Postoperative Hyperamylasemia (POH) is an Early Predictor of Pancreatic Fistula Occurrence and Severity after Distal Pancreatectomy: Results from a European Multicentric Study.

OBJECTIVES: The aim of this international multicentric study is to characterize postoperative hyperamylasemia (POH) after distal pancreatectomy (DP), with particular focus on its relationship with postoperative pancreatic fistula (POPF) occurrence and severity. BACKGROUND: The clinical relevance of POH after DP and its relationship with the occurrence and severity of POPF have not been explored yet. METHODS: All patients undergoing DP for any indication between 2015 and 2021 at three European referral Centers for pancreatic surgery were retrospectively analyzed. Drain fluid amylase (DFA), C-reactive protein (C-RP), and serum amylase were examined from postoperative-day (POD) 1 to 3. Biochemical leak (BL), POPF, POH, and post-pancreatectomy hemorrhage (PPH) were defined and graded according to ISGPS definitions. RESULTS: In total 1192 patients were included. Overall rates of POH and POPF were 18% (n= 210) and 29% (n= 344), respectively. The presence of DFA ≥2000 U/L on POD 1 (OR=2.11, 95% CI 1.68-2.86), C-RP ≥200 mg/L on POD 3 (OR=2.19, 95% CI 1.68-2.86), and POH (OR=1.58, 95% CI 1.14-2.19) were all independent early predictors of POPF (all P< 0.01). The presence of POH almost doubled the rate of POPF (43% vs. 26%, P<0.001), and higher POPF severity presented also higher POH rates (no POPF= 12%; BL= 19%; B POPF= 24%; C POPF= 52%). Among patients developing POPF, patients with POH had higher rates of PPH (22% vs 9%, P= 0.001), sepsis (24% vs 13%; P=0.011), re-operation (21% vs 8%; P< 0.01), and mortality (3% vs 0.3%; P= 0.025). CONCLUSIONS: The occurrence of POH is an early predictor of POPF and its severity after DP. The diagnosis of POH might define patients at higher risk for a complicated course, targeting them for prevention / mitigation strategies against pancreas specific complications.

Comparing the accuracy of prediction models to detect clinically relevant post-hepatectomy liver failure early after major hepatectomy.

BACKGROUND: Arterial lactate measurements were recently suggested as an early predictor of clinically relevant post-hepatectomy liver failure (PHLF). This needed to be evaluated in the subgroup of major hepatectomies only. METHOD: This observational cohort study included consecutive elective major hepatectomies at Karolinska University Hospital from 2010 to 2018. Clinical risk factors for PHLF, perioperative arterial lactate measurements and routine lab values were included in uni- and multivariable regression analysis. Receiver operating characteristics and risk cut-offs were calculated. RESULTS: In total, 649 patients constituted the study cohort, of which 92 developed PHLF grade B/C according to the International Study Group of Liver Surgery (ISGLS). Lactate reached significantly higher intra- and postoperative levels in PHLF grades B and C compared to grade A or no liver failure (all P < 0.002). Lactate on postoperative day (POD) 1 was superior to earlier measurement time points in predicting PHLF B/C (AUC 0.75), but was outperformed by both clinical risk factors (AUC 0.81, P = 0.031) and bilirubin POD1 (AUC 0.83, P = 0.013). A multivariable logistic regression model including clinical risk factors and bilirubin POD1 had the highest AUC of 0.87 (P = 0.006), with 56.6% sensitivity and 94.7% specificity for PHLF grade B/C (cut-off ≥0.32). The model identified 46.7% of patients with 90-day mortality and had an equally good discriminatory potential for mortality as the established ISGLS criteria for PHLF grade B/C but could be applied already on POD1. CONCLUSION: The potential of lactate to predict PHLF following major hepatectomy was inferior to a prediction model consisting of clinical risk factors and bilirubin on first post-operative day.

MicroRNAs as Plasma Biomarkers of Hepatocellular Carcinoma in Patients with Liver Cirrhosis-A Cross-Sectional Study.

