A case report of an angiomyxoma in the liver.

Angiomyxomas are uncommon myxoid tumours arising most commonly from the pelvis. A 46-year-old woman with a history of polycystic kidney disease presented asymptomatically for surveillance ultrasonography; changes were noted in the size and morphology of her liver cysts. Subsequent radiological assessment displayed features suspicious of malignancy and a right hemihepatectomy was performed with curative intent. Pathological examination of the resected specimen found histology consistent with an angiomyxoma arising primarily from the liver parenchyma. Follow-up review of the patient has been uneventful with annual imaging showing no evidence of recurrence. Angiomyxomas do not characteristically invade other tissues. However, any liver lesion displaying suspicious features of malignancy should be resected in the absence of disseminated disease.

Improved outcomes for hepatic trauma in England and Wales over a decade of trauma and hepatobiliary surgery centralisation.

BACKGROUND: Over the last decade trauma services have undergone a reconfiguration in England and Wales. The objective is to describe the epidemiology, management and outcomes for liver trauma over this period and examine factors predicting survival. METHODS: Patients sustaining hepatic trauma were identified using the Trauma Audit and Research Network database. Demographics, management and outcomes were assessed between January 2005 and December 2014 and analysed over five, 2-year study periods. Independent predictor variables for the outcome of liver trauma were analysed using multiple logistic regression. RESULTS: 4368 Patients sustained hepatic trauma (with known outcome) between January 2005 and December 2014. Median age was 34 years (interquartile range 23-49). 81% were due to blunt and 19% to penetrating trauma. Road traffic collisions were the main mechanism of injury (58.2%). 241 patients (5.5%) underwent liver-specific surgery. The overall 30-day mortality rate was 16.4%. Improvements were seen in early consultant input, frequency and timing of computed tomography (CT) scanning, use of tranexamic acid and 30-day mortality over the five time periods. Being treated in a unit with an on-site HPB service increased the odds of survival (odds ratio 3.5, 95% confidence intervals 2.7-4.5). CONCLUSIONS: Our study has shown that being treated in a unit with an on-site HPB service increased the odds of survival. Further evaluation of the benefits of trauma and HPB surgery centralisation is warranted.

Lessons from a national audit of acute pancreatitis: A summary of the NCEPOD report 'Treat the Cause'.

The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) is an independent organisation whose remit is to review the quality of medical and surgical care provided in the United Kingdom. We undertook a review into the care provided to patients treated for acute pancreatitis during a 6 month study period between 1st January and 30th June 2014. This included assessment of care at an organisational level, clinical level within hospitals and external peer review. From a random sample, 712 patients underwent hospital clinician review and 418 patients had external peer review. Overall, we found that there was room for improvement in care in over 50% of patients with acute pancreatitis. Case reviewers felt that efforts to prevent recurrent episodes due to gallstones and alcohol were inadequate as 21% of patients in the study had one or more previous episodes of acute pancreatitis. Aspects of general care where improvements could be made include better antibiotic stewardship; as 1/5 of patients were considered to have been given antibiotics unnecessarily. Overall management of the patients' nutrition was considered adequate by the case reviewers in only 85% of cases. The use of an early warning score was omitted in 31% of emergency department admissions. Recommendations include standardised early warning scoring systems to be used throughout the hospital and commenced in the emergency department. The development of better networking arrangements and regional pancreatitis units, with shared management guidelines, is also essential to improve the coordination of care.

Prognostic factors for disease relapse in patients with neuroendocrine tumours who underwent curative surgery.

