Systematic Reviews and Meta-analyses of the Procedure-specific Risks of Thrombosis and Bleeding in General Abdominal, Colorectal, Upper Gastrointestinal, and Hepatopancreatobiliary Surgery.

OBJECTIVE: To provide procedure-specific estimates of symptomatic venous thromboembolism (VTE) and major bleeding after abdominal surgery. BACKGROUND: The use of pharmacological thromboprophylaxis represents a trade-off that depends on VTE and bleeding risks that vary between procedures; their magnitude remains uncertain. METHODS: We identified observational studies reporting procedure-specific risks of symptomatic VTE or major bleeding after abdominal surgery, adjusted the reported estimates for thromboprophylaxis and length of follow-up, and estimated cumulative incidence at 4 weeks postsurgery, stratified by VTE risk groups, and rated evidence certainty. RESULTS: After eligibility screening, 285 studies (8,048,635 patients) reporting on 40 general abdominal, 36 colorectal, 15 upper gastrointestinal, and 24 hepatopancreatobiliary surgery procedures proved eligible. Evidence certainty proved generally moderate or low for VTE and low or very low for bleeding requiring reintervention. The risk of VTE varied substantially among procedures: in general abdominal surgery from a median of <0.1% in laparoscopic cholecystectomy to a median of 3.7% in open small bowel resection, in colorectal from 0.3% in minimally invasive sigmoid colectomy to 10.0% in emergency open total proctocolectomy, and in upper gastrointestinal/hepatopancreatobiliary from 0.2% in laparoscopic sleeve gastrectomy to 6.8% in open distal pancreatectomy for cancer. CONCLUSIONS: VTE thromboprophylaxis provides net benefit through VTE reduction with a small increase in bleeding in some procedures (eg, open colectomy and open pancreaticoduodenectomy), whereas the opposite is true in others (eg, laparoscopic cholecystectomy and elective groin hernia repairs). In many procedures, thromboembolism and bleeding risks are similar, and decisions depend on individual risk prediction and values and preferences regarding VTE and bleeding.

Sarcopenia and Sarcopenic Obesity on Body Composition Analysis is a Significant Predictor of Mortality in Severe Acute Pancreatitis: A Longitudinal Observational Study.

BACKGROUND: The prevalence and impact of sarcopenia and sarcopenic obesity noted on body composition analysis in severe acute pancreatitis (SAP) is unknown. This study investigates the prevalence of sarcopenia at different timepoints and its effect on post-pancreatitis complications and mortality. METHODS: A prospective database of SAP admissions with organ failure at a single institution from 2015 to 2019 were analysed. Sarcopenia was determined by IMAGE J software on CT. Database was further queried for post-pancreatitis complications and mortality. RESULTS: 141 patients with a median age of 59 (range 18-88) and M:F ratio 1.52:1 of were analysed. Sarcopenia was present in 111/141 (79%) patients at admission, 78/79 (99%) at 3 months and 26/36 (72%) at 12 months. 67/111 patients with sarcopenia on admission had sarcopenic obesity. The mortality at 30 days, 3 months and 12 months was 16/141 (11%), 30/141 (21%) and 42/141 (30%) respectively. Mortality was significantly higher in sarcopenic patients at admission (35.14%) compared to the non-sarcopenic group (10%), P = 0.008). Mortality in the sarcopenic obesity group was significantly higher (45%) compared to the sarcopenic non-obese group (20%), P = 0.009) at admission. Multivariate logistic regression identified sarcopenic obesity (OR: 2.880), age (OR: 1.048) and number of organ failures (OR: 3.225) as significant predictors of mortality. CONCLUSIONS: Sarcopenia and Sarcopenic obesity are highly prevalent in SAP patients on admission and during follow up. Furthermore, sarcopenic obesity was shown to be a significant predictor of mortality at admission, suggesting that body composition analysis could be a potential predictive marker of mortality in SAP patients.

Upfront surgery vs. neoadjuvant therapy for resectable pancreatic cancer: a narrative review of available evidence.

