The Role of Targeted Versus Standard Antibiotic Prophylaxis in Pancreatoduodenectomy in Reducing Postoperative Infectious Complications: A Systematic Review and Meta-analysis.

INTRODUCTION: Infectious complications are common after pancreatoduodenectomy, which in turn are associated with preoperative biliary drainage. Current guidelines recommend a first-generation cephalosporin as perioperative antibiotic prophylaxis. However, some studies support the use of targeted antibiotics. The aim of this systematic review and meta-analysis is to evaluate the role of prophylactic targeted antibiotics compared to standard antibiotics in reducing postoperative infections after pancreatoduodenectomy. METHODS: A search from MEDLINE, EMBASE, and Cochrane library from 1946 to July 2020 was conducted. Studies were included if they compared targeted antibiotics with standard perioperative antibiotics while including outcome data on surgical site infections (SSI). Targeted therapy was defined as perioperative antibiotics targeting organisms prevalent in bile instrumentation or by culture data obtained from the patient or institution. Outcomes assessed were the rate of SSIs and their microbiology profile. Analyses included demographic data, perioperative antibiotics, postoperative outcomes including microbiology data, and meta-analysis was performed where applicable. RESULTS: Seven studies were included, with a total of 849 patients undergoing pancreatoduodenectomy. Targeted antibiotics were associated with a significantly lower rate of postoperative SSI compared to standard antibiotic therapy [21.1% vs 41.9%; risk ratios (RR) 0.55, 95% confidence interval 0.37-0.81]. Wound/incisional site infections and organ space infections were lower in patients receiving targeted antibiotic prophylaxis (RR 0.33, P = 0.0002 and RR 0.54, P = 0.0004, respectively). Enterococcus species were the most common bacteria reported. CONCLUSION: There was a significant reduction in overall SSI rates when targeted antibiotics was used. Current standard antibiotic prophylaxis is inadequate in covering microbes prevalent in postoperative infections developing after pancreatoduodenectomy.

Pancreatectomy is underused in NSW regions with low institutional surgical volumes: a population data linkage study.

OBJECTIVE: To examine differences in the proportions of people diagnosed with pancreatic cancer who underwent pancreatectomy, post-operative outcomes and 5-year survival in different New South Wales administrative health regions of residence. DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of NSW data on pancreatic cancer incidence and surgery, 2005-2013. MAIN OUTCOME MEASURES: The proportion of newly diagnosed patients with pancreatic cancer who were resected in each region; 90-day post-operative mortality; one-year post-operative survival; 5-year post-diagnosis survival. RESULTS: 14% of people diagnosed with pancreatic cancer during 2010-2013 (431 of 3064) underwent pancreatectomy, an average of 108 resections per year. After adjusting for age, sex and comorbidities, the proportion that underwent resection varied significantly between regions, ranging between 8% and 21% (P<0.001). Higher resection rates were not associated with higher post-operative 90-day mortality or lower one-year survival (unadjusted and risk-adjusted analyses). Higher resection rates were associated with higher 5-year post-diagnosis survival: the mean survival in regions with resection rates below 10% was 3.4%, compared with 7.2% in regions with rates greater than 15% (unadjusted and adjusted survival analyses; P<0.001). There was a positive association between regional resection rate and the pancreatectomy volume of hospitals during 2005-2009. An additional 32 people would be resected annually if resection rates in low rate regions were increased to the 80th percentile regional resection rate (18%). CONCLUSION: There is significant geographic variation in the proportion of people with pancreatic cancer undergoing pancreatectomy, and the 5-year survival rate is higher in regions where this proportion is higher.

Patient Selection for Oesophagectomy: Impact of Age and Comorbidities on Outcome.

