Joan Figueras

Posthepatectomy liver failure: A definition and grading by the International Study Group of Liver Surgery (ISGLS)

BACKGROUNDnPosthepatectomy liver failure is a feared complication after hepatic resection and a major cause of perioperative mortality. There is currently no standardized definition of posthepatectomy liver failure that allows valid comparison of results from different studies and institutions. The aim of the current article was to propose a definition and grading of severity of posthepatectomy liver failure.nnnMETHODSnA literature search on posthepatectomy liver failure after hepatic resection was conducted. Based on the normal course of biochemical liver function tests after hepatic resection, a simple and easily applicable definition of posthepatectomy liver failure was developed by the International Study Group of Liver Surgery. Furthermore, a grading of severity is proposed based on the impact on patients clinical management.nnnRESULTSnNo uniform definition of posthepatectomy liver failure has been established in the literature addressing hepatic surgery. Considering the normal postoperative course of serum bilirubin concentration and International Normalized Ratio, we propose defining posthepatectomy liver failure as the impaired ability of the liver to maintain its synthetic, excretory, and detoxifying functions, which are characterized by an increased international normalized ratio and concomitant hyperbilirubinemia (according to the normal limits of the local laboratory) on or after postoperative day 5. The severity of posthepatectomy liver failure should be graded based on its impact on clinical management. Grade A posthepatectomy liver failure requires no change of the patients clinical management. The clinical management of patients with grade B posthepatectomy liver failure deviates from the regular course but does not require invasive therapy. The need for invasive treatment defines grade C posthepatectomy liver failure.nnnCONCLUSIONnThe current definition of posthepatectomy liver failure is simple and easily applicable in clinical routine. This definition can be used in future studies to allow objective and accurate comparisons of operative interventions in the field of hepatic surgery.

Bile leakage after hepatobiliary and pancreatic surgery: A definition and grading of severity by the International Study Group of Liver Surgery

BACKGROUNDnDespite the potentially severe impact of bile leakage on patients perioperative and long-term outcome, a commonly used definition of this complication after hepatobiliary and pancreatic operations has not yet been established. The aim of the present article is to propose a uniform definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy.nnnMETHODSnAn international study group of hepatobiliary and pancreatic surgeons was convened. A consensus definition of bile leakage after hepatobiliary and pancreatic operative therapy was developed based on the postoperative course of bilirubin concentrations in patients serum and drain fluid.nnnRESULTSnAfter evaluation of the postoperative course of bilirubin levels in the drain fluid of patients who underwent hepatobiliary and pancreatic operations, bile leakage was defined as bilirubin concentration in the drain fluid at least 3 times the serum bilirubin concentration on or after postoperative day 3 or as the need for radiologic or operative intervention resulting from biliary collections or bile peritonitis. Using this criterion severity of bile leakage was classified according to its impact on patients clinical management. Grade A bile leakage causes no change in patients clinical management. A Grade B bile leakage requires active therapeutic intervention but is manageable without relaparotomy, whereas in Grade C, bile leakage relaparotomy is required.nnnCONCLUSIONnWe propose a simple definition and severity grading of bile leakage after hepatobiliary and pancreatic operative therapy. The application of the present proposal will enable a standardized comparison of the results of different clinical trials and may facilitate an objective evaluation of diagnostic and therapeutic modalities in the field of hepatobiliary and pancreatic operative therapy.

The oncosurgery approach to managing liver metastases from colorectal cancer: a multidisciplinary international consensus

An international panel of multidisciplinary experts convened to develop recommendations for the management of patients with liver metastases from colorectal cancer (CRC). The aim was to address the main issues facing the CRC hepatobiliary multidisciplinary team (MDT) when managing such patients and to standardize the treatment patients receive in different centers. Based on current evidence, the group agreed on a number of issues including the following: (a) the primary aim of treatment is achieving a long disease-free survival (DFS) interval following resection; (b) assessment of resectability should be performed with high-quality cross-sectional imaging, staging the liver with magnetic resonance imaging and/or abdominal computed tomography (CT), depending on local expertise, staging extrahepatic disease with thoracic and pelvic CT, and, in selected cases, fluorodeoxyglucose positron emission tomography with ultrasound (preferably contrast-enhanced ultrasound) for intraoperative staging; (c) optimal first-line chemotherapy-doublet or triplet chemotherapy regimens combined with targeted therapy-is advisable in potentially resectable patients; (d) in this situation, at least four courses of first-line chemotherapy should be given, with assessment of tumor response every 2 months; (e) response assessed by the Response Evaluation Criteria in Solid Tumors (conventional chemotherapy) or nonsize-based morphological changes (antiangiogenic agents) is clearly correlated with outcome; no imaging technique is currently able to accurately diagnose complete pathological response but high-quality imaging is crucial for patient management; (f) the duration of chemotherapy should be as short as possible and resection achieved as soon as technically possible in the absence of tumor progression; (g) the number of metastases or patient age should not be an absolute contraindication to surgery combined with chemotherapy; (h) for synchronous metastases, it is not advisable to undertake major hepatic surgery during surgery for removal of the primary CRC; the reverse surgical approach (liver first) produces as good an outcome as the conventional approach in selected cases; (i) for patients with resectable liver metastases from CRC, perioperative chemotherapy may be associated with a modestly better DFS outcome; and (j) whether initially resectable or unresectable, cure or at least a long survival duration is possible after complete resection of the metastases, and MDT treatment is essential for improving clinical and survival outcomes. The group proposed a new system to classify initial unresectability based on technical and oncological contraindications.

