Randomised controlled trial to establish the clinical and cost-effectiveness of expectant management versus preoperative imaging with magnetic resonance cholangiopancreatography in patients with symptomatic gallbladder disease undergoing laparoscopic cholecystectomy at low or moderate risk of common bile duct stones (The Sunflower Study): a study protocol.

INTRODUCTION: Surgery to remove the gallbladder (laparoscopic cholecystectomy (LC)) is the standard treatment for symptomatic gallbladder disease. One potential complication of gallbladder disease is that gallstones can pass into the common bile duct (CBD) where they may remain dormant, pass spontaneously into the bowel or cause problems such as obstructive jaundice or pancreatitis. Patients requiring LC are assessed preoperatively for their risk of CBD stones using liver function tests and imaging. If the risk is high, guidelines recommend further investigation and treatment. Further investigation of patients at low or moderate risk of CBD stones is not standardised, and the practice of imaging the CBD using magnetic resonance cholangiopancreatography (MRCP) in these patients varies across the UK. The consequences of these decisions may lead to overtreatment or undertreatment of patients. METHODS AND ANALYSIS: We are conducting a UK multicentre, pragmatic, open, randomised controlled trial with internal pilot phase to compare the effectiveness and cost-effectiveness of preoperative imaging with MRCP versus expectant management (ie, no preoperative imaging) in adult patients with symptomatic gallbladder disease undergoing urgent or elective LC who are at low or moderate risk of CBD stones. We aim to recruit 13 680 patients over 48 months. The primary outcome is any hospital admission within 18 months of randomisation for a complication of gallstones. This includes complications of endoscopic retrograde cholangiopancreatography for the treatment of gallstones and complications of LC. This will be determined using routine data sources, for example, National Health Service Digital Hospital Episode Statistics for participants in England. Secondary outcomes include cost-effectiveness and patient-reported quality of life, with participants followed up for a median of 18 months. ETHICS AND DISSEMINATION: This study received approval from Yorkshire & The Humber - South Yorkshire Research Ethics Committee. Results will be submitted for publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ISRCTN10378861.

Understanding the influences on successful quality improvement in emergency general surgery: learning from the RCS Chole-QuIC project.

BACKGROUND: Acute gallstone disease is the highest volume Emergency General Surgical presentation in the UK. Recent data indicate wide variations in the quality of care provided across the country, with national guidance for care delivery not implemented in most UK hospitals. Against this backdrop, the Royal College of Surgeons of England set up a 13-hospital quality improvement collaborative (Chole-QuIC) to support clinical teams to reduce time to surgery for patients with acute gallstone disease requiring emergency cholecystectomy. METHODS: Prospective, mixed-methods process evaluation to answer the following: (1) how was the collaborative delivered by the faculty and received, understood and enacted by the participants; (2) what influenced teams' ability to improve care for patients requiring emergency cholecystectomy? We collected and analysed a range of data including field notes, ethnographic observations of meetings, and project documentation. Analysis was based on the framework approach, informed by Normalisation Process Theory, and involved the creation of comparative case studies based on hospital performance during the project. RESULTS: Chole-QuIC was delivered as planned and was well received and understood by participants. Four hospitals were identified as highly successful, based upon a substantial increase in the number of patients having surgery in line with national guidance. Conversely, four hospitals were identified as challenged, achieving no significant improvement. The comparative analysis indicate that six inter-related influences appeared most associated with improvement: (1) achieving clarity of purpose amongst site leads and key stakeholders; (2) capacity to lead and effective project support; (3) ideas to action; (4) learning from own and others' experience; (5) creating additional capacity to do emergency cholecystectomies; and (6) coordinating/managing the patient pathway. CONCLUSION: Collaborative-based quality improvement is a viable strategy for emergency surgery but success requires the deployment of effective clinical strategies in conjunction with improvement strategies. In particular, achieving clarity of purpose about proposed changes amongst key stakeholders was a vital precursor to improvement, enabling the creation of additional surgical capacity and new pathways to be implemented effectively. Protected time, testing ideas, and the ability to learn quickly from data and experience were associated with greater impact within this cohort.