Ultrasound screening for hepatocellular carcinoma (HCC) in patients with liver cirrhosis has a poor sensitivity for small tumors. Circulating microRNAs (miRNAs) have been explored as HCC biomarkers, but results are diverging. Here, we evaluate if miRNAs up-regulated in HCC tissue can be detected in plasma and used as screening biomarkers for HCC. In this cross-sectional study, plasma, HCC tissue and surrounding non-tumorous liver tissue were collected from liver resections. Tissue miRNAs were identified and quantitated by RNA-sequencing analysis, and the fold-changes between HCC and surrounding liver tissue were calculated. The miRNAs up-regulated in HCCs were then re-analyzed in plasma from the same patients, and the miRNAs with the highest plasma levels were subsequently measured in plasma from an independent cohort of patients with cirrhosis or HCC. In tissues from 84 resected patients, RNA-sequencing detected 197 differentially expressed miRNAs, 40 of which had a raw count above 200 and were analyzed in plasma from the same cohort. Thirty-one miRNAs were selected for further analysis in 200 patients with HCC or cirrhosis. Of these, eleven miRNAs were significantly increased in HCC as compared to cirrhosis patients. Only miR-93-5p and miR-151a-3p were significantly associated with HCC, with an AUC of 0.662. In comparison, alpha-fetoprotein and des-gamma-carboxy prothrombin yielded an AUC of 0.816, which increased to 0.832 if miR-93-5p and miR-151a-3p were added. When including sex and age, the addition of miR-93-5p and miR-151a-3p did not further improve the AUC (from 0.910 to 0.911). In conclusion, micro-RNAs up-regulated in HCCs are detectable in plasma but have a poor performance as screening biomarkers of HCC.

European fellowship training opportunities for hepato-pancreato-biliary surgery: an international survey of fellows and program directors.

BACKGROUND: There are no established training pathways for hepato-pancreato-biliary (HPB) surgery in Europe. This study aims to overview the current status of fellowship training from both fellows' and institutions' perspectives. METHODS: A web-based snapshot survey was distributed to all members of the European-African Hepato-Pancreato-Biliary Association (E-AHPBA) to reach for former fellows and program directors of European HPB surgery fellowships held between 2013 and 2023. RESULTS: A total of 37 fellows and 13 program directors replied describing 32 different programs in 13 European countries. The median (range) age at fellowship start was 34 (30-45 years). Fellowship duration was most commonly one (36 %) or two (40 %) years. Fellowships were funded in 70 % and fellows were required to learn a new language in 27 %. Most fellows performed between none and 10 pancreatic (68 %), major (67 %) and minor (60 %) liver resections as 1st surgeon, while the number of operations performed as 1st assistant were more heterogeneous. Program directors estimated a higher number of operations performed by fellows as first surgeons. The percentage of procedures performed minimally invasively did not exceed 10 %. CONCLUSION: There is substantial heterogeneity between HPB fellowship programs in Europe. A wider standardization of clinical curriculum, including minimally invasive surgery, is desirable.

An APRI+ALBI Based Multivariable Model as Preoperative Predictor for Posthepatectomy Liver Failure.

OBJECTIVE AND BACKGROUND: Clinically significant posthepatectomy liver failure (PHLF B+C) remains the main cause of mortality after major hepatic resection. This study aimed to establish an APRI+ALBI, aspartate aminotransferase to platelet ratio (APRI) combined with albumin-bilirubin grade (ALBI), based multivariable model (MVM) to predict PHLF and compare its performance to indocyanine green clearance (ICG-R15 or ICG-PDR) and albumin-ICG evaluation (ALICE). METHODS: 12,056 patients from the National Surgical Quality Improvement Program (NSQIP) database were used to generate a MVM to predict PHLF B+C. The model was determined using stepwise backwards elimination. Performance of the model was tested using receiver operating characteristic curve analysis and validated in an international cohort of 2,525 patients. In 620 patients, the APRI+ALBI MVM, trained in the NSQIP cohort, was compared with MVM's based on other liver function tests (ICG clearance, ALICE) by comparing the areas under the curve (AUC). RESULTS: A MVM including APRI+ALBI, age, sex, tumor type and extent of resection was found to predict PHLF B+C with an AUC of 0.77, with comparable performance in the validation cohort (AUC 0.74). In direct comparison with other MVM's based on more expensive and time-consuming liver function tests (ICG clearance, ALICE), the APRI+ALBI MVM demonstrated equal predictive potential for PHLF B+C. A smartphone application for calculation of the APRI+ALBI MVM was designed. CONCLUSION: Risk assessment via the APRI+ALBI MVM for PHLF B+C increases preoperative predictive accuracy and represents an universally available and cost-effective risk assessment prior to hepatectomy, facilitated by a freely available smartphone app.

