Systematic review of management of incidental gallbladder cancer after cholecystectomy.

BACKGROUND: Gallbladder cancer is rare, but cancers detected incidentally after cholecystectomy are increasing. The aim of this study was to review the available data for current best practice for optimal management of incidental gallbladder cancer. METHODS: A systematic PubMed search of the English literature to May 2018 was conducted. RESULTS: The search identified 12 systematic reviews and meta-analyses, in addition to several consensus reports, multi-institutional series and national audits. Some 0·25-0·89 per cent of all cholecystectomy specimens had incidental gallbladder cancer on pathological examination. Most patients were staged with pT2 (about half) or pT1 (about one-third) cancers. Patients with cancers confined to the mucosa (T1a or less) had 5-year survival rates of up to 100 per cent after cholecystectomy alone. For cancers invading the muscle layer of the gallbladder wall (T1b or above), reresection is recommended. The type, extent and timing of reresection remain controversial. Observation time may be used for new cross-sectional imaging with CT and MRI. Perforation at initial surgery had a higher risk of disease dissemination. Gallbladder cancers are PET-avid, and PET may detect residual disease and thus prevent unnecessary surgery. Routine laparoscopic staging before reresection is not warranted for all stages. Risk of peritoneal carcinomatosis increases with each T category. The incidence of port-site metastases is about 10 per cent. Routine resection of port sites has no effect on survival. Adjuvant chemotherapy is poorly documented and probably underused. CONCLUSION: Management of incidental gallbladder cancer continues to evolve, with more refined suggestions for subgroups at risk and a selective approach to reresection.

Meta-analysis of ischaemic preconditioning for liver resections.

BACKGROUND: Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping. METHODS: This was a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating IP in adults undergoing liver resection under either continuous clamping (CC) or intermittent clamping (IC). Primary outcomes were mortality, liver failure and morbidity. Secondary outcomes included duration of operation, blood loss, length of hospital stay, length of intensive therapy unit stay, transfusion requirements, prothrombin time, and bilirubin and aminotransferase levels. Weighted mean differences were calculated for continuous data, and pooled odds ratios (ORs) for dichotomous data. Results were produced with a random-effects model with 95 per cent confidence intervals (c.i.). RESULTS: A total of 2960 records were identified and 11 RCTs included 669 patients (IP 331, control 338). No significant difference in mortality (6 RCTs; IP 186, control 190; OR 1·36, 95 per cent c.i. 0·13 to 13·68; P = 0·80) or morbidity (6 RCTs; IP 186, control 190; OR 0·58, 0·31 to 1·07; P = 0·08) was found for IP plus CC versus CC. Nor was there a significant difference in mortality (4 RCTs; IP 122, control 121; OR 1·33, 0·24 to 7·32; P = 0·74) or morbidity (4 RCTs; IP 122, control 121; OR 0·87, 0·52 to 1·47; P = 0·61) for IP plus (CC or IC) versus IC. No significant differences were found for secondary outcome measures. CONCLUSION: This meta-analysis failed to find a significant benefit of IP in liver resection.

ATOM, the all-inclusive, nominal EAES classification of bile duct injuries during cholecystectomy.

BACKGROUND: Several studies seem to indicate at least a 2-fold increase in bile duct injuries (BDI) since the inception of laparoscopic cholecystectomy. Moreover, injuries seem to be more proximal, seem to be revealed earlier, are expressed by leaks more often than by strictures, are repaired more frequently by nonspecialists (either during the index operation or soon after), and appear to be more often associated with loss of substance and ischemia. The plethora of prior classifications probably attests to the evolving clinical spectrum, the mounting wealth of ever-increasing diagnostic methods, and an acknowledgment of insufficiencies or lack of data in earlier classification reports. Previous attempts at uniformity remain incomplete. The purpose of this study was to devise a nominal classification, combining all existing classification items, taking into account the changing pattern of BDI. METHODS: Extensive bibliographic research, analysis of each category within the individual classifications combined into one uniform classification. RESULTS: Fifteen classifications were retained. All items were integrated into the European Association for Endoscopic Surgery (EAES) classification, using semantic connotations, grouped in three easy-to-remember categories, A (for anatomy), To (for time of), M (for mechanism): (1) the anatomic characteristics of the injury: NMBD for non-main bile duct or MBD for main bile duct (followed by a number 1-6, corresponding to the anatomic level on the MBD), followed by Oc (for occlusion) or D (division), P (partial) or C (complete), LS (loss of substance), VBI (vasculobiliary injury in general), and whenever known, the vessel; (2) time of detection: Ei (early intraoperative), Ep (early postoperative) or L (late); and (3) mechanism of injury: Me (mechanical) or ED (energy-driven). CONCLUSIONS: The EAES composite, all-inclusive, nominal classification ATOM (anatomic, time of detection, mechanism) should allow combination of all information on BDI, irrespective of the original classification used, and thus facilitate epidemiologic and comparative studies; indicate simple, appropriate preventive measures; and better guide therapeutic indications for iatrogenic BDI occurring during cholecystectomy.