Percutaneous transhepatic cholangioscopy and lithotripsy in treating difficult biliary ductal stones: Two case reports.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is preferred for managing biliary obstruction in patients with bilio-enteric anastomotic strictures (BEAS) and calculi. In patients whose duodenal anatomy is altered following upper gastrointestinal (UGI) tract surgery, ERCP is technically challenging because the biliary tree becomes difficult to access by per-oral endoscopy. Advanced endoscopic therapies like balloon-enteroscopy or rendevous-ERCP may be considered but are not always feasible. Biliary sepsis and comorbidities may also make these patients poor candidates for surgical management of their biliary obstruction. CASE SUMMARY: We present two 70-year-old caucasian patients admitted as emergencies with obstructive cholangitis. Both patients had BEAS associated with calculi that were predominantly extrahepatic in Patient 1 and intrahepatic in Patient 2. Both patients were unsuitable for conventional ERCP due to surgically-altered UGl anatomy. Emergency biliary drainage was by percutaneous transhepatic cholangiography (PTC) in both cases and after 6-weeks' maturation, PTC tracts were dilated to perform percutaneous transhepatic cholangioscopy and lithotripsy (PTCSL) for duct clearance. BEAS were firstly dilated fluoroscopically, and then biliary stones were flushed into the small bowel or basket-retrieved under visualization provided by the percutaneously-inserted video cholangioscope. Lithotripsy was used to fragment impacted calculi, also under visualization by video cholangioscopy. Satisfactory duct clearance was achieved in Patient 1 after one PTCSL procedure, but Patient 2 required a further procedure to clear persisting intrahepatic calculi. Ultimately both patients had successful stone clearance confirmed by check cholangiograms. CONCLUSION: PTCSL offers a pragmatic, feasible and safe method for biliary tract clearance when neither ERCP nor surgical exploration is suitable.

Optimum timing of emergency cholecystectomy for acute cholecystitis in England: population-based cohort study.

BACKGROUND: Cholecystectomy on index admission for acute cholecystitis is associated with improved patient outcomes. The timing of intervention is mainly driven by service provision. This population-based cohort study aimed to evaluate timing of emergency cholecystectomy in England. METHODS: Data from all consecutive patients undergoing surgery for acute cholecystitis on index admission in England from 1997 to 2012 were captured from the Hospital Episodes Statistics database. Data were analysed based on whether patients underwent surgery 0-3 days, 4-7 days or ≥ 8 days from admission. Outcome measures were rate of post-operative biliary complications, conversion to open and length of stay. RESULTS: Forty-three thousand eight hundred and seventy patients underwent emergency cholecystectomy. 64.6% of patients underwent surgery between days 0 and 3 of admission, 24.3% between days 4-7 and 11.0% had surgery after day 8. Patients undergoing early surgery had significantly reduced rates of intra-operative laparoscopic conversion to open (0-3 days: 3.6%; 4-7 days: 4.0%; ≥ 8 days 4.7%, p = 0.001), post-operative ERCP (0-3 days: 1.1%; 4-7 days: 1.5%; ≥ 8 days 1.9%, p < 0.001) and bile duct injury (0-3 days: 0.6%; 4-7 days: 1.0%; ≥ 8 days 1.8%, p < 0.001). Early cholecystectomy was also associated with a shorter post-operative length of stay (LOS) [0-3 days group: median post-operative LOS 3 days (IQR: 1-6); 4-7 days group: 3 days (IQR 2-6); ≥ 8 days group: 4 days (IQR 2-9) (p < 0.001)]. High-volume centres undertook a significantly greater proportion of cholecystectomies within 3 days of presentation (high-volume: 67.3%; medium-volume: 64.8%; low-volume: 61.2%). In multivariate analysis greater time to surgery was independently associated with increased risk of post-operative ERCP and bile duct injury. CONCLUSIONS: Early cholecystectomy within 3 days of admission reduces intra-operative conversion, post-operative biliary complications and length of stay. Centres undertaking the greatest numbers of emergency cholecystectomies perform a larger proportion within 3 days of admission.

Short-term outcomes after emergency surgery for complicated peptic ulcer disease from the UK National Emergency Laparotomy Audit: a cohort study.

