Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis.

OBJECTIVE: To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer. DESIGN: Prospectively registered systematic review and meta-analysis of literature. DATA SOURCES: Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors. ELIGIBILITY CRITERIA: Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm). RESULTS: 68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins. CONCLUSIONS: Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised. SYSTEMATIC REVIEW REGISTRATION: CRD42021232115.

A Network Meta-Analysis of Induction Immunosuppression for Simultaneous Pancreas-Kidney Transplant From Randomized Clinical Trials.

OBJECTIVES: Induction immunosuppression for simultaneous pancreas-kidney transplant has helped reduce graft loss due to early rejection. Both thymoglobulin and interleukin 2 receptor antagonists are the most commonly used induction agents; however, some high-volume centers prefer alemtuzumab.Thisnetwork meta-analysis aimedto compare differentinductionregimens for simultaneouspancreaskidney transplantin terms ofbothpancreas and patient graft survival, as well to assess acute rejection. MATERIALS AND METHODS: A systematic review was conducted to identify randomized clinical trials up to October 31, 2019, that examined induction regimens for simultaneous pancreas-kidney transplant. Study characteristics, postoperative data (patient, pancreas, and kidney graft survival), complications (eg, bleeding), infection rates, and malignancy rates were extracted. We compared all regimens using randomeffects network meta-analyses to maintain randomization within trials. RESULTS: This study identified 7 randomized clinical trials that involved 536 patients, which reported 5 induction regimens. These regimens included antithymocyte globulin (97 patients), alemtuzumab (42 patients), 2 doses (113 patients) or 5 doses (164 patients) of daclizumab, and no induction therapy (120 patients). In the network meta-analysis, a regimen with 2 doses of daclizumab was consistently ranked first for patient survival and kidney and pancreas graft survival. In contrast, alemtuzumab was ranked best for acute rejection (both pancreas and kidney). Rates of majorinfection (ie, cytomegalovirus) and malignancy were reported in 3 studies, precluding a reliable analysis. CONCLUSIONS: Daclizumab with 2 doses, given before simultaneous pancreas-kidney transplant, was associated with the best rates of patient and graft survival. Despite the recent withdrawal of daclizumab, an alternative anti-interleukin 2 induction regimen (basiliximab) has demonstrated promising results in nonrandomized series, warranting that further highquality large-scale randomized clinical trials are still needed.

Elderly patients have increased perioperative morbidity and mortality from oesophagectomy for oesophageal cancer: A systematic review and meta-analysis.

BACKGROUND: Although oesophagectomy remains technically challenging and associated with high morbidity and mortality, it is now increasingly performed in an ever-ageing population with improvement in perioperative care. However, the risks in the elderly population are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of oesophagectomy for cancer in the elderly population compared to younger patients. METHOD: A systematic literature search of PubMed, EMBASE and the Cochrane Library databases was conducted including studies reporting oesophagectomy for cancer in the elderly population. A meta-analysis was reported in accordance with the recommendations of the Cochrane Library and PRISMA guidelines. Primary outcome was overall complications and secondary outcomes were pulmonary and cardiac complications, anastomotic leaks, overall and disease-free survival. RESULTS: This review identified 37 studies incorporating 30,836 patients. Increasing age was significantly associated with increased rates of overall complications (OR 1.67, CI95%: 1.42-1.96), pulmonary complications (OR 1.87, CI95%: 1.48-2.35), and cardiac complications (OR: 2.22, CI95%: 1.95-2.53). However, there was no increased risk of anastomotic leak (OR: 0.98, CI95%: 0.85-1.18). Elderly patients were significantly more likely to have lower rates of 5-year overall survival (OR: 1.36, CI95%: 1.11-1.66) and 5-year disease-free survival (OR: 1.72, CI95%: 1.51-1.96). CONCLUSION: Elderly patients undergoing oesophagectomy for cancer are at increased risk of overall, pulmonary and cardiac complications, irrespective of age subgroups, albeit no difference in anastomotic leaks. Therefore, they represent high-risk patients warranting implementation of preoperative pathways such as prehabilitation to improve cardiopulmonary fitness prior to surgery, although benefit of prehabilitation is yet to be proven. This information will also aid future pre-operative counselling and informed consent.

Long-term survival after minimally invasive resection versus open pancreaticoduodenectomy for periampullary cancers: a systematic review, meta-analysis and meta-regression.