BACKGROUND AND OBJECTIVE: Though the use of neoadjuvant therapy (NAT) is increasing in the setting of borderline resectable (BRPC) and locally advance pancreatic cancer (LAPC), the role of NAT in resectable pancreatic cancer (RPC) remains uncertain. METHODS: This is a narrative review, summarising the contemporary evidence and emerging studies comparing neoadjuvant therapy to upfront resection and adjuvant therapy in RPC. KEY AND CONTENT AND FINDINGS: Upfront resection followed by adjuvant chemotherapy is currently the standard of care for RPC. Though BRPC and LAPC have reported significant overall survival benefits with NAT, those results have yet to be translated to RPC. Downstaging is only reported in a small proportion of patients who receive NAT; most have stable disease and a small number have progression. Preliminary trial data have largely been consistent with that observed in the past whereby a modest improvement in R0 resection rates and pathological findings is observed with NAT, however rates of distant recurrence and overall survival remain similar to upfront resection. A significant proportion further fail to achieve resection due to the side effects, deconditioning and delays to surgery. Most international recommendations have been guided by non-randomised data sets and long-term data from emerging phase III trials are yet to be published. CONCLUSIONS: Although we have observed improved R0 resection rates with NAT, this has yet to translate to a robust improvement in overall survival. Concerns regarding delays to resection, and limited response to NAT remain a topic of ongoing investigation.

Systematic reviews of observational studies of Risk of Thrombosis and Bleeding in General and Gynecologic Surgery (ROTBIGGS): introduction and methodology.

BACKGROUND: Venous thromboembolism (VTE) and bleeding are serious and potentially fatal complications of surgical procedures. Pharmacological thromboprophylaxis decreases the risk of VTE but increases the risk of major post-operative bleeding. The decision to use pharmacologic prophylaxis therefore represents a trade-off that critically depends on the incidence of VTE and bleeding in the absence of prophylaxis. These baseline risks vary widely between procedures, but their magnitude is uncertain. Systematic reviews addressing baseline risks are scarce, needed, and require innovations in methodology. Indeed, systematic summaries of these baseline risk estimates exist neither in general nor gynecologic surgery. We will fill this knowledge gap by performing a series of systematic reviews and meta-analyses of the procedure-specific and patient risk factor stratified risk estimates in general and gynecologic surgeries. METHODS: We will perform comprehensive literature searches for observational studies in general and gynecologic surgery reporting symptomatic VTE or bleeding estimates. Pairs of methodologically trained reviewers will independently assess the studies for eligibility, evaluate the risk of bias by using an instrument developed for this review, and extract data. We will perform meta-analyses and modeling studies to adjust the reported risk estimates for the use of thromboprophylaxis and length of follow up. We will derive the estimates of risk from the median estimates of studies rated at the lowest risk of bias. The primary outcomes are the risk estimates of symptomatic VTE and major bleeding at 4 weeks post-operatively for each procedure stratified by patient risk factors. We will apply the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate evidence certainty. DISCUSSION: This series of systematic reviews, modeling studies, and meta-analyses will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding in general and gynecologic surgeries. Our work advances the standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at the best estimates of risk (including modeling of the timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the GRADE approach. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021234119.

Meta-analysis of survival outcomes following surgical and non surgical treatments for colorectal cancer metastasis to the lung.

BACKGROUND: Controversy exists regarding the optimal management of colorectal lung metastases (CRLM). This meta-analysis compared surgical (Surg) versus interventional (chemotherapy and/or radiotherapy) and observational non-surgical (NSurg) management of CRLM. METHODS: A systematic review of the major databases including Medline, Embase, SCOPUS and the Cochrane library was performed. RESULTS: One randomized and nine observational studies including 2232 patients: 1551 (69%) comprised the Surg cohort, 521 (23%) the interventional NSurg group and 160 (7%) the observational NSurg group. A significantly higher overall survival (OS) was observed when Surg was compared to interventional NSurg at 1 year (Surg 88%, 310/352; interventional NSurg 64%, 245/383; odds ratio (OR) 2.77 (confidence interval (CI) 1.94-3.97), P = 0.001), at 3 years (Surg 59%, 857/1444; interventional NSurg 26%, 138/521; OR 2.61 (CI 1.65-4.15), P = 0.002), at 5 years (Surg 47%, 533/1144; interventional NSurg 23%, 45/196; OR 3.24 (CI 1.42-7.39), P = 0.009) and at 10 years (Surg 27%, 306/1122; interventional NSurg 1%, 2/168; OR 15.64 (CI 1.87-130.76), P = 0.031). Surg was associated with a greater OS than observational NSurg at only 1 year (Surg 92%, 98/107; observational NSurg 83%, 133/160; OR 6.69 (CI 1.33-33.58), P = 0.037) and was similar to observational NSurg at all other OS time points. Comparable survival was observed among Surg and overall NSurg cohorts at 3- and 5-year survival in articles published within the last 3 years. CONCLUSIONS: Recent evidence suggests comparable survival with Surg and NSurg modalities for CRLM, contrasting to early evidence where Surg had an improved survival. Significant selection bias contributes to this finding, prompting the need for high powered randomized controlled trials and registry data.

A Network Meta-analysis of Surgery for Chronic Pancreatitis: Impact on Pain and Quality of Life.

