Blood flow restriction Exercise in the perioperative setting to Prevent loss of muscle mass in patients with pancreatic, biliary tract, and liver cancer: study protocol for the PREV-Ex randomized controlled trial.

BACKGROUND: Patients diagnosed with pancreatic, biliary tract, and liver cancer often suffer from a progressive loss of muscle mass. Given the considerable functional impairments in these patients, high musculoskeletal weight loads may not be well tolerated by all individuals. The use of blood-flow restricted resistance training (BFR-T) which only requires low training loads may allow for a faster recovery of muscle due to avoidance of high levels of mechanical muscle stress associated with high-load resistance exercise. This study aims to investigate whether BFR-T can prevent or slow down the loss of skeletal muscle mass and enhance the functional capacity and mental health of patients with pancreatic, biliary tract, and liver cancer. METHODS: The PREV-Ex exercise trial is a multicenter two-armed randomized controlled trial. Patients will be randomized to an exercise program consisting of home-based low-load BFR-T during a combined pre- and postoperative period for a total of 6-10 weeks (prehabilitation and rehabilitation), or to a control group. Protein supplementation will be given to both groups to ensure adequate protein intake. The primary outcomes, skeletal muscle thickness and muscle cross-sectional area, will be assessed by ultrasound. Secondary outcomes include the following: (i) muscle catabolism-related and inflammatory bio-markers (molecular characteristics will be assessed from a vastus lateralis biopsy and blood samples will be obtained from a sub-sample of patients); (ii) patient-reported outcome measures (self-reported fatigue, health-related quality of life, and nutritional status will be assessed through validated questionnaires); (iii) physical fitness/performance/activity (validated tests will be used to evaluate physical function, cardiorespiratory fitness and maximal isometric muscle strength. Physical activity and sedentary behavior (assessed using an activity monitor); (iv) clinical outcomes: hospitalization rates and blood status will be recorded from the patients' medical records; (v) explorative outcomes of patients' experience of the exercise program which will be evaluated using focus group/individual interviews. DISCUSSION: It is worthwhile to investigate new strategies that have the potential to counteract the deterioration of skeletal muscle mass, muscle function, strength, and physical function, all of which have debilitating consequences for patients with pancreatic, biliary tract, and liver cancer. The expected findings could improve prognosis, help patients stay independent for longer, and possibly reduce treatment-related costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05044065. Registered on September 14, 2021.

Development and validation of a novel risk score to predict overall survival following surgical clearance of bilobar colorectal liver metastases.

BACKGROUND: Bilobar liver metastases from colorectal cancer pose a challenge for obtaining a satisfactory oncological outcome with an adequate future liver remnant. This study aimed to assess the clinical and pathological determinants of overall survival and recurrence-free survival among patients undergoing surgical clearance of bilobar liver metastases from colorectal cancer. METHODS: A retrospective international multicentre study of patients who underwent surgery for bilobar liver metastases from colorectal cancer between January 2012 and December 2018 was conducted. Overall survival and recurrence-free survival at 1, 2, 3 and 5 years after surgery were the primary outcomes evaluated. The secondary outcomes were duration of postoperative hospital stay, and 90-day major morbidity and mortality rates. A prognostic nomogram was developed using covariates selected from a Cox proportional hazards regression model, and internally validated using a 3:1 random partition into derivation and validation cohorts. RESULTS: A total of 1236 patients were included from 70 centres. The majority (88 per cent) of the patients had synchronous liver metastases. Overall survival at 1, 2, 3 and 5 years was 86.4 per cent, 67.5 per cent, 52.6 per cent and 33.8 per cent, and the recurrence-free survival rates were 48.7 per cent, 26.6 per cent, 19.2 per cent and 10.5 per cent respectively. A total of 25 per cent of patients had recurrent disease within 6 months. Margin positivity and progressive disease at liver resection were poor prognostic factors, while adjuvant chemotherapy in margin-positive resections improved overall survival. The bilobar liver metastases from colorectal cancer-overall survival nomogram was developed from the derivation cohort based on pre- and postoperative factors. The nomogram's ability to forecast overall survival at 1, 2, 3 and 5 years was subsequently validated on the validation cohort and showed high accuracy (overall C-index = 0.742). CONCLUSION: Despite the high recurrence rates, overall survival of patients undergoing surgical resection for bilobar liver metastases from colorectal cancer is encouraging. The novel bilobar liver metastases from colorectal cancer-overall survival nomogram helps in counselling and informed decision-making of patients planned for treatment of bilobar liver metastases from colorectal cancer.