BACKGROUND: It remains unclear whether minimally invasive pancreaticoduodenectomy (MIPD) and open pancreaticoduodenectomy (OPD) influences long-term survival in periampullary cancers. This review aims evaluate long-term survival between MIPD and OPD for periampullary cancers. METHODS: A systematic review was performed to identify studies comparing long-term survival after MIPD and OPD. The I2 test was used to test for statistical heterogeneity and publication bias using Egger test. Random-effects meta-analysis was performed for all-cause 5-year (main outcome) and 3-year survival, and disease-specific 5-year and 3-year survival. Meta-regression was performed for the 5-year and 3-year survival outcomes with adjustment for study (region, design, case matching), hospital (centre volume), patient (ASA grade, gender, age), and tumor (stage, neoadjuvant therapy, subtype (i.e. ampullary, distal bile duct, duodenal, pancreatic)). Sensitivity analyses performed on studies including pancreatic ductal adenocarcinoma (PDAC) only. RESULTS: The review identified 31 relevant studies. Among all 58,622 patients, 8716 (14.9%) underwent MIPD and 49,875 (85.1%) underwent OPD. Pooled analysis revealed similar 5-year overall survival after MIPD compared with OPD (HR: 0.78, 95% CI 0.50-1.22, p = 0.2). Meta-regression indicated case matching, and ASA Grade II and III as confounding covariates. The statistical heterogeneity was limited (I2 = 12, χ2 = 0.26) and the funnel plot was symmetrical both according to visual and statistical testing (Egger test = 0.32). Sensitivity subset analyses for PDAC demonstrated similar 5-year overall survival after MIPD compared with OPD (HR 0.69, 95% CI: 0.32-1.50, p = 0.3). CONCLUSION: Long-term survival after MIPD is non-inferior to OPD. Thus, MIPD can be recommended as a standard surgical approach for periampullary cancers.

Peri-operative Outcomes and Survival Following Palliative Gastrectomy for Gastric Cancer: a Systematic Review and Meta-analysis.

BACKGROUND: Many patients with gastric cancer present with late stage disease. Palliative gastrectomy remains a contentious intervention aiming to debulk tumour and prevent or treat complications such as gastric outlet obstruction, perforation and bleeding. METHODS: We conducted a systematic review of the literature for all papers describing palliative resections for gastric cancer and reporting peri-operative or survival outcomes. Data from peri-operative and survival outcomes were meta-analysed using random effects modelling. Survival data from patients undergoing palliative resections, non-resective surgery and palliative chemotherapy were also combined. This study was registered with the PROSPERO database (CRD42019159136). RESULTS: One hundred and twenty-eight papers which included 58,675 patients contributed data. At 1 year, there was a significantly improved survival in patients who underwent palliative gastrectomy when compared to non-resectional surgery and no treatment. At 2 years following treatment, palliative gastrectomy was associated with significantly improved survival compared to chemotherapy only; however, there was no significant improvement in survival compared to patients who underwent non-resectional surgery after 1 year. Palliative resections were associated with higher rates of overall complications versus non-resectional surgery (OR 2.14; 95% CI, 1.34, 3.46; p < 0.001). However, palliative resections were associated with similar peri-operative mortality rates to non-resectional surgery. CONCLUSION: Palliative gastrectomy is associated with a small improvement in survival at 1 year when compared to non-resectional surgery and chemotherapy. However, at 2 and 3 years following treatment, survival benefits are less clear. Any survival benefits come at the expense of increased major and overall complications.

Treatment strategies for early stage hepatocellular carcinoma: a systematic review and network meta-analysis of randomised clinical trials.

BACKGROUND: Several treatment strategies for early stage hepatocellular cancers (HCC) have been evaluated in randomised controlled trials (RCTs). This network meta-analysis (NMA) aimed to explore the relative effectiveness of these different approaches on their impact on overall (OS) and recurrence-free survival (RFS). METHODS: A systematic review was conducted to identify RCT's reported up to 23rd January 2020. Indirect comparisons of all regimens were simultaneously compared using random-effects NMA. RESULTS: Twenty-eight RCT's, involving 3,618 patients, reporting 13 different treatment strategies for early stage HCC were identified. Median follow-up, reported in 22 studies, ranged from 12-93 months. In this NMA, RFA in combination with iodine-125 was ranked first for both RFS (HR: 0.50, 95% CI: 0.19-1.31) and OS (HR: 0.41, 95% CI: 0.19-0.94). In subgroup with solitary HCC, lack of studies reporting RFS precluded reliable analysis. However, RFA in combination with iodine-125 was associated with markedly better OS (HR: 0.21, 95% CI: 0.05-0.93). CONCLUSION: This NMA identified RFA in combination with iodine-125 as a treatment delivering better RFS and OS, in patients with early stage HCC, especially for those with solitary HCC. This technique warrants further evaluation in both Asia and Western regions.

