Background Reports on recurrence and outcomes of US patients with gastric cancer are scarce. The aim of this study was to determine incidence and pattern of recurrence after curative intent surgery ...for gastric cancer. Study Design Using the multi-institutional US Gastric Cancer Collaborative database, we identified 817 patients undergoing curative intent resection for gastric cancer between 2000 and 2012. Patterns and rates of recurrence along with associated risk factors were identified using adjusted regression analysis. Recurrences were classified as locoregional, peritoneal, or hematogenous. Results Median patient age was 65.8 years (interquartile range IQR 56.4, 74.7); the majority of patients were male (n = 462, 56.6%) and white (n = 511, 62.5%). At the time of surgery, the majority of patients underwent a partial gastrectomy (n = 481, 59.2%) with a complete R0 resection achieved in 91.6% (n = 748) of patients. At the time of last follow-up, 244 (29.9%) of 817 patients developed a recurrence; 163 (66.8%) patients had recurrence at only a single site; the remaining 81 (33.2%) had multiple sites of initial recurrence. Among patients who recurred at a single site, recurrence was most common at a distant location and included hematogenous (n = 57, 23.4%) or peritoneal (n = 47, 19.3%) only metastasis. Tumors at the gastroesophageal junction (odds ratio OR 3.18, 95% CI 1.08 to 9.40; p = 0.04) were associated with higher risk of locoregional recurrence, while the presence of multiple lesions (OR 10.82, 95% CI 3.56 to 32.85; p < 0.001) remained associated with an increased risk of distant hematogenous recurrence after adjusted analysis. Recurrence was associated with worse survival, with a median recurrence-free survival of 10.8 months (IQR 8.9, 12.8) among those who experienced a recurrence. Conclusions Nearly one-third of patients experienced recurrence after gastric cancer surgery. The most common site of recurrence was distant.
Background The decision as to whether a patient can tolerate surgery is often subjective and can misjudge a patient's true physiologic state. The concept of frailty is an important assessment tool in ...the geriatric medical population, but has only recently gained attention in surgical patients. Frailty potentially represents a measureable phenotype, which, if quantified with a standardized protocol, could reliably estimate the risk of adverse surgical outcomes. Study Design Frailty was prospectively evaluated in the clinic setting in patients consenting for major general, oncologic, and urologic procedures. Evaluation included an established assessment tool (Hopkins Frailty Score), self-administered questionnaires, clinical assessment of performance status, and biochemical measures. Primary outcome was 30-day postoperative complications. Results There were189 patients evaluated: 117 from urology, 52 from surgical oncology, and 20 from general surgery clinics. Mean age was 62 years, 59.8% were male, and 71.4% were Caucasian. Patients who scored intermediately frail or frail on the Hopkins Frailty Score were more likely to experience postoperative complications (odds ratio OR 2.07, 95% CI 1.05 to 4.08, p = 0.036). Of all other preoperative assessment tools, only higher hemoglobin (p = 0.033) had a significant association and was protective for 30-day complications. Conclusions The aggregate score of patients as “intermediately frail or frail” on the Hopkins Frailty Score was predictive of a patient experiencing a postoperative complication. This preoperative assessment tool may prove beneficial when weighing the risks and benefits of surgery, allowing objective data to guide surgical decision-making and patient counseling.
Abstract Background Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as one entity, yet direct comparisons are lacking. Our aim was to utilize two, large, ...multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases. Study Design Patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000-2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums were included. Primary endpoint was disease-specific survival (DSS). Results Of 1463pts, 224(15%) were DC and 1239(85%) were PDAC. Compared to PDAC, DC patients were less likely to be margin-positive (19% vs 25%;p=0.005), lymph node (LN)-positive (55% vs 69%;p<0.001), and receive adjuvant therapy (57% vs 71%;p<0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. DC was associated with improved median-DSS (40mos) compared to PDAC (22mos,p<0.001), which persisted on multivariable analysis (HR,0.65; 95%CI,0.50-0.84;p=0.001). LN-involvement was the only factor independently associated with decreased DSS for both DC and PDAC. DC/LN-positive patients had similar DSS as PDAC/LN-negative (p=0.74). Adjuvant therapy (chemotherapy+/-radiation) was associated with improved median-DSS for PDAC/LN-positive patients (21 vs 13mos;p=0.001), but not for DC patients (38 vs 40mos;p=0.62), regardless of LN status. Conclusions Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. DC has a favorable prognosis compared to PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Thus, treatment paradigms utilized for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.
