Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

De novo transcriptomic subtyping of colorectal cancer liver metastases in the context of tumor heterogeneity.

BACKGROUND: Gene expression-based subtyping has the potential to form a new paradigm for stratified treatment of colorectal cancer. However, current frameworks are based on the transcriptomic profiles of primary tumors, and metastatic heterogeneity is a challenge. Here we aimed to develop a de novo metastasis-oriented framework. METHODS: In total, 829 transcriptomic profiles from patients with colorectal cancer were analyzed, including primary tumors, liver metastases, and non-malignant liver samples. High-resolution microarray gene expression profiling was performed of 283 liver metastases from 171 patients treated by hepatic resection, including multiregional and/or multi-metastatic samples from each of 47 patients. A single randomly selected liver metastasis sample from each patient was used for unsupervised subtype discovery by nonnegative matrix factorization, and a random forest prediction model was trained to classify multi-metastatic samples, as well as liver metastases from two independent series of 308 additional patients. RESULTS: Initial comparisons with non-malignant liver samples and primary colorectal tumors showed a highly variable degree of influence from the liver microenvironment in metastases, which contributed to inter-metastatic transcriptomic heterogeneity, but did not define subtype distinctions. The de novo liver metastasis subtype (LMS) framework recapitulated the main distinction between epithelial-like and mesenchymal-like tumors, with a strong immune and stromal component only in the latter. We also identified biologically distinct epithelial-like subtypes originating from different progenitor cell types. LMS1 metastases had several transcriptomic features of cancer aggressiveness, including secretory progenitor cell origin, oncogenic addictions, and microsatellite instability in a microsatellite stable background, as well as frequent RAS/TP53 co-mutations. The poor-prognostic association of LMS1 metastases was independent of mutation status, clinicopathological variables, and current subtyping frameworks (consensus molecular subtypes and colorectal cancer intrinsic subtypes). LMS1 was also the least heterogeneous subtype in comparisons of multiple metastases per patient, and tumor heterogeneity did not confound the prognostic value of LMS1. CONCLUSIONS: We report the first large study of multi-metastatic gene expression profiling of colorectal cancer. The new metastasis-oriented subtyping framework showed potential for clinically relevant transcriptomic classification in the context of metastatic heterogeneity, and an LMS1 mini-classifier was constructed to facilitate prognostic stratification and further clinical testing.

Survival Outcomes After Portal Vein Embolization and Liver Resection Compared With Liver Transplant for Patients With Extensive Colorectal Cancer Liver Metastases.

Importance: Portal vein embolization (PVE) has been implemented in patients with extensive colorectal liver metastases to increase the number of patients able to undergo liver resection. Liver transplant could be an alternative in selected patients with extensive liver-only disease, and we have recently shown promising survival outcomes. Objective: To compare overall survival (OS) among patients with colorectal cancer and high liver metastasis tumor load who were treated with liver transplant or with PVE and liver resection. Design, Setting, and Participants: This comparative effectiveness research study assessed 50 patients with colorectal cancer liver metastases who were previously enrolled in liver transplant studies between November 2006 and August 2019 at Oslo University Hospital in Norway. Those patients were compared with a retrospective cohort of 53 patients in the Oslo University Hospital PVE database from March 2006 through November 2015 with similar selection criteria who underwent PVE and liver resection. Main Outcomes and Measures: The OS among patients with high tumor load after liver transplant was compared with that among patients with high tumor load who underwent PVE and liver resection. High tumor load was defined as 9 or more metastatic tumors or a diameter of 5.5 cm or longer for the largest liver lesion. Results: In the PVE cohort of 53 patients, the median age was 61.8 years (range, 34.3-71.3 years), and 36 patients (68%) were men. The 5-year OS rate among 38 patients who underwent liver resection after PVE was 44.6%. The 5-year OS rate for patients with high tumor load was 33.4% for those who underwent liver transplant and 6.7% for those who underwent PVE. Among patients with high tumor load and left-sided primary tumors, the 5-year OS rate was 45.3% for those receiving a liver allograft and 12.5% for those treated with PVE and liver resection. Conclusions and Relevance: Patients with nonresectable disease, an extensive liver tumor load, and left-sided primary tumors had long OS after liver transplant, exceeding the survival outcome for those patients treated with PVE and liver resection.