Systematic review and meta-analysis of factors associated with post-operative pancreatic fistula following pancreatoduodenectomy.

BACKGROUND: Many studies have explored factors relating to post-operative pancreatic fistula (POPF); however, the original definition (All-POPF) was revised to include only 'clinically relevant' (CR) POPF. This study identified variables associated with the two International Study Group on Pancreatic Surgery definitions to identify which variables are more strongly associated with CR-POPF. METHODS: A systematic review identified all studies reporting risk factors for POPF (using both International Study Group on Pancreatic Fistula definitions) following pancreatoduodenectomy. The primary outcome was factors associated with CR-POPF. Meta-analyses (random effects models) of pre-, intra- and post-operative factors associated with POPF in more than two studies were included. RESULTS: Among 52 774 patients All-POPF (n = 69 studies) and CR-POPF (n = 53 studies) affected 27% (95% confidence interval (CI95% ) 23-30) and 19% (CI95% 17-22), respectively. Of the 176 factors, 24 and 17 were associated with All- and CR-POPF, respectively. Absence of pre-operative pancreatitis, presence of renal disease, no pre-operative neoadjuvant therapy, use of post-operative somatostatin analogues, absence of associated venous or arterial resection were associated with CR-POPF but not All-POPF. CONCLUSION: In conclusion this study demonstrates wide variation in reported rates of POPF and that several risk factors associated with CR-POPF are not used within risk prediction models. Data from this study can be used to shape future studies, research and audit across ethnic and geographic boundaries in POPF following pancreatoduodenectomy.

Prehabilitation prior to surgery for pancreatic cancer: A systematic review.

INTRODUCTION: Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection. METHODS: A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting. RESULTS: Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes. CONCLUSION: Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

Perioperative outcomes after laparoscopic cholecystectomy in elderly patients: a systematic review and meta-analysis.

BACKGROUND: Laparoscopic cholecystectomy is increasingly performed in an ever ageing population; however, the risks are poorly quantified. The study aims to review the current evidence to quantify further the postoperative risk of cholecystectomy in the elderly population compared to younger patients. METHOD: A systematic literature search of PubMed, EMBASE and the Cochrane Library databases were conducted including studies reporting laparoscopic cholecystectomy in the elderly population. A meta-analysis was reported in accordance with the recommendations of the Cochrane Library and PRISMA guidelines. Primary outcome was overall complications and secondary outcomes were conversion to open surgery, bile leaks, postoperative mortality and length of stay. RESULTS: This review identified 99 studies incorporating 326,517 patients. Increasing age was significantly associated with increased rates of overall complications (OR 2.37, CI95% 2.00-2.78), major complication (OR 1.79, CI95% 1.45-2.20), risk of conversion to open cholecystectomy (OR 2.17, CI95% 1.84-2.55), risk of bile leaks (OR 1.50, CI95% 1.07-2.10), risk of postoperative mortality (OR 7.20, CI95% 4.41-11.73) and was significantly associated with increased length of stay (MD 2.21 days, CI95% 1.24-3.18). CONCLUSION: Postoperative outcomes such as overall and major complications appear to be significantly higher in all age cut-offs in this meta-analysis. This study demonstrated there is a sevenfold increase in perioperative mortality which increases by tenfold in patients > 80 years old. This study appears to confirm preconceived suspicions of higher risks in elderly patients undergoing cholecystectomy and may aid treatment planning and informed consent.

Impact of neoadjuvant therapy on post-operative pancreatic fistula: a systematic review and meta-analysis.