OBJECTIVES: This study used national audit data to describe current management and outcomes of patients undergoing surgery for complications of peptic ulcer disease (PUD), including perforation and bleeding. It was also planned to explore factors associated with fatal outcome after surgery for perforated ulcers. These analyses were designed to provide a thorough understanding of current practice and identify potentially modifiable factors associated with outcome as targets for future quality improvement. DESIGN: National cohort study using National Emergency Laparotomy Audit (NELA) data. SETTING: English and Welsh hospitals within the National Health Service. PARTICIPANTS: Adult patients admitted as an emergency with perforated or bleeding PUD between December 2013 and November 2015. INTERVENTIONS: Laparotomy for bleeding or perforated peptic ulcer. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was 60-day in-hospital mortality. Secondary outcomes included length of postoperative stay, readmission and reoperation rate. RESULTS: 2444 and 382 procedures were performed for perforated and bleeding ulcers, respectively. In-hospital 60-day mortality rates were 287/2444 (11.7%, 95% CI 10.5% to 13.1%) for perforations, and 68/382 (17.8%, 95% CI 14.1% to 22.0%) for bleeding. Median (IQR) 2-year institutional volume was 12 (7-17) and 2 (1-3) for perforation and bleeding, respectively. In the exploratory analysis, age, American Society of Anesthesiology score and preoperative systolic blood pressure were associated with mortality, with no association with time from admission to operation, surgeon grade or operative approach. CONCLUSIONS: Patients undergoing surgery for complicated PUD face a high 60-day mortality risk. Exploratory analyses suggested fatal outcome was primarily associated with patient rather than provider care factors. Therefore, it may be challenging to reduce mortality rates further. NELA data provide important benchmarking for patient consent and has highlighted low institutional volume and high mortality rates after surgery for bleeding peptic ulcers as a target for future research and improvement.

Variation in laparoscopic anti-reflux surgery across England: a 5-year review.

BACKGROUND: Laparoscopic anti-reflux surgery (LARS) remains central to the management of gastro-oesophageal reflux disease but the scale and variation in provision in England is unknown. The aims of this study were firstly to examine the processes and outcomes of anti-reflux surgery in England and compare them to national guidelines and secondly to explore potential variations in practice nationally and establish peer benchmarks. METHODS: All adult patients who underwent LARSin England during the Financial years FY 2011/2012-FY 2016/2017 were identified in the Surgeon's Workload Outcomes and Research Database (SWORD), which is based on the Hospital Episode Statistics (HES) data warehouse. Outcomes included activity volume, day-case rate, short-stay rate, 2- and 30-day readmission rates and 30-day re-operation rates. Funnel plots were used to identify national variation in practice. RESULTS: In total, 12,086 patients underwent LARS in England during the study period. The operation rate decreased slightly over the study period from 5.2 to 4.6 per 100,000 people. Most outcomes were in line with national guidelines including the conversion rate (0.76%), 30-day re-operation rate (1.43%) and 2- and 30-day readmission rates (1.65 and 8.54%, respectively). The day-case rate was low but increased from 7.4 to 15.1% during the 5-year period. Significant variation was found, particularly in terms of hospital volume, and day-case, short-stay and conversion rates. CONCLUSION: Although overall outcomes are comparable to studies from other countries, there is significant variation in anti-reflux surgery activity and outcomes in England. We recommend that units use these data to drive local quality improvement efforts.

Coding in surgery: impact of a specialized coding proforma in hepato-pancreato-biliary surgery.

BACKGROUND: Coding inaccuracies in surgery misrepresent the productivity of hospitals and outcome data of surgeons. The aim of this study was to audit the extent of coding inaccuracies in hepato-pancreato-biliary (HPB) surgery and assess the financial impact of introducing a coding proforma. METHODS: Coding of patients who underwent elective HPB surgery over a 3-month period was audited. Codes were based on International Classification of Diseases 10 and Office of Population and Census Surveys-4 codes. A coding proforma was introduced and assessed. New human resource group codes were re-assigned and new tariffs calculated. A cost analysis was also performed. RESULTS: Prior to the introduction of the coding proforma, 42.0% of patients had the incorrect diagnosis and 48.5% had missing co-morbidities. In addition, 14.5% of primary procedures were incorrect and 37.6% had additional procedures that were not coded for at all. Following the introduction of the coding proforma, there was a 27.5% improvement in the accuracy of primary diagnosis (P < 0.001) and 21% improvement in co-morbidities (P = 0.002). There was a 7.2% improvement in the accuracy of coding primary procedures (P = not significant) and a 21% improvement in the accuracy of coding of additional procedures (P < 0.001). Financial loss as a result of coding inaccuracy over our 3-month study period was £56 073 with an estimated annual loss of £228 292. CONCLUSION: Coding in HPB surgery is prone to coding inaccuracies due to the complex nature of HPB surgery and the patient case-mix. A specialized coding proforma completed 'in theatre' significantly improves the accuracy of coding and prevents loss of income.

