Significance of predicted future liver remnant volume on liver failure risk after major hepatectomy: a case matched comparative study.

Introduction: Future liver remnant volume (FLRV), a risk factor for liver failure (PHLF) after major hepatectomy (MH), is not routinely measured. This study aimed to evaluate the association between FLRV and PHLF. Patients and methods: All patients undergoing MH (4 + segments) between 2011 and 2018 were identified from a prospectively maintained single-centre database. Perioperative data were collected for patients with PHLF, who were matched (1:2) with non-PHLF controls. FLRV and FLRV% (i.e., % of total liver volume) were calculated retrospectively from preoperative CT scans using Synapse-3D software, and compared between the PHLF and matched control groups. Results: Of 711 patients undergoing MH, PHLF occurred in 27 (3.8%), of whom 24 had preoperative CT scans available. These patients were matched to 48 non-PHLF controls, 98% of whom were classified as being at high risk of PHLF on preoperative risk scoring. FLRV% was significantly lower in the PHLF group, compared to matched controls (median: 28.7 vs. 35.2%, p = 0.010), with FLRV% < 30% in 58% and 29% of patients, respectively. Assessment of the ability of FLRV% to differentiate between PHLF and matched controls returned an area under the ROC curve of 0.69, and an optimal cut-off value of FLRV% < 31.5%, which yielded 79% sensitivity and 67% specificity. Conclusions: FLRV% is significantly predictive of PHLF after MH, with over half of patients with PHLF having FLRV% < 30%. In light of this, we propose that all patients should undergo risk stratification prior to MH, with the high risk patients additionally being assessed with CT volumetry.

Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?

BACKGROUND: Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the 'Fast Recovery' programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated. RESULTS: The N = 44 patients treated after the introduction of the 'Fast Recovery' programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m. CONCLUSIONS: The multimodal 'Fast Recovery' programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

Evaluation of the clinical and economic impact of delays to surgery in patients with periampullary cancer.

Background: Early treatment is the only potential cure for periampullary cancer. The pathway to surgery is complex and involves multiple procedures across local and specialist hospitals. The aim of this study was to analyse variability within this pathway, and its impact on cost and outcomes. Methods: Patients undergoing surgery for periampullary cancer (2011-2016) were identified retrospectively and their pathway to surgery was analysed. Patients who had early surgery (shortest quartile, Q1) were compared with those having late surgery (longest quartile, Q4). Results: A total of 483 patients were included in the study, with 121 and 124 patients in Q1 and Q4 respectively. The median time from initial CT to surgery was 21 days for Q1 versus 112 days for Q4 (P < 0·001). Diagnostic delays were common in Q4; these patients required significantly more investigations than those in Q1 (endoscopic ultrasonography (EUS): 74·2 versus 18·2 per cent respectively, P < 0·001; MRI: 33·6 versus 20·6 per cent, P = 0·036). The median time to diagnostic EUS was 13 days in Q1 versus 59 days in Q4 (P < 0·001). Some 42·1 per cent of jaundiced patients in Q1 underwent preoperative biliary drainage, compared with all patients in Q4. There were significantly more unplanned admissions and associated longer duration of hospital stay per patient and costs in Q4 than in Q1 (median: 8 versus 3 days respectively; €5652 versus €2088; both P < 0·001). There was a higher likelihood of potentially curative surgery in Q1 (82·6 per cent versus 66·9 per cent in Q4; P = 0·005). Conclusion: There is wide variation across the entire pathway, suggesting that multiple strategies are required to enable early surgery. Defining an effective pathway by anticipating the need for investigations and avoiding biliary drainage reduces unplanned admissions and costs and increases resection rates.

Propensity-matched analysis of the influence of perioperative statin therapy on outcomes after liver resection.

Background: Perioperative use of statins is reported to improve postoperative outcomes after cardiac and non-cardiovascular surgery. The aim of this study was to investigate the influence of statins on postoperative outcomes including complications of grade IIIa and above, posthepatectomy liver failure (PHLF), and 90-day mortality rates after liver resection. Methods: Patients who underwent hepatectomy between 2013 and 2017 were reviewed to identify statin users and non-users (controls). Propensity matching was conducted for age, BMI, type of surgery and preoperative co-morbidities to compare subgroups. Univariable and multivariable analyses were performed for the following outcomes: 90-day mortality, significant postoperative complications and PHLF. Results: Of 890 patients who had liver resection during the study period, 162 (18·2 per cent) were taking perioperative statins. Propensity analysis selected two matched groups, each comprising 154 patients. Overall, 81 patients (9·1 per cent) developed complications of grade IIIa or above, and the 90-day mortality rate was 3·4 per cent (30 patients), with no statistically significant difference when the groups were compared before and after matching. The rate of PHLF was significantly lower in patients on perioperative statins than in those not taking statins (10·5 versus 17·3 per cent respectively; P = 0·033); similar results were found after propensity matching (10·4 versus 20·8 per cent respectively; P = 0·026). Conclusion: The rate of PHLF was significantly lower in patients taking perioperative statins, but there was no statistically significant difference in severe complications and mortality rates.