INTRODUCTION: The use of neoadjuvant therapy (NAT) for pancreatic cancer is increasing, although its impact on post-operative pancreatic fistula (POPF) is variably reported. This systematic review and meta-analysis aimed to assess the impact of NAT on POPF. METHODS: A systematic literature search until October 2019 identified studies reporting POPF following NAT (radiotherapy, chemotherapy or chemoradiotherapy) versus upfront resection. The primary outcome was overall POPF. Secondary outcomes included grade B/C POPF, delayed gastric emptying (DGE), post-operative pancreatic haemorrhage (PPH) and overall and major complications. RESULTS: The search identified 24 studies: pancreatoduodenectomy (PD), 19 studies (n = 19 416) and distal pancreatectomy (DP), five studies (n = 477). Local staging was reported in 17 studies, with borderline resectable and locally advanced disease comprising 6% (0-100%) and 1% (0-33%) of the population, respectively. For PD, any NAT was significantly associated with lower rates of overall POPF (OR: 0.57, P < 0.001) and grade B/C POPF (OR: 0.55, P < 0.001). In DP, NAT was not associated with significantly lower rates of overall or grade B/C POPF. CONCLUSION: NAT is associated with significantly lower rates of POPF after PD but not after DP. Further studies are required to determine whether NAT should be added to POPF risk calculators.

Meta-analysis of prognostic factors of overall survival in patients undergoing oesophagectomy for oesophageal cancer.

INTRODUCTION: Currently, the American Joint Commission on Cancer (AJCC) staging system is used for prognostication for oesophageal cancer. However, several prognostically important factors have been reported but not incorporated. This meta-analysis aimed to characterize the impact of preoperative, operative, and oncological factors on the prognosis of patients undergoing curative resection for oesophageal cancer. METHODS: This systematic review was performed according to PRISMA guidelines and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling to determine pooled univariable hazard ratios (HRs). The study was prospectively registered with the PROSPERO database (Registration: CRD42018157966). RESULTS: One-hundred and seventy-one articles including 73,629 patients were assessed quantitatively. Of the 122 factors associated with survival, 39 were significant on pooled analysis. Of these. the strongly associated prognostic factors were 'pathological' T stage (HR: 2.07, CI95%: 1.77-2.43, P < 0.001), 'pathological' N stage (HR: 2.24, CI95%: 1.95-2.59, P < 0.001), perineural invasion (HR: 1.54, CI95%: 1.36-1.74, P < 0.001), circumferential resection margin (HR: 2.17, CI95%: 1.82-2.59, P < 0.001), poor tumor grade (HR: 1.53, CI95%: 1.34-1.74, P < 0.001), and high neutrophil:lymphocyte ratio (HR: 1.47, CI95%: 1.30-1.66, P < 0.001). CONCLUSION: Several tumor biological variables not included in the AJCC 8th edition classification can impact on overall survival. Incorporation and validation of these factors into prognostic models and next edition of the AJCC system will enable personalized approach to prognostication and treatment.

Critical appraisal of gastric conduit ischaemic conditioning (GIC) prior to oesophagectomy: A systematic review and meta-analysis.

INTRODUCTION: Anastomotic leaks remain a major complication following oesophagectomy, accounting for high morbidity and mortality. Recently, gastric ischaemic conditioning (GIC) has been proposed to improve anastomotic integrity through neovascularisation of the gastric conduit. This systematic review and meta-analysis aim to determine the impact of GIC on postoperative outcomes following oesophagectomy. METHODS: A systematic literature search was performed to identify studies reporting GIC for any indication of oesophageal resection up to April 25, 2019. The primary outcome was anastomotic leak. Secondary outcomes were conduit necrosis, anastomotic strictures, overall and major complications or in-hospital mortality. Meta-analyses were conducted using random-effects modelling. RESULTS: Nineteen studies reported on GIC, of which 13 were comparative studies. GIC was performed through ligation in 13 studies and embolisation in six studies. GIC did not appear to reduce anastomotic leakages (OR 0.80, CI95: 0.51-1.24, p = 0.3), anastomotic strictures (OR 0.75, CI95: 0.35-1.60, p = 0.5), overall complications (OR 1.02, CI95: 0.48-2.16, p = 0.9), major complications (OR 1.06, CI95: 0.53-2.11, p = 0.9), or in-hospital mortality (OR 0.70, CI95: 0.32-1.53, p = 0.4). However, GIC was associated with reduced rates of conduit necrosis (OR 0.30, CI95: 0.11-0.77, p = 0.013). CONCLUSION: GIC does not appear to reduce overall rates of anastomotic leakage after oesophagectomy but seems to reduce severity of leakages. More in depth studies are recommended.

A Systematic Review and Network-Meta-Analysis of Gastro-Enteric Reconstruction Techniques Following Pancreatoduodenectomy to Reduce Delayed Gastric Emptying.