Background Level 1 data demonstrate that adjuvant chemotherapy (ACT) improves survival after surgical resection of pancreatic ductal adenocarcinoma (PDAC), (adjuvant gemcitabine, CONKO-001 study; ...adjuvant 5-FU, ESPAC3 study). The role of adjuvant chemoradiation therapy (ACRT) remains controversial. What is less clear is whether adjuvant therapy influences patterns of recurrence. The purpose of this study was to perform the first multicenter study analyzing patterns of recurrence after adjuvant therapy for PDAC. Study Design Patients undergoing resection for PDAC from 8 medical centers over a 10-year period were analyzed. Demographics, tumor characteristics, operative treatment, type of adjuvant therapy, recurrence pattern, and survival were reviewed. Using Cox-proportional hazards multivariate (MV) regression, the impact of ACT and ACRT on overall survival (OS), local recurrence (LR), and distant recurrence (DR) was investigated. Results There were 1,130 patients who were divided into those having surgery alone (n = 392), ACT (n = 291), or ACRT (n = 447). Median follow-up was 18 months. Compared with patients undergoing surgery alone, ACT, but not ACRT, demonstrated a significant OS advantage on MV analysis. Patients receiving ACT had significantly fewer recurrences (LR and DR); those receiving ACRT had significantly less LR but not DR. On subset MV analysis, ACT and ACRT resulted in less LR in patients with lymph node (LN) positive and margin negative disease. No improvements in LR, DR, or OS were seen in margin positive patients with either ACT or ACRT. Conclusions This is the first analysis demonstrating differences in recurrence patterns in PDAC patients based on type of adjuvant therapy. Adjuvant chemotherapy provided an OS advantage likely related to its effect on reducing both LR and DR. Adjuvant chemoradiation therapy appears to decrease LR, but not DR, and therefore has less impact on OS. Future investigations and treatment protocols should consider additional ACT rather than ACRT in the treatment of PDAC.
Abstract Background Controversy persists regarding the management of patients with IPMN. International consensus guidelines stratify patients into high risk, worrisome, and low risk categories. Study ...Design The medical records of 7 institutions were reviewed for patients that underwent surgical management of IPMN between 2000-2015. Results 324 patients were included in the analysis. 60.4% of patients had main-duct / mixed type, and 39.7% had branch-duct IPMN. The median cyst size was 2.65 cm, while invasive cancer (IC) or high-grade dysplasia (HGD) was present in 42% (n=136). 68.9% of patients with high risk, 40.0% of patients with worrisome, and 24.6% of patients with low risk features exhibited HGD/ IC. Multivariate analysis demonstrated that only one of three high risk features and two of seven worrisome features predicted the presence of HGD/IC. Positive predictive values for HGD/ IC in patients with obstructive jaundice and lymphadenopathy were 0.83 (95% CI = 0.65-0.94) and 0.69 (95% CI= 0.39-0.91), respectively. In the absence of high risk features, HGD/ IC was still present in 57.4% of patients with two or more worrisome features. Regression analysis demonstrated that each additional worrisome factor present was additive in predicting HGD/ IC in a linear fashion (OR 1.39, 95% CI=1.08-1.80, p<0.01). Conclusions These data demonstrate that the current consensus guidelines for surgical resection of IPMN may not adequately stratify and identify patients at risk for having HGD or invasive cancer. Patients with multiple worrisome features, in the absence of high-risk factors, should be considered for resection.
Background Frailty is an objective method of quantifying a patient’s fitness for surgery. Its clinical use is limited by the time needed to complete, as well as a lack of evidence-based interventions ...to improve outcomes in identified frail patients. The purpose of this study was to critically analyze the components of the Fried Frailty Criteria, among other preoperative variables, to create a simplified risk assessment amenable to a busy clinical setting, while maintaining prognostic ability for surgical outcomes. Study Design We performed a prospective evaluation of patients that included the 5-component Fried Frailty Criteria, traditional surgical risk assessments, biochemical laboratory values, and clinical and demographic data. Thirty-day postoperative outcomes were the outcomes of interest. Results There were 351 consecutive patients undergoing major intra-abdominal operations enrolled. Analysis demonstrated that shrinking and grip strength alone hold the same prognostic information as the full 5-component Fried Frailty Criteria for 30-day morbidity and mortality. The addition of American Society of Anesthesia (ASA) score and serum hemoglobin creates a composite risk score, which facilitates easy classification of patients into discrete low (ref), intermediate (odds ratio OR 1.974, 95% CI 1.006 to 3.877, p = 0.048), and high (OR 4.889, 95% CI 2.220 to 10.769, p < 0.001) risk categories, with a corresponding stepwise increase in risk for 30-day postoperative complications. Internal validation by bootstrapping confirmed the results. Conclusions This study demonstrated that 2 components of the Fried Frailty Criteria, shrinking and grip strength, hold the same predictive value as the full frailty assessment. When combined with American Society of Anesthesiologists score and serum hemoglobin, they form a straightforward, simple risk classification system with robust prognostic information.
