AssociationofEarlyvsDelayedCholecystectomy ...

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vival found with increasing CD4+ cell levels. Patients were also divided into groups with high (n = 26) and low (n = 27) levels of CD3+ using median expression as a cutoff. Median survival was 20.5 and 18.8 months, respectively, and the 5-year survival estimate was 18.0 months (95% CI, 6.0-35.1 months) and 5.56 months (95% CI, 0.5-2.6 months), respectively. A similar analysis was performed for those with high (n = 22) and low (n = 22) levels of postoperative circulating monocytes. Median survival was 25.3 and 21.6 months, respectively; 5-year estimate of survival, 21.3 months (95% CI, 4.7-45.9 months) and 9.5 months (95% CI, 0.9-31.1 months), respectively.

Multivariate Cox proportional hazards regression was performed using clinicopathologic and immunohistochemical information. Initially, all variables significant on the univariate analysis were included, and subsequently nonsignificant variables were removed in a stepwise fashion until the final model was generated. American Joint Committee on Cancer stage, CD3+ tumor infiltrate, lymphovascular invasion, and postoperative circulating monocytes remained significant (Table 2).

Discussion | Only a subgroup of patients with pancreatic cancer present with malignant neoplasms that are eligible for surgical resection, and these are skewed toward early-stage disease. Within our study population and within the immune cell types studied, preoperative analysis of peripheral lymphocytes was not associated with survival and was not reflective of the intratumoral immune infiltrate. However, higher levels of tumor-infiltrating CD3+ T cells and higher postoperative circulating levels of monocytes were associated with an improved prognosis. These data suggest that, although peripheral blood immunocytes do not reflect the immune environment of the tumor, consideration of the systemic immune response during recovery from resection may be of value. Our data suggest a possible role for the patient's immune response on the outcome of pancreatic tumor resection and that interventions that change the tumor immune environment and the systemic response in the postresection period could influence patient outcomes.

Ephraim S. Tang, MD, MSc Philippa H. Newell, MD Ronald F. Wolf, MD Paul Daniel Hansen, MD Benjamin Cottam, BSc Carmen Ballesteros-Merino, PhD Michael J. Gough, PhD

Concept and design: Tang, Newell, Hansen, Gough. Acquisition, analysis, or interpretation of data: Tang, Newell, Wolf, Cottam, Ballestros-Merino, Gough. Drafting of the manuscript: Tang, Ballestros-Merino, Gough. Critical revision of the manuscript for important intellectual content: Tang, Newell, Wolf, Hansen, Cottam, Gough. Statistical analysis: Tang. Obtained funding: Hansen, Gough. Administrative, technical, or material support: Tang, Hansen, Cottam, Gough. Supervision: Newell, Hansen, Gough. Conflict of Interest Disclosures: None reported. Funding/Support: This study was supported by research scholar grant RSG-12168-01-LIB from the American Cancer Society and the Providence Opportunity Fund. Role of the Funder/Sponsor: The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Additional Contributions: Marka Crittenden, MD, PhD, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon, assisted in the design and execution of these studies. This contribution was not compensated. 1. Clark CE, Hingorani SR, Mick R, Combs C, Tuveson DA, Vonderheide RH. Dynamics of the immune reaction to pancreatic cancer from inception to invasion. Cancer Res. 2007;67(19):9518-9527. 2. Carstens JL, Correa de Sampaio P, Yang D, et al. Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer. Nat Commun. 2017;8:15095. 3. Inman KS, Francis AA, Murray NR. Complex role for the immune system in initiation and progression of pancreatic cancer. World J Gastroenterol. 2014;20 (32):11160-11181. 4. Hiller JG, Perry NJ, Poulogiannis G, Riedel B, Sloan EK. Perioperative events influence cancer recurrence risk after surgery. Nat Rev Clin Oncol. 2018;15(4):205-218.