BACKGROUND: The surgical operation associated with improved pain and quality of life (QoL) in patients with chronic pancreatitis (CP) is unknown. METHOD: The Scopus, EMBASE, Medline and Cochrane databases were systematically searched until May 2019, and all randomised trials (RCTs) comparing surgical operations for CP pain were included in a network meta-analysis (NMA). RESULTS: Four surgical operations for treating CP were directly compared in eight RCTs including 597 patients. Patients were mainly male (79%, 474/597) with alcoholic CP (85%, 382/452). Surgical operations included were pancreatoduodenectomy (224, 38%), Berne procedure (168, 28%), Beger procedure (133, 22%) and Frey procedure (72, 12%). The NMA revealed that the Beger procedure ranked best for pain relief, whilst the Frey procedure ranked best for postoperative QoL, postoperative pancreatic fistula rate and postoperative exocrine insufficiency rate during a median follow-up of 26 months (reported range 6-58 months). Overall the Frey procedure ranked best for the combination of primary outcome measures based on surface under cumulative ranking curve scores. CONCLUSIONS: Overall the Frey procedure may perform the best for both pain relief and postoperative QoL in patients with CP. Further trials are warranted in defining the role of surgery in relation to endotherapy.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

The Impact of the Depth of Venous Invasion on Survival Following Pancreatoduodenectomy for Pancreatic Cancer: a Meta-analysis of Available Evidence.

PURPOSE: The prognostic significance of portal/superior mesenteric vein (PV/SMV) invasion at the time of pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC) is contentious. The aim of this meta-analysis was to compare the survival outcomes in patients with histologically proven adventitial (superficial) versus media/intimal (deep) PV/SMV invasion at the time of PD for PDAC. METHODS: A systematic search of the PubMed, MEDLINE and SCOPUS databases were performed in accordance with PRISMA guidelines. All articles reporting outcomes specific to the depth of PDAC invasion into the PV/SMV wall were included. The primary outcome measure was overall survival. RESULTS: Six studies including 310 patients who underwent pancreatic resection with PV/SMV resection for PDAC were included in this meta-analysis. There was no difference in overall survival comparing superficial vs deep invasion at 12 months (64% vs 58% respectively, risk difference, - 0.09; CI, - 0.21-0.04; P = 0.183), 36 months (22% vs 18% respectively, risk difference, - 0.05; CI, - 0.16-0.19; P = 0.857) and mean overall survival (42.8 months vs 25.7 months respectively, standard mean difference, - 0.27; CI, - 0.58, 0.03; P = 0.078). Although larger tumours were seen in those with confirmed deep vein wall invasion (P < 0.001), no difference was observed between the superficial and deep invasion groups with regard to age (P = 0.298), R1 resection (P = 0.896), nodal metastatic disease (P = 0.120) and perineural invasion (P = 0.609). CONCLUSIONS: This meta-analysis suggests that the depth of PV/SMV wall invasion by PDAC may not impact survival after PD. However, given the limited sample size, further research is warranted with homogenous cohorts and longer follow-up.

Critical appraisal of the techniques of pancreatic anastomosis following pancreaticoduodenectomy: A network meta-analysis.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains a major cause of morbidity following pancreaticoduodenectomy (PD). This network meta-analysis (NMA) compared techniques of pancreatic anastomosis following PD to determine the technique with the best outcome profile. METHODS: A systematic literature search was performed on the Scopus, EMBASE, Medline and Cochrane databases to identify RCTs employing the international study group of pancreatic fistula (ISGPF) definition of POPF. The primary outcome was clinically relevant POPF. RESULTS: Five techniques of pancreatic anastomosis following PD were directly compared in 15 RCTs comprising 2428 patients. Panreatojejunostomy (PJ) end-to-side invagination vs. PJ end-to-side duct-to-mucosa was the most frequent comparison (n = 7). Overall, 971 patients underwent PJ end-to-side duct-to-mucosa, 791 patients PJ end-to-side invagination, 505 patients pancreatogastrostomy (PG) end-to-side invagination, 98 patients PG end-to-side duct-to-mucosa, and 63 patients PJ end-to-side single layer. PG duct-to-mucosa was associated with the lowest rates of clinically relevant POPF, delayed gastric emptying, intra-abdominal abscess, all postoperative morbidity and postoperative mortality, the shortest operative time and postoperative hospital stay and the lowest volume of intra-operative blood loss. CONCLUSION: Duct-to-mucosa pancreaticogastrostomy was associated with the lowest rates of clinically relevant POPF and had the best outcome profile among all techniques of pancreatico-anastomosis following PD.

Sarcopenic obesity and post-operative morbidity after pancreatic surgery: a cohort study.