Risk Factors, Management, and Outcome of Gastric Venous Congestion After Total Pancreatectomy: An Underestimated Complication Requiring Standardized Identification, Grading, and Management.

BACKGROUND: Gastric venous congestion (GVC) after total pancreatectomy (TP) is rarely studied despite its high 5% to 28% incidence and possible association with mortality. This study aimed to provide insight about incidence, risk factors, management, and outcome of GVC after TP. METHODS: This retrospective observational single-center study included all patients undergoing elective TP from 2008 to 2021. The exclusion criteria ruled out a history of gastric resection, concomitant (sub)total gastrectomy for oncologic indication(s) or celiac axis resection, and postoperative (sub)total gastrectomy for indication(s) other than GVC. RESULTS: The study enrolled 268 patients. The in-hospital major morbidity (Clavien-Dindo grade ≥IIIa) rate was 28%, and the 90-day mortality rate was 3%. GVC was identified in 21% of patients, particularly occurring during index surgery (93%). Intraoperative GVC was managed with (sub)total gastrectomy for 55% of the patients. The major morbidity rate was higher for the patients with GVC (44% vs 24%; p = 0.003), whereas the 90-day mortality did not differ significantly (5% vs 3%; p = 0.406). The predictors for major morbidity were intraoperative GVC (odds ratio [OR], 2.207; 95% confidence interval [CI], 1.142-4.268) and high TP volume (> 20 TPs/year: OR, 0.360; 95% CI, 0.175-0.738). The predictors for GVC were portomesenteric venous resection (PVR) (OR, 2.103; 95% CI, 1.034-4.278) and left coronary vein ligation (OR, 11.858; 95% CI, 5.772-24.362). CONCLUSIONS: After TP, GVC is rather common (in 1 of 5 patients). GVC during index surgery is predictive for major morbidity, although not translating into higher mortality. Left coronary vein ligation and PVR are predictive for GVC, requiring vigilance during and after surgery, although gastric resection is not always necessary. More evidence on prevention, identification, classification, and management of GVC is needed.

Risk factors for acute kidney injury after pancreatoduodenectomy, and association with postoperative complications and death.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality after general surgery, although little is known among patients undergoing pancreatoduodenectomy. The objective was to investigate the association between AKI and postoperative complications and death after pancreatoduodenectomy. METHODS: All patients ≥18 years who underwent a pancreatoduodenectomy 2008-2019 at the Karolinska University Hospital, Stockholm, Sweden, were included. Standardized criteria for AKI, including estimated glomerular filtration rate (eGFR) and urine volume measurements, were used to grade postoperative AKI. RESULTS: In total, 970 patients were included with a median age of 68 years (IQR 61-74) of whom 517 (53.3%) were men. There were 137 (14.1%) patients who developed postoperative AKI. Risk factors for AKI included lower preoperative eGFR, cardiovascular disease and treatment with renin-angiotensin system inhibitors or diuretics. Those who developed AKI had a higher risk of severe postoperative complications, including Clavien-Dindo score ≥ IIIa (adjusted OR 3.35, 95% CI 2.24-5.01) and ICU admission (adjusted OR 7.83, 95% CI 4.39-13.99). In time-to-event analysis, AKI was associated with an increased risk for both 30-day mortality (adjusted HR 4.51, 95% CI 1.54-13.27) and 90-day mortality (adjusted HR 4.93, 95% CI 2.37-10.26). Patients with benign histology and AKI also had an increased 1-year mortality (HR 4.89, 95% CI 1.88-12.71). CONCLUSIONS: Postoperative AKI was associated with major postoperative complications and an increased risk of postoperative mortality. Monitoring changes in serum creatinine levels and urine volume output could be important in the immediate perioperative period to improve outcomes after pancreatoduodenectomy.