Post-hepatectomy haemorrhage: a definition and grading by the International Study Group of Liver Surgery (ISGLS)

BACKGROUNDnA standardized definition of post-hepatectomy haemorrhage (PHH) has not yet been established.nnnMETHODSnAn international study group of hepatobiliary surgeons from high-volume centres was convened and a definition of PHH was developed together with a grading of severity considering the impact on patients clinical management.nnnRESULTSnThe definition of PHH varies strongly within the hepatic surgery literature. PHH is defined as a drop in haemoglobin level > 3 g/dl post-operatively compared with the post-operative baseline level and/or any post-operative transfusion of packed red blood cells (PRBC) for a falling haemoglobin and/or the need for radiological intervention (such as embolization) and/or re-laparotomy to stop bleeding. Evidence of intra-abdominal bleeding should be obtained by imaging or blood loss via the abdominal drains if present. Transfusion of up to two units of PRBC is considered as being Grade A PHH. Grade B PHH requires transfusion of more than two units of PRBC, whereas the need for invasive re-intervention such as embolization and/ or re-laparotomy defines Grade C PHH.nnnCONCLUSIONnThe proposed definition and grading of severity of PHH enables valid comparisons of results from different studies. It is easily applicable in clinical routine and should be applied in future trials to standardize reporting of complications.

Urgent Need for a New Staging System in Advanced Colorectal Cancer

Despite recent advances in the medical treatment of metastatic colorectal cancer (mCRC), which include irinotecan- and oxaliplatin-based first-line regimens, the concept of planned sequential therapy involving three active agents during the course of a patients treatment and the increasing use of targeted monoclonal antibodies, 5-year survival rates for patients with advanced CRC remain unacceptably low. For patients with CRC liver metastases, liver resection remains the only chance of cure, with 5-year survival rates ranging from 25% to 40%. However, 80% to 85% of patients with stage IV CRC have liver disease which is considered unresectable at presentation. The rapid expansion in the use of improved combination chemotherapy regimens plus or minus biologics, to render initially unresectable metastases resectable has increased the percentage of patients eligible for potentially curative surgery. However, the current staging criteria for CRC patients with metastatic disease do not reflect these recent changes or the fact that there is also a large variation in the survival of patients with stage IV CRC. For example the survival for a patient with a solitary, resectable liver metastasis is better than that for a patient with stage III disease. A new staging system is therefore needed that acknowledges both the improvements that have been made in surgical techniques for resectable metastases and the impact of modern chemotherapy on rendering initially unresectable CRC liver metastases resectable, while at the same time distinguishing between patients with a chance of cure at presentation and those for whom only palliative treatment is possible.

Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus

An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.

Complex liver resection for hepatic tumours involving the inferior vena cava

BACKGROUNDnResection of liver tumours with involvement of inferior vena cava (IVC) is considered to have a high surgical risk.nnnAIMnWe retrospectively reviewed 23 patients who underwent hepatectomy with IVC resection in two West-European liver surgery Units.nnnMETHODSnThe tumours included liver metastases (n = 13), hepatocellular carcinoma (n = 4), intrahepatic cholangiocarcinoma (n = 3), liver haemangioma (n = 1), primary hepatic lymphoma (n = 1) and recurrent right adrenal gland carcinoma (n = 1).nnnRESULTSnIVC resection was associated with right hepatectomy in 8 cases, extended right hepatectomy in 9 cases, extended left hepatectomy in 3 cases, minor liver resection in 2 cases, and right hepatectomy with nephrectomy in one case. In 16 patients the IVC wall involvement was <30% of its circumference, and a tangential vena cava resection was performed. In 7 patients (30%) with >50% involvement, a caval segment was resected and replaced with a 20 mm ringed polytetrafluoroethylene graft. R0-resection was achieved in all patients. Median intraoperative blood loss was 1.100 ml (range 490-15,000). Fourteen patients were transfused with a median of 3 PRC units per patient (range 1-25). Major complications occurred in 9 patients. Postoperative stay in ICU was 2.3 ± 3.4 days (range 1-14) and hospital stay was 17.3 ± 2.6 days (range 5-62). In 14 patients, final pathology demonstrated microscopic IVC infiltration.nnnCONCLUSIONSnIn selected patients with malignant involvement of the liver and IVC, surgical resection en bloc with IVC is the only possibility to achieve R0 resection, with acceptable mortality and morbidity, in units specialized in liver surgery.