Genomic and prognostic heterogeneity among RAS/BRAFV600E /TP53 co-mutated resectable colorectal liver metastases.

Hepatic resection is potentially curative for patients with colorectal liver metastases, but the treatment benefit varies. KRAS/NRAS (RAS)/TP53 co-mutations are associated with a poor prognosis after resection, but there is large variation in patient outcome within the mutation groups, and genetic testing is currently not used to evaluate benefit from surgery. We have investigated the potential for improved prognostic stratification by combined biomarker analysis with DNA copy number aberrations (CNAs), and taking tumor heterogeneity into account. We determined the mutation status of RAS, BRAFV600 , and TP53 in 441 liver lesions from 171 patients treated by partial hepatectomy for metastatic colorectal cancer. CNAs were profiled in 232 tumors from 67 of the patients. Mutations and high-level amplifications of cancer-critical genes, the latter including ERBB2 and EGFR, were predominantly homogeneous within patients. RAS/BRAFV600E and TP53 co-mutations were associated with a poor patient outcome (hazard ratio, HR, 3.9, 95% confidence interval, CI, 1.3-11.1, P = 0.012) in multivariable analyses with clinicopathological variables. The genome-wide CNA burden and intrapatient intermetastatic CNA heterogeneity varied within the mutation groups, and the CNA burden had prognostic associations in univariable analysis. Combined prognostic analyses of RAS/BRAFV600E /TP53 mutations and CNAs, either as a high CNA burden or high intermetastatic CNA heterogeneity, identified patients with a particularly poor outcome (co-mutation/high CNA burden: HR 2.7, 95% CI 1.2-5.9, P = 0.013; co-mutation/high CNA heterogeneity: HR 2.5, 95% CI 1.1-5.6, P = 0.022). In conclusion, DNA copy number profiling identified genomic and prognostic heterogeneity among patients with resectable colorectal liver metastases with co-mutated RAS/BRAFV600E /TP53.

Patient-Derived Organoids from Multiple Colorectal Cancer Liver Metastases Reveal Moderate Intra-patient Pharmacotranscriptomic Heterogeneity.

PURPOSE: Molecular tumor heterogeneity may have important implications for the efficacy of targeted therapies in metastatic cancers. Inter-metastatic heterogeneity of sensitivity to anticancer agents has not been well explored in colorectal cancer. EXPERIMENTAL DESIGN: We established a platform for ex vivo pharmacogenomic profiling of patient-derived organoids (PDO) from resected colorectal cancer liver metastases. Drug sensitivity testing (n = 40 clinically relevant agents) and gene expression profiling were performed on 39 metastases from 22 patients. RESULTS: Three drug-response clusters were identified among the colorectal cancer metastases, based primarily on sensitivities to EGFR and/or MDM2 inhibition, and corresponding with RAS mutations and TP53 activity. Potentially effective therapies, including off-label use of drugs approved for other cancer types, could be nominated for eighteen patients (82%). Antimetabolites and targeted agents lacking a decisive genomic marker had stronger differential activity than most approved chemotherapies. We found limited intra-patient drug sensitivity heterogeneity between PDOs from multiple (2-5) liver metastases from each of ten patients. This was recapitulated at the gene expression level, with a highly proportional degree of transcriptomic and pharmacological variation. One PDO with a multi-drug resistance profile, including resistance to EGFR inhibition in a RAS-mutant background, showed sensitivity to MEK plus mTOR/AKT inhibition, corresponding with low-level PTEN expression. CONCLUSIONS: Intra-patient inter-metastatic pharmacological heterogeneity was not pronounced and ex vivo drug screening may identify novel treatment options for metastatic colorectal cancer. Variation in drug sensitivities was reflected at the transcriptomic level, suggesting potential to develop gene expression-based predictive signatures to guide experimental therapies.

Limitations of molecular biomarkers in patients with resectable colorectal liver metastases.