INTRODUCTION: Surgical resection of oesophageal cancer is a major procedure with potential for significant morbidity and mortality. Patient selection can be challenging, as operative benefit must be balanced against risk and impact on quality of life. This study defines modern trends in patient selection, and evaluates the impact of age, stage, and comorbidities on complications and survival following oesophagectomy, in a tertiary Australian experience. METHODS: Data were compiled across two 15-year operative eras ('Era 1': 1981-1995; and 'Era 2': 1996-2010), with patients followed minimum 3 years. A total of 180 unselected records were analysed (powered for a relative hazard ratio of 0.5). Analyses defined patient selection trends, and for Era 2, the impact of age, comorbidities (Charlson score), and disease (T/N stage) on complications (Clavien-Dindo grade) and survival (Kaplan-Meier). A further sub-analysis was conducted with data divided into three 10-year periods. RESULTS: The age of operated patients increased from Era 1 to 2 (mean+5 years; P<0.001), but survival and complication rates were unchanged, including in patients≥75 years (P>0.5). In Era 2, reflecting recent practice, survival duration matched T/N stage (P<0.001) but was independent of age at surgery (P=0.56) and comorbidity score (P=0.78). However, grade of worst post-operative complication, including death (rate: 3.8%), was correlated with both age (P<0.01) and comorbidity score (P<0.01). DISCUSSION: Older patients are now undergoing oesophagectomy. However, if they are selected appropriately, then older patients and those with comorbidities can expect similar stage-matched survival outcomes to younger fitter patients, despite their higher operative risk. Poor outcomes persist in patients with locally advanced disease, and selection in this group should prioritise quality of life.

Use of pre-operative steroids in liver resection: a systematic review and meta-analysis.

BACKGROUND: By attenuating the systemic inflammatory response to major surgery, the pre-operative administration of steroids may reduce the incidence of complications. METHODS: A systematic review was conducted to identify randomized controlled trials (RCT) comparing pre-operative steroid administration with placebo during a liver resection. Meta-analyses were performed. RESULTS: Five RCTs were identified including a total of 379 patients. Pre-operative steroids were associated with statistically significant reductions in the levels of serum bilirubin and interleukin 6 (IL-6) on post-operative day one. There was a trend towards a lower incidence of post-operative complications and prothrombin time (PT), but this did not reach statistical significance. CONCLUSION: Pre-operative steroids may be associated with a clinically significant benefit in liver resection.

A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases.

BACKGROUND: Since the liver metastases rather than the colorectal cancer itself is the main determinant of patient's survival, the 'Liver-First Approach (LFA)' with upfront chemotherapy followed by a hepatic resection of colorectal liver metastases (CLM) and finally a colorectal cancer resection was proposed. The aim of this review was to analyse the evidence for LFA in patients with colorectal cancer and synchronous CLM. METHODS: A literature search of databases (MEDLINE and EMBASE) to identify published studies of LFA in patients with colorectal cancer and synchronous CLM was undertaken focussing on the peri-operative regimens of LFA and survival outcomes. RESULTS: Three observational studies and one retrospective cohort study were included for review. A total of 121 patients with colorectal cancer and synchronous CLM were selected for LFA. Pre-operative chemotherapy was used in 99% of patients. One hundred and twelve of the initial 121 patients (93%) underwent a hepatic resection of CLM. In total, 60% had a major liver resection and the R0 resection rate was 93%. Post-operative morbidity and mortality after the hepatic resection were 20% and 1%, respectively. Ultimately, 89 of the initial 121 (74%) patients underwent a colorectal cancer resection. Post-operative morbidity and mortality after a colorectal resection were 50% and 6%, respectively. The median overall survival was 40 months (range 19-50) with a recurrence rate of 52%. CONCLUSIONS: Current evidence suggests that LFA is safe and feasible in selected patients with colorectal cancer and synchronous CLM. Future studies are required to further define patient selection criteria for LFA and the exact role of LFA in the management of synchronous CLM.

Hypothermic machine perfusion in deceased donor kidney transplantation: a systematic review.

