Liver resection and ablation for squamous cell carcinoma liver metastases.

BACKGROUND: Limited evidence exists to guide the management of patients with liver metastases from squamous cell carcinoma (SCC). The aim of this retrospective multicentre cohort study was to describe patterns of disease recurrence after liver resection/ablation for SCC liver metastases and factors associated with recurrence-free survival (RFS) and overall survival (OS). METHOD: Members of the European-African Hepato-Pancreato-Biliary Association were invited to include all consecutive patients undergoing liver resection/ablation for SCC liver metastases between 2002 and 2019. Patient, tumour and perioperative characteristics were analysed with regard to RFS and OS. RESULTS: Among the 102 patients included from 24 European centres, 56 patients had anal cancer, and 46 patients had SCC from other origin. RFS in patients with anal cancer and non-anal cancer was 16 and 9 months, respectively (P = 0.134). A positive resection margin significantly influenced RFS for both anal cancer and non-anal cancer liver metastases (hazard ratio 6.82, 95 per cent c.i. 2.40 to 19.35, for the entire cohort). Median survival duration and 5-year OS rate among patients with anal cancer and non-anal cancer were 50 months and 45 per cent and 21 months and 25 per cent, respectively. For the entire cohort, only non-radical resection was associated with worse overall survival (hazard ratio 3.21, 95 per cent c.i. 1.24 to 8.30). CONCLUSION: Liver resection/ablation of liver metastases from SCC can result in long-term survival. Survival was superior in treated patients with liver metastases from anal versus non-anal cancer. A negative resection margin is paramount for acceptable outcome.

Colorectal cancer with synchronous hepatic metastases: Systematic review of reports comparing synchronous surgery with sequential bowel-first or liver-first approaches.

BACKGROUND: The management of colorectal cancer with synchronous liver-limited metastases currently lacks randomised trial evidence to inform case selection for any of the bowel-first, liver-first or synchronous surgery routes. We examine the literature to report outcome data from reports utilising all three approaches. METHODS: A systematic review was conducted using OvidSP (including Embase, EBM Reviews and MEDLINE databases) to find articles reporting discrete peri-operative and long-term outcomes for patients undergoing sequential bowel-first, liver-first surgery or synchronous liver and bowel surgery. RESULTS: Of 223 unique citations, 3 cohort studies were identified comprising a pooled population of 1203 patients who completed treatment protocols between 1982 and 2011. Patients were allocated to bowel-first surgery (748 patients, 62.2%), liver-first surgery (75, 6.2%) or synchronous liver/bowel surgery (380, 31.6%). Minor complications were similar between procedures. Major complications were consistent with a pooled fixed estimate of 9.1% (95%CI: 7.6%-10.8%, I(2) = 48%). Post-operative death was rare and consistent with a pooled fixed effect estimate of 3.1% (95%CI: 2.2%-4.3%, I(2) = 0%). Median follow-up ranged from 25.1 to 40.0 months, with a pooled underlying 5-year survival fixed effect estimate of 44% (I(2) = 39%). CONCLUSION: This review assesses outcomes of patients with colorectal cancer with synchronous liver metastases managed by either synchronous, sequential liver-first or bowel-first surgery. Overall treatment-related mortality is low and survival is similar among the three groups. These findings provide support for the continued use of all three pathways until better evidence to guide selection of an individual treatment option is available.

Cardiopulmonary exercise testing for preoperative risk assessment before pancreaticoduodenectomy for cancer.