AIM: Surgery is the only modality of cure in patients diagnosed with neuroendocrine tumours (NETs). The aim of this study was to identify prognostic factors associated with disease relapse in patients with NETs treated by potentially-curative surgery. METHODS: Sequential patients registered in The Christie European NET Society (ENETS) Centre of Excellence, with grade (G)1 or G2 NETs who had undergone curative surgery (February 2002-June 2014) were included. Investigated prognostic factors for relapse were: age, gender, TNM stage, tumour-localisation, functionality, genetic predisposition, presence of multiple NETs, second malignancy, grade (Ki-67-based), presence of vascular and/or perineural invasion, necrosis, surgical margin (R0/R1), Eastern Cooperative Oncology Group performance status and Adult Comorbidity Evaluation co-morbidity score. RESULTS: One hundred and eighty-eight patients were identified [median age of 60 years (range 16-89)]. With a median follow-up of 2.6 years, 43 relapses occurred. The estimated median relapse-free survival (RFS) for the entire cohort was 8.0 years (95% confidence interval [CI] 5.9-10.0 years). In univariate analysis, primary NET location (p = 0.01), ENETS T-(HR-1.4; 95%-CI 1.0-2.0, p = 0.026), N-(HR-2.0, 95%-CI 1.1-3.9, p = 0.026) and M-stage (HR-2.6, 95%-CI 1.1-6.3, p = 0.052), grade (Ki-67%-based) (HR-2.5; 95%-CI 1.4-4.7; p = 0.003) and perineural invasion (HR-2.1; 95%-CI 1.1-3.9; p = 0.029) were prognostic for relapse. Factors remaining significant after multivariable analysis were tumour size (HR-1.67; 95%-CI 1.04-2.70; p = 0.03), nodal involvement (HR-2.61; 95%-CI 1.17-5.83; p = 0.013) and Ki-67 at the time of diagnosis (HR-1.93; 95%-CI 1.24-3.0; p = 0.002). CONCLUSION: Size of tumour, lymph node involvement and Ki-67 were independent prognostic factors for relapse after potentially curative surgery in NET.

Digital histology quantification of intra-hepatic fat in patients undergoing liver resection.

BACKGROUND: High intra-hepatic fat (IHF) content is associated with insulin resistance, visceral adiposity, and increased morbidity and mortality following liver resection. However, in clinical practice, IHF is assessed indirectly by pre-operative imaging [for example, chemical-shift magnetic resonance (CS-MR)]. We used the opportunity in patients undergoing liver resection to quantify IHF by digital histology (D-IHF) and relate this to CT-derived anthropometrics, insulin-related serum biomarkers, and IHF estimated by CS-MR. METHODS: A reproducible method for quantification of D-IHF using 7 histology slides (inter- and intra-rater concordance: 0.97 and 0.98) was developed. In 35 patients undergoing resection for colorectal cancer metastases, we measured: CT-derived subcutaneous and visceral adipose tissue volumes, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), fasting serum adiponectin, leptin and fetuin-A. We estimated relative IHF using CS-MR and developed prediction models for IHF using a factor-clustered approach. RESULTS: The multivariate linear regression models showed that D-IHF was best predicted by HOMA-IR (Beta coefficient(per doubling): 2.410, 95% CI: 1.093, 5.313) and adiponectin (ß(per doubling): 0.197, 95% CI: 0.058, 0.667), but not by anthropometrics. MR-derived IHF correlated with D-IHF (rho: 0.626; p = 0.0001), but levels of agreement deviated in upper range values (CS-MR over-estimated IHF: regression versus zero, p = 0.009); this could be adjusted for by a correction factor (CF: 0.7816). CONCLUSIONS: Our findings show IHF is associated with measures of insulin resistance, but not measures of visceral adiposity. CS-MR over-estimated IHF in the upper range. Larger studies are indicated to test whether a correction of imaging-derived IHF estimates is valid.

The epidemiology of and outcome from pancreatoduodenal trauma in the UK, 1989-2013.

INTRODUCTION: Pancreatoduodenal (PD) injury is an uncommon but serious complication of blunt and penetrating trauma, associated with high mortality. The aim of this study was to assess the incidence, mechanisms of injury, initial operation rates and outcome of patients who sustained PD trauma in the UK from a large trauma registry, over the period 1989-2013. METHODS: The Trauma Audit and Research Network database was searched for details of any patient with blunt or penetrating trauma to the pancreas, duodenum or both. RESULTS: Of 356,534 trauma cases, 1,155 (0.32%) sustained PD trauma. The median patient age was 27 years for blunt trauma and 27.5 years for penetrating trauma. The male-to-female ratio was 2.5:1. Blunt trauma was the most common type of injury seen, with a ratio of blunt-to-penetrating PD injury ratio of 3.6:1. Road traffic collision was the most common mechanism of injury, accounting for 673 cases (58.3%). The median injury severity score (ISS) was 25 (IQR: 14-35) for blunt trauma and 14 (IQR: 9-18) for penetrating trauma. The mortality rate for blunt PD trauma was 17.6%; it was 12.2% for penetrating PD trauma. Variables predicting mortality after pancreatic trauma were increasing age, ISS, haemodynamic compromise and not having undergone an operation. CONCLUSIONS: Isolated pancreatic injuries are uncommon; most coexist with other injuries. In the UK, a high proportion of cases are due to blunt trauma, which differs from US and South African series. Mortality is high in the UK but comparison with other surgical series is difficult because of selection bias in their datasets.