Preoperative immunological plasma markers TRAIL, CSF1 and TIE2 predict survival after resection for biliary tract cancer.

Introduction: Systemic inflammatory markers have been validated as prognostic factors for patients with biliary tract cancer (BTC). The aim of this study was to evaluate specific immunologic prognostic markers and immune responses by analyzing preoperative plasma samples from a large prospectively collected biobank. Methods: Expression of 92 proteins representing adaptive and innate immune responses was investigated in plasma from 102 patients undergoing resection for BTC 2009-2017 (perihilar cholangiocarcinoma n=46, intrahepatic cholangiocarcinoma n=27, gallbladder cancer n=29), by means of a high-throughput multiplexed immunoassay. Association with overall survival was analyzed by Cox regression, with internal validation and calibration. Tumor tissue bulk and single-cell gene expression of identified markers and receptors/ligands was analyzed in external cohorts. Results: Three preoperative plasma markers were independently associated with survival: TRAIL, TIE2 and CSF1, with hazard ratios (95% confidence intervals) 0.30 (0.16-0.56), 2.78 (1.20-6.48) and 4.02 (1.40-11.59) respectively. The discrimination of a preoperative prognostic model with the three plasma markers was assessed with concordance-index 0.70, while the concordance-index of a postoperative model with histopathological staging was 0.66. Accounting for subgroup differences, prognostic factors were assessed for each type of BTC. TRAIL and CSF1 were prognostic factors in intrahepatic cholangiocarcinoma. In independent cohorts, TRAIL-receptor expression was higher in tumor tissue and seen in malignant cells, with TRAIL and CSF1 expressed by intra- and peritumoral immune cells. Intratumoral TRAIL-activity was decreased compared to peritumoral immune cells, while CSF1-activity was increased. The highest CSF1 activity was seen in intratumoral macrophages, while the highest TRAIL-activity was seen in peritumoral T-cells. Discussion: In conclusion, three preoperative immunological plasma markers were prognostic for survival after surgery for BTC, providing good discrimination, even compared to postoperative pathology. TRAIL and CSF1, prognostic factors in intrahepatic cholangiocarcinoma, showed marked differences in expression and activity between intra- and peritumoral immune cells.

Joint EANM/SNMMI/IHPBA procedure guideline for [99mTc]Tc-mebrofenin hepatobiliary scintigraphy SPECT/CT in the quantitative assessment of the future liver remnant function.

PURPOSE: The aim of this joint EANM/SNMMI/IHPBA procedure guideline is to provide general information and specific recommendations and considerations on the use of [99mTc]Tc-mebrofenin hepatobiliary scintigraphy (HBS) in the quantitative assessment and risk analysis before surgical intervention, selective internal radiation therapy (SIRT) or before and after liver regenerative procedures. Although the gold standard to estimate future liver remnant (FLR) function remains volumetry, the increasing interest in HBS and the continuous request for implementation in major liver centers worldwide, demands standardization. METHODS: This guideline concentrates on the endorsement of a standardized protocol for HBS elaborates on the clinical indications and implications, considerations, clinical appliance, cut-off values, interactions, acquisition, post-processing analysis and interpretation. Referral to the practical guidelines for additional post-processing manual instructions is provided. CONCLUSION: The increasing interest of major liver centers worldwide in HBS requires guidance for implementation. Standardization facilitates applicability of HBS and promotes global implementation. Inclusion of HBS in standard care is not meant as substitute for volumetry, but rather to complement risk evaluation by identifying suspected and unsuspected high-risk patients prone to develop post-hepatectomy liver failure (PHLF) and post-SIRT liver failure.

