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Background: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear. Methods: Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup. Results: Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]. Conclusion: The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM. info:eu-repo/semantics/publishedVersion

Background: Liver resection in patients with neuroendocrine liver metastasis (NELM) provides a survival benefit, yet the optimal extent of resection remains unknown. We sought to examine outcomes of patients undergoing non-anatomic (NAR) versus anatomic liver resection (AR) for NELM using a large international cohort of patients. Methods: Two hundred and fifty-eight patients who underwent curative intent liver resection from January 1990 to December 2016 were identified from eight institutions. Patients were excluded if they underwent concurrent ablation, had extrahepatic disease, underwent a debulking operation, or had mixed anatomic and non-anatomic resections. Overall (OS) and recurrence-free (RFS) survival were compared among patients based on the extent of liver resection (AR vs. NAR). Results: Most primary tumors were located in the pancreas (n = 117, 45.4%) or the small intestine (n = 65, 25.2%). Liver resection consisted of NAR (n = 126, 48.8%) or AR (n = 132, 51.2%) resection. The overwhelming majority of patients who underwent NAR had an estimated liver involvement of < 50% (NAR 109, 97.3% vs. AR n = 82, 65.6%; P < 0.001). Patients who underwent NAR also had higher rates of primary tumor lymph node metastasis (NAR n = 79, 71.2% vs. AR n = 37, 33.6%; P < 0.001) and microscopically positive margins (R1) (NAR n = 29, 25.7% vs. AR n = 16, 12.5%; P = 0.009). After a median follow-up of 47.7 months, 48 (18.6%) patients died and 37.0% (n = 95) had evidence of disease recurrence. Patients who underwent AR had both longer median OS (not reached) and RFS (not reached) versus patients who underwent NAR (median OS 138.3 months; median RFS 31.3 months) (both P < 0.01). After controlling for patient and disease-related factors, extent of liver resection was independently associated with an increased risk of recurrence (HR 2.39, 95% CI 1.04-5.48; P = 0.04) but not death (HR 1.92, 95% CI 0.40-9.28; P = 0.42). Conclusion: NAR was independently associated with a higher incidence of recurrence versus patients who undergo a formal anatomic hepatectomy among patients with NELM. info:eu-repo/semantics/publishedVersion

Background: The aim of the current study was to develop an online calculator to predict survival after liver resection for intrahepatic cholangiocarcinoma (ICC) based on the "metro-ticket" paradigm. Methods: Between 1990 and 2016, patients who underwent liver resection for ICC were identified in an international multi-institutional database. The final multivariable model of survival was used to develop an online prognostic calculator of survival. Results: Among 643 patients, actual 5-year overall survival (OS) after resection for ICC was 42.7%. On multivariable analysis, CA19-9 > 200 (hazard ratio (HR), 2.62; 95% CI, 2.01-3.42), sum of the number and largest tumor size >7 (HR, 1.88; 95% CI, 1.46-2.42), N1 disease (HR, 2.87; 95% CI, 1.98-4.16), R1 resection (HR, 1.72; 95% CI, 1.21-2.46), poor/undifferentiated tumor grade (HR, 1.74; 95% CI, 1.25-2.44), major vascular invasion (HR, 1.47; 95% CI, 1.03-2.10), and adjuvant chemotherapy (HR, 0.64; 95% CI, 0.45-0.89) were significantly associated with survival and were included in the online calculator. The predictive accuracy of the model was good to very good as the C-statistics to predict 5-year OS was 0.696 in the training dataset and 0.672 with bootstrapping resamples (n = 5000) in the test dataset. Conclusion: A novel, online calculator was developed to estimate the 5-year survival probability for patients undergoing resection for ICC. This tool could help provide useful information to guide treatment decision-making and inform conversations about prognosis. info:eu-repo/semantics/publishedVersion