BACKGROUND: Hypothermic machine perfusion (HMP) of kidneys is intended to mitigate the deleterious effects of cold storage on organ quality, particularly when the cold ischemic time is prolonged or the donor is otherwise marginal. The use of HMP has remained controversial; however, a number of randomized controlled trials (RCTs) have recently been conducted to clarify its benefits. METHODS: We undertook a systematic search of the Medline and Embase databases and of the Cochrane Central Register of Controlled Trials. We included only RCTs in the meta-analysis. Outcomes analyzed were the incidence of delayed graft function (DGF), primary nonfunction (PNF), graft loss, and patient death at 1 y. RESULTS: We identified seven RCT trials and subjected them to meta-analysis, including 1353 kidney transplant recipients. Hypothermic machine perfusion significantly reduced the incidence of DGF (risk ratio [RR] 0.83, 95% confidence interval [CI] 0.72-0.96). There was no difference in the incidence of PNF (RR 0.78, 95% CI 0.36-1.68), graft loss at 1 y (RR 0.87, 95% CI 0.64-1.19), and patient death at 1 y (RR 0.91, 95% CI 0.60-1.37) between HMP and donor kidneys preserved using cold storage. CONCLUSIONS: There are few RCT comparing HMP and cold storage of kidneys in deceased donor kidney transplantation. Although these studies are small and heterogeneous in design, HMP appeared to be associated with a reduced incidence of DGF. No difference in the incidence of PNF, graft loss, or patient death at 1 y could be demonstrated.

Transarterial chemoembolization with irinotecan beads in the treatment of colorectal liver metastases: systematic review.

PURPOSE: For patients with unresectable colorectal liver metastasis (CRLM), transarterial embolization with the use of drug-eluting beads with irinotecan (DEBIRI) represents a novel alternative to systemic chemotherapy or local treatments alone. The present systematic review evaluates available data on the efficacy and safety of DEBIRI embolization. MATERIALS AND METHODS: A comprehensive search of medical literature identified studies describing the use of DEBIRI in the treatment of CRLM. Data describing adverse events, pharmacokinetics, tumor response, and overall survival were collected. RESULTS: Five observational studies and one randomized controlled trial (RCT) were reviewed. A total of 235 patients were included in the descriptive analysis of observational studies. Postembolization syndrome was the most common adverse event. Peak plasma levels of irinotecan were observed at 1-2 hours after administration. Wide variations in tumor response were observed. The median survival time ranged from 15.2 months to 25 months. In the RCT, treatment with DEBIRI was superior to systemic chemotherapy with 5-fluorouracil/leucovorin/irinotecan in terms of quality of life and progression-free survival. CONCLUSIONS: For patients with unresectable CRLM, particularly after failure to respond to first-line regimens, DEBIRI represents a novel alternative to systemic chemotherapy alone, transarterial embolization with other agents, or other local treatments (eg, microwave or radiofrequency ablation). In these reports, DEBIRI was safe and effective in the in the treatment of unresectable CRLM. Further RCTs comparing DEBIRI with alternative management strategies are required to define the optimal role for this treatment.

A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases.

OBJECTIVES: Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable using the two-stage hepatectomy (TSH) approach. This review was conducted with the aim of collating and evaluating published evidence for TSH in patients with initially unresectable CLM. METHODS: Searches of the MEDLINE and EMBASE databases were undertaken to identify studies of TSH in patients with initially unresectable CLM. Studies were required to focus on the perioperative treatment regimen, operative strategy, morbidity, technical success and survival outcomes. RESULTS: Ten observational studies were reviewed. A total of 459 patients with initially unresectable CLM were selected for the first stage of TSH. Preoperative chemotherapy was used in 88% of patients and achieved partial and stable response rates of 59% and 39%, respectively. Postoperative morbidity and mortality after the first stage of TSH were 17% and 0.5%, respectively. Portal vein embolization (PVE) was used in 76% of patients. Ultimately, 352 of the initial 459 (77%) patients underwent the second stage of TSH. Major liver resection was undertaken in 84% of patients; the negative margin (R0) resection rate was 75%. Postoperative morbidity and mortality after the second stage of TSH were 40% and 3%, respectively. Median overall survival was 37 months (range: 24-44 months) in patients who completed both stages of TSH. In patients who did not complete both stages of TSH, median survival was 16 months (range: 10-29 months). The 3-year disease-free survival rate was 20% (range: 6-27%). CONCLUSIONS: Two-stage hepatectomy is safe and effective in selected patients with initially unresectable CLM. Further studies are required to better define patient selection criteria for TSH and the exact roles of PVE and preoperative and interval chemotherapy.