Outcomes following a dedicated period of research during surgical training.

With recent 'working-time'-related changes to surgical training structure, the value of dedicated research during surgical training has been questioned. Online survey examining career and academic outcomes following a period of surgically related dedicated research at a Scottish University between 1972 and 2007. Of 58 individuals identified, contact details were available for 49 and 43 (88%) responded. Ninety-five percent (n = 41) of respondents continue to pursue a career in surgery and 41% (n = 17) are currently in academic positions. Ninety-one percent (n = 39) had published one or more first-author peer-reviewed articles directly related to their research, with 53% (n = 23) publishing three or more. Respondents with a clinical component to their research published significantly more papers than those with purely laboratory-based research (P = 0.04). Eighty-one percent (n = 35) thought that research was necessary for career progression, but only 42% (n = 18) felt research should be integral to training. In conclusion, the majority of surgical trainees completing a dedicated research period, published papers and continued to pursue a surgical career with a research interest. A period of dedicated research was thought necessary for career progression, but few thought dedicated research should be integral to surgical training.

Perioperative platelet and monocyte activation in patients with critical limb ischemia.

BACKGROUND: Patients with critical limb ischemia (CLI) have a high rate of adverse cardiovascular events, particularly when undergoing surgery. We sought to determine the effect of surgery and vascular disease on platelet and monocyte activation in vivo in patients with CLI. METHODS: An observational, cross-sectional study was performed at a tertiary referral hospital in the southeast of Scotland. Platelet and monocyte activation were measured in whole blood in patients with CLI scheduled for infrainguinal bypass and compared with matched healthy controls, patients with chronic intermittent claudication, patients with acute myocardial infarction, and those undergoing arthroplasty (n = 30 per group). Platelet and monocyte activation were quantified using flow cytometric assessment of platelet-monocyte aggregation, platelet P-selectin expression, platelet-derived microparticles, and monocyte CD40 and CD11b expression. RESULTS: Compared with those with intermittent claudication, subjects with CLI had increased platelet-monocyte aggregates (41.7% +/- 12.2% vs 32.6% +/- 8.5%, respectively), platelet microparticles (178.7 +/- 106.9 vs 116.9 +/- 53.4), and monocyte CD40 expression (70.0% +/- 12.2% vs 52.4% +/- 15.2%; P < .001 for all). Indeed, these levels were equivalent (P-selectin, 4.4% +/- 2.0% vs 4.9% +/- 2.2%; P > .05) or higher (platelet-monocyte aggregation, 41.7% +/- 12.2% vs 33.6% +/- 7.0%; P < .05; platelet microparticles, 178.7 +/- 106.9 vs 114.4 +/- 55.0/microL; P < .05) than in patients with acute myocardial infarction. All platelet and monocyte activation markers remained elevated throughout the perioperative period in patients with CLI (P < .01) but not those undergoing arthroplasty. CONCLUSIONS: Patients undergoing surgery for CLI have the highest level of in vivo platelet and monocyte activation, and these persist throughout the perioperative period. Additional antiplatelet therapy may be of benefit in protecting vascular patients with more severe disease during this period of increased risk.

Randomized clinical trial of laxatives and oral nutritional supplements within an enhanced recovery after surgery protocol following liver resection.

