Xu-Feng Zhang

Evaluation of the 8th edition American Joint Commission on Cancer (AJCC) staging system for patients with intrahepatic cholangiocarcinoma: A surveillance, epidemiology, and end results (SEER) analysis

The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry.

Trends in the Mortality of Hepatocellular Carcinoma in the United States.

IntroductionPrimary liver cancer mortality rates have been increasing in the US, but reported decreases among 35–49xa0year olds may foreshadow future declines. We sought to use age-period-cohort (APC) modeling to evaluate the contribution of cohort effects to hepatocellular carcinoma (HCC) mortality trends in the US.MethodsData on HCC mortality were obtained from the Centers for Disease Control and Prevention National Center for Health Statistics WONDER Online Multiple Cause of Death database, 1999–2015. Crude mortality rates were plotted by gender and age at death. Gender-specific restricted cubic spline APC models were fit to determine influence of birth cohort on incidence of HCC mortality, in reference to the 1940 birth cohort.ResultsHighest mortality rates were found among men ages 70+, with steepest increase in mortality observed among men 55–69xa0years old. Similar trends were found among females. Accounting for the cohort effect in the APC model markedly improved model fit (likelihood ratio test pxa0<xa00.001). Relative to the 1940 birth cohort, risk of mortality due to HCC was significantly higher in later as well as earlier cohorts.ConclusionsHCC-associated mortality continues to increase, secondary to an increase in the risk of HCC-associated mortality in more recent birth cohorts among both men and women.

Role of exosomes in treatment of hepatocellular carcinoma

Exosomes are nanovesicles that may play a role in intercellular communication by acting as carriers of functional contents such as proteins, lipids, RNA molecules and circulating DNA from donor to recipient cells. In addition, exosomes may play a potential role in immunosurveillance and tumor pathogenesis and progression. Recently, research has increasingly focused on the role of exosomes in hepatocellular carcinoma (HCC), the most common primary liver malignancy. We herein review data on emerging experimental and clinical studies focused on the role of exosomes in the pathogenesis, diagnosis, progression and chemotherapy response of patients with HCC. Beyond their diagnostic value in HCC, exosomes are involved in different mechanisms of HCC tumor pathogenesis and progression including angiogenesis and immune escape. Moreover, exosomes have been demonstrated to change the tumor microenvironment to a less tolerogenic state, favoring immune response and tumor suppression. These results underline a practical and potentially feasible role of exosomes in the treatment of patients with HCC, both as a target and a vehicle for drug design. Future studies will need to further elucidate the exact role and reliability of exosomes as screening, diagnostic and treatment targets in patients with HCC.

Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent

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.

Defining Early Recurrence of Hilar Cholangiocarcinoma After Curative-intent Surgery: A Multi-institutional Study from the US Extrahepatic Biliary Malignancy Consortium

BackgroundTime to tumor recurrence may be associated with outcomes following resection of hepatobiliary cancers. The objective of the current study was to investigate risk factors and prognosis among patients with early versus late recurrence of hilar cholangiocarcinoma (HCCA) after curative-intent resection.MethodsA total of 225 patients who underwent curative-intent resection for HCCA were identified from 10 academic centers in the USA. Data on clinicopathologic characteristics, pre-, intra-, and postoperative details and overall survival (OS) were analyzed. The slope of the curves identified by linear regression was used to categorize recurrences as early versus late.ResultsWith a median follow-up of 18.0xa0months, 99 (44.0%) patients experienced a tumor recurrence. According to the slope of the curves identified by linear regression, the functions of the two straight lines were yxa0=xa0−0.465xxa0+xa016.99 and yxa0=xa0−0.12xxa0+xa07.16. The intercept value of the two lines was 28.5xa0months, and therefore, 30xa0months (2.5xa0years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (nxa0=xa080, 80.8%) occurred within the first 2.5xa0years (early recurrence), while 19.2% of recurrences occurred beyond 2.5xa0years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, pxa0=xa00.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4xa0months, pxa0<xa00.001). On multivariable analysis, poor tumor differentiation (HR 10.3, pxa0=xa00.021), microvascular invasion (HR 3.3, pxa0=xa00.037), perineural invasion (HR 3.9, pxa0=xa00.029), lymph node metastases (HR 5.0, pxa0=xa00.004), and microscopic positive margin (HR 3.5, pxa0=xa00.046) were independent risk factors associated with early recurrence.ConclusionsEarly recurrence of HCCA after curative resection was common (~35.6%). Early recurrence was strongly associated with aggressive tumor characteristics, increased risk of distant metastatic recurrence and a worse long-term survival.

Patient-Provider Communication and Health Outcomes Among Individuals with Hepato-Pancreato-Biliary Disease in the USA

BackgroundPatient-provider communication (PPC) is utilized as a value-based metric in pay-for-performance programs. We sought to evaluate the association of PPC with patient-reported health outcomes, as well as healthcare resource utilization among a nationally representative cohort of patients with hepato-pancreato-biliary (HPB) diagnoses.MethodsPatients with HPB diseases were identified from the 2008–2014 Medical Expenditure Panel Survey cohort. A weighted PPC composite score was categorized using the responses from the CAHPS (Consumer Assessment of Healthcare Providers and Systems) survey as optimal, average, or poor. Multivariate analysis was performed using logistic regression.ResultsAmong 1951 adult-patients, representing 21.7 million HPB patients, reported PPC was optimal (33.4%), average (46.3%), or poor (15.3%). Patients who were older and patients with low income were more likely to report poor PPC (both pxa0<xa00.05). Statin use, a quality of care measure, was associated with optimal PPC (OR 1.70, 95% CI 1.10–2.64; pxa0=xa00.01). In contrast, patients who reported poor PPC were more likely to have a poor physical (20.8%) or mental (8.8%) health component on their SF12 (both pxa0<xa00.05). Furthermore, patients with poor PPC were more likely to report poor mental status (OR 2.97, 95% CI 1.60–5.52), as well as higher emergency department visits (OR 1.95, 95% CI 1.25–3.05) and hospitalizations (OR 1.90, 95% CI 1.02–3.55) (both pxa0<xa00.05). Reported PPC was not associated with differences in overall healthcare expenditures or out-of-pocket expenditures.ConclusionsPPC was associated with a wide spectrum of patient-specific demographic and health utilization factors. Self-reported patient satisfaction with provider communication may be impacted by other considerations than simply the patient-provider interaction.