Management of pancreaticoduodenal artery aneurysm associated with coeliac artery stenosis.

Pancreaticoduodenal and gastroduodenal artery aneurysms are rare but require early radiological or surgical intervention due to a high risk (61%) of rupture. A 71-year-old woman presented with an incidental 30-mm aneurysm arising from the inferior pancreaticoduodenal artery associated with coeliac axis stenosis. She underwent embolisation of the pancreaticoduodenal aneurysm, but the coeliac axis stenosis was not amenable to radiological intervention. She remained well at six months of follow-up and a repeat computed tomography angiogram six months later reported stable appearances. The management of pancreaticoduodenal aneurysms is discussed.

Development and multicentre validation of a prognostic model to predict resectability of pancreatic head malignancy.

BACKGROUND: At the time of planned pancreatoduodenectomy patients frequently undergo exploratory laparotomy without resection, leading to delayed systemic therapy. This study aimed to develop and validate a prognostic model for the preoperative prediction of resectability of pancreatic head tumours. METHODS: This was a retrospective study of patients undergoing attempted resection for confirmed malignant tumours of the pancreatic head in a university hospital in Hannover, Germany. The prognostic value of patient and tumour characteristics was investigated in a multivariable logistic regression model. External validation was performed using data from two other centres. RESULTS: Some 109 patients were included in the development cohort, with 51 and 175 patients in the two validation cohorts. Eighty patients (73·4 per cent) in the development cohort underwent resection, and 37 (73 per cent) and 141 (80·6 per cent) in the validation cohorts. The main reasons for performing no resection in the development cohort were: local invasion of vasculature or arterial abutment (15 patients, 52 per cent), and liver (12, 41 per cent), peritoneal (8, 28 per cent) and aortocaval lymph node (6, 21 per cent) metastases. The final model contained the following variables: time to surgery (odds ratio (OR) 0·99, 95 per cent c.i. 0·98 to 0·99), carbohydrate antigen 19-9 concentration (OR 0·99, 0·99 to 0·99), jaundice (OR 4·45, 1·21 to 16·36) and back pain (OR 0·02, 0·00 to 0·22), with an area under the receiver operating characteristic (ROC) curve (AUROC) of 0·918 in the development cohort. AUROC values were 0·813 and 0·761 in the validation cohorts. The positive predictive value of the final model for prediction of resectability was 98·0 per cent in the development cohort, and 91·7 and 94·7 per cent in the two external validation cohorts. [Corrections added on 18 July 2018, after first online publication: The figures for OR of the variables time to surgery and CA19-9 in the abstract and in Table 3 and Table 4 were amended from 1·00 to 0·99]. CONCLUSION: For preoperative prediction of the likelihood of resectability of pancreatic head tumours, this validated model is a valuable addition to CT findings.

Comparison of preoperative CT-based imaging parameters to predict postoperative pancreatic fistula.

AIM: To review all reported methods of preoperative computed tomography (CT) in one patient cohort and to identify which were the strongest to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. MATERIALS AND METHODS: Consecutive patients undergoing pancreatoduodenectomy were included if they had unenhanced CT images for review. Eighteen variables and two scores were tested. Receiver operator characteristics (ROC) were explored. RESULTS: POPF affected 26 of 107 patients (24.3%). Nine variables were significantly related to POPF with pancreatic duct width having the largest area under the ROC curve (AUROC; 0.808, p<0.001). An obese body habitus was associated with POPF with six of nine related variables using data from CT images associated with POPF; of these intra-abdominal wall thickness yielded the largest AUROC (0.713, p=0.001). This corresponded to the finding that body mass index (BMI) was related to POPF (AUROC 0.705, p=0.002). The largest AUROC of all was associated with one of the predictive scores (0.828, p<0.001). Substituting BMI for intra-abdominal wall thickness in this score yielded a non-significant increase to predict POPF (AUROC 0.840, p=0.676). None of the assessments of organ density (in Hounsfield Units) were associated with POPF. CONCLUSION: Data from preoperative CT imaging provides valuable information regarding a patient's risk of POPF. Obesity as assessed by CT images strongly relates to POPF, but the largest single risk factor for POPF is a narrow pancreatic duct.

Manganese-enhanced MRI predicts the histological grade of hepatocellular carcinoma in potential surgical candidates.