Background and Aims: The role of lymph node dissection (LND) in patients with small intrahepatic cholangiocarcinoma (ICC) is still under debate. The aims of this study were to compare the lymph node (LN) status and its correlation with survival among patients with ICC stratified by tumor size. Methods: A retrospective analysis of a multi-institutional series of 259 patients undergoing curative-intent surgery was carried out. Patients were stratified into Small-ICC (≤ 3cm) and Large-ICC (> 3cm) based on tumor size. Results: There were 53 and 206 patients in Small-ICC and Large-ICC groups, respectively. The incidence of LND was 62% among Small-ICC patients and 78% among Large-ICC patients (p = 0.016). LN metastases were identified in 30.3% and 38.5% of Small-ICC and Large-ICC patients, respectively (p = 0.37). No differences in terms of number of harvested LN and LN metastases were identified comparing Small- and Large-ICC patients. The 5-year overall survival (OS) was 52.6% for Small-ICC and 36.2% for Large-ICC (p = 0.024). The 5-year OS according to the LN status (N0 vs N+) was 84.8% and 36.0% (p = 0.032) in Small-ICC, and 45.7% and 12.1% in Large-ICC (p < 0.001), respectively. Conclusion: While Small-ICC patients with no LN metastasis had a good long-term survival, the LN resulted in an important variable associated with survival also for patients in this group. Moreover, the incidence of LN metastasis did not differ when comparing Small-ICC and Large-ICC patients, suggesting that LND is mandatory in the surgical treatment of ICC regardless of tumor size.

Background Surgery is considered the only potentially curative treatment option for patients with hepatocellular carcinoma. However, the chance that patients will eventually be “cured” after liver resection for hepatocellular carcinoma remains ill defined. Methods Patients who underwent curative-intent hepatectomy for hepatocellular carcinoma between 1998 and 2017 were identified using an international multi-institutional database. A nonmixture cure model was used with disease-free survival as a primary measure to estimate cure fractions after matching patients with the general population by age, race, and sex. Results Among 1,010 patients, the median and 5-year disease-free survival were 2.8 years and 36.6%, respectively. The probability of being cured after hepatocellular carcinoma resection was 42.2% and the median time to cure was 3.35 years. The multivariable cure model revealed preoperative alpha-fetoprotein level, tumor size, tumor number, and margin status as independent predictors of cure. The cure fraction for patients with an alpha-fetoprotein level ≤ 10 ng/mL, largest tumor size ≤5 cm, ≤3 nodules, and R0 resection was 61.6%. In contrast, patients who had all 4 unfavorable prognostic factors (ie, alpha-fetoprotein >11 ng/mL, nodules ≥4, size >5cm, R1 resection) had a cure fraction of 15.8%. Although the probability of cure was 47.6% among Barcelona Clinic Liver Cancer-A patients, patients undergoing resection for Barcelona Clinic Liver Cancer-B hepatocellular carcinoma had a 37.6% cure fraction. Only alpha-fetoprotein levels predicted the probability of cure among Barcelona Clinic Liver Cancer-B patients. Conclusion Roughly 4 in 10 patients could be considered “cured” after liver resection for hepatocellular carcinoma. Although cure was achieved more often after resection for Barcelona Clinic Liver Cancer-A hepatocellular carcinoma, surgery still provided a reasonable probability of cure among select patients with Barcelona Clinic Liver Cancer-B hepatocellular carcinoma.

Background: Progression of colorectal liver metastasis (CRLM) on preoperative chemotherapy has been associated with a worse prognosis compared with patients who have responsive disease. Defining response can be challenging as traditional criteria largely assess only tumor size. Methods: Patients who underwent hepatectomy between 2010 and 2017 were identified using a multi-centric database. This study aimed to define the impact of preoperative chemotherapy response relative to initial tumor burden score (TBS) and determine impact of clinico-pathological variables on overall survival (OS). Results: Among 784 patients who received preoperative chemotherapy, the regimen was oxaliplatin- (66%) or irinotecan-based (34%). Among patients with a TBS