The dilemma of the disappearing colorectal liver metastases: defining international trends in management.

OBJECTIVE: This survey sought to appraise the degree of consistency in the management of disappeared colorectal liver metastases (dCRLM) among liver surgeons in different countries. BACKGROUND: Colorectal liver metastases (CRLM) account for half of the deaths secondary to colorectal cancer. Due to the high utilization of chemotherapy before surgery, some or all CRLM can disappear (dCRLM) but management of dCRLMs remains unclear. METHODS: Seven simulated scenarios of dCRLM were presented to experienced liver surgeons using an online platform. Treatment decisions were submitted and analysed using the multi-rater kappa method. The effect of the experience, complexity of scenarios, and location and number of dCRLM on treatment decision were analysed. RESULTS: Sixty-seven liver surgeons from 25 countries completed the survey. There was no agreement about the therapeutic strategies of dCRLM in all scenarios (kappa 0.12, IQR 0.20-0.32). In scenarios with lower difficulty scores, surgeons tended to offer surgical resection for dCRLM alongside the visible CRLM (vCRLM), however, with poor agreement (kappa 0.32, IQR 0.19-0.51). No agreement was seen for clinical scenario in which all CRLM lesions disappeared (kappa 0.20). CONCLUSION: There are clear inconsistencies in the management decisions of dCRLM. Better evidence is required to define optimal management strategies.

CANOPTIPHYS study protocol: Optimising PHYSical function before CANcer surgery: effects of pre-operative optimisation on complications and physical function after gastrointestinal cancer surgery in older people at risk-a multicentre, randomised, parallel-group study.

BACKGROUND: This multicentre study explores the effects of pre-operative exercise on physical fitness, post-operative complications, recovery, and health-related quality of life in older individuals with low pre-operative physical capacity scheduled to undergo surgery for colorectal cancer. We hypothesise that this group of patients benefit from pre-operative exercise in terms of improved pre-operative physical function and lower rates of post-operative complications after surgery compared to usual care. Standardised cancer pathways in Sweden dictate a timeframe of 14-28 days from suspicion of cancer to surgery for colorectal cancer. Therefore, an exercise programme aimed to enhance physical function in the limited timeframe requires a high-intensity and high-frequency approach. METHODS: Participants will be included from four sites in Stockholm, Sweden. A total of 160 participants will be randomly assigned to intervention or control conditions. Simple randomisation (permuted block randomisation) is applied with a 1:1 allocation ratio. The intervention group will perform home-based exercises (inspiratory muscle training, aerobic exercises, and strength exercises) supervised by a physiotherapist (PT) for a minimum of 6 sessions in the pre-operative period, complemented with unsupervised exercise sessions in between PT visits. The control group will receive usual care with the addition of advice on health-enhancing physical activity. The physical activity behaviour in both groups will be monitored using an activity monitor. The primary outcomes are (1) change in physical performance (6-min walking distance) in the pre-operative period and (2) post-operative complications 30 days after surgery (based on Clavien-Dindo surgical score). DISCUSSION: If patients achieve functional benefits by exercise in the short period before surgery, this supports the implementation of exercise training as a clinical routine. If such benefits translate into lower complication rates and better post-operative recovery or health-related quality of life is not known but would further strengthen the case for pre-operative optimisation in colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT04878185. Registered on 7 May 2021. https://clinicaltrials.gov/ct2/home.

Changes in apparent diffusion coefficient and pathological response in colorectal liver metastases after preoperative chemotherapy.