OBJECTIVE: Pancreaticoduodenectomy is the standard of care for tumors confined to the head of pancreas and can be undertaken with low operative mortality. The procedure has a high morbidity, particularly in older patient populations with preexisting comorbidities. This study evaluated the role of cardiopulmonary exercise testing to predict postoperative morbidity and outcome in high-risk patients undergoing pancreaticoduodenectomy. METHODS: In a prospective cohort of consecutive patients undergoing pancreaticoduodenectomy, those aged over 65 years (or younger with comorbidity) were categorized as high risk and underwent preoperative assessment by cardiopulmonary exercise testing (CPET) according to a predefined protocol. Data were collected on functional status, postoperative complications, and survival. RESULTS: A total of 143 patients underwent preoperative assessment, 50 of whom were deemed to be at low risk for surgery per study protocol. Of 93 high-risk patients, 64 proceeded to surgery after preoperative CPET. Neither anaerobic threshold (AT) nor maximal oxygen consumption ([Formula: see text] O 2 MAX) predicted patient mortality or morbidity. However, ventilatory equivalent of carbon dioxide ([Formula: see text] E/[Formula: see text] CO 2) at AT was a predictive marker of postoperative mortality, with an area under the curve (AUC) of 0.84 (95 % confidence interval [CI] 0.63-1.00, p = 0.020); a threshold of 41 was 75 % sensitive and 95 % specific (positive predictive value 50 %, negative predictive value 98 %). Above this threshold, raised [Formula: see text] E/[Formula: see text] CO 2 predicted poor long-term survival (hazard ratio 2.05, 95 % CI 1.09-3.86, p = 0.026). CONCLUSIONS: CPET is a useful adjunctive test for predicting postoperative outcome in patients being assessed for pancreaticoduodenectomy. Raised CPET-derived [Formula: see text] E/[Formula: see text] CO 2 predicts early postoperative death and poor long-term survival.

Peripheral oxygen extraction in patients with malignant obstructive jaundice.

Malignant obstructive jaundice is associated with poor aerobic capacity. We measured oxygen consumption and oxygen extraction (arterial-venous oxygen content) in the legs of nine patients during cardiopulmonary exercise testing before pancreaticoduodenectomy. The median (IQR [range]) peak oxygen consumption was 67 (49-77 [32-84])% of predicted. Normal patterns of oxygen extraction were seen with increasing power towards lactate threshold. Near maximal oxygen extraction occurred at peak exercise. Femoral venous oxygen pressure and saturation exceeded baseline values whilst recovering from exercise. These findings suggest that peripheral oxygen extraction is normal during exercise in patients with malignant obstructive jaundice. The primary limitation in oxygen consumption is reduced oxygen delivery.

[International multidisciplinary classification of acute pancreatitis severity: the 2013 Spanish edition]. / Clasificación Internacional y Multidisciplinaria de la Pancreatitis Aguda: Edición Española 2013.

OBJECTIVE: To develop a new classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of the published evidence, and worldwide consultation. BACKGROUNDS: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of specialist in pancreatic diseases, but are suboptimal because these definitions are based on the empiric description of events not associated with severity. METHODS: A personal invitation to contribute to the development of a new classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists and radiologists currently active in the field of clinical acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global web-based survey was conducted, and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new classification of severity is based on the actual local and systemic determinants of severity, rather than on the description of events that are non-causally associated with severity. The local determinant relates to whether there is (peri) pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another, whereby the presence of both infected (peri) pancreatic necrosis and persistent organ failure has a greater impact upon severity than either determinant alone. The derivation of a classification based on the above principles results in four categories of severity: mild, moderate, severe, and critical. CONCLUSIONS: This classification is the result of a consultative process among specialists in pancreatic diseases from 49 countries spanning North America, South America, Europe, Asia, Oceania and Africa. It provides a set of concise up to date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

[Multidisciplinar international classification of the severity of acute pancreatitis: Italian version 2013]. / Classificazione Internazionale Multidisciplinare della Gravità della Pancreatite Acuta Versione Italiana 2013.

AIM: The aim of this paper was to present the 2013 Italian edition of a new international classification of acute pancreatitis severity. The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric description of occurrences that are merely associated with severity. METHODS: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensivists, and radiologists who are currently active in clinical research on acute pancreatitis. A global web-based survey was conducted and a dedicated international symposium was organized to bring contributors from different disciplines together and discuss the concept and definitions. RESULTS: The new international classification is based on the actual local and systemic determinants of severity, rather than description of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity-mild, moderate, severe, and critical. CONCLUSION: This classification provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research.

[Determinant-based classification of acute pancreatitis severity. International multidisciplinary classification of acute pancreatitis severity: the 2013 German edition]. / Einteilung des Schweregrads der akuten Pankreatitis. Internationale, multidisziplinäre klinische Klassifikation auf Basis pathogenetischer Determinanten: Deutsche Version 2013.