IMPORTANCE: Composite measures may be superior to individual measures for the analysis of hospital performance and quality of surgical care. OBJECTIVE: To determine the incidence of a so-called textbook outcome, a composite measure of the quality of surgical care, among patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved an analysis of a multinational, multi-institutional cohort of patient from 15 major hepatobiliary centers in North America, Europe, Australia, and Asia who underwent curative-intent resection of intrahepatic cholangiocarcinoma between 1993 and 2015. Data analysis was conducted from April 2018 to May 2018. MAIN OUTCOMES AND MEASURES: Hospital variation in the composite end point of textbook outcome, defined as negative margins, no perioperative transfusion, no postoperative surgical complications, no prolonged length of stay, no 30-day readmissions, and no 30-day mortality. Secondary end points were factors associated with achieving textbook outcomes. RESULTS: Among 687 patients (of whom 370 [53.9%] were men; median patient age, 61 [range, 18-86] years) undergoing curative-intent resection of intrahepatic cholangiocarcinoma, a textbook outcome was achieved in 175 patients (25.5%). Being 60 years or younger (odds ratio [OR], 1.61 [95% CI, 1.04-2.49]; P = .03), absence of preoperative jaundice (OR, 4.40 [95% CI, 1.28-15.15]; P = .02), no neoadjuvant chemotherapy (OR, 2.57 [95% CI, 1.05-6.29]; P = .04), T1a/T1b-stage disease (OR, 1.58 [95% CI, 1.01-2.49]; P = .049), N0 status (OR, 3.89 [95% CI, 1.77-8.54]; P = .001), and no bile duct resection (OR, 2.46 [95% CI, 1.25-4.84]; P = .009) were independently associated with achieving a textbook outcome after resection. A prolonged length of stay had the greatest negative association with a textbook outcome. A nomogram to assess the probability of textbook outcome was developed and had good accuracy in both the training data set (area under the curve, 0.755) and validation data set (area under the curve, 0.763). CONCLUSIONS AND RELEVANCE: In this study, while hepatic resection for intrahepatic cholangiocarcinoma was performed with less than 5% mortality in specialized centers, a textbook outcome was achieved in only approximately 26% of patients. A textbook outcome may be useful for the reporting of patient-level hospital performance and hospital variation, leading to quality improvement efforts after resection of intrahepatic cholangiocarcinoma.

Invasive breast cancer is the most common malignancy in women. Its most common site of metastasis is represented by the lymph nodes of axilla, and the sentinel lymph node (SLN) is the first station of nodal metastasis. Axillary SLN biopsy accurately predicts axillary lymph node status and has been accepted as standard of care for nodal staging in breast cancer. To date, the morphologic aspects of SLN metastasis have not been considered by the oncologic staging system. Extranodal extension (ENE) of nodal metastasis, defined as extension of neoplastic cells through the nodal capsule into the peri-nodal adipose tissue, has recently emerged as an important prognostic factor in several types of malignancies. It has also been considered as a possible predictor of non-sentinel node tumor burden in SLN-positive breast cancer patients. We sought out to clarify the prognostic role of ENE in SLN-positive breast cancer patients in terms of overall and disease-free survival by conducting a systematic review and meta-analysis. Among 172 screened articles, 5 were eligible for the meta-analysis; they globally include 624 patients (163 ENE+ and 461 ENE−) with a median follow-up of 58 months. ENE was associated with a higher risk of both mortality (RR=2.51; 95% CI: 1.66–3.79, p&nbsp

Background Multiple tumor foci of intrahepatic cholangiocarcinoma (ICC) are often considered a contra-indication for resection. We sought to define long-term outcomes after resection of ICC in patients with multiple foci. Methods Patients who underwent resection for ICC between 1990 and 2017 were identified from 12 major HPB centers. Outcomes of patients with solitary lesions, multiple lesions (ML), and oligometastases (OM) were compared. OM were defined as extrahepatic metastases spread to a single organ. Results One thousand thirteen patients underwent resection of ICC. On final pathology, 185 patients (18.4%) had ML and 27 (2.7%) had OM. Median survival of patients with a solitary tumor was 43.2 months, while the median survival of patients with 2 tumors was 21.2 months; the median survival of patients with 3 or more tumors was 15.3 months (p

Background: The role of liver transplant (LT) for neuroendocrine liver metastasis (NELM) has not been completely defined. While international guidelines included LT as a potential treatment for highly selected patients with advanced NELM, recently, LT has been proposed as an alternative curative treatment for NELM for patients meeting restrictive criteria (Milan criteria). Methods: Using a multi-institutional cohort of patients undergoing liver resection for NELM, the long-term outcomes of patients meeting Milan criteria (resected NET drained by the portal system, stable disease/response to therapies for at least 6 months, metastatic diffusion to < 50% of the total liver volume, a confirmed histology of low-grade, and ≤ 60 years) were investigated. Results: Among the 238 patients included in the study, 28 (12%) patients met the Milan criteria for LT with a 5-year OS of 83%. Furthermore, among patients meeting Milan criteria, subsets of patients with favorable clinic-pathological characteristics had 5-year OS rates greater than 90% including G1 patients (5-year OS, 92%), patients undergoing minor liver resection (5-year OS, 94%), patients with low number of NELM (1–2 NELM), and small tumor size (< 3 cm) (for both groups of patients, 5-year OS, 100%). Conclusions: In our series, only 12% of patients met Milan criteria, and the 5-year OS after liver resection for this small selected group of patients was comparable with that reported in the literature for patients undergoing LT for NELM within Milan criteria. While LT might be the optimal treatment for patients with unresectable NELM, surgical resection should be the first option for patients with resectable NELM.