BACKGROUND: The pathological response to preoperative chemotherapy of colorectal liver metastases (CRLMs) is predictive of long-term prognosis after liver resection. Accurate preoperative assessment of chemotherapy response could enable treatment optimization. PURPOSE: To investigate whether changes in lesion-apparent diffusion coefficient (ADC) measured with diffusion-weighted magnetic resonance imaging (MRI) can be used to assess pathological treatment response in patients with CRLMs undergoing preoperative chemotherapy. MATERIAL AND METHODS: Patients who underwent liver resection for CRLMs after preoperative chemotherapy between January 2011 and December 2019 were retrospectively included if they had undergone MRI before and after preoperative chemotherapy on the same 1.5-T MRI scanner with diffusion-weighted imaging with b-values 50, 400, and 800 s/mm2. The pathological chemotherapy response was assessed using the tumor regression grade (TRG) by AJCC/CAP. Lesions were divided into two groups: pathological responding (TRG 0-2) and non-responding (TRG 3). The change in lesion ADC after preoperative chemotherapy was compared between responding and non-responding lesions. RESULTS: A total of 27 patients with 49 CRLMs were included, and 24/49 lesions showed a pathological chemotherapy response. After chemotherapy, ADC increased in both pathological responding (pretreatment ADC: 1.26 [95% confidence interval (CI)=1.06-1.37] vs. post-treatment ADC: 1.33 [95% CI=1.13-1.56] × 10-3 mm2/s; P = 0.026) and non-responding lesions (1.12 [95% CI=0.980-1.21] vs. 1.20 [95% CI=1.09-1.43] × 10-3 mm2/s; P = 0.018). There was no difference in median relative difference in ADC after chemotherapy between pathological responding and non-responding lesions (15.8 [95% CI=1.42-26.3] vs. 7.17 [95% CI=-4.31 to 31.2]%; P = 0.795). CONCLUSION: Changes in CRLM ADCs did not differ between pathological responding and non-responding lesions.

Incidence and risk factors for anastomotic bile leakage in hepatic resection with bilioenteric reconstruction - A international multicenter study.

BACKGROUND: Anastomotic leak (AL) after bilioenteric reconstruction (BR) is a feared complication after bile duct resection, especially in combination with liver resection. Literature on surgical outcome is sparse. This study aimed to determine the incidence and risk factors for AL after combined liver and bile duct resection with a focus on operative or endoscopic reinterventions. METHODS: Data from consecutive patients who underwent liver resection and BR between 2004 and 2018 in 11 academic institutions in Europe were collected from prospectively maintained databases. RESULTS: Within 921 patients, AL rate was 5.4% with a 30d mortality of 9.6%. Pringle maneuver (p<0.001),postoperative external biliary (p=0.007) and abdominal drainage (p<0.001) were risk factors for clinically relevant AL. Preoperative biliary drainage (p<0.001) was not associated with a higher rate of AL. AL was more frequent in stented patients (76.5%) compared to PTCD (17.6%) or PTCD+stent (5.9%,p=0.017). AL correlated with increased incidence of postoperative liver failure (p=0.036), cholangitis, hemorrhage and sepsis (all p<0.001). CONCLUSION: This multicenter data provides the largest series to date of LR with BR and could help in the management of these patients which are often challenging and hampering the patients' postoperative course negatively.

Distinguishing tumor from healthy tissue in human liver ex vivo using machine learning and multivariate analysis of diffuse reflectance spectra.

The aim of this work was to evaluate the capability of diffuse reflectance spectroscopy to distinguish malignant liver tissues from surrounding tissues and to determine whether an extended wavelength range (450-1550 nm) offers any advantages over using the conventional wavelength range. Furthermore, multivariate analysis combined with a machine learning algorithm, either linear discriminant analysis or the more advanced support vector machine, was used to discriminate between and classify freshly excised human liver specimens from 18 patients. Tumors were distinguished from surrounding liver tissues with a sensitivity of 99%, specificity of 100%, classification rate of 100% and a Matthews correlation coefficient of 100% using the extended wavelength range and a combination of principal component analysis and support vector techniques. The results indicate that this technology may be useful in clinical applications for real-time tissue diagnostics of tumor margins where rapid classification is important.

Pure biliary leak vs. pancreatic fistula associated: non-identical twins following pancreatoduodenectomy.