A systematic review of clinical response and survival outcomes of downsizing systemic chemotherapy and rescue liver surgery in patients with initially unresectable colorectal liver metastases.

BACKGROUND: Selected patients with unresectable colorectal liver metastases (CLM) may be rendered resectable after systemic chemotherapy. We reviewed the evidence of downsizing systemic chemotherapy followed by rescue liver surgery in patients with initially unresectable CLM. METHODS: Literature search of databases (Medline and PubMed) to identify published studies of neoadjuvant chemotherapy followed by liver resection in patients with initially unresectable CLM was undertaken and focused on response rate of chemotherapy and survival outcomes. RESULTS: Ten observational studies were reviewed. A total of 1,886 patients with initially unresectable CLM underwent systemic chemotherapy. An objective response was observed in 64% (range, 43-79%) of patients after systemic chemotherapy. Of these, 22.5% underwent macroscopically curative liver resection. Median overall survival was 45 (range, 36-60) months with 19% of patients alive and recurrence-free. CONCLUSIONS: Current evidence suggests that downsizing systematic chemotherapy followed by rescue liver resection is safe and effective for selected patients with initially unresectable CLM. Further studies are required to examine response rates and secondary resectability using new targeted molecular therapy-based regimens.

Portal triad clamping versus other methods of vascular control in liver resection: a systematic review and meta-analysis.

BACKGROUND: Portal triad clamping (PTC) is the most commonly used method of achieving vascular control during liver resection. However, the efficacy and safety of PTC, compared with those of other methods of vascular control, are uncertain. METHODS: A systematic review was conducted to identify randomized controlled trials (RCTs) comparing PTC with other methods of vascular control during liver resection. Endpoints included in-hospital mortality, need for transfusion, number of complications and length of hospital stay. Meta-analyses were performed using a random-effects model. RESULTS: Ten RCTs were identified; these included a total of 820 patients. No statistically significant differences between PTC and other forms of vascular control in liver resection were demonstrated. CONCLUSIONS: There is no evidence, on the basis of this meta-analysis of RCTs, of any difference between PTC and other forms of vascular control in liver resection.

Laparoscopic or open cholecystectomy in cirrhosis: a systematic review of outcomes and meta-analysis of randomized trials.

BACKGROUND: Cholecystectomy is associated with increased risks in patients with cirrhosis. The well-established advantages of laparoscopic surgery may be offset by the increased risk for complications relating particularly to portal hypertension and coagulopathy. METHODS: A systematic search was undertaken to identify studies comparing open cholecystectomy (OC) and laparoscopic cholecystectomy (LC) in patients with cirrhosis. A meta-analysis was performed of the available randomized controlled trials (RCTs). RESULTS: Forty-four studies were analysed. These included a total of 2005 patients with cirrhosis who underwent laparoscopic (n= 1756) or open (n= 249) cholecystectomy, with mortality rates of 0.74% and 2.00%, respectively. A meta-analysis of three RCTs involving a total of 220 patients was conducted. There was a reduction in the overall incidences of postoperative complications and infectious complications and a shorter length of hospital stay in LC. However, frequencies of postoperative hepatic insufficiency did not differ significantly. CONCLUSIONS: There are few RCTs comparing OC and LC in patients with cirrhosis. These studies are small, heterogeneous in design and include almost exclusively patients with Child-Pugh class A and B disease. However, LC appears to be associated with shorter operative time, reduced complication rates and reduced length of hospital stay.

Systematic review of actual 10-year survival following resection for hepatocellular carcinoma.