Surgeons are exploring the use of molecular biomarkers in patients with colorectal liver metastases (CLM) to improve preoperative prognostication and selection. This is important because surrogate markers of tumor biology remain insufficient to predict clinical outcomes. In the current literature, there is agreement for the association between RAS and BRAF mutations and poor long-term outcome after hepatectomy. While this knowledge is gradually being implemented in the clinical work-up of patients, their limitations and implications have yet to be fully understood. Recent data indicate that combinations of coexisting mutations may refine the molecular scoring into footprints of good and bad. This already complex information must be interpreted in light of recent understanding of clonal heterogeneity and genetic diversity of colorectal cancer and CLM. In the clinical settings, it is important to approach new insight into molecular biomarkers with caution. However, it is likely that in the future, genomic analysis will determine which patient is amenable to surgery or not, the timing of surgery versus other modalities, as well as how to approach the metastases technically. Here we review current knowledge about molecular biomarkers in the treatment of CLM and the limitations to consider at the translation to clinical practice.

Treatment Options for Metastatic Gastrointestinal Stromal Tumors to the Liver: A Review.

Up to half of patients with a gastrointestinal stromal tumor (GIST) will present with metastatic disease, most commonly involving the liver. Prior to the introduction of tyrosine kinase inhibitors, treatment options were limited for patients with metastatic GIST to the liver resulting in dismal survival rates. However, with the advent of effective systemic chemotherapy and continued advancements in both surgical and local adjunctive therapy options, significant improvements in survival have been achieved. In this review, the authors characterize the evolution of the treatment approach for metastatic GIST to the liver, including the roles of both surgical resection and adjunctive therapies in today's practice.

RAS Mutation Clinical Risk Score to Predict Survival After Resection of Colorectal Liver Metastases.

OBJECTIVE: To determine the impact of RAS mutation status on the traditional clinical score (t-CS) to predict survival after resection of colorectal liver metastases (CLM). BACKGROUND: The t-CS relies on the following factors: primary tumor nodal status, disease-free interval, number and size of CLM, and carcinoembryonic antigen level. We hypothesized that the addition of RAS mutation status could create a modified clinical score (m-CS) that would outperform the t-CS. METHODS: Patients who underwent resection of CLM from 2005 through 2013 and had RAS mutation status and t-CS factors available were included. Multivariate analysis was used to identify prognostic factors to include in the m-CS. Log-rank survival analyses were used to compare the t-CS and the m-CS. The m-CS was validated in an international multicenter cohort of 608 patients. RESULTS: A total of 564 patients were eligible for analysis. RAS mutation was detected in 205 (36.3%) of patients. On multivariate analysis, RAS mutation was associated with poor overall survival, as were positive primary tumor lymph node status and diameter of the largest liver metastasis >50 mm. Each factor was assigned 1 point to produce a m-CS. The m-CS accurately stratified patients by overall and recurrence-free survival in both the initial patient series and validation cohort, whereas the t-CS did not. CONCLUSIONS: Modifying the t-CS by replacing disease-free interval, number of metastases, and CEA level with RAS mutation status produced an m-CS that outperformed the t-CS. The m-CS is therefore a simple validated tool that predicts survival after resection of CLM.

Risk for hemorrhage after pancreatoduodenectomy with venous resection.

