The Continuing Problem of Expert Evidence in Medical Litigation - A Surgical Perspective with Reference to Daubert.

The tension that exists between the medical and legal professions regarding expert evidence is longstanding. In this article, we will examine some of the issues regarding expert evidence particularly as it relates to matters involving surgeons. Many of the current aspects of the Australian uniform evidence law in relation to expert testimony were based on the Federal Rules of Evidence promulgated in the United States in 1975. We will discuss some of the problems of expert evidence in surgical matters, particularly in New South Wales, and offer some thoughts on how the so-called Daubert trilogy could form a basis on which to re-examine the concept of an "expert". Our analysis offers suggestions for further improvements to the process of adducing expert evidence in claims involving surgical matters.

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.

Attitudes towards Enhanced Recovery after Surgery (ERAS) interventions in colorectal surgery: nationwide survey of Australia and New Zealand colorectal surgeons.

BACKGROUND: Whilst Enhanced Recovery after Surgery (ERAS) has been widely accepted in the international colorectal surgery community, there remains significant variations in ERAS programme implementations, compliance rates and best practice recommendations in international guidelines. METHODS: A questionnaire was distributed to colorectal surgeons from Australia and New Zealand after ethics approval. It evaluated specialist attitudes towards the effectiveness of specific ERAS interventions in improving short term outcomes after colorectal surgery. The data were analysed using a rating scale and graded response model in item response theory (IRT) on Stata MP, version 15 (StataCorp LP, College Station, TX). RESULTS: Of 300 colorectal surgeons, 95 (31.7%) participated in the survey. Of eighteen ERAS interventions, this study identified eight strategies as most effective in improving ERAS programmes alongside early oral feeding and mobilisation. These included pre-operative iron infusion for anaemic patients (IRT score = 7.82 [95% CI: 6.01-9.16]), minimally invasive surgery (IRT score = 7.77 [95% CI: 5.96-9.07]), early in-dwelling catheter removal (IRT score = 7.69 [95% CI: 5.83-9.01]), pre-operative smoking cessation (IRT score = 7.68 [95% CI: 5.49-9.18]), pre-operative counselling (IRT score = 7.44 [95% CI: 5.58-8.88]), avoiding drains in colon surgery (IRT score = 7.37 [95% CI: 5.17-8.95]), avoiding nasogastric tubes (IRT score = 7.29 [95% CI: 5.32-8.8]) and early drain removal in rectal surgery (IRT score = 5.64 [95% CI: 3.49-7.66]). CONCLUSIONS: This survey has demonstrated the current attitudes of colorectal surgeons from Australia and New Zealand regarding ERAS interventions. Eight of the interventions assessed in this study including pre-operative iron infusion for anaemic patients, minimally invasive surgery, early in-dwelling catheter removal, pre-operative smoking cessation, pre-operative counselling, avoidance of drains in colon surgery, avoiding nasogastric tubes and early drain removal in rectal surgery should be considered an important part of colorectal ERAS programmes.

Bile Duct Injuries as a Result of Cholecystectomy: An Australian Perspective.

Cholecystectomy remains the mainstay treatment for symptomatic gallstones. Despite the evolution of surgical techniques and approaches, bile duct injury represents a significant complication, even in experienced hands. It is associated with significant postoperative morbidity, resource utilisation and costs. Compared to the international data, there is a paucity of data on malpractice cases involving bile duct injuries (BDIs) proceeding to definitive judgment and defence. This article examines the surgical literature and the case law in Australia as it relates to BDIs following cholecystectomy. This article aims to discuss the issues surrounding major bile duct injury litigation and compares the Australian perspective with international experience.

The role of mechanical bowel preparation and oral antibiotics for left-sided laparoscopic and open elective restorative colorectal surgery with and without faecal diversion.