INTRODUCTION: This network meta-analysis aimed to identify the reconstruction technique associated with lowest rates of DGE following pancreatoduodenectomy (PD) from randomised controlled trials (RCTs). METHODS: A systematic literature search of PubMed, Embase and MEDLINE databases was carried out using the PRISMA framework to identify all RCTs comparing reconstruction techniques of gastrojejunostomy after PD, with overall DGE as the primary endpoint. The primary outcome measure was overall DGE. Secondary outcomes were grade B/C DGE, duration of nasogastric tube, time to solid food intake, overall and grade B/C pancreatic fistula, bile leaks, reoperation, length of hospital stay and in-hospital mortality. RESULTS: The search strategy identified eight RCTs including 761 patients. Six RCTs compared antecolic (n = 291 patients) and retrocolic Billroth II (n = 289 patients) reconstruction (n = 6 studies), and two RCTs compared antecolic Billroth II (n = 92 patients) and Roux-en-Y (n = 89 patients) reconstruction. Overall, antecolic Billroth II ranked best for overall and grade B/C DGE, bile leak, surgical site infection, length of stay and in-hospital mortality. Roux-en-Y was best for overall and grade B/C pancreatic fistula. CONCLUSION: Antecolic Billroth II gastroenteric reconstruction is associated with the lowest rates of delayed gastric emptying after PD amongst the currently available techniques of gastrojejunostomy reconstructions.

A systematic review and network meta-analysis of phase III randomised controlled trials for adjuvant therapy following resection of pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Several randomised controlled trials (RCTs) have reported various systemic adjuvant therapy regimens following resection of pancreatic ductal adenocarcinoma (PDAC). The most commonly applied include modified FOLFRINOX (mFFX), Gemcitabine/Capecitabine (GemCap) and S1, usually compared to gemcitabine (Gem) alone. However, many of these regimens have not been directly compared in RCTs. This network meta-analysis aims to characterise the impact of adjuvant therapies on overall and disease-free survival in patients having resection of PDAC. METHODS: A systematic review was conducted using MEDLINE, EMBASE, Cochrane Central and American Society of Clinical Oncology (ASCO) abstracts to identify published phase III RCTs articles up to 9th May 2019 that examined adjuvant systemic therapy in resected pancreatic cancer. Data including study characteristics and outcomes including overall survival (OS) and disease-free survival (DFS) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. RESULTS: Twelve phase III RCTs involving 4947 patients and nine different regimens (5-Flourouracil/Folinic acid (5-FU/FA), Gemcitabine, Gemcitabine/Erlotinib (GemErl), GemCap), mFFX, S1, chemoradiotherapy (CRT), CRT with either 5-FU or Gemcitabine) were identified. S1 was ranked best for overall and disease-free survival followed by mFFX. Whilst there were no significant difference between S1 and mFFX for overall survival (mean difference: 1.6 months, p = 0.8), S1 had significantly longer disease-free survival than mFFX (mean difference: 2.8 months, p < 0.001). Furthermore, S1 was ranked best for lowest overall and haematological grade 3/4 toxicities. CONCLUSION: This network meta-analysis demonstrates that chemotherapy with S1 or mFFX is superior to GemCap for adjuvant treatment for PDAC, improves survival after surgical resection and should be considered as reasonable standard treatment options in the adjuvant setting and as control arm for future adjuvant clinical trials.

Risk factors and outcomes associated with anastomotic leaks following esophagectomy: a systematic review and meta-analysis.

Anastomotic leaks (AL) are a major complication after esophagectomy. This meta-analysis aimed to determine identify risks factors for AL (preoperative, intra-operative, and post-operative factors) and assess the consequences to outcome on patients who developed an AL. This systematic review was performed according to PRISMA guidelines, and eligible studies were identified through a search of PubMed, Scopus, and Cochrane CENTRAL databases up to 31 December 2018. A meta-analysis was conducted with the use of random-effects modeling and prospectively registered with the PROSPERO database (Registration CRD42018130732). This review identified 174 studies reporting outcomes of 74,226 patients undergoing esophagectomy. The overall pooled AL rates were 11%, ranging from 0 to 49% in individual studies. Majority of studies were from Asia (n = 79). In pooled analyses, 23 factors were associated with AL (17 preoperative and six intraoperative). AL were associated with adverse outcomes including pulmonary (OR: 4.54, CI95%: 2.99-6.89, P < 0.001) and cardiac complications (OR: 2.44, CI95%: 1.77-3.37, P < 0.001), prolonged hospital stay (mean difference: 15 days, CI95%: 10-21 days, P < 0.001), and in-hospital mortality (OR: 5.91, CI95%: 1.41-24.79, P = 0.015). AL are a major complication following esophagectomy accounting for major morbidity and mortality. This meta-analysis identified modifiable risk factors for AL, which can be a target for interventions to reduce AL rates. Furthermore, identification of both modifiable and non-modifiable risk factors will facilitate risk stratification and prediction of AL enabling better perioperative planning, patient counseling, and informed consent.

