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 The goal of this study was to investigate the surgical management and outcomes of patients with primary colorectal cancer (CRC) and synchronous liver metastasis (sCRLM). Study Design Using ...a multi-institutional database, we identified 1,004 patients treated for sCRLM between 1982 and 2011. Clinicopathologic and outcomes data were evaluated with uni- and multivariable analyses. Results A simultaneous CRC and liver operation was performed in 329 (33%) patients; 675 (67%) underwent a staged approach (“classic” staged approach, n = 647; liver-first strategy, n = 28). Patients managed with the liver-first approach had more hepatic lesions and were more likely to have bilateral disease than those in the other 2 groups (p < 0.05). The use of staged operative strategies increased over the time of the study from 58% to 75% (p < 0.001). Liver-directed therapy included hepatectomy (90%) or combined resection + ablation (10%). A major resection (>3 segments) was more common with a staged approach (39% vs 24%; p < 0.001). Overall, 509 patients (50%) received chemotherapy in either the preoperative (22%) or adjuvant (28%) settings, with 11% of patients having both. There were 197 patients (20%) who had a complication in the postoperative period, with no difference in morbidity between staged and simultaneous groups or major vs minor hepatectomies (p > 0.05). Ninety-day postoperative mortality was 3.0%, with no difference between simultaneous and staged approaches (p = 0.94). The overall median and 5-year survivals were 50.9 months and 44%, respectively; long-term survival was the same regardless of the operative approach (p > 0.05). Conclusions Simultaneous and staged resections for sCRLM can be performed with comparable morbidity, mortality, and long-term oncologic outcomes.
Background The incidence and associated risk factors for readmission after hepato-pancreato-biliary surgery are poorly characterized. The objective of the current study was to compare readmission ...after pancreatic vs hepatobiliary surgical procedures, as well as to identify potential factors associated with higher readmission within 30 days of discharge. Study Design Using Surveillance, Epidemiology and End Results–Medicare linked data from 1986–2005, we identified 9,957 individuals aged 66 years and older who underwent complex hepatic, biliary, or pancreatic procedures for cancer treatment and were eligible for analysis. In-hospital morbidity, mortality, and 30-day readmission were examined. Results Primary surgical treatment consisted of a pancreatic (46.7%), hepatic (50.0%), or biliary (3.4%) procedure. Mean patient age was 72.6 years and most patients were male (53.2%). The number of patients with multiple preoperative comorbidities increased over time (patients with Elixhauser's comorbidity score >13: 1986–1990, 47.0% vs 2001–2005, 62.9%; p < 0.001). Pancreatic operations had higher inpatient mortality vs hepatobiliary procedures (9.2% vs 7.3%; p < 0.001). Mean length of stay after pancreatic procedures was longer compared with hepatobiliary procedures (19.7 vs 10.3 days; p < 0.001). The proportion of patients readmitted after a pancreatic (1986–1990, 17.7%; 1991–1995, 16.1%; 1996–2000, 18.6%; 2001–2005, 19.6%; p = 0.15) or hepatobiliary (1986–1990, 14.3%; 1991–1995, 14.1%; 1996–2000, 15.2%; 2001–2005, 15.5%; p = 0.69) procedure did not change over time. Factors associated with increased risk of readmission included preoperative Elixhauser comorbidities >13 (odds ratio = 1.90) and prolonged index hospital stay ≥10 days (odds ratio = 1.54; both p < 0.05). During the readmission, additional morbidity and mortality were 46.5% and 8.0%, respectively. Conclusions Although the incidence of readmission did not change across the time periods examined, readmission was higher among patients undergoing a pancreatic procedure vs a hepatobiliary procedure. Other factors associated with risk of readmission included number of patient comorbidities and prolonged hospital stay. Readmission was associated with additional short-term morbidity and mortality.
Background Endoscopic ultrasound (EUS) can be used to guide the therapeutic plan for patients with gastric adenocarcinoma (GAC), but data on its use and accuracy remain poorly defined. We sought to ...define the use of EUS, as well as characterize the diagnostic accuracy of EUS among patients with GAC. Study Design We identified 960 patients who underwent resection of GAC between 2000 and 2012 from 7 major academic institutions participating in the US Gastric Cancer Collaborative. Clinicopathologic and EUS data were collected and analyzed using chi and kappa statistics. Results Of 960 patients, 223 (23.2%) underwent evaluation with preoperative EUS. Among patients who underwent EUS, 74 (33.2%) received neoadjuvant chemotherapy; 149 (66.8%) proceeded directly to resection. Among patients who did not receive neoadjuvant therapy and received curative intent gastric resection, the EUS T classifications were T1 (33.3%), T2 (35.6%), T3 (18.9%), T4 (12.1%) and the N classifications were N0 (68.1%) and N ≥ 1 (31.9%). In contrast, when tumor stage was based on the final surgical specimen, there was a higher proportion of cases with more advanced T stage (T1, 36.4%; T2, 14.4%; T3, 23.5%; T4, 25.7%) and N stage (N0, 51.3%; N ≥ 1, 48.7%). The agreement of preoperative EUS compared with surgical staging for T (kappa = 0.28, p < 0.001) and N (kappa = 0.33, p < 0.001) classification was only fair. Conclusions Less than one-quarter of patients with GAC underwent preoperative EUS staging. In patients who did not receive preoperative chemotherapy, tumor stage on EUS often did not correlate with T stage and N stage on final pathologic analysis. Endoscopic ultrasound should be combined with other staging modalities to optimize staging of patients with GAC.