PURPOSE: No consensus exists on the optimal anticoagulation therapy after pancreatoduodenectomy with venous resection (PDVR). The aim of the study was to analyze perioperative outcomes of patients receiving low- vs high-dose anticoagulation therapy and to identify risk factors for postpancreatectomy hemorrhage in patients undergoing PDVR. METHODS: Retrospective study of patients undergoing PDVR at a tertiary referral center between January 2006 and April 2017. Patients were investigated according to the dose of postoperative anticoagulation given (low- or high-dose low-molecular-weight heparin). Uni- and multivariate analysis were performed to assess risk factors for postpancreatectomy hemorrhage. RESULTS: A total of 141 patients underwent PDVR. Low-dose anticoagulation was given to 45 (31.9%) patients. Operative time (428 min vs 398 min, p = 0.025) and the use of interposition grafts (27% vs 11%, P = 0.033) were significantly higher in the high-dose group. There was no difference in the rate of early portal vein thrombosis (4.4% vs 4.2%, p = 0.939) or postpancreatectomy hemorrhage (13.3% vs 16.7%, p = 0.611) between the low- and high-dose groups. On multivariate analysis, serum bilirubin ≥ 200 µmol/L and clinically relevant postoperative fistula were the only factors associated with postpancreatectomy hemorrhage (OR 10.28, 95% CI 3.51-30.07, P < 0.001, and OR 6.39, 95% CI 1.59-25.74, P = 0.009). CONCLUSION: Preoperative hyperbilirubinemia and clinically relevant postoperative fistula are risk factors for postpancreatectomy hemorrhage after PDVR. Rates of postpancreatectomy hemorrhage did not differ between patients receiving high- vs low-dose low-molecular-weight heparin.

Survival Impact of Primary Tumor Lymph Node Status and Circulating Tumor Cells in Patients with Colorectal Liver Metastases.

OBJECTIVE: The aim of this study was to analyse the survival impact of primary tumor nodal status (N0/N+) in patients with resectable colorectal liver metastases (CLM), and to determine the value of circulating and disseminated tumor cells (CTCs/DTCs) in this setting. METHODS: In this prospective study of patients undergoing resection of CLM from 2008 to 2011, peripheral blood was analyzed for CTCs using the CellSearch System®, and bone marrow was sampled for DTC analyses just prior to hepatic resection. The presence of one or more tumor cells was scored as CTC/DTC-positive. Following resection of the primary tumor, the lymph nodes (LNs) were examined by routine histopathological examination. RESULTS: A total of 140 patients were included in this study; 38 patients (27.1%) were negative at the primary colorectal LN examination (N0). CTCs were detected in 12.1% of all patients; 5.3% of patients in the N0 group and 14.7% of patients in the LN-positive (N+) group (p = 0.156), with the LN-positive group (N+) consisting of both N1 and N2 patients. There was a significant difference in recurrence-free survival (RFS) when analysing the N0 group versus the N+ group (p = 0.007) and CTC-positive versus CTC-negative patients (p = 0.029). In multivariate analysis, CTC positivity was also significantly associated with impaired overall survival (OS) [p = 0.05], whereas DTC positivity was not associated with survival. CONCLUSION: In this cohort of resectable CLM patients, 27% had primary N0 colorectal cancer. Assessment of CTC in addition to nodal status may contribute to improved classification of patients into high- and low-risk groups, which has the potential to guide and improve treatment strategies.

Validation of clinical risk scores for laparoscopic liver resections of colorectal liver metastases: A 10-year observed follow-up study.

OBJECTIVE: The aim of this study was to validate clinical risk scores in patients underwent laparoscopic resection of colorectal liver metastases (CLM) with 5 years follow-up or more, and assess 5- and 10-year actual survival in this group. METHODS: A total of 516 laparoscopic liver resections were performed in 406 patients with CLM between February 1998 and September 2015. A follow-up of 5 and 10 years could be assessed in 144 and 29 patients, respectively. The Fong score, pre- and postoperative Basingstoke Predictive Index (BPI), Nordlinger score, and Iwatsuki score were validated. RESULTS: Five- and ten-year cancer-related actual survival was 54% and 32%, respectively. The Fong score, pre- and postoperative BPI and the Nordlinger score divided patients into risk groups with significant difference in survival between the groups. However, predicted 5-year survival rates were lower than the actual 5-year survival (mean difference in 17%,13%, 20%, and 30%, respectively). CONCLUSION: The Fong score, pre- and postoperative BPI and the Nordlinger score systems can be used to predict survival for laparoscopically operated patients in the era of multimodal-treatment after adjusting of survival rates. The actual five- and 10-year survival after laparoscopic resection of CLM is similar to results previously published for open liver resection. J. Surg. Oncol. 2016;114:757-763. © 2016 Wiley Periodicals, Inc.

Is Extended Lymphadenectomy Needed for Elderly Patients With Gastric Adenocarcinoma?