Background: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC. Methods: The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification. Results: Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (< 18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69). Conclusion: While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.

Extranodal extension (ENE) of nodal metastasis is defined as the extension of metastatic cells through the nodal capsule into the perinodal tissue. This morphological parameter, recently proposed as an important prognostic factor in different types of malignancy, has not been included in the TNM staging system for non-small cell lung cancer (NSCLC). In this systematic review with meta-analysis, we weighted the prognostic role of ENE in patients with lymph node-positive NSCLC. Two independent authors searched SCOPUS and PubMed through 28 February 2017. Prospective and retrospective studies on NSCLC, comparing patients with presence of ENE (ENE+) ENE+) vs. only intranodal extension (ENE–) and including data regarding prognosis, were considered as eligible. Data were summarized using risk ratios (RR) for the number of deaths/recurrences, and hazard ratios (HR) with 95% confidence intervals (CI) for time-dependent risk related to ENE+, adjusted for potential confounders. We identified 13 studies, including 1709 patients (573 ENE+ and 1136 ENE–) with a median follow-up of 60months. ENE was associated with a significantly increased risk of mortality of all causes (RR = 1.39, 95% CI: 1.18–1.65, P < 0.0001, I2= 70%; HR = 1.30, 95% CI: 1.01–1.67, P = 0.04, I2= 0%) and of disease recurrence (RR = 1.32, 95% CI: 1.04–1.68, P = 0.02, I2= 42%; HR = 1.93, 95% CI: 1.53–2.44, P < 0.0001, I2= 0%). We conclude that in NSCLC, requirements for assessment of ENE should be included in gross sampling and ENE status should be included in the pathology report. Inclusion of ENE status in oncology staging systems will allow further assessment of its role as prognostic parameter. © 2018, Springer-Verlag GmbH Germany, part of Springer Nature.

Background The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. Methods Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. Results A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). Conclusion Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.

INTRODUCTION: We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi-center patient cohort. METHODS: The overall (OS) and disease free survival (DFS) prognostic discriminatory ability of various commonly used models were assessed in a large retrospective cohort. Harrell's concordance index (c-index) was used to determine accuracy of model prediction. RESULTS: Among 1054 ICC patients, median OS was 37.7 months and 1-, 3-, and 5-year survival, were 78.8%, 51.5%, and 39.3%, respectively. Recurrence of disease occurred in 454 (43.0%) patients with a median DFS of 29.6 months. One-, 3- and 5- year DFS were 64.6%, 46.5 % and 44.4%, respectively. The prognostic models associated with the best OS prediction were the Wang nomogram (c-index 0.668) and the Nathan staging system (c-index 0.639). No model was proficient in predicting DFS. Only the Wang nomogram exceeded a c-index of 0.6 for DFS (c-index 0.602). The c-index for the AJCC staging system was 0.637 for OS and 0.582 for DFS. CONCLUSIONS: While the Wang nomogram had the best discriminatory ability relative to OS and DFS, no ICC staging system or nomogram demonstrated excellent prognostic discrimination. The AJCC staging for ICC performed reasonably, although its overall discrimination was only modest-to-good. info:eu-repo/semantics/publishedVersion

BACKGROUND: Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection. METHODS: A total of 481 patients who underwent curative-intent resection for NELM were identified from a multi-institutional database. Data on clinicopathological characteristics, intraoperative details, and outcomes were documented. The optimal cutoff value to differentiate early and late recurrence was determined to be 3 years based on linear regression. RESULTS: With a median follow-up of 60 months, 223 (46.4%) patients developed a recurrence, including 158 (70.9%) early and 65 (29.1%) late recurrences. On multivariable analysis, pancreatic NET, primary tumor lymph node metastasis, and a microscopic positive surgical margin were independent risk factors for early intrahepatic recurrence. While recurrence patterns and treatments were comparable among patients with early and late recurrences, early recurrence was associated with worse disease-specific survival than late recurrences (10-year NELM-specific survival, 44.5 vs 75.8%, p < 0.001). Among the 34 (21.5%) patients who underwent curative treatment for early recurrence, post-recurrence disease-specific survival was better than non-curatively treated patients (10-year NELM-specific survival, 54.2 vs 26.3%, p = 0.028), yet similar to patients with late recurrences treated with curative intent (10-year NELM-specific survival, 54.2 vs 37.4%, p = 0.519). CONCLUSIONS: Early recurrence after surgery for NELM was associated with the pancreatic type, primary lymph node metastasis, and extrahepatic disease. Re-treatment with curative intent prolonged survival after recurrence, and therefore, operative intervention even for early recurrences of NELM should be considered. info:eu-repo/semantics/publishedVersion