Gallbladder cancer mimicking perihilar cholangiocarcinoma-considerable rate of postoperative reclassification with implications for prognosis.

BACKGROUND: For some patients undergoing resection under the suspicion of a perihilar cholangiocarcinoma (pCCA), postoperative diagnosis may differ from the preoperative diagnosis. While a postoperative finding of benign bile duct stricture is known to affect 3-15% of patients, less has been described about the consequences of finding other biliary tract cancers postoperatively. This study compared pre- and postoperative diagnoses, risk characteristics, and outcomes after surgery for suspected pCCA. METHODS: Retrospective single-center study, Karolinska University Hospital, Stockholm, Sweden (January 2009-May 2017). The primary postoperative outcome was overall survival. Secondary outcomes were disease-free survival and postoperative complications. Survival analysis was performed by the Kaplan-Meier method. RESULTS: Seventy-one patients underwent resection for suspected pCCA. pCCA was confirmed in 48 patients (68%). Ten patients had benign lesions (14%), 2 (3%) were diagnosed with other types of cholangiocarcinoma (CCA, distal n = 1, intrahepatic n = 1), while 11 (15%) were diagnosed with gallbladder cancer (GBC). GBC patients were older than patients with pCCA (median age 71 versus 58 years, p = 0.015), with a large proportion of patients with a high tumor extension stage (≥ T3, 91%). Median overall survival was 20 months (95% CI 15-25 months) for patients with pCCA and 17 months (95% CI 11-23 months) for patients with GBC (p = 0.135). Patients with GBC had significantly shorter median disease-free survival (DFS), 10 months (95% CI 3-17 months) compared 17 months (95% CI 15-19 months) for patients with pCCA (p = 0.010). CONCLUSIONS: At a large tertiary referral center, 15% of patients resected for suspected pCCA were postoperatively diagnosed with GBC. Compared to patients with pCCA, GBC patients were older, with advanced tumors and shorter DFS. The considerable rate of re-classification stresses the need for improved preoperative staging, as these prognostic differences could have implications for treatment strategies.

Symptoms and life changes after total pancreatectomy: a qualitative study.

BACKGROUND: Total pancreatectomy (TP) is a major surgical procedure that involves lifelong exocrine and endocrine pancreatic insufficiency. Qualitative evidence is sparse regarding patients' experiences after the operation. The aim of this study was to explore patients' experiences of symptoms that occur after TP and how these symptoms affect their health and life situations. METHODS: A qualitative design with prospective consecutive sampling and an inductive thematic analysis was used. Semistructured interviews were postoperatively performed at 6-9 months with 20 patients undergoing TP in two university hospitals in Sweden. RESULTS: Two main themes emerged from the analysis: "Changes in everyday life" and "Psychological journey". Patients experienced symptoms related to diabetes as the major life change after the operation, and they were also limited by symptoms of exocrine insufficiency, difficulties with food intake and physical weakness. In the psychological journey that patients underwent, the support received from family, friends and the health care system was important. Moreover, patients experienced a general need for more extensive information, especially regarding diabetes. CONCLUSION: Patients experience a lack of sufficient support and education after TP, particularly concerning their diabetes. Further efforts should be undertaken to improve information and the organization of diabetes care for this patient group.

Liver transplantation in patients with post-hepatectomy liver failure - A Northern European multicenter cohort study.