BACKGROUND: Extensive surgery is associated with greater mortality for elderly patients. For gastric adenocarcinoma (GA), it is unclear whether the benefit of an extended lymphadenectomy in this population outweighs the associated risks. This study aimed to determine the impact of lymphadenectomy on postoperative outcomes and survival for the elderly. OBJECTIVE: To determine the impact of lymphadenectomy on postoperative outcomes and survival for elderly. METHODS: From a cohort of 19 centers, patients who underwent resection of GA with curative intent between 1997 and 2010 were included in this study. Lymphadenectomy was defined according to the total number of lymph nodes in the surgical specimen (limited, <15; intermediate, 15-25; extended, >25). Postoperative outcomes and survival were compared between elderly (≥75 years) and younger patients and regarding the extent of lymphadenectomy for the elderly. RESULTS: Of 1348 patients, 386 were elderly. The elderly presented with a higher American Society of Anesthesiologist (ASA) score (ASA 3-4: 45 vs. 16.5 %; p < 0.001) as well as greater postoperative morbidity (45 vs. 37 %; p = 0.009) and mortality (8 vs. 2.5 %; p < 0.001) despite less aggressive treatment including less neoadjuvant chemotherapy (5 vs. 20 %; p < 0.001) and adjuvant chemotherapy (7 vs. 44 %; p < 0.001), fewer total gastrectomies (41.5 vs. 60 %; p < 0.001), and less extended lymphadenectomy (38 vs. 48.5 %; p < 0.001). Among the elderly patients, limited lymphadenectomy (n = 116), intermediate lymphadenectomy (n = 125), and extended lymphadenectomy (n = 145) were comparable with respect to tumor stage, perioperative treatment, morbidity, and mortality. For the elderly patients, overall survival (OS) was 30.8 months, and disease-specific survival (DSS) was 63.9 months. The extent of the lymphadenectomy did not have an impact on OS or DSS for the elderly patients. CONCLUSION: The expected benefit in terms of long-term survival did not justify an extended lymphadenectomy for elderly patients.

A Nomogram to Predict Hypertrophy of Liver Segments 2 and 3 After Right Portal Vein Embolization.

BACKGROUND: Portal vein embolization (PVE) reduces the risks of hepatic insufficiency after major hepatectomy for small predicted liver remnant. The extent of liver hypertrophy after PVE depends on various clinical factors. We sought to develop a nomogram for predicting the increase in the volume of segments 2 and 3 after right PVE (RPVE). METHOD: In 360 patients who underwent RPVE from 1998 through 2013, clinicopathologic data were analyzed, including body mass index (BMI), diabetes, aspirin use, viral hepatitis status, preoperative albumin level, total bilirubin level, prothrombin time, platelet count, type of liver neoplasm, preoperative chemotherapy, previous laparotomy or hepatectomy, segment 4 embolization, two-stage hepatectomy, and liver volumes before and after PVE. Multivariate linear regression analysis was used to identify variables predicting the degree of hypertrophy of segments 2 and 3. RESULTS: Multivariate regression analysis revealed that BMI (p = 0.002), previous hepatectomy (p = 0.03), RPVE in the setting of two-stage hepatectomy (p < 0.001), and segment 4 embolization (p = 0.003) independently predicted the degree of hypertrophy of segments 2 and 3. Based on the fitted model, a nomogram was constructed. CONCLUSION: The constructed nomogram predicts the degree of hypertrophy of segments 2 and 3 after RPVE and can be used in clinical decision making for patients undergoing right hepatectomy.

Advances in hepatectomy technique: Toward zero transfusions in the modern era of liver surgery.