Updated guideline on the management of common bile duct stones (CBDS).

Common bile duct stones (CBDS) are estimated to be present in 10-20% of individuals with symptomatic gallstones. They can result in a number of health problems, including pain, jaundice, infection and acute pancreatitis. A variety of imaging modalities can be employed to identify the condition, while management of confirmed cases of CBDS may involve endoscopic retrograde cholangiopancreatography, surgery and radiological methods of stone extraction. Clinicians are therefore confronted with a number of potentially valid options to diagnose and treat individuals with suspected CBDS. The British Society of Gastroenterology first published a guideline on the management of CBDS in 2008. Since then a number of developments in management have occurred along with further systematic reviews of the available evidence. The following recommendations reflect these changes and provide updated guidance to healthcare professionals who are involved in the care of adult patients with suspected or proven CBDS. It is not a protocol and the recommendations contained within should not replace individual clinical judgement.

Critical review of the prognostic significance of pathological variables in patients undergoing resection for colorectal liver metastases.

OBJECTIVE: The aim of this study was to identify prognostic factors, particularly pathological variables, that influence disease-free and overall survival following resection for colorectal liver metastases (CRLM). METHODS: Patients undergoing CRLM resection from January 2005 to December 2011 were included. Data analysed included information on demographics, laboratory results, operative findings, histopathological features and survival. RESULTS: A total of 259 patients were included. Of these, 138 (53.3%) patients developed recurrent disease, of which 95 died. The median length of follow-up in the remaining patients was 28 months (range: 12-96 months). There were significant associations between recurrence and higher tumour number (P = 0.002), presence of perineural invasion (P = 0.009) and positive margin (R1) resection (P = 0.002). Multivariate analysis showed all three prognostic factors to be independent predictors of disease-free survival. Significantly poorer overall survival after hepatic resection for CRLM was observed in patients undergoing hemi-hepatectomy or more radical resection (P = 0.021), patients with a higher number of tumours (P = 0.024) and patients with perineural invasion (P < 0.001). Multivariate analysis showed perineural invasion to be the only independent predictor of overall survival. CONCLUSIONS: The presence of perineural invasion, multiple tumours and an R1 margin were associated with recurrent disease. Perineural invasion was also an independent prognostic factor with respect to overall survival.

Outcomes in patients with indeterminate pulmonary nodules undergoing resection for colorectal liver metastases.

OBJECTIVES: This study aimed to assess outcomes in patients who underwent hepatic resection for colorectal liver metastases (CRLM) with subcentimetre indeterminate pulmonary nodules (IPN) and to devise a management pathway for these patients. METHODS: Patients undergoing CRLM resection from January 2006 to December 2010 were included. Survival differences following liver resection in patients with and without IPN were determined. RESULTS: A total of 184 patients were included, 30 of whom had IPN. There were no significant differences between the IPN and non-IPN groups in terms of demographics, surgery and pathological factors. There were no significant differences between patients with and without IPN with respect to disease-free (P= 0.190) and overall (P= 0.710) survival. Fifteen patients with IPN progressed to metastatic lung disease over a median period of 10 months (range: 3-18 months); six of these patients underwent lung resection. Of the remaining 15 patients with IPN, eight showed no IPN progression and subsequent CT scans did not identify IPN in the remaining seven. CONCLUSIONS: Colorectal liver metastases patients with IPN who have resectable disease should be treated with liver resection and should be subject to intensive surveillance post-resection. Although 50% of these patients will progress to develop lung metastases, this does not appear to influence survival following liver resection.

An international multicenter randomized controlled trial of G17DT in patients with pancreatic cancer.