BACKGROUND: Liver transplantation (LTX) has been described as a rescue treatment option in severe, intractable post-hepatectomy liver failure (PHLF), but is not considered to be indicated for this condition by many hepatobiliary and transplant surgeons. In this article we describe the clinical experience of five northern European tertiary centers in using LTX to treat selected patients with severe PHLF. METHODS: All patients subjected to LTX due to PHLF at the participating centers were identified from prospective clinical databases. Preoperative variables, surgical outcome (both resection surgery and LTX) and follow-up data were assessed. RESULTS: A total of 10 patients treated with LTX due to severe PHLF from September 2008 to May 2020 were identified and included in the study. All patients but one were male and the median age was 70 years (range 49-72). In all patients the indication for liver resection was suspected malignancy, but in six patients post-resection pathology revealed benign or pre-malignant disease. There was no 90-day mortality after LTX. Patients were followed for a median of 49 months (13-153) and eight patients were alive without recurrence at last follow-up. DISCUSSION: In selected patients with PHLF LTX can be a life-saving procedure with low short-term risk.

Outcome after resection for invasive intraductal papillary mucinous neoplasia is similar to conventional pancreatic ductal adenocarcinoma.

BACKGROUND/OBJECTIVES: Resections for intraductal papillary mucinous neoplasm (IPMN) have increased last decades. Overall survival (OS) for conventional pancreatic ductal adenocarcinoma (PDAC) is well known but OS for invasive IPMN (inv-IPMN) is not as conclusive. This study aims to elucidate potential differences in clinicopathology and OS between these tumor types and to investigate if the raised number of resections have affected outcome. METHODS: Consecutive patients ≥18 years of age resected for inv-IPMN and PDAC at Karolinska University Hospital between 2009 and 2018 were included. Clinicopathological variables were analyzed in multivariable regression models. Outcome was assessed calculating two-year OS, estimating OS using the Kaplan-Meier model and comparing survival functions with log-rank test. RESULTS: 513 patients were included, 122 with inv-IPMN and 391 with PDAC. During the study period both the proportion resected inv-IPMN and two-year OS, irrespective of tumor type, increased (2.5%-45%; p < 0.001 and 44%-57%; p = 0.005 respectively). In Kaplan-Meier survival analysis inv-IPMN had more favorable median OS (mOS) compared to PDAC (33.6 months vs 19.3 months, p = 0.001). However, in multivariable Cox Regression analysis, tumor type was not a predictor for death, but so were resection period, tumor subtype and N-stage (all p < 0.001). CONCLUSION: In this large single center observational cohort study, inv-IPMN seemed to have favorable survival outcome compared to PDAC, but after adjusting for predictors for death this benefit vanished. The combination of a pronounced increase in resected inv-IPMN and a concurrent hazard abatement for death within 2 years during the study period proved to be a principal factor.

Systematic review of MARS treatment in post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) remains a serious complication after major liver resection with severe 90-day mortality. Molecular adsorbent recirculating system (MARS) is a potential treatment option in PHLF. This systematic review sought to analyze the experiences and results of MARS in PHLF. METHODS: Following the PRISMA guidelines, a systematic literature review using PubMed and Embase was performed. Non-randomized trials were assessed by the MINORS criteria. RESULTS: 2884 records were screened and 22 studies were extracted (no RCT). They contained 809 patients including 82 patients with PHLF. Five studies (n = 34) specifically investigated the role of MARS in patients with PHLF. In these patients, overall 90-day survival was 47%. Patients with primary PHLF had significantly better 90-day survival compared to patients with secondary PHLF (60% vs 14%, p = 0.03) and treatment was started earlier (median POD 6 (range 2-21) vs median POD 30 (range 15-39); p < 0.001). Number of treatments differed non-significantly in these groups. Safety and feasibility of early MARS treatment following hepatectomy was demonstrated in one prospective study. No major adverse events have been reported. CONCLUSION: Early MARS treatment is safe and feasible in patients with PHLF. Currently, MARS cannot be recommended as standard of care in these patients. Further prospective studies are warranted.