BACKGROUND: Biliary leak (BL) after pancreatoduodenectomy (PD) may have diffrent severity depending on its association with postoperative pancreatic fistula (POPF). METHODS: Data of 2715 patients undergoing PD between 2011 and 2020 at two European third-level referral Centers for pancreatic surgery were retrospectively reviewed. These included BL incidences, grading, outcomes, specific treatments, and association with POPF. RESULTS: BL occurred in 6% of patients undergoing PD. Among 143 BL patients, 47% had an associated POPF and 53% a pure BL. Major morbidity (64% vs 36%) and mortality (19% vs 4%) were higher in POPF-associated BL group (all P< 0.01). Day of BL onset was similar between groups (POD 2 vs 3; P = 0.2), while BL closure occurred earlier in pure BL (POD 12 vs 23; P < 0.01). Conservative treatment was more frequent (55% vs 15%; P < 0.01), and the rate of percutaneous and/or trans-hepatic drain placement was lower (30% vs 16%; P = 0.04) in pure BL group. Relaparotomy was more common in POPF-associated BL group (42% VS 17%; P < 0.01) but was performed earlier in pure BL (POD 2 vs 10; P = 0.02). CONCLUSIONS: Pure BL represents a more benign entity, managed conservatively in half of the cases.

Treatment intention and outcome in patients with simultaneously diagnosed liver and lung metastases from colorectal cancer.

BACKGROUND: The aim was to assess the likelihood of patients with simultaneously diagnosed liver and lung metastases (SLLM) from colorectal cancer (CRC) to receive the curative treatment decided upon multidisciplinary team meeting (MDT) and to elaborate on the reasons for treatment intention failure and survival outcomes depending on final treatment strategy. METHOD: The study included a retrospective review of all patients discussed at the MDT at a single centre between 2010 and 2018 to identify all patients presenting with SLLM from CRC. Treatment intention, actual treatment outcome and reasons for treatment failure was documented. Descriptive and survival statistics were applied. RESULTS: Of the 160 patients who had SLLM, resection of all metastatic sites was deemed possible in 107 patients (67%) of whom 39 patients (36%) finalized the curative treatment plan. The most common reason for noncompliance with management recommendations was disease progression or recurrence. Complete resection resulted in longer survival compared to patients who did not undergo resection of all metastatic sites with median survival of 63 and 27 months, respectively (p < 0.001). CONCLUSION: A low proportion of patients completed the initially intended curative resections. Simultaneous resection of liver/lung metastases and primary tumour might increase the proportion of fulfilled hepatopulmonary resections.

Redefining resection margins and dissection planes in perihilar cholangiocarcinoma-radical resection is a rare event.

Radical tumor resection (pR0) is prognostic for disease-free and overall survival after resection of perihilar cholangiocarcinoma (pCCA). However, no universal agreement exists on the definition of radical resection and histopathological reporting. The aim of this study was to provide a standardized protocol for histopathological assessment and reporting of the surgical specimen obtained after resection for pCCA. All consecutive patients operated for pCCA with curative intent at the Karolinska University Hospital, Stockholm, Sweden between 2012 and 2021 were included. A standardized protocol for histopathological assessment and reporting of the surgical specimen after liver resection for pCCA is presented. A detailed mapping of the transection margins and dissection planes was performed. The results of applying different existing pR0 definitions were compared. Sixty-eight patients with pCCA were included. Five transection margins and two dissection planes were defined. By defining pR0 as cancer-free margins and planes tolerating distances <1mm, the pR0 rate was 66%. However, when pR0 was set as >1mm from invasive cancer to all resection margins and dissection planes, the pR0 rate fell to 16%. This study supports the use of thorough and standardized pathological handling, assessment and reporting of resection margins and dissection planes of surgical specimens of pCCA.

Imaging in disappearing colorectal liver metastases and their accuracy: a systematic review.