BACKGROUND: Routine laxatives may expedite gastrointestinal recovery and early tolerance of food within an enhanced recovery after surgery (ERAS) programme. Combined with carbohydrate loading and oral nutritional supplements (ONS), it may further enhance recovery of gastrointestinal function and promote earlier overall recovery. METHODS: Seventy-four patients undergoing liver resection were randomized in a two-by-two factorial design to receive either postoperative magnesium hydroxide as a laxative, preoperative carbohydrate loading and postoperative ONS, their combination or a control group. Patients were managed within an ERAS programme of care. The primary outcome measure was time to first passage of stool. Secondary outcome measures were gastric emptying, postoperative oral calorie intake, time to functional recovery and length of hospital stay. RESULTS: Sixty-eight patients completed the trial. The laxative group had a significantly reduced time to passage of stool: median (interquartile range) 4 (3-5) versus 5 (4-6) days (P = 0.034). The ONS group showed a trend towards a shorter time to passage of stool (P = 0.076) but there was no evidence of interaction in patients randomized to the combination regimen. Median length of hospital stay was 6 (4-7) days. There were no differences in secondary outcomes between groups. CONCLUSION: Within an ERAS protocol for patients undergoing liver resection, routine postoperative laxatives result in an earlier first passage of stool but the overall rate of recovery is unaltered.

The relationship between hospital volume and post-operative mortality rates for upper gastrointestinal cancer resections: Scotland 1982-2003.

BACKGROUND: Centralisation of surgical treatment of cancer has resulted in improved outcomes. We aimed to determine evidence of benefit for specialised management of upper gastrointestinal cancer in high-volume centres in Scotland. METHODS: Discharge records of patients undergoing oesophagectomy, gastrectomy, hepatectomy or pancreatectomy between 1982 and 2003 were identified. Hospital data were analysed on a year-by-year basis to derive 'hospital-years'. Hospital-years were divided into quartiles by volume, and were analysed with regard to in-hospital mortality during the operative admission [Chi-square test (chi(2)) and Chi-square test for trend (chi(2)(trend))]. RESULTS: 10,625 patients and 982 in-hospital deaths were included. In-hospital mortality rates declined during the study period: oesophagectomy 11.7-7.9%; gastrectomy 11.2-7.2%; hepatectomy 11.1-3.0%; and pancreatectomy 8.3-4.9%. For all resections except gastrectomy, mortality decreased as quartile of hospital-year volume increased (oesophagectomy: chi(2)p=0.006, chi(2)(trend)p=0.001; hepatectomy: chi(2)p=0.004, chi(2)(trend)p=0.003; pancreatectomy: chi(2)p=0.002, chi(2)(trend)p=0.001). ORs of death were lower for oesophagectomy (OR=0.58; 95%CI=0.39, 0.88; p=0.009) and pancreatectomy (OR=0.35; 95%CI=0.19, 0.64; p<0.001) in hospital-years within highest-volume quartiles compared with lowest. Scattergraphs of all resection types demonstrated inverse power relationships between number of resections per hospital-year and mortality. CONCLUSION: Concentration of cancer care has had major effects on health service delivery in Scotland. Centralisation should be supported in surgical management of upper gastrointestinal cancer.

Validation of a prognostic nomogram in patients undergoing resection for pancreatic ductal adenocarcinoma in a UK tertiary referral centre.

INTRODUCTION: Survival following resection for pancreatic ductal adenocarcinoma (PDAC) remains poor. The aim of this study was to validate a survival nomogram designed at the Memorial Sloan-Kettering Cancer Centre (MSKCC) in a UK tertiary referral centre. METHODS: Patients who underwent resection for PDAC between 1995 and 2005 were analysed retrospectively. Standard prognostic factors and nomogram-specific data were collected. Continuous data are presented as median (inter-quartile range). RESULTS: Sixty-three patients were analysed. The median survival was 326 (209-680) days. On univariate analysis lymph node status (node +ve 297 (194-471) days versus node -ve 367 (308-1060) days, p=0.005) and posterior margin involvement (margin +ve 210 (146-443) days versus margin -ve 355 (265-835) days, p=0.024) were predictors of a poor survival. Only lymph node positivity was significant on multivariate analysis (p=0.006). The median nomogram score was 217 (198-236). A nomogram score of 113-217 predicted a median survival of 367 (295-847) days compared to 265 (157-443) days for a score of 218-269, p=0.012. CONCLUSION: Increasing nomogram score was associated with poorer survival. However the accuracy demonstrated by MSKCC could not be replicated in the current cohort of patients and may reflect differences in patient demographics, accuracy of pathological staging and differences in treatment regimens between the two centres.

Continuing professional development for surgeons.

With the introduction of revalidation, continuing professional development (CPD) is becoming an increasingly important part of a surgeon's professional life. There is minimal existing information describing the CPD practices and attitudes of surgeons to CPD. This review describes the current CPD expectations of the General Medical Council and the current CPD activities and attitudes of surgeons, based around the results of an on-line study performed by the Royal College of Surgeons of Edinburgh.