BACKGROUND: Neuroendocrine tumors typically arise from pancreatic (PNET) vs. gastrointestinal or thoracic origins (non-PNET). The impact of primary tumor site on long-term prognosis following resection of neuroendocrine liver metastasis (NELM) remains poorly defined. The objective of the current study was to define the association of primary tumor location on prognosis of patients undergoing curative intent liver resection for NELM. METHODS: Between 1990 and 2014, 421 patients who underwent resection of NELM were identified from a multi-institutional database. Clinicopathological characteristics, operative details, and outcomes were stratified and analyzed by location of the primary tumor (PNET vs. non-PNET). A propensity score-matched analysis was utilized to assess the impact of primary tumor location on long-term survival. RESULTS: Among the 421 patients, 197 (46.8%) patients had NELM from a PNET primary while 224 (53.2%) had a non-PNET primary (small bowel, n = 145; rectal, n = 10; bronchial, n = 22; other, n = 47). There were no differences in tumor burden and tumor site, while presence of extrahepatic disease was more common among patients with non-PNET NELM (extrahepatic disease, PNET NELM, n = 11 27.5% vs. non-PNET NELM, n = 29 72.5%; p = 0.010). Patients with PNET NELM were more likely to have non-functional disease compared with patients who had non-PNET NELM (non-functional, PNET NELM, n = 117 54.9% vs. non-PNET NELM, n = 96 45.1%; p = 0.011). On the final pathological specimen of the resected NELM, patients with PNET NELM were more likely to have a moderately differentiated tumor (59.3%), while patients with non-PNET NELM were more likely to have a poorly differentiated tumor (67.8%) (p = 0.005). Patients with PNET NELM had a worse 5-year DFS and 5-year OS compared with patients who had non-PNET NELM (DFS, PNET 36.2% vs. non-PNET 55.2%; p = 0.001 and OS, PNET 79.5% vs. non-PNET 83.4%; p = 0.008). After propensity score matching, both 5-year DFS and 5-year OS of the PNET and non-PNET groups were comparable (DFS, PNET 46.2% vs. non-PNET 55.9%; p = 0.22 and OS, PNET 81.5% vs. non-PNET 84.3%; p = 0.19). CONCLUSION: PNET patients more often present with non-functional NELM and moderately differentiated tumors. On propensity-matched analysis, factors such as extrahepatic disease and tumor grade, but not primary tumor location, were associated with prognosis of patients undergoing curative intent liver surgery for NELM. info:eu-repo/semantics/publishedVersion

INTRODUCTION: The role of routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) is still controversial. The AJCC eighth edition recommends a minimum of six harvested lymph nodes (HLNs) for adequate nodal staging. We sought to define outcome and risk of death among patients who were staged with ≥6 HLNs versus

BACKGROUND: We sought to evaluate and validate the 8th edition of the AJCC classification using a multi-institutional cohort of patients with intrahepatic cholangiocarcinoma (ICC). METHODS: Patients undergoing curative-intent hepatic resection for ICC between 1990 and 2015 at 14 major hepatobiliary centers were included and were staged according to 7th and 8th editions AJCC criteria. RESULTS: A total of 1154 patients underwent liver resection for ICC. When patients were staged using the AJCC 7th edition, T2a, T2b, and T4 patients had a higher hazard ratio (HR) of death compared with T1 (T2a, HR 1.43, P = 0.004; T2b, HR 1.99, P