AIM: To evaluate the role of manganese-enhanced magnetic resonance (Mn-MRI) in predicting tumour differentiation prior to liver transplant or resection for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The inclusion criteria were patients with HCC who underwent Mn-MRI prior to transplantation or resection from 2001-2008. T1-weighted MRI images were acquired at 0 and 24h after manganese dipyridoxal diphosphate (MnDPDP) intravenous contrast medium and reviewed prospectively. Manganese retention at 24h was correlated with tumour differentiation and disease-free survival. RESULTS: Eighty-six patients underwent Mn-MRI (transplantation 60, resection 26); 114/125 lesions (91%) that were arterialised as evidenced at computed tomography (CT) and had manganese uptake on MRI were HCC. There were 11 false positives (9%) that were regenerative nodules. Ten of fourteen non-manganese-retaining HCC (71%) were poorly differentiated, compared with only 13/114 manganese-retaining HCC (11%) (p<0.0001). Sensitivity, specificity, positive and negative predictive values of non-retention of MnDPDP in predicting poorly differentiated tumours were 0.43, 0.96, 0.71 and 0.88. Median disease-free survival of patients with non-manganese-retaining HCC was less than for patients with manganese-retaining HCC (14±5 months versus 39±3 months, log rank p=0.025). CONCLUSION: Non-manganese-retaining HCCs are likely to be poorly differentiated and have a poor prognosis. Manganese-enhanced MRI appears to have a role in preoperative assessment of HCC and warrants further evaluation.

Spontaneous perforation of cervical oesophagus: a rare variant of Boerhaave's syndrome.

BACKGROUND: A 29-year-old man presented with sudden onset of severe pain in his throat, difficulty breathing and a hoarse voice, following an episode of vomiting. INVESTIGATIONS: Initial laboratory tests were normal. The patient underwent fibre-optic nasendoscopy, which demonstrated a haematoma in the piriform fossa. Lateral neck radiography and subsequent computed tomography scanning confirmed a 2 cm, loculated, gas-containing collection at the level of the vallecula in the right posterolateral wall, extending to the false vocal folds and communicating between the right parapharyngeal space and the right carotid sheath. Water-soluble contrast swallow confirmed the diagnosis. DIAGNOSIS: Contained oesophageal perforation. MANAGEMENT: Conservative treatment was adopted involving nil orally, intravenous antibiotics and nasogastric feeding. The patient made an uneventful recovery.

Transhiatal oesophagectomy: techniques, tips and outcomes.

AIM: To demonstrate our technique and valuable tips for transhiatal oesophagectomies. METHOD: 215 patients underwent transhiatal oesophagectomies in our unit between 2000 and 2006. RESULTS: In-hospital mortality was 0.9%. Anastomotic leak in 12 patients (5.6%). Chyle leak was seen in five patients and recurrent nerve neuropraxia in six patients. Iatrogenic splenectomy rate was 6%. The median operative time was 151 minutes (range 93-276 minutes). Overall median length of hospital stay was 15 days (range 8-95 days). The median survival for all patients undergoing transhiatal oesophagectomy for invasive malignancy was 42.9 months and the one-year and five-year survival were 81% and 48% respectively. CONCLUSION: This is a safe and oncologically sound procedure. We feel that the tips can be helpful for anyone performing this procedure.

Anastomotic strictures and delayed gastric emptying after esophagectomy: incidence, risk factors and management.

The aim of this study was to report the incidence, risk factors, and management of gastric conduit dysfunction after esophagectomy in 177 patients over a 3-year period in a single center. Patients with anastomotic strictures or delayed gastric emptying (DGE) were identified from a prospective database. Anastomotic strictures occurred in 48 patients (27%). Eighty-three percent of early anastomotic strictures (<1 year) were benign, and all late strictures (>1 year) were malignant. Dilatation was effective in 98% of benign and 64% of malignant strictures. DGE occurred in 21 patients (12%), and was associated with both anastomotic leak (P = 0.001) and anastomotic stricture (P = 0.001). 4/8 patients with late DGE (>3 months postesophagectomy) were tumor-related. Pyloric dilatation was effective in 92% of early and 63% of late DGE. Pyloric stents were inserted in 3 patients with tumor-related DGE. After esophagectomy, early anastomotic strictures (within 1 year) and early delayed gastric emptying (within 3 months) are usually benign and respond to dilatation. However, patients presenting later with tumor-related obstruction are unlikely to respond to anastomotic or pyloric dilatation and should be stented.

From frown lines to fissures: therapeutic uses for botulinum toxin.

INTRODUCTION: Since the pharmacological mode of action of botulinum toxin (BTX) has been elucidated, its therapeutic potential has been increasingly recognised. The aims of this review were to summarize our current understanding of the pharmacological action of this agent and to review its therapeutic uses. METHODS: An electronic literature search with Medline (January 1965 to December 2004) was carried out to identify articles related to the pharmacological mode of action and clinical uses for botulinum toxin using the keyword "botulinum toxin". RESULTS AND CONCLUSION: Botulinum toxin A is emerging as a valuable clinical tool, both for diagnostic and therapeutic purposes in a wide variety of disorders, and is already the treatment of choice for selected conditions. Better understanding of its modes of action may identify alternative targets for pharmacological intervention, and may allow development of longer acting drugs with lower immunogenicity. Therapeutic uses of BTX-A must be assessed systematically in prospective studies, and the clinical role of other subtypes requires evaluation.