Background Examination of at least 16 lymph nodes (LNs) has been traditionally recommended during gastric adenocarcinoma resection to optimize staging, but the impact of this strategy on survival is ...uncertain. Because recent randomized trials have demonstrated a therapeutic benefit from extended lymphadenectomy, we sought to investigate the impact of the number of LNs removed on prognosis after gastric adenocarcinoma resection. Study Design We analyzed patients who underwent gastrectomy for gastric adenocarcinoma from 2000 to 2012, at 7 US academic institutions. Patients with M1 disease or R2 resections were excluded. Disease-specific survival (DSS) was calculated using the Kaplan-Meier method and compared using log-rank and Cox regression analyses. Results Of 742 patients, 257 (35%) had 7 to 15 LNs removed and 485 (65%) had ≥16 LNs removed. Disease-specific survival was not significantly longer after removal of ≥16 vs 7 to 15 LNs (10-year survival, 55% vs 47%, respectively; p = 0.53) for the entire cohort, but was significantly improved in the subset of patients with stage IA to IIIA (10-year survival, 74% vs 57%, respectively; p = 0.018) or N0-2 disease (72% vs 55%, respectively; p = 0.023). Similarly, for patients who were classified to more likely be “true N0-2,” based on frequentist analysis incorporating both the number of positive and of total LNs removed, the hazard ratio for disease-related death (adjusted for T stage, R status, grade, receipt of neoadjuvant and adjuvant therapy, and institution) significantly decreased as the number of LNs removed increased. Conclusions The number of LNs removed during gastrectomy for adenocarcinoma appears itself to have prognostic implications for long-term survival.
Abstract Background The role of routine lymphadenectomy for perihilar cholangiocarcinoma (PHCC) is still controversial and no study has defined the minimum number of lymphnodes examined (TNLE). We ...sought to assess the prognostic performance of AJCC/UICC 7th N stage, lymph-node ratio (LNR), and log-odds (LODDS-logarithm of the ratio between metastatic and non-metastatic nodes) in patients with PHCC, and identify the optimal TNLE to accurately stage patients. Methods A multi-institutional database was queried to identify 437 patients who underwent hepatectomy for PHCC between 1995-2014. The prognostic abilities of the LN staging systems were assessed using the Harrell's c-index. A Bayesian model was developed to identify the minimum TNLE. Results 158 (36.2%) patients had LN metastasis. The median TNLE was 3 (IQR, 1-7). LODDS had a slightly better prognostic performance than LNR and AJCC, in particular among patients with <4 TNLE (c-index:0.568). For 2 TNLE, the Bayesian model showed a poor discriminatory ability to distinguish patients with favorable and poor prognosis. When TNLE was >2, the HR for N1 patients resulted statistically significant, and the HR for N1 patients increased from 1.51 with 4 TNLE to 2.10 with 10 TNLE. While the 5-year OS of N1 patients was only slightly affected by TNLE, the 5-year OS of N0 patients significantly increased with TNLE. Conclusions PHCC patients undergoing radical resection should ideally have at least 4 LNs harvested to be accurately staged. Furthermore, while LODDS performed better at determining prognosis among patients with <4 TNLE, both LNR and LODDS outperformed compared to AJCC N stage among patients with ≥4 TNLE.
Background Gastric cancer constitutes a major public health problem. This study sought to evaluate the relevance of race in gastric cancer and its prognostic effect in the overall outcomes of ...patients with gastric adenocarcinoma. Study Design Patients who underwent curative intent resection of gastric adenocarcinoma in 8 institutions of the US Gastric Cancer Collaborative were included, from 2000 to 2012. Nonparametric descriptive statistics were used to evaluate characteristics of standard demographic data. Multivariate Cox proportional hazards regression was used to identify factors associated with recurrence-free survival and overall survival. Results There were 1,077 patients included in the study, the majority of whom were of Caucasian race (n = 698, 68%), followed by African-American (n = 164, 15%), Asian (n = 132, 12%), Hispanic (n = 34, 3.2%), and other (n = 49, 4.5%). Clinicopathologic data were similarly distributed among the 5 groups. Mean follow-up was 27.1 months. By multivariate, stage-specific analysis, Asian race was a significant predictor of recurrence (all stages hazard ratio HR 0.45 95% CI 0.23, 0.97, p = 0.041) and of overall survival (all stages HR 0.35 95% CI 0.18, 0.68, p = 0.002). Recurrence-free survival was significantly increased in the Asian population compared with the non-Asian population (25th percentile: 38.6 vs 17.7 months, p = 0.0096), as was overall median survival (141 vs 38.8 months, p < 0.001). Conclusions Patients of Asian race undergoing curative gastrectomy for gastric adenocarcinoma appear to have a better prognosis stage for stage. Further studies are required to elucidate the underlying etiology of this phenomenon.
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.
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