BACKGROUND: Perioperative blood transfusions suppress immunity and increase hospital costs. Despite multiple improvements in perioperative care, rates of transfusion during/after hepatectomy are reported to range from 25 to 50%. The purpose of this study was to determine the current risk factors for perihepatectomy transfusion by assessing the impact of recent technical advances in liver surgery on transfusion rates. METHODS: Using our prospectively maintained hepatobiliary tumor database from a high-volume center, a modern cohort of 2,249 hepatectomies (2004-2013) were identified. Patient and operative characteristics were compared between 2 time periods, 2004-2008 (n = 1,139) and 2009-2013 (n = 1,110). Throughout the study interval, transfusions were given based on clinical assessment and not triggered by laboratory thresholds. RESULTS: Compared with the early cohort, the recent cohort had more patients with an American Society of Anesthesiologists score of ≥ 3 (79 vs 74%), preoperative chemotherapy (73 vs 68%), and a lesser median preoperative hemoglobin (12.9 vs 13.1 mg/dL) and platelet (215,000 vs 243,000) values (all P < .001). Despite these adverse risk factors, with an increasing use of the 2-surgeon resection technique (63 vs 50%), estimated blood loss (309 vs 394 mL), transfusion rates (6 vs 15%), and duration of stay (7.0 vs 8.4 days) were decreased (all P < .001) with no change in overall morbidity or mortality. Multivariate analysis of the recent cohort determined that the independent risk factors associated with transfusion were preoperative anemia and >350 mL of blood loss. The only independent factor associated with less transfusion was use of the 2-surgeon technique for hepatic parenchymal transection. CONCLUSION: With the exception of patients with moderate to severe preoperative anemia requiring major hepatectomy, recent technical advances have decreased significantly the need for transfusion in liver surgery.

After Pancreatectomy, the "90 Days from Surgery" Definition Is Superior to the "30 Days from Discharge" Definition for Capture of Clinically Relevant Readmissions.

BACKGROUND: Previous studies by different authors have reported their readmission rates after pancreatectomy as either "30 days from discharge" or "90 days from surgery." The objective of this study was to determine which of these definitions captures the most surgery-related complications. METHODS: A prospectively maintained database at a high volume center was queried to identify all individuals who underwent pancreatectomy between 2000 and 2012 for any diagnosis. The data was analyzed at 30 days after discharge and 90 days after operation. The optimal timing for complication reporting was defined as the time point that maximized the capture of surgery-related readmissions and direct major surgical complications while minimizing the capture of disease (cancer)-related readmissions. RESULTS: There were 1123 patients included during the study time period. The median age was 63 years old, and 55.6% were male. Operations included 833 (74.2%) pancreaticoduodenectomies, 257 (22.9%) distal pancreatectomies, 18 (1.6%) total pancreatectomies, and 15 (1.3%) central pancreatectomies. Surgery-related readmissions occurred in 248 (22%) individuals, while readmission related to malignant disease progression occurred in 25 (2%) individuals. The 30 days from discharge definition captured 184 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.74, specificity 0.96). The 90 days from surgery definition captured 215 surgery-related readmissions and 1 disease-related readmission (sensitivity 0.87, specificity 0.96). Major surgical complication was the only independent factor associated with readmission not captured by the 30 days from discharge definition (p = 0.002, HR 3.94, 95% CI 1.44­12.22). CONCLUSION: The 90 days from surgery definition was superior to the 30 days from discharge definition, especially with regards to readmission related to major surgical complications.

Parenchymal-sparing Hepatectomy in Colorectal Liver Metastasis Improves Salvageability and Survival.

OBJECTIVE: To investigate prognostic impact of parenchymal-sparing hepatectomy (PSH) for solitary small colorectal liver metastasis (CLM). BACKGROUND: It is unclear whether PSH confers an oncologic benefit through increased salvageability or is a detriment through increasing recurrence rate. METHODS: Database of 300 CLM patients with a solitary tumor (≤ 30 mm in size) was reviewed from 1993 to 2013. A total of 156 patients underwent PSH and 144 patients underwent right hepatectomy, left hepatectomy, or left lateral sectionectomy (non-PSH group). RESULTS: The rate of PSH increased over the study period (P < 0.01). PSH did not impact negatively on overall (OS), recurrence-free, and liver-only recurrence-free survival, compared with non-PSH (P = 0.53, P = 0.97, and P = 0.69, respectively). Liver-only recurrence was observed in 22 patients (14%) in the PSH and 25 (17%) in the non-PSH group (P = 0.44). Repeat hepatectomy was more frequently performed in the PSH group (68% vs 24%, P < 0.01). Subanalysis of patients with liver-only recurrence revealed better 5-year overall survival from initial hepatectomy and from liver recurrence in the PSH than in the non-PSH group [72.4% vs 47.2% (P = 0.047) and 73.6% vs 30.1% (P = 0.018), respectively]. Multivariate analysis revealed that non-PSH was a risk of noncandidacy for repeat hepatectomy (hazard ratio: 8.18, confidence interval: 1.89-45.7, P < 0.01). CONCLUSIONS: PSH did not increase recurrence in the liver remnant but more importantly improved 5-year survival in case of recurrence (salvageability). PSH should be the standard approach to CLM to allow for salvage surgery in case of liver recurrence.