BACKGROUND: Several indices of sarcopenia (SARC) exist in the literature, however, there is no consensus as to the best SARC index to predict post-operative morbidity following pancreatic surgery. METHODS: A prospectively collected database was reviewed in a single institution including a total of 89 consecutive patients who had undergone pancreatic resection between 2015 and 2018. RESULTS: A total of 89 patients comprised the cohort. Seventy-one percent (63/89) underwent pancreaticoduodenectomy. SARC was identified in 49 patients (55%) using psoas muscle index, 44 patients (49%) using the skeletal muscle index and 25 patients (28%) using the skeletal muscle attenuation. Post-operative morbidity did not differ between SARC and non-SARC (NSARC) patients using all three preoperative computed tomography measures (skeletal muscle index SARC 64%, 28/44, NSARC 64%, 29/45, P = 1.000; psoas muscle index SARC 63%, 31/49, NSARC 65%, 26/40, P = 0.810; skeletal muscle attenuation SARC 17/25, NSARC 40/64, P = 0.247). However, sarcopenic obesity was a significant independent risk factor for overall post-operative morbidity on multivariate analysis (odds ratio 1.241 (SE 0.608), P = 0.041) with the highest specificity (81%). CONCLUSION: Preoperative sarcopenic obesity can be an important independent predictor of post-operative morbidity following pancreatic resection. There remains a need for standardization of SARC indices.

Prophylactic Negative Pressure Wound Therapy in Closed Abdominal Incisions: A Meta-analysis of Randomised Controlled Trials.

INTRODUCTION: Negative pressure wound therapy (NPWT) may prevent subcutaneous fluid accumulation in a closed wound and subsequently reduce surgical site infections (SSI). This meta-analysis aimed to determine the effect of prophylactic NPWT on SSI incidence following abdominal surgery. METHODS: A systematic search of MEDLINE and EMBASE databases was performed using PRISMA methodology. All randomised trials reporting the use of NPWT in closed abdominal incisions were included, regardless of the type of operation. The primary outcome measure was the incidence of SSI, stratified by superficial and deep and organ/space infections. Secondary outcomes were wound dehiscence and length of hospital stay. RESULTS: Ten randomised trials met the inclusion criteria (five Caesarean, five midline laparotomy). The use of NPWT reduced overall SSI (11.6% vs. 16.7%, RR 0.67, 95% CI 0.48-0.95, p = 0.02). The rate of superficial SSI rate was also reduced (6.3% vs. 11.3%, RR 0.57, 95% CI 0.35-0.94, p = 0.03). There was no effect on deep or organ/space SSI (3.2% vs. 4.2%, RR 0.77, 95% CI 0.51-1.18, p = 0.23), wound dehiscence (9.7% vs. 10.9%, RR 0.92, 95% CI 0.69-1.21, p = 0.54), or length of hospital stay (MD 0.06 days, 95% CI-0.11 to 0.23, p = 0.51). CONCLUSIONS: Prophylactic use of NPWT may reduce the incidence of superficial SSI in closed abdominal incisions but has no effect on deep or organ space SSI.

Multicenter randomized crossover trial evaluating the provox luna in laryngectomized subjects.

OBJECTIVES: The aim of this study was to compare the relative compliance and the dermatological and pulmonary outcomes when the Provox Luna system (Atos Medical, Malmö, Sweden) is added during the night to the usual tracheastoma care of laryngectomized subjects. METHODS: This was a multicenter randomized crossover trial conducted in the Netherlands Cancer Institute, Erasmus Medical Center, and Maastricht University Medical Center in The Netherlands. The study included 46 laryngectomized subjects with prior heat and moisture exchanger (HME) and adhesive experience. RESULTS: A significant improvement in the number of compliant individuals was found: Luna: n = 43 of 45 (96%); usual care: n = 35 of 46 (76%), P = 0.02. The Luna period was associated with longer intervals of daily HME use (Luna 23.2 hours [range: 15.6-24.0 hours], usual care [UC]: 21.5 hours [range: 6.0-24.0 hours], P = 0.003) and an increased frequency of skin improvement overnight (Luna 3.9 days [standard deviation (SD)]: 7.0 days), Usual Care: 8.1 days ([SD: 10.8 days], P = 0.008). Fifty-six percent (n = 26) of participants wanted to continue using the Provox Luna system at the conclusion of the study. CONCLUSION: An improvement in compliance and skin recovery overnight was observed when the Provox Luna was added to the usual adhesive and HME use. Therefore, there is utility in supplementing the usual post-total laryngectomy care with the Provox Luna system at night, particularly in the setting of compliance concerns and in subjects who desire dermatological relief overnight. LEVEL OF EVIDENCE: 1b Laryngoscope, 129:2354-2360, 2019.