Background Reliable criteria to predict mortality after hepatectomy remain poorly defined. We sought to identify factors associated with 90-day mortality, as well as validate the “50-50” and peak ...bilirubin of >7 mg/dL prediction rules for mortality after liver resection. In addition, we propose a novel integer-based score for 90-day mortality using a large cohort of patients. Study Design Data from 2,056 patients who underwent liver resection at 2 major hepatobiliary centers between 1990 and 2011 were identified. Perioperative laboratory data, as well as surgical and postoperative details, were analyzed to identify factors associated with liver-related 90-day death. Results Indications for liver resection included colorectal metastasis (39%), hepatocellular carcinoma (19%), benign mass (17%), or noncolorectal metastasis (14%). Most patients had normal underlying liver parenchyma (71%) and resection involved ≥3 segments (36%). Overall morbidity and mortality were 19% and 2%, respectively. Only 1 patient fulfilled the 50-50 criteria; this patient survived and was discharged on day 8. Twenty patients had a peak bilirubin concentration >7 mg/dL and 5 died within 90 days; the sensitivity and specificity of the >7-mg/dL rule were 25% and 99.3%, respectively, but overall accuracy was poor (area under the curve 0.574). Factors associated with 90-day mortality included international normalized ratio (odds ratio = 11.87), bilirubin (odds ratio = 1.16), and serum creatinine (odds ratio = 1.87) on postoperative day 3, as well as grade of postoperative complications (odds ratio = 5.08; all p < 0.05). Integer values were assigned to each factor to develop a model that predicted 90-day mortality (area under the curve 0.89). A score of ≥11 points had a sensitivity and specificity of 83.3% and 98.8%, respectively. Conclusions The 50-50 and bilirubin >7-mg/dL rules were not accurate in predicting 90-day mortality. Rather, a composite integer-based risk score based on postoperative day 3 international normalized ratio, bilirubin, creatinine, and complication grade more accurately predicted 90-day mortality after hepatectomy.
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.
Abstract Background The American College of Surgeons recently added liver-specific variables to the National Surgical Quality Improvement Program (NSQIP). We sought to use these variables to define ...patterns of care, as well as characterize perioperative outcomes among patients undergoing hepatic resection. Methods The American College of Surgeons-NSQIP database was queried for all patients undergoing hepatic resection between January 1, 2013 and December 31, 2013 ( n = 2448). Liver-specific variables were summarized. Results Preoperatively, 11.3% of patients had hepatitis B or C or both, whereas 9.2% had cirrhosis. The indication for hepatic resection was benign (20.8%) or malignant (74.2%) disease. Among patients with a malignant indication, metastatic disease (47.3%) was more common than primary liver cancer (26.9%). Preoperative treatment included neoadjuvant chemotherapy (25.5%), portal vein embolization (2.1%), and intra-arterial therapy (0.9%). At surgery, most patients underwent an open hepatic resection (70.7%), whereas 21.4% and 1.1% underwent a laparoscopic or robotic procedure. The Pringle maneuver was used in 27.7% of patients. Although 6.5% of patients had a concomitant hepaticojejunostomy, 10.1% had a concurrent ablation. An operative drain was placed in half of patients (46.5%, minor resection: 42.0% versus major resection: 53.4%; P < 0.001). Among the entire cohort, bile leak (7.3%, minor resection: 4.9% versus major resection: 10.9%; P < 0.001) and liver insufficiency and/or failure (3.8%, minor resection: 1.9% versus major resection: 6.9%; P < 0.001) were relatively uncommon. A subset of patients (9.5%) did experience major liver-specific complications that required intervention (drainage of collection and/or abscess: 38.4%; stenting for biliary obstruction and/or leak: 21.2%; biloma drainage: 18.4%). Conclusions In addition to standard variables, the new inclusion of liver-specific variables provides a unique opportunity to study NSQIP outcomes and practice patterns among patients undergoing hepatic resection.
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 Current treatment guidelines recommend adjuvant mitotane after resection of adrenocortical carcinoma with high-risk features (eg, tumor rupture, positive margins, positive lymph nodes, ...high grade, elevated mitotic index, and advanced stage). Limited data exist on the outcomes associated with these practice guidelines. Study Design Patients who underwent resection of adrenocortical carcinoma from 1993 to 2014 at the 13 academic institutions of the US Adrenocortical Carcinoma Group were included. Factors associated with mitotane administration were determined. Primary end points were recurrence-free survival (RFS) and overall survival (OS). Results Of 207 patients, 88 (43%) received adjuvant mitotane. Receipt of mitotane was associated with hormonal secretion (58% vs 32%; p = 0.001), advanced TNM stage (stage IV: 42% vs 23%; p = 0.021), adjuvant chemotherapy (37% vs 5%; p < 0.001), and adjuvant radiation (17% vs 5%; p = 0.01), but was not associated with tumor rupture, margin status, or N-stage. Median follow-up was 44 months. Adjuvant mitotane was associated with decreased RFS (10.0 vs 27.9 months; p = 0.007) and OS (31.7 vs 58.9 months; p = 0.006). On multivariable analysis, mitotane was not independently associated with RFS or OS, and margin status, advanced TNM stage, and receipt of chemotherapy were associated with survival. After excluding all patients who received chemotherapy, adjuvant mitotane remained associated with decreased RFS and similar OS; multivariable analyses again showed no association with recurrence or survival. Stage-specific analyses in both cohorts revealed no association between adjuvant mitotane and improved RFS or OS. Conclusions When accounting for stage and adverse tumor and treatment-related factors, adjuvant mitotane after resection of adrenocortical carcinoma is not associated with improved RFS or OS. Current guidelines should be revisited and prospective trials are needed.
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