A systematic review and network meta-analysis of different surgical approaches for pancreaticoduodenectomy.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a demanding surgical procedure, thus explaining its slow expansion and limited popularity amongst Hepato-Pancreatico-Biliary (HPB) surgeons. However, three main advantages of robotic assisted pancreaticoduodenectomy (PD) including improved dexterity, 3D vision less surgical fatigue, may overcome some of the hurdles and ultimately lead to a wider adoption. This systematic review and network meta-analysis aims to evaluate the current literature on open and MIPD. METHODS: A systematic literature search was conducted for studies reporting robotic, laparoscopic and open surgery for PD. Network meta-analysis of intraoperative (operating time, blood loss, transfusion rate), postoperative (overall and major complications, pancreatic fistula, delayed gastric emptying, length of hospital stay) and oncological outcomes (R0 resection, lymphadenectomy) were performed. RESULTS: Sixty-one studies including 62,529 patients were included in the network meta-analysis, of which 3% (n = 2131) were totally robotic (TR) and 10% (n = 6514) were totally laparoscopic (TL). There were no significant differences between surgical techniques for major complications, overall and grade B/C fistula, biliary leak, mortality and R0 resections. Transfusion rates were significantly lower in TR compared to TL and open. Operative time for TR was longer compared with open and TL. Both TL and TR were associated with significantly lower rates of wound infections, pulmonary complications, shorter length of stay and higher lymph nodes examined when compared to open. TR was associated with significantly lower conversion rates than TL. CONCLUSION: In summary, this network meta-analysis highlights the variability in techniques within MIPD and compares other variations to the conventional open PD. Current evidence appears to demonstrate MIPD, both laparoscopic and robotic techniques are associated with improved rates of surgical site infections, pulmonary complications, and a shorter hospital stay, with no compromise in oncological outcomes for cancer resections.

A systematic review and network meta-analysis of parenchymal transection techniques during hepatectomy: an appraisal of current randomised controlled trials.

BACKGROUND: Major liver resection can lead to significant morbidity and mortality. Blood loss is one of the most important factors predicting a good outcome. Although various transection methods have been reported, there is no consensus on the best technique. This systematic review and network meta-analysis aims to characterise and identify the best reported technique for elective parenchymal liver transection based on published randomised controlled trials (RCT's). METHODS: A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Central to identify RCT's up to 5th June 2019 that examined parenchymal transection for liver resection. Data including study characteristics and outcomes including intraoperative (blood loss, operating time) and postoperative measures (overall and major complications, bile leaks) were extracted. Indirect comparisons of all regimens were simultaneously compared using random-effects network meta-analyses (NMA) which maintains randomisation within trials. RESULTS: This study identified 22 RCT's involving 2360 patients reporting ten parenchymal transection techniques. Bipolar cautery has lower blood loss and shorter operating time than stapler (mean difference: 85 mL; 22min) and Tissue Link (mean difference: 66 mL; 29min). Bipolar cautery was ranked first for blood loss and operating time followed by stapler and TissueLink. Harmonic scalpel is associated with lower overall complications than Hydrojet (Odds ratio (OR): 0.48), BiClamp forceps (OR: 0.46) and clamp crushing (OR: 0.41). CONCLUSION: Bipolar cautery techniques appear to best at reducing blood loss and associated with shortest operating time. In contrast, Harmonic scalpel appears best for overall and major complications. Given the paucity of data and selective outcome reporting, it is still hard to identify what is the best technique for liver resection. Therefore, further high-quality large-scale RCT's are still needed.

The emerging roles of ribosomal histidyl hydroxylases in cell biology, physiology and disease.

Hydroxylation is a novel protein modification catalyzed by a family of oxygenases that depend on fundamental nutrients and metabolites for activity. Protein hydroxylases have been implicated in a variety of key cellular processes that play important roles in both normal homeostasis and pathogenesis. Here, in this review, we summarize the current literature on a highly conserved sub-family of oxygenases that catalyze protein histidyl hydroxylation. We discuss the evidence supporting the biochemical assignment of these emerging enzymes as ribosomal protein hydroxylases, and provide an overview of their role in immunology, bone development, and cancer.