BACKGROUND: Hepatic resection is a potentially curative therapy for hepatocellular carcinoma (HCC), but recurrence of disease is very common. Few studies have reported 10-year actual survival rates following hepatic resection; instead, most have used actuarial measures based on the Kaplan-Meier method. This systematic review aims to document 10-year actual survival rates and to identify factors significant in determining prognosis. METHODS: A comprehensive search was undertaken of MEDLINE and EMBASE. Only studies reporting the absolute number of patients alive at 10 years after first resection for HCC were included; these figures were used to calculate the actual 10-year survival rate. A qualitative review and analysis of the prognostic factors identified in the included studies were performed. RESULTS: Fourteen studies, all of which were retrospective case series, including data on 4197 patients with HCC were analysed. Ten years following resection, 303 of these patients were alive. The 10-year actual survival rate was 7.2%, whereas the actuarial survival quoted from the same studies was 26.8%. Positive prognostic factors included better hepatic function, a wider surgical margin and the absence of satellite lesions. CONCLUSIONS: The actual long-term survival rate after resection of HCC is significantly inferior to reported actuarial survival rates. The Kaplan-Meier method of actuarial survival analysis tends to overestimate survival outcomes as a result of censorship of data and subgroup analysis.

Endoscopic necrosectomy of pancreatic necrosis: a systematic review.

AIM: To review the current status of the novel technique of endoscopic necrosectomy in the management of pancreatic necrosis after acute pancreatitis. METHODS: Studies were identified by searching Medline, PubMed and Embase databases for articles from January 1990 to December 2009 using the keywords "acute pancreatitis", "pancreatic necrosis" and "endoscopy". Additional papers were identified by a manual search of the references from the key articles. Case series of fewer than five patients and case reports were excluded. RESULTS: Indications, techniques and outcomes of endoscopic necrosectomy were analysed. There were no randomised controlled trials identified. Ten case series were included in this analysis. There were a total of more than 1,100 endoscopic necrosectomy procedures in 260 patients with pancreatic necrosis. One hundred fifty-five were proven to be infected necrosis on culture. The overall mortality rate was 5%. The mean procedure-related morbidity rate was 27%. The rate of complete resolution of pancreatic necrosis with the endoscopic method alone was 76%. CONCLUSIONS: Endoscopic necrosectomy is a safe and effective treatment option in selected patients with pancreatic necrosis after acute pancreatitis. Future studies will be required to further define the selection criteria and the techniques for the endoscopic procedure.

Management of Boerhaave syndrome in Australasia: a retrospective case series and systematic review of the Australasian literature.

BACKGROUND: Boerhaave syndrome is a rare and life-threatening condition characterized by a spontaneous transmural tear of the oesophagus. There remains wide variation in the condition's management with non-operative management (NOM) and surgery being the two main treatment strategies. The aim was to review the presentation, management and outcomes for patients treated for Boerhaave syndrome at our institution and to compare these data with that previously reported within the Australasian literature. METHODS: A retrospective case series was performed for consecutive patients diagnosed with Boerhaave syndrome at our institution between January 2000 and January 2020. A systematic review of the Australasian literature was also performed. RESULTS: In case series, 15 patients were included (n = 2 NOM, n = 13 operative). The most common operative technique was primary repair with intercostal drainage via thoracotomy. Major complications occurred in 11 (73%) patients. Median Comprehensive Complication Index was 53.4 (interquartile range: 50). There was a significantly lower Comprehensive Complication Index associated with primary repair when compared to oesophageal resection (P = 0.01). There was one death, in the operative management group. Median length of hospital stay was 33 days (interquartile range: 58). In systematic review, 11 articles were included; four case series and seven case reports. From these, 23 patients met inclusion criteria. The majority of patients (83%) were managed operatively, with only four undergoing NOM. Seven patients died, representing an overall mortality rate of 30%. CONCLUSIONS: We provide an updated overview of the management of Boerhaave syndrome within Australasia. Aggressive operative management is associated with reasonable outcomes.

Day-only elective cholecystectomy: early experience and barriers to implementation in Australia.