Which Patients Require Extended Thromboprophylaxis After Colectomy? Modeling Risk and Assessing Indications for Post-discharge Pharmacoprophylaxis

BackgroundGiven the conflicting nature of reported risk factors for post-discharge venous thromboembolism (VTE) and unclear guidelines for post-discharge pharmacoprophylaxis, we sought to determine risk factors for 30-day post-discharge VTE after colectomy to predict which patients will benefit from post-discharge pharmacoprophylaxis.MethodsPatients who underwent colectomy in the American College of Surgeons National Surgical Quality Improvement Project Participant Use Files from 2011 to 2015 were identified. Logistic regression modeling was used. Receiver-operating characteristic curves were used and the best cut-points were determined using Youden’sxa0J index (sensitivityxa0+xa0specificityxa0−xa01). Hosmer–Lemeshow goodness-of-fit test was used to test model calibration. A random sample of 30% of the cohort was used as a validation set.ResultsAmong 77,823 cases, the overall incidence of VTE after colectomy was 1.9%, with 0.7% of VTE events occurring in the post-discharge setting. Factors associated with post-discharge VTE risk including body mass index, preoperative albumin, operation time, hospital length of stay, race, smoking status, inflammatory bowel disease, return to the operating room and postoperative ileus were included in logistic regression equation model. The model demonstrated good calibration (goodness of fit Pxa0=xa00.7137) and good discrimination (area under the curve (AUC)xa0=xa00.68; validation set, AUCxa0=xa00.70). A score of ≥−5.00 had the maxim sensitivity and specificity, resulting in 36.63% of patients being treated with prophylaxis for an overall VTE risk of 0.67%.ConclusionApproximately one-third of post-colectomy VTE events occurred after discharge. Patients with predicted post-discharge VTE risk of ≥−5.00 should be recommended for extended post-discharge VTE prophylaxis.

Lymphadenectomy for Intrahepatic Cholangiocarcinoma: Has Nodal Evaluation Been Increasingly Adopted by Surgeons over Time?A National Database Analysis

BackgroundSurgical management of intrahepatic cholangiocarcinoma routinely includes resection of the hepatic parenchyma, yet the role of lymphadenectomy (LND) is more controversial. The objective of the current study was to define overall utilization, as well as temporal trends, in the utilization of LND among patients undergoing curative-intent hepatectomy for ICC using a nationwide database.Materials and MethodsOne thousand four hundred ninety-six patients who underwent curative-intent resection for ICC were identified using the SEER database from 2000 to 2013. The utilization of LND was assessed over time and by geographic region. LND utilization and the incidence of lymph node metastasis (LNM) were evaluated relative to AJCC T categories.ResultsAt the time of surgery, slightly over one-half of patients (nu2009=u2009784, 52.4%) had at least one LN evaluated. Specifically, 613 (41.0%) patients had 1–5 LNs evaluated, whereas 171 (11.4%) patients had ≥u20096 LNs evaluated. The proportion of patients who had at least one LN evaluated at the time of surgery did not change with time (2000–2004: 50.5% vs. 2005–2009: 52.0% vs. 2010–2013: 53.7%) (pu2009=u20090.636). In contrast, the proportion of patients who had ≥u20096 LNs examined did increase (2000–2004: 6.9% vs. 2005–2009: 10.6% vs. 2009–2013: 14.3%) (pu2009=u20090.003). The risk of LNM was higher among patients with advanced T category tumors (Referent T1; T2a: OR 4.2, 95% CI 2.0–8.8, pu2009<u20090.001; T2b: OR 2.4, 95% CI 1.1–4.9, pu2009=u20090.018; T3: OR 3.6, 95% CI 1.6–7.9, pu2009=u20090.001; T4: OR 2.2, 95% CI 1.0–4.9, pu2009=u20090.049). In addition, the portion of patients with LNM varied among the different T categories (T1, 23.2%, T2a, 55.3%, T2b, 42.0%, T3, 51.4%, and T4, 39.5%; pu2009=u20090.001).ConclusionsUtilization of LND in the surgical management of ICC across the USA remained relatively low and did not change over the last decade. Selective utilization of LND may be problematic as T-stage was not a reliable predictor of nodal status with almost a quarter of patients with early stage disease having LNM.

Margin status and long-term prognosis of primary pancreatic neuroendocrine tumor after curative resection: Results from the US Neuroendocrine Tumor Study Group

Background: The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long‐term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. Methods: Patients who underwent curative‐intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence‐free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. Results: Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence‐free survival (10‐year recurrence‐free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10‐year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence‐free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor‐specific factors, such as cellular differentiation, perineural invasion, Ki‐67 index, and major vascular invasion, rather than surgical margin, were associated with long‐term outcomes. Conclusion: Margin status was not associated with long‐term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal‐sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

Early recurrence of well-differentiated (G1) neuroendocrine liver metastasis after curative-intent surgery: Risk factors and outcome: XIANG et al.

The objective of the current study was to identify the risk of early vs late recurrence of well‐differentiated (G1) neuroendocrine liver metastasis (NELM) after curative‐intent resection.