Definition of Readmission in 3,041 Patients Undergoing Hepatectomy.

BACKGROUND: Readmission rates of 9.7% to 15.5% after hepatectomy have been reported. These rates are difficult to interpret due to variability in the time interval used to monitor readmission. The aim of this study was to refine the definition of readmission after hepatectomy. STUDY DESIGN: A prospectively maintained database of 3,041 patients who underwent hepatectomy from 1998 through 2013 was merged with the hospital registry to identify readmissions. Area under the curve (AUC) analysis was used to determine the time interval that best captured unplanned readmission. RESULTS: Readmission rates at 30 days, 90 days, and 1 year after discharge were 10.7% (n = 326), 17.3% (n = 526), and 31.9% (n = 971) respectively. The time interval that best accounted for unplanned readmissions was 45 days after discharge (AUC, 0.956; p < 0.001), during which 389 patients (12.8%) were readmitted (unplanned: n = 312 [10.3%]; planned: n = 77 [2.5%]). In comparison, the 30 days after surgery interval (used in the ACS-NSQIP database) omitted 65 (26.3%) unplanned readmissions. Multivariate analysis revealed the following risk factors for unplanned readmission: diabetes (odds ratio [OR] 1.6; p = 0.024), right hepatectomy (OR 2.1; p = 0.034), bile duct resection (OR 1.9; p = 0.034), abdominal complication (OR 1.8; p = 0.010), and a major postoperative complication (OR 2.4; p < 0.001). Neither index hospitalization > 7 days nor postoperative hepatobiliary complications were independently associated with readmission. CONCLUSIONS: To accurately assess readmission after hepatectomy, patients should be monitored 45 days after discharge.

Survival After Resection of Gastrointestinal Stromal Tumor and Sarcoma Liver Metastases in 146 Patients.

BACKGROUND: We investigated outcomes by primary tumor type in patients who underwent resection of liver metastases from gastrointestinal stromal tumors (GIST), leiomyosarcomas, and other sarcomas. METHOD: Our institutional liver database was used to identify patients who underwent resection from 1998 through 2013. Histopathological, clinical, and survival data were analyzed. RESULTS: One hundred forty-six patients underwent resection of liver metastases from GIST (n = 49), leiomyosarcomas (n = 47), or other sarcomas (n = 50). The 5-year overall survival (OS) rates in patients with GIST, leiomyosarcomas, and other sarcomas were 55.3, 48.4, and 44.9%, respectively, and the 10-year OS rates were 52.5, 9.2, and 23.0%, respectively. The 5-year recurrence-free survival (RFS) rate was better for GIST (35.7%; p = 0.003) than for leiomyosarcomas (3.4%) and other sarcomas (21.4%). Lung recurrence was more common for leiomyosarcomas (36% of patients; p < 0.0001) than for other sarcomas (12%) and GIST (2%). For GIST, the findings support a benefit of imatinib regarding the 5-year RFS rate compared to resection alone (47.1 vs. 9.5%; p = 0.013). For leiomyosarcoma, primary tumor location did not affect the 5-year RFS rate (intraabdominal 14.5%; other location 0%; p = 0.182). CONCLUSION: Liver metastases from GIST, leiomyosarcomas, and other sarcomas should be assessed separately as their survival and recurrence patterns are different. This is especially important for GIST, for which imatinib is now available.