OBJECTIVE: The aim of this study was to develop a new international classification of acute pancreatitis severity on the basis of a sound conceptual framework, comprehensive review of published evidence, and worldwide consultation. BACKGROUND: The Atlanta definitions of acute pancreatitis severity are ingrained in the lexicon of pancreatologists but suboptimal because these definitions are based on empiric descriptions of occurrences that are merely associated with severity. METHODS: A personal invitation to contribute to the development of a new international classification of acute pancreatitis severity was sent to all surgeons, gastroenterologists, internists, intensive medicine specialists, and radiologists who are currently active in clinical research on acute pancreatitis. The invitation was not limited to members of certain associations or residents of certain countries. A global Web-based survey was conducted and a dedicated international symposium was organised to bring contributors from different disciplines together and discuss the concept and definitions. RESULT: The new international classification is based on the actual local and systemic determinants of severity, rather than descriptions of events that are correlated with severity. The local determinant relates to whether there is (peri)pancreatic necrosis or not, and if present, whether it is sterile or infected. The systemic determinant relates to whether there is organ failure or not, and if present, whether it is transient or persistent. The presence of one determinant can modify the effect of another such that the presence of both infected (peri)pancreatic necrosis and persistent organ failure have a greater effect on severity than either determinant alone. The derivation of a classification based on the above principles results in 4 categories of severity - mild, moderate, severe, and critical. CONCLUSIONS: This classification is the result of a consultative process amongst pancreatologists from 49 countries spanning North America, South America, Europe, Asia, Oceania, and Africa. It provides a set of concise up-to-date definitions of all the main entities pertinent to classifying the severity of acute pancreatitis in clinical practice and research. This ensures that the determinant-based classification can be used in a uniform manner throughout the world.

Thoracic surgical management of colorectal lung metastases: a questionnaire survey of members of the Society for Cardiothoracic Surgery in Great Britain and Ireland.

INTRODUCTION: Distant metastases to liver and lung are not uncommon in colorectal cancer. Resection of metastases is accepted widely as the standard of care. However, there is no firm evidence base for this. This questionnaire survey was carried out to assess the current practice preferences of cardiothoracic surgeons in Great Britain and Ireland. METHODS: An online questionnaire survey was emailed to cardiothoracic surgeons in Great Britain and Ireland. The survey was live for 12 weeks. Responses were collated with SurveyMonkey(®). RESULTS: Overall, there were 75 respondents. The majority (83%) indicated thoracic surgery as a specialist interest. Almost all (99%) used thoracic computed tomography (CT) for staging; 70% added liver CT and 51% added pelvic CT. Fluorodeoxy-glucose positron emission tomography was used by 86%. The most frequent indication for pulmonary resection (97%) was solitary lung metastasis without extrathoracic disease. Video assisted thoracoscopic surgery (VATS) was used by 85%. In addition, thoracotomy was used by 96%. A third (33%) used radiofrequency ablation. Synchronous liver and lung resection was contraindicated for 83% of respondents. Over three-quarters (77%) thought that scientific equipoise exists presently for lung resection for colorectal lung metastases but only 21% supported a moratorium on this type of surgery until further evidence becomes available. CONCLUSIONS: The results confirm that the majority of respondents use conventional cross-sectional imaging and either VATS or formal thoracotomy for resection. The results emphasise the continuing need for formal randomised trials to provide evidence of any survival benefit from pulmonary metastasectomy for colorectal lung metastases.

In vivo evaluation of the chitosan-based haemostatic agent Omni-stat® in porcine liver resection and in liver injury.

BACKGROUND: Omni-stat®, a polysaccharide made by de-acetylation of chitin, is currently in use as a battlefield topical haemostat. This experimental study undertakes the first evaluation of Omni-stat in an in vivo porcine hepatectomy and liver trauma model. METHODS: A model of sequential liver resection was employed: following liver resection, further resections were undertaken in the same animal provided that there was cessation of bleeding from the earlier resection and that haemodynamic stability was maintained. An additional liver trauma injury was undertaken after completion of all resections. Data were collected on heart rate, blood pressure, haematocrit, resection volumes, blood loss and the efficacy of Omni-stat in haemostasis. RESULTS: Eight minor resections and 12 major resections were undertaken. Topical application of Omni-stat to raw post-transection surfaces immediately upon completion of resection achieved complete haemostasis with a single application in 14 of 15 (93%) resections. There was no recurrence of bleeding during the 5-hour protocol. The median time for cessation of bleeding after resection in the Omni-stat group was 3 min (range 3-6). This was not significantly different from time to cessation of bleeding in 5 control resections. There was no difference in blood loss or haemodynamic parameters. Respiratory rate was significantly faster after application of Omni-stat. In 2 liver lacerations, Omni-stat was effective in achieving cessation of haemorrhage. CONCLUSION: Omni-stat is an effective haemostat in experimental in vivo porcine liver resection and liver trauma. Further evaluation is required to assess its physiological absorption profile in man and its comparative efficacy against commercially established agents.