OBJECTIVE: We sought to characterize the treatment, as well as define the long-term outcomes, of patients with recurrent neuroendocrine liver metastasis (NELM). METHODS: Between 1990 and 2014, 322 patients undergoing curative intent liver surgery for NELM were identified from a multi-institutional database. Recurrences were classified as intrahepatic, extrahepatic, and both intra- and extra-hepatic. RESULTS: Overall, median, 1-, 5-, 10-year DFS were 3.1 years, 75.5%, 40.4%, and 32.1%, respectively. After curative intent liver surgery, 209 patients (64.9%) recurred within a median follow-up of 4.5 years, while 113 (35.1%) patients were alive without disease with a follow-up time ≥3 years. The site of recurrence was intrahepatic only (n = 111, 65.7%), extrahepatic only (n = 19, 11.2%), or intra- and extra-hepatic (n = 39, 23.1%). Compared with intrahepatic only recurrence, extrahepatic only, and combined intra- and extra-hepatic recurrence were associated with a worse long-term outcome (10-year OS: intrahepatic only, 42.5%, 95%CI, 24.9-59.0 vs extrahepatic only, 0% and combined intra- and extra-hepatic, 21.5%, 95%CI, 5.3-44.0) (P

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. METHODS: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (

BACKGROUND: The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC. METHODS: A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases. RESULTS: Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95). CONCLUSION: Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC. info:eu-repo/semantics/publishedVersion

Background and Objective: Neuroendocrine liver metastasis tumors (NELM) are a heterogeneous group of neoplasms with varied histologic features and a wide range of clinical behaviors. We aimed to identify the fraction of patients cured after liver surgery for NELM. Methods: Cure fraction models were used to analyze 376 patients who underwent hepatectomy with curative intent for NELM. Results: The median and 5-year disease-free survival (DFS) were 4.5 years and 46%, respectively. The probability of being cured from NELM by liver surgery was 44%; the time to cure was 5.1 years. In a multivariable cure model, type of neuroendocrine tumor (NET), grade of tumor differentiation, and rate of liver involvement resulted as independent predictors of cure. The cure fraction for patients with well differentiated NELM from gastrointestinal NET or a functional pancreatic NET, and with < 50% of liver-involvement was 95%. Patients who had moderately/poorly differentiated NELM from a non-functional pancreatic NET, and with < 50% of liver-involvement was 43%. In the presence of all the three unfavorable prognostic factors (nonfunctional PNET, liver involvement > 50%, moderately/poorly differentiation), the cure fraction was 8%. Conclusions: Statistical cure after surgery for NELM is possible, and allow for a more accurate prediction of long-term outcome among patients with NELM undergoing liver resection.

Even though surgery remains the only potentially curative option for patients with neuroendocrine liver metastases, the factors determining a patient's prognosis following hepatectomy are poorly understood. Using a multicentric database including patients who underwent hepatectomy for NELMs at seven tertiary referral hepato-biliary-pancreatic centers between January 1990 and December 2014, we sought to identify the predictors of survival and develop a clinical tool to predict patient's prognosis after liver resection for NELMs. The median age of the 238 patients included in the study was 61.9 years (interquartile range 51.5-70.1) and 55.9 % (n = 133) of patients were men. The number of NELMs (hazard ratio = 1.05), tumor size (HR = 1.01), and Ki-67 index (HR = 1.07) were the predictors of overall survival. These variables were used to develop a nomogram able to predict survival. According to the predicted 5-year OS, patients were divided into three different risk classes: 19.3, 55.5, and 25.2 % of patients were in low (> 80 % predicted 5-year OS), medium (40-80 % predicted 5-year OS), and high (< 40 % predicted 5-year OS) risk classes. The 10-year OS was 97.0, 55.9, and 20.0 % in the low, medium, and high-risk classes, respectively (p < 0.001). We developed a novel nomogram that accurately (c-index > 70 %) staged and predicted the prognosis of patients undergoing liver resection for NELMs.

Introduction: The extranodal extension (ENE) of nodal metastases (the extension of neoplastic cells through the nodal capsule into the perinodal soft tissue) is a histological feature that has been considered a prognostic factor in several cancers, but the role in gastric cancer was not yet investigated. We aimed to investigate the prognostic role of ENE in patients affected by gastric cancer through a systematic review and meta-analysis. Material and Methods: Two independent authors searched major databases until 09/30/2015 to identify studies providing data on gastric cancer patients’ prognostic parameters and comparing patients with ENE (ENE+) vs intra-nodal extension (ENE−). The data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) with 95% confidence intervals (CI), adjusted for potential confounders. Results: Nine studies followed up 3250 patients with gastric cancer (1064 ENE+ and 2186 ENE−). ENE+ was associated with a significantly higher risk of all-cause mortality (RR = 1.70; 95% CI: 1.43–2.03, I2 = 66%; HR = 2.14; 95% CI: 1.66–2.75, I2 = 0%), cancer-specific mortality (RR = 1.59; 95% CI: 1.42–1.79; HR = 1.52; 95% CI: 1.19–1.96), and disease recurrence (RR = 3.43, 95% CI: 1.80–6.54, I2 = 0%). Discussion: Judging from our results, ENE in gastric cancer patients should be considered for prognostic purposes from the gross sample to the pathology report. © 2016, The Society for Surgery of the Alimentary Tract.