Staging laparoscopy for cholangiocarcinoma.

The precise role of laparoscopic assessment of biliary tract malignancy is yet to be defined. The evidence for its use has been reviewed to establish the role of laparoscopy for preoperative staging of cholangiocarcinoma. Published papers were reviewed for the evidence relevant to intrahepatic, proximal intrahepatic and distal biliary carcinoma. There is no randomized trial evaluating staging laparoscopy or laparoscopic ultrasound in the assessment of cholangiocarcinoma and the quality of the available data is extremely variable. There is a need for further studies to determine the specific role of laparoscopic staging of cholangiocarcinoma. The current standard of management should be to perform laparoscopic staging prior to proceeding to resection for patients with cholangiocarcinoma as it may prevent unnecessary laparotomy in up to 30% of patients. However, a selective approach identifying high-risk patients who will not benefit from surgical palliation may be more cost effective and future studies should be performed to identify such patients.

Initial experience with a multimodal enhanced recovery programme in patients undergoing liver resection.

BACKGROUND: Accelerated recovery from surgery has been achieved when patients are managed within a multimodal Enhanced Recovery After Surgery (ERAS) protocol. This study evaluated the benefit of an ERAS programme for patients undergoing liver resection. METHODS: The ERAS protocol of epidural analgesia, early oral intake and early mobilization was studied prospectively in a consecutive series of 61 patients. Outcomes were compared with those in a consecutive series of 100 patients who underwent liver resection before the start of the study. Endpoints were postoperative length of hospital stay, postoperative resumption of oral intake, readmissions, morbidity and mortality. RESULTS: Fifty-six patients (92 per cent) in the ERAS group tolerated fluids within 4 h of surgery and a normal diet on day 1 after surgery. Median hospital stay, including readmissions, was 6.0 days compared with 8.0 days in the control group (P < 0.001). There were no significant differences in rates of readmission (13 and 10.0 per cent respectively), morbidity (41 and 31.0 per cent) and mortality (0 and 2.0 per cent) between ERAS and control groups. CONCLUSION: The ERAS fast-track protocol is safe and effective for patients undergoing liver resection. It allows early oral intake, promotes faster postoperative recovery and reduces hospital stay.

Tryptophan catabolites in mesenteric lymph may contribute to pancreatitis-associated organ failure.

BACKGROUND: Multiple organ failure (MOF) is the key determinant of mortality in acute pancreatitis (AP). Mesenteric lymph cytotoxicity contributes to organ failure in experimental models of systemic inflammation. The aim of this study was to evaluate the mesenteric lymph pathway and the lymph injury proteome in experimental AP-associated MOF, and to test the hypothesis that immunoregulatory tryptophan catabolites contribute to mesenteric lymph cytotoxicity. METHODS: Using an experimental model of AP in rats, the humoral component of mesenteric lymph in AP was compared with that from sham-operated control animals, using in vitro and in vivo cytotoxicity assays, high-throughput proteomics and high-performance liquid chromatography. The experimental findings were corroborated in a cohort of 34 patients with AP. RESULTS: Compared with biologically inactive lymph from sham-operated rats, mesenteric lymph in AP became cytotoxic 3 h after induction. Hierarchical clustering of lymph proteomic mass spectra predicted the biological behaviour of lymph. Levels of the immunoregulatory tryptophan catabolite, 3-hydroxykynurenine, were increased in cytotoxic lymph and re-created cytotoxicity in vitro. In humans with AP, plasma kynurenine concentrations correlated in real time with MOF scores and preceded a requirement for mechanical ventilation and haemodialysis. CONCLUSION: These results support the concept that mesenteric lymph-borne kynurenines may contribute to pancreatitis-associated MOF.

The selective use of magnetic resonance cholangiopancreatography in the imaging of the axial biliary tree in patients with acute gallstone pancreatitis.