Cardiopulmonary exercise testing for preoperative risk assessment before hepatic resection.

BACKGROUND: Contemporary liver surgery practice must accurately assess operative risk in increasingly elderly populations with greater co-morbidity. This study evaluated preoperative cardiopulmonary exercise testing (CPET) in high-risk patients undergoing hepatic resection. METHODS: In a prospective cohort referred for liver resection, patients aged over 65 years (or younger with co-morbidity) were evaluated by preoperative CPET. Data were collected prospectively on functional status, postoperative complications and survival. RESULTS: Two hundred and four patients were assessed for hepatic resection, of whom 108 had preoperative CPET. An anaerobic threshold (AT) of 9·9 ml O(2) per kg per min predicted in-hospital death and subsequent survival. Below this value, AT was 100 per cent sensitive and 76 per cent specific for in-hospital mortality, with a positive predictive value (PPV) of 19 per cent and a negative predictive value (NPV) of 100 per cent: no deaths occurred above the threshold. Age and respiratory efficiency in the elimination of carbon dioxide (VE/VCO(2)) at AT were statistically significant predictors of postoperative complications. Receiver operating characteristic (ROC) curve analysis showed that a threshold of 34·5 for VE/VCO(2) at AT provided a specificity of 84 per cent and a sensitivity of 47 per cent, with a PPV of 76 (95 per cent confidence interval (c.i.) 58 to 88) per cent and a NPV of 60 (48 to 72) per cent for postoperative complications. Long-term survival of those with an AT of less than 9·9 ml O(2) per kg per min was significantly worse than that of patients with a higher AT (hazard ratio for mortality 1·81, 95 per cent c.i. 1·04 to 3·17; P = 0·036). CONCLUSION: CPET provides a useful prognostic adjunct in the preoperative assessment of patients undergoing hepatic resection.

Poly(A) RT-PCR measurement of diagnostic genes in pancreatic juice in pancreatic cancer.

BACKGROUND: The last decade has seen significant progress in understanding the molecular biology of pancreatic adenocarcinoma. There is now an urgent need to translate these molecular techniques to clinical practice in order to improve diagnosis and prediction of response to treatment. The objectives of this study are to utilise poly(A) RT-PCR to measure expression levels of diagnostic Indicator genes, selected from microarray studies, of RNA from intraoperatively sampled pancreatic ductal juice and to correlate these expression levels with those in matched pancreatic tissue resection samples. METHODS: Intraoperative sampling of pancreatic juice and collection of matched tissue samples was undertaken in patients undergoing pancreaticoduodenectomy for suspected tumour. RNA was isolated and poly(A) PCR and real-time PCR used to measure expression levels of 30 genes. Spearman's rank correlation test was used to examine the relationship of gene expression between pancreatic juice and tissue. RESULTS: Of the 30 Indicator genes measured, just one, ANXA1, showed a significant correlation of expression level between pancreatic juice and tissue samples, whereas three genes, IGFBP3 (P0.035), PSCA (P0.001) and SPINK1 (P0.05), showed significantly different expression between cancerous and benign pancreatic tissue samples. CONCLUSIONS: These results demonstrate that RNA analysis of pancreatic juice is feasible using the poly(A) cDNA technique, that correlation of gene expression exists between pancreatic juice and tissue for very few genes and that gene expression profiling can distinguish between benign and malignant pancreatic tissue. This indicates possible use of the technique for measurement of Indicator genes in pancreatic tissue for diagnosis of pancreatic cancer from very small tissue samples.

Current status of gene expression profiling of pancreatic cancer.

Pancreatic cancer is an important cause of morbidity and mortality but there are presently few if any prognostic markers available beyond tumour stage and grade. As tumours are detected and treated at earlier stages these factors are less prognostically informative and there is a growing need for development of novel diagnostic markers to guide pre- and post-operative treatment. Additionally the outcome of surgery for pancreatic cancer remains poor, largely due to late clinical presentation of most cases, and early detection, particularly in high risk groups, such as those with chronic pancreatitis, Intraductal papillary mucinous cystadenoma (IPMN) would enable earlier surgical intervention and improved survival. Use of gene expression profiles represents an innovative approach to cancer classification and prognostication and has been applied to an increasingly wide range of cancers. Recent studies have identified prognostically informative gene signatures for pancreatic cancer, and there is now an urgent need to develop methods for their measurement in routine clinical samples.