BACKGROUND: There is significant variation in the use of mechanical bowel preparation and oral antibiotics prior to left-sided elective colorectal surgery. There has been no consensus internationally. METHODS: This was a retrospective analysis of the 2015 American College of Surgeons National Surgical Quality Improvement Program database. Patients were divided into four groups: those who had mechanical bowel preparation with oral antibiotics, mechanical bowel preparation alone, oral antibiotics alone and no preparation. The main outcome measures included overall, superficial, deep and organ/space surgical site infections. Secondary outcomes included anastomotic leak, ileus and rate of Clostridium difficile. RESULTS: A total of 5729 patients were included for analysis. The overall surgical site infection rate (any superficial, deep or organ/space infection) was significantly lower in the mechanical bowel preparation and oral antibiotics approach when compared to no preparation (OR = 0.46, 95% CI 0.36-0.59, P < 0.0001). On multivariable logistic regression analysis, mechanical bowel preparation with oral antibiotics maintained a lower risk of overall surgical site infections. MBP and OAB also had a protective effect on anastomotic leak in both the laparoscopic and open cohorts (laparoscopic multivariable adjusted OR = 0.42 (0.19-0.94), P = 0.035; open multivariable adjusted OR = 0.3 (0.12-0.77), P = 0.012). Mechanical bowel preparation alone and oral antibiotics alone was not associated with a significant decrease in surgical site infections. There was no increase in C. difficile occurrences with the use of oral antibiotics. CONCLUSION: Mechanical bowel preparation with oral antibiotics significantly minimised surgical site infections and anastomotic leak following both laparoscopic and open left-sided restorative colorectal surgery. Mechanical bowel preparation alone did not reduce surgical site infections. There was a trend to reduction in surgical site infections with oral antibiotics alone.

Endoscopic resection of large duodenal and papillary lateral spreading lesions is clinically and economically advantageous compared with surgery.

Background and study aims Adenomas of the duodenum and ampulla are uncommon. For lesions ≤ 20 mm in size and confined to the papillary mound, endoscopic resection is well supported by systematic study. However, for large laterally spreading lesions of the duodenum or papilla (LSL-D/P), surgery is often performed despite substantial associated morbidity and mortality. We aimed to compare actual endoscopic outcomes of such lesions and costs with those predicted for surgery using validated prediction tools. Patients and methods Patients who underwent endoscopic resection of LSL-D/P were analyzed. Two surgeons assigned the hypothetical surgical management. The National Surgical Quality Improvement Program (NSQIP), and the Portsmouth Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (P-POSSUM) were used to predict morbidity, mortality, and length of hospital stay. Actual endoscopic and hypothetical surgical outcomes and costs were compared. Results A total of 102 lesions were evaluated (mean age of patients 69 years, 52 % male, mean lesion size 40 mm). Complete endoscopic resection was achieved in 93.1 % at the index procedure. Endoscopic adverse events occurred in 18.6 %. Recurrence at first surveillance endoscopy was seen in 17.7 %. For patients with ≥ 2 surveillance endoscopies (n = 55), 90 % were clear of disease and considered cured (median follow-up 27 months). Compared with hypothetical surgical resection, endoscopic resection had less morbidity (18 % vs. 31 %; P = 0.001) and shorter hospital stay (median 1 vs. 4.75 days; P < 0.001), and was less costly than surgery (mean $ 11 093 vs. $ 19 358; P < 0.001). Conclusion In experienced centers, even extensive LSL-D/P can be managed endoscopically with favorable morbidity and mortality profiles, and reduced costs, compared with surgery.

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.

The Abdominal Reapproximation Anchor Device.

INTRODUCTION: Achieving primary fascial closure after damage control laparostomy can be challenging. A number of devices are in use, with none having yet emerged as best practice. In July 2013, at Westmead Hospital, we started using the abdominal reapproximation anchor (ABRA; Canica Design, Almonte, Ontario, Canada) device. We report on our experience. METHODS: A retrospective review of medical records for patients who had open abdomens managed with the ABRA device between July to December 2013 was done. Data extracted included age, sex, body mass index (BMI), reason for the open abdomen, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, number of laparostomies prior to ABRA placement, duration of placement, device complications, length of hospital and intensive care unit (ICU) stay, and outcomes. RESULTS: Four cases of open abdomens managed using the ABRA device were identified, with 3 a consequence of intra-abdominal sepsis and 1 a consequence of penetrating trauma. Mean BMI was 33.5 kg/m2, APACHE II score was 14.5, duration with open abdomen prior to ABRA placement was 11.75 days, duration with ABRA in situ was 9 days, duration of hospital stay was 64.25 days, and ICU stay was 37.75 days. Three patients (75%) achieved fascial closure, and 1 achieved skin closure. No incidences of enterocutaneous fistulae occurred. CONCLUSION: The ABRA is a unique emerging alternative to aid in achieving fascial closure in patients managed with open abdomens. Our case series demonstrates that it can be used effectively in selected patients. Studies are needed to compare its efficacy with more traditional methods.

Percutaneous vs. endoscopic pre-operative biliary drainage in hilar cholangiocarcinoma - a systematic review and meta-analysis.