PACIFIC COAST SURGICAL ASSOCIATION

Association of Early vs Delayed Cholecystectomy for Mild Gallstone Pancreatitis With Perioperative Outcomes

Gallstones are the most common cause of acute pancreatitis in the United States.1-5 The timing of cholecystectomy among

Figure. Flow of Included Patients

Reviewed NSQIP database (2011-2014) ? Identified adult patients with pancreatitis (ICD-9 code 577.0)

Identified patients undergoing same-admission cholecystectomy ? CPT codes 47562, 47563, 47564, 47600, 47605, and 47610 ? Eliminated outpatient and elective procedures

Excluded patients undergoing other procedures ? Exception: concurrent CBD exploration, IOC, or intraoperative ERCP

Author Affiliations: Liver and Pancreatic Surgery Program, Providence Portland Cancer Center, Portland, Oregon (Tang, Newell, Wolf, Hansen); Division of Gastrointestinal and Minimally Invasive Surgery, The Oregon Clinic, Portland (Newell, Wolf, Hansen); Integrated Therapies Laboratory, Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon (Newell, Cottam, Ballesteros-Merino, Gough). Accepted for Publication: April 22, 2018. Corresponding Author: Michael J. Gough, PhD, Integrated Therapies Laboratory, Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan St, Ste 2N35, Portland, OR 97213 (michael.gough@). Published Online: August 8, 2018. doi:10.1001/jamasurg.2018.1757

Author Contributions: Drs Gough and Tang had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Excluded patients with clinical indicators of severe pancreatitis ? Dyspnea, ventilator dependence, ascites, acute kidney injury, dialysis,

impaired sensorium, coma, pneumonia, preoperative sepsis, or preoperative transfusion

Grouped remaining patients (with mild GSP undergoing same-admission cholecystectomy) ? Early cholecystectomy (48 h Pulmonary embolism DVT or thrombophlebitis Postoperative sepsis Septic shock Acute renal failure

Progressive renal insufficiency Urinary tract infection Pneumonia Superficial SSI Deep incisional SSI Organ space SSI Transfusion

Patients, No. (%)

Early LC (n = 824)

Delayed LC (n = 1113)

50.1 (18.3) 580 (70.4) 139 (17.6) 253 (30.7) 123 (14.9)

91 (11.0) 287 (34.8)

2 (0.2) 18 (2.2) 12 (1.5)

3 (0.4) 5 (0.6) 38 (4.6) 5 (0.6) 1.2 (1.1)

53.6 (18.8) 664 (59.7) 194 (18.8) 513 (46.2) 189 (17.0) 191 (17.2) 491 (44.1)

7 (0.6) 31 (2.8) 19 (1.7)

4 (0.4) 19 (1.7) 55 (4.9)

7 (0.6) 1.1 (1.0)

2 (0.2) 24 (2.9) 790 (95.9) 419 (50.8)

3.3 (3.7) 1.5 (0.6) 70.1 (39.8) 6 (0.7) 38 (4.8) 1 (0.1) 0 0 2 (0.2) 1 (0.1) 0 0 6 (0.7) 1 (0.1) 0 0 7 (0.8) 6 (0.7) 4 (0.5) 0 3 (0.4) 8 (1.0)

5 (0.4) 60 (5.4) 1043 (93.7) 422 (37.9)

7.1 (5.4) 4.6 (2.7) 78 (43.2) 22 (2.0) 69 (6.4) 1 (0.1) 1 (0.1) 3 (0.3) 6 (0.5) 3 (0.3) 2 (0.2) 3 (0.3) 7 (0.6) 6 (0.5) 3 (0.3) 1 (0.1) 10 (0.9) 8 (0.7) 9 (0.8) 2 (0.2) 18 (1.6) 27 (2.4)

OR (95% CI)

NA NA NA NA NA NA NA NA NA NA NA NA NA NA NA

0.54 (0.10-2.79) 0.53 (0.33-0.85) 1.56 (1.03-2.37) 1.69 (1.41-2.03) NA NA NA 0.37 (0.15-0.91) 0.74 (0.49-1.11) 1.35 (0.08-21.63) NA NA 0.45 (0.09-2.23) 4.50 (0.05-4.33) NA NA 1.16 (0.39-3.46) 0.22 (0.03-1.87) NA NA 0.95 (0.36-2.49) 1.01 (0.35-2.93) 0.60 (0.18-1.95) NA 0.22 (0.07-0.76) 0.39 (0.18-0.87)

P Value

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