OBJECTIVES: This study aimed to investigate G17DT, an immunogen producing neutralizing antibodies against the tumor growth factors amidated and glycine-extended forms of gastrin-17, in the treatment of pancreatic cancer. METHODS: A randomized, double-blind, placebo-controlled, group-sequential multicenter trial of G17DT in patients with advanced pancreatic cancer unsuitable for or unwilling to take chemotherapy. Inclusion criteria were a Karnofsky performance score of 60 or higher and a life expectancy of more than 2 months. Patients received G17DT or placebo emulsion at weeks 0, 1, 3, 24, and 52. The primary end point was survival, and secondary end points were tolerability, Karnofsky performance. RESULTS: A total of 154 patients were recruited: 79 G17DT and 75 placebo. A final analysis of the intention-to-treat population, using a proportional hazards model, stratifying by disease stage and adjusting for interim analysis, gave a hazard ratio for mortality of 0.75 (95% confidence interval, 0.51-1.10, P = 0.138; G17DT/placebo). A conventional analysis without adjustment for disease stage or interim analysis, censoring for chemotherapy and excluding protocol violators, gave median survival periods of 151 (G17DT) and 82 days (placebo) (log-rank test, P = 0.03).Patients developing anti-G17DT responses (73.8%) survived longer than nonresponders or those on placebo (median survival, 176 vs 63 vs 83; log-rank test, P = 0.003). G17DT was well tolerated.

Heat shock protein 70 expression following hepatic radiofrequency ablation is affected by adjacent vasculature.

BACKGROUND: Heat shock proteins are a highly conserved family of stress response proteins. Members of the heat shock protein 70 (Hsp70) family prevent protein misfolding and aggregation. Following radiofrequency ablation of unresectable liver tumors an interface appears between the irreversibly damaged and normal liver. The fate of this transition zone is critical and is believed to be responsible for local recurrences. Hsp70 is expressed in response to thermal stress and may influence the fate of cells in this transitional zone. It is also recognized that the presence of large vessels or a perivascular location of tumors also influences the recurrence rate. The aim of this study is to examine the transition zone and observe the effect of local blood flow on ablation morphology and Hsp70 expression. METHODS: Radiofrequency ablation was performed in 25 rats at various distances from the liver hilum. Tissue was retrieved and analysed at time points 0, 4, 24, 48 h, and 2 wk following treatment. Tissue was analyzed histologically with hematoxylin and eosin staining (H and E,) and immunohistochemically for Hsp70 expression. RESULTS: All rats survived the procedure. H and E staining revealed previously unreported foci of apoptosis at the ablation edge and deep in the normal hepatic parenchyma. Hsp70 was expressed in the transition zone at 4 h and peaked at 24 h. The degree of Hsp70 expression was significantly influenced by the distance from surrounding vasculature. CONCLUSIONS: This study reports several previously unreported findings. There is increased apoptosis distal to the ablated zone suggests leakage of radiofrequency (RF) current down blood vessels originating in the ablation zone. The degree of Hsp70 expression in the transition zone correlates with time after treatment and the size and location of any adjacent vasculature. These findings suggest that heat shock proteins may play a role in the ability of damaged cells to recover and survive at the periphery of an ablation zone.

Scaffolds containing growth factors and extracellular matrix induce hepatocyte proliferation and cell migration in normal and regenerating rat liver.

BACKGROUND & AIMS: Intrahepatic drug delivery from implantable scaffolds is being developed as a strategy to modulate growth and enhance regeneration at the time of liver resection. In this study we examine the effects of scaffolds containing hepatocyte growth factor, epidermal growth factor, fibroblast growth factor 1, fibroblast growth factor 2, and liver-derived extracellular matrix (L-ECM) when implanted into normal and partially hepatectomized rat livers. METHODS: Scaffolds loaded with combinations of growth factors and L-ECM were implanted into normal livers (controls=L-ECM, polymer or sham) and livers following partial hepatectomy (controls=partial hepatectomy or sham). The primary end points were hepatocyte DNA synthesis and liver tissue penetration into scaffolds. Secondary end points included non-parenchymal cell DNA synthesis, liver weight analysis, liver function, and histological characterisation of the peri-implant parenchyma. RESULTS: Four days after implantation in normal livers, there was significantly more hepatocyte proliferation around growth factor scaffolds than controls. Seven days after implantation, there was significantly more tissue penetration into growth factor scaffolds than control scaffolds. ED-1 and desmin positive cells were present in the pores of scaffolds. Two days after partial hepatectomy, there was significantly more hepatocyte proliferation around scaffold implanted livers than after partial hepatectomy alone. CONCLUSIONS: Growth factors and L-ECM accelerated non-parenchymal cell migration into scaffolds and increased hepatocyte and non-parenchymal cell proliferation around them. These results demonstrate the potential for intrahepatic implantation of scaffolds containing growth factors and L-ECM to modulate growth in the normal and regenerating liver.