BACKGROUND: The strategy for preoperative management of biliary obstruction in hilar cholangiocarcinoma (HCCA) patients with regards to drainage by endoscopic (EBD) or percutaneous (PTBD) methods is not clearly defined. The aim of this study was to investigate the utility, complications and therapeutic efficacy of these methods in HCCA patients, with a secondary aim to assess the use of portal vein embolization (PVE) in patients undergoing drainage. METHODS: Studies incorporating HCCA patients undergoing biliary drainage prior to curative resection were included (EMBASE and Medline databases). Analyses included baseline drainage data, procedure-related complications and efficacy, post-operative parameters, and meta-analyses where applicable. RESULTS: Fifteen studies were included, with EBD performed in 536 patients (52%). Unilateral drainage of the future liver remnant was undertaken in 94% of patients. There was a trend towards higher procedure conversion (RR 7.36, p = 0.07) and cholangitis (RR 3.36, p = 0.15) rates in the EBD group. Where specified, 134 (30%) drained patients had PVE, in association with a major hepatectomy in 131 patients (98%). Post-operative hepatic failure occurred in 22 (11%) of EBD patients compared to 56 (13%) of PTBD patients, whilst median 1-year survival in these groups was 91% and 73%, respectively. DISCUSSION: The accepted practice is for most jaundiced HCCA patients to have preoperative drainage of the future liver remnant. EBD may be associated with more immediate procedure-related complications, although it is certainly not inferior compared to PTBD in the long term.

Improving Outcomes in Adrenocortical Cancer: An Australian Perspective.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignancy that carries a poor prognosis. There has yet to be a large Australian series that documents the characteristics of ACC and there are a paucity of data on management and the long-term outcomes. We sought to provide a unique insight into the management of ACC in Australia as well as to identify factors associated with prognosis and survival. METHODS: A multivariate analysis of a cohort of patients identified with ACC between 1998 and 2013 was undertaken. Recurrence-free survival (RFS) and overall survival (OS) were assessed as the main outcome measures and correlated with multiple clinical variables in order to identify prognostic markers. RESULTS: Of the 104 patients identified, a total of 98 patients with complete clinical and outcome data were included in the study. Median OS was 56 months, with the 5-year survival being 48 % (95 % confidence interval 36-59). On multivariate analysis, age ≥50 years, metastases at presentation, and evidence of extra-adrenal invasion were found to be statistically associated with reduced OS. RFS was analyzed in patients without metastases. On multivariate analysis, extra-adrenal invasion and no preoperative endocrine investigations were found to be statistically significant poor prognostic factors, with a non-significant trend for higher individual surgeon volume to be associated with improved resection margins and RFS. CONCLUSIONS: We present clinical outcomes and prognostic factors for patients with ACC in a landmark Australian series. We suggest that management in a specialized tertiary endocrine and/or surgical oncology unit is more likely to lead to improved outcomes.

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.

Association between volume and cost in low-resection volume regions: a population-level study on pancreatoduodenectomy for pancreatic cancer patients.

BACKGROUND: Pancreatoduodenectomy (PD) is a highly complex, invasive, and costly surgical procedure. Limited evidence on the PD volume-cost relationship in countries with a low population density exists. This study aimed to investigate this issue in Australia. METHODS: This retrospective cohort study included pancreatic cancer patients who had a PD at any public hospital in New South Wales, Australia between 2016 and 2019. The primary outcome was the total hospital cost during PD admission (not including patient financial burden). Study hospitals were grouped into low-volume hospitals (LVHs; <10 PDs per annum) or high-volume hospitals (HVHs). Multivariable modelling was applied to examine the association between volume and cost. RESULTS: Of 443 PDs, the median total hospital cost per patient at HVHs was AU$55398; significantly lower than that at LVHs (AU$62859; P = 0.001). After adjusting for available patient and clinical factors, the total cost per patient at LVHs was 22% higher than that of HVHs (adjusted estimate: 1.22, 95% CI: 1.08-1.37; P = 0.002). Similar patterns were found in three main cost components: 24% higher employee cost at LVHs than at HVHs (1.24, 95% CI: 1.10-1.41; P < 0.001), 15% higher operating cost (1.15, 95% CI: 1.00-1.31; P = 0.047), and 31% higher other costs (1.31, 95% CI: 1.12-1.53; P < 0.001). CONCLUSION: Performance of PDs at HVHs was associated with substantially lower hospital costs. Our findings demonstrate the likely economic benefit of centralizing PDs in countries with a relatively low population density. Future studies should investigate related patient financial burdens.