Equivalent survival in patients with and without steatosis undergoing resection for colorectal liver metastases following pre-operative chemotherapy.

BACKGROUND: We previously reported that the presence of steatosis did not adversely influence survival in patients undergoing resection for colorectal liver metastases (CLM) without pre-operative chemotherapy. Here, this hypothesis is tested in patients undergoing resection for CLM following pre-operative chemotherapy. METHODS: We assessed the effects of background liver pathology, categorized as 'normal', 'steatosis' and 'other', on perioperative mortality, overall survival (OS) and cancer-specific survival (CSS) in LiverMetSurvey patients. Survival analyses included log-rank tests and multivariate Cox models, incorporating well-established prognosticators. In secondary analyses, re-populating the model with non-chemotherapy patients, the effect modification of chemotherapy on the impact of steatosis on survival was tested. RESULTS: Of 4329 patients undergoing first-time liver resection following pre-operative chemotherapy, histologies were normal in 1913 (44%), steatosis in 1675 (39%), and other abnormal pathologies in 741 (17%). For normal, steatosis and other, 90-day mortalities were 2.1%, 2.3%, and 3.5% (P = 0.103). For the three histo-pathological groups, 5-year OS rates were 39%, 42%, and 36% (Plogrank = 0.363); 5-year CSS rates were 43%, 45% and 41% (Plogrank = 0.496), respectively. The associations of steatosis with OS and CSS were materially unchanged in the multivariate models. Chemotherapy did not interact with the effect of steatosis on survival. CONCLUSION: The findings of equivalent survivals challenge the common perception that steatosis in CLM patients after pre-operative chemotherapy is associated with increased peri-operative mortality and poorer long-term survival.

Excess adiposity and gastrointestinal cancer.

BACKGROUND: Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice. METHODS: Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention. RESULTS AND CONCLUSION: A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future.

A comparison of diagnostic imaging modalities for colorectal liver metastases.

AIMS: The aims of this study were to compare the diagnostic performance of CT scan, MR liver, PET-CT and intra-operative ultrasound (IOUS) for the detection of liver metastases against the histopathological findings, and to compare PET-CT with CT for the detection of distant disease in metastatic colorectal cancer patients eligible for surgical treatment. METHODS: A prospective study was performed that measured concordance between the number and stage of metastatic lesions identified with various preoperative imaging modalities and histology of patients undergoing surgical treatment for CRLM. RESULTS: Compared with histopathology, concordance for the number of metastatic liver lesions was moderate for CT scan (K = 0.477, 95% CI: 0.28-0.66), moderate for MR scan (K = 0.574, 95% CI: 0.39-0.75), good for FDG PET-CT (K = 0.703, 95% CI: 0.52-0.87) and very good for IOUS (K = 0.904, 95% CI: 0.81-0.99). Additional CRLM were identified intraoperatively in six patients (9.1%) with IOUS and in 7.5% of the cases surgical strategy was changed according to the new intraoperative findings. The diagnosis of intra abdominal lymph node metastatic disease was made with PET-CT only in nine patients (13.6%) DISCUSSION: Our study supports the recent recommendations of the Oncosurg Multidisciplinary International Consensus regarding the importance of high quality CT and MR in the staging of CRLM but provides further evidence for the added value of PET-CT, especially in detecting extrahepatic intra-abdominal metastatic disease that may be amenable to potentially curative resection. Despite these advances in preoperative staging, there still remains a role for IOUS in detecting additional metastases at the time of surgery.

Intestinal ciprofloxacin efflux: the role of breast cancer resistance protein (ABCG2).