The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible. Data were summarised using risk ratios (RRs) for number of deaths/recurrences and HRs together with 95% CIs for time-dependent risk related to ENE+, adjusted for potential confounders. Fourteen studies were selected; they followed-up 1437 patients with oesophageal cancer for a median follow-up of 39.4months. The presence of ENE was associated with a significantly increased risk of all-cause mortality (RR=1.33; 95% CI 1.18 to 1.50, p

BACKGROUND: Regret-based decision curve analysis (DCA) is a framework that assesses the medical decision process according to physician attitudes (expected regret) relative to disease-based factors. We sought to apply this methodology to decisions around the operative management of intrahepatic cholangiocarcinoma (ICC). METHODS: Utilizing a multicentric database of 799 patients who underwent liver resection for ICC, we developed a prognostic nomogram. DCA tested 3 strategies: (1) perform an operation on all patients, (2) never perform an operation, and (3) use the nomogram to select patients for an operation. RESULTS: Four preoperative variables were included in the nomogram: major vascular invasion (HR = 1.36), tumor number (multifocal, HR = 1.18), tumor size (>5 cm, HR = 1.45), and suspicious lymph nodes on imaging (HR = 1.47; all P < .05). The regret-DCA was assessed using an online survey of 50 physicians, expert in the treatment of ICC. For a patient with a multifocal ICC, largest lesion measuring >5 cm, one suspicious malignant lymph node, and vascular invasion on imaging, the 1-year predicted survival was 52% according to the nomogram. Based on the therapeutic decision of the regret-DCA, 60% of physicians would advise against an operation for this scenario. Conversely, all physicians recommended an operation to a patient with an early ICC (single nodule measuring 3 cm, no suspicious lymph nodes, and no vascular invasion at imaging). CONCLUSION: By integrating a nomogram based on preoperative variables and a regret-based DCA, we were able to define the elements of how decisions rely on medical knowledge (postoperative survival predicted by a nomogram, severity disease assessment) and physician attitudes (regret of commission and omission). info:eu-repo/semantics/publishedVersion

BACKGROUND: The role of routine lymphadenectomy (LD) among patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC) remains poorly defined. This study aimed to evaluate the role of routine LD as well as to quantify the impact of not assessing nodal station on disease-specific survival (DSS) among patients undergoing liver surgery for ICC. STUDY DESIGN: Using data from 12 major hepatobiliary centers, 561 patients undergoing liver surgery for ICC between 1990 and 2012 were identified. The association between nodal status and DSS was assessed using Cox proportional and Aalen's linear hazards models. RESULTS: Among the 272 (48.5%) patients who underwent LD, 123 (45.2%) had lymph node metastasis (N1). Although differences in DSS were noted between N0 and Nx patients within the first 18 months after surgery (DSS at 18 months: N0 vs Nx, 70.2% vs 60.6%, respectively, p = 0.019) among patients who had survived to 18 months, the DSS at 60 months of Nx patients was comparable to that of N0 patients (p = 0.48). Conversely, although the DSS of N1 and Nx patients was comparable in the short-term (DSS at 18 months: p = 0.13), among patients who had survived to 18 months, N1 patients had a lower DSS compared with Nx patients (DSS at 60 months among patients who had survived to 18 months: N1 vs Nx, 15.2% vs 45.8%, respectively, p < 0.001; all p values were based on the log-rank test comparing 2 survival curves). CONCLUSIONS: Although Nx patients and N1 patients had comparable DSS in the short-term, Nx patients who survived past 18 months had a survival comparable to that of N0 patients. Lack of nodal staging may lead to heterogeneous and potentially incorrect prognostic classification of patients with ICC. (C) 2015 by the American College of Surgeons. Published by Elsevier Inc. All rights reserved