Failure to rescue following oesophagectomy in Australia: a multi-site retrospective study using American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Failure to rescue (FTR), defined as death after a major complication, is increasingly being used as a surrogate for assessing quality of care following major cancer resection. The aim of this paper is to determine the failure to rescue (FTR) rate after oesophagectomy and explore factors that may contribute to FTR within Australia. METHODS: A retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2015 to 2023 at five Australian hospitals was conducted to identify patients who underwent an oesophagectomy. The primary outcome was FTR rate. Perioperative parameters were examined to evaluate predictive factors for FTR. Secondary outcomes include major complications, overall morbidity, mortality, length of stay and 30-day readmissions. RESULTS: A total of 155 patients were included with a median age of 65.2 years, 74.8% being male. The FTR rate was 6.3%. In total, 50.3% of patients (n = 78) developed at least one postoperative complication with the most common complication being pneumonia (20.6%) followed by prolonged intubation (12.9%) and organ space SSI/anastomotic leak (11.0%). Multivariate logistic regression analysis was performed to determine any factors that were predictive for FTR however none reached statistical significance. CONCLUSION: This study is the first to evaluate the FTR rates following oesophagectomy within Australia, with FTR rates and complication profile comparable to international benchmarks. Integration of multi-institutional national databases such as ACS NSQIP into units is essential to monitor and compare patient outcomes following major cancer surgery, especially in low to moderate volume centres.

Multidisciplinary protocol to reduce surgical readmissions in Australia: American College of Surgeons National Surgical Quality Improvement Program.

INTRODUCTION: Unplanned readmissions in general surgery are an important quality indicator of patient care and are associated with increased costs to healthcare services. This study aims to implement a multidisciplinary protocol in a single institution in a tertiary referral hospital to monitor and reduce unplanned readmission rates. METHODS: A prospective cohort study using an institution-based protocol was conducted over an 18-month period including patients undergoing a general surgical procedure. The protocol included: (i) implementation of a surgical readmissions nurse-patient liaison; (ii) access to a surgical walk-in clinic; and (iii) early post-discharge phone contact. Data included demographic details, index procedure, hospital length of stay (LOS), and whether contact between patient/nurse occurred upon discharge. The primary outcome was the cause and rate of 30-day readmissions. Secondary outcomes were mortality, use of surgical clinic, emergency department presentations, and complications. RESULTS: After protocol implementation, 874 patients underwent a general surgical procedure, with 354 (49%) being male and an overall median age of 53.0 years (interquartile range: 36.0-67.0). The overall readmission rate was 5.6% (n = 49), with a median LOS after readmission of 4 days. Compared with historical pre-protocol ACS-NSQIP data, this reflects a 30% reduction compared to that of readmission rate of 7.9%, P = 0.03. CONCLUSION: The multidisciplinary protocol was efficacious in significantly reducing unplanned readmissions. Continued audits and monitoring of factors associated with readmissions are required to help design targeted projects that may lead to improved outcomes, lower costs, increased patient satisfaction, and better efficiency within our healthcare system.

Systematic Review of Preoperative Prognostic Biomarkers in Perihilar Cholangiocarcinoma.

Perihilar cholangiocarcinoma (pCCA) is an uncommon malignancy with generally poor prognosis. Surgery is the primary curative treatment; however, the perioperative mortality and morbidity rates are high, with a low 5-year survival rate. Use of preoperative prognostic biomarkers to predict survival outcomes after surgery for pCCA are not well-established currently. This systematic review aimed to identify and summarise preoperative biomarkers associated with survival in pCCA, thereby potentially improving treatment decision-making. The Embase, Medline, and Cochrane databases were searched, and a systematic review was performed using the PRISMA guidelines. English-language studies examining the association between serum and/or tissue-derived biomarkers in pCCA and overall and/or disease-free survival were included. Our systematic review identified 64 biomarkers across 48 relevant studies. Raised serum CA19-9, bilirubin, CEA, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and tumour MMP9, and low serum albumin were most associated with poorer survival; however, the cutoff values used widely varied. Several promising molecular markers with prognostic significance were also identified, including tumour HMGA2, MUC5AC/6, IDH1, PIWIL2, and DNA index. In conclusion, several biomarkers have been identified in serum and tumour specimens that prognosticate overall and disease-free survival after pCCA resection. These, however, require external validation in large cohort studies and/or in preoperatively obtained specimens, especially tissue biopsy, to recommend their use.

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.