify evidence gaps. METHODS: PubMed, CENTRAL and Web of Science were searched systematically. Predefined data were extracted and organized in a database. Quantity and quality were compared for three intervals of the study period comprising more than three decades. Evidence maps were constructed to identify gaps in evidence. RESULTS: The search yielded 8210 results, of which 246 trials containing data on 26 154 patients were finally included. The number of RCTs per year increased continuously from a mean of 2·8, to 5·7 and up to 13·1 per year over the three intervals of the study. Most trials were conducted in Europe (46·3 per cent), followed by Asia (35·0 per cent) and North America (14·2 per cent). Overall, the quality of RCTs was moderate; however, with the exception of blinding, all domains of the Cochrane risk-of-bias tool improved significantly in the later part of the study. Evidence maps showed lack of evidence from RCTs for operations other than pancreatoduodenectomy and for specific diseases such as neuroendocrine neoplasms or intraductal papillary mucinous neoplasms. CONCLUSION: The quantity and quality of RCTs in pancreatic surgery have increased. Evidence mapping showed gaps for specific procedures and diseases, indicating priorities for future research.

Network meta-analysis of topical haemostatic agents in thyroid surgery.

BACKGROUND: The objective of this study was to investigate the potential benefit of local haemostatic agents for the prevention of postoperative bleeding after thyroidectomy. METHODS: A systematic literature search was performed, and RCTs involving adult patients who underwent thyroid surgery using either active (AHA) or passive (PHA) haemostatic agents were included in the review. The main outcome was the rate of cervical haematoma that required reoperation. A Bayesian random-effects model was used for network meta-analysis with minimally informative prior distributions. RESULTS: Thirteen RCTs were included. The rate of cervical haematoma requiring reoperation ranged from 0 to 9·1 per cent, and was not reduced by haemostatic agents: AHA versus control (odds ratio (OR) 1·53, 95 per cent credibility interval 0·21 to 10·77); PHA versus control (OR 2·74, 0·41 to 16·62) and AHA versus PHA (OR 1·77, 0·12 to 25·06). No difference was observed in the time required for drain removal, duration of hospital stay, and the rate of postoperative hypocalcaemia or recurrent nerve palsy. AHA led to a significantly lower total postoperative blood loss and reduced operating time in comparison with both the control and PHA groups. CONCLUSION: The general use of local haemostatic agents has not been shown to reduce the rate of clinically relevant bleeding.

Comparison of chlorhexidine-isopropanol with isopropanol skin antisepsis for prevention of surgical-site infection after abdominal surgery.

BACKGROUND: Prevention of surgical-site infection (SSI) has received increasing attention. Clinical trials have focused on the role of skin antisepsis in preventing SSI. The benefit of combining antiseptic chlorhexidine with alcohol has not been compared with alcohol-based skin preparation alone in a prospective controlled clinical trial. METHODS: Between August and October 2014, patients undergoing abdominal surgery received preoperative skin antisepsis with 70 per cent isopropanol (PA). Those treated between November 2014 and January 2015 received 2 per cent chlorhexidine with 70 per cent isopropanol (CA). The primary endpoint was SSI on postoperative day (POD) 10, which was evaluated using univariable analysis, and a multivariable logistic regression model correcting for known independent risk factors for SSI. The study protocol was published in the German Registry of Clinical Studies (DRKS00011174). RESULTS: In total, 500 patients undergoing elective midline laparotomy were included (CA 221, PA 279). The incidence of superficial and deep SSIs was significantly different on POD 10: 14 of 212 (6·6 per cent) among those treated with CA and 32 of 260 (12·3 per cent) in those who received PA (P = 0·038). In the multivariable analysis, skin antisepsis with CA was an independent factor for reduced incidence of SSI on POD 10 (P = 0·034). CONCLUSION: This study showed a benefit of adding chlorhexidine to alcohol for skin antisepsis in reducing early SSI compared with alcohol alone.