Intestinal secretory movement of the fluoroquinolone antibiotic, ciprofloxacin, may limit its oral bioavailability. Active ATP-binding cassette (ABC) transporters such as breast cancer resistance protein (BCRP) have been implicated in ciprofloxacin transport. The aim of this study was to test the hypothesis that BCRP alone mediates intestinal ciprofloxacin secretion. The involvement of ABC transport proteins in ciprofloxacin secretory flux was investigated with the combined use of transfected cell lines [bcrp1/BCRP-Madin-Darby canine kidney II (MDCKII) and multidrug resistance-related protein 4 (MRP4)-human embryonic kidney (HEK) 293] and human intestinal Caco-2 cells, combined with pharmacological inhibition using 3-(6-isobutyl-9-methoxy-1,4-dioxo-1,2,3,4,6, 7,12,12a-octahydropyrazino[1',2':1,6]pyrido[3,4-b]indol-3-yl)-propionic acid tert-butyl ester (Ko143), cyclosporine, 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK571), and verapamil as ABC-selective inhibitors. In addition, the regional variation in secretory capacity was investigated using male Han Wistar rat intestine mounted in Ussing chambers, and the first indicative measurements of ciprofloxacin transport by ex vivo human jejunum were made. Active, Ko143-sensitive ciprofloxacin secretion was observed in bcrp1-MDCKII cell layers, but in low-passage (BCRP-expressing) Caco-2 cell layers only a 54% fraction was Ko143-sensitive. Ciprofloxacin accumulation was lower in MRP4-HEK293 cells than in the parent line, indicating that ciprofloxacin is also a substrate for this transporter. Ciprofloxacin secretion by Caco-2 cell layers was not inhibited by MK571. Secretory flux showed marked regional variability in the rat intestine, increasing from the duodenum to peak in the ileum. Ciprofloxacin secretion was present in human jejunum and was reduced by Ko143 but showed marked interindividual variability. Ciprofloxacin is a substrate for human and rodent BCRP. An additional pathway for ciprofloxacin secretion exists in Caco-2 cells, which is unlikely to be MRP(4)-mediated. BCRP is likely to be the dominant transport mechanism for ciprofloxacin efflux in both rat and human jejunum.

Organophosphate poisoning in a 12-day-old infant: case report.

A 12-day-old infant girl was admitted with increasing lethargy and respiratory distress. Initial treatment was for pneumonia but deterioration despite appropriate treatment prompted review of her diagnosis and consideration of organophosphate poisoning. There was a brisk response to atropine. To our knowledge, this is the youngest infant reported to have been exposed to poisoning by organophosphates.

Evaluation of surgical outcome scores according to ISGPS definitions in patients undergoing pancreatic resection.

AIMS: To evaluate the role of the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM), the Portsmouth variant (p-POSSUM) and the Glasgow Prognostic Score (GPS) in predicting outcome after pancreatic surgery with reference to the International Study Group of Pancreatic Surgery (ISGPS) definitions of post-pancreatectomy complications. METHODS: All consecutive patients undergoing major pancreatic resection over a 32- month period were included. POSSUM, p-POSSUM and GPS score were calculated for each patient and correlated against the observed mortality and morbidity using the ISGPS definitions. RESULTS: The observed:expected ratios for POSSUM mortality, POSSUM morbidity and p-POSSUM mortality were 0.24 (p < 0.0001), 0.86 (p < 0.0001) and 0.79 (p = 0.09), respectively. POSSUM had a 'poor fit' with respect to predicting morbidity (χ(2) = 16.4, 8 d.f., p = 0.04). Multifactorial regression analysis revealed the GPS as an independent predictor of post-operative outcome (GPS 1, p = 0.03, OR 2.99, 95% CI 1.4-7.9, and GPS 2, p = 0.02, OR 4.3, 95% CI 1.8-15.5). CONCLUSION: POSSUM has a limited role as an outcome score in pancreatic resection. The GPS may be a novel alternative to POSSUM as a pre-operative predictor of outcome.

The prognostic significance of the preoperative full blood count after resection of colorectal liver metastases.

INTRODUCTION: Increased preoperative platelet and neutrophil counts are risk factors for decreased survival in several different malignancies. Our aim was to investigate the relationship between overall or disease-free survival after resection of CRLM and the preoperative haematological parameters. METHODS: We reviewed a cohort of 140 patients who underwent resection of CRLM with curative intent, utilising prospectively maintained databases. Patient demographics, operative details, FBC, CRP, INR, histopathology results, and survival data were examined. Kaplan-Meier survival and Cox regression analyses were used to determine the impact of all variables on survival. RESULTS: 140 patients (96 males) with a median age of 67 years (range 33-82 years) underwent resection of CRLM. A significant correlation was exhibited between preoperative platelet count and neutrophil count (rho = 0.186, P = .028). When modelled as continuous covariates in a Cox regression hazards, an increased preoperative platelet (P = .02) and neutrophil counts (P

Perioperative use of the LiMON method of indocyanine green elimination measurement for the prediction and early detection of post-hepatectomy liver failure.