BACKGROUND: Approximately 30% of patients with colorectal cancer develop colorectal liver metastases (CRLM). CRLM that become undetectable by imaging after chemotherapy are called disappearing liver metastases (DLM). But a DLM is not necessarily equal to cure. An increasing incidence of patients with DLM provides surgeons with a difficult dilemma: to resect or to not resect the original sites of DLM? The aim of this review was to investigate to what extent a DLM equates a complete response (CR) and to compare outcomes. METHODS: This review was conducted in accordance with the PRISMA guidelines and registered in Prospero (registration number CRD42017070441). Literature search was made in the PubMed and Embase databases. During the process of writing, PubMed was repeatedly searched and reference lists of included studies were screened for additional studies of interest for this review. Results were independently screened by two authors with the Covidence platform. Studies eligible for inclusion were those reporting outcomes of DLM in adult patients undergoing surgery following chemotherapy. RESULTS: Fifteen studies were included with a total of 2955 patients with CRLM. They had 4742 CRLM altogether. Post-chemotherapy, patients presented with 1561 DLM. Patients with one or more DLM ranged from 7 to 48% (median 19%). Median DLM per patient was 3.4 (range 0.4-5.6). Patients were predominantly evaluated by contrast-enhanced computed tomography (CE-CT) before and after chemotherapy, with some exceptions and with addition of magnetic resonance imaging (MRI) in some studies. Intraoperative ultrasound (IOUS) was universally performed in all but two studies. If a DLM remained undetectable by IOUS, this DLM represented a CR in 24-96% (median 77.5%). Further, if a DLM on preoperative CE-CT remained undetectable by additional workup with MRI and CE-IOUS, this DLM was equal to a CR in 75-94% (median 89%). Patients with resected DLM had a longer disease-free survival compared to patients with DLM left in situ but statistically significant differences in overall survival could not be found. CONCLUSION: Combination of CE-CT, MRI, and IOUS showed promising results in accurately identifying DLM with CR. This suggests that leaving DLM in situ could be an alternative to surgical resection when a DLM remains undetectable by MRI and IOUS.

Quality-of-life after bile duct injury repaired by hepaticojejunostomy: a national cohort study.

OBJECTIVES: Reports on quality-of-life (QoL) after bile duct injury (BDI) show conflicting results. The aim of this cohort study was to evaluate QoL stratified according to type of treatment. METHODS: QoL assessment using the SF-36 (36-item short form health survey) questionnaire. Patients with post-cholecystectomy BDI needing hepaticojejunostomy (HJ) were compared to all other treatments (BDI repair) and to patients without BDI at cholecystectomy (controls). RESULTS: Patients needing a HJ after BDI reported reduced long-term QoL irrespective of time for diagnosis and repair in both the physical (PCS; p < .001) and mental (MCS; p < .001) domain compared to both controls and patients with less severe BDI. QoL was comparable for BDI repair (n = 86) and controls (n = 192) in both PCS (p = .171) and MCS (p = .654). As a group, patients with BDI (n = 155) reported worse QoL than controls, in both the PCS (p < .001) and MCS (p = .012). Patients with a BDI detected intraoperatively (n = 124) reported better QoL than patients with a postoperative diagnosis. Patients with an immediate intraoperative repair (n = 99), including HJ, reported a better long-term QoL compared to patients subjected to a later procedure (n = 54). CONCLUSIONS: Patients with postoperative diagnosis and patients with BDIs needing biliary reconstruction with HJ both reported reduced long-term QoL.

Outcomes of Simultaneous Resections and Classical Strategy for Synchronous Colorectal Liver Metastases in Sweden: A Nationwide Study with Special Reference to Major Liver Resections.