Meta-analysis of delayed gastric emptying after pylorus-preserving versus pylorus-resecting pancreatoduodenectomy.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pylorus-preserving pancreatoduodenectomy. Recent studies have suggested that resection of the pylorus is associated with decreased rates of DGE. However, superiority of pylorus-resecting pancreatoduodenectomy was not shown in a recent RCT. This meta-analysis summarized evidence of the effectiveness and safety of pylorus-preserving compared with pylorus-resecting pancreatoduodenectomy. METHODS: RCTs and non-randomized studies comparing outcomes of pylorus-preserving and pylorus-resecting pancreatoduodenectomy were searched systematically in MEDLINE, Web of Science and CENTRAL. Random-effects meta-analyses were performed and the results presented as weighted odds ratios (ORs) or mean differences with their corresponding 95 per cent confidence intervals. Subgroup analyses were performed to account for interstudy heterogeneity between RCTs and non-randomized studies. RESULTS: Three RCTs and eight non-randomized studies with a total of 992 patients were included. Quantitative synthesis across all studies showed superiority for pylorus-resecting pancreatoduodenectomy regarding DGE (OR 2·71, 95 per cent c.i. 1·48 to 4·96; P = 0·001) and length of hospital stay (mean difference 3·26 (95 per cent c.i. -1·04 to 5·48) days; P = 0·004). Subgroup analyses including only RCTs showed no significant statistical differences between the two procedures regarding DGE, and for all other effectiveness and safety measures. CONCLUSION: Pylorus-resecting pancreatoduodenectomy is not superior to pylorus-preserving pancreatoduodenectomy for reducing DGE or other relevant complications.

Meta-analysis of metabolic surgery versus medical treatment for microvascular complications in patients with type 2 diabetes mellitus.

BACKGROUND: This study aimed to examine the effect of metabolic surgery on pre-existing and future microvascular complications in patients with type 2 diabetes mellitus (T2DM) in comparison with medical treatment. Although metabolic surgery is the most effective treatment for obese patients with T2DM regarding glycaemic control, it is unclear whether the incidence or severity of microvascular complications is reduced. METHODS: A systematic literature search was performed in MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) with no language restrictions, looking for RCTs, case-control trials and cohort studies that assessed the effect of metabolic surgery on the incidence of microvascular diabetic complications compared with medical treatment as control. The study was registered in the International prospective register of systematic reviews (CRD42016042994). RESULTS: The literature search yielded 1559 articles. Ten studies (3 RCTs, 7 controlled clinical trials) investigating 17 532 patients were included. Metabolic surgery reduced the incidence of microvascular complications (odds ratio 0·26, 95 per cent c.i. 0·16 to 0·42; P < 0·001) compared with medical treatment. Pre-existing diabetic nephropathy was strongly improved by metabolic surgery versus medical treatment (odds ratio 15·41, 1·28 to 185·46; P = 0·03). CONCLUSION: In patients with T2DM, metabolic surgery prevented the development of microvascular complications better than medical treatment . Metabolic surgery improved pre-existing diabetic nephropathy compared with medical treatment.

Meta-analysis of immunonutrition in major abdominal surgery.

BACKGROUND: The objective of this study was to evaluate the potential benefits of immunonutrition in major abdominal surgery with special regard to subgroups and influence of bias. METHODS: A systematic literature search from January 1985 to July 2015 was performed in MEDLINE, Embase and CENTRAL. Only RCTs investigating immunonutrition in major abdominal surgery were included. Outcomes evaluated were mortality, overall complications, infectious complications and length of hospital stay. The influence of different domains of bias was evaluated in sensitivity analyses. Evidence was rated according to the GRADE Working Group grading of evidence. RESULTS: A total of 83 RCTs with 7116 patients were included. Mortality was not altered by immunonutrition. Taking all trials into account, immunonutrition reduced overall complications (odds ratio (OR) 0·79, 95 per cent c.i. 0·66 to 0·94; P = 0·01), infectious complications (OR 0·58, 0·51 to 0·66; P < 0·001) and shortened hospital stay (mean difference -1·79 (95 per cent c.i. -2·39 to -1·19) days; P < 0·001) compared with control groups. However, these effects vanished after excluding trials at high and unclear risk of bias. Publication bias seemed to be present for infectious complications (P = 0·002). Non-industry-funded trials reported no positive effects for overall complications (OR 1·13, 0·88 to 1·46; P = 0·34), whereas those funded by industry reported large effects (OR 0·66, 0·48 to 0·91; P = 0·01). CONCLUSION: Immunonutrition after major abdominal surgery did not seem to alter mortality (GRADE: high quality of evidence). Immunonutrition reduced overall complications, infectious complications and shortened hospital stay (GRADE: low to moderate). The existence of bias lowers confidence in the evidence (GRADE approach).

Prospective trial to evaluate the prognostic value of different nutritional assessment scores in pancreatic surgery (NURIMAS Pancreas).