The impact of post-hepatectomy liver failure on mortality: a population-based study.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is considered a main reason for death after major hepatectomy. The reported PHLF-related mortality differs largely and the data mainly originate from single centers. AIM: A retrospective, population-based register study was designed to evaluate the impact of PHLF on 90-day mortality after hepatectomy. METHOD: All patients who underwent liver resection in Sweden between 2005 and 2009 were retrospectively identified using the Swedish Hospital Discharge Registry. 30- and 90-day mortality were identified by linkage to the Registry of Causes of Death. Additional clinical data were obtained from the medical charts in all seven university hospitals in Sweden. PHLF was defined according to Balzan criteria (Bilirubin >50 µg/L and international normalized ratio >1.5) on postoperative day 5. RESULTS: A total of 2461 liver resections were performed (2194 in university hospitals). 30- and 90-day mortality were 1.3% and 2.5%, respectively. 90-day mortality at university hospitals was 2.1% (n = 46). In 41% (n = 19) of these patients, PHLF alone or in combination with multi-organ failure was identified as cause of death. Between the PHLF and non-PHLF group, there was no significant difference regarding age, sex, American Society of Anesthesiologists-classification, or preoperative chemotherapy. Cholangiocarcinoma as indication for surgery, need for vascular reconstruction and an extended resection were significantly overrepresented in the PHLF-group. Between groups, the incidence of 50:50 criteria differed significantly already on postoperative day 3. CONCLUSION: Overall mortality is very low after hepatectomy in Sweden. PHLF represents the single most important cause of death even in a population-based setting.

Serial Assessment of Growth Factors Associated with Liver Regeneration in Patients Operated with Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.

BACKGROUND: There is limited knowledge about the mechanisms behind the unparalleled growth of the future liver remnant (FLR) linked to associating liver partition and portal vein ligation for staged hepatectomy (ALPPS). In this study, liver regenerative markers were examined in patients subjected to ALPPS. METHODS: Ten patients with colorectal liver metastases treated with neoadjuvant chemotherapy and ALPPS were included. Plasma was sampled at 6 time points and biopsies from both liver lobes were collected at both stages of ALPPS. The levels of interleukin (IL)-6, hepatocyte growth factor (HGF), tumor necrosis factor-α, epidermal growth factor, and vascular endothelial growth factor in plasma were measured at each time point. Expression of mRNA for markers of proliferation and apoptosis was studied in the biopsies from both liver lobes taken at both stages. RESULTS: ALPPS resulted in a peak of IL-6 after stage 1 (p = 0.004), which decreased rapidly and did not increase again after stage 2. HGF also increased after stage 1 (p = 0.048), and the HGF levels correlated significantly with the degree of growth of the FLR before stage 2 (p = 0.02, r2 = 0.47). There was a correlation between peak levels of IL-6 and HGF (p = 0.03, r2 = 0.84). CONCLUSIONS: IL-6 and HGF seem to be early mediators of hypertrophy after stage 1 in the ALPPS procedure. The peak HGF plasma level correlates with the degree of FLR growth in patients subjected to ALPPS.

Rescue ALPPS is efficient and safe after failed portal vein occlusion in patients with colorectal liver metastases.

PURPOSE: The aim of this study was to investigate whether associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can be used as an effective and safe rescue procedure in patients with colorectal liver metastases (CRLM) and insufficient effect on the future liver remnant (FLR) after previous portal vein occlusion (PVO). METHODS: Eleven patients with bilobar CRLM treated with neoadjuvant chemotherapy and previous PVO with insufficient effect on the FLR were analyzed retrospectively from a prospective database. FLR was evaluated with computed tomography volumetry 6 days after stage 1, and stage 2 was performed on day seven. RESULTS: Six days after stage 1, the median increase of the FLR was 209 ml (range 87-314, P < 0.001). This corresponded to a median FLR growth of 61.8 % (range 19.3-120) resulting in an FLR/BW ratio >0.5 % in all patients and successful subsequent removal of the tumor bearing liver (segments IV-VIII) in all patients with no 90-day mortality. No patient had a 3b-complication or more according to Clavien-Dindo. No patient developed severe posthepatectomy liver failure. CONCLUSIONS: The powerful hypertrophy of the FLR associated with ALPPS seems to be maintained in patients with CRLM and previous failed PVO.