Nationwide questionnaire survey of the contemporary surgical management of pancreatic cancer in the United Kingdom & Ireland.

This paper reports the results of a questionnaire-based survey of pancreatic surgical specialists in the United Kingdom addressing aspects of staging, resection volume and outcome. A postal survey was undertaken of the 517 members of the Association of upper Gastrointestinal Surgeons of Great Britain and Ireland (AUGIS). 57 surgeons undertook pancreatic resection from 162 overall respondents. Cross-checking with the list of members of the Pancreatic Society of Great Britain and Ireland yielded 64 pancreatic surgeons. 734 pancreaticoduodenectomy (PD) were reported by respondents compared with 822 procedures according to Government maintained Hospital Episode Statistics. The modal resection volume performed per annum was 6-10. There were 24 in-hospital deaths in 732 resections (3%) mortality. For individual respondents the modal percentage mortality was 5% (0 to 16%). All clinicians with mortality rates in excess of 10% did less than 10 resections per annum. Respondents favoured "amylase rich discharge beyond 7th post-operative day" as optimal for definition of post-resection pancreatic fistula. Accepting the limitations of questionnaire surveys, the results provide an important overview of pancreatic surgical practice: pancreaticoduodenectomy is carried out by a range of specialists, lower volume resectionists appear to have poorer outcomes and this study shows widespread agreement on optimum terminology for post-operative pancreatic fistula.

Systematic review of carbohydrate antigen (CA 19-9) as a biochemical marker in the diagnosis of pancreatic cancer.

BACKGROUND: Although many biochemical markers have been examined in pancreatic cancer none are definitive for pre-operative diagnosis. This systematic review examines studies using biochemical markers for the diagnosis of pancreatic cancer in order to appraise their role in contemporary management algorithms. METHODS: A search of the MEDLINE database was undertaken using the key words pancreatic neoplasm and serum tumour marker. Only studies providing original data on sensitivity and specificity are included and data are presented on diagnostic accuracy, effect of cholestasis and the relation of tumour stage to blood levels of markers. RESULTS: CA 19-9 is the most extensively evaluated with pooled data from 2283 patients. The median sensitivity of CA 19-9 for diagnosis is 79 (70-90%) and median specificity 82 (68-91%). CA 19-9 elevation in non-malignant jaundice results in a fall in specificity. Combination with other markers improves accuracy. CONCLUSION: As the most extensively evaluated marker, CA 19-9 should be used in contemporary algorithms for the diagnosis of pancreatic cancer. Elevated values should be repeated after relief of jaundice.

Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer.

BACKGROUND: Tumour clearance during pancreatectomy may be facilitated by resection of the portal-superior mesenteric vein, but this is associated with increased perioperative risk. There is no consensus about which patients benefit from portal-superior mesenteric vein resection. METHODS: A systematic appraisal was carried out of the literature on portal-superior mesenteric vein resection during pancreatectomy to identify recurrent themes to guide management. A computerized search of the Medline and Embase databases found 52 non-duplicated studies providing relevant data in 1646 patients. Pooled data were examined for information on outcome categories relating to operation, complications, histopathology and overall outcome. RESULTS: The median (range) number of patients with portal-superior mesenteric vein resection per cohort was 23 (4-172). Median operating time was 513 (168-1740) min and blood loss 1750 (300-26000) ml. Postoperative morbidity ranged from 9 to 78 per cent with a median per cohort of 42 per cent. There were 73 perioperative deaths (5.9 per cent of 1235 for whom mortality data were provided). Median survival was 13 months, and 1-, 3- and 5-year survival rates were 50, 16 and 7 per cent respectively. Specimen histopathology confirmed positive nodes in 67.4 per cent. CONCLUSIONS: This is the largest collective report to date on portal-superior mesenteric vein resection in pancreatectomy. The high rate of nodal metastases and low 5-year survival rates suggest that by the time of tumour involvement of the portal vein cure is unlikely, even with radical resection.