BACKGROUND: Day-only laparoscopic cholecystectomy (DOLC) has been shown to be safe and feasible yet has not been widely implemented in Australia. This study explores the introduction of routine DOLC to Westmead Hospital, and highlights the barriers to its implementation. METHODS: Routine day-only cholecystectomy protocol was introduced at Westmead Hospital in 2014. A retrospective review of patients who underwent elective laparoscopic cholecystectomy during a 12-month period in 2014 was compared to a 12-month period in 2018, to examine the changes in practice after implementation of a unit protocol. Data were collected on patient demographics, admission category, outcomes and re-presentations. RESULTS: A total of 282 patients were included in the study, of these 169 were booked as day procedures, with 124 (73%) successfully discharged on the same day. There was a significant increase in the proportion of patients booked as day-only from 2014 to 2018 (48% versus 73%, P < 0.001). Day-only failure rates (unplanned overnight admissions), readmissions and complication rates were comparable between the two periods. The most common reason for unplanned overnight admissions were due to intraoperative findings (n = 28/45). CONCLUSION: Routine DOLC can be adopted in Australian hospitals without compromise to patient safety. Unplanned overnight admission is predominantly due to unexpected surgical pathology and can be reduced by protocols for the use of drains and planned outpatient endoscopic retrograde cholangiopancreatography. Unplanned outpatient review can be minimized by optimizing both intra- and post-operative pain management. Individual surgeon and anaesthetist preferences remain an obstacle to a standardized protocol in the Australian setting.

Quality improvement in surgery: introduction of the American College of Surgeons National Surgical Quality Improvement Program into New South Wales.

BACKGROUND: Quality improvement in surgery requires accurate, reliable, risk-adjusted and comparative data. The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) takes reliable clinical data and provides risk-adjusted comparisons with more than 800 hospitals. This paper describes the early outcomes of introducing this programme into New South Wales (NSW). METHODS: Four NSW hospitals formed a collaborative. Surgical clinical reviewers were trained and data collected. Risk-adjusted reports were returned to individual hospitals and the NSW Collaborative. RESULTS: The results identified that the NSW Collaborative were outliers for the following causes of morbidity: urinary tract infections, surgical site infections, pneumonia and 30-day readmissions. CONCLUSION: We have shown that ACS-NSQIP can be adapted to Australia and there is a plan to widen the programme in NSW.

Association of Mechanical Bowel Preparation and Oral Antibiotics Before Elective Colorectal Surgery With Surgical Site Infection: A Network Meta-analysis.

Importance: There has been a resurgence of interest in the use of mechanical bowel preparation (MBP) and oral antibiotics (OAB) before elective colorectal surgery. Until now, clinical trials and meta-analyses have not compared all 4 approaches (MBP with OAB, OAB only, MBP only, or no preparation) simultaneously. Objective: To perform a network meta-analysis to clarify which approach in colorectal surgery is associated with the lowest rate of surgical site infection (SSI). Data Sources: Five electronic databases were searched, including PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, ACP Journal Club. and Database of Abstracts of Review of Effectiveness from database inception to November 27, 2017. Study Selection: Only data from randomized clinical trials were included. Inclusion criteria were RCTs that reported on SSI rates or other complications based on MBP or OAB status. Quality of studies was appraised by the Cochrane Collaboration risk of bias tool. Data Extraction and Synthesis: The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Main Outcomes and Measures: Total, incisional, and organ/space SSI rates. Secondary outcomes included rates of anastomotic leak, mortality, readmissions/reoperations, urinary tract infection, and pulmonary complications. Results: Thirty-eight randomized clinical trials among 8458 patients (52.1% male) were included, providing 4 direct comparisons and 2 indirect comparisons for 8 outcome measures. On Bayesian analysis, MBP with OAB vs MBP only was associated with reduced SSI (odds ratio [OR], 0.71; 95% equal-tail credible interval [CrI], 0.57-0.88). There was no significant difference between MBP with OAB vs OAB only (OR, 0.95; 95% CrI, 0.56-1.62). Oral antibiotics without MBP was not associated with a statistically significant reduction in SSI compared with any other group (except for a risk reduction in organ/space SSI when indirectly compared with no preparation) (OR, 0.13; 95% CrI, 0.02-0.55). There was no difference in SSI between MBP only vs no preparation (OR, 0.84; 95% CrI, 0.69-1.02). Conclusions and Relevance: In this network meta-analysis of randomized clinical trials, MBP with OAB was associated with the lowest risk of SSI. Oral antibiotics only was ranked as second best, but the data available on this approach were limited. There was no difference between MBP only vs no preparation. In addition, there was no difference in rates of anastomotic leak, readmissions, or reoperations between any groups.