Progression while Receiving Preoperative Chemotherapy Should Not Be an Absolute Contraindication to Liver Resection for Colorectal Metastases

PurposeTumor progression while receiving neoadjuvant chemotherapy (PD) has been associated with poor outcome and is commonly considered a contraindication to liver resection (LR). This study aims to clarify in a large multicenter setting whether PD is always a contraindication to LR.MethodsData from the LiverMetSurvey international registry were analyzed. Patients undergoing LR for colorectal metastases without extrahepatic disease after neoadjuvant chemotherapy between 1990 and 2009 were reviewed.ResultsAmong 2143 patients, PD occurred in 176 (8.2xa0%). Risk of progression was increased after 5-FU or irinotecan (22.7xa0% vs. 6.8xa0% after other regimens, pxa0<xa00.0001; 14.9xa0% vs. 7.2xa0%, pxa0<xa00.0001), while it was reduced after oxaliplatin (5.6xa0% vs. 12.0xa0%, pxa0<xa00.0001) and still diminished among patients receiving targeted therapies (2.6xa0%). PD was an independent prognostic factor of survival at multivariate analysis (35xa0% vs. 49xa0%, pxa0=xa00.0006). In the PD group, 3 independent prognostic factors were identified: carcinoembryonic antigen (CEA) ≥200xa0ng/mL (pxa0=xa00.003), >3 metastases (pxa0=xa00.028), and tumor diameter ≥50xa0mm (pxa0=xa00.002). A survival predictive model showed that patients without any risk factors had 5-year survival rates of 53.3xa0%; good survival results were still observed if metastases were >3 or ≥50xa0mm (29.9 and 19.1xa0%, respectively). On the contrary, survival was less than 10xa0% at 3xa0years in the presence of >1 prognostic factor or CEA of ≥200xa0ng/mL.ConclusionsPD is a negative prognostic factor, but it is not an absolute contraindication to LR. Patients with PD could be scheduled for LR except for those with >3 metastases and ≥50xa0mm, or CEA ≥200xa0ng/mL in whom further chemotherapy is recommended.

Prospective evaluation of the International Study Group for Liver Surgery definition of bile leak after a liver resection and the role of routine operative drainage: An international multicentre study

BACKGROUNDnThe International Study Group for Liver Surgery (ISGLS) proposed a definition for bile leak after liver surgery. A multicentre international prospective study was designed to evaluate this definition.nnnMETHODSnData collected prospectively from 949 consecutive patients on specific datasheets from 11 international centres were collated centrally.nnnRESULTSnBile leak occurred in 69 (7.3%) of patients, with 31 (3.3%), 32 (3.4%) and 6 (0.6%) classified as grade A, B and C, respectively. The grading system of severity correlated with the Dindo complication classification system (P < 0.001). Hospital length of stay was increased when bile leak occurred, from a median of 7 to 15 days (P < 0.001), as was intensive care stay (P < 0.001), and both correlated with increased severity grading of bile leak (P < 0.001). 96% of bile leaks occurred in patients with intra-operative drains. Drain placement did not prevent subsequent intervention in the bile leak group with a 5-15 times greater risk of intervention required in this group (P < 0.001).nnnCONCLUSIONnThe ISGLS definition of bile leak after liver surgery appears robust and intra-operative drain usage did not prevent the need for subsequent drain placement.

Practical questions in liver metastases of colorectal cancer: general principles of treatment

Liver metastases of colorectal cancer are currently treated by multidisciplinary teams using strategies that combine chemotherapy, surgery and ablative techniques. Many patients classically considered non-resectable can now be rescued by neoadjuvant chemotherapy followed by liver resection, with similar results to those obtained in initial resections. While many of those patients will recur, repeat resection is a feasible and safe approach if the recurrence is confined to the liver. Several factors that until recently were considered contraindications are now recognized only as adverse prognostic factors and no longer as contraindications for surgery. The current evaluation process to select patients for surgery is no longer focused on what is to be removed but rather on what will remain. The single most important objective is to achieve a complete (R0) resection within the limits of safety in terms of quantity and quality of the remaining liver. An increasing number of patients with synchronous liver metastases are treated by simultaneous resection of the primary and the liver metastatic tumours. Multilobar disease can also be approached by staged procedures that combine neoadjuvant chemotherapy, limited resections in one lobe, embolization or ligation of the contralateral portal vein and a major resection in a second procedure. Extrahepatic disease is no longer a contraindication for surgery provided that an R0 resection can be achieved. A reverse surgical staged approach (liver metastases first, primary second) is another strategy that has appeared recently. Provided that a careful selection is made, elderly patients can also benefit from surgical treatment of liver metastases.