Long-term outcome of laparoscopic Nissen and laparoscopic Toupet fundoplication for gastroesophageal reflux disease: a prospective, randomized trial.

BACKGROUND: A prospective, randomized trial was performed to evaluate the long-term outcome and patient satisfaction of laparoscopic complete 360 degrees fundoplication compared with partial posterior 270 degrees fundoplication. Partial fundoplication is purported to have fewer side effects with a higher failure rate in controlling gastroesophageal reflux disease (GERD), while complete fundoplication is thought to result in more dysphagia and gas-related symptoms. METHODS: Patients were randomized to either laparoscopic Nissen (LN) or laparoscopic Toupet (LT) fundoplication. Esophageal manometry, 24-h pH studies, a detailed questionnaire, and a visual analog symptom (VAS) score were completed before and after surgery. A final global outcome questionnaire was performed. Failure was defined as recurrent GERD requiring revision surgery, maintenance proton pump inhibitor (PPI) therapy, or surgery for postoperative dysphagia. RESULTS: One hundred patients were randomized to LN (50) or LT (50). There were no differences between LN and LT with respect to postoperative symptoms and physiological variables except a higher wrap pressure in the LN group (15.2 vs. 12.0 mmHg). Dysmotility improved in 8/14 (57%) and 6/11 (54%) patients in the LN group and the LT group, respectively, after surgery. There was no correlation between dysmotility and dysphagia both pre- and post surgery in the two groups. Recurrent symptoms of GERD occurred in 8/47 (17.0%) and 8/48 (16.6%) in the LN group and the LT group, respectively. Outcome of patients with dysmotility was similar to those with normal motility in both groups. At final follow-up (59.76 + or - 24.23 months), in the LN group, 33/37 (89.1%) would recommend surgery to others, 32/37 (86.4%) would have repeat surgery, and 34/37 (91.8%) felt they were better off than before surgery. The corresponding numbers for the LT group (follow-up = 55.18 + or - 25.97 months) were 35/36 (97.2%), 30/36 (83.3%), and 33/36 (91.6%). CONCLUSION: LN and LT are equally effective in restoring the lower esophageal sphincter function and provide similar long-term control of GERD with no difference in dysphagia. Esophageal dysmotility had no influence on the outcome of either operation.

Is a T-tube necessary after common bile duct exploration?

BACKGROUND: T-tube drainage used to be standard practice after surgical choledocholithotomy, but there is now a tendency in some centers to close the common bile duct (CBD) primarily. This study was designed to review the complications associated with T-tube drainage after CBD exploration and to determine whether primary closure of the bile duct reduces postoperative morbidity. METHODS: A retrospective audit was performed on patients undergoing CBD exploration between July 1997 and March 2007, who were identified from the theatre database of one teaching hospital. Intraoperative findings and postoperative complications were recorded from the clinical notes. RESULTS: During the study period, 158 patients (97 women; median age 65 (range, 25-90) years) underwent CBD exploration. A T-tube was inserted in 91 patients (group I) and the CBD was closed primarily in 67 (group II). One or more biliary complications occurred in 26 patients (16.5%): 20 (22.0%) in group I and 6 (8.9%) in group II (p = 0.03). In group I, 15 had a biliary leak (3 needed reoperation), 2 had accidental slippage of the tube, 2 an entrapped T-tube, and 1 a retained stone. In group II, six patients had biliary leakage, two of whom were re-explored. Six patients in group I also had peritubal infection, necessitating the use of antibiotics. There were three deaths: two in group I (1 T-tube-related) and 1 in group II (p = 1, not significant). CONCLUSION: There is a lower biliary complication rate associated with primary closure of the CBD than after T-tube drainage.

The pathological response to neoadjuvant chemotherapy with FOLFOX-4 for colorectal liver metastases: a comparative study.