BACKGROUND: About 20% of patients with colorectal cancer have liver metastases at the time of diagnosis, and surgical resection offers a chance for cure. The aim of the present study was to compare outcomes for patients that underwent simultaneous resection to those that underwent a staged procedure with the bowel-first (classical) strategy by using information from two national registries in Sweden. METHODS: In this prospectively registered cohort study, we analyzed clinical, pathological, and survival outcomes for patients operated in the period 2008-2015 and compared the two strategies. RESULTS: In total, 537 patients constituted the study cohort, where 160 were treated with the simultaneous strategy and 377 with the classical strategy. Patients managed with the simultaneous strategy had less often rectal primary tumors (22% vs. 31%, p = 0.046) and underwent to a lesser extent a major liver resection (16% vs. 41%, p < 0.001), but had a shorter total length of stay (11 vs. 15 days, p < 0.001) and more complications (52% vs. 36%, p < 0.001). No significant 5-year overall survival (p = 0.110) difference was detected. Twenty-five patients had a major liver resection in the simultaneous strategy group and 155 in the classical strategy group without difference in 5-year overall survival (p = 0.198). CONCLUSION: Simultaneous resection of the colorectal primary cancer and liver metastases can possibly have more complications, with no difference in overall survival compared to the classical strategy.

Hepatopancreatoduodenectomy -a controversial treatment for bile duct and gallbladder cancer from a European perspective.

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.

Prognostic value of preoperative inflammatory markers in resectable biliary tract cancer - Validation and comparison of the Glasgow Prognostic Score and Modified Glasgow Prognostic Score in a Western cohort.

INTRODUCTION: Established preoperative prognostic factors for risk stratification of patients with biliary tract cancer (BTC) are lacking. A prognostic value of the inflammation-based Glasgow Prognostic Score (GPS) and Modified Glasgow Prognostic Score (mGPS) in BTC has been indicated in several Eastern cohorts. We sought to validate and compare the prognostic value of the GPS and the mGPS for overall survival (OS), in a large Western cohort of patients with BTC. MATERIAL AND METHODS: We performed a retrospective single-center study for the period 2009 until 2017. 216 consecutive patients that underwent surgical exploration with a diagnosis of perihilar cholangiocarcinoma (PHCC), intrahepatic cholangiocarcinoma (IHCC), or gallbladder cancer (GBC) were assessed. GPS and mGPS were calculated where both CRP and albumin were measured pre-operatively (n = 168/216). Survival was analyzed by Kaplan-Meier estimate and uni-/multivariate Cox regression. RESULTS: GPS and mGPS were negatively associated with survival (p < 0.001/p < 0.001), and the association was significant in all three subgroups. GPS, but not the mGPS, identified an intermediate risk group: with GPS = 1 having better OS than GPS = 2 (p = 0.003), but worse OS than GPS = 0 (p = 0.008). In multivariate analyses of resected patients, GPS (p = 0.001) and mGPS (p = 0.03) remained significant predictors of survival, independent of postoperatively available risk factors. CONCLUSIONS: Preoperative GPS and mGPS are independent prognostic factors in BTC. The association to OS was shown in all patients undergoing exploration, in resected patients only, and in both cholangiocarcinoma and gallbladder cancer. Furthermore, GPS - which weights hypoalbuminemia higher - could identify an intermediate risk group.

Repeat procedures for recurrent colorectal liver metastases: analysis of long-term liver regeneration and outcome.

Background and aim: Repeat hepatectomy is increasingly performed for the management of recurrent colorectal liver metastases (CRLM). The aim of this study was to evaluate long-term functional liver volume (FLV) after a second hepatic procedure and to measure survival outcome. Methods: In this retrospective cohort study, patients treated for recurrent CRLM in the years 2005-2015 at two liver centers were included. Total FLV was calculated before the first procedure and before and after the second procedure. Overall survival was calculated. Results: Eighty-two patients were identified. The median follow-up was 53 (40-71) months from the first procedure. The median interval between first and second procedure was 13 (8-22) months. The initial FLV was 1584 (1313-1927) mL. The FLV was 1438 (1204-1896) mL after the first procedure and 1470 (1172-1699) mL after the second procedure (P<0.001). After the second procedure, a total of ten patients (12%) had a residual liver volume of less than 75% of the initial liver volume. The 5-year overall survival was 37 (26-54)% after the second procedure. Conclusion: Small changes in FLV were found after two hepatic procedures but with considerable inter-individual variation. Patients selected for a repeated hepatic procedure for recurrent CRLM had an acceptable survival.