Mortality-related risk factors and long-term survival after 4460 liver resections in Sweden-a population-based study.

PURPOSE: The objectives of this study were to analyze the outcome after hepatectomy and to identify contributing factors to mortality and long-term survival in a population-based setting. METHOD: A retrospective, nationwide register study was performed. All patients who underwent hepatectomy in Sweden between 2002 and 2011 were identified in the Swedish Hospital Discharge Registry using their unique personal identification numbers. This cohort was linked to the National Cancer Registry (cancer diagnosis), the National Registry of Causes of Death, and the Migration Registry. Survival analysis by Kaplan-Meier method was performed to assess long-term outcome. A Cox regression model was used to analyze risk factors affecting long-term survival. RESULTS: Overall, 4460 hepatectomies were performed. The 30- and 90-day mortalities were 1.8 and 3.1 %, respectively. The overall 5- and 10-year survival rates for all diagnoses were 45 and 38 %, respectively. Independent risk factors for 5-year mortality were as follows: patient age, comorbidity, male gender, intrahepatic/extrahepatic cholangiocarcinoma, gallbladder cancer, extent of hepatectomy, and hepatectomies performed at non-university hospitals. Re-resection (78.1 % with diagnosis "metastasis") was performed on 374 patients. In these patients, mortality risk decreased by >50 % (HR 0.42; 95 %, CI 0.33-0.53). CONCLUSION: In a population-based analysis, liver resections are done with a low mortality risk and good long-term outcome. Patients who underwent resection at a University Hospital showed a significant better outcome compared to patients resected at non-University Hospitals. These results support further centralization of liver surgery. Re-resection should be performed if feasible.

Hepatocellular carcinoma in cirrhotic versus non-cirrhotic liver: Treatment and survival differences in a nationwide cohort.

BACKGROUND AND AIMS: Numerous studies have reported superior outcome for patients with hepatocellular carcinoma (HCC) in non-cirrhotic compared to cirrhotic livers. This cohort study aims to describe the clinical presentation, disease course, treatment approaches, and survival differences in a population-based setting. METHODS: Data on patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry (SweLiv). Descriptive and survival statistics were applied. RESULTS: Among the 4259 identified patients, 34% had HCC in a non-cirrhotic liver. Cirrhotic patients presented at a younger age (median = 64 vs 74 years, p < 0.001) and with a poorer performance status (Eastern Cooperative Oncology Group (ECOG) = 0-1: 64% vs 69%, p = 0.024). Underlying liver disease was more prevalent among cirrhotic patients (81% vs 19%, p < 0.001). Tumors in non-cirrhotic livers were diagnosed at a more advanced stage (T3-T4: 46% vs 31%) and more frequently with metastatic disease at diagnosis (22% vs 10%, p < 0.001). Tumors were significantly larger in non-cirrhotic livers (median size of largest tumor 7.5 cm) compared to cirrhotic livers (3.5 cm) (p < 0.001). Curative interventions were more commonly intended (45% vs 37%, p < 0.001) and performed (40% vs 31%, p < 0.001) in the cirrhotic vs non-cirrhotic patients. Median survival was 19 months (95% confidence interval (CI) = 18-21 months), in patients with cirrhosis as compared to 13 months in non-cirrhotic patients (95% CI = 11-15) (p < 0.001). In the multivariable Cox regression model, cirrhosis was not an independent predictor of survival, neither among curatively nor palliatively treated patients. CONCLUSION: These population-based data show that patients with HCC in a cirrhotic liver receive curative treatment to a greater extent and benefit from superior survival compared to those with HCC in a non-cirrhotic liver. The differences in survival are more attributable to patient and tumor characteristics rather than the cirrhotic status itself. CLINICAL TRIAL REGISTRATION: not applicable. Patient confidentially: not applicable.

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.