INTRODUCTION: A non-invasive liver function monitoring system, the LiMON, has been developed that measures indocyanine green (ICG) elimination by pulse spectrophotometry. The aim was to assess the relationship between pre and post-operative ICG plasma disappearance rate (ICG PDR %/min) values and the onset of post-hepatectomy liver dysfunction. METHODS: 37 patients scheduled for major liver resections were selected. None had chronic liver disease. IGC PDR was measured preoperatively and on days 1, five and 10 postoperatively. On the same day, serum liver function tests were measured. RESULTS: The median preoperative and post-operative day 1 ICG PDR for the patients who developed liver dysfunction was significantly lower compared to those who did not (p=0.044, p=0.014). Significant correlation was found between ICG PDR measurement taken on postoperative day 1 and bilirubin level on day 1 (p=0.002), 5 (p=<0.001) and 10 (p=0.001). The same was true for ICG PDR on post-operative day 1 and albumin level on day 5 and 10 (p=0.003, p<0.001). DISCUSSION: LiMON ICG PDR measured by pulse spectophotometry is a quick, non-invasive and reliable liver function test in patients undergoing liver resection that aids in the prediction and early detection of post-hepatectomy liver dysfunction.

The Oncosurge strategy for the management of colorectal liver metastases - an external validation study.

INTRODUCTION: Because most patients with colorectal liver metastases (CRLM) present to general surgeons and oncologists without a specialist interest in their management, a computer program (OncoSurge) has been created that identifies individual patient resectability and recommends optimal treatment strategies. The aim of this study was to validate the Oncosurge strategy by comparing its recommendations with the decisions made by a multidisciplinary (MDT) meeting, in a supra-regional hepatobiliary referral centre, using real cases with known outcomes. METHODS: We reviewed the records and imaging of 98 consecutive patients with CRLM, who had been referred for decision making to our MDT meeting between January 1, 2004 and December 31, 2004. All patient and tumour characteristics were entered onto the Oncosurge decision model, which was accessed at www.evidis.com/oncosurge/ RESULTS: There was concordance between Oncosurge and MDT decisions in 93/98 cases. The observed kappa (kappa) was 0.850 (95% CI: 0.728-0.972). In descriptive terms, a kappa score greater than 0.8 equates to "almost perfect agreement". CONCLUSIONS: Our results demonstrate the validity of the Oncosurge system when compared to one year of decision making in an established hepatobiliary MDT meeting. This confirms the utility of the Oncosurge system for decision making, audit and educational purposes.

Endoscopic stent insertion for the palliation of malignant gastric outlet obstruction.

BACKGROUND/AIMS: Controversy exists as to whether endoscopic or minimally invasive/open bypass is superior in cases of malignant gastric outlet obstruction. METHODS: Retrospective observational study following those patients admitted to the hospital between January 1999 and December 2004 (n = 23) with gastric outlet obstruction. In all suitable patients endoscopic stent insertion was attempted. Symptomatic improvement was monitored as was time until discharge as well as need for readmission. We also recorded morbidity and mortality associated with the procedure as well as final survival in days. RESULTS: Stents were inserted successfully in 21 patients. Two patients went on to have a laparoscopic bypass. Stent placement relieved obstructive symptoms in all patients. A median inpatient stay of 4 days was achieved (range 2-9 days). One patient was admitted with recurrent symptoms 9 months following his initial treatment. Investigation showed the distal end of the stent to be occluded by further tumor. His symptoms were relieved by the insertion of a second stent. In 19 patients death was due to metastatic disease. Operative mortality: cerebrovascular accident day 2 (n = 1), duodenal perforation day 4 (n = 1). CONCLUSION: Patients with malignant gastric outlet obstruction not suitable for resection should be assessed for insertion of an enteral stent.

Muir-Torre syndrome: a case for surveillance of the ampulla of Vater.

A 64-year-old man with Muir-Torre syndrome (MTS), a condition characterized by the association of multiple sebaceous tumours and kerato-acanthomas with internal malignancies, developed a carcinoma of the ampulla of Vater. This is the 2nd reported ampullary carcinoma in 205 reported cases of MTS, suggesting a higher prevalence in MTS patients than in the general population. As an ampullary carcinoma is potentially amenable to surgical resection, particularly when detected early, patients with MTS should undergo regular endoscopic surveillance of the ampulla of Vater.