FOLFOX-4 (folinic acid/5-fluorouracil/oxaliplatin) chemotherapy is used to treat patients with colorectal liver metastases. We aimed to assess hepatic histopathological responses to neoadjuvant FOLFOX-4 chemotherapy in patients with colorectal liver metastases. We selected all patients (n = 54) treated with FOLFOX-4 for colorectal liver metastases between June 2002 and June 2005. Only 25 underwent hepatectomy and formed the study group. Histological responses were assessed in the study group and a matched control group (n = 25) that did not receive neoadjuvant chemotherapy. The median (IQR) body mass index in the study and control groups was 24 (22-26) and 24 (23-25) kg/m(2), respectively, (P = NS). Complete histological resolution of tumour occurred in six (24%) patients in the study group. Median residual tumour cellularity was less (35 vs 70%) and fibrosis greater (50 vs 5%) in patients in the study group when compared with controls (P < 0.001). The liver surrounding the tumour was steatotic in 17 (68%) patients in the study group and five (20%) controls (P = 0.001). Hepatic sinusoidal dilatation was more pronounced in patients in the study group than in controls (P < 0.001). The response to FOLFOX-4 was associated with tumour necrosis, fibrosis and inflammation. More than two thirds of patients undergoing hepatectomy after FOLFOX-4 had steatosis despite being non-obese.

The effect of hepatic vascular inflow occlusion on liver tissue pH, carbon dioxide, and oxygen partial pressures: defining the optimal clamp/release regime for intermittent portal clamping.

BACKGROUND: The optimal duration of hepatic vascular inflow occlusion (Pringle maneuver) and reperfusion during liver resection are not defined. The aim of this study was to describe the changes that occur in liver tissue pH, partial pressure of carbon dioxide (P(L)CO(2)), and partial pressure of oxygen (P(L)O(2)) and by using the P(L)CO(2) as a predictor of hepatocellular damage define the optimal clamp/release regime for intermittent portal clamping during liver resection. METHODS: Continuous pH, P(L)CO(2), and P(L)O(2) measurements were obtained using a Paratrend multi-parameter sensor (Diametrics Medical Inc., Roseville, MN) in 13 patients undergoing elective partial liver resection. Patients were randomly allocated to undergo a 10-min clamp/5-min release regime (group 1) or a 20-min clamp/10-min release regime (group 2). RESULTS: In group 1 (n = 6) P(L)CO(2) increased and pH decreased significantly after 10 min of clamping and returned to baseline within 5 min of reperfusion. In group 2 (n = 7) the P(L)CO(2) increased and pH decreased significantly after 10 min of clamping, with a further significant change after 20 min. Following 10 min of reperfusion, pH and P(L)CO(2) had not returned to baseline. P(L)O(2) did not change significantly with either intermittent portal clamping regime. CONCLUSIONS: A reperfusion of 5 min is sufficient to restore the P(L)CO(2) and liver tissue pH to normal after 10 min of clamping, but more than 10 min of reperfusion is required after 20 min of clamping. To minimize hepatic ischemia during liver resection, a 10-min clamp/5-min release regime should be used.

The position of the vermiform appendix at laparoscopy.

BACKGROUND: The vermiform appendix has no constant position and the data on the variations in its position are limited. The aim of this study was to determine the frequency of the various positions of the appendix at laparoscopy. METHODS: Patients undergoing emergency or elective laparoscopy at a university teaching hospital between April and September 2004 were studied prospectively. The positions of the appendix and the caecum were determined after insertion of the laparoscope, prior to any other procedure and the relative frequencies calculated. RESULTS: A total of 303 (102 males and 201 females) patients with a median age of 52 years (range 18-93 years) were studied. An emergency appendicectomy was performed in 67 patients, 49 had a diagnostic laparoscopy, 179 underwent a laparoscopic cholecystectomy and eight had other procedures. The caecum was at McBurney's point in 245 (80.9%) patients, pelvic in 45 (14.9%) and high lying in 13 (4.3%). The appendix was pelvic in 155 (51.2%) patients, pre-ileal in 9 (3.0%), para-caecal in 11 (3.6%), post-ileal in 67 (22.1%) and retrocaecal in 61 (20.1%) patients. CONCLUSION: Contrary to the common belief the appendix is more often found in the pelvic rather than the retrocaecal position. There is also considerable variation in the position of the caecum.