BACKGROUND: Preoperative nutritional status has an impact on patients' clinical outcome. For pancreatic surgery, however, it is unclear which nutritional assessment scores adequately assess malnutrition associated with postoperative outcome. METHODS: Patients scheduled for elective pancreatic surgery at the University of Heidelberg were screened for eligibility. Twelve nutritional assessment scores were calculated before operation, and patients were categorized as either at risk or not at risk for malnutrition by each score. The postoperative course was monitored prospectively by assessors blinded to the nutritional status. The primary endpoint was major complications evaluated for each score in a multivariable analysis corrected for known risk factors in pancreatic surgery. RESULTS: Overall, 279 patients were analysed. A major complication occurred in 61 patients (21·9 per cent). The proportion of malnourished patients differed greatly among the scores, from 1·1 per cent (Nutritional Risk Index) to 79·6 per cent (Nutritional Risk Classification). In the multivariable analysis, only raised amylase level in drainage fluid on postoperative day 1 (odds ratio (OR) 4·91, 95 per cent c.i. 1·10 to 21·84; P = 0·037) and age (OR 1·05, 1·02 to 1·09; P = 0·005) were significantly associated with major complications; none of the scores was associated with, or predicted, postoperative complications. CONCLUSION: None of the nutritional assessment scores defined malnutrition relevant to complications after pancreatic surgery and these scores may thus be abandoned.

Meta-analysis of prophylactic abdominal drainage in pancreatic surgery.

BACKGROUND: Intra-abdominal drains are frequently used after pancreatic surgery whereas their benefit in other gastrointestinal operations has been questioned. The objective of this meta-analysis was to compare abdominal drainage with no drainage after pancreatic surgery. METHODS: PubMed, the Cochrane Library and Web of Science electronic databases were searched systematically to identify RCTs comparing abdominal drainage with no drainage after pancreatic surgery. Two independent reviewers critically appraised the studies and extracted data. Meta-analyses were performed using a random-effects model. Odds ratios (ORs) were calculated to aggregate dichotomous outcomes, and weighted mean differences for continuous outcomes. Summary effect measures were presented together with their 95 per cent confidence intervals. RESULTS: Some 711 patients from three RCTs were included. The 30-day mortality rate was 2·0 per cent in the drain group versus 3·4 per cent after no drainage (OR 0·68, 95 per cent c.i. 0·26 to 1·79; P = 0·43). The morbidity rate was 65·6 per cent in the drain group and 62·0 per cent in the no-drain group (OR 1·17, 0·86 to 1·60; P = 0·31). Clinically relevant pancreatic fistulas were seen in 11·5 per cent of patients in the drain group and 9·5 per cent in the no-drain group. Reinterventions, intra-abdominal abscesses and duration of hospital stay also showed no significant difference between the two groups. CONCLUSION: Pancreatic resection with, or without abdominal drainage results in similar rates of mortality, morbidity and reintervention.

Incidence, risk factors and clinical implications of chyle leak after pancreatic surgery.

BACKGROUND: Chyle leak is a well known but poorly characterized complication after pancreatic surgery. Available data on incidence, risk factors and clinical significance of chyle leak are highly heterogeneous. METHODS: For this cohort study all patients who underwent pancreatic surgery between January 2008 and December 2012 were identified from a prospective database. Chyle leak was defined as any drainage output with triglyceride content of 110 mg/dl or more. Risk factors for chyle leak were assessed by univariable and multivariable analyses. The clinical relevance of chyle leak was evaluated using hospital stay and resolution by 14 days for short-term outcome and overall survival for long-term outcome. RESULTS: Chyle leak developed in 346 (10·4 per cent) of 3324 patients. Pre-existing diabetes, resection for malignancy, distal pancreatectomy, duration of surgery 180 min or longer, and concomitant pancreatic fistula or abscess were independent risk factors for chyle leak. Both isolated chyle leak and coincidental chyle leak (with other intra-abdominal complications) were associated with prolonged hospital stay. Some 178 (87·7 per cent) of 203 isolated chyle leaks and 90 (70·3 per cent) of 128 coincidental chyle leaks resolved with conservative management within 14 days. Initial and maximum drainage volumes were associated with duration of hospital stay and success of therapy by 14 days. Impact on survival was restricted to chyle leaks that persisted at 14 days in patients with cancer undergoing palliative surgery. CONCLUSION: Chyle leak is a relevant complication, with an incidence of more than 10 per cent after pancreatic surgery, and has a major impact on hospital stay. Drainage volume is associated with hospital stay and success of therapy.