BACKGROUND: Magnetic resonance cholangiopancreatography (MRCP) is an emerging modality in the management of acute gallstone pancreatitis (AGP). The aim of this study was to assess the impact following the introduction of MRCP in the management of AGP in a tertiary referral unit. METHODS: Patients presenting with AGP from January 2002 to December 2004 were reviewed to assess the impact of the introduction of MRCP in June 2003. The indication for MRCP was suspected common bile duct (CBD) stones in the absence of biliary sepsis. Definitive treatment for AGP was laparoscopic cholecystectomy, with endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy reserved for patients unfit for cholecystectomy and those with biliary sepsis. RESULTS: 249 patients were identified of whom 36 (14.5%) underwent ERCP and sphincterotomy as definitive treatment. 96 patients with a non-dilated CBD and normal or resolving liver function tests proceeded to laparosocopic cholecystectomy and intraoperative cholangiogram (IOC), 8 (8.5%) of whom had CBD stones intraoperatively. Eleven patients underwent cholecystectomy during pancreatic necrosectomy. Of those undergoing preoperative diagnostic biliary tract imaging, ERCP was undertaken in 57 patients and MRCP in 49 patients. There was no significant difference in serum bilirubin levels [ERCP 43 mmol/l (18-204) vs. MRCP 39 mmol/l (24-180), p = NS] or the proportion of patients with CBD stones [ERCP 10 (17.5%) vs. MRCP 7 (14.2%), p = NS] between the two groups. Patients who underwent MRCP had a shorter median hospital stay [MRCP 5 days (range: 3-14) vs. ERCP 9 days (range: 4-20), p < 0.01] and higher rate of cholecystectomy during the index admission (MRCP 83.3% vs. ERCP 67.2%, p < 0.05). There was a high degree of correlation between preoperative MRCP results and findings of subsequent IOC or therapeutic ERCP (area under ROC curve: 0.94). CONCLUSIONS: MRCP is an accurate modality for imaging the axial biliary tree in patients with AGP. Selective use of MRCP reduces the need for ERCP and results in shorter hospital stay. and IAP.

Liver resection and transplantation in the management of iatrogenic biliary injury.

BACKGROUND: Biliary injury during cholecystectomy can be managed successfully by biliary reconstruction in the majority of patients; however, a proportion of patients may require hepatic resection or even liver transplantation. METHODS: Data on all patients referred with biliary injuries were recorded prospectively. The details of patients who required hepatic resection or transplantation were analyzed and compared to those patients managed with biliary reconstruction alone. RESULTS: From November 1984 until November 2003 there were 119 patients referred with Strasberg grade E injuries to the biliary tree, 14 of whom (9 women, 5 men) required hepatic resection or transplantation. The median age of these 14 patients was 48 (range: 30-81) years. Nine patients were considered for hepatic resection, and of these six underwent right hepatectomy, two had a left lateral sectionectomy, and one patient was deemed unfit for surgery and underwent metal stenting of the right hepatic duct. All patients are alive and remain well. Five patients developed hepatic failure and were considered for liver transplantation. Two patients who were unfit for transplantation died, and another died while on the waiting list for transplantation. The remaining two patients underwent liver transplantation, and one of them died from overwhelming sepsis. Concomitant vascular injury was demonstrated in 8 of the 14 patients (57%), and in 3 of the 4 (75%) patients that died. CONCLUSIONS: Hepatic atrophy or sepsis after biliary injury can be managed successfully with hepatic resection. Liver transplantation is required occasionally for patients with secondary biliary cirrhosis, but is rarely successful for early hepatic failure following iatrogenic biliary injury.

Clinical prognostic scoring system to aid decision-making in gastro-oesophageal cancer.

BACKGROUND: Accurate prediction of prognosis in gastro-oesophageal cancer remains challenging. The aim of this study was to develop a robust model for outcome prediction. METHODS: The study included 220 patients with gastric or oesophageal cancer newly diagnosed over a 2-year period. Patients were staged and underwent treatment following discussion at a multidisciplinary team (MDT) meeting. Clinical and investigative variables were collected, including performance and nutritional status, and serum C-reactive protein (CRP) level. Primary endpoints were death within 12 and 24 months. RESULTS: Overall median survival was 13 months. Advanced clinical stage (P < 0.001), reduced performance score (P < 0.001), weight loss exceeding 2.75 per cent per month (P = 0.026) and serum CRP concentration above 5 mg/l (P = 0.031) were identified as independent prognostic indicators in multivariable analysis. A prognostic score was constructed using these four variables to estimate a probability of death. Applying the model gave an area under the receiver-operator characteristic curve of 0.84 and 0.85 for prediction of death at 12 and 24 months respectively (both P < 0.001). CONCLUSION: This model accurately estimated the probability of death within 12 and 24 months. This may aid the MDT decision-making process.