Bergquist, John R.

AbstractIntroductionAlthough surgical resection is necessary, it is not sufficient for long‐term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up‐front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19‐9; and (C) receipt of adjuvant chemotherapy.MethodsThe National Cancer Data Base (2010–2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre‐operative CA19‐9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention‐to‐treat (ITT) basis.ResultsTwelve thousand and eighty‐nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT‐neoadjuvant cohort (27.9 vs. 22 months) to UFS.ConclusionDespite the perceived benefit of UFS, only 1‐in‐5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT‐neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of ‘optimal’ survival benefit with UFS in anatomically resectable PDAC.

Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan–Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0–27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62–0.84,p<0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53–0.97,p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months,p<0.001), less than 15 cm (104.1 vs. 84.2 months,p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months,p<0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.

BACKGROUND: Excessive perioperative fluid administration likely increases postoperative cardiovascular, infectious, and GI complications. Early administration of diuretics after elective surgery facilitates rapid mobilization of excess fluid, potentially leading to decreased bowel edema, more rapid return of bowel function, and reduced length of hospital stay. OBJECTIVE: This study aimed to evaluate the benefit of early diuresis after elective colon and rectal surgery in the setting of an enhanced recovery after surgery practice. DESIGN: This was a prospective study. SETTINGS: The study was conducted at a quaternary referral center. PATIENTS: A randomized, open-label, parallel-group trial was conducted in patients undergoing elective colon and rectal surgery at a single quaternary referral center. INTERVENTION: The primary intervention was administration of intravenous furosemide plus enhanced recovery after surgery on postoperative day 1 and 2 versus enhanced recovery after surgery alone. MAIN OUTCOME MEASURES: The primary outcome was length of hospital stay. Secondary outcomes included 30-day readmission rate, time to stool output during hospitalization after surgery, and incidence of various complications within the first 48 hours of hospital stay. RESULTS: In total, 123 patients were randomly assigned to receive either furosemide plus enhanced recovery after surgery (n = 62) or enhanced recovery after surgery alone (n = 61). Groups were evenly matched at baseline. At interim analysis, length of hospital stay was not superior in the intervention group (80.6 vs 99.6 hours, p = 0.564). No significant difference was identified in the rates of nasogastric tube replacement (1.6% vs 9.7%, p = 0.125). Time to return of bowel function was significantly longer in the intervention group (45.4 vs 48.8 hours, p = 0.048). The decision was made to end the study early because the conditional power of the study favored futility. LIMITATIONS: This was a single-center study. CONCLUSIONS: Early administration of furosemide does not significantly reduce the length of hospital stay after elective colon and rectal surgery in the setting of enhanced recovery after surgery practice. See Video Abstract at http://links.lww.com/DCR/A714.

291 Background: Cholangiocarcinoma (CCA) is a rare malignancy with poor survival. The only curative therapy is resection and the role of adjuvant therapy is not well defined. Despite the unproven benefit, adjuvant therapy is used in resected CCA. The aim of this study is to analyze our institution’s outcomes for peri-operative treatment of resected intrahepatic and extrahepatic CCA. Methods: We retrospectively analyzed 145 intrahepatic (iCCA) and 109 extrahepatic (eCCA) CCA patients who underwent resection at the Mayo Clinic, Rochester. The majority of treated patients received adjuvant chemotherapy; however neo-adjuvant and radiation were also included. Results: In stage 1-2 iCCA patients, the HR indicated worse outcomes for time to recurrence and death. For stage 3-4 or node positive disease, outcomes were not significantly different. Those with node unknown/negative disease had significantly worse time to recurrence but not OS. There was a significant difference in stage and treatment modality between these groups (see table). Among eCCA, for any stage and node positive disease, outcomes were not different. In the node unknown/negative group, neither time to recurrence nor OS differed significantly. In controlling for different features in multi-variable analyses, no significant differences were observed (see table). Conclusions: This retrospective study does not show a significant difference in recurrence free or OS for treated patients. The apparent lack of benefit most likely reflects selection bias among treatment groups. Prospective, randomized trials are needed to make sound recommendations in adjuvant treatment for CCA. [Table: see text] [Table: see text]

BACKGROUND: Clinical trials demonstrate that postresection chemotherapy conveys survival benefit to patients with stage III colon cancer. It is unclear whether this benefit can be extrapolated to the elderly, who are underenrolled in clinical trials. OBJECTIVE: The purpose of this study was to determine outcomes of selected octogenarians with stage III colon cancer with/without postresection adjuvant therapy. DESIGN: This was a retrospective cohort study (2006–2011) using unadjusted Kaplan–Meier and adjusted Cox proportional hazards analyses of overall survival. SETTING: The study was conducted with the National Cancer Database. PATIENTS: We included patients 80 to 89 years of age who were undergoing curative-intent surgery for stage III colon cancer and excluded patients who received neoadjuvant therapy, died within 6 weeks of surgery, or had high comorbidity. MAIN OUTCOME MEASURES: Overall survival was the main measure. RESULTS: A total of 8141 octogenarians were included; 3483 (42.8%) received postresection chemotherapy, and 4658 (57.2%) underwent surgery alone. Patients receiving chemotherapy were younger (82.0 vs 84.0 years; p < 0.001), healthier (73.1% vs 70.4% with no comorbidities; p = 0.009), and more likely to have N2 disease (40.4% vs 32.8%; p < 0.001). Overall survival was improved in patients receiving adjuvant chemotherapy (median = 61.7 vs 35.0 months; p < 0.001). Subgroup analysis of patients offered chemotherapy but refusing (n = 1315) demonstrated overall survival worse than those receiving adjuvant chemotherapy (median = 42.7 vs 61.7 months; p < 0.001). Multivariable analysis adjusting for potential confounders showed therapy with surgery alone to be independently associated with increased mortality hazard (HR = 1.83; p < 0.001), and the mortality hazard remained elevated in patients who voluntarily refused adjuvant therapy (HR = 1.45; p < 0.001). LIMITATIONS: The study was limited by its retrospective, nonrandomized design. CONCLUSIONS: In selected octogenarians with stage III colon cancer, postresection adjuvant chemotherapy was associated with superior overall survival. However, less than half of the octogenarians with stage III colon cancer in the National Cancer Database received it. The remaining majority, who were all fit and survived ≥6 weeks postsurgery, could have derived benefit from adjuvant chemotherapy. This represents a substantial opportunity for quality improvement in